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Science of Synthesis Houben–Weyl Methods of Molecular Transformations Category 1: Organometallics 1 Compounds with Transition Metal-Carbon ð-Bonds and Compounds of Groups 10–8 (Ni, Pd, Pt, Co, Rh, Ir, Fe, Ru, Os) M. Lautens 2 Compounds of Groups 7–3 (Mn…,Cr…,V…, Ti…,Sc…, La…,Ac…) T. Imamoto 3 Compounds of Groups 12 and 11 (Zn, Cd, Hg, Cu, Ag, Au) I. O Neil 4 Compounds of Group 15 (As, Sb, Bi) and Silicon Compounds I. Fleming 5 Compounds of Group 14 (Ge, Sn, Pb) M. G. Moloney 6 Boron Compounds D. Kaufmann and D. S. Matteson 7 Compounds of Groups 13 and 2 (Al, Ga, In, Tl, Be … Ba) H. Yamamoto 8 Compounds of Group 1 (Li … Cs) V. Snieckus and M. Majewski b 2003 Georg Thieme Verlag Stuttgart · New York

Science of Synthesis

Houben–Weyl Methods of Molecular Transformations

Category 1:

Organometallics

1 Compounds with Transition Metal-Carbon ð-Bonds and Compounds

of Groups 10–8 (Ni, Pd, Pt, Co, Rh, Ir, Fe, Ru, Os)

M. Lautens

2 Compounds of Groups 7–3 (Mn…,Cr…,V…, Ti…,Sc…, La…,Ac…)

T. Imamoto

3 Compounds of Groups 12 and 11 (Zn, Cd, Hg, Cu, Ag, Au)

I. O Neil

4 Compounds of Group 15 (As, Sb, Bi) and Silicon Compounds

I. Fleming

5 Compounds of Group 14 (Ge, Sn, Pb)

M. G. Moloney

6 Boron Compounds

D. Kaufmann and D. S. Matteson

7 Compounds of Groups 13 and 2 (Al, Ga, In, Tl, Be … Ba)

H. Yamamoto

8 Compounds of Group 1 (Li … Cs)

V. Snieckus and M. Majewski

b

2003

Georg Thieme Verlag

Stuttgart · New York

Science of Synthesis

Houben–Weyl Methods of Molecular Transformations

Editorial Board D. Bellus P. J. Reider

E. N. Jacobsen E. Schaumann

S. V. Ley I. Shinkai

R. Noyori E. J. Thomas

M. Regitz B. M. Trost

Managing Director G. F. Herrmann

Managing Editor M. F. Shortt de Hernandez

Science of Synthesis

Houben–Weyl Methods of Molecular Transformations

www.science-of-synthesis.com

2003 Georg Thieme Verlag

Rüdigerstrasse 14

D-70469 Stuttgart

distribution, multiplication and reproduction, as well as of translation. No

part of this publication may be reproduced by any process, whether by photostat

or microfilm or any other procedure, without previous written consent by

the publisher. This also includes the use of electronic media of data processing

on reproduction of any kind.

If you have any queries or comments about the content

of Science of Synthesis, please contact:

Dr. M. Fiona Shortt de Hernandez

Managing Editor

Science of Synthesis/Houben–Weyl

Thieme Chemistry

Georg Thieme Verlag

Rüdigerstrasse 14

D-70469 Stuttgart

Phone: +49 711 8931-783

Fax: +49 711 8931-777

E-mail: fiona.shortt@thieme.de

www.science-of-synthesis.com

Table of Contents

Preface ................................................................ 9

Tables of Contents

Volume 1 Compounds with Transition Metal–Carbon ð-Bonds

and Compounds of Groups 10–8 (Ni, Pd, Pt, Co, Rh, Ir, Fe, Ru, Os) ........... 11

Volume 2 Compounds of Groups 7–3 (Mn…, Cr…, V…, Ti…, Sc…, La…, Ac…) .......... 13

Volume 4 Compounds of Group 15 (As, Sb, Bi) and Silicon Compounds ................ 15

Volume 5 Compounds of Group 14 (Ge, Sn, Pb) ..................................... 18

Sample Contributions

Volume 1 Product Class 1: Organometallic Complexes of Nickel

J. Montgomery .......................................................... 25

Volume 2 Product Class 6: Organometallic Complexes of Chromium,

Molybdenum, and Tungsten without Carbonyl Ligands

R. Poli and K. M. Smith .................................................... 83

Volume 4 Product Subclass 4.4.27: Æ-Haloalkylsilanes

N. J. Lawrence .......................................................... 141

Volume 5 Product Subclass 22: Aryl- and Heteroarylgermanes

A. C. Spivey and C. M. Diaper .............................................. 163

Abbreviations .......................................................... 177

8 Science of Synthesis Category 1: Organometallics

Preface

As our understanding of the natural world increases, we begin to understand complex

phenomena at molecular levels. This level of understanding allows for the design of molecular

entities for functions ranging from material science to biology. Such design requires

synthesis and, as the structures increase in complexity as a necessity for specificity,

puts increasing demands on the level of sophistication of the synthetic methods. Such

needs stimulate the improvement of existing methods and, more importantly, the development

of new methods. As scientists confront the synthetic problems posed by the molecular

targets, they require access to a source of reliable synthetic information. Thus, the

need for a new, comprehensive, and critical treatment of synthetic chemistry has become

apparent. To meet this challenge, an entirely new edition of the esteemed reference work

Houben–Weyl Methods of Organic Chemistry will be published starting in the year 2000.

To reflect the new broader need and focus, this new edition has a new title, Science of

Synthesis, Houben–Weyl Methods of Molecular Transformations. Science of Synthesis

will benefit from more than 90 years of experience and will continue the tradition of excellence

in publishing synthetic chemistry reference works. Science of Synthesis will be a

balanced and critical reference work produced by the collaborative efforts of chemists,

from both industry and academia, selected by the editorial board. All published results

from journals, books, and patent literature from the early 1800s until the year of publication

will be considered by our authors, who are among the leading experts in their field.

The 48 volumes of Science of Synthesis will provide chemists with the most reliable methods

to solve their synthesis problems. Science of Synthesis will be updated periodically

and will become a prime source of information for chemists in the 21st century.

Science of Synthesis will be organized in a logical hierarchical system based on the

target molecule to be synthesized. The critical coverage of methods will be supported by

information intended to help the user choose the most suitable method for their application,

thus providing a strong foundation from which to develop a successful synthetic

route. Within each category of product, illuminating background information such as

history, nomenclature, structure, stability, reactivity, properties, safety, and environmental

aspects will be discussed along with a detailed selection of reliable methods. Each

method and variation will be accompanied by reaction schemes, tables of examples, experimental

procedures, and a background discussion of the scope and limitations of the

reaction described.

The policy of the editorial board is to make Science of Synthesis the ultimate tool for

the synthetic chemist in the 21st century.

We would like to thank all of our authors for submitting contributions of such outstanding

quality, and, also for the dedication and commitment they have shown throughout

the entire editorial process.

The Editorial Board October 2000

D. Bellus (Basel, Switzerland) E. Schaumann (Clausthal-Zellerfeld, Germany)

S. V. Ley (Cambridge, UK) I. Shinkai (Tsukuba, Japan)

R. Noyori (Nagoya, Japan) E. J. Thomas (Manchester, UK)

M. Regitz (Kaiserslautern, Germany) B. M. Trost (Stanford, USA)

P. J. Reider (New Jersey, USA)

Volume 1:

Compounds withTransition Metal–Carbon ð-Bonds

and Compounds of Groups 10–8 (Ni, Pd, Pt, Co, Rh,

Ir, Fe, Ru, Os)

Introduction

M. Lautens

1.1 Product Class 1: Organometallic Complexes of Nickel

J. Montgomery

1.2 Product Class 2: Organometallic Complexes of Palladium

1.2.1 Product Subclass 1: Palladium–Diene Complexes

J. M. Takacs, X. Jiang, and S. Vayalakkada

1.2.2 Product Subclass 2: Palladium–Allyl Complexes

R. W. Friesen

1.2.3 Product Subclass 3: Palladium–Alkyne Complexes

J. M. Takacs, S. Vayalakkada, and X. Jiang

1.2.4 Product Subclass 4: Palladium–Alkene Complexes

J. M. Takacs and S. Vayalakkada

1.3 Product Class 3: Organometallic Complexes of Platinum

A. Ogawa and T. Hirao

1.4 Product Class 4: Organometallic Complexes of Cobalt

M. Malacria, C. Aubert, and J.-L. Renaud

1.5 Product Class 5: Organometallic Complexes of Rhodium

I. Ojima, A. T. Vu, and D. Bonafoux

1.6 Product Class 6: Organometallic Complexes of Iridium

J. M. O Connor

1.7 Product Class 7: Organometallic Complexes of Iron

1.7.1 Product Subclass 1: Iron–Arene Complexes

G. R. Stephenson

1.7.2 Product Subclass 2: Iron–Dienyl Complexes

G. R. Stephenson

1.7.3 Product Subclass 3: Iron–Diene Complexes

G. R. Stephenson

12 Science of Synthesis Category 1: Organometallics

1.7.4 Product Subclass 4: Iron–Allyl Complexes

G. R. Stephenson

1.7.5 Product Subclass 5: Iron–Alkene Complexes

G. R. Stephenson

1.7.6 Product Subclass 6: Iron–Carbene Complexes

G. R. Stephenson

1.7.7 Product Subclass 7: Iron–Alkyl Complexes

G. R. Stephenson

1.7.8 Product Subclass 8: Ferrocenes

M. Perseghini and A. Togni

1.8 Product Class 8: Organometallic Complexes of Ruthenium

N. Chatani

1.9 Product Class 9: Organometallic Complexes of Osmium

J. Gonzalez and W. D. Harman

Table of Contents Volume 2 13

Volume 2:

Compounds of Groups 7–3

(Mn…, Cr…, V…,Ti…, Sc…, La…, Ac…)

Introduction

T. Imamoto

2.1 Product Class 1: Organometallic Complexes of Manganese

K. Oshima

2.2 Product Class 2: Organometallic Complexes of Technetium

I. D. Gridnev and T. Imamoto

2.3 Product Class 3: Organometallic Complexes of Rhenium

F. E. Kühn, C. C. Rom¼o, and W. A. Herrmann

2.4 Product Class 4: Arene Organometallic Complexes of Chromium,

Molybdenum, and Tungsten

E. P. Kündig and S. H. Pache

2.5 Product Class 5: Organometallic ð-Complexes of Chromium,

Molybdenum, and Tungsten Excluding Arenes

K. H. Theopold, A. Mommertz, and B. A. Salisbury

2.6 Product Class 6: Organometallic Complexes of Chromium,

Molybdenum, and Tungsten without Carbonyl Ligands

R. Poli and K. M. Smith

2.7 Product Class 7: Carbonyl Complexes of Chromium, Molybdenum,

and Tungsten with ó-Bonded Ligands

T. Ito and M. Minato

2.8 Product Class 8: Organometallic Complexes of Vanadium

T. Imamoto and I. D. Gridnev

2.9 Product Class 9: Organometallic Complexes of Niobium and Tantalum

K. Mashima and A. Nakamura

2.10 Product Class 10: Organometallic Complexes of Titanium

K. Mikami, Y. Matsumoto, and T. Shiono

2.11 Product Class 11: Organometallic Complexes of Zirconium and Hafnium

E.-i. Negishi and T. Takahashi

14 Science of Synthesis Category 1: Organometallics

2.12 Product Class 12: Organometallic Complexes of Scandium, Yttrium

and the Lanthanides

Z. Hou and Y. Wakatsuki

2.13 Product Class 13: Organometallic Complexes of the Actinides

A. Dormond and D. Barbier-Baudry

Table of Contents 15

Volume 4:

Compounds of Group 15 (As, Sb, Bi)

and Silicon Compounds

Introduction

Ian Fleming

4.1 Product Class 1: Arsenic Compounds

M. D. Smith

4.2 Product Class 2: Antimony Compounds

J. W. Burton

4.3 Product Class 3: BismuthCompounds

H. Suzuki and T. Ikegami

4.4 Product Class 4: Silicon Compounds

4.4.1 Product Subclass 1: Disilenes

K. M. Baines and M. S. Samuel

4.4.2 Product Subclass 2: Silenes

K. M. Baines and M. S. Samuel

4.4.3 Product Subclass 3: Silylenes

P. P. Gaspar and D. Zhou

4.4.4 Product Subclass 4: Silyl Hydrides

J. Pietruszka

4.4.5 Product Subclass 5: Disilanes

J. R. Hwu and K. S. Ethiraj

4.4.6 Product Subclass 6: Silyltin Reagents

I. Hemeon and R. D. Singer

4.4.7 Product Subclass 7: Silylboron Reagents

I. Hemeon and R. D. Singer

4.4.8 Product Subclass 8: Silylaluminum Reagents

I. Hemeon and R. D. Singer

4.4.9 Product Subclass 9: Silylzinc Reagents

I. Hemeon and R. D. Singer

4.4.10 Product Subclass 10: Silylcopper Reagents

R. D. Singer

16 Science of Synthesis Category 1: Organometallics

4.4.11 Product Subclass 11: Silyllithium Reagents

R. D. Singer

4.4.12 Product Subclass 12: Haloorganosilanes

M. Nilsson †

4.4.13 Product Subclass 13: Silyl Diethers

T. Skrydstrup

4.4.14 Product Subclass 14: Silyl Esters

M. Jaspars

4.4.15 Product Subclass 15: Silyl Imidic Esters (Silylimino Ethers)

E. Lukevics and O. Pudova

4.4.16 Product Subclass 16: Silyl Enol Ethers

S. Kobayashi, K. Manabe, H. Ishitani, and J.-I. Matsuo

4.4.17 Product Subclass 17: Silyl Ethers

J. D. White and R. G. Carter

4.4.18 Product Subclass 18: Silyl Peroxides

K. Tamao, J.-I. Yoshida and K. Itami

4.4.19 Product Subclass 19: Silyl Sulfides and Selenides

A. Ricci and M. Comes-Franchini

4.4.20 Product Subclass 20: Silyl Azides

C. Moberg and H. Adolfsson

4.4.21 Product Subclass 21: Silylamines

K. Tamao and A. Kawachi

4.4.22 Product Subclass 22: Silyl Phosphines

J. Pietruszka

4.4.23 Product Subclass 23: Silylmethyl Anions

D. Wang and T. H. Chan

4.4.24 Product Subclass 24: Silyl Cyanides

M. North

4.4.25 Product Subclass 25: Acylsilanes

P. C. B. Page and M. J. McKenzie

4.4.26 Product Subclass 26: 1-Diazo-1-silylalkanes

T. Aoyama and T. Shioiri

Table of Contents 17

4.4.27 Product Subclass 27: Æ-Haloalkylsilanes

N. J. Lawrence

4.4.28 Product Subclass 28: Æ-Silyl Alcohols, Ethers, and Amines

J. M. Aizpurua and C. Palomo

4.4.29 Product Subclass 29: Æ,â-Epoxysilanes

G. H. Whitham

4.4.30 Product Subclass 30: Alkynyl[Ethynyl]silanes

T. Hiyama and A. Mori

4.4.31 Product Subclass 31: Silylketenes

J.-M. Pons and P. J. Kocienski

4.4.32 Product Subclass 32: Allenylsilanes

J. Pornet

4.4.33 Product Subclass 33: Arylsilanes

B. A. Keay

4.4.34 Product Subclass 34: Vinylsilanes

K. Oshima

4.4.35 Product Subclass 35: Æ-Silyl Carbonyl Compounds

Y. Landais

4.4.36 Product Subclass 36: â-Silyl Alkyl Halides

W. E. Billups and R. K. Saini

4.4.37 Product Subclass 37: â-Silyl Alcohols and the Peterson Reaction

D. J. Ager

4.4.38 Product Subclass 38: Propargylsilanes

J. Pornet

4.4.39 Product Subclass 39: Benzylsilanes

B. Bennetau

4.4.40 Product Subclass 40: Allylsilanes

T. K. Sarkar

4.4.41 Product Subclass 41: â-Silyl Carbonyl Compounds

Ian Fleming

4.4.42 Product Subclass 42: ª-Silyl Alkyl Halides, Alcohols, and Esters Thereof

J. P. Michael and C. B. de Koning

18 Science of Synthesis Category 1: Organometallics

Volume 5:

Compounds of Group 14 (Ge, Sn, Pb)

Introduction

E. J. Thomas and M. G. Moloney

5.1 Product Class 1: Germanium Compounds

E. J. Thomas

5.1.1 Product Subclass 1: Germanium Hydrides

K. Oshima

5.1.2 Product Subclass 2: Digermenes and Digermanes

N. Takeda, N. Tokitoh, and R. Okazaki

5.1.3 Product Subclass 3: Metalated Germanium Compounds

N. Takeda, N. Tokitoh, and R. Okazaki

5.1.4 Product Subclass 4: Germanium Oxides, Sulfides, Selenides,

and Tellurides (Double Bonded)

N. Takeda, N. Tokitoh, and R. Okazaki

5.1.5 Product Subclass 5: Iminogermanes

N. Takeda, N. Tokitoh, and R. Okazaki

5.1.6 Product Subclass 6: Germenes

N. Takeda, N. Tokitoh, and R. Okazaki

5.1.7 Product Subclass 7: Germylenes

N. Takeda, N. Tokitoh, and R. Okazaki

5.1.8 Product Subclass 8: Organogermanium Halides

P. Thornton

5.1.9 Product Subclass 9: Germanium Oxides

P. Thornton

5.1.10 Product Subclass 10: Germanium Carboxylates, Phosphates,

and Related Compounds

P. Thornton

5.1.11 Product Subclass 11: Germanium Sulfides, Sulfoxides,

and Related Compounds

P. Thornton

Table of Contents 19

5.1.12 Product Subclass 12: Germanium Selenides, Tellurides,

and Related Compounds

P. Thornton

5.1.13 Product Subclass 13: Germylamines

P. Thornton

5.1.14 Product Subclass 14: Germanium Phosphines, Arsines, and Stibines

P. Thornton

5.1.15 Product Subclass 15: Germanium Cyanides

A. C. Spivey and C. M. Diaper

5.1.16 Product Subclass 16: Acylgermanes

A. C. Spivey and C. M. Diaper

5.1.17 Product Subclass 17: Imidoylgermanes (Æ-Iminoalkylgermanes)

and Æ-Diazoalkylgermanes

A. C. Spivey and C. M. Diaper

5.1.18 Product Subclass 18: Æ-Halo- and Æ-Alkoxyvinylgermanes

A. C. Spivey and C. M. Diaper

5.1.19 Product Subclass 19: Æ-Halo-, Æ-Hydroxy-, Æ-Alkoxy-,

and Æ-Aminoalkylgermanes

A. C. Spivey and C. M. Diaper

5.1.20 Product Subclass 20: Alkynylgermanes

A. C. Spivey and C. M. Diaper

5.1.21 Product Subclass 21: Germylketenes and Germylketenimines

A. C. Spivey and C. M. Diaper

5.1.22 Product Subclass 22: Aryl- and Heteroarylgermanes

A. C. Spivey and C. M. Diaper

5.1.23 Product Subclass 23: Vinylgermanes

A. C. Spivey and C. M. Diaper

5.1.24 Product Subclass 24: Propargyl- and Allenylgermanes

A. C. Spivey and C. M. Diaper

5.1.25 Product Subclass 25: Benzylgermanes

A. C. Spivey and C. M. Diaper

20 Science of Synthesis Category 1: Organometallics

5.1.26 Product Subclass 26: Allylgermanes

A. C. Spivey and C. M. Diaper

5.1.27 Product Subclass 27: Alkylgermanes

A. C. Spivey and C. M. Diaper

5.2 Product Class 2: Tin Compounds

E. J. Thomas

5.2.1 Product Subclass 1: Tin Hydrides

A. J. Clark

5.2.2 Product Subclass 2: Distannenes and Distannanes

J. Podlech

5.2.3 Product Subclass 3: Metalated Tin Compounds

J. Podlech

5.2.4 Product Subclass 4: Tin Oxides, Sulfides, Selenides, and Tellurides

(Double Bonded)

N. Takeda, N. Tokitoh, and R. Okazaki

5.2.5 Product Subclass 5: Iminostannanes

N. Takeda, N. Tokitoh, and R. Okazaki

5.2.6 Product Subclass 6: Stannenes

N. Takeda, N. Tokitoh, and R. Okazaki

5.2.7 Product Subclass 7: Stannylenes

N. Takeda, N. Tokitoh, and R. Okazaki

5.2.8 Product Subclass 8: Tin Halides and Organotin Halides

M. E. Wood

5.2.9 Product Subclass 9: Tin Oxides

B. Jousseaume

5.2.10 Product Subclass 10: Tin Carboxylates and Phosphates

B. Jousseaume

5.2.11 Product Subclass 11: Tin Enol Ethers

B. Jousseaume

5.2.12 Product Subclass 12: Tin Sulfides, Thioalkoxides,

and Related Compounds

B. Jousseaume

Table of Contents 21

5.2.13 Product Subclass 13: Tin Selenides and Tellurides

B. Jousseaume

5.2.14 Product Subclass 14: Organostannylamines and Related Compounds

B. Jousseaume

5.2.15 Product Subclass 15: Organostannylphosphines

B. Jousseaume

5.2.16 Product Subclass 16: Tin Cyanides and Fulminates

P. B. Wyatt

5.2.17 Product Subclass 17: Acylstannanes (Including S, Se, and Te Analogues)

P. B. Wyatt

5.2.18 Product Subclass 18: Imidoylstannanes, Diazoalkylstannanes,

Tin Isocyanates, and Tin Isothiocyanates

P. B. Wyatt

5.2.19 Product Subclass 19: 1-Halo-, 1-Alkoxy-, and 1-Aminovinylstannanes

I. Coldham and G. P. Vennall

5.2.20 Product Subclass 20: 1-Halo-, 1-Hydroxy-, 1-Alkoxy-, and

1-Aminoalkylstannanes

I. Coldham and G. P. Vennall

5.2.21 Product Subclass 21: Alkynylstannanes

G. T. Crisp

5.2.22 Product Subclass 22: Ketenylstannanes and Derivatives

G. T. Crisp

5.2.23 Product Subclass 23: Allenylstannanes

G. T. Crisp

5.2.24 Product Subclass 24: Arylstannanes

G. T. Crisp

5.2.25 Product Subclass 25: Alk-1-enylstannanes

G. T. Crisp

5.2.26 Product Subclass 26: Propargylstannanes

D. Young

5.2.27 Product Subclass 27: Benzylstannanes

R. L. Marshall

22 Science of Synthesis Category 1: Organometallics

5.2.28 Product Subclass 28: Allylstannanes

R. L. Marshall

5.2.29 Product Subclass 29: Alkylstannanes

D. Young

5.3 Product Class 3: Lead Compounds

M. G. Moloney

5.3.1 Product Subclass 1: Lead Hydrides

M. G. Moloney

5.3.2 Product Subclass 2: Diplumbenes and Diplumbanes

N. Takeda, N. Tokitoh, and R. Okazaki

5.3.3 Product Subclass 3: Metalated Lead Compounds

N. Takeda, N. Tokitoh, and R. Okazaki

5.3.4 Product Subclass 4: Organoplumbyl Oxides, Sulfides, Selenides,

and Tellurides (Double Bonded)

N. Takeda, N. Tokitoh, and R. Okazaki

5.3.5 Product Subclass 5: Plumbylenes

N. Takeda, N. Tokitoh, and R. Okazaki

5.3.6 Product Subclass 6: Halo(organo)plumbanes

P. J. Guiry and P. J. McCormack

5.3.7 Product Subclass 7: Organoplumboxanes and Related Compounds

P. J. Guiry and P. J. McCormack

5.3.8 Product Subclass 8: Acyloxy(organo)plumbanes

P. J. Guiry and P. J. McCormack

5.3.9 Product Subclass 9: Plumbyl Enol Ethers

P. J. Guiry and P. J. McCormack

5.3.10 Product Subclass 10: Organoplumbane Sulfur Compounds

P. J. Guiry and P. J. McCormack

5.3.11 Product Subclass 11: Organoplumbyl Selenides, Tellurides,

and Related Compounds

P. J. Guiry and P. J. McCormack

5.3.12 Product Subclass 12: Organoplumbanamines and Related Compounds

P. J. Guiry and P. J. McCormack

Table of Contents 23

5.3.13 Product Subclass 13: Organoplumbyl Phosphines and Phosphine Oxides

P. J. Guiry and P. J. McCormack

5.3.14 Product Subclass 14:

Triorganolead Cyanides and Triorganolead Cyanates

P. A. C. Eagle

5.3.15 Product Subclass 15: Acylplumbanes

P. A. C. Eagle

5.3.16 Product Subclass 16: Lead Isocyanates, Isothiocyanates, Diazoplumbanes,

and Iminoplumbanes

P. A. C. Eagle

5.3.17 Product Subclass 17: 1- or 2-Alkoxy- and 1- or 2-(Alkylsulfanyl) and

1- or 2-Aminoalkenyl(triorgano)plumbanes

P. A. C. Eagle

5.3.18 Product Subclass 18: 1-Halo-, 1-Alkoxy-, 1-Hydroxy-, and

1-Aminoalkylplumbanes

P. A. C. Eagle

5.3.19 Product Subclass 19: Alkynylplumbanes

P. A. C. Eagle

5.3.20 Product Subclass 20: Allenylplumbanes

P. A. C. Eagle

5.3.21 Product Subclass 21: Arylplumbanes

P. A. C. Eagle

5.3.22 Product Subclass 22: Vinylplumbanes

P. A. C. Eagle

5.3.23 Product Subclass 23: Benzylplumbanes

P. A. C. Eagle

5.3.24 Product Subclass 24: Allylplumbanes

P. A. C. Eagle

5.3.25 Product Subclass 25: Alkylplumbanes

P. A. C. Eagle

Science of Synthesis

Houben–Weyl Methods of Molecular Transformations

Sample Contribution

Category Organometallics

Volume 1 Compounds with Transition Metal-Carbon

ð-Bonds and Compounds of Groups 10 –8

(Ni, Pd, Pt, Co, Rh, Ir, Fe, Ru, Os)

Product Class 1.1 Organometallic Complexes of Nickel

Written by J. Montgomery

2001 Georg Thieme Verlag

Rüdigerstrasse 14

D-70469 Stuttgart

Printed in Germany

Typesetting: Ziegler + Müller, Kirchentellinsfurt

Printing: Konrad Triltsch, Ochsenfurt-Hohestadt

Binding: Koch, Tübingen

Die Deutsche Bibliothek – CIP-Einheitsaufnahme

Science of Synthesis : Houben–Weyl methods

of molecular transformations /

ed. board: D. Bellus … Managing ed. G. F. Herrmann. –

Stuttgart ; New York : Thieme

Früher u.d. T.: Methoden der organischen Chemie

Category 1. Organometallics

Vol. 1: Compounds with transition metal-carbon

ð-bonds and compounds of groups 10-8(Ni, Pd, Pt, Co,

Rh, Ir, Fe, Ru, Os) / vol. ed. M. Lautens. Responsible

member of the ed. Board B. M. Trost.

Authors N. Chatani .... – 2001

Library of Congress Cataloging in Publication Data

Science of synthesis : Houben–Weyl methods of

molecular transformations.

p. cm.

Includes bibliographical references and index.

Contents: category 1. Organometallics. v. 1. Compounds

with transition metal-carbon [pi]-bonds and

compounds of groups 10-8(Ni, Pd, Pt, Co, Rh, Ir, Fe,

Ru, Os) / volume editor, M. Lautens

ISBN 3-13-112131-9 – ISBN 0-86577-940-6 (v. 1)

1. Organic compounds–Synthesis. I. Title: Houben–

Weyl methods of molecular transformations.

QD262 .S35 2000

547'.2–dc21

00-061560

British Library Cataloguing in Publication Data

Science of Synthesis : Houben–Weyl methods

of molecular transformation

Category 1: Organometallics:

Vol. 1: Compounds with transition metal-carbon

pi-bonds and compounds of groups 10-8(Ni, Pd, Pt, Co,

Rh, Ir, Fe, Ru, Os) . – (Houben–Weyl methods

of organic chemistry)

1. Organicmetallic compounds – Synthesis

I. Lautens, M., II. Chatani, N.

547 .05

ISBN 3-13-112131-9

(Georg Thieme Verlag, Stuttgart)

ISBN 0-86577-940-6

(Thieme New York)

Date of publication: August 29, 2001

27

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28

Biographical Sketch

John Montgomery was born in 1965 in Concord, N.C. He received his

A.B degree from the University of North Carolina at Chapel Hill in

1987, and he carried out undergraduate research under the direction

of Professors Joe Templeton and Maurice Brookhart. He received his

Ph.D. at Colorado State University in 1991 under the direction of Professor

Lou Hegedus. He was an American Cancer Society Postdoctoral

Fellow at the University of California at Irvine from 1991 –1993 with

Professor Larry Overman. In 1993, he began his independent career at

Wayne State University where he is now Professor of Chemistry. His

work at Wayne State has focused on applications of organonickel chemistry in reaction

discovery, synthetic methodology development, and total synthesis, and on the development

of new methods for the synthesis of amino acids utilizing nitroacetates as glycine

templates. He has received a number of awards including an Arthur C. Cope Scholar

Award, a Camille Dreyfus Teacher Scholar Award, and an NSF Career Award.

1.1 Product Class 1: Organometallic Complexes of Nickel

J. Montgomery

1.1 Product Class 1: Organometallic Complexes of Nickel ..................... 31

1.1.1 Product Subclass 1: Nickel Complexes of 1,3-Dienes ...................... 32

Synthesis of Product Subclass 1 ............................................ 32

1.1.1.1 Method 1: Ligand Exchange with Bis(ç 4 -cycloocta-1,5-diene)nickel(0) ... 32

Applications of Product Subclass 1 in Organic Synthesis ..................... 33

1.1.1.2 Method 2: Diene–Diene Cycloadditions ................................ 33

1.1.1.3 Method 3: Diene–Alkyne Cycloadditions ............................... 34

1.1.1.4 Method 4: Diene–Aldehyde Reductive Cyclizations ..................... 35

1.1.1.4.1 Variation 1: Triethylsilane-Mediated Reactions ........................... 35

1.1.1.4.2 Variation 2: Triethylborane-Mediated Reactions ......................... 36

1.1.1.5 Method 5: 1,4-Dialkylation of Dienes .................................. 36

1.1.1.6 Method 6: Hydrocyanation of Dienes .................................. 37

1.1.2 Product Subclass 2: Nickel–Allyl Complexes ............................... 37

Synthesis of Product Subclass 2 ............................................ 37

1.1.2.1 Method 1: Oxidative Addition of Nickel(0) with Allylic Electrophiles ...... 37

1.1.2.2 Method 2: Addition of Allylmagnesium Halides to Nickel(II) Salts ........ 38

1.1.2.3 Method 3: Oxidative Addition of Nickel(0) with Enones in

the Presence of Lewis Acids ................................. 39

1.1.2.4 Method 4: Oxidative Cyclization of Nickel(0) Complexes of

Conjugated Dienes ......................................... 40

Applications of Product Subclass 2 in Organic Synthesis ..................... 41

1.1.2.5 Method 5: Coupling of Allyl Halide Derived Nickel–Allyl Complexes

with Alkyl Halides and Other Electrophiles ................... 41

1.1.2.6 Method 6: Coupling of Enal-Derived Nickel–Allyl Complexes

with Alkyl Halides and Other Electrophiles ................... 42

1.1.2.7 Method 7: Coupling of Nickel–Allyl Complexes with

Main Group Organometallics ............................... 44

1.1.2.7.1 Variation 1: Allylic Ether Derived ð-Allyl Complexes ...................... 44

1.1.2.7.2 Variation 2: Enal-Derived ð-Allyl Complexes ............................. 46

1.1.2.7.3 Variation 3: Allylic Alcohol Derived ð-Allyl Complexes .................... 46

1.1.2.8 Method 8: Addition of Stabilized Nucleophiles to Nickel–Allyl Complexes 47

1.1.2.9 Method 9: Alkyne Insertions with Nickel–Allyl Complexes ............... 47

1.1.2.10 Method 10: Alkene Insertions with Nickel–Allyl Complexes ............... 49

1.1.3 Product Subclass 3: Nickel–Alkyne Complexes ............................ 49

Synthesis of Product Subclass 3 ............................................ 50

1.1.3.1 Method 1: Ligand Exchange with Nickel–Alkene Complexes ............. 50

Applications of Product Subclass 3 in Organic Synthesis ..................... 51

1.1.3.2 Method 2: Coupling of Alkynes with Carbon Dioxide .................... 51

1.1.3.3 Method 3: Coupling of Alkynes with Isocyanides ....................... 52

30

1.1.3.4 Method 4: Coupling of Alkynes with Aldehydes ......................... 52

1.1.3.5 Method 5: Coupling of Two Alkynes ................................... 55

1.1.3.6 Method 6: Coupling of Alkynes with Alkenes ........................... 56

1.1.3.7 Method 7: [2 +2+2] Cycloadditions .................................... 58

1.1.3.8 Method 8: Alkyne Carbonylation ...................................... 60

1.1.3.9 Method 9: Alkyne Hydrocyanation ..................................... 60

1.1.3.10 Method 10: Alkyne Hydrosilylation ...................................... 60

1.1.3.11 Method 11: Alkyne Carbozincation ..................................... 61

1.1.4 Product Subclass 4: Nickel–Alkene Complexes ............................ 62

Synthesis of Product Subclass 4 ............................................ 62

1.1.4.1 Method 1: Ligand Exchange with Nickel(0) Complexes .................. 62

Applications of Product Subclass 4 in Organic Synthesis 63

1.1.4.2 Method 2: Conjugate Addition to Electrophilic Double Bonds ........... 63

1.1.4.2.1 Variation 1: Organoaluminums ......................................... 63

1.1.4.2.2 Variation 2: Organozincs ............................................... 64

1.1.4.2.3 Variation 3: Organozirconiums ......................................... 66

1.1.4.2.4 Variation 4: Direct Conjugate Addition of Alkyl Halides ................... 67

1.1.4.3 Method 3: Coupling of Two Alkenes ................................... 68

1.1.4.4 Method 4: Alkene Carbonylation ...................................... 71

1.1.4.5 Method 5: Alkene Hydrocyanation ..................................... 72

1.1.4.6 Method 6: Alkene Hydrosilylation ..................................... 73

1.1.4.7 Method 7: Alkene Hydroalumination .................................. 73

1.1.4.8 Method 8: Alkene Hydrozincation ..................................... 75

1.1.4.9 Method 9: Alkene Carbozincation ..................................... 76

1.1.4.10 Method 10: Homo-Diels–Alder Cycloadditions ........................... 77

1.1.4.11 Method 11: Alkene Polymerization ...................................... 77

1.1 Product Class 1:

Organometallic Complexes of Nickel

J. Montgomery

General Introduction

This contribution provides an overview of contemporary synthetic methods of broad applicability

that involve the preparation and use of nickel ð-complexes as starting materials

or reactive intermediates. Numerous excellent reviews on the chemistry of nickel

have appeared that are complementary to this contribution in subject and scope. An outstanding

review by Chetcuti describes the known ð-complexes of nickel, [1] and several

other structural classes of nickel complexes have been reviewed; [2–4] ó-bonded organonickel

compounds are reviewed in Houben–Weyl, Vol. 13/9b, pp 632–700. The historical development

and early applications of nickel chemistry have been reviewed by Wilke [5] and

Jolly, [6] industrial applications have been reviewed by Keim, [7] and several other reviews

on specific groups of synthetic transformations have appeared. [8–12,187] The organometallic

chemistry of nickel has a rich history dating back more than 100 years. [5] Despite its long

history, fundamentally new reactions are still being developed at a rapid pace. Furthermore,

existing reactions are being applied in new and creative ways to solve long-standing

challenges in organic synthesis. More and more of the synthetic organic community is

beginning to realize that nickel catalysis provides preparatively convenient reactions of

broad scope in a variety of contexts. In many cases, the reactivity exhibited by nickel may

not be achieved by any other transition element. At this time, organonickel chemistry

seems to be well poised to provide an increasing number of new reactions and interesting

mechanistic questions, as well as to gain an increasingly important role in the organic

chemist s repertoire of mainstream synthetic transformations.

The most commonly employed catalysts in nickel-catalyzed reactions are bis(acetylacetonato)nickel(II)

(1), which is commercially available, bis(ç 4 -cycloocta-1,5-diene)nickel(0)

(2) which is also commercially available or may be easily prepared (Scheme 1), [13]

and dichlorobis(triphenylphosphine)nickel(II) (3) which can also be easily prepared

(Scheme 2). [14]

SAFETY: Tetracarbonylnickel(0) should be handled with extreme caution due to its

volatility and high toxicity. All nickel compounds should be handled with care since

many are cancer suspect agents. [188]

Scheme 1 Synthesis of Bis(ç 4 -cycloocta-1,5-diene)nickel(0) [13]

Ni(acac)2

1

1. cod, THF, −78 oC 2. DIBAL-H, THF, −78 oC 72%

Ni(cod)2

2

Scheme 2 Synthesis of Dichlorobis(triphenylphosphine)nickel(II) [14]

NiCl 2•6H 2O

Ph 3P, AcOH, rt, 24 h

84%

NiCl2(PPh3) 2

3

31

for references see p 79

32 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2): [13]

A 250-mL Schlenk flask equipped with a stirring bar and a pressure-equalizing addition

funnel was charged with technical grade [Ni(acac) 2](1; 4.67 g, 0.0182 mol, 1.00 equiv) and

briefly dried under vacuum with a heat gun. After cooling and establishing a positive N 2

atmosphere, the solid was suspended in THF (25 mL) and treated with cycloocta-1,5-diene

(7.93 g, 0.0723 mol, 4.00 equiv). The suspension was cooled to –78 8C with a dry ice/acetone

bath to give a green slurry. A 1.0 M soln of DIBAL-H in THF (45.4 mL, 0.0454 mol,

2.50 equiv) was transferred to the addition funnel under N 2 via a cannula. The DIBAL-H

soln was added over 1 h to give a dark, reddish-brown soln which was allowed to warm

to 0 8C over a 1 h period. The soln was treated with Et 2O (65 mL) to give a light yellow precipitate.

The suspension was cooled to –788C and allowed to stand for 12 h to complete

precipitation. The solid product was isolated by filtration at –788C via a filter paper tipped

cannula, washed with cold Et 2O (15 mL portions) until the brown residues were removed,

and dried in vacuo. [Ni(cod) 2](2) was obtained as a pale yellow powder and was suitable for

immediate use; yield: 3.2 g (72%).

The material may be recrystallized by the following procedure. In a glovebox, crude

[Ni(cod) 2] (3.2 g) was dissolved in a minimum volume of toluene (25 mL • g –1 )at258C and

rapidly filtered through Celite to remove metallic nickel. The deep yellow soln was allowed

to stand at –788C for 12 h to give bright yellow-orange needles. Removal of the supernatant

at –788C through a filter paper tipped cannula, followed by a pentane wash

(2 ” 15 mL), gave pure material; yield: 1.28g (40%).

Dichlorobis(triphenylphosphine)nickel(II) (3): [14]

A soln of NiCl 2 •6H 2O (2.38g, 0.01 mol) in H 2O (2 mL) was diluted with glacial AcOH

(50 mL), and Ph 3P (5.25 g, 0.02 mol) in glacial AcOH (25 mL) was added. The olive-green microcrystalline

precipitate, when kept in contact with its mother liquor for 24 h, gave dark

blue crystals which were filtered off, washed with glacial AcOH, and dried in a vacuum

desiccator (H 2SO 4, KOH); yield: 3.81 g (84%).

1.1.1 Product Subclass 1:

Nickel Complexes of 1,3-Dienes

Nickel complexes with 1,3-dienes are important intermediates in a variety of catalytic

processes. In contrast to many classes of metal–diene complexes, such as those of iron

and palladium in which metal complexation activates the ð-system towards nucleophilic

attack, (ç 4 -diene)nickel complexes are most useful in cycloaddition processes and in couplings

to polar ð-systems such as carbonyls. Few examples of diene–nickel complexes are

structurally well characterized, but they are commonly invoked in the mechanisms of

many synthetic procedures.

Synthesis of Product Subclass 1

1.1.1.1 Method 1:

Ligand Exchange with Bis(ç 4 -cycloocta-1,5-diene)nickel(0)

The high reactivity of nickel–diene complexes, which renders them very useful in catalytic

applications, makes their isolation quite difficult in most cases. The few cases in which

nickel–1,3-diene complexes (e.g., 4) have been isolated generally involve displacement of

a ligand with a low binding constant such as cyclooctadiene. This should, in theory, be

possible using nickel(II) salts reduced in situ, although bis(ç 4 -cycloocta-1,5-diene)nickel(0)

or (ç 6 -cyclododeca-1,5,9-triene)nickel(0) (Scheme 3; cdt = cyclododeca-1,5,9-triene) are typically

employed. [15]

1.1.1 Nickel Complexes of 1,3-Dienes 33

Scheme 3 Preparation of a (ç 4 -Buta-1,3-diene)nickel(0) Complex [15]

Ni(cdt)

+

P P

Pri Pri Pri Pri +

Et 2O

−78 o C

85%

Pri P

P

Ni Pri Pri Pri Pri [ì-(1,2,3,9-ç:6,7,8,10-ç)-3,6-Dimethyleneocta-1,7-diene]bis[ethane-1,2-diylbis(diisopropylphosphine-k

2 P)]nickel (4): [15]

3,6-Dimethyleneocta-1,7-diene (0.56 mL, 3.30 mmol) and iPr 2P(CH 2) 2P-iPr 2 (1.03 mL,

3.30 mmol) were added to a suspension of Ni(cdt) (0.83 g, 3.31 mmol) in Et 2O (200 mL)

cooled to –788C. The mixture was allowed to warm to rt over 5 h. A yellow solid precipitated

which then redissolved to give a red soln. The mixture was stirred for 2 d, filtered

through a pad of Avicel, and evaporated to dryness. The residue was dissolved in toluene

(50 mL) at 508C and filtered. Cooling the filtrate to –788C gave compound 4 as red needles

which were washed with precooled pentane (10 mL) at –788C and dried under high vacuum;

yield: 1.09 g (85%).

Applications of Product Subclass 1 in Organic Synthesis

1.1.1.2 Method 2:

Diene–Diene Cycloadditions

The most widely used application of nickel–diene complexes is the dimerization of 1,3dienes.

Pioneering studies by Wilke demonstrated many different modes of coupling, including

dimerization, trimerization, and oligomerization of 1,3-dienes. [5,7] An overview of

the product classes that may be obtained from 1,3-dienes is provided in Scheme 4 (see also

Houben–Weyl, Vol. E 18, pp 93 and 932–937). The initially formed nickel complexes 5 and

6 have not been isolated. However, the complexes may be stabilized by the addition of

phosphines, and ð-allyl complexes 7–9 have been prepared and characterized.

Scheme 4 Products of Nickel-Catalyzed Butadiene Dimerization and Trimerization [5,7]

L nNi

[Ni(0)] L nNi L nNi

5

Ni

9

7

L nNi

8

6

Pr i

4

Ni

P

Pr i

for references see p 79

34 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Despite the detail in which this process has been studied, its synthetic utility is limited

owing to the low regio- and/or stereoselectivity in reactions of unsymmetrical dienes.

This limitation was overcome in studies by Wender, on the intramolecular variant. [16–21]

An impressive variety of structurally complex eight-membered rings can be synthesized

by the nickel-catalyzed [4+4]-cycloaddition reaction (Scheme 5). This method provides

one of the most direct and efficient procedures for synthesizing eight-membered rings.

Scheme 5 A Synthetic Application of a Nickel-Catalyzed [4+4] Cycloaddition [19]

OTBDMS

10

20% Ni(cod)2 2

60% P(OC6H4-2-Ph)3 toluene, 85 oC, 3 h

74%

OTBDMS

(7R ∗ ,10R ∗ )-11

+

7:1

OTBDMS

(7R ∗ ,10S ∗ )-11

(7R*,10R*)-10-(tert-Butyldimethylsiloxy)-7-methylbicyclo[5.3.1]undeca-1,5-diene

[(7R*,10R*)-11] and (7R*,10S*)-10-(tert-Butyldimethylsiloxy)-7-methylbicyclo[5.3.1]undeca-

1,5-diene [(7R*,10S*)-11]: [19]

To a 200-mL Schlenk flask were added bis(diene) 10 (151 mg, 0.517 mmol), toluene

(100 mL), heptadecane (50 ìL, GC internal standard), and tris(biphenyl-2-yl) phosphite

(167 mg, 0.310 mmol) in toluene (10 mL) under argon. The flask was then heated to 85 8C

and 0.09 M [Ni(cod) 2](2) in toluene (1.15 mL) was added by syringe from a stock soln, and

the flask was sealed. Monitoring of the heptadecane/product ratio by GC indicated the

completion of the reaction (3 h). The reaction was allowed to cool and then quenched by

exposure to air for 1 h. Filtration of the toluene soln through a plug of silica gel and elution

with Et 2O removed the nickel salts. Concentration in vacuo followed by flash chromatography

(silica gel, 20 mm ” 15 cm, hexane) provided (7R*,10R*)-11 and (7R*,10S*)-11

as clear oils; yields: 97.7 mg (65%) and 14.0 mg (9%), respectively.

1.1.1.3 Method 3:

Diene–Alkyne Cycloadditions

The nickel-catalyzed [4+2] reaction is also a highly useful synthetic procedure. [22–26] At

first glance, it may seem less useful because a strictly thermal counterpart does exist, unlike

the nickel-catalyzed [4+4] cycloaddition. However, compared with the thermal process,

nickel-catalyzed [4+2] cycloadditions proceed at low temperatures and are not subject

to the often restrictive electronic requirements of the thermal Diels–Alder reaction

(Scheme 6). Despite the involvement of a stepwise pathway, the reaction has been shown

to be stereospecific.

Scheme 6 A Synthetic Application of a Nickel-Catalyzed [4+2] Cycloaddition [26]

MeO

TMSO

OMOM

10% Ni(cod) 2 2

20% P[OCH(CF3) 2] 3

cyclohexane, rt, 1 h

90%

MeO

OMOM

12 13

H

OTMS

1.1.1 Nickel Complexes of 1,3-Dienes 35

(1R*,5S*,7aR*)-4-[2-(Methoxymethoxy)ethyl]-5-(4-methoxyphenyl)-7amethyl-1-(trimethylsiloxy)-2,3,5,7a-tetrahydro-1H-indene

(13): [26]

To an acid-washed, base-washed, 200-mL Schlenk flask was added dienyne 12 (665 mg,

1.595 mmol, 1.0 equiv). Under a positive N 2 flow, freshly distilled cyclohexane (160 mL)

and tris[2,2,2-trifluoro-1-(trifluoromethyl)ethyl] phosphite (170 mg, 0.319 mmol,

0.2 equiv) were added, followed by 0.075 M [Ni(cod) 2](2) in THF (2.13 ìL, 0.160 mmol,

0.1 equiv) and the reaction was stirred at rt for 1 h. The clear soln slowly changed to a golden

yellow soln which was then warmed to 808C and stirred for 17.5 h. The reaction was

quenched by opening to air and stirring for 30 min. Purification by flash filtration

through a 2.5-cm plug of silica gel (Et 2O/hexanes 1:4) followed by flash chromatography

(silica gel, Et 2O/hexanes 1:7) gave the cyclohexa-1,4-diene 13; yield: 600 mg (90%).

1.1.1.4 Method 4:

Diene–Aldehyde Reductive Cyclizations

Additions of dienes to aldehydes have emerged as a synthetically useful reaction class.

The reaction is formally a reductive coupling and may produce either ª,ä-unsaturated or

ä,å-unsaturated alcohols as products (Scheme 7). [27–31] Two mechanisms have been proposed,

and it is likely that the reaction is initiated either by formation of an oxametallacycle

or by hydrometalation of the diene.

Scheme 7 Diene–Aldehyde Reductive Coupling [27–31]

O

R 1 H

R2 +

Ni catalyst

reducing agent

1.1.1.4.1 Variation1:

Triethylsilane-Mediated Reactions

OH

R 1 R 2

or

OH

R 1 R 2

Studies by Mori demonstrate that triethylsilane and dienals undergo reductive cyclization

in the presence of bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2) and triphenylphosphine (1:2) to

produce the silyl ether of cycloalkanols; [27–30] in this instance, ª,ä-unsaturated products

are obtained. However, if the reaction is carried out in the presence of cyclohexa-1,3-diene,

an analogous reaction proceeds to give ä,å-unsaturated products. This effect is reported

to be derived from selective diene hydrometalation followed by addition of the organonickel

intermediate to the tethered aldehyde. The reaction proceeds with five-, six-,

and seven-membered ring formation and with heterocyclic substrates. Several synthetic

applications of this cyclization methodology are reported (Scheme 8). Intermolecular

processes with simple dienes and aldehydes to afford ª,ä-unsaturated silyl ethers are

also possible.

Scheme 8 Reductive Coupling with Triethylsilane [27–30]

O

H

N

CHO

20 mol% Ni(cod)2 2

40 mol% Ph3P Et3SiH (5 equiv), THF

O

H

N

40%

OTES

+

O

H

N

38%

OTES

for references see p 79

36 Science of Synthesis 1.1 Organometallic Complexes of Nickel

1.1.1.4.2 Variation2:

Triethylborane-Mediated Reactions

The intermolecular process between simple dienes and aldehydes is reported by Tamaru.

[31] Triethylborane is employed as the reducing agent, and yields are good for a variety

of substituted electron-rich and electron-poor dienes. Interestingly, reactions employing

triethylborane and bis(acetylacetonato)nickel(II) (1) produce 4,5-unsaturated alcohols

(Scheme 9), whereas reactions employing bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2), triphenylphosphine,

and triethylsilane produce 3,4-unsaturated silyl ethers. The mechanistic basis

for this reversal of regioselectivity has not been established.

Scheme 9 Reductive Coupling with Triethylborane [31]

O

BEt3 (2.4 equiv)

OH

CO2Me +

H Ph

10 mol% Ni(acac) 2 1

91%

Ph

CO2Me 14 15

Methyl (2R*,4E)-2-[(R*)-Hydroxy(phenyl)methyl]hex-4-enoate (15): [31]

Into a N 2-purged flask containing [Ni(acac) 2](1; 12.8mg, 0.05 mmol) were introduced successively

freshly dried (Na benzophenone ketyl) THF (3 mL), methyl (2E,4E)-hexa-2,4-dienoate

(14; 2.52 g, 20 mmol), PhCHO (530 mg, 5 mmol), and 1 M BEt 3 in hexane (12.0 mL)

via a syringe. The homogeneous mixture was stirred at rt for 66 h until the PhCHO disappeared

completely. After dilution with EtOAc (50 mL), the mixture was washed successively

with 2 M HCl, sat. NaHCO 3, and sat. NaCl, and then dried (MgSO 4), and concentrated in

vacuo. The residual oil was subjected to column chromatography (silica gel, hexanes/

EtOAc 16:1) to give an analytically pure sample of 15; yield: 1.07 g (91%).

1.1.1.5 Method 5:

1,4-Dialkylationof Dienes

Studies by Chang demonstrate that two molecules of an iodoalkene (e.g., 17) readily add

across a 1,3-diene (e.g., 16) to give predominantly symmetrical 1,4-addition products such

as (18) (Scheme 10). [32] Nickel(0) is consumed in the reaction; however, the use of zinc

powder as a reductant allows the nickel to be used in catalytic amounts. Generally, a cis

orientation of the internal double bond is obtained. With cyclic dienes, a cis orientation of

the two alkenyl substituents is obtained.

Scheme 10 1,4-Dialkylation of a Conjugated Diene [32]

16

+

O

NiBr2, Zn

Ph3P, MeCN

O O

82%

I

17 18

2,3-Dimethyl-1,4-bis(3-oxocyclohex-1-enyl)but-2-ene (18): [32]

To a 50-mL side-arm flask were added NiBr 2 (0.0204 g, 0.100 mmol), Ph 3P (0.0262 g,

0.100 mmol), and Zn powder (0.082 g, 1.25 mmol). The system was purged with N 2 three

times. MeCN (0.50 mL), 3-iodocyclohex-2-en-1-one (17; 0.222 g, 1.00 mmol), and 2,3-dimethylbuta-1,3-diene

(16; 0.246 g, 3.00 mmol) were added by syringe, and the soln was

stirred at 808C for 2 h. During the reaction the soln gradually turned from yellow to red.

At the end of the reaction the system was filtered through Celite. The filtrate was concen-

1.1.2 Nickel–Allyl Complexes 37

trated on a rotary evaporator and was separated by column chromatography (silica gel,

EtOAc/hexane) to afford 18 as an oil; yield: 0.112 g (82%).

1.1.1.6 Method 6:

Hydrocyanation of Dienes

The hydrocyanation of butadienes is the basis of DuPont s process for the production of

adiponitrile [hexanedinitrile (19), Scheme 11]. [33,34] The first step of the process involves

hydrocyanation of buta-1,3-diene to produce an isomeric mixture of pentenenitriles. In a

second step, nickel-catalyzed double-bond isomerization occurs to produce pent-4-enenitrile

followed by alkene hydrocyanation to produce adiponitrile (19). The details of the alkene

hydrocyanation reaction are discussed in further detail in Section 1.1.4.5.

Scheme 11 Hydrocyanation of Buta-1,3-diene [33,34]

HCN, Ni(0)

1.1.2 Product Subclass 2:

Nickel–Allyl Complexes

CN

+

CN

Ni(0)

CN

HCN, Ni(0) CN

NC

Nickel complexes with ç 3 -allyl ligands are important intermediates in a variety of catalytic

processes. The most straightforward methods of preparation involving the addition of

allyl electrophiles to nucleophilic nickel complexes and the addition of allyl nucleophiles

to electrophilic nickel complexes unambiguously lead to ð-allyl complexes. Aside from

these general classes of reactions, many other important catalytic processes potentially

involve ð-allyl intermediates although their intermediacy has not, in most cases, been established.

A very large variety of synthetic procedures involving nickel–ð-allyl complexes

have been developed including the addition of hard and soft nucleophiles, addition of

S N2-active and S N2-inactive electrophiles, and migratory insertions of alkenes and alkynes.

Synthesis of Product Subclass 2

1.1.2.1 Method 1:

Oxidative Additionof Nickel(0) with Allylic Electrophiles

A variety of nickel(0) complexes, when treated with allylic electrophiles, afford ð-allyl

complexes (see also Houben–Weyl, Vol. E 18, pp 64 and 76). [6,8] In early studies, tetracarbonylnickel(0)

was widely employed. However, owing to its extreme toxicity, it is now rarely

used. Direct treatment of bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2) with allyl halides such as

20 is now the method of choice for the stoichiometric preparation of nickel–ð-allyl complexes.

In the absence of strong donor ligands such as phosphines, halo-bridged dimers

(e.g., 21) are typically obtained (Scheme 12). [35] In the presence of phosphines, monomeric

species such as 22 may be obtained. [35] Other less-electrophilic allylic substrates such as

allylic ethers and allylic alcohols also serve as precursors to nickel–ð-allyl complexes in

catalytic procedures. However, these precursors are less widely used than allyl halides in

the stoichiometric preparation of the ð-allyl complexes.

19

for references see p 79

38 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Scheme 12 Preparation of a Nickel–ç 3 -Allyl Complex from Nickel(0) and

Allyl Electrophiles [35]

Ni(cod) 2 +

2

OMe

20

Br

MeO Ni Ni OMe

Br

21

benzene

4−25 oC 55%

Br

MeO Ni Ni OMe

Br

21

+ Ph3P Et2O

97%

MeO

Br

Ni

PPh3

22

Di-ì-bromobis[(ç 3 -2-methoxyallyl)nickel] (21): [35]

[Ni(cod) 2](2; 2.63 g, 9.60 mmol) was suspended in argon-sat. benzene (40 mL) in a 100-mL

two-necked flask fitted with a stopcock and a dropping funnel and was cooled to 4 8C. 3-

Bromo-2-methoxypropene (20; 1.45 g, 9.6 mmol) in benzene (5 mL) was added dropwise to

the stirred slurry. A deep red color developed immediately, and some metallic nickel precipitated.

The mixture was allowed to warm to 25 8C and was stirred at this temperature

for 0.5 h. It was then filtered under argon and concentrated to ~ 20 mL under aspirator

vacuum, and petroleum ether (75 mL) was added. The resulting red slurry was cooled to

–20 8C to complete crystallization, and the supernatant was removed with a syringe. Compound

21 was obtained as a brick-red solid; yield: 1.00 g (55%).

Bromo(ç 3 -2-methoxyallyl)(triphenylphosphine)nickel (22): [35]

Ph 3P (0.29 g, 1.10 mmol) in Et 2O (5 mL) was added to complex 21 (0.23 g, 0.55 mmol) in

Et 2O (10 mL) under argon at 25 8C. An orange precipitate formed immediately. After stirring

at 258C for 0.5 h the slurry was allowed to settle, and the supernatant was removed

with a syringe. Washing with Et 2O (10 mL) and drying under vacuum afforded compound

22; yield: 0.50 g (97%).

1.1.2.2 Method 2:

Additionof Allylmagnesium Halides to Nickel(II) Salts

Electrophilic nickel(II) salts, when treated with allyl organometallics, afford nickel(II)–ðallyl

complexes. [8,36] Rather than producing dimeric halo-bridged complexes as observed

by the oxidative addition route (Section 1.1.2.1), monomeric bis(allyl) complexes are instead

obtained (Scheme 13). Although both the method described in Section 1.1.2.1 and

this method afford structurally different ð-allyl complexes, disproportionation may, in

some instances, allow the interconversion of a bis(allyl) complex 23 and the corresponding

halo-bridged dimer 24 if a dihalonickel species is present.

Scheme 13 Preparation of a ç 3 -Allylnickel Complex from Nickel(II) and

Allyl Nucleophiles [8,36]

MgBr

Ni

23

+

NiBr2

+

NiBr 2

Et2O, −10 o C

Ni

23

Br

Ni Ni

Br

24

+

MgBr2

1.1.2 Nickel–Allyl Complexes 39

Bis(ç 3 -2-methylallyl)nickel (23): [8]

Following the general procedure of Wilke, [37,190] anhyd NiBr 2 (18.7 g, 0.086 mmol) was suspended

in anhyd Et 2O (100 mL) in a 1-L three-necked flask fitted with a 500-mL dropping

funnel, a mechanical stirrer, and a Claisen head containing a low-temperature thermometer

and a three-way stopcock. The system was alternately evacuated to aspirator vacuum

and filled with inert gas (N 2 or argon) several times, and cooled to –108C. 2-Methylallylmagnesium

bromide (27.1 g, 0.17 mol) in Et 2O (300 mL) was added dropwise to the vigorously

stirred soln over 2 h. The mixture was stirred for an additional 0.4 h at –108C,

warmed to 258C, and filtered under inert gas. (The simplest technique is to use a reaction

flask with a fritted disk and two-way stopcock attached to the bottom; the soln can be

forced through the frit with positive pressure into a second flask which is also under inert

gas.) The residue was washed with Et 2O (50 mL), filtered, and the combined Et 2O filtrates

were concentrated under aspirator vacuum at –308C. Pentane (125 mL) was added, the resulting

slurry was filtered under inert gas (most of the pentane was removed from the filtrate

at aspirator vacuum), and the remaining brown soln was cooled to –788C. Impure

brown crystals (mp 358C) of 23 were isolated by decanting the supernatant liquid under

inert gas. (It is convenient to store the complex at this stage at –208C and then sublime the

requisite quantity into the vessel for further reaction.) Sublimation at 258C/0.1 Torr with

a –788C receiver afforded yellow crystals. No precise yield has been reported for this

method.

1.1.2.3 Method 3:

Oxidative Addition of Nickel(0) with Enones in the Presence of Lewis Acids

An advance by Mackenzie has made nickel–ð-allyl complexes accessible from enals and

enones. [38,39] In a reaction that is mechanistically analogous to Method 1 in Section

1.1.2.1, enals, when treated with bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2) in the presence

of chlorosilanes, afford chloro-bridged dimeric ç 3 -allylnickel complexes such as 25

(Scheme 14). Enones are less reactive in the process and require pyridine to facilitate the

oxidative addition. Rather than using bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2), a more convenient

and less expensive alternative involves the in situ reduction of dichlorotetrakis(pyridine)nickel(II)

(26) with sodium metal in the presence of cyclooctadiene to give

enone-derived ç 3 -allylnickel complexes (e.g., 27).

Scheme 14 Preparation of Enone-Derived ç 3 -Allylnickel Complexes [38,39]

H

O

NiCl2 6H2O

+

Ni(cod) 2

2

py

+

TMSCl

NiCl2(py)4

26

86%

TMSO

1. 2Na, excess cod

2. cyclopent-2-enone

TBDMSCl

Cl

Ni Ni

Cl

25

OTMS

NiCl(py) 2

27

OTBDMS

Di-ì-chlorobis{[ç 3 -1-(trimethylsiloxy)allyl]nickel(II)} (25): [38]

In a drybox, a 50-mL Schlenk tube was charged with [Ni(cod) 2](2; 500 mg, 1.82 mmol,

1.00 equiv). On a Schlenk line, a soln of propenal (244 ìL, 3.64 mmol, 2.00 equiv) in benzene

(8mL) in a 25-mL Schlenk vessel was treated with (MeO)(TMSO)C=CMe 2 (185 ìL,

0.909 mmol, 0.500 equiv; added as a proton-scavenging reagent), stirred for 5 min, and

for references see p 79

40 Science of Synthesis 1.1 Organometallic Complexes of Nickel

then transferred by cannula onto the [Ni(cod) 2]. The resulting purple-red slurry was stirred

for 10 min and then treated with TMSCl (462 ìL, 3.64 mmol, 2.00 equiv) to afford a deep

red soln. After 45 min, the volatiles were removed at 0.1 Torr to obtain an orange-red powder.

This was extracted with pentane (20 mL) through a filter paper tipped cannula. The

clear red filtrate was concentrated under vacuum to ca. 5 mL and then cooled to –208C for

24 h to induce crystallization. The precipitate was isolated by removal of the supernatant

through a filter paper tipped cannula while maintaining the mixture at –208C, and

washed with pentane (2 ” 3 mL) to afford 25 as a burgundy-red crystalline solid; yield:

0.35 g (86%).

[(1,2,3-ç)-1-(tert-Butyldimethylsiloxy)cyclopentenyl]chlorobis(pyridine)nickel(II) (27): [38]

A 100-mL Schlenk tube equipped with a magnetic stirring bar and rubber septum was

charged with [NiCl 2(py) 4](26; 10.0 g, 22.4 mmol, 1.00 equiv) and evacuated and refilled

with N 2 twice to establish an inert atmosphere. THF (40 mL) was added, followed by cycloocta-1,5-diene

(8.20 mL, 67.2 mmol, 3.00 equiv), and the resulting mixture was cooled to

0 8C. A second 100-mL Schlenk tube containing Na metal strips (1.03 g, 44.8mmol,

2.00 equiv; each ca. 2 cm ” 0.4 cm ” 0.1 cm) was connected to this flask with a flexible

adapter (available from Aldrich) under a rapid flow of N 2 (an inert atmosphere having previously

been established in the second Schlenk tube and adapter by capping the free end

of the adapter and evacuating and refilling with N 2). The Na strips were then transferred

to the stirred 0–5 8C mixture in four portions over 1.5 h to give, after an additional 40 min at

0–5 8C, a very dark brown (but not black) supernatant, a small amount of precipitated yellow

[Ni(cod) 2], and no apparent blue [NiCl 2(py) 4]. This was treated with a soln of cyclopent-2enone

(1.88mL, 22.4 mmol, 1.00 equiv) and TBDMSCl (3.38g, 22.4 mmol, 1.00 equiv) in THF

(15 mL) and stirred at 258C for 30 min to afford an orange mixture. The soln of 27 thus obtained

was directly used in coupling reactions; no purification or yield was reported.

1.1.2.4 Method 4:

Oxidative Cyclization of Nickel(0) Complexes of Conjugated Dienes

ð-Allyl complexes are commonly invoked as intermediates in the reactions of (ç 4 -diene)nickel

complexes. If a nickel(0) complex possesses both a conjugated diene ligand and another

ð-bound ligand, an oxidative cyclization may occur to form a ð-allyl ligand within a

nickel(II) metallacycle. Much of the [4+4]- and [4 +2]-cycloaddition chemistry described

for ç 4 -diene complexes probably involves the intermediacy of nickel metallacycles that

possess a ç 3 -allyl ligand. Oxidative cyclizations of this type are also useful in the stoichiometric

preparation of nickel–ð-allyl complexes. The spectator ligand properties play a significant

role in determining the position of the equilibrium for oxidative cyclization–reductive

cleavage processes (Scheme 15). [40]

Scheme 15 Ligand Dependence in the Formation of ð-Allyl Complexes by

Oxidative Cyclization [40]

CO2Me + Ni(cod)2 + Ph3P

MeO2C

Ph3P Ni

2

MeO2C CO 2Me

+ Ni(cod) 2 + bipy

2

MeO2C

MeO 2C

Ni(bipy)

1.1.2 Nickel–Allyl Complexes 41

Applications of Product Subclass 2 in Organic Synthesis

1.1.2.5 Method 5:

Coupling of Allyl Halide Derived Nickel–Allyl Complexes

with Alkyl Halides and Other Electrophiles

Dimeric chloro-bridged nickel–ð-allyl complexes (e.g, 28) undergo a facile coupling reaction

with a variety of electrophiles. Highly polar solvents are required, and light is often

used to initiate the process. Interestingly, sp 2 -hybridized halides are more reactive than

sp 3 -hybridized halides. Coupling generally occurs at the less-substituted terminus of the

ð-allyl complex. Whereas couplings with aryl, alkenyl, and alkyl halides are often quite

efficient, leading to products such as 29 (Scheme 16), couplings between nickel–ð-allyl

complexes and allylic electrophiles are of limited utility since allylic scrambling leading

to homocoupling often occurs (Scheme 17). [8]

Scheme 16 Couplings of Nickel–ð-Allyl Complexes with Alkyl, Alkenyl, and Aryl Halides [8]

Br

Ni Ni

Br

28

+

2 R 1 X

DMF

Scheme 17 Potential Scrambling with Allylic Electrophiles [8]

R2 R2 R

Br

Ni Ni

Br

1

R 1

+

R 2

R 3

R 2

In addition to the widely used couplings of alkyl, alkenyl, and aryl halides with ð-allyl

complexes, couplings of nickel–ð-allyl complexes with aldehydes and ketones are also efficient.

[35,41] Couplings involving the 3-bromo-2-methoxypropene derived complex 30 are

particularly useful as a method for introducing the acetonyl functional group into organic

substrates to give ketones such as 31 (Scheme 18).

Scheme 18 The Use of a 3-Bromo-2-methoxypropene Derived Complex for

the Introduction of the Acetonyl Functionality by Coupling with Iodobenzene [35,41]

Br

MeO Ni Ni OMe

Br

+

PhI

Br

R 1

+

DMF

30 31

A detailed mechanistic study of the coupling of ð-allyl complexes and organic halides has

been carried out. [42] A mechanism involving the establishment of a pre-equilibrium between

bis(allyl)nickel complexes and monoallyl halo-bridged dimers is proposed. A single-electron-transfer

mechanism then initiates cross coupling via nickel(I) intermediates.

R 1

R 2

29

O

R 1

R 3

Ph

+

R 3

for references see p 79

42 Science of Synthesis 1.1 Organometallic Complexes of Nickel

4-(2-Methylallyl)cyclohexanol (29,R 1 = 4-hydroxycyclohexyl); Typical Procedure: [8]

Di-ì-bromobis[(ç 3 -2-methylallyl)nickel] (28; 0.55 g, 1.42 mmol) was weighed under N 2 or

argon into a flask equipped with a three-way stopcock and rubber septum. DMF (4.0 mL,

distilled at 508C/30 Torr from CaH 2 and rendered air-free by alternately evacuating and

filling with inert gas several times) was added via a syringe. Then a soln of trans-4-iodocyclohexanol

(0.643 g, 2.84 mmol, prepared by reaction of 1,4-epoxycyclohexane with HI,

mp 60–61 8C) in DMF (2.0 mL, air-free as above) was added rapidly by syringe. After addition,

the soln was allowed to warm to 23 8C during 1 h and stirred at this temperature for

22 h under a positive pressure of an inert gas. The mixture, now green, was poured into

Et 2O and the Et 2O soln was washed with H 2O (4 ”), dried (MgSO 4), and concentrated at aspirator

vacuum to afford 29 (R 1 = 4-hydroxycyclohexyl); yield: 388 mg (89%).

Other alkyl halides used, together with products and yields, were iodobenzene fi (2methylallyl)benzene

(98%), iodocyclohexane fi (2-methylallyl)cyclohexane (91%), bromoethene

fi 2-methylpenta-1,4-diene (70%).

1-Substituted Acetones; General Procedure: [35]

Reactions were carried out in a 100-mL one-necked flask with a side arm capped with a

septum, and containing a magnetic stirring bar and fitted with a stopcock. The reaction

flask was flushed with argon and placed in a N 2-filled glove bag along with a flask containing

complex 30. The desired amount of 30 (1–2 mmol) was transferred into the reaction

flask through the side arm (in the glove bag), the side arm was recapped with the septum,

and the reaction flask was removed from the glove bag. The complex was dissolved in argon-sat.

DMF (30 mL solvent/mmol complex), giving a deep red soln. Liquid reactants (1.8–

3.6 mmol) were directly added to the reaction flask, while solid reactants were dissolved

in a minimum amount of DMF and added as solns. With organic halides as reactants, the

soln turned emerald-green upon completion, whereas with ketones and aldehydes it

turned brown-orange. Upon completion, the mixture was poured into a separatory funnel

containing 3% aq HCl (50 mL) and Et 2O (50 mL), and was thoroughly shaken. The aqueous

phase was washed with Et 2O (3 ” 20 mL), and the combined Et 2O extracts were washed

with 3% aq HCl (3 ” 50 mL) to ensure complete hydrolysis of the enol ether and complete

removal of DMF. The organic phase was dried (MgSO 4) and the solvent was removed under

vacuum. The crude product, usually more than 90% pure, was purified by preparative layer

chromatography (silica gel) or distillation.

1.1.2.6 Method 6:

Coupling of Enal-Derived Nickel–Allyl Complexes

with Alkyl Halides and Other Electrophiles

Most features of the couplings described for allyl halide-derived nickel–ð-allyl complexes

also hold true for the closely related enone- and enal-derived complexes. Once the enoneor

enal-derived complex is generated (e.g., 27, 32), couplings with alkyl halides generally

are accomplished in dimethylformamide upon photolysis of the mixture with a sunlamp,

to give products such as 33 and 34 (Scheme 19). [38] Strong donor ligands are not required

for coupling reactions of enals, whereas couplings involving enones require the presence

of pyridine.

Scheme 19 Enone or Enal Couplings with Alkyl Halides [38]

TBDMSO

Br

Ni Ni

Br

32

OTBDMS

+

I

DMF

photolysis

68%

33

OTBDMS

1.1.2 Nickel–Allyl Complexes 43

NiCl(py)2

27

OTBDMS

+

Br

DMF

photolysis

72%

34

OTBDMS

(E)-1-(tert-Butyldimethylsiloxy)-4-methylpent-1-ene (33): [38]

A 100-mL Schlenk tube, equipped with a magnetic stirring bar, was sequentially charged

with TBDMSCl (3.56 g, 23.6 mmol, 1.30 equiv), MeCN (30 mL), (MeO)(TMSO)C=CMe 2

(3.69 mL, 18.2 mmol, 1.00 equiv; added as a proton-scavenging reagent), and propenal

(2.43 mL, 36.4 mmol, 2.00 equiv). The mixture was stirred for 5 min, during which time

N 2 was bubbled through the soln. The soln was then transferred via a cannula into a 100mL

Schlenk tube containing [Ni(cod) 2](2; 5.00 g, 18.2 mmol, 1.00 equiv) and a spinning

stirrer bar, followed by an MeCN wash (5 mL) to complete the transfer. The resulting

deep burgundy-red soln was stirred for 1 h and then concentrated under reduced pressure

(0.01 Torr) for 14 h to afford a dark red solid contaminated with cycloocta-1,5-diene. The

solid was dissolved in MeCN (30 mL) and sequentially treated with (MeO)(TMSO)C=CMe 2

(0.10 mL, 0.49 mmol, 0.03 equiv), DMF (14 mL, 182 mmol, 10.0 equiv), and 2-iodopropane

(14.1 mL, 181 mmol, 10.0 equiv). The resulting burgundy-red soln was stirred for 5 min

and then irradiated with sunlight or a 275-W GE Model RSW sunlamp until the burgundy-red

color of the allylnickel complex had been completely discharged (ca. 12 h), during

which time a brown-green crystalline precipitate was deposited and the supernatant became

light blue-green or nearly colorless (depending on the completeness of the precipitation).

The supernatant was transferred via a cannula into a round-bottomed flask containing

pentane, and the cloudy mixture was stirred for 30 min to complete precipitation

of the nickel dihalide coproduct. The supernatant was then transferred through a filter

paper tipped cannula onto a stirred aq KH 2PO 4/NaOH buffer (150 mL, pH 7) (an emulsion

tended to form at this stage if most of the nickel dihalide had not been removed through

the prescribed procedure). The pentane layer was separated, washed with H 2O(3”20mL),

dried (MgSO 4), and concentrated under reduced pressure (15 Torr) to afford the crude

product [(E/Z) 10:1] as a clear, yellow oil, contaminated by cycloocta-1,5-diene and 2-iodopropane.

Column chromatography (silica gel, 343 g, hexane/EtOAc 98:2) afforded pure 33;

yield: 2.64 g (68%); bp 768C/15 Torr; (E/Z) > 40:1.

1-(tert-Butyldimethylsiloxy)-3-vinylcyclopentene (34): [38]

A 100-mL Schlenk tube equipped with a magnetic stirring bar and rubber septum was

charged with [NiCl 2(py) 4] (10.0 g, 22.4 mmol, 1.00 equiv) and evacuated and refilled with

N 2 twice to establish an inert atmosphere. THF (40 mL) was added, followed by cycloocta-

1,5-diene (8.20 mL, 67.2 mmol, 3.00 equiv), and the resulting mixture cooled to 0 8C. A second

100-mL Schlenk tube containing Na metal strips (1.03 g, 44.8mmol, 2.00 equiv; each

ca. 2 cm ” 0.4 cm ” 0.1 cm) was connected to this flask with a flexible adapter (available

from Aldrich) under a rapid flow of N 2 (an inert atmosphere having previously been established

in the second Schlenk tube and adapter by capping the free end of the adapter and

evacuating and refilling with N 2). The Na strips were then transferred to the stirred 0–58C

mixture in four portions over 1.5 h to give, after an additional 40 min at 0–58C, a very

dark brown (but not black) supernatant, a small amount of precipitated yellow [Ni(cod) 2],

and no apparent blue [NiCl 2(py) 4]. The mixture was treated with a soln of cyclopent-2enone

(1.88mL, 22.4 mmol, 1.00 equiv) and TBDMSCl (3.38g, 22.4 mmol, 1.00 equiv) in

THF (15 mL) and stirred at 258C for 30 min to afford an orange mixture. A soln of bromoethene

(4.74 mL, 67.2 mmol, 3.00 equiv) in THF (5 mL) was added via a cannula, and the

mixture was irradiated at 10 8C with a 275-W GE Model RSW sunlamp for 12.5 h to afford

an olive-green precipitate and a light brown supernatant. The mixture was poured into a

2-L separatory funnel containing pentane (400 mL) and aq KH 2PO 4/NaOH buffer (400 mL,

for references see p 79

44 Science of Synthesis 1.1 Organometallic Complexes of Nickel

pH 7), and shaken to give an emulsion that was filtered with suction through Celite to

achieve separation. The organic phase was washed with H 2O (3 ” 300 mL), dried (MgSO 4),

filtered, and concentrated under reduced pressure (15 Torr) to afford a mixture of 34 and

cycloocta-1,5-diene. Distillation through a 20-cm Vigreux column under reduced pressure

afforded 34 as a clear, colorless oil; yield: 3.62 g (72%); bp 80–82 8C/3 Torr.

1.1.2.7 Method 7:

Coupling of Nickel–Allyl Complexes with Main Group Organometallics

Nickel–ð-allyl complexes generated by a variety of methods undergo efficient coupling

with nonstabilized main group organometallic reagents. Magnesium reagents have been

most extensively investigated as the main group organometallic, [43] although organostannanes

[39] and organoborates [44] have also been reported to participate in catalytic allylations.

In some instances, efficient allylic reductions may be observed if the main group

organometallic possesses a â-hydrogen. The mechanism typically proceeds by oxidative

addition to afford the nickel–ð-allyl complex, transmetalation of the main group organometallic

to produce an alkyl/allylnickel species, and reductive elimination to afford the

coupled product (Scheme 20). The reductive elimination step has been studied in detail

by Kurosawa who demonstrated that the rate of reductive elimination from an 18-electron

(ç 3 -allyl)nickel complex is significantly greater than reductive elimination from either

the ç 3 or ç 1 16-electron complexes. [45,46] Although nickel(0) and nickel(II) complexes

are commonly invoked in this reaction class, the involvement of paramagnetic nickel

species is well documented in related reaction classes and cannot be ruled out here.

Scheme 20 Nickel-Catalyzed Allylation of Allylic Ethers and Enals [39,43,44]

allylic ether or enal

M = main group metal

+

NiLn 1.1.2.7.1 Variation1:

Allylic Ether Derived ð-Allyl Complexes

In contrast to the very widely used palladium-catalyzed allylations involving allylic acetates,

the corresponding nickel-catalyzed reactions commonly employ allylic ethers. The

nickel-catalyzed allylation of main group organometallics normally favors the more-substituted

regioisomer, and the reaction proceeds with overall inversion of configuration of

the allylic ether (e.g., 35 fi 36; Scheme 21). [43] Hoveyda has demonstrated that substratedirected

alkylations are possible by employing allylic ethers such as 37 with a tethered

phosphine moiety. [47,48] Phosphine-containing substrates direct alkylation to the distal position

of the allyl unit, giving products such as 38. Reductions employing ethylmagnesium

bromide, however, are directed to the proximal position of the allyl unit (Scheme

21). [49] Several asymmetric variants of allylations of Grignard reagents are utilized in relatively

simple systems (Scheme 22). Interestingly, whereas the Hoveyda studies on directed

reductions lead cleanly to hydrogen-atom incorporation in the presence of ethylmagnesium

bromide and dichlorobis(triphenylphosphine)nickel(II) (3), [49] the asymmetric variants

with chiral chelating phosphines give high yields of ethyl-group incorporation

with ethylmagnesium bromide. [50,51] Related additions to unsaturated acetals are discussed

in Section 1.1.4.9.

R 1 M

R 1

NiL n

R 1

1.1.2 Nickel–Allyl Complexes 45

Scheme 21 Regio- and Stereochemistry of Nickel-Catalyzed Allylations [43,47,48]

( ) 5

35

OTES

or

OTES

Ar 1 MgBr, NiCl2(dppf)

OTES Ar 1

MeO PPh 2

37

PhMgBr, NiCl 2(dppf) Ph

major isomer

MeMgBr, NiCl2(PPh3)2 3

73%

EtMgBr, NiCl2(PPh 3) 2 3

82%

Scheme 22 Asymmetric Alkylation of Allylic Ethers [51]

Ph

OMe

Ph

EtMgBr, Ni(cod) 2 2

(S,S-Chiraphos) Ph

91%

( ) 5

36 major isomer

38 99:1 regioselectivity

( ) 5

99:1 regioselectivity

3-Phenylbut-1-ene (36): [43]

NiCl 2(dppf) (13.7 mg, 0.04 mmol) was added to a 25-mL two-necked flask equipped with a

stirring bar, a septum, and a three-way stopcock. The vessel was then cooled to –788C,

evacuated, and filled with argon. (E)-1-(Triethylsiloxy)but-2-ene (35; 373 mg, 2.0 mmol)

and 1.2 M PhMgBr in Et 2O (3.3 mL, 4.0 mmol) were then added. The resulting mixture

was stirred at rt for 4 h, and hydrolyzed with 10% HCl (5 mL) at 0 8C. An appropriate internal

standard (normally an alkane) was added to the organic layer. GC analysis of the organic

layer indicated the formation of 0.22 mmol (11%) of (E)-1-phenylbut-2-ene,

0.02 mmol (1%) of (Z)-1-phenylbut-2-ene, and 1.76 mmol (88%) of 3-phenylbut-1-ene (36).

The organic layer and Et 2O extracts from the aqueous layer were combined, washed

with sat. NaHCO 3 soln and then H 2O, and dried (Na 2SO 4). After evaporation of the solvent,

bulb-to-bulb distillation (95–110 8C bath temp/20 Torr) of the residue gave 224 mg (85%) of

a mixture of coupling products, which were separated by preparative GC (Silicone DC550

30% on Celite); no isolated yields were reported.

(E)-1-(Diphenylphosphino)-5-methylundec-3-ene (38); Typical Procedure: [47]

In a glovebox, NiCl 2(PPh 3) 2 (3; 8.8 mg, 13 ìmol) was transferred to a 10-mL flame-dried

round-bottomed flask. The flask was then sealed with a rubber septum, removed from

the glovebox, and kept under argon. (E)-1-(Diphenylphosphino)-3-methoxyundec-4-ene

(37; 1.0 g, 0.27 mmol) was dissolved in anhyd THF (1.7 mL), and the resulting soln was

then added by cannula to the original flask containing the catalyst. The soln was cooled

to 08C, MeMgBr (1.0 mL, 1.3 mmol) was added in a dropwise fashion, and the mixture was

stirred at 22 8C for 18h under argon. The mixture was cooled to 08C and quenched by the

addition of H 2O (1.0 mL). After addition of more H 2O (15 mL), the mixture was washed

R

Et

73% ee

Ph

PPh 2

for references see p 79

46 Science of Synthesis 1.1 Organometallic Complexes of Nickel

with CH 2Cl 2 (3 ” 35 mL). The combined organic layers were dried (MgSO 4). Removal of the

drying agent through filtration, followed by solvent evaporation in vacuo, afforded a yellow

oil. Chromatography (silica gel, hexanes/EtOAc 15:1) afforded 38 as a colorless oil;

yield: 69 mg (73%).

1.1.2.7.2 Variation2:

Enal-Derived ð-Allyl Complexes

Enal-derived nickel–ð-allyl complexes are efficient partners in cross-coupling reactions

with alkenyl- and arylstannanes leading to products such as 39 (Scheme 23). [39] As described

for the allylic ether derived complexes, the mechanism of the coupling process

involves transmetalation followed by reductive elimination. The reaction is catalytic in

nickel, unlike couplings of enals with alkyl halides which require stoichiometric quantities

of nickel. Many other variants of nickel-catalyzed conjugate additions may involve ðallyl

complexes, but these are treated separately in a section on alkenes (Section 1.1.4.2)

because the mechanism is poorly defined in most nickel-catalyzed conjugate additions.

Scheme 23 Addition of Organotins to Enal-Derived ð-Allyl Complexes [39]

H

O

Bu3SnCH CH2 TBDMSCl, Ni(cod)2 2

TBDMSO

Cl

Ni Ni

Cl

75%

OTBDMS

39

OTBDMS

(E)-1-(tert-Butyldimethylsiloxy)penta-1,4-diene (39): [39]

A 25-mL Schlenk tube equipped with a stirring bar was sequentially charged with propenal

(74.0 ìL, 1.11 mmol), (MeO)(TMSO)C=CMe 2 (30.0 mg, 0.148mmol), TBDMSCl (168mg,

1.12 mmol), and CH 2Cl 2 (1.5 mL). The soln was stirred for 5 min, treated with [Ni(cod) 2](2;

27 mg, 0.098mmol), stirred for an additional 5 min, and then treated with tributyl(vinyl)stannane

(293 ìL, 1.00 mmol) to give a clear red soln. This was stirred at 258C for

48h, near the end of which time the mixture turned black and deposited a metallic nickel

precipitate. The mixture was diluted with pentane (25 mL) and washed with aq 0.1 M

KH 2PO 4/NaOH buffer (2 ” 25 mL, pH 7). The organic layer was separated and the product

was dried (MgSO 4), filtered, and concentrated under reduced pressure (15 Torr) to afford

an oil [(E/Z) 19:1] which was chromatographed (silica gel, 35 g, hexane/EtOAc 98:2) to give

39 as a clear, colorless oil; yield: 149 mg (75%); (E/Z) > 50:1 by 1 H NMR analysis.

1.1.2.7.3 Variation3:

Allylic Alcohol Derived ð-Allyl Complexes

Allylic alcohols readily undergo nickel-catalyzed allylation with Grignard reagents

(Scheme 24). [52–55] Both isomers of 40 produce similar product ratios, and the reaction presumably

proceeds via nickel–ð-allyl intermediates. Only simple Grignard reagents that

lack â-hydrogens such as methylmagnesium bromide and phenylmagnesium bromide

are reported, but considerable variation of the allylic alcohol is tolerated.

1.1.2 Nickel–Allyl Complexes 47

Scheme 24 Addition of Grignard Reagents to Allylic Alcohols [52–55]

MeMgBr, NiCl2(PPh3) 2 3

Bu +

50%

OH

t But But 40

41 4:1

42

4-tert-Butyl-1-methyl-1-vinylcyclohexane (41): [52]

A 0.74 M soln of MeMgBr in Et 2O (35 mL) was distilled under N 2 nearly to dryness, and dry

benzene (20 mL), NiCl 2(PPh 3) 2 (3; 417 mg), and a soln of a 5:3 mixture of cis- and trans-isomers

of 40 (1.00 g, 5.5 mmol) in dry benzene (15 mL) were added successively. The mixture

was heated at reflux under N 2 for 24 h, and sat. NH 4Cl soln (25 mL) was added. The

organic layer was washed with H 2O, dried (Na 2SO 4), and evaporated. Distillation of the residue

afforded a 77:20 mixture of 41 and 42; yield: 500 mg (50%); bp 93–988C/16 Torr, accompanied

by a 3% yield of the diastereomer of 41.

1.1.2.8 Method 8:

Additionof Stabilized Nucleophiles to Nickel–Allyl Complexes

The allylic alkylation with weak nucleophiles employing nickel catalysts is generally not

as efficient as the corresponding palladium-catalyzed methods. However, allylic acetates,

allyl phenyl ethers, and allylic carbonates undergo efficient couplings with amines, phenols,

and malonates in the presence of nickel(0) catalysts (Scheme 25). [56,57]

Scheme 25 Addition of Weak Nucleophiles to Allylic

Acetates, Carbonates, and Ethers [56,57]

OR 1

+

NuH

R1 = Ac, Ph, CO2Me Nu = NEt2, OPh, CH(CO2R2 ) 2

Ni(dppe)2 Nu

1.1.2.9 Method 9:

Alkyne Insertions with Nickel–Allyl Complexes

Migratory insertion of an alkyne into a nickel–ð-allyl complex has not been rigorously established.

However, this mechanistic scenario has been postulated in several synthetically

useful processes. Ikeda has demonstrated that treatment of a mixture of allyl chlorides,

terminal alkynes, and alkynyltin reagents with catalytic amounts of nickel(0) without

phosphine leads to the production of conjugated enynes (e.g., 43; Scheme 26). [58–60]

Whereas couplings with allyl chlorides proceed in high yield, the analogous procedure

with allyl acetates and allyl carbonates is less efficient. Interestingly, reactions carried

out in the presence of triphenylphosphine afford the product derived from direct coupling

of the allyl chloride and alkynyltin. [60] Both inter- and intramolecular variants are

quite general.

for references see p 79

48 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Scheme 26 Nickel-Catalyzed Coupling of an Allylic Acetate, an Alkyne, and an Organotin

[58–60]

R 1

Cl

+

R 2

H + R SnBu3 3

Ni(acac) 2 1

DIBAL-H

67−83%

Carbonylative cyclizations have also been developed that likely involve the insertion of

alkynes into nickel–ð-allyl complexes. [61,62] Chiusoli, who was the pioneer in this area,

demonstrated that either cyclic or acyclic products may be isolated depending on the concentration

of methanol (Scheme 27). Allyl halides are the more commonly used allyl complex

precursor, and enals are also utilized; an example of the latter is the formation of 44

and 45. [63]

Scheme 27 Carbonylative Cyclizations of Nickel–ð-Allyl Complexes [61–63]

OC CO

OC Ni

Cl

CO + H H

CO, MeOH

O Ni

Cl

OTMS

Cl

Ni Ni

Cl

TMSO R1 R1 +

R 3

R 2

O

OMe

if high conc. of MeOH

R 3

CO, MeOH

R 2 R 1

O

44

OMe

or

+

R 3

R 2

43

O

H

R 1

OMe

O

if low conc. of MeOH

R 2 R 1

(Z)-3-Butyl-1-phenylhepta-3,6-dien-1-yne (43,R 1 =H;R 2 = Bu; R 3 = Ph); Typical Procedure: [58]

To a soln of [Ni(acac) 2](1; 26 mg, 0.1 mmol) in THF (5 mL) was added 1.0 M DIBAL-H in toluene

(0.1 mL, 0.1 mmol) at 0 8C under N 2, and the mixture was stirred for 5 min. To this

black soln were then added tributyl(phenylethynyl)stannane (380 mg, 0.97 mmol), hex-1yne

(99 mg, 1.21 mmol), 3-chloroprop-1-ene (73 mg, 0.95 mmol), at 08C, and then the mixture

was stirred at reflux for 1 h. To this soln was added aq NH 4F (30 mL), and stirring was

continued for 30 min to remove the Bu 3SnCl. After filtration through Celite, the aqueous

layer was extracted with Et 2O (40 mL ” 3). The combined organic layers were washed with

brine, dried (MgSO 4) for 30 min, filtered, and concentrated in vacuo [40 8C (bath)/25 Torr].

The residue was purified by column chromatography, R f = 0.64 (silica gel, hexane) to give

43 as a pale yellow oil; yield: 149 mg (70%). An analytical sample of the product was obtained

by bulb-to-bulb distillation [140 8C (oven)/4 Torr). The isomeric purity of the obtained

product was determined by 1 H NMR and GC.

O

45

OMe

OMe

1.1.3 Nickel–Alkyne Complexes 49

Carbonylative Cyclizations to Cyclopentenes 44 and 45; General Procedure: [63]

To a 100-mL Schlenk flask filled with argon was added [Ni(cod) 2](2; 1.24 g, 4.51 mmol) and

anhyd toluene (20 mL). The temperature was maintained at –40 8C and propenal (0.50 g,

9.02 mmol) was added dropwise. Soon, a red insoluble complex of Ni(CH 2=CHCHO) 2 was

formed. The temperature was allowed to warm to –20 8C, when TMSCl (0.49 g, 4.51 mmol)

was added dropwise. The original red solid gradually dissolved. At –108C the oxidative addition

was complete and a deep red homogeneous soln resulted. The temperature was

lowered again to –788C. At this point, the alkyne (4.51 mmol) was added and the argon

was replaced by CO by means of a vacuum line. The temperature was again allowed to

rise and an excess of MeOH was added at –158C for activated alkynes and at rt for unactivated

alkynes. The reaction was allowed to proceed for 4 h, and the solvent was completely

evaporated in vacuo. The residue was treated with H 2O and extracted several times with

Et 2O. The combined organic phases were dried (Na 2SO 4) and evaporated to dryness. The

crude oil was chromatographed (hexane/EtOAc) on silica gel that had been treated with

a soln of Et 3N, and the solvent was removed to obtain the adducts 44 and 45.

1.1.2.10 Method 10:

Alkene Insertions with Nickel–Allyl Complexes

The cyclization of allylic acetates tethered with alkenes has been extensively investigated

by Oppolzer, employing a number of transition metals including nickel. The process has

been termed a “metallo-ene” reaction; however, the mechanism likely involves a sequence

of oxidative addition to generate a ð-allyl complex, alkene insertion, and â-hydride

elimination. [64] The process is quite general in scope and provides a very useful

method for the preparation of 1,4-dienes such as 46 (Scheme 28).

Scheme 28 Intramolecular Nickel-Catalyzed Alkene–Allylic Acetate Couplings [64]

AcO

Ts

N

1.1.3 Product Subclass 3:

Nickel–Alkyne Complexes

Ni(cod)2 2, dppb

Ts

N

+

Ni

Ln +

H Ni

Ln

Nickel complexes of alkynes are involved in many important catalytic transformations. A

fundamental transformation of nickel(0)–alkyne complexes that forms the basis of a

number of useful stoichiometric and catalytic reactions is the oxidative cyclization of

one alkyne and a second unsaturated unit to form a five-membered metallacyclopentene

47 (Scheme 29). If the second unsaturated unit is also an alkyne, linear oligomerizations

or cyclooligomerizations result. The catalytic tetramerization of acetylene to octatetraene

was discovered more than 50 years ago by Reppe, [65] and an excellent review on the

historical development of this area has appeared. [5] The complexities of the mechanistic

Ts

N

88%

LnNi +

Ts

N

46

Ts

N

for references see p 79

50 Science of Synthesis 1.1 Organometallic Complexes of Nickel

steps of alkyne cyclooligomerizations have been further documented by Eisch. [66] Alternatively,

many selective transformations have been reported in which one alkyne and a different

unsaturated unit couple in an oxidative cyclization. Oxidative cyclizations of this

class form the basis of many useful procedures. [187] An outstanding review on the formation

of oxa- and azametallacycles has appeared. [9]

Scheme 29 Oxidative Cyclization of an Alkyne

and a Second Unsaturated Unit [9,187]

R 1

L L

Ni

Y

X

R1 Ni

R

Y

X

1

R1 L L

47

Synthesis of Product Subclass 3

1.1.3.1 Method 1:

Ligand Exchange with Nickel–Alkene Complexes

Nickel–alkyne complexes are typically unstable owing to their propensity to catalyze alkyne

polymerization to yield polyacetylenes. The most common preparative method involves

the displacement of alkenes under conditions in which the stoichiometry is carefully

controlled. Numerous bis(ligand)nickel(0)–mono(alkyne) complexes (e.g., 48) have

been reported and fully characterized by Pörschke (Scheme 30). [67] Further treatment of

the monoalkyne complex with alkyne leads to formation of the bis(alkyne) complex. (ç 6 -

Cyclododeca-1,5,9-triene)nickel(0) [Ni(cdt)] [68] is a common starting nickel(0) complex for

the preparation of alkyne complexes. Bis(alkyne)nickel(0) complexes 50 have also been

prepared by Rosenthal and Pörschke from nickel(0) complexes of hepta-1,6-diene (e.g.,

49) by ligand displacement (Scheme 31). [69]

Scheme 30 Preparation of Nickel(0)–Alkyne Complexes [67]

Ni(cdt) + H 2C

CH2 + Cy 3P Cy 3P Ni

Scheme 31 Preparation of Nickel(0)–Bis(alkyne) Complexes [69]

N Ni

49

+

Ph

TMS

80%

H H

82%

TMS

N Ni

TMS

50

Ph

Cy 3P Ni

(Acetylene)(ethene)(tricyclohexylphosphine)nickel(0) (48): [67]

Acetylene (50 mL, 6 mmol) was added at –508C without stirring to an Et 2O soln (40 mL) of

[Ni(C 2H 4) 2(PCy 3)] (5.0 mmol) [prepared from Ni(cdt) (1.165 g, 5.0 mmol Ni), ethene, and

Cy 3P (1.40 g, 5.0 mmol)]. The color of the yellow soln changed to light red, and at –788C

over the course of 2 d small yellow crystals formed. The mother liquor was decanted,

and the crystals were washed with cold Et 2O (2 ”) and dried in vacuo at –308C to afford

48; yield: 1.62 g (82%).

1.1.3 Nickel–Alkyne Complexes 51

(2,6-Dimethylpyridine)bis[phenyl(trimethylsilyl)acetylene]nickel(0) (50): [69]

PhC”CTMS (810 mg, 4.66 mmol) was added at 208C to the light yellow soln of 49 (610 mg,

2.33 mmol) in pentane (10 mL). Upon heating the mixture for a short period to 458C the

color turned intense red. Cooling to –788C afforded red cubes which were separated from

the mother liquor using a capillary frit, washed with cold pentane (2 ”), and dried in vacuo

at 208C to afford 50; yield: 960 mg (80%).

Applications of Product Subclass 3 in Organic Synthesis

1.1.3.2 Method 2:

Coupling of Alkynes with Carbon Dioxide

Nickel(0) complexes of alkynes in the presence of carbon dioxide undergo oxidative cyclization

to produce oxametallacycles 51 (Scheme 32). [70,71] Direct cleavage of the oxametallacycle

in the presence of strong acids affords unsaturated carboxylic acids 52 (Scheme

33). [72] The coupling of diynes with carbon dioxide leads to an efficient synthesis of bicyclic

Æ-pyrones such as 53 by a formal [2+2+2] cycloaddition (Scheme 33). [73,74]

Scheme 32 Coupling of Alkynes and Carbon Dioxide: Metallacycle Formation [70,71]

Me2

N

NiLn N

Me2

+

CO 2

+

Et

Me2 N

Ni

N O

Me2

51

Scheme 33 Coupling of Alkynes and Carbon Dioxide: Synthetic Utility [72–74]

R 1

Et

+ CO 2

1. Ni(cod) 2 2, bipy

2. H2SO4 Ni(cod)2 2, Cy3P

64%

R 1

H

R 1

CO2H 52

1,4-Diethyl-5,6,7,8-tetrahydro-3H-benzopyran-3-one (53): [74]

In a 50-mL stainless steel autoclave were placed, under N 2, a soln of [Ni(cod) 2](2; 0.024 g,

0.090 mmol) in THF (1.8mL), a soln of Cy 3P (0.05 g, 0.18mmol) in toluene (0.17 mL), and

THF (8.2 mL). The mixture was stirred for several min, dodeca-3,9-diyne (0.19 mL,

0.90 mmol) was added, followed by CO 2 gas to a compression of 3.7 ” 10 4 Torr at rt. The

mixture was magnetically stirred for 20 h at rt. The unreacted CO 2 gas was purged and

the mixture was transferred to a flask using Et 2O (20 mL). The soln was concentrated to

give a residue that was purified by preparative layer chromatography (hexane/Et 2O 2:1)

to give 53; yield: 0.12 g (64%).

Et

53

O

Et

O

for references see p 79

52 Science of Synthesis 1.1 Organometallic Complexes of Nickel

1.1.3.3 Method 3:

Coupling of Alkynes with Isocyanides

Little is known about the mechanistic details of isocyanide–alkyne couplings. However, a

useful stoichiometric cyclization of enynes and diynes with isocyanides was developed by

Tamao and Ito, [75] and Buchwald later developed a catalytic variant (Scheme 34). [76] The resulting

cyclopentenimines may be hydrolyzed to cyclopentenones. A variety of carbocyclic

and heterocyclic templates are tolerated in the sequence.

Scheme 34 Cyclizations of Enynes and Isocyanides [75,76]

O

Ph

+

NC

Ni(cod) 2 2, bipy

Cyclization of Enynes To Form Bicyclic Cyclopentenones; General Procedure: [76]

In an inert-atmosphere glovebox, [Ni(cod) 2](2; 14 mg, 0.05 mmol), bis(diphenylmethylene)ethylenediamine

(24 mg, 0.06 mmol), the enyne (1.0 mmol), and TIPSCN (201 mg,

1.1 mmol) were dissolved in DMF (46 mL) in a 100-mL sealable Schlenk flask. The Schlenk

flask was sealed, removed from the glovebox, and heated at 110–135 8C until the enyne

was consumed (as determined by GC, 8–36 h). The flask was cooled to 0 8C, treated with

sat. aq oxalic acid (10 mL), and stirred at rt for 12–24 h. Et 2O (80 mL) and sat. aq NaHCO 3

(40 mL) were added to the soln and the layers were separated. The aqueous layer was extracted

with Et 2O (3 ” 50 mL) and the combined Et 2O extracts were washed with H 2O

(3 ” 40 mL) and brine (40 mL). The Et 2O soln was dried (MgSO 4) and concentrated in vacuo

to give an oily residue which was purified by flash chromatography (silica gel, Et 2O/hexane

1:1–2) to give the desired cyclopentenone, typically as a colorless to pale yellow oil.

1.1.3.4 Method 4:

Coupling of Alkynes with Aldehydes

Couplings of alkynes and aldehydes have been investigated in a number of contexts. Although

no metallacycles derived from oxidative couplings of one alkyne and one aldehyde

have been isolated, the reaction probably proceeds in a fashion similar to the coupling

of alkynes and carbon dioxide (Section 1.1.3.2). Tsuda and Saegusa have reported

the formal hydroacylation of alkynes by a process that involves the coupling of an alkyne

and an aldehyde (Scheme 35). [77] Two possible mechanisms are proposed for the formation

of the enone 54, and one involving the formation of an oxametallacycle is depicted.

The corresponding coupling of diynes and aldehydes is also reported by the same investigators

to afford the dihydropyran 55. [78]

80%

O

Ph

1.1.3 Nickel–Alkyne Complexes 53

Scheme 35 Nickel-Catalyzed Aldehyde–Alkyne Couplings [77,78]

X

O

H

+

Pr

Ni(cod) 2 2

L L

Ni

Pr

O

L L

H

Ni Pr

R

Ni(cod) 2 2, Cy3P +

1 O

R2 X

R1 R

H O

2

O

Pr

R 1

55

60%

O

H Pr

Montgomery has developed a procedure for the three-component coupling of aldehydes,

alkynes, and organozincs to produce allylic alcohols (Scheme 36). [79] Two-component couplings

involving ynals are also reported. If no phosphine is employed, the organozinc ligand

is incorporated into the allylic alcohol product 56. However, if bis(ç 4 -cycloocta-1,5diene)nickel(0)

(2) and tributylphosphine are employed and if the organozinc possesses a

â-hydrogen, a hydrogen atom is instead introduced from the organozinc to generate product

57. Triethylsilane may also be employed as the reducing agent, and this variant has

been utilized in the total synthesis of allopumiliotoxin 267A (58; Scheme 37). [80] The ynal

cyclization method is quite general with functionalized substrates.

Scheme 36 Three-Component Aldehyde, Alkyne, Organozinc Couplings [79]

O

R 1 H

+

R 2

L L

Ni

R

O

3

R2 R1 H

R 3

ZnR 4 2

L nNi(0)

R 4 ZnO

R 1

R

LnNi

4

R 1

H

L L

O Ni

H

OH R 4

R2 56

R2 H R1

L = THF

R 3

R 2

R 3

large substituent

small substituent

(or tether chain)

L = Bu3P

R 4 ZnO

H

LnNi

R 1 H

54

R 3

R 2

Pr

OH H

R3 R2 R1 H

57

(intramolecular variant only)

for references see p 79

54 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Scheme 37 Ynal Cyclizations in Pumiliotoxin Synthesis [80]

N

H

O

OBn

Et 3SiH

Ni(cod) 2 2

Bu3P N

H

OTES

OBn

N

H

OH

58 allopumiliotoxin 267A

Hodgson has developed a variant on the Nozaki–Kishi coupling [81] in which a haloalkene,

an alkyne, and an aldehyde undergo coupling to produce allylic alcohols with a tetrasubstituted

alkene (Scheme 38). [82] Only the fully intramolecular procedure is reported.

Scheme 38 Aryl Iodide–Aldehyde–Alkyne Coupling [82]

I

O

H

CrCl 2, NiCl 2

DMF, 25 o C

2-Methyl-4-propyloct-4-en-3-one (54): [77]

In a 50-mL stainless steel autoclave were placed under N 2, THF (8.50 mL), a soln of

[Ni(cod) 2] (2; 14 mg, 0.050 mmol) in THF (1.20 mL), and trioctylphosphine (0.046 mL,

0.10 mmol). The mixture was stirred for several min, then oct-4-yne (0.147 mL,

1.00 mmol) and isobutyraldehyde (0.136 mL, 1.50 mmol) were added. The mixture was

magnetically stirred for 20 h at 808C. The soln was concentrated to give a residue which

was purified by preparative layer chromatography (hexane/Et 2O 15:1) to give a 7:1 mixture

of 54 and a 2:1 adduct; yield: 0.124 g (60%).

Alkylative Cyclization of Ynals; General Procedure: [79]

A 0.5–0.6 M soln of ZnCl 2 (2.5–3.0 equiv) in THF was stirred at 0 8C, and the organolithium

or Grignard reagent (3.7–4.5 equiv) was added by syringe followed by stirring for 10–

15 min at 08C. A 0.02–0.04 M soln of [Ni(cod) 2](2; 0.05–0.20 equiv) in THF was added and

the resulting mixture was immediately transferred by cannula to a 0.1–0.2 M soln of the

ynal (1.0 equiv). After consumption of starting material as measured by TLC analysis (typically

0.25–0.5 h at 08C), the mixture was subjected to an extractive workup with NH 4Cl/

NH 4OH buffer (pH 8) and Et 2O followed by flash chromatography (silica gel).

Reductive Cyclization of Ynals; General Procedure: [79]

A 0.04–0.05 M soln of Bu 3P {4 equiv relative to [Ni(cod) 2]} in THF was added to [Ni(cod) 2](2;

0.05–0.20 equiv) at 25 8C followed by stirring for 3–5 min. The nickel soln was transferred

to a 0.5–0.6 M soln of commercial Et 2Zn (2.5–3.5 equiv) in THF at 0 8C, and the resulting

mixture was immediately transferred by cannula to a 0.10 M soln of the ynal (1.0 equiv)

in THF at 08C. After consumption of starting material as measured by TLC analysis (typically

0.25–2.0 h at 0 8C), the mixture was subjected to an extractive workup with NH 4Cl/

NH 4OH buffer (pH 8) and Et 2O followed by flash chromatography (silica gel).

Three-Component Couplings; General Procedure: [79]

A 1.0 M soln of ZnCl 2 (2.5–3.0 equiv) in THF was stirred at 0 8C, and the organolithium or

Grignard reagent (4.5–5.4 equiv) was added by syringe followed by stirring for 10–15 min

1.1.3 Nickel–Alkyne Complexes 55

at 0 8C. A 0.05 M soln of [Ni(cod) 2](2; 0.20 equiv) in THF and a soln containing the aldehyde

(3.0 equiv) and alkyne (1.0 equiv, 0.3–0.4 M relative to the alkyne) in THF were added sequentially

to the organozinc reagent. After consumption of starting material as measured

by TLC analysis (typically 0.25–0.5 h at 0 8C), the mixture was subjected to an extractive

workup with NH 4Cl/NH 4OH buffer (pH 8) and Et 2O followed by flash chromatography (silica

gel). With the alkyne as the limiting reagent, the product derived from direct addition

of the organozinc to the aldehyde was observed as a significant byproduct. In cases in

which separation of this byproduct was problematic, slightly lower yields were obtained

by employing the aldehyde as the limiting reagent; however, the purification was simpler.

1.1.3.5 Method 5:

Coupling of Two Alkynes

The couplings of diynes with a third unsaturated component are described in several subsections

throughout Section 1.1.3. However, several other processes merit discussion

here that do not fall into the other categories described. The hydrosilylation of diynes provides

an excellent route to cyclic dienylsilanes. A mechanism was proposed that involves

Si-H oxidative addition, alkyne silylmetalation, alkyne insertion, and C-H bond reductive

elimination to give 59 (Scheme 39). [83] A related process ensues when diynes are treated

with hydrodisilanes, and bicyclic silacyclopentadienes 60 are produced (Scheme 40). [83]

The intermolecular version of this process was first reported by Lappert. [84]

Scheme 39 Diyne Hydrosilylation [83]

R 1

R1 SiX3

Ni

H

+ HSiX 3

Ni(acac) 2 1, DIBAL-H

L nNi

R 1

H

SiX3 H

Scheme 40 Diyne Hydrosilylation with Hydrodisilanes [83]

R 1

R 2

+ HSiR 3 2SiX 3

Ni(acac) 2 1, DIBAL-H, R 1 3P

H

R

59

1

SiX3

H

R 1

R

60

2

SiR 3 2

H

SiX3

Ni

R1 Ln

H

Cheng has demonstrated that spirocyclic cyclopentadienes such as 61 may be produced

upon treatment of an iodoalkene with an alkyne (Scheme 41). [85] A mechanism involving

oxidative addition of nickel(0) to the iodoalkene followed by two sequential alkyne insertions

has been proposed.

for references see p 79

56 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Scheme 41 Iodoalkene–Alkyne Couplings [85]

O

I

+

Et Et

NiBr 2, Zn

85%

6,7,8,9-Tetraethylspiro[4.4]nona-6,8-dien-2-one (61): [85]

To a mixture of NiBr 2 (0.080 g, 0.36 mmol), Zn powder (0.14 g, 2.2 mmol), and 3-iodocyclopent-2-enone

(0.40 g, 1.8mmol) in MeCN (1.0 mL) was added hex-3-yne (0.30 g, 3.6 mmol).

The system was then heated under N 2 at 608C with stirring for 20 h. During the course of

catalysis, the color of the soln changed from light green to a persistent dark red in the

first few hours. The MeCN soln was cooled, the soln was concentrated, and the resulting

compounds were separated by column chromatography (silica gel, hexane/EtOAc 10:1) to

give the desired product 61; yield: 0.40 g (85%).

1.1.3.6 Method 6:

Coupling of Alkynes with Alkenes

The couplings of enynes with a third unsaturated component are described in Sections

1.1.3.3 and 1.1.3.7. However, several other processes merit discussion here that do not

fall into the other categories described. For example, Ikeda and Montgomery have extensively

investigated intermolecular couplings of enones and alkynes with organometallic

reagents such as organozincs [86,87] and organotins. [88,89] Intermolecular couplings efficiently

produce ª,ä-unsaturated ketones with highly selective tri- or tetrasubstituted alkene

formation (Scheme 42). The scope of the process is quite broad, and the mechanism is

likely to involve the formation of metallacycles as key intermediates.

Scheme 42 Enone–Alkyne Couplings with Organozincs or Organoaluminums [86–89]

O

L L

Ni

M = AlR 3 2 or ZnR 2

H

+

R 1

R1 H + MR2 MR 2

MO

Et

O

Et

61

Et

Ni(acac) 2 1 or Ni(cod) 2 2, Ph 3P

LnNi

R1 R2 Montgomery has investigated the intramolecular variant of this process. [90–93] The addition

of triphenylphosphine promotes a â-hydride elimination process that leads to hydrogen-atom

introduction instead of alkyl-group introduction. In both cases, the exocyclic

double bond is created with complete selectivity (Scheme 43). A formal synthesis of (+)-

Æ-allokainic acid (62) was completed employing this methodology as the key step

(Scheme 44). [94]

H

MO

O

R 2

H

R 1

R 1

1.1.3 Nickel–Alkyne Complexes 57

Scheme 43 Alkynyl Enone Cyclization with Alkylation or Reduction [90–93]

R 1

O

R 2

+ R 3 2Zn

Ni(cod) 2 2

Ni(cod)2 2, Ph3P

R 3 = Et

Scheme 44 Alkyne-Unsaturated Acyloxazolidinone Cyclizations in (+)-Æ-Allokainic Acid

Synthesis [94]

O

O N

O

N

O

OTBDMS

Me 3Al, Ni(cod) 2 2

O

N

O

R 1

O

R 1

O

N

HO

O

R 3

H

R 2

OTBDMS

HO

N

O

H

62 (+)-α-allokainic acid

Trost has developed a cycloisomerization of enynes involving a nickel–chromium catalyst

system (Scheme 45). [95] High yields among a broad range of substrates are noted.

Scheme 45 Nickel-Catalyzed Enyne Cycloisomerization [95]

OH

NiCl2(PPh3)2 3, CrCl2

Alkylative Cyclization of Alkynyl Enones; General Procedure: [91]

A 0.3–0.5 M soln of ZnCl 2 (2.5–3.0 equiv) in THF was stirred at 0 8C, and the organolithium

or Grignard reagent (3.7–4.5 equiv) was added by syringe followed by stirring for 0.25–1 h

at 0 8C. A 0.02–0.04 M soln of [Ni(cod) 2](2; 0.04–0.06 equiv) in THF was added and the resulting

mixture was immediately transferred by cannula to a 0.1–0.2 M soln of the unsaturated

substrate (1.0 equiv). After consumption of starting material as judged by TLC analysis

(typically 0.25–2.0 h at 0 8C), the mixture was subjected to an extractive workup with

NaHCO 3/EtOAc or NH 4Cl/NH 4OH buffer (pH 8) and Et 2O followed by flash chromatography

(silica gel). Although the above procedure was typically used, commercially available diorganozinc

reagents performed comparably.

OH

H

for references see p 79

58 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Reductive Cyclization of Alkynyl Enones; General Procedure: [91]

A 0.03–0.06 M soln of Ph 3P (0.2–0.3 equiv) in THF was added to [Ni(cod) 2] (2; 0.04–

0.06 equiv) at 258C and stirred for 3–5 min. This soln was then transferred to a 0.5–0.6 M

soln of Et 2Zn in THF at 08C, and the resulting mixture was immediately transferred by

cannula to a 0.10–0.50 M soln of the unsaturated substrate (1.0 equiv) in THF at 0 8C. After

consumption of starting material as judged by TLC analysis (typically 0.25–2.0 h at 0 8C),

the mixture was subjected to an extractive workup of NaHCO 3/EtOAc or NH 4Cl/NH 4OH

(pH 8) buffer and Et 2O followed by flash chromatography (silica gel).

1.1.3.7 Method 7:

[2+2+2] Cycloadditions

Dating from the original discovery from Reppe [65] on the cyclooligomerization of acetylene,

nickel-catalyzed multicomponent cycloadditions have attracted considerable attention

(see also Houben–Weyl, Vol. E 18, pp 987, 993). [96] Metallacycles have been proposed as

important intermediates in most classes of cyclotrimerizations. The mechanism is likely

to involve initial oxidative cyclization to a five-membered metallacycle, followed by insertion

of a third unsaturated component, and finally reductive elimination to afford sixmembered

ring products (Scheme 46).

Scheme 46 General Mechanism of Nickel-Catalyzed [2+2+2] Cycloadditions [96]

R 1

L n

Ni

R 1

Ni

R 1

1 R R1

R 1

L n

Ni

R 1 R 1

A common limitation of most classes of cyclotrimerizations is the difficulty associated

with controlling the chemoselectivity of the process. In most instances involving intermolecular

couplings, multiple incorporation of the same alkyne unit is unavoidable.

However, with systems in which two alkynes, or one alkene and one alkyne are tethered,

synthetically useful processes become possible. The first example of a selective addition

of two equivalents of an alkyne and one alkene was reported by Chalk. [97] Tsuda has applied

this process to applications in polymer chemistry, [98] and Ikeda has developed a similar

method employing cyclic enones (Scheme 47). [99]

Scheme 47 Fully Intermolecular [2 + 2+2] Cycloadditions [99]

O

+

H

R 1

Me3Al, Ni(acac) 2 1

Ph3P, PhOH

O

R 1

major isomer

(after oxidation)

Bhatarah and Smith have reported that nickel(0)-promoted cyclizations of diynes and simple

alkynes afford good yields of substituted benzenes. [100] Mori has developed the corresponding

cyclotrimerization to 63 in an asymmetric fashion by using bis(ç 4 -cycloocta-1,5diene)nickel(0)

(2) and a chiral phosphine (Scheme 48). [101] Ikeda has developed a cyclotrimerization

to 64 that introduces two sp 3 -hybridized centers by cycloaddition of a diyne

with an enone (Scheme 48). [102] Montgomery reported that four contiguous stereocenters

may be introduced to give 65 by the 1:1 cycloaddition of alkynyl enones and simple

R 1

R 1

1.1.3 Nickel–Alkyne Complexes 59

enones (Scheme 48). [103] This latter process was found to be highly stereoselective but nonstereospecific.

Scheme 48 Partially Intramolecular [2+2+2] Cycloadditions [101–103]

R 2

TMS

O

NR 1

R 2

OTBDMS

Ph Ph

+ H H

+

O

Ni(cod)2 2

chiral phosphine

NiCl 2, Zn, ZnCl 2

80%

Ni(cod) 2 2, Ph 3P

75%

R 2

NR1 ∗

R 2

63 12−73% ee

O

Ph

TMS

H

64

65

OTBDMS

A fully intramolecular version involving an enediyne substrate is reported to undergo reasonably

efficient cyclization to afford the tricyclic cyclohexadiene 66 (Scheme 49). [93] Only

one example of the process is reported.

Scheme 49 Fully Intramolecular [2 + 2+2] Cycloadditions [93]

Ph

O

Ni(cod) 2 2

t-BuLi, ZnCl2 52%

Cotrimerization and Aromatization of Enones and Alkynes; General Procedure: [99]

To a soln of [Ni(acac) 2](1; 13 mg, 0.05 mmol) and Ph 3P (26 mg, 0.1 mmol) in THF (5 mL) was

added 1.0 M Me 3Al in hexane (0.4 mL) at 0 8C under N 2. After stirring for 5 min, PhOH

(92 mg, 1.0 mmol) was added to this soln, and the mixture was stirred for 5 min. To this

dark red soln were added the alkyne (2.05 mmol) and the enone (1.0 mmol) at 0 8C, and

the mixture was then stirred at rt for 2 h. DBU (350 mg, 2.3 mmol) was added to the mixture,

and the soln was opened to the air and stirred at rt overnight. Aq 0.2 M HCl (30 mL)

was added, and stirring was continued for 10 min. The aqueous layer was extracted with

Et 2O (3 ” 40 mL) and the combined organic layers were washed with aq NaHCO 3 (50 mL)

and then with brine (50 mL), dried (MgSO 4) for 30 min, filtered, and concentrated in vacuo.

The residue was purified by column chromatography (silica gel) to yield aromatic

compounds.

O

Ph

H

66

O

Ph

for references see p 79

60 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Nickel-Catalyzed [2 +2+2] Cycloadditions; General Procedure: [103]

A 0.02–0.04 M soln of Ph 3P (0.4–1.0 equiv) in THF was added to [Ni(cod) 2](2; 0.20–0.25 equiv)

at 0 8C and stirred for 2 min. The nickel soln was transferred by cannula to a 0.4–0.5 M soln

of the simple enone (5.0 equiv) and the alkynyl enone substrate (1.0 equiv) in THF at 0 8C.

The reaction was stirred at 0 8C for 5 min and then at 258C until the starting material was

consumed (generally 1.5–3.0 h). The mixture was subjected to an extractive workup with

NH 4Cl/NH 4OH (pH 8) buffer and Et 2O followed by flash chromatography (silica gel).

1.1.3.8 Method 8:

Alkyne Carbonylation

The carbonylation of alkynes in the presence of methanol or water and carbon monoxide

produces Æ,â-unsaturated carboxylic acids or esters (Scheme 50). [7,104] This reaction is rarely

used in large-molecule synthetic applications; however, it has been very important in

the industrial preparation of acrylic acid from acetylene.

Scheme 50 Preparation of Acrylic Acid From Acetylene [104]

H H + H 2O + CO

1.1.3.9 Method 9:

Alkyne Hydrocyanation

The hydrocyanation of alkynes provides a direct method for preparing Æ,â-unsaturated

nitriles such as 67. The reactions proceed at 1208C in an autoclave with hydrogen cyanide

and catalytic tetrakis(triphenyl phosphite)nickel(0) (Scheme 51). [105] Lower temperatures

may be employed if the alkyne and hydrogen cyanide are added very slowly. The hydrocyanation

of dienes and alkenes (Sections 1.1.1.6 and 1.1.4.5) are much more widely used

procedures than the hydrocyanation of alkynes.

Scheme 51 Hydrocyanation of Alkynes [105]

Ph Ph + HCN

(E)-2,3-Diphenylprop-2-enenitrile (67): [105]

Ni

Ni[P(OPh) 3] 4

93%

Ph

H

Ph

CN

67

CAUTION: Hydrogen cyanide is highly toxic! Appropriate safety precautions and procedures

should be adopted during all stages of the handling and disposal of this reagent.

Into a 75-mL stainless steel autoclave were placed Ni[P(OPh) 3] 4 (0.24 g, 0.2 mmol), P(OPh) 3

(0.8g, 2.5 mmol), PhC”CPh (7 g, 39 mmol), HCN (1.25 mL, 32 mmol), and benzene (25 mL).

The vessel was heated at 1208C for 18h. After cooling, the benzene was removed by distillation.

Column chromatography (basic alumina, activity II, Et 2O/petroleum ether 1:9)

followed by distillation gave the unsaturated nitrile 67; yield: 6.12 g (93%).

1.1.3.10 Method 10:

Alkyne Hydrosilylation

Two distinct product classes, silylethenes and 1,2-disilylethenes, may be obtained from

the hydrosilylation of alkynes. The addition of trichlorosilane to alkynes in the presence

CO2H

1.1.3 Nickel–Alkyne Complexes 61

of (2,2¢-bipyridyl)diethylnickel(II) leads to the production of a mixture of both of these

product classes (Scheme 52). The mechanism for the formation of the unusual disilyl substituted

ethenes may involve a novel nickel disilyl species. [106] Hydrosilylations of bis(alkynes)

are described in the section on the couplings of two alkynes (Section 1.1.3.5).

Scheme 52 Hydrosilylation of Alkynes

R 1 R 1 + HSiCl 3

1.1.3.11 Method 11:

Alkyne Carbozincation

NiEt 2(bipy)

R1 Cl3Si R1 SiCl3 R1 H

R1 SiCl3 +

major minor

Knochel has demonstrated that phenylacetylenes undergo a highly stereoselective syncarbozincation

reaction by treatment with dialkylzincs or diphenylzinc in the presence

of catalytic bis(acetylacetonato)nickel(II) (1). [107,108] With alkynes that possess one aromatic

and one aliphatic substituent, the regioselectivity is very high, favoring the addition of

the organozinc substituent to the carbon that bears the aliphatic alkyne substituent,

whereas the regiochemical outcome reverses with aryl(silyl)alkynes (Scheme 53). The intermediate

alkenylzinc reagents may be quenched with a proton, iodine, or a variety of

other electrophiles in copper-catalyzed alkylations (Scheme 54). The combination of the

above methods provides a very versatile entry to tetrasubstituted alkenes.

Scheme 53 Nickel-Catalyzed Alkyne Carbozincation [107,108]

Ar 1 R 1 + R 2 2Zn

Ni(acac) 2 1

Ar1 H

R1 R2 Ar1 R2 R1 H

R1 = aliphatic R1 or

= TMS

Scheme 54 Sequential Alkyne Carbozincation and Electrophilic Trapping [107,108]

Ph Ph + R 1 2Zn

R 1

Ph

Ni(acac) 2 1

I

Ph

I 2

R 1

Ph

ZnR 1

Ph

1. CuCN 2LiCl

Br

2.

CO2Et

1. CuCN 2LiCl

2. R2COCl R 1

Ph

O

Ph

R 2

R 1

Ph

CO2Et

Ph

68 71%

Ethyl (Z)-2-Methylene-4,5-diphenylhept-4-enoate (68,R 1 = Et); Typical Procedure: [108]

[Ni(acac) 2](1; 320 mg, 1.25 mmol, 25%) and PhC”CPh (0.89 g, 5 mmol, 1 equiv) were dissolved

in THF (3.8mL) and NMP (1.3 mL) at –408C under argon. Et 2Zn (1.0 mL, 10 mmol,

2 equiv) was carefully added via syringe at –78 8C. The mixture was allowed to warm to

–35 8C and was stirred for 2.5 h. Meanwhile, a mixture of CuCN (1.79 g, 20 mmol, 4 equiv)

and LiCl (1.69 g, 40 mmol, 8equiv) was dried in vacuo at 1308C for 2 h and then dissolved in

THF (10 mL). The soln was cooled to –608C and added by syringe to the mixture at –788C.

The resulting dark soln was warmed to 0 8C for a few min and then cooled again to –788C.

Ethyl (2-bromomethyl)acrylate (4.82 g, 25 mmol, 5 equiv) was added and the mixture was

for references see p 79

62 Science of Synthesis 1.1 Organometallic Complexes of Nickel

allowed to warm to 258C and worked up. The crude product was purified by flash chromatography

(silica gel, hexane/Et 2O 20:1), affording the ester 68 as a white powder; yield:

1.13 g (71%); (Z/E) > 99:1.

1.1.4 Product Subclass 4:

Nickel–Alkene Complexes

Nickel complexes of alkenes are involved in many catalytic transformations. Many of the

reaction classes of alkenes involve migratory insertion of an alkylnickel or a hydridonickel

species. Alternatively, some transformations are initiated by the oxidative cyclization

of nickel–alkene complexes with a second unsaturated component to produce five-membered

metallacycles. Several examples of nickel–bis(alkene) complexes and nickel

metallacyclopentanes are known, and the interconversion of these two structural classes

has been studied (Scheme 55). [109,110]

Scheme 55 Ligand Dependence of Nickel Metallacycle Decomposition [109,110]

LNi L 2Ni L 3Ni

L = trialkyl- or triarylphosphine

Synthesis of Product Subclass 4

1.1.4.1 Method 1:

Ligand Exchange with Nickel(0) Complexes

2 H 2C CH 2

Many crystal structures of nickel–alkene complexes have been reported. As demonstrated

in Scheme 55, bis(alkene) complexes may exist in equilibrium with the corresponding

metallacyclopentane complex. However, several alkene complexes which have the potential

to undergo oxidative cyclization to a metallacycle have been fully characterized. The

substitution chemistry of bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2) is representative of most

nickel(0)–alkene complexes, which are readily substituted by a variety of ligands.

Bis(ç 2 -ethene)(tricyclohexylphosphine)nickel(0) has been prepared and fully characterized,

[111,189] and a variety of complexes of electron-deficient alkenes such as 69 have been

prepared which tend to be more stable than the complexes of ethene (Scheme 56). [112–114]

The alkene complexes may be prepared directly from bis(ç 4 -cycloocta-1,5-diene)nickel(0)

(2) [113] or from nickel(II) chloride [112] that is reduced by zinc metal.

Scheme 56 Preparation of Bis(methyl acrylate)(pyridine)nickel(0) [112]

NiCl 2 6H 2O + Zn +

N

+

CO2Me THF, 60 oC 70%

N Ni

CO2Me

CO2Me 69

1.1.4 Nickel–Alkene Complexes 63

Bis(methyl acrylate)(pyridine)nickel(0) (69): [112]

To NiCl 2 •6H 2O (4.7 g, 20 mmol), methyl acrylate (5.0 mL, 55 mmol), and pyridine (5.0 mL,

61 mmol) in THF (50 mL) was added Zn powder (5.0 g, 76 mmol). The suspension was heated

to 608C, and the oil bath was removed. After 2 h the mixture was filtered, and the solid

residue was washed with THF (3 ” 15 mL). After removal of the solvent in vacuo, extraction

with Et 2O (50 mL) left behind the insoluble zinc salts. Filtration and evaporation of

the extract in vacuo gave a red oil which was treated with hexane to dissolve the excess

pyridine and methyl acrylate. The hexane layer was discarded, and the residual oil was

dissolved in Et 2O (50 mL). Cooling to –188C afforded 69 as a pale orange powder; yield:

4.3 g (70%); mp 808C (dec).

Applications of Product Subclass 4 in Organic Synthesis

1.1.4.2 Method 2:

Conjugate Addition to Electrophilic Double Bonds

Nickel-catalyzed conjugate additions are among the most widely used synthetic applications

of nickel chemistry. Conjugate additions of a broad range of main-group and transition-metal

organometallics have been reported to be accelerated by nickel catalysis.

Bis(acetylacetonato)nickel(II) (1) is the most widely used catalyst due to its low cost and

air stability, although bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2) is an excellent catalyst for

most conjugate additions. Bis(acetylacetonato)nickel(II) (1) may be reduced by the nucleophilic

organometallic reagent (organozinc, organoaluminum, etc.), or more typically it

may be reduced with diisobutylaluminum hydride prior to treatment with the nucleophilic

organometallic reagent. The primary advantages of nickel-catalyzed conjugate additions

relative to organocuprates are increased thermal stability of the reagents and increased

efficiency with sterically hindered substrates. Several asymmetric variants have

been reported, but no general solution to the problem of asymmetric catalysis has been

reported. The four variations listed below have received the most attention, although additions

of triorganoindiums, [115] alkenylboranes, [116] and organotitaniums [117] have been reported.

Mackenzie has reported a related procedure with organotins that likely bears

mechanistic similarity to the procedures described here. [39] However, since this reaction

class was demonstrated to involve nickel–ð-allyl complexes, its description is included

in Section 1.1.2.7.2. It is worth noting that the variations described below may possibly

involve ð-allyl complexes as reactive intermediates in direct analogy to the model proposed

by Mackenzie. A comprehensive review of nickel-catalyzed nucleophilic additions

to activated alkenes has appeared. [186]

1.1.4.2.1 Variation1:

Organoaluminums

The bis(acetylacetonato)nickel(II)-catalyzed addition of trimethylaluminum was the firstreported

variant of nickel-catalyzed conjugate additions, [118,119] and a later report demonstrated

that the process is efficient with sterically demanding substrates such as 70 that

possess â,â-disubstituted enones (Scheme 57). [120] Significantly, alkynylaluminum reagents

efficiently transfer the alkynyl unit in a conjugate fashion to enones such as 71

(Scheme 57). [121,122] This transformation is notoriously difficult with organocopper chemistry.

Therefore, the nickel-catalyzed procedure is exceptionally useful.

for references see p 79

64 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Scheme 57 Nickel-Catalyzed Conjugate Addition of Organoaluminums [120–122]

O

70

71

O

+

Me 3Al

Ni(acac)2 1

87%

Me2Al Bu t

O

dr 1.5:1

Ni(acac) 2 1, DIBAL-H

Trimethylaluminum Conjugate Addition; General Procedure: [120]

CAUTION: Neat Me 3Al is highly pyrophoric! Appropriate safety precautions and procedures

should be adopted during all stages of the handling and disposal of this reagent.

To a stirred soln of [Ni(acac) 2](1; 128mg, 0.5 mmol), dry THF (15 mL) or EtOAc (15 mL), and

the enone (10 mmol) was added Me 3Al (1 mL, 10.5 mmol) dropwise at 0 8C. After an appropriate

time, the reaction was diluted with hexane (15 mL) and quenched by careful addition

of sat. aq NH 4Cl (1.5 mL) and worked up.

1.1.4.2.2 Variation2:

Organozincs

The conjugate addition of organozinc reagents under the influence of nickel catalysis is

by far the most widely used and most studied of the different variations. The original report

from Luche describes the conjugate addition of organozincs generated from a broad

range of alkyl, alkenyl, and aryl iodides, lithium metal, and anhydrous zinc(II) bromide to

give species such as 72 (Scheme 58). [123–125] Alternatively, the organozinc may be used as

the commercially available, salt-free organozinc, or as the in situ-generated diorganozinc

from transmetalation of zinc(II) chloride with an organolithium or organomagnesium reagent.

An interesting report from Houpis demonstrates that triorganozincates are more

effective than diorganozincs with less electrophilic substrates such as vinyl sulfoxides

and vinylpyridines (Scheme 58). [126,127] Organozinc conjugate additions have been widely

used in a variety of complex synthetic applications (Scheme 59). [128–130]

Scheme 58 Nickel-Catalyzed Conjugate Additions of Organozincs [123–127]

R 1

O

R 2

R 3 R 4

MeO

O

+

R 5 I

Li, ZnBr 2

Ni(acac) 2 1, )))

N

50−90%

R 1

67%

O

R 3

PhMgCl/ZnCl2 (3:1)

Ni(acac) 2 1

93%

72

R 4

R 2

R 5

MeO

O

73

Bu t

Ph

O

1.1.4 Nickel–Alkene Complexes 65

Scheme 59 Applications of Nickel-Catalyzed Conjugate Additions in Total Synthesis [128–130]

O

Me 2Zn, LiBr

Ni(acac) 2 1, Et2O

78%

1. Me2Zn, Ni(acac)2 1

2. TMSCl, Et 3N

O

TMSO

Advantages of organozinc conjugate additions compared with cuprate additions are the

thermal stability of the organozincs and increased reactivity of the kinetic zinc enolate

formed during the addition. The high reactivity of the kinetic zinc enolates allows conjugate

addition–enolate alkylation sequences to be quite effective, although some applications

require the use of sp 2 -hybridized organozincs, e.g. in the synthesis of (1R*,2R*,3R*)and

(1S*,2R*,3R*)-75 from bis(enone) 74 (Scheme 60). [91,131] Many asymmetric variants

have been reported with varying degrees of success. [132–138]

Scheme 60 Tandem Conjugate Additions of Bis(enones) with Organozincs [91,131]

O O

74

PhLi, ZnCl2

Ni(cod)2 2

Ph

Ac

(1R ∗ ,2R ∗ ,3R ∗ )-75 58%

+

Ph

O

Ac

(1S ∗ ,2R ∗ ,3R ∗ )-75 12%

Nickel-Catalyzed Conjugate Addition of Organozincs by Ultrasonication;

General Procedure: [125]

Solvents used were pure Et 2O, pure THF, or a mixture of toluene/THF (5:1 or 10:1). The organic

halide (10 mmol) and ZnBr 2 (1.13 g, 5.0 mmol) in the required solvent (23 mL) were

placed in the reaction flask under argon. The Li wire (150 mg, 21 mmol) was placed in the

holder under the ultrasonic probe. The flask was cooled in an ice bath, and stirring with a

magnetic bar ensured a homogeneous temperature. The energy level of the sonication

was adjusted to the minimum giving the cavitation noise, and a black color immediately

developed. After 30 min, irradiation was discontinued, and the resulting black soln (colorless

in reactions of MeI or MeBr) was transferred via a syringe into a round-bottomed flask

with a magnetic bar, under argon. When necessary, the flask was cooled in an ice or dry

ice/acetone bath. A soln of the substrate (2.5–4.8mmol) and [Ni(acac) 2](1; 20 mg) in the

required solvent (2 mL) was then added dropwise over a few min. When necessary, this

addition was made at a lower temperature and then allowed to warm slowly. After disappearance

of the starting material (TLC), the mixture was poured into sat. aq NH 4Cl, and

the product was worked up and isolated in the usual manner. Purification was effected

by column chromatography (silica gel) and the material was identified by the usual physical

methods.

4-{2-[3-(Cyclopentyloxy)-4-methoxyphenyl]-2-phenylethyl}pyridine (73): [127]

A soln of 0.5 M ZnCl 2 in THF (4 mL, 2 mmol) was cooled to 08C and treated with 2 M

PhMgCl in THF (3 mL, 6 mmol) so that the internal temperature did not exceed 108C.

for references see p 79

66 Science of Synthesis 1.1 Organometallic Complexes of Nickel

The slurry was then warmed to rt and stirred for 30 min. Additional THF (1 mL) was added

to facilitate stirring. The alkene (288 mg, 0.98 mmol) and [Ni(acac) 2](1; 18mg, 0.07 mmol)

were added sequentially as solids, and the resulting dark soln was heated immediately to

49–50 8C for 2–3 h. The reaction was monitored by HPLC and upon completion was

quenched with aq 1 M NH 4Cl. The resulting mixture was partitioned with EtOAc and the

organic layer was dried (Na 2SO 4) and concentrated under reduced pressure. The residue

was chromatographed to afford 73; yield: 348mg (93%).

1-[(1R*,2R*,3R*)-2-Acetyl-3-phenylcyclohexyl]acetone [(1R*,2R*,3R*)-75]: [131]

A1.59Mt-BuLi soln in pentane (1.7 mL, 2.7 mmol) was added dropwise to a soln of PhI

(0.273 g, 0.150 mL, 1.34 mmol) in THF (6 mL) at –788C. After stirring for 30 min at –788C

the yellow mixture was allowed to warm to 08C, and 1.0 M ZnCl 2 in Et 2O (0.90 mL,

0.90 mmol) was added dropwise by syringe. After 1 h, the resulting mixture and a soln of

[Ni(cod) 2](2; 5 mg, 0.018mmol) in THF (2 mL) were simultaneously transferred by cannula

to a soln of 74 (72 mg, 0.40 mmol) in THF (1 mL) at 08C. After stirring at 0 8C for 2 h the

brown mixture was quenched with sat. NaHCO 3 (25 mL), extracted with EtOAc

(3 ” 25 mL), dried (Na 2SO 4), filtered, and concentrated. Flash chromatography (silica gel,

hexanes/EtOAc 5:1) afforded, in order of elution, (1S*,2R*,3R*)-75 as a pale yellow oil and

(1R*,2R*,3R*)-75 as a white solid; both were homogeneous as judged by TLC analysis;

yields: (1S*,2R*,3R*)-75, 12 mg (12%); (1R*,2R*,3R*)-75, 60 mg (58%).

1.1.4.2.3 Variation3:

Organozirconiums

The conjugate addition of organozirconium reagents in the presence of catalytic amounts

of bis(acetylacetonato)nickel(II) (1) has received a modest level of attention (Scheme

61). [139–142] The alkenylzirconium 76 may be generated in situ by treatment of alkynes

with chloro(hydrido)zirconocene. It has perhaps received less attention than might be expected

owing to the popularity of the copper-catalyzed conjugate addition of organozirconiums.

[143]

Scheme 61 Conjugate Addition of Alkenylzirconiums [140–143]

ZrCp2Cl(H)

H Cp2ClZr H

H

76

O

Ni(acac)2 1

3-[(E)-3,3-Dimethylbut-1-enyl]cyclohexanone (77): [139]

Complex 76 (1.924 g, 5.67 mmol) and cyclohex-2-enone (0.623 g, 6.48mmol) were dissolved

in THF (30 mL) and cooled to 08C. [Ni(acac) 2](1; 0.151 g, 0.59 mmol) was added and

the mixture was stirred at 0 8C for 6.5 h. The mixture was quenched with NH 4Cl and extracted

with Et 2O. Compound 77 was isolated by distillation of the Et 2O solvent, followed

by preparative liquid chromatography of the resulting oil. Distillation of solvent from the

fraction containing the product gave 77; yield: 0.744 g (73%).

73%

O

1.1.4 Nickel–Alkene Complexes 67

1.1.4.2.4 Variation4:

Direct Conjugate Addition of Alkyl Halides

In contrast to each of the above variations, alkyl iodides may also be utilized directly in

nickel-catalyzed conjugate additions. The mechanism of this class of reactions is not well

defined; however, the related stoichiometric coupling of enals (e.g., 79) with alkyl halides

(e.g., 78) has been demonstrated to proceed through nickel–ð-allyl intermediates. [38] The

most widely used variant employs nickel(II) chloride hexahydrate in either catalytic or

stoichiometric quantities with activated zinc as a stoichiometric reductant (Scheme

62). [144–148] The organic halide may be either sp 2 or sp 3 hybridized, and alkene geometry

in the final product (e.g., 80) is maintained with alkenyl iodides.

Scheme 62 Conjugate Addition of Alkyl Iodides [145]

TBDMSO

O O

S

H

OTBDMS

78

H

I

+

NiCl2 6H2O

Zn, py

73%

CO2Et

79

TBDMSO

O O

S

H

OTBDMS

80

H

CO 2Et

The intramolecular conjugate addition of alkenyl iodides (e.g., 81) in the presence of a sixto

sevenfold excess of bis(ç 4 -cycloocta-1,5-diene)nickel(0) (2) has been reported (Scheme

63). [149,150] A large excess of nickel is required owing to its dual role of conjugate-addition

catalyst and nitroaromatic reducing agent. This provides an effective route to (€)-19,20-didehydrotubifoline

(80). Alkenyl iodides also add to nonactivated double bonds. [151,152]

Scheme 63 Conjugate Addition of Alkenyl Iodides [149,150]

O

O2N N

81

I

Ni(cod) 2 2

Et3N, LiCN

40%

N

82

H

for references see p 79

68 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Ethyl (5R)-5-[(1R,3aS,4E,7aR)-4-{[(4S,6R)-4,6-Bis(tert-butyldimethylsiloxy)-2,2-dioxo-

1,3,4,5,6,7-hexahydrobenzo[c]thiophen-1-yl]methylene}-7a-methyloctahydro-1Hinden-1-yl]hexanoate

(80): [145]

A mixture of pulverized NiCl 2 •6H 2O (2.38g, 10 mmol), Zn powder (3.27 g, 50 mmol), and

ethyl acrylate (79; 4.88 mL, 45 mmol) in pyridine (20 mL) was stirred at 608C under argon

for 30 min. The resulting dark red, heterogeneous mixture was cooled to 23 8C and treated

with a soln of 78 (7.49 g, 10 mmol) in pyridine (20 mL), producing a slight exotherm (23–

288C). After being stirred at rt for 2.5 h the mixture was worked up to give a pale yellow

foam (7.22 g), which was purified by flash chromatography (silica gel, 95 g, EtOAc/hexane

3:97; then EtOAc/hexane 5:95) to give, after evaporation of the solvents, 80; yield: 5.28g

(73%).

(€)-19,20-Didehydrotubifoline (82): [150]

A soln of the vinyl iodide 81 (47 mg, 0.11 mmol), 0.5 M LiCN in DMF (2.15 mL, 1.1 mmol),

and Et 3N (45 ìL, 0.32 mmol) in MeCN (5 mL) was added at rt to [Ni(cod) 2](2; 195 mg,

0.71 mmol). The resulting mixture was stirred at rt for 2.5 h and filtered through Celite,

washing carefully with Et 2O. The filtrate was sequentially washed with sat. aq Na 2CO 3

and brine. The dried organic phase was concentrated and chromatographed (Florisil,

CH 2Cl 2/MeOH 95:5) to give 82; yield: 11 mg (40%).

1.1.4.3 Method 3:

Coupling of Two Alkenes

The oxidative coupling of two unsaturated components coordinated to nickel(0) is a common

mechanistic theme throughout nickel chemistry (see also Houben–Weyl, Vol. E 18,

p 865). In the case of nickel–bis(alkene) complexes, a saturated nickel metallacyclopentane

is produced from such an oxidative cyclization. The interconversion of nickel(0)–

bis(alkene) complexes and nickel(II) metallacycles has been documented and carefully

studied (Scheme 55). However, most catalytic applications of this process have not been

rigorously defined from a mechanistic perspective. One case, however, that has been rigorously

studied is the formal [2+2+1] cycloaddition of an oxygen atom with two alkenes

to produce tetrahydrofurans. [153] The reaction proceeds by oxidative cyclization of a nickel(0)–bis(alkene)

complex to give a metallacycle 83, insertion of an oxygen atom from dinitrogen

monoxide into a C-Ni bond of metallacycle 83 to produce 84, and then oxidatively

induced reductive elimination with diiodine to produce the substituted tetrahydrofuran

85 (Scheme 64). Each of the intermediates shown was isolated and characterized.

Only strained alkenes were shown to participate in the process.

Scheme 64 [2+2+1] Cycloaddition of an Oxygen Atom and Two Alkenes [153]

Ni(cod)(bipy)

(bipy)Ni

83

N2O

44%

O

(bipy)Ni

The involvement of metallacycles has been proposed for the [3+2] cycloaddition of methylenecyclopropanes

with alkenes to produce methylenecyclopentanes. [154–156] Oxidative

cyclization of a methylenecyclopropane and an electron-deficient alkene produces a spirocyclic

metallacyclopentane 86. Cyclopropane ring opening followed by reductive elimination

affords the observed methylenecyclopentane products 87 and 88 (Scheme 65). Another

report describes the novel use of nanostructured nickel clusters as catalysts. [157]

84

I2

47%

O

1.1.4 Nickel–Alkene Complexes 69

Scheme 65 [3+2] Cycloadditions Involving Methylenecyclopropanes [154–156]

L nNi

E

R 1

+

R 2

R 1

E

E = electron-withdrawing group

Ni(cod)2 2

L nNi

E

86

R 1

R 2

R 1

E R 2

87

+

R 1

LnNi

E R 2

88

R 1

E R 2

+ L nNi

R 1

E R 2

The reductive coupling of bis(enones) is another reaction class that may involve alkenederived

metallacyclopentanes. Treatment of a symmetrical bis(enone) 89 with bis(ç 4 -cycloocta-1,5-diene)nickel(0)

(2) and butyllithium/zinc(II) chloride leads to coupling of the

two enone â-carbons followed by an intramolecular aldol addition to afford bicyclo[3.3.0]octanols

90 (Scheme 66). [91,131] Sterically hindered enones have also been shown to participate

in this reaction class, as evidenced by the spirocyclization of a substituted cyclopentenone

to produce an angular triquinane (Scheme 66). [158]

Scheme 66 Reductive Cyclization–Aldol Addition of Bis(enones) [91,131,158]

R 1

O

89

O

R 1

N

O

Ni(cod) 2 2

BuLi, ZnCl2 BuZnO O

R 1

R 1 = Ph 60%

O

Ni(cod)2 2

Et2Zn, ZnCl2

O H

58% H

R 1

O

HO

R 1

H H

The dimerization of alkenes has been extensively studied by Wilke (Scheme 67). [5] In the

tail-to-tail dimerization of methyl acrylate, cationic nickel hydride species have been proposed

as the active catalysts. The mechanism of this process proceeds by alkene hydrometalation,

insertion of a second equivalent of methyl acrylate, and then â-hydride elimination

to release the product and generate the nickel hydride catalyst.

90

for references see p 79

70 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Scheme 67 Tail-to-Tail Dimerization of Methyl Acrylate [5]

MeO2C

MeO 2C

Ni PMe + 3

CO 2Me

MeO2C

MeO 2C

Ni PMe + 3

CO 2Me

MeO 2C

MeO2C

H + PMe3

Ni

CO 2Me

CO2Me

RajanBabu has developed an asymmetric protocol for the heterodimerization of vinylarenes

and ethene. [159] The use of Hayashi s novel, weakly chelating phosphine 91 is critical

to the success of this asymmetric reaction (Scheme 68). 1,6-Dienes (e.g., 92) also undergo

direct cycloisomerization in the presence of bis[allyl(bromo)nickel] to afford methylenecyclopentane

products (e.g., 93; Scheme 69). The scope of the intramolecular process

allows preparation of a variety of carbocyclic and heterocyclic ring systems. A reaction

mechanism involving in situ generation of a nickel hydride catalyst, alkene hydrometalation,

cyclization, and â-hydride elimination has been proposed. [160]

Scheme 68 Asymmetric Hydrovinylation of Alkenes [159]

H

Ar 1

L ∗ =

R 1 = Me, Bn

+

91

OR 1

PPh2

[NiBr(H2C CHCH 2)] 2, NaBAr 4, L ∗

Scheme 69 Cycloisomerization of Dienes [160]

R 1

92

Ar 1

O O

[NiBr(H 2C CHCH 2)] 2, R 1 3P

[NiHL n] +

R 1

81%

NiL n +

R 1

R 1 NiL n +

− [NiHLn] +

92%

R 1

1.1.4 Nickel–Alkene Complexes 71

[5,5¢-Bi(bicyclo[2.2.1]hept-2-en)-6-yl-kC 6 -6¢-olato-kO](2,2¢-bipyridyl-k 2 N 1 ,N 1 ¢)nickel (84): [153]

A sample of 83 (0.35 g, 0.94 mmol) and benzene (10 mL) were placed in a round-bottomed

flask attached to a swivel-frit assembly. The soln was stirred under N 2O (1 atm) at 55 8C for

3 d, after which the soln was filtered and the filtrate was taken to dryness under vacuum.

The resulting solid was washed with petroleum ether (3 ” 5 mL), and the blue product was

collected on a filter frit to give microcrystalline 84; yield: 0.16 g (44%).

exo-trans-endo-3-Oxapentacyclo[9.2.1.1 5,8 .0 2,10 .0 4,9 ]pentadeca-6,12-diene (85): [153]

A sample of 84 (0.12 g, 0.31 mmol) and benzene (10 mL) were placed in a round-bottomed

flask, to which I 2 (0.08g, 0.31 mmol) was added under an argon counterflow. There was an

immediate color change from blue to brown. The soln was stirred for 30 min at rt and filtered,

and the filtrate was evaporated using a rotary evaporator. The residue was chromatographed

(silica gel, hexane/EtOAc 100:3) to give 85 as a colorless oil; yield: 0.03 g

(47%).

(1R*,2S*,3R*,5R*)-2-Benzoyl-3-phenylbicyclo[3.3.0]octane-3-ol (90, R 1 = Ph);

Typical Procedure: [131]

A mixture of 2.44 M BuLi in hexane (0.43 mL, 1.05 mmol) and 1.0 M ZnCl 2 in Et 2O (0.70 mL,

0.70 mmol) in THF (5 mL) was stirred for 1 h at 08C. A soln of [Ni(cod) 2] (2; 3mg,

0.01 mmol) in THF (2 mL) was added by syringe, and the resulting soln was immediately

transferred by cannula to a soln of 89 (91 mg, 0.30 mmol) in THF (3 mL) at 08C. After stirring

for 1.5 h at 0 8C the deep red mixture was quenched with sat. NaHCO 3 (20 mL), extracted

with EtOAc (3 ” 25 mL), dried (Na 2SO 4), filtered, and concentrated. The residue

was chromatographed (silica gel, Et 2O/pentane 1:15) to afford 90 (R 1 = Ph) as a white crystalline

solid; yield: 56 mg (60%).

Dimethyl 3-Methyl-4-methylenecyclopentane-1,1-dicarboxylate (93,R 1 =CO 2Me);

Typical Procedure: [160]

The catalyst precursor was prepared as follows. To a soln of [{Ni(allyl)Br} 2] (4.2 mg,

0.012 mmol, 2.5 mol%, 0.05 equiv in Ni) in CH 2Cl 2 (1 mL) was added tris(4-methoxyphenyl)phosphine

(8.5 mg, 0.024 mmol) in CH 2Cl 2 (1 mL). The mixture was stirred for 30 min, after

which AgOTf (6 mg, 0.024 mmol) was added in one lot. After 30 min of stirring, a precipitate

was formed (AgBr), which was subsequently removed by filtration through a pipet

containing a plug of Celite. The catalyst was cooled to –348C and introduced into a

soln of 92 (100 mg, 0.47 mmol) in CH 2Cl 2 (2 mL) at rt. The soln was stirred at rt for 2 h, after

which the reaction was stopped and the mixture was concentrated. Analysis of the crude

product showed it to be 92% of the expected product 93 and 8% starting material. The

crude product was chromatographed on a column (silica gel, hexane/Et 2O 9:1) to afford

pure 93 (R 1 =CO 2Me); yield: 92 mg (92%).

1.1.4.4 Method 4:

Alkene Carbonylation

The carbonylation of alkenes proceeds readily upon treatment of an alkene with a nickel

catalyst in the presence of carbon monoxide and an alcohol or water (Scheme 70). [7,11,104]

Tetracarbonylnickel(0) is the most commonly used nickel catalyst, although it is highly

toxic. [188] This process is very useful for the carbonylation of simple alkenes such as

ethene, but it has seen little use with complex organic molecules.

Scheme 70 Carbonylation of Alkenes [104]

H 2C CH 2 + CO + H 2O

Ni

CO 2H

for references see p 79

72 Science of Synthesis 1.1 Organometallic Complexes of Nickel

1.1.4.5 Method 5:

Alkene Hydrocyanation

The hydrocyanation of alkenes is a well-studied and synthetically useful process. [33,161,162]

A significant amount of the attention that this reaction has received is derived from its

utility in the preparation of adiponitrile from butadiene (Section 1.1.1.6). A complete catalytic

cycle for the hydrocyanation of alkenes is shown in Scheme 71. Steric effects in the

Lewis acid promoter have been shown to affect critically the reaction selectivities. [163]

Scheme 71 Mechanism of Alkene Hydrocyanation [33]

EtCN

L C2H4 L

NC

Ni Et

L

Ni

L

L Ni Et L Ni H

CN

H2C CH2 HCN

L2 Ni

CN

H

The asymmetric hydrocyanation of alkenes has also received considerable attention.

[164,165] In a representative example by RajanBabu, the glucose-derived phosphine ligand

94 allows useful enantioselectivities to be obtained in the hydrocyanation of arylsubstituted

alkenes (Scheme 72).

Scheme 72 Asymmetric Hydrocyanation of Alkenes [164,165]

1 Ar + HCN

L = Ph O

O

Ar2 Ar

2P

2 2P

94

OPh

NiL

Ar 1

CN

up to 90% ee

Asymmetric Hydrocyanation; General Procedure: [164]

CAUTION: Hydrogen cyanide is highly toxic! Appropriate safety precautions and procedures

should be adopted during all stages of the handling and disposal of this reagent.

Catalyst scouting reactions were carried out by the dropwise addition of a toluene soln of

HCN (typically 0.05–1.0 equiv of HCN per equiv of alkene) to a hexane soln of the alkene

(0.1–0.2 M), [Ni(cod) 2](2; 0.01–0.5 equiv), and the chiral ligand (0.01–0.05 equiv). Ligands

that were insoluble in hexane were stirred separately with [Ni(cod) 2] in benzene. The resulting

catalyst solns were evaporated to dryness and then the residue dissolved or slurried

with hexane and the substrate. Hydrocyanation reactions were usually stirred at rt

(~ 258C) overnight. The product nitriles were isolated by flash chromatography (typically

silica gel, hexane/Et 2O 90:10).

1.1.4 Nickel–Alkene Complexes 73

1.1.4.6 Method 6:

Alkene Hydrosilylation

The hydrosilylation of alkenes is an effective method for converting terminal or cyclic alkenes

into functionalized silanes (Scheme 73). [12,166] Silicon is directed to the more electron-rich

alkene terminus. Trichlorosilane is generally the most effective silane, and a variety

of nickel catalysts may be employed. Relatively high temperatures are required

(1208C), and nickel catalysts substituted with electron-rich phosphines generally are the

most efficient.

Scheme 73 Hydrosilylation of Alkenes [166]

R 1

R 2

+

HSiCl 3

NiCl2(PR 3 3)2

Alkene Hydrosilylation; General Procedure: [166]

Alkene (1 equiv), hydrosilane (2 equiv), and nickel catalyst (10 –3 equiv) were placed in a

glass ampule and degassed at –1968C, and the ampule was then sealed. After heating for

a given period of time, the ampule was cooled to –788C before opening. Products were

isolated by fractional distillation where possible, or by preparative GC after flash distillation.

1.1.4.7 Method 7:

Alkene Hydroalumination

The nickel-catalyzed hydroalumination of alkenes has been extensively investigated in a

variety of contexts. The interaction of aluminum hydrides with nickel(0) and the mechanism

of alkene hydroalumination has been studied in detail by Wilke, [5] Eisch, [167] and

Zweifel. [168] The most extensive synthetic applications from Lautens involve the hydroalumination

of oxabicyclic alkenes followed by ring opening to produce substituted cyclohexenes

and cycloheptenes (Scheme 74). [169–171] An asymmetric variant employing

2,2¢-bis(diphenylphosphino)-1,1¢-binaphthyl (BINAP) is also quite general for various oxabicyclic

starting materials.

Cl 3Si

Scheme 74 Nickel-Catalyzed Hydroalumination–Ring-Opening Sequence [169–171]

O

OMe

OBn

OMe

DIBAL-H

10 mol% Ni(cod) 2 2

DIBAL-H

10 mol% Ni(cod) 2 2

DIBAL-H

3 mol% Ni(cod) 2 2

5 mol% (R)-BINAP

95%

O

Bu

H

i 2Al

O

Bui H

2Al

R 1

H

R 2

OMe

OBn

OH

97% ee

OMe

iBu2AlCl

HO

OMe

OH

OBn

OMe

for references see p 79

74 Science of Synthesis 1.1 Organometallic Complexes of Nickel

It is unclear whether the hydroalumination proceeds by hydronickelation or aluminonickelation,

and the mechanistic details may vary according to substrate and catalyst

structure. However, the pathways shown in Scheme 75 are likely mechanistic pathways

based on the data obtained.

Scheme 75 Mechanism of the Hydroalumination–Ring-Opening Sequence [169–171]

O

H Ni AlR2 2

O

H Ni AlR 2 2

O

R 2 2Al Ni H

O

H AlR 2 2

O

product

A related procedure for the cleavage of allyl ethers has been developed by Ogasawara.

Treatment of an allyl ether with diisobutylaluminum hydride and catalytic [1,3-bis(diphenylphosphino)propane]dichloronickel

leads to facile cleavage of the allylic C-O

bond (Scheme 76). [172,173] A mechanism similar to that proposed for the hydroalumination–ring

opening of oxabicyclic alkenes is suggested.

Scheme 76 Nickel-Catalyzed Allyl Ether Cleavage [172,173]

R 1 O

95

DIBAL-H (1.5 equiv)

1 mol% NiCl2(dppp) R 1 O

AlBui 2

H

R 1 = 4-MeOC6H4 90%

R 1 OH +

Reductive Ring Opening; General Procedure: [171]

The reaction scale was typically 0.3–0.5 mmol. [Ni(cod) 2](2; 0.1 equiv) in toluene (1.0 mL)

was added to dppb (0.2 equiv), and the resulting light brown soln was stirred at rt for 1 h.

Substrates bearing a free hydroxy moiety were premixed with 1.0 M DIBAL-H in hexanes

(1.1 equiv) in toluene (1.0 mL) to form the aluminum alkoxide. Protected alcohols were

dissolved in toluene (1.0 mL) and added directly to the flask containing [Ni(cod) 2] and

dppb. DIBAL-H (1.1–1.9 equiv) was added via a syringe pump over the indicated time. The

reaction was quenched by the addition of sat. aq NH 4Cl, and sufficient 10% HCl was added

to make the aqueous layer transparent. The organic layer was separated, and the aqueous

layer was extracted with Et 2O (3 ”). The combined organics were dried (MgSO 4). Removal

of the solvent in vacuo yielded a product mixture that was purified by chromatography. If

the reaction product was a diol, the reaction was quenched by 1.1 M potassium sodium

tartrate soln (1.0 mL). The resulting suspension was stirred at rt for 4 h and filtered, and

the white gel was washed with hot EtOAc several times. The combined filtrate was dried

(Na 2SO 4) and removal of the solvent in vacuo yielded a product mixture that was purified

by chromatography.

1.1.4 Nickel–Alkene Complexes 75

4-Methoxyphenol (96,R 1 = 4-MeOC 6H 4); Typical Procedure: [172]

A 1.5 M soln of DIBAL-H in toluene (600 ìL, 0.9 mmol) was added dropwise to a stirred soln

of 95 (R 1 = 4-MeOC 6H 4; 100 mg, 0.6 mmol) and NiCl 2(dppp) (3 mg, 6 ìmol) in Et 2O(2mL)

under argon at 0 8C. The mixture was stirred for 5 min at the same temperature and then

for 2 h at rt. The mixture was diluted with Et 2O (3 mL), quenched by addition of H 2O

(600 ìL) and, after stirring for 1 h, dried (MgSO 4), filtered through a Celite pad, and concentrated

under reduced pressure to leave the crude product which was chromatographed

(silica gel, 3 g, Et 2O/hexane 1:4) to give pure 96 (R 1 = 4-MeOC 6H 4); yield: 68mg

(90%).

1.1.4.8 Method 8:

Alkene Hydrozincation

The nickel-catalyzed hydrozincation of alkenes provides a novel method for the preparation

of functionalized organozincs such as (97) (Scheme 77). [174,175] The resulting functionalized

organozincs may be transformed into cuprate reagents and then alkylated with a

variety of electrophiles. A hydronickelation step is likely involved in the reaction pathway.

Scheme 77 Nickel-Catalyzed Hydrozincation of Alkenes [174,175]

2

R 1

ZnEt 2

+ ZnEt 2

Ni(acac) 2 1

R 1

Dioctylzinc [97,R 1 =(CH 2) 5Me]: [175]

2

1−2 mol% Ni(acac)2 1

1−4 mol% cod

acac

LnNi Et

Zn

R 1 = (CH 2) 5Me 38%

ZnEt 2

acac

LnNi

H

acac

LnNi Zn

1 R +

2

97

R 1

acac

LnNi H

2 H 2C CH 2

H2C CH2

CAUTION: Large quantities of gaseous ethene are produced in the reaction, especially for largescale

reactions!

A 50-mL two-necked flask equipped with an argon inlet, a magnetic stirring bar, and a septum

cap was charged with [Ni(acac) 2](1; 26 mg, 0.10 mmol, 1 mol%) and cycloocta-1,5-diene

(22 mg, 0.20 mmol, 2 mol%), followed by oct-1-ene (1.12 g, 10.0 mmol). The mixture

was cooled to 0 8C, and ZnEt 2 (0.61 mL, 6.0 mmol, 0.6 equiv) was added dropwise. The cooling

bath was removed, and the mixture was stirred in a preheated oil bath at 50–60 8C for

3 h. The conversion was checked by iodolysis of an aliquot of the mixture (40–45%). The

excess ZnEt 2 and unreacted alkene was distilled off in vacuo, yielding 97 [R 1 =(CH 2) 5Me];

yield: 0.65 g (38%).

R 1

for references see p 79

76 Science of Synthesis 1.1 Organometallic Complexes of Nickel

1.1.4.9 Method 9:

Alkene Carbozincation

The nickel-catalyzed carbozincation has been developed into a broadly useful method for

the cyclization of alkenes tethered to alkyl iodides (Scheme 78). [176–178] The functionalized

organozincs (e.g., 99) prepared by the nickel-catalyzed cyclizations may be further utilized

in a wide variety of copper-mediated alkylations of reactive electrophiles. The reaction

mechanism may not involve the formation of nickel–alkene complexes; however,

this reaction class is included owing to its synthetic relationship to many processes that

do include nickel–alkene complexes. A free-radical cyclization appears to be most consistent

with the data provided.

Scheme 78 Nickel-Catalyzed Carbozincation [176–178]

I

O

OR 1 R 2

98

+ ZnEt2

Ni(acac)2 1

R 1 O

O

99

CH2ZnI

A nickel-catalyzed carbozincation in which an allylzinc adds across the double bond of an

unsaturated acetal has also been reported (Scheme 79). [179] This procedure effectively provides

a reverse-polarity approach to the functionalization of unsaturated carbonyl derivatives.

Non-allylic Grignard reagents, however, add to cyclic unsaturated acetals with the

opposite regiochemistry. This latter procedure provides the basis for an enantioselective

conjugate addition to cyclic enones (in 53% ee for the cyclopentenyl substrate and 85% ee

for the cyclohexenyl homologue). [180]

Scheme 79 Addition of Organozincs to Unsaturated Acetals [179,180]

O

R 1 O OR 1

R 2 = alkyl or aryl

+

R 2 MgBr

ZnBr

Ph2

P

NiCl2

P

Ph2

NiBr2(PBu3)2

[(5-Butoxytetrahydrofuran-3-yl)methyl](iodo)zinc(II) (99, R 1 = Bu; R 2 =H);

Typical Procedure: [176]

A 50-mL three-necked flask equipped with an argon inlet, a magnetic stirring bar, an internal

thermometer, and a septum cap was charged with [Ni(acac) 2](1; 15 mg, 0.06 mmol,

2 mol%), and a soln of the iodoalkane 98 (R 1 = Bu, R 2 = H; 0.85 g, 3.0 mmol, 1 equiv) in THF

(5 mL) was added. The resulting green suspension was cooled to –788C, and ZnEt 2 (0.6 mL,

6.0 mmol, 2 equiv) was added dropwise. The mixture was allowed to warm to 0 8C and

stirred at this temperature for 2 h. The excess of Et 2Zn and the solvent were removed in

vacuo (rt, 2 h) to leave the crude product; no yield was reported.

OR 1

R 2

ZnBr

O

1.1.4 Nickel–Alkene Complexes 77

1.1.4.10 Method 10:

Homo-Diels–Alder Cycloadditions

The nickel-catalyzed homo-Diels–Alder cycloaddition with norbornadienes and electrondeficient

alkenes is an effective method for generating strained polycyclic compounds. [181]

At the time of writing, this method is the only strategy for carrying out a nickel-catalyzed

[2+2+2] cycloaddition with three alkene ð-systems such that six contiguous stereocenters

may be generated. Both acyclic and cyclic enones participate in the process (Scheme

80).

Scheme 80 Nickel-Catalyzed Homo-Diels–Alder Reactions [181]

+

O

5−10 mol% Ni(cod) 2 2

10−20 mol% Ph3P 56% H H

Nickel-Catalyzed Diels–Alder Cycloaddition; General Procedure: [181]

[Ni(cod) 2](2; 10–25 mol%) was added to a flame-dried flask equipped with a magnetic stirring

bar and a rubber septum in the glovebox. Ph 3P (2 equiv, with respect to Ni) was introduced

against a positive flow of N 2, and the diene (1 mmol) was added in 1,2-dichloroethane

or toluene followed by the dienophile (2 mmol) as a neat liquid. The mixture was

stirred at the desired temperature under N 2 for 16–48h. The workup was as follows: The

catalyst was oxidized by stirring with the flask open to the air for 1–2 h. The reaction mixture

was filtered through a plug of silica gel using CH 2Cl 2 (100 mL) as the eluant. Evaporation

of the solvent gave a crude product, which was purified by Kugelrohr (bulb-to-bulb)

distillation or flash chromatography on silica gel.

1.1.4.11 Method 11:

Alkene Polymerization

While not emphasized in this review, the oligomerization and polymerization of ethene

forms the basis of some of the most significant industrial processes involving nickel catalysis

(see also Houben–Weyl, Vol. E 18, pp 847–863; E 20/II, pp 807–813). The Shell Higher

Order Process (SHOP), nicely described in a review by Keim, involves the oligomerization

of ethene to produce Æ-alkenes (Scheme 81). [7] Nickel polymerization catalysts were first

reported in the 1950s; [7] however, cationic nickel diimine complexes have been identified

by Brookhart as highly efficient ethene polymerization catalysts (Scheme 82). [182–185] The

unique ligand class with highly hindered ortho-substituted aryl rings on the nitrogens of

the diimine ligand results in rates of chain propagation which are much greater than

chain transfer rates, thus allowing the formation of high-molecular-weight polymers.

Scheme 81 Shell Higher Order Process [7]

H2C CH2 LnNi H LnNi C2H5 O

L =

−

O

PPh2

O

L nNi CH 2CH 2R 1

L nNi C 4H 9

R 1

L nNi H

for references see p 79

78 Science of Synthesis 1.1 Organometallic Complexes of Nickel

Scheme 82 Nickel-Catalyzed Ethene Polymerization [182–185]

Ar 1 =

R 1

Ar 1

N

Ni

N

Ar 1

Br

H2C CH2

methylaluminoxane

Ar

N

Ni

N

1

Ar1 +

Ar

N

Ni

N

1

Ar1 + Me

n

polyethene

References 79

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[165] Horiuchi, T.; Shirakawa, E.; Nozaki, K.; Takaya, H., Tetrahedron: Asymmetry, (1997) 8, 57.

[166] Kiso, Y.; Kumada, M.; Tamao, K.; Umeno, M., J. Organomet. Chem., (1973) 50, 297.

[167] Eisch, J. J., In Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford,

(1991); Vol. 8, p 733.

[168] Zweifel, G.; Miller, J. A., Org. React., (1984) 32, 375.

[169] Lautens, M.; Chiu, P.; Ma, S.; Rovis, T., J. Am. Chem. Soc., (1995) 117, 532.

[170] Lautens, M.; Rovis, T., J. Am. Chem. Soc., (1997) 119, 11090.

[171] Lautens, M.; Ma, S.; Chiu, P., J. Am. Chem. Soc., (1997) 119, 6478.

[172] Taniguchi, T.; Ogasawara, K., Angew. Chem., (1998) 110, 1137; Angew. Chem. Int. Ed. Engl., (1998)

37, 1136.

[173] Taniguchi, T.; Ogasawara, K., Tetrahedron Lett., (1998) 39, 4679.

[174] Vettel, S.; Vaupel, A.; Knochel, P., Tetrahedron Lett., (1995) 36, 1023.

[175] Vettel, S.; Vaupel, A.; Knochel, P., J. Org. Chem., (1996) 61, 7473.

[176] Vaupel, A.; Knochel, P., J. Org. Chem., (1996) 61, 5743.

[177] Vaupel, A.; Knochel, P., Tetrahedron Lett., (1994) 35, 8349.

[178] Stadmüller, H.; Vaupel, A.; Tucker, C. E.; Stüdemann, T.; Knochel, P., Chem. Eur. J., (1996) 2, 1204.

[179] Yanagisawa, A.; Habaue, S.; Yamamoto, H., J. Am. Chem. Soc., (1989) 111, 366.

[180] Gomez-Bengoa, E.; Heron, N. M.; Didiuk, M. T.; Luchaco, C. A.; Hoveyda, A. H., J. Am. Chem. Soc.,

(1998) 120, 7649.

[181] Lautens, M.; Edwards, L. G.; Tam, W.; Lough, A. J., J. Am. Chem. Soc., (1995) 117, 10276.

[182] Johnson, L. K.; Killian, C. M.; Brookhart, M., J. Am. Chem. Soc., (1995) 117, 6414.

[183] Killian, C. M.; Tempel, D. J.; Johnson, L. K.; Brookhart, M., J. Am. Chem. Soc., (1996) 118, 11664.

[184] Killian, C. M.; Johnson, L. K.; Brookhart, M., Organometallics, (1997) 16, 2005.

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Science of Synthesis

Houben–Weyl Methods of Molecular Transformations

Sample Contribution

Category Organometallics

Volume 2 Compounds of Groups 7–3

(Mn…,Cr…,V…, Ti…,Sc…,La…,Ac…)

Product Class 2.6 Organometallic Complexes of

Chromium, Molybdenum, and Tungsten

without Carbonyl Ligands

Written by R. Poli and K. M. Smith

2003 Georg Thieme Verlag

Rüdigerstrasse 14

D-70469 Stuttgart

Printed in Germany

Typesetting: epline, Kirchheim unter Teck

Printing: Konrad Triltsch, Ochsenfurt-Hohestadt

Binding: Koch, Tübingen

Bibliographic Information published by Die Deutsche

Bibliothek

Die Deutsche Bibliothek lists this publication in the

Deutsche Nationalbibliografie; detailed bibliographic

data is available on the internet at

Library of Congress Cataloging in Publication Data

Science of synthesis : Houben–Weyl methods of

molecular transformations.

p. cm.

Includes bibliographical references and index.

Contents: category 1. Organometallics. v. 2. Compounds

of groups 7–3 (Mn … ,Cr … ,V … ,Ti … ,Sc … ,

La … ,Ac … ) / volume editor, T. Imamoto

ISBN 3-13-112141-6 – ISBN 0-86577-941-4 (v. 2)

1. Organic compounds–Synthesis. I. Title: Houben–

Weyl methods of molecular transformations.

QD262 .S35 2000

547'.2–dc21

00-061560

(Houben–Weyl methods of organic chemistry)

British Library Cataloguing in Publication Data

Science of Synthesis : Houben–Weyl methods

of molecular transformation

Category 1: Organometallics:

Vol. 2: Compounds of groups 7–3 (Mn … ,Cr … ,V … ,

Ti … ,Sc … ,La … ,Ac … ). – (Houben–Weyl methods

of organic chemistry)

1. Organometallic compounds – Synthesis

I. Imamoto, T., II. Barbier-Baudry, D.

547' .05

ISBN 3-13-112141-6

(Georg Thieme Verlag, Stuttgart)

ISBN 0-86577-941-4

(Thieme New York)

Date of publication: October 9, 2002

85

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86

Biographical Sketches

Rinaldo Poli obtained his Ph.D. in 1985 from the Scuola Normale Superiore

in Pisa under the supervision of Fausto Calderazzo. He spent one

year with Geoffrey Wilkinson (exchange student, 1983–1984) and two

years with Al Cotton (research associate, 1985–1987). He started his

career at the University of Maryland, College Park, where he rose the

ranks to Full Professor, and moved to his current Professor position in

1996. He has been Camille and Henry Dreyfus Distinguished New

Faculty (1987), Presidential Young Investigator (1990), Alfred P. Sloan

Research Fellow (1992), Alexander von Humboldt Forschungsstipendiat

(1993), and a recipient of the Medaglia Nasini from the Italian Chemical Society (1992).

Visiting Professor positions include the Technische Universität München (1993–1994),

Tokyo Metropolitan University (1995), the Inorganic Chemistry Laboratory in Oxford

(1998), and Los Alamos National Laboratory (2001 and 2002).

Kevin Smith was born in 1969 in Toronto, Canada. He received a B. Sc.

degree in chemistry from the University of Toronto in 1992 and a Ph.D.

in inorganic chemistry from the University of British Columbia in 1998

with Peter Legzdins. After postdoctoral research with Rinaldo Poli, he

joined the faculty at the University of Prince Edward Island in 2000,

where he is now Assistant Professor.

2.6 Product Class 6: Organometallic Complexes of Chromium,

Molybdenum, and Tungsten without Carbonyl Ligands

R. Poli and K. M. Smith

2.6 Product Class 6: Organometallic Complexes of Chromium, Molybdenum,

and Tungsten without Carbonyl Ligands .................................. 90

2.6.1 Product Subclass 1: Metal–Carbene Complexes ........................... 90

Synthesis of Product Subclass 1 ............................................ 91

2.6.1.1 Method 1: By Æ-Hydrogen Elimination from Alkyl Complexes ........... 91

2.6.1.1.1 Variation 1: Alkylation of Chloride Precursors ............................ 91

2.6.1.1.2 Variation 2: Ligand Addition ............................................ 92

2.6.1.1.3 Variation 3: Replacement of an Oxo or Imido Ligand ..................... 93

2.6.1.1.4 Variation 4: Deprotonation with an External Base ........................ 94

2.6.1.2 Method 2: By Stoichiometric Alkene Metathesis ........................ 94

2.6.1.3 Method 3: By Carbene Transfer ........................................ 95

2.6.1.4 Method 4: From Carbyne Complexes .................................. 96

Applications of Product Subclass 1 in Organic Synthesis ..................... 97

2.6.1.5 Method 5: Alkene Metathesis ......................................... 97

2.6.1.5.1 Variation 1: Ring-Opening Metathesis Polymerization (ROMP) ............ 98

2.6.1.5.2 Variation 2: Alkyne Polymerization ...................................... 98

2.6.1.5.3 Variation 3: Ring-Closing Metathesis .................................... 99

2.6.1.5.4 Variation 4: Other Selective Metathesis Processes ...................... 101

2.6.1.6 Method 6: Carbonylmethylenation ................................... 102

2.6.2 Product Subclass 2: Metal–Carbyne Complexes .......................... 103

Synthesis of Product Subclass 2 ........................................... 104

2.6.2.1 Method 1: By Æ,Æ-Hydrogen Elimination from Alkyl Complexes ........ 104

2.6.2.2 Method 2: By Addition of Alkynes to Compounds with

Metal-Metal Triple Bonds ................................. 105

2.6.2.3 Method 3: By Stoichiometric Alkyne Metathesis ....................... 106

2.6.2.4 Method 4: By Oxidation of Fischer-Type Carbyne Complexes ........... 107

2.6.2.5 Method 5: By Rearrangement of Vinyl Complexes ..................... 108

2.6.2.6 Method 6: By Other Rearrangement Processes ........................ 109

Applications of Product Subclass 2 in Organic Synthesis .................... 110

2.6.2.7 Method 7: Alkyne Metathesis ........................................ 110

2.6.3 Product Subclass 3: Metal–ó-Alkyl and –ó-Aryl Homoleptic Complexes .. 110

Synthesis of Product Subclass 3 ........................................... 111

2.6.3.1 Method 1: By Transmetalation ........................................ 111

2.6.4 Product Subclass 4: Metal–ó-Alkyl and –ó-Aryl Non-homoleptic Complexes 112

Synthesis of Product Subclass 4 ........................................... 113

2.6.4.1 Method 1: By Transmetalation ........................................ 113

2.6.4.2 Method 2: By Oxidative Addition of Alkyl Halides ...................... 114

2.6.4.2.1 Variation 1: One-Electron Oxidative Additions .......................... 114

88

2.6.4.2.2 Variation 2: Two-Electron Oxidative Additions .......................... 114

2.6.4.3 Method 3: By Oxidative Addition of Alkanes and Arenes ............... 115

2.6.4.4 Method 4: By Protonation of Carbene and Carbyne Ligands ............ 116

Applications of Product Subclass 4 in Organic Synthesis .................... 116

2.6.4.5 Method 5: Addition of Organochromium(III) Compounds to

Carbonyl Compounds ..................................... 117

2.6.4.5.1 Variation 1: Reaction of Organochromium(III) Compounds Prepared

from Organochromium(III) Chloride by Transmetalation ..... 117

2.6.4.5.2 Variation 2: Reaction of Organochromium(III) Compounds Prepared

from Chromium(II) Chloride by Oxidative Addition

(The Nozaki–Hiyama–Kishi Procedure) ..................... 118

2.6.4.5.3 Variation 3: Catalytic Nozaki–Hiyama–Kishi Reaction

(The Fürstner Procedure) .................................. 119

2.6.4.6 Method 6: Additive–Reductive Carbonyl Dimerization ................. 119

2.6.5 Product Subclass 5: Metallacyclic Complexes ............................ 120

Synthesis of Product Subclass 5 ........................................... 121

2.6.5.1 Method 1: By Transmetalation ........................................ 121

2.6.5.2 Method 2: By Reductive Coupling of Alkenes .......................... 122

2.6.5.3 Method 3: By Addition of Alkenes to Carbene Complexes .............. 123

2.6.6 Product Subclass 6: Complexes with Triply Bonded

Heteroelement Ligands .................................................. 123

2.6.7 Product Subclass 7: Complexes with Doubly Bonded

Heteroelement Ligands .................................................. 124

Synthesis of Product Subclass 7 ........................................... 125

2.6.7.1 Method 1: From Complexes Containing Singly Bonded

Heteroelement Ligands ................................... 125

2.6.7.2 Method 2: From Other Complexes Containing Doubly Bonded

Heteroelement Ligands ................................... 126

2.6.7.3 Method 3: From Complexes Containing Triply Bonded

Heteroelement Ligands ................................... 127

2.6.7.4 Method 4: By Oxidative Processes .................................... 128

Applications of Product Subclass 7 in Organic Synthesis .................... 129

2.6.7.5 Method 5: Catalytic Epoxidation of Alkenes ........................... 129

2.6.8 Product Subclass 8: Complexes with Singly Bonded

Heteroelement Ligands .................................................. 130

Synthesis of Product Subclass 8 ........................................... 130

2.6.8.1 Method 1: By Oxidative Addition of Compounds with Single Bonds

between Heteroelements ................................. 130

2.6.8.2 Method 2: By Transmetalation ........................................ 131

2.6.8.3 Method 3: From ó-Alkyl Complexes ................................... 131

2.6.8.4 Method 4: From Carbene or Carbyne Complexes ...................... 132

2.6.8.5 Method 5: From Complexes Containing Doubly Bonded

Heteroelement Ligands ................................... 133

2.6.9 Product Subclass 9: Miscellaneous Complexes ........................... 133

Synthesis of Product Subclass 9 ........................................... 133

2.6.9.1 Method 1: Allylidene Complexes from Cyclopropenes ................. 133

90

2.6 Product Class 6:

Organometallic Complexes of Chromium, Molybdenum,

and Tungsten without Carbonyl Ligands

R. Poli and K. M. Smith

General Introduction

Almost all of the complexes described in this product class are air- and/or moisture-sensitive,

both as solids and in solution. Prior to use all solvents should be dried and distilled

under nitrogen or argon, and the compounds should be synthesized, handled, and stored

under an inert atmosphere using Schlenk or glovebox techniques. The bonds between

group 6 metals and carbon are often readily hydrolyzed, with the notable exception of

several alkylchromium(III) species. In general, these compounds are less sensitive to oxygen

when the metals are formally in the +6 oxidation state, and are thus incapable of being

oxidized further, although the extreme atmospheric sensitivity of molybdenum(VI)

ring-closing metathesis catalysts (Section 2.6.1.5.3) provides a striking exception to this

trend. [1]

Due in part to their hydrolytic instability, the toxicity of the organometallic complexes

described in this product class have generally not been investigated. A prominent

exception is dichlorobis(cyclopentadienyl)molybdenum(IV), which has been studied as an

antitumor agent. [2,3] Purely inorganic compounds of chromium(VI) are well-established

carcinogens, in contrast to the relatively low toxicity characteristic of chromium(III) species.

While chromium(III) compounds are not readily transported through cell walls, the

negative charge and tetrahedral structure of the chromate dianion makes it analogous to

the phosphate and sulfate ions, and so chromium(VI) is brought into the cell via nonspecific

anion transport channels. Chromium(VI) is then reduced to chromium(III) inside the

cell, leading to the DNA lesions responsible for the carcinogenic activity. [4] In the absence

of more detailed toxicity studies for organometallic group 6 complexes, care should be

taken when handling all the compounds in this product class.

2.6.1 Product Subclass 1:

Metal–Carbene Complexes

While group 6 complexes containing carbonyl ligands (Fischer-type) are most common

for chromium, those without carbonyl ligands (Schrock-type, also called alkylidene complexes)

are more typical of molybdenum and tungsten. Although a few chromium examples

are known, [5] our attention will be almost completely devoted to molybdenum and

tungsten systems. These complexes are generally found in high oxidation states (‡4) and

supported by electronegative, ð-donor ligands (alkoxo, amido, imido). These ligands have

the possibility of stabilizing low-coordination environments by ð-donation in excess of

the valence requirement (e.g., ó +2ð M”OorM”NR for oxo and imido derivatives), resulting

in tetrahedral species. Often, however, these complexes allow expansion of the coordination

sphere by formation of dimers (e.g., halide bridged) or by addition of a two-electron

donor with formation of five-coordinate and occasionally six-coordinate species, the

formation of which is more likely for tungsten than for molybdenum and when the metal

bears electron-withdrawing ligands. [6]

Group 6 metal–carbene complexes are most stable when devoid of â-hydrogen atoms

on the carbene ligand, the latter leading to decomposition by 1,2-H migration and formation

of alkene derivatives. [7] The carbene ligand usually bears hydrogen or alkyl substitu-

2.6.1 Metal–Carbene Complexes 91

ents, and is normally considered as a dinegative (=CR 1 R 2 ) 2– ligand for the purpose of formal

oxidation state assignment. Like all other Schrock-type carbene complexes, those of

group 6 metals present marked nucleophilic reactivity and undergo Wittig chemistry

with X=Y molecules, the thermodynamics favoring the M=X and R 2C=Y combination

where X is harder than Y. [8] This reaction, however, does not represent particular advantages

over classical Wittig reagents for organic synthesis, a major use being the metal removal

at the end of organic transformations carried out on carbene complexes (e.g., alkene

metathesis, see Section 2.6.1.5).

Synthesis of Product Subclass 1

2.6.1.1 Method 1:

By Æ-Hydrogen Elimination from Alkyl Complexes

High oxidation state dialkyl complexes may undergo transfer of an Æ-hydrogen atom

from one alkyl ligand to the second one under suitable conditions, with formation of a

carbene product and elimination of alkane. The reaction is favored by an increase of steric

bulk in the metal coordination sphere. This has been achieved in a number of ways, as

outlined in the following variations.

2.6.1.1.1 Variation 1:

Alkylation of Chloride Precursors

The replacement of a halide with a bulky alkyl group is often sufficient to induce the alkane

elimination process. Thus, while the complex tert-butylimidochlorotris(2,2-dimethylpropyl)molybdenum(VI)

(1) does not spontaneously undergo the Æ-hydrogen elimination

process, substitution of the chloride ligand with a fourth 2,2-dimethylpropyl ligand

directly affords the carbene product 2 (Scheme 1). [9] For the analogous tungsten system,

tetraalkylimido intermediates, e.g. phenylimidotetrakis[(trimethylsilyl)methyl]tungsten(VI),

have been isolated, and their slow first-order elimination to the alkylidene product

has been investigated. [10] Other alkane eliminations from stable dialkyl derivatives

may be induced by simple irradiation, [11,12] e.g. the transformation of 3 into 4. [13]

Scheme 1 Æ-Hydrogen Elimination Induced by Alkylation [9,13]

Cl

Mo

CH2But NBut ButH2C ButH2C W

3

1

t-BuCH2Li, benzene

rt, 10 min

75%

toluene, hν (Xe, 340 nm)

26 h

64%

= 4-t-Bu-calix[4]-(O)4

H Pr

W

4

Bu

Mo

tH2C But NBu

H2C

t

CHBut {4-tert-Butylcalix[4]-(O) 4}butylidenetungsten(VI) (4): [13]

A soln of W(cyclo-C 4H 8){4-t-Bu-calix[4]-(O) 4} (8.45 g, 8.77 mmol) in toluene (200 mL) was irradiated

with a Xe lamp (540 W •m –2 at 340 nm) for 26 h. Volatiles were removed in vacuo,

pentane (60 mL) was added to the residue, and pale brown 4 was collected and dried in

vacuo; yield: 5.62 g (64%); 1 H NMR (benzene-d 6, ä): 10.0 [t, 3 J = 7.5 Hz, 1H, WC(Pr)H], 5.47

[m, 2H, WC(H)CH 2CH 2CH 3], 1.69 [m, 2H, WC(H)CH 2CH 2CH 3], 1.15 [t, 3 J = 7.2 Hz, 3H, WC(H)-

2

for references see p 135

92 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

CH 2CH 2CH 3]; 13 C NMR (benzene-d 6, ä): 272 [d, WC(Pr)H, 1 J CW = 180 Hz, 1 J CH = 142 Hz], 41.6

(WCCH 2CH 2CH 3), 29.5 (WCCH 2CH 2CH 3), 14.5 (WCCH 2CH 2CH 3).

2.6.1.1.2 Variation 2:

Ligand Addition

When di- or polyalkyl complexes do not spontaneously give rise to Æ-hydrogen elimination,

this process may often be accomplished by addition of two-electron ligands (e.g.,

phosphines). [14,15] Thus, the tris(2,2-dimethylpropyl)(2,2-dimethylpropylidyne)tungsten

complex 5 transforms into the (2,2-dimethylpropyl)(2,2-dimethylpropylidene)(2,2-dimethylpropylidyne)

product 6 upon addition of trimethylphosphine (Scheme 2). The conditions

required to induce this process depend on the system, from –788C for dibromotetrakis[(trimethylsilyl)methyl]dimolybdenum(III)(Mo”Mo)

[15] to room temperature for cyclopentadienylbis(2,2-dimethylpropyl)nitrosylmolybdenum(II).

[16]

In the synthesis of compound 7, substitution of two alkoxide ligands with the less

sterically encumbering (and also poorer ð-donor) chlorides opens up the coordination

sphere to the coordination of a bidentate 1,2-dimethoxyethane molecule, inducing carbene

formation. The dialkoxo precursor, albeit five coordinate, does not spontaneously

undergo the alkane elimination process. [17] The increase of the coordination sphere can

also be achieved by replacement of a monodentate ligand (e.g., chloride) with a polyfunctional

ligand, e.g. hydrotris(pyrazolyl)borate [18] or 2-[(dimethylamino)methyl]phenyl (see

synthesis of 8) (Scheme 2). [19] This strategy has also been utilized in other cases via replacement

of a bulky alkyl with chloride by protonation with LH + Cl – in the presence of excess

ligand L. [10]

Scheme 2 Æ-Hydrogen Elimination Induced by Ligand Addition [14,17,19]

ButH2C W CBut But Bu

H2C

tH2C 5

OBu

W N

t

OBut ButH2C But Pr

H2C i

Pri CH2TMS

NPh

Cl W

CH2TMS

CH2TMS Me3P (neat)

100 oC, 5 min

quant

PCl5, DME

−35 oC 90%

2-Me 2NCH 2C 6H 4Li

Et 2O, −78 o C

70%

But Me3P t CBu

H2C W

CHBu

Me3P

t

6

Pr i

Cl

N

W

Cl

CHBut O

O

Pri Me

Me

8

7

NMe2

NPh

W

CHTMS

CH2TMS Dichloro[(2,6-diisopropylphenyl)imido](1,2-dimethoxyethane-O,O¢)(2,2-dimethylpropylidene)tungsten(VI)

(7); Typical Procedure: [17]

Finely ground PCl 5 (2.25 g, 10.8 mmol) was added to a chilled (–358C) soln of [W(CH 2t-

Bu) 2(Ot-Bu 2) 2(=NC 6H 3-2,6-iPr 2) (7.0 g, 10.8 mmol) in DME (120 mL). The mixture was

warmed to rt and stirred for an additional 1 h after all the solids had disappeared. The

mixture was then concentrated in vacuo until an orange powder formed. This material

was washed with cold pentane to give the product as a yellow-orange powder. This synthesis

can fail virtually completely if the DME is not scrupulously dried and the PCl 5 not

2.6.1 Metal–Carbene Complexes 93

rigorously purified; yield: 5.75 g (90%); 1 H NMR (benzene-d 6, ä): 9.97 (s, J HW = 7.3 Hz, CHt-

Bu); 13 C NMR (benzene-d 6, ä): 283.8 (d, W=C, 1 J CH = 114 Hz, 1 J CW = 163 Hz).

2.6.1.1.3 Variation 3:

Replacement of an Oxo or Imido Ligand

Replacement of an oxo [20–22] or imido [23] ligand with two singly bonded heteroelement ligands

has often proven to be an efficient method for inducing the Æ-elimination process

from dialkyl compounds. Examples of syntheses of these types are shown in Scheme 3.

The interaction between a dialkoxodialkyloxo complex of tungsten(VI) and a Lewis acid

(AX n, viz. aluminum trichloride, tin(IV) chloride, magnesium bromide, etc.) proceeds via

an isolable adduct containing the W=O-AX n moiety when conducted in hexane, which

then yields the dialkoxodihalocarbene product. [24] Although this procedure is not general,

subsequent ligand exchange or stoichiometric alkene metathesis (see Section 2.6.1.2) allows

the preparation of a much broader series of derivatives. [21,22] Lewis base adducts such

as compound 9 easily undergo exchange of the Lewis base, or can be converted into the

base-free material. The reaction yielding 10 is the most convenient entry into the catalytically

active dialkoxo(alkylidene)imido complexes of molybdenum and tungsten, since

the trifluoromethanesulfonate ligands can be easily replaced with a variety of alkoxide

groups, and the dialkyldiimido precursor complex is readily available in two high-yield

steps from commercially available dichlorodioxotungsten(VI) or ammonium dimolybdate.

[17,25]

Scheme 3 Æ-Hydrogen Elimination Induced by Substitution of Oxo or Imido

Ligands [8,17,23,29]

ButN Mo

But CH2Bu

N

t

CH2But Pr i

Pri N

M

Pr N

i

CH2R1 CH2R1 Pr i

M = Mo, W

R1 = t-Bu, CMe2Ph

(CF3) 2CHOH (2 equiv)

pentane, rt

80%

TfOH (3 equiv)

DME, −30 oC 65−78%

OCH(CF3) 2

Mo NH2Bu OCH(CF3) 2

t

ButN ButHC 9

M

R1 Pr

N

OTf

O

HC O

OTf

i

Pri Me

Me

[(2,6-Diisopropylphenyl)imido](1,2-dimethoxyethane-O,O¢)(2,2-dimethylpropylidene)bis(trifluoromethanesulfonato-O)molybdenum(VI)

(10,M=Mo;R 1 = t-Bu);

Typical Procedure: [8]

A prechilled soln of TfOH (3.15 mL, 35.5 mmol, 3 equiv) in DME (20 mL) was added in a

dropwise manner to an orange soln of Mo(CH 2t-Bu) 2(=NC 6H 3-2,6-iPr 2) 2 (7.00 g, 11.8 mmol)

in DME (200 mL) at –308C over a period of 10 min. [It is important in this step that the soln

be homogeneous and cold. It is best to grind the crystals of the molybdenum starting complex

to a fine powder to aid dissolution; the addition of some pentane (15–30 mL) may facilitate

this step.] The soln was allowed to warm up to rt and stirred for 3 h. During this

period the color changed from orange to dark yellow. The solvent was evaporated in vacuo

to yield a yellow solid, which was then extracted with cold toluene (100–150 mL). The

10

for references see p 135

94 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

extract was filtered through a bed of Celite and the toluene removed from the filtrate in

vacuo to give the product as yellow flakes. The product should be checked by NMR for

contamination by anilinium trifluoromethanesulfonate, which is slightly soluble in toluene;

yield: 5.9 g (65%); 1 H NMR (benzene-d 6, ä): 14.29 (s, CHt-Bu); 13 C NMR (benzene-d 6, ä):

331.9 (d, Mo=C, 1 J CH = 121 Hz).

2.6.1.1.4 Variation 4:

Deprotonation with an External Base

Deprotonation of alkyl ligands at the Æ-position is another potentially general method for

forming carbene complexes from alkyl compounds that are either electronically unsaturated

or possess labile ligands. However, this method is little documented for group 6

metals as well as for metals of other groups. The neutral dialkyl compound 11 reacts

with a range of lithium reagents to yield the dimeric, anionic alkyl–alkylidene complex

12, as shown in Scheme 4. [26] Methylidene product 13 is only stable at low temperature,

decomposing upon warming in a nonselective manner to yield alkylidene-bridged dinuclear

products. [27]

Scheme 4 Deprotonation of Alkyl Complexes [26,27]

Mo

ON CH 2TMS

CH 2TMS

11

[W(Me) 4Cp ∗ ] + PF 6 − + Et3N

+

LiHMDS

THF

−100 oC to rt

62%

CH2Cl2

< −40 o C

TMS

W(Me)3Cp ∗ (

13

THF

Li

Mo NO ON Mo

CH2TMS Li TMSH2C THF THF

12

TMS

Bis{nitrosyl(ç 5 -pentamethylcyclopentadienyl)[(trimethylsilyl)methyl][(trimethylsilyl)methylidene]molybdenum(II)}

(Dilithium)tris(tetrahydrofuran) (12): [26]

[Mo(CH 2TMS) 2Cp*(NO)] (200 mg, 0.46 mmol) and LiHMDS (90 mg, 0.46 mmol) were intimately

mixed and cooled to –1008C in a small flask. THF was slowly poured down the

sides of the flask and allowed to freeze onto the solid mixture. Over the course of 4 h, a

color change from purple to red occurred; the final mixture was taken to dryness in vacuo.

The remaining red solid was extracted into pentane (2 mL), and the extracts were filtered

through Celite. Slow evaporation of the pentane filtrate resulted in the deposition

of pale red crystals, which were recrystallized (pentane) to obtain pale yellow crystals of

12; yield: 143 mg (62%).

2.6.1.2 Method 2:

By Stoichiometric Alkene Metathesis

The addition of an alkene to a carbene complex may lead to a metathesis reaction with

exchange of the carbene ligand with one of the two halves of the alkene. The reaction proceeds

via formation of an alkene–carbene complex, which rearranges via a metallacyclobutane

intermediate. [28] This reaction is synthetically useful when a terminal alkene is

used and vacuum evaporation of the more volatile alkene product (typically 3,3-dimethylbut-1-ene)

is possible to displace the equilibrium. [22] An excess of the alkene reagent is also

used to ensure a favorable equilibrium position (see Scheme 5). The properties of the an-

CH 2)

2.6.1 Metal–Carbene Complexes 95

cillary alkoxide ligands can influence whether this reaction results in metathesis or the

formation of stable tungstacyclobutane derivatives (see Section 2.6.5). [17,29]

Scheme 5 Stoichiometric Alkene Metathesis [8,17,22]

M( CHBu t )(L) n + H 2C CR 1 R 2 M( CR 1 R 2 )(L) n + H 2C CHBu t

M(L) n R1 R2 Conditions Yield (%) of

[M(=CR1R2 )(L) n]

Ref

[WBr2(OCH2t-Bu) 2] (CH2) 4 CH2Cl2,rt,4h 87 [22]

[Mo(=NC6H3-2,6-iPr2){OCMe(CF3) 2} 2] H TMS pentane,

–308C, 2.5 h

74

[8]

[W(OR3 ) 2(=NC6H3-2,6-iPr2)] a H Si(OMe) 3 pentane, rt,

30 min to 2.5 h

50–78

[17]

a R 3 = 2,6-iPr2C 6H 3,CMe 2(CF 3), CMe(CF 3) 2.

Dibromo(cyclopentylidene)bis(2,2-dimethylpropan-1-olato)tungsten(VI);

Typical Procedure: [30]

Methylenecyclopentane (0.36 mL, 3.42 mmol) was added to an orange soln of [WBr 2(=CHt-

Bu)(OCH 2t-Bu) 2] (0.127 g, 0.215 mmol) in CH 2Cl 2 (10 mL). After 4 h, the volatiles of the red

mixture were removed in vacuo, and the orange residue was washed twice with pentane

to give the product as an orange powder; yield: 110 mg (87%); 13 C NMR (CD 2Cl 2, ä, gated

decoupled): 47.1 (t, 1 J CH = 134 Hz, W=CCH 2), 28.2 (t, 1 J CH = 131 Hz, W=CCH 2CH 2); the W=C

signal could not be observed.

2.6.1.3 Method 3:

By Carbene Transfer

The carbene ligand may be either directly added to the metal center or exchanged for two

X groups. The first strategy requires preparation of the metal in a reactive, reduced form.

For the preparation of compound 14 (Scheme 6), this is achieved by sodium reduction of

the dichloro precursor complex. [31] The phosphorane carbene transfer agent is readily accessible

with a variety of carbene functionalities and the triphenylphosphine byproduct

does not coordinate with the metal center, allowing its easy removal by scavenging with

copper(I) chloride. For the tungsten(II) system 15 (L= tertiary phosphine), even ketones

and imines are sufficiently good carbene transfer reagents, providing alkylideneoxo and

alkylideneimido tungsten(VI) products 16, respectively, in remarkable four-electron oxidative

addition reactions. [32] For ketones different than cyclopentanone, stable and unreactive

bis(ç 2 -ketone) adducts are obtained by use of an excess of the ketone, but the

use of one equivalent still leads to the alkylideneoxo product.

The exchange strategy involves the use of reactive tantalum alkylidene complexes,

resulting in the replacement of alkoxo ligands. This method, which is also accompanied

by the scrambling of other ligands, applies equally well to the synthesis of the oxo and

imido tungsten products 17, [33] but is limited by the availability of the tantalum alkylidene

reagent and has not been reported for molybdenum.

for references see p 135

96 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Scheme 6 Carbene Transfer [31–33]

R 1

N

R 1 = H, Me, iPr

Cl

L

L W L

Cl L

15

L = PMe 2Ph

E = O, N-4-Tol

R1 ,R2 = (CH2) 4, Me2 E

W

ButO OBut OBut ButO E = O, NPh

Cl

W

Cl

OCMe(CF3) 2

E

R1 , benzene

2 R

45−88%

Na/Hg,

TaCl3( CHBut )(PMe3)2

Et2O, rt, 12 h

79−83%

OMe

benzene, THF, rt, 8 h

71%

E

Cl W CR

Cl

1R2 L

L

16

PPh3

PMe3 Cl E

W

Cl CHBu

PMe3 17

t

MeO

(F3C) 2MeCO

THF W

OCMe(CF

N

3)2

R 1 R 1

(2,6-Dimethylphenylimido)bis(1,1,1,3,3,3-hexafluoro-2-methylpropan-2-olato)(2-methoxybenzylidene-kC)(tetrahydrofuran)tungsten(VI)

(14,R 1 = Me); Typical Procedure: [31]

The compounds [WCl 2{OCMe(CF 3) 2} 2(=NC 6H 3-2,6-Me 2)(THF)] (16.0 g, 19.8 mmol) and

Ph 3P=CH(C 6H 4-2-OMe) (7.78 g, 20.3 mmol) were dissolved in a mixture of benzene and

THF (160 mLand 2.5 mL, respectively) and the resulting soln was added to 1% Na/Hg

(3.59 g of Na, 7.90 equiv). After being stirred for 8 h at rt, the mixture was allowed to settle,

and the orange-brown supernatant was added via a cannula to CuCl (2.07 g, 20.9 mmol).

The residual Na/Hg was washed with Et 2O (120 mL), and the combined benzene/Et 2O soln

was stirred with CuCl for 12 h before removal of the solvent in vacuo. The brown solid

was then extracted with Et 2O (260 mL). After addition of THF (2 mL) to the extract and filtering,

the soln was slowly cooled to –508C to yield the product as an olive-yellow powder;

yield: 12.0 g (71%); 1 H NMR (benzene-d 6, ä): 10.81 (s, W=CHAr).

2.6.1.4 Method 4:

FromCarbyne Complexes

Addition of a proton to a carbyne ligand may transform it into a carbene. The proton can

be provided by an external source or by transfer from another ligand. Examples of the

first kind are provided by the addition of acids to complex 18 (see Scheme 7). [7] The use

of pyridinium salts yields more stable pyridine adducts. This reaction can be reversed by

the addition of a strong base (see Section 2.6.2). When an acid containing a noncoordinating

anion is used, e.g. trifluoromethanesulfonic acid, cationic derivatives may be obtained.

[34] Depending on the nature of the coligands, the proton may preferentially add

to another position in the molecule (see Section 2.6.2).

Internal proton transfer is observed for amido ligands. The reaction between the 1,2dimethoxyethane

adduct of trichloro(carbyne)molybdenum or -tungsten complexes and

(trimethylsilyl)arylamines produces the stable intermediates 20. The latter, however, re-

2.6.1 Metal–Carbene Complexes 97

arrange by a base-catalyzed proton transfer to the final carbene–imido products 21. [8,17,29]

These proton-transfer processes occur much more slowly or not at all for the dialkoxo analogues,

although the anticipated proton-transfer products are stable systems. A mechanism

of reversible amine-assisted dehydrohalogenation has been proposed for this transformation.

This synthetic route is inconvenient for the molybdenum system, mainly because

of difficulties in the preparation of the precursors to the trichlorocarbyne complex

of molybdenum. The tungsten analogue is more easily prepared (see Section 2.6.2). [29]

However, even the tungsten product is more conveniently prepared by another procedure

[Æ-H elimination from a bis(2,2-dimethylpropyl) precursor, Section 2.6.1.1]. [17]

Scheme 7 Protonation of Carbyne Complexes [7,8,17]

Bu t O

CBu t

W

OBut OBut 18

HX (2 equiv), toluene, rt

51−85%

X = Cl, Br, OAc, OBz, OPh, OC 6F 5, 4-ClC 6H 4O

M( CBu t )Cl 3(DME)

M = Mo, W; R 1 = Me, iPr

R 1

NH

R1 Et2O, −40 o TMS

C

>95%

X

Bu

W

t Bu

O

tO X

CHBut R 1

19

Cl

N

M

CBu

Cl

t R1 Me

O H

O

Me

20

Et3N

>95%

R 1

Cl

N

M

CHBu

Cl

t

R1 Me

O

Me

Di-tert-butoxodichloro(2,2-dimethylpropylidene)(pyridine)tungsten(VI);

Typical Procedure: [7]

The alkylidyne complex [W(”Ct-Bu)(Ot-Bu) 3] (1.00 g, 2.12 mmol) was added at rt as a solid

to a CH 2Cl 2 soln (25 mL) of pyridine hydrochloride (4.2 mmol). After 10 min the solvent

was removed in vacuo and the residue was recrystallized (pentane) to yield the product

as orange crystals; yield: 0.92 g (79%); 1 H NMR (benzene-d 6, ä): 10.76 (s, CHt-Bu);

13 C{ 1 H} NMR (benzene-d6, ä): 302.3 (CHt-Bu).

Applications of Product Subclass 1 in Organic Synthesis

2.6.1.5 Method 5:

Alkene Metathesis

High-valent molybdenum–carbene complexes bearing electronegative ancillary ligands

are efficient catalysts for alkene metathesis reactions (Scheme 8). [20,35] This reaction proceeds

via [2 +2] cycloaddition and formation of metallacyclobutane intermediates, some

of which have been isolated under controlled conditions (see Section 2.6.5.3). [36] In order

to make the reaction synthetically useful, it is necessary to have a driving force and high

selectivities, and to suppress the self-metathesis if a cross-metathesis (e.g., R 1 „ R 2 ) is desired.

The driving force may be provided by conjugation or by formation of polymeric materials.

Selective processes often result from the removal of a volatile byproduct, such as

ethene.

21

for references see p 135

98 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Scheme 8 Alkene Metathesis

R 1 R 2

+

R 1

R 2

+ H 2C CH 2

2.6.1.5.1 Variation 1:

Ring-Opening Metathesis Polymerization (ROMP)

The living polymerization of strained cyclic alkenes such as norbornenes and substituted

norbornadienes is catalyzed by molybdenum and tungsten carbene complexes (Scheme

9). [35] The living nature of this process allows control of the chain length and the preparation

of block copolymers, which may also have a high level of tacticity. [37] A Wittig-like

capping reaction with aldehydes can be used to cleave the metal fragment off the living

polymer. Essentially monodisperse products 22 with x up to 500 have been obtained from

norbornene by using di-tert-butoxo[(2,6-diisopropylphenyl)imido](2,2-dimethylpropylidene)tungsten(VI)

as a ROMP initiator. [38] The catalyst does not attack the less reactive

double bonds in the polymeric product. The use of 7,8-bis(trifluoromethyl)tricyclo[4.2.2.0

2,5 ]deca-3,7,9-triene as monomer gives oligomers from which polyenes with up

to 15 conjugated double bonds have been obtained via a retro-Diels–Alder ejection of an

arene upon thermolysis. [39] Other substrates suitable for the ROMP process are substituted

cyclooctatetraenes, leading to functionalized and soluble polyacetylenes of low polydispersities.

[40]

Scheme 9 Ring-Opening Metathesis Polymerization of Norbornene [35]

[W] CHBu t + x

[W] = W(Ot-Bu) 2( NC6H3-2,6-iPr2)

−80 o C

[W] CHBut x

PhCHO

PhHC CHBut x

22

1,4-Dihydro-1,4-methanonaphthalene, Homopolymer (x = 100); Typical Procedure: [41]

A soln of 1,4-dihydro-1,4-methanonaphthalene (291 mg, 2.05 mmol) in toluene (3.0 mL)

was added dropwise to a rapidly stirred soln of [Mo(=CHt-Bu)(Ot-Bu) 2(=NC 6H 3-2,6-iPr 2)]

(10 mg, 0.020 mmol) in toluene (3.0 mL) and the soln was stirred for 20 min. The polymerization

was quenched by addition of pivalaldehyde (25 ìL). After 20 min, the soln was

added to hexane (250 mL), and the precipitated polymer was isolated by centrifugation,

washed with hexane, and placed under vacuum overnight; yield: 280 mg (94%).

2.6.1.5.2 Variation 2:

Alkyne Polymerization

Terminal alkynes have yielded polyenes 23 with up to 150 conjugated double bonds under

molybdenum–carbene catalysis (Scheme 10). [42] The nature (in particular the size) of

the ancillary ligands is important in controlling the selective Æ-addition. Acetylene itself

produces insoluble and air-sensitive polymers that are difficult to characterize. Cyclopolymerization

of dipropargyl derivatives such as 24 have been shown to yield polyenes of

low polydispersity containing only six-membered rings, following a selective â-addition

2.6.1 Metal–Carbene Complexes 99

of the first triple bond. [43] The nature of the coordination sphere on the carbene initiator is

of capital importance, as polymers containing both five- and six-membered rings that are

a consequence of an initial Æ- orâ-addition, respectively, have been obtained with other

initiators. [44]

Scheme 10 Alkyne Polymerization [42,43]

x R 1

[Mo] CHCMe2Ph toluene, rt

[Mo]

[Mo] =

OCMe(CF3)2

N Mo

OCMe(CF3) 2

; R1 =

TMS

x

EtO 2C

[Mo] =

24

CO 2Et

Bu t

[Mo] CHt-Bu

N Mo(O 2CCPh 3) 2

R 1

EtO2C

EtO2C [Mo]

CHCMe 2Ph

x

β-addition

; x = up to 150

CHBu t

PhCHO

PhCH

EtO 2C

[Mo]

R 1

x

23

CO2Et

CHCMe 2Ph

CHBut x

2,2-Diprop-2-ynylmalonic Acid, Diethyl Ester, Homopolymer (x = 20);

Typical Procedure: [43]

Polymerization stock solutions of diethyl 2,2-diprop-2-ynylmalonate (24; 0.406 M) and

[Mo(=CHt-Bu)(O 2CCPh 3) 2(=NC 6H 42-t-Bu)] (0.00676 M) in toluene that had been distilled

over sodium benzophenone ketyl, stored over molecular sieves (4 Š), and passed through

alumina, were prepared. To the catalyst stock soln (3.007 mL), toluene (3 mL) was added

and the monomer stock soln (1.0 mL) was squirted in. Within 30 s the mixture turned

deep red. After 6 h, benzaldehyde (16 ìL) was added. After stirring for a further 3 h, the

soln was concentrated in vacuo to about 1.5 mL. The polymer was precipitated in pentane

(60 mL), collected on a frit, and dried in vacuo to yield a red, powdery material. All operations

were carried out under a nitrogen atmosphere and the polymers were only briefly

exposed to air for sample preparation for GC analysis; yield: 90 mg (91%); 13 C{ 1 H} NMR

(CDCl 3, ä): 170.7 (CO 2Et), 54.5 (C quaternary).

2.6.1.5.3 Variation 3:

Ring-Closing Metathesis

Ring-closing metathesis (Scheme 11) affords cyclic products 25 in competition with intermolecular

metathesis processes to form polymeric materials. [45] The reaction is also complicated

by the possibility of ROMP (Section 2.6.1.5.1). Which products are obtained is the

result of an interplay of thermodynamic and kinetic parameters. Entropy (the generation

of two molecules from one) and evaporative subtraction of the volatile acyclic alkene

from solution provide the necessary driving force for the desired cyclization. The ringclosing

metathesis procedure can be applied to the construction of macrocyclic natural

products, although mixtures of E- and Z-isomers are often obtained in these cases (see

also Section 2.6.2.7). [46] The most widely used group 6 catalyst for this process is 26, although

ruthenium-based catalysts are generally preferred owing to their greater func-

for references see p 135

100 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

tional group tolerance and relatively low sensitivity to air, moisture, or solvent impurities.

[47] The process has proven particularly useful for the formation of cyclic ethers, e.g.

27. [48] A number of functional groups, including tertiary alcohols, do not interfere with

the course of the reaction. Amine and amide functional groups can be tolerated if they

cannot form unreactive chelated adducts for steric reasons. [49] A variant of this method

follows the initial ring-closing metathesis step with a carbonyl alkenation process, e.g.

the synthesis of 28, [50] which is, however, stoichiometric in metal because of the formation

of a catalytically inactive metal–oxo byproduct. The success of this strategy rests on

the fact that compound 26 metathesizes alkenes more rapidly than it alkenates ketones.

Chiral analogues of 26 have been prepared using C 2 symmetric diol ligands, and these

complexes, 29 [51] and 30, [52] have been used to perform the asymmetric ring-closing metathesis

of dienes [52–54] and the synthesis of chiral furans via enantioselective desymmetrization

reactions. [55]

Scheme 11 Cycloalkenes by Ring-Closing Metathesis of Dienes [48,50]

[M ]

X X

O

F 3C

O

Ph

25

Pri N Pri O

CF3

Mo

O CHCMe2Ph CF3

29

+ H2C CH 2

Pr i

N Pri (F3C) 2MeCO

Mo

(F3C) 2MeCO CHCMe2Ph 26 (cat.)

benzene, 20 oC, 15 min

Pr i

92%

N Pri (F3C) 2MeCO

Mo

(F3C) 2MeCO CHCMe2Ph

26

benzene, 20 oC, 30 min

84%

Pri But O

O

Bu t

O Ph

27

O

28

N Pri Mo

CHCMe2Ph 1-[(2-Methyl-3-phenylallyl)oxy]methylcyclohex-1-ene (28); Typical Procedure: [50]

1-[(2-Methyl-3-phenylallyl)oxy]oct-7-en-2-one (35 mg, 0.13 mmol) was added to a homogeneous

yellow soln of catalyst 26 (100 mg, 0.13 mmol) in anhyd benzene (12 mL) under argon.

The resulting mixture was stirred at 20 8C for 30 min, at which time TLC showed the

reaction to be complete. The mixture was quenched by exposure to air, concentrated, and

30

2.6.1 Metal–Carbene Complexes 101

purified by flash chromatography (0–7% EtOAc/hexane) to yield the substituted cyclohexene

as a colorless oil; yield: 27 mg (84%); 1 H NMR (benzene-d 6, ä): 5.72 (br s, CHCH 2),

2.05–1.45 (m, 8H, CH 2CH 2CH 2CH 2).

2.6.1.5.4 Variation 4:

Other Selective Metathesis Processes

These processes are usually restrained to monosubstituted alkenes, yielding ethene as the

byproduct. Fairly selective cross-coupling processes have been reported from a combination

of an electron-poor alkene, especially one containing a ð-substituent (e.g., styrenes,

acrylonitrile), [56,57] and a more nucleophilic one containing a small, electron-rich, nonconjugated

substituent (see, for example, the synthesis of 31 in Scheme 12), [56] or with allylsilanes.

[58] The electron-poor alkene self-metathesizes only slowly and, in addition, inhibits

the self-metathesis of the nucleophilic alkene. Greater than 95% trans selectivity is observed

in the reactions with styrene substrates, [56] while the cis-product is highly favored

for cross-metatheses with acrylonitrile. [57]

The formation of the homo dimer may also be significantly slowed down by steric

bulk. For example, compounds 32 and 33 yield the cross-coupling product 34 without

any self-metathesis of 32 and with only 26% yield of the 33 homo dimer. [59] The E/Z selectivities,

however, are usually low for nonconjugated alkene products.

Scheme 12 Cross-Coupling Alkene Metathesis [56,59]

Ph

O

+

CO 2Me

( ) 5

+

1.5

32 33

Pr i

N Pri (F3C) 2MeCO

Mo

(F3C)2MeCO CHCMe2Ph 26 (cat.)

CH2Cl2, rt, 1 h

CO2Me

Ph

( )

5

+

( ) 5

31 89%; E 100% 2%

Pr i

N Pri (F3C)2MeCO

Mo

(F3C) 2MeCO CHCMe2Ph 26 (cat.)

83%

O

CO 2Me

( ) 5

34 (E/Z) 2:1

CO2Me

for references see p 135

102 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

(E)-1-Phenyloct-1-ene (31); Typical Procedure: [56]

To a mixture containing styrene (208 mg, 2 mmol) and oct-1-ene (112 mg, 1 mmol) in

CH 2Cl 2 (2 mL) was added [Mo(=CHCMe 2Ph){OCMe(CF 3) 2} 2(=NC 6H 32,6-iPr 2)] (7.7 mg,

1 mol%). The resulting mixture was stirred at rt for 1 h, then passed through a pad of silica

gel and rinsed with CH 2Cl 2. The solvent was removed under reduced pressure, and the

crude residue was chromatographed on silica gel to give 31 as a colorless oil; yield:

166 mg (89%). A similar reaction run with styrene (9.29 g, 89.2 mmol), oct-1-ene (5 g,

44.6 mmol), and catalyst (342 mg, 1 mol%) in CH 2Cl 2 (60 mL) afforded 31; yield: 7.9 g

(94%). 1 H NMR (CDCl 3, ä): 2.16 (q, J = 6.8 Hz, 2H, allylic CH 2), 6.20 (dt, J = 15.5 and 6.8 Hz,

1H, PhCH=CH), 6.33 (d, J = 15.5 Hz, 1H, PhCH=CH).

2.6.1.6 Method 6:

Carbonylmethylenation

The reaction of methyllithium or trimethylaluminum with molybdenum(V), molybdenum(VI),

tungsten(V), and tungsten(VI) chlorides in tetrahydrofuran or diethyl ether at

low temperatures produces complexes that liberate methane and convert into thermolabile

ì-methylene complexes upon warming. The exact nature of these reagents has not

been determined, but their subsequent addition to aldehydes and ketones results in their

methylenation at the carbonyl function. The low basicity of these compounds proves advantageous

in carbonylmethylenation of base-sensitive substrates, such as readily enolizable

ketones as in the synthesis of 35 (Scheme 13). [60] By comparison, methylidenetriphenylphosphorane

(Ph 3P=CH 2) provides only a 16% yield of 35. The base-sensitive ketone

36 is cleaved via a retro-aldol process by methylidenetriphenylphosphorane as well

as weakly basic chromium reagents. In contrast, molybdenum(V) and tungsten(V) reagents

are capable of methylenating 36 with high regioselectivities. [61] The activity of

these reagents is restricted only to a surprisingly small degree by alcohol and water,

thus permitting carbonylmethylenation in aqueous or alcoholic media with useful applications

to hydrophilic substances.

The molybdenum reagents in particular display high aldehyde selectivities, paralleling

those observed for alkylchromium(III) reagents in carbonylalkylation (Section 2.6.4.5).

This is illustrated in Scheme 13 by the carbonylmethylenation of 37. [61,62] Basic groups

such as hydroxy, alkoxy, dimethylamino, or alkylsulfanyl, in Æ- orâ-positions relative to

a carbonyl group, exercise an accelerating effect. This neighboring effect permits the

selective monomethylenation of diketones such as 36, the selectivity depending on the

solvent in the order dichloromethane < tetrahydrofuran < 1,2-dimethoxyethane. 1,3-Diketones

and 1,3,5-triketones can be selectively monomethylenated. In the case of triketones,

a peripheral oxo group is methylenated. Ketones react faster than enones. The

reagents obtained from trichlorooxomolybdenum(V), tetrachlorooxomolybdenum(VI),

or decachlorodimolybdenum(V) in tetrahydrofuran do not alter a number of functional

groups that are attacked by other methylenating agents. These include acyl chlorides, anhydrides,

esters, amides, diaryl-substituted 1,2-diketones, nitro aromatics, alkenes, and

dienes, as well as the individual compounds diphenylketene, benzonitrile, diphenylacetylene,

chlorobenzene, benzyl chloride, and dichloromethane. [60] The corresponding tungsten

compounds have not been well investigated. The reason for this lack of reactivity is

in some cases due to the formation of stable reagent–substrate complexes, from which

the substrate is released unchanged on addition of water. Functional groups that, on the

other hand, interfere with the carbonylmethylenation reaction are azomethines, epoxides,

and nitroso aromatics. A comparison of these molybdenum and tungsten reagents

with other carbonylmethylenating agents in various applications is available. [60]

2.6.2 Metal–Carbyne Complexes 103

Scheme 13 Carbonylmethylenation [60–62]

Ph

O

Ph

37

36

WOCl 3/MeLi (1:2) (1.5 equiv)

THF, −78 to 45 o C, 18 h

95%

Ph

O

1. A or B

2. H + OH OH OH

, H2O +

O

35

Ph

O

A: WOCl3/MeLi (1:2) (1 equiv) 43%

B: MoOCl3/MeLi (1:2) (1 equiv) 38%

MoOCl3/MeLi (1:2) (2 equiv)

THF, −78 to 20 oC, 18 h

Carbonylmethylenation of 4-(4-Acetylphenyl)-4-hydroxypentan-2-one (36);

Typical Procedure: [61]

To a red-brown suspension obtained by methylation of MoOCl 3(THF) 2 (1.57 g, 4.3 mmol)

with MeLi (8.7 mmol) in THF (30 mL) at –708C was added dropwise a soln of 4-(4-acetylphenyl)-4-hydroxypentan-2-one

(36; 0.48 g, 2.16 mmol) in THF (2 mL). The mixture was

further stirred at –708C for 4 h, followed by warming to rt over 12 h. This was hydrolyzed

with sat. aq NaHCO 3 (10 mL). After separation of the two phases and Et 2O extraction of the

aqueous phase, the combined organic fractions were dried (Na 2SO 4), and the solvent was

removed by rotary evaporation. Flash chromatography (3 cm ” 16 cm, silica gel, CH 2Cl 2/

acetone 40:1) afforded 2-(4-isopropenylphenyl)-4-methylpent-4-en-2-ol {fraction 1; yield:

0.04 g (9%); IR í~ max: 3500 cm –1 (br, OH); 1 H NMR (CDCl 3, ä): 4.77 [m, 1H, CH 2C(CHH)CH 3],

4.91 [m, 1H, CH 2C(CHH)CH 3], 5.09 [m, 1H, aryl-C(CHH)CH 3], 5.40 (m, 1H, aryl-

C(CHH)CH 3]} as a colorless oil, 2-(4-acetylphenyl)-4-methylpent-4-en-ol [fraction 2; yield:

0.18 g (38%); IR í~ max: 3420 cm –1 (br, OH); 1 H NMR (CDCl 3, ä): 4.75 (m, 1H, C=CHH), 4.91

(m, 1H, C=CHH)] as a yellow oil, and unreacted 4-(4-acetylphenyl)-4-hydroxypentan-2one

[fraction 3; yield: 0.08 g (17%)].

2.6.2 Product Subclass 2:

Metal–Carbyne Complexes

As for the case of carbene complexes, carbonyl-free carbyne (Schrock-type alkylidyne)

complexes are most common for high oxidation state (‡4) molybdenum and tungsten systems,

[63] although chromium examples are known. [64] For the purpose of formal oxidation

state assignment, the carbyne ligand is considered as (RC 3– ). The majority of d 0 complexes

possess the formula M(”CR)X 3, but many adducts with neutral two-electron donor ligands

L,M(”CR)X 3L n (n = 1 or 2), are also known. Derivatives with more electronegative X groups

(e.g., fluorinated alkoxides) form base adducts more readily. The most common supporting

ligands (X) are bulky alkyl ligands, alkoxides, and halides, but derivatives with

amides, and alkyl- and arylthiolates are also known. Typical ligands (L) are amines, ethers,

and phosphines. In lower formal oxidation states (+4 and +5), phosphines and halides or

cyclopentadienyl coligands are usually found. The halide derivatives are the most versa-

Ph

O

89%

+

Ph

5%

9%

2%

for references see p 135

104 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

tile for further transformations by ligand exchange. Exchange of the carbyne and an alkyl

ligand by intramolecular scrambling of the Æ-H atoms is possible. [65,66] Since the carbyne

function is polarized as M(ä + )”C(ä – ), these compounds are susceptible to electrophilic attack

at the carbyne ligand (e.g., protonation) and nucleophilic attack at the metal center

(e.g., ligand addition). The addition of acids (HX) converts carbyne complexes into carbene

complexes (see Section 2.6.1.4), [7] although, in many cases, the reagents attack other ancillary

ligands and the carbyne function remains intact. Examples are the reactions of trialkyl

derivatives with hydrochloric acid, ammonium chloride, or carboxylic acids. [67–69]

Synthesis of Product Subclass 2

2.6.2.1 Method 1:

By Æ,Æ-Hydrogen Elimination from Alkyl Complexes

The increase of steric bulk in a high oxidation state complex containing alkyl ligands, or

the in situ generation of encumbered complexes of this type by transmetalation reactions

(see Section 2.6.1.1), induces Æ,Æ-hydrogen elimination processes with formation of carbyne

products. The alkylation reaction works better from oxo or alkoxo derivatives than

from the corresponding chlorides, because these are less susceptible to competing reductive

processes. [70] This reaction appears to be the preferred entry into 2,2-dimethylpropylidyne

derivatives of molybdenum(VI) and tungsten(VI) through formation of the tris(2,2dimethylpropyl)

derivatives 38 and 39 (see Scheme 14). Other 2,2-dimethylpropylidyne

derivatives are then readily obtained by treating 38 and 39 with sufficiently strong acids,

e.g. hydrochloric or carboxylic acid, or by further ligand exchange from the trichloride

derivatives. This process is presumed to take place stepwise, via intermediate carbene

complexes (see Section 2.6.1.4), even when these are not observed. Some carbyne products

have been obtained by alkane elimination from carbene complexes, [15] although

this strategy does not appear to have general synthetic utility.

A particular case of Æ,Æ-hydrogen elimination from an alkyl ligand leads to the formation

of complex 40. [71] The two hydrogen atoms are eliminated as dihydrogen rather

than being transferred to alkyl ligands. Thus, the reaction involves a formal metal oxidation

and is so far limited to the system shown. The process is much faster for tungsten

than for molybdenum, this being ascribed to a more favorable pre-equilibrium yielding

the alkylidene–hydride intermediate. While the alkyl precursors can be isolated for molybdenum,

they may only be obtained in situ for tungsten by transmetalation from the

corresponding chloride. Other related rearrangements for cycloalkyl derivatives, leading

to carbyne products in some cases, have also been observed for this system (see Section

2.6.2.5). [72] The synthesis of 41 [73] may be mechanistically related to the synthesis of 40,

the dihydrogen byproduct being transferred to the vinyl group.

Scheme 14 Æ,Æ-Hydrogen Elimination Processes [67,68]

MoO 2Cl 2

WCl 3(OMe) 3

t-BuCH2MgCl (6 equiv)

Et2O, −78 oC 34%

t-BuCH2MgCl (6 equiv)

Et2O, −78 oC 50−70%

CBu t

Mo

But CH2Bu

H2C t

CH2But 38

Bu t H 2C

CBu t

W CH2But CH2But 39

2.6.2 Metal–Carbyne Complexes 105

N

M

N

Cl TMS

TMS

N

TMS

R 1 CH2Li

Et 2O

or THF

M = Mo, W; R 1 = H, Me, Pr, Ph, TMS, t-Bu

WBr 2(PMe 3) 4

THF, 69 o TMS

C

90%

TMS

TMS N

N

CH2R

N

M

1

TMS

N

CEt

PMe3

Me3P W PMe3 Me3P Br

41

25−80 o C

− H 2

73−91%

TMS

TMS N

N

CR 1 TMS

Tris(2,2-dimethylpropyl)(2,2-dimethylpropylidyne)tungsten(VI) (39): [68]

A soln of WCl 3(OMe) 3 (19.1 g, 50 mmol) in a mixture of THF and Et 2O was added very slowly

to 1 M t-BuCH 2MgCl (0.3 mol) in Et 2Oat–78 8C with vigorous stirring. The color of the

soln gradually turned yellow-green. After the addition was complete, no significant

amount of precipitate was apparent. The mixture was allowed to warm slowly from –78

to 258C over a period of 10 h to give a red-brown soln and abundant precipitate. After filtration

from Celite followed by washing of the filter cake with Et 2O, the solvent was removed

in vacuo to give a thick red-brown oily liquid. Pentane (200 mL) was added to the

residue, followed by another filtration and evaporation to dryness. The resulting oily red

liquid was distilled at ca. 808C/0.001 Torr through a short-path distillation apparatus;

yield 55–60%. An additional 5–10% yield can usually be recovered by extracting the tarlike

residue with pentane, filtering off the insolubles, removing the pentane in vacuo, and

again distilling the residue as before. 1 H NMR (benzene-d 6, ä): 1.66 (Ct-Bu); 13 C{ 1 H} NMR

(benzene-d 6, ä): 316.2 (W”C).

Ethylidyne(N¢-(trimethylsilyl)-N,N-bis{2-[(trimethylsilyl)amino-kN]ethyl}ethane-1,2-diamido-kN,kN¢)tungsten(VI)

(40, M=W;R 1 = Me); Typical Procedure: [71]

An Et 2O (25 mL) soln of [WCl{N(CH 2CH 2NTMS) 3}] (0.20 g, 0.345 mmol) was treated with

EtLi (0.019 g, 0.52 mmol) at 258C. The mixture turned light yellow as gas evolved. The resulting

mixture was stirred for another 3 h and then evaporated to dryness in vacuo. The

yellow residue was extracted with pentane (60 mL), and the extract was filtered. The filtrate

was concentrated to ca. 5 mLin vacuo and chilled at –408C for several h to yield the

product as light yellow crystals; yield: 0.16 g (81%); 1 H NMR (benzene-d 6, ä): 3.73

(W”CCH 3, 3 J WH = 7.9 Hz); 13 C{ 1 H} NMR (benzene-d 6, ä): 274.33 (W”C).

2.6.2.2 Method 2:

By Addition of Alkynes to Compounds with Metal-Metal Triple Bonds

Symmetrical alkynes provide access to carbyne complexes 42 upon reaction with symmetrical

triply bonded tungsten alkoxy, aryloxy, and mixed alkyl–alkoxy complexes

(Scheme 15). [74,75] This reaction occurs readily when R 1 is a simple alkyl group but also

for functionalized alkynes, more easily so in the presence of nitrogen donors (in which

case the base adducts are obtained). [74] This reaction is very sensitive to steric factors.

The formation of alkyne adducts, bis-alkyne adducts, and products of C-C couplings are

possible alternatives. [75,76] Other group 6 triply bonded dimers such as hexakis(dimethylamido)-

or hexaalkylditungsten(III) and molybdenum alkoxides do not cleave internal alkynes.

M

N

40

N

for references see p 135

106 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Unsymmetrical alkynes can often be cleaved even if one of the substituents is bulky,

giving a 1:1 mixture of the two carbyne products. However, use of an excess of the alkyne

increases the yield of one carbyne product, e.g. 43, by the metathesis procedure described

in Section 2.6.2.3, provided the lower-boiling alkyne is removed. Some of these reactions

afford satisfactory results only in the presence of a stabilizing base, e.g. quinuclidine. [74]

Terminal alkynes react with both tungsten and molybdenum alkoxides, but the CH product

is not isolable unless a stabilizing base is present. [77] The triple bond of selected nitriles

is also cleaved to afford a mixture of the carbyne and the sparingly soluble nitride products.

[78,79]

Scheme 15 Addition of an Alkyne to a Compound Containing

a Metal-Metal Triple Bond [74,79]

X 3W WX 3 + R 1 C CR 1

pentane, Et2O DME or THF

−40 oC to rt

47−91%

WX 3 = W(Ot-Bu) 3, W(CH 2t-Bu)(O-iPr) 2

R 1 = Me, Et, Pr, CH 2NMe 2, CH 2NEt 2, MOM, CH 2OTMS

(Bu t O) 3W W(OBu t ) 3 + R 1 C CR 2

pentane, Et2O

DME or THF

−40 oC to rt

R1 = t-Bu, TMS, Ph,

R2 CH CH2, CH(OEt)2, CO2Me, CH2CO2Me, Ac, St-Bu

= Me, Et

2 W( CR1 )X3 42

W( CR

43

1 )(OBut ) 3 W( CR2 )(OBut +

) 3

Tri-tert-butoxy(ethylidyne)tungsten(VI) (42,X=Ot-Bu; R 1 = Me); Typical Procedure: [74]

But-2-yne (80.1 ìL, 1.02 mmol) was added to a soln of [W 2(Ot-Bu) 6] (0.75 g, 0.93 mmol) in

pentane (30 mL) at –408C. The soln was maintained at –408C for 1 h and allowed to

warm to rt. The orange color faded to light amber, and after 2 h at rt the volatile components

were removed in vacuo, leaving a light brown solid. Larger scale preparations sometimes

yielded a brown oil initially, but the oil always crystallized with time in vacuo or

when seeded. Sublimation of the light brown residue at 258C/10 –6 Torr onto a –788C

probe afforded the pure, white product; yield: 0.59 g (74%). This material is very oxygenand

moisture-sensitive and darkens slightly when removed from the probe in a drybox. It

was generally prepared in pentane or THF and utilized directly for further reactions, assuming

a quantitative yield. 13 C{ 1 H} NMR (benzene-d 6, ä): 254.3 (W”CMe).

2.6.2.3 Method 3:

By Stoichiometric Alkyne Metathesis

A variety of alkoxo–carbyne complexes may be obtained from a preexisting carbyne complex

and an alkyne by a metathesis process (Scheme 16). This exchange takes place via a

metallacyclobutadiene intermediate 44, which has been observed or isolated for the corresponding

aryloxo and fluorinated alkoxo systems. Such intermediates have greater stability

for the tungsten systems. [67] This procedure is synthetically useful for symmetrical,

unsymmetrical, and terminal alkynes. Like the reactions examined in Section 2.6.2.2,

these are also sensitive to steric factors. [67,74] Electronic factors are also important, however,

fluoroalkoxo complexes reacting more readily than the corresponding alkoxo complexes

without fluorine substituents. Terminal acetylenes also react with bulkier carbyne

complexes, but the reaction is often complicated and other products (e.g., deprotonated

metallacyclobutadiene derivatives) may be obtained, limiting the synthetic utility. [67]

Scheme 16 Stoichiometric Alkyne Metathesis [67,74]

M( CR 2 )(OR 1 ) 3(L) + R 3 C CR 4 (excess) (R 1 O) 3(L)M

44

R 2

R 3

M( CR 3 )(OR 1 ) 3(L)

R 4

+ R 2 C CR 4

M L R 1 R 2 R 3 R 4 Conditions Yield (%) of

[M(”CR 3 )

(=OR 1 ) 3(L)]

Mo DMECMe(CF 3) 2 t-Bu a a Et 2O, rt,

15 min

Mo – t-Bu t-Bu b H E t 2O, rt,

30 min

W quinoline t-Bu Me C”CEt Et pentane, rt,

2d

a R 3 =R 4 = Me, Et, Pr, Ph.

b R 3 = Pr, iPr, Ph.

2.6.2 Metal–Carbyne Complexes 107

80–90

quant.

Addition of one equivalent of an internal alkyne, trichloro(1,2-dimethoxyethane-O,O¢)-

(2,2-dimethylpropylidyne)tungsten(VI) affords a stable tungstacyclobutadiene product,

but reaction with additional alkyne yields ç 5 -cyclopentadienyl products of further alkyne

insertion rather than products of alkyne metathesis. [69,80]

Butylidynetris(1,1,1-trifluoro-2-methylpropan-2-olato)molybdenum(VI);

Typical Procedure: [67]

Excess PrC”CPr (125 ìL, 0.85 mmol) was added to [Mo(”Ct-Bu){OCMe 2(CF 3)} 3] (0.09 g,

0.16 mmol) dissolved in Et 2O (3 mL). After 30 min, the solvent was removed in vacuo, leaving

white needles that were pure by NMR; 13 C{ 1 H} NMR (benzene-d 6, ä): 299.3 (Mo”CPr).

2.6.2.4 Method 4:

By Oxidation of Fischer-Type Carbyne Complexes

The dibromine oxidation of (alkylidyne)bromotetracarbonyl complexes of molybdenum

and tungsten in the presence of 1,2-dimethoxyethane (DME) provides a direct access to

DME-stabilized (alkylidyne)tribromo complexes, while the corresponding chromium systems

lead to complete degradation. [81] The advantage of this procedure is the direct access

to complexes with a wide variety of carbyne substituents starting from the corresponding,

easily accessible Fischer-type carbyne precursor. The phenyl derivative 45, in particular,

is easily synthesized in a one-pot procedure from the precursor as shown in Scheme

17.

Scheme 17 Oxidation of Fischer-Type Carbyne Complexes [81,82]

Me 4N[M(COPh)(CO) 5]

oxalyl bromide

CH2Cl2, −78 oC MBr( CPh)(CO) 4

Br2, DME

CH2Cl2 −78 oC M = Mo 80%

M = W 88%

64

Ref

[67]

[74]

MBr3( CPh)(DME)

45

for references see p 135

108 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Benzylidynetribromo(1,2-dimethoxyethane-O,O¢)tungsten(VI) (45,M=W): [81,82]

Me 4N[W(COPh)(CO) 5] (10.00 g, 19.87 mmol) was completely dissolved in CH 2Cl 2 (300 mL)

then the soln was cooled to –788C. Oxalyl bromide (1.87 mL, 20.0 mmol) was dissolved in

CH 2Cl 2 (40 mL) and cooled to –78 8C, then quickly added against a N 2 stream to the acyl

soln. This soln was left to stir at –788C for 15 min, then warmed in an ice bath just until

a bright yellow color developed. It was immediately recooled to –788C; then this soln was

filtered through a dry-ice jacketed frit, having a 2-cm layer of dry cellulose on it, into a

cooled (–78 8C) receiving flask (500-mLSchlenk). To the soln of [WBr(”CPh)(CO) 4] at

–78 8C was added DME (10 mL). A freshly prepared 1.0 M soln of Br 2 in CH 2Cl 2 (20 mL)

with an additional quantity of CH 2Cl 2 (20 mL) was cooled to –788C and added (poured)

against a strong N 2 stream as quickly as possible. The color became red briefly then dark

orange. The stirred soln was allowed to warm to rt under vacuum; much gas was evolved

during the warming step. The solvent was removed in vacuo and the dark brown oily solid

was washed with pentane (50 mL). The solid was then dissolved in CH 2Cl 2 (30 mL) and filtered.

The volume was reduced to 15 mLand pentane (100 mL) was added gradually to precipitate

the product as a green-brown solid. This precipitation process was repeated until

the product in CH 2Cl 2 was emerald green. The final product was a dark green microcrystalline

powder; yield: 10.49 g (88%); 13 C{ 1 H} NMR (benzene-d 6, ä): 331.7 (W”CPh).

2.6.2.5 Method 5:

By Rearrangement of Vinyl Complexes

Vinyl complexes can, under favorable circumstances, rearrange by a [1,2]-H shift to carbyne

complexes (Scheme 18). [83] The reaction appears to proceed via a ç 2 -vinyl complex

46, which has been isolated in some cases, [84] and thus requires an open coordination

site on the metal center. The vinyl precursors are often prepared in situ by hydride addition

to alkyne complexes, e.g. for the synthesis of 47 and indenyl analogues, [84] by deprotonation

of alkene complexes, [13] or by transmetalation, as for the synthesis of 48. [73] The

vinyl complex intermediate may not be observed in some cases. ç 3 -Allyl complexes are

possible byproducts of this reaction when the substituents R 2 and R 3 bear Æ-hydrogen atoms

(e.g., 47), [85] in which case the rearrangement to the carbyne product is favored by the

presence of free ligands and higher temperatures.

Scheme 18 [1,2]-H Shift from Vinyl Complexes [73,84]

[M]

R 3

R 1

R 2

Mo

(MeO)3P

WCl 2(PMe 3) 4

H

Pr i

+

[M]

R 3

R 2

R1 46

NaBH4 P(OMe) 3 (excess)

THF, rt, 2 h

58%

(5 equiv)

Si(OMe) 3

THF, reflux, 8 h

93%

[1,2]-R 1 shift

Mo

(MeO) 3P

(MeO)3P

47

CMe

PMe3 Me3P W PMe3 Me3P Cl

48

[M]

CH 2Pr i

R1 R3 R2

2.6.2 Metal–Carbyne Complexes 109

ç 5 -Cyclopentadienyl(3,3-dimethylbutylidyne)bis(trimethyl phosphite-P)molybdenum(IV):

[84]

A soln of [MoCp{ó-(E)-CH=CHt-Bu}{P(OMe) 3} 3] (0.35 g, 0.5 mmol) in hexane (10 mL) contained

in an evacuated sealed tube (50 mL) fitted with a Westoff stopcock was heated at

808C for 12 h. The mixture became bright yellow. The volatile material was removed in

vacuo and the residue was dissolved in Et 2O (5 mL) and chromatographed on an aluminapacked

column. Elution with hexane gave a bright yellow band, which was collected and

the volume of the solvent was reduced (to 5 mL); cooling (–788C, 3 d) afforded the product

as bright yellow crystals; yield: 0.21 g (85%); 1 H NMR (benzene-d 6, ä): 5.2 (s, 5H, Cp), 2.2 (t,

2H, CH 2t-Bu, 3 J HP = 4.0 Hz); 13 C{ 1 H} NMR (benzene-d 6, ä): 299.8 (t, Mo”C, 2 J CP = 27.0 Hz).

2.6.2.6 Method 6:

By Other Rearrangement Processes

The stability of the metal–alkylidyne bond, especially for tungsten, induces other remarkable

rearrangements from a variey of systems. The high-yield synthesis of compound 49

upon photolysis of hexamethyltungsten(VI) in neat trimethylphosphine involves a methyl

migration onto a proposed carbyne intermediate (Scheme 19). [86]

Other rearrangement processes have been established for selected cycloalkyl complexes.

[13,72] For molybdenum complexes, the cyclobutyl complex 50 converts into the butylidyne

product 52 without observation of a metallacyclopentene intermediate 51. [72] For

tungsten complexes, on the other hand, alkylation of the chloro precursor complex with

cyclobutyllithium yields the stable complex 51 directly, which is further transformed to

the carbyne product 52 upon warming (Scheme 19). [71] Cyclopropyl derivatives undergo

elimination of ethene and formation of a methylidyne product, while the cyclopentyl derivatives

do not undergo the ring-opening step.

Scheme 19 Other Rearrangement Processes [71,72,86]

WMe 6

Me3P (neat), hν

− 2CH4 TMS

TMS

TMS N

N

M

N

50

[W( CH)(Me) 3(PMe 3) n]

TMS

TMS N

N

M

N

51

M = W quant

− CH 4

90%

[W(Me) 2( CHMe)(PMe 3) n]

W(Me)( CMe)(PMe3) 4

49

TMS

TMS N

N

M

N

52 M = Mo 86%

Butylidyne(N¢-(trimethylsilyl)-N,N-bis{2-[(trimethylsilyl)amino-kN]ethyl}ethane-1,2diamido-kN,kN¢)molybdenum(VI)

(52, M = Mo); Typical Procedure: [72]

Compound 50 (M = Mo; 124 mg, 0.243 mmol) was dissolved in toluene (5 mL), and the soln

was heated in a sealed tube to 608C for 2 h. The toluene was removed in vacuo, and the

residue was dissolved in a minimum amount of pentane. The pentane soln was cooled to

–40 8C to give brown crystals of the product after 24 h; yield: 107 mg (86%); 13 C{ 1 H} NMR

(benzene-d 6, ä): 298.3 (Mo”C).

for references see p 135

110 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Applications of Product Subclass 2 in Organic Synthesis

The reactivity of Schrock-type carbyne complexes has to date been little exploited in organic

synthetic applications in comparison with that of the corresponding carbene complexes

(Section 2.6.1.5). For the most part, the interest has been limited to stoichiometric

transformations to other organometallic products. Some carbyne compounds ([M]”CR)

undergo Wittig-like reactions with X”Y molecules, affording [M]”X and RC”Y products.

[63] As seen in Section 2.6.2.3, the addition of an alkyne (R 2 C”CR 2 ) to a carbyne complex

([M]”CR 1 ) may afford the metathetical products (R 2 C”CR 1 +[M]”CR 2 ). Some of these

complexes catalyze the alkyne metathesis reaction. [87]

2.6.2.7 Method 7:

Alkyne Metathesis

Medium-large cycloalkynes 53 have been synthesized from diyne precursors by a ringclosing

metathesis process in which a tungsten carbyne complex acts as a catalyst

(Scheme 20). [46] The cycloalkyne obtained by this methodology can be partially reduced

to obtain the cycloalkene exclusively as the Z-isomer. The stereoselectivity of this route

is particularly notable, since current molybdenum- and ruthenium-based ring-closing metathesis

catalysts usually provide mixtures of E- and Z-configured cycloalkenes from diene

precursors (see Section 2.6.1.5.3). The catalyst tolerates various functional groups: lactones,

lactams, and silyl ethers have been obtained by this method. The catalyst is incompatible

with terminal acetylenes; thus, it is necessary to use precursors with R 1 ,R 2 „ H.

The use of a high boiling point solvent (e.g., 1,2,4-trichlorobenzene) allows the removal

of the alkyl byproduct (R 1 C”CR 2 ) under reduced pressure, with a positive effect on the

conversion.

Scheme 20 Cycloalkynes by Ring-Closing Metathesis of Diynes [46]

X

R 1

W( Ct-Bu)(Ot-Bu) 3

52−97%

R 1 = Me, Et; X = (CH 2) 2OC(O)(CH 2) 4C(O)O(CH 2) 2

1,6-Dioxacyclotetradec-9-yne-2,5-dione [53,X=(CH 2) 2OC(O)(CH 2) 4C(O)O(CH 2) 2];

Typical Procedure: [46]

A soln of the diyne [MeC”C(CH 2) 2O(O)C(CH 2) 2] 2 (121 mg, 0.43 mmol) and [W(”Ct-Bu)(Ot-

Bu) 3] (12 mg, 6 mol%) in chlorobenzene (20 mL) was stirred under argon at 808C for 2 h.

The solvent was removed in vacuo, and the residue purified by flash chromatography

(Merck silica gel, hexane/EtOAc 4:1). This led to the recovery of some unchanged starting

material (12 mg, 10%) and afforded the cycloalkyne product as colorless crystals; yield:

70 mg (73%); mp 106–1078C; 13 CNMR(ä): 173.0 (alkyne).

2.6.3 Product Subclass 3:

Metal–ó-Alkyl and –ó-Aryl Homoleptic Complexes

Compounds of this class are rather limited, their syntheses are generally low yielding,

and have no general applications in organic synthesis. As is usually the case for any metal,

the more robust complexes are those without â-hydrogens and aryl complexes. Well-characterized

members of this class have the stoichiometries MR 6,MR 4,[MR 6] 3– ,[MR 5] 2– ,

[MR 4] – ,MR 3, and [MR 4] 2– . The MR 6 complexes are known only for tungsten and have a

X

53

+

R 1

R 1

2.6.3 Metal–s-Alkyl and –s-Aryl Homoleptic Complexes 111

strong tendency to decompose by Æ-hydrogen elimination. The tetrahedral MR 4 complexes

can only be obtained with sterically demanding ligands and are unexpectedly unreactive.

While M(III) complexes with three unpaired electrons are common for chromium,

no unambiguous example has been reported for molybdenum or tungsten. Delicate

equilibria may exist between different species as a function of the size of R, the nature of

the counterion, or even the solvent. For example, orange-yellow hexaphenylchromate(III),

blue-green pentaphenylchromate(III), and cherry-red tetraphenylchromate(III) have been

isolated under different conditions. [88–90] Neutral trialkylchromium(III) compounds are

known only with very bulky R groups, e.g. bis(trimethylsilyl)methyl [CH(TMS) 2]. [91] Unambiguous

M(II) complexes exist only for chromium. These are either paramagnetic (S =2)

and square planar tetraalkylchromate(2–) monomers or diamagnetic tetraanionic dimers.

The choice of nuclearity is highly dependent on the counterion and the solvent; for example,

the lithium salt of tetramethylchromate(II) adopts a monomeric or a dimeric structure

depending on whether the lithium cations are surrounded by tetramethylethylenediamine

or by diethyl ether molecules. [92]

The relatively high polarity of the metal-alkyl bonds makes these derivatives rather

sensitive toward proton sources including water, especially when the latter can be

activated by coordination to the metal center. Thus, these compounds must generally be

synthesized and handled under scrupulously dry conditions.

Synthesis of Product Subclass 3

2.6.3.1 Method 1:

By Transmetalation

The only synthetic method that allows access to homoleptic alkyl and aryl complexes of

group 6 metals is the transmetalation reaction (Scheme 21). Competitive electron-transfer

processes and equilibria of association/dissociation of the alkylating reagent are often

the reasons for the moderate yields usually associated with these syntheses. There is no

general rule as to the best reagents and conditions to use for a specific product. Lithium

and magnesium reagents are typically used, although other alkylating sources have also

been employed. This is exemplified by the synthesis of hexamethyltungsten(VI) (54) [93,94]

and tetracyclohexylchromium(IV) (55). [95] As a general rule, lithium reagents are more reactive

than Grignard reagents, but have a greater tendency to engage in single-electrontransfer

(SET) side reactions. The choice of solvent may also be a determinant factor.

Tetrahydrofuran, diethyl ether, and toluene are the most commonly used solvents, the

latter disfavoring SET processes. The group 6 metal sources are typically the halides, but

the alkoxides have also been used, the latter usually reducing the SET reactivity. Many

neutral metal(IV) compounds are obtained from lower oxidation state precursors in

112 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Hexamethyltungsten(VI) (54): [94]

CAUTION: Hexamethyltungsten(VI) is known to decompose explosively. Proper safety precautions

should be taken during its synthesis, storage, and handling.

A 50-mLglass container with two openings was attached to a vacuum line, and WF 6 (1.1 g,

3.7 mmol) and pentane (10 mL) were condensed into it in vacuo and with cooling (liq N 2).

A 1 M soln of ZnMe 2 in heptane (11.5 mL) was slowly added dropwise at –788C. The mixture

was stirred at –358C for 2 d, filtered at –10 8C, and concentrated in vacuo at –708Cto

afford an orange soln. The yield (53%) was determined by the quantitative reaction of 54

with NO and weighing the resulting product [WMe 4{ON(Me)NO} 2].

2.6.4 Product Subclass 4:

Metal–ó-Alkyl and –ó-Aryl Non-homoleptic Complexes

Non-homoleptic (heteroleptic) complexes containing alkyl and aryl ligands are much

more common, exist in a wider variety of formal oxidation states and coordination environments,

and are more versatile in organic synthesis than the homoleptic complexes.

The use of ancillary ligands with strong ð-donating properties increases the relative stability

of high oxidation state derivatives. Thus, M(V) and M(VI) (M = Cr, Mo) alkyl and aryl

complexes exist when supported by oxo, imido, or nitrido ligands, [96–99] whereas no homoleptic

counterparts are known. Non-homoleptic tungsten(VI) complexes are more common

and stable than the homoleptic ones.

Like the homoleptic complexes (Section 2.6.3), the non-homoleptic complexes tend

to decompose more readily when they bear hydrogen atoms on the â-position, via the

ubiquitous â-hydrogen elimination pathway. As this pathway necessitates an empty metal

orbital cis relative to the alkyl group and a coplanar transition state, stable complexes

with â-hydrogen-bearing alkyl ligands may only be obtained when one or more of the

above requirements are not met. [100] In particular, these compounds may be isolated

when each valence-shell metal orbital is occupied by at least one electron and when the

ligands cis to the alkyl group do not easily dissociate. Complexes whose alkyl substituents

bear hydrogen atoms on the Æ-position may also decompose, this process being especially

favored for high-valent molybdenum and tungsten complexes, providing good synthetic

methods for carbene and carbyne complexes (see Sections 2.6.1 and 2.6.2, respectively).

Other methods of decomposition are associated with intramolecular C-H bond activation

of ancillary ligands, which is promoted by the metal electron richness, e.g. see

Scheme 22. [101] Finally, homolytic cleavage of the metal-alkyl bond may occur with production

of radicals and reduced metal complexes. Aryl derivatives are more robust than

the alkyl complexes toward this decomposition pathway.

Scheme 22 Decomposition of Alkyl Complexes by Alkane Elimination [101]

Mo

Me3P Me

Me 3P PMe 3

benzene-d6, >40

− CH4 oC Me3P

Mo

Me3P P

Me2

Like the homoleptic complexes, the transmetalation reaction represents the most convenient

entry to alkyl and aryl non-homoleptic complexes of group 6 metals. The metal-alkyl

and metal-aryl bonds may also be formed, however, by oxidative addition reactions.

2.6.4 Metal–s-Alkyl and –s-Aryl Non-homoleptic Complexes 113

Synthesis of Product Subclass 4

2.6.4.1 Method 1:

By Transmetalation

The ancillary ligands often provide steric and electronic protection to the transition-metal

center, resulting in a greater selectivity and higher yields for the transmetalation reactions

relative to those leading to the homoleptic counterparts (see Scheme 23). A typical

example is the synthesis of 56. [102] The empiricism in the choice of alkylating/arylating

agent and conditions parallels that discussed for the homoleptic products in Section

2.6.3. In addition to lithium and magnesium reagents, the occasional use of dialkylzinc

is also reported. The synthesis of compound 57 proceeds in good yields from the tri-tertbutoxo

precursor, whereas no product is recovered when starting from the corresponding

trichloride. [103] While the bis(imido)chromium(VI) precursors 58 afford products

59 [96,97,104] and mesitylmagnesium bromide reacts cleanly with dichlorodioxomolybdenum(VI)

to afford the corresponding dimesityldioxo product, use of mesitylmagnesium

bromide with dichlorodioxochromium(VI) leads to chromium(V) and chromium(III) products.

[97]

The reaction between phenylmagnesium bromide and chromium(III) chloride in diethyl

ether leads to chromium(I)-ð-arene complexes as final products. [105,106] The initial

reaction does, however, generate chromium(III)-ó-phenyl species, and the greater coordinating

ability of tetrahydrofuran permits the isolation of triphenyltris(tetrahydrofuran)chromium(III).

[107] In some cases, the reduction accompanying transmetalation may be

synthetically useful, e.g. the synthesis of 60. [108]

Scheme 23 Transmetalation [96,97,102,103,108]

W(Cp ∗ ) 2Cl 2

MeLi (2 equiv), toluene

80 oC, 2 h

65%

WMe 2(Cp ∗ ) 2

Mo( N)(OBu

t-BuCH2MgBr (3 equiv)

83%

57

t )3 Mo(CH2But ) 3( N)

R2 CrX2( NR

MgY (2 equiv)

58

59

1 ) 2 CrR2 2( NR1 ) 2

X = OTMS; R 1 = t-Bu; R 2 = Mes, 2,6-Me 2C 6H 3

X = Cl; R 1 = t-Bu, 2,6-iPr 2C 6H 3; R 2 = Me, Bn

MOCl 4

M = Mo, W

MeLi or MeMgCl

22−28%

56

[Mg(THF) 4][MOMe4] 2

60

Dimethylbis(ç 5 -pentamethylcyclopentadienyl)tungsten(IV) (56); Typical Procedure: [102]

[W(Cp*) 2Cl 2] (2.0 g, 3.8 mmol) and MeLi (0.40 g, 18.2 mmol) were treated with toluene

(20 mL) and heated to 80 8C for 2 h, giving a red-orange soln. The mixture was filtered

and the toluene was removed under reduced pressure. The residue was extracted into

pentane and cooled to –788C, giving orange needles of [W(Me) 2(Cp*) 2]; yield: 1.2 g (65%);

1 H NMR (benzene-d6, ä): 1.60 (s, 30H, C 5Me 5), –0.54 (s, 6H, WMe).

for references see p 135

114 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

2.6.4.2 Method 2:

By Oxidative Addition of Alkyl Halides

This method has mostly been used for the synthesis of chromium(III) compounds, with

wide application in the Nozaki–Hiyama–Kishi reaction (Section 2.6.4.5). Other group 6 derivatives

have been prepared as well.

2.6.4.2.1 Variation 1:

One-Electron Oxidative Additions

Chromium(II) precursors react with alkyl halide reagents to afford a 1:1 mixture of chromium(III)

halide and alkylchromium(III) products. The mechanism involves single-electron-transfer

steps and radical intermediates (Scheme 24). Other radical sources may be

used instead, including hydroperoxides or alkane/hydrogen peroxide mixtures under

thermal, flash photolysis, or pulse radiolysis conditions. [109] This procedure has been

used to produce the alkylpentaaquachromium(III) ion 61. [110] The latter is long-lived but

cannot be isolated and must be generated in situ. Activated alkyl halides react thermally

with the chromium(III) ion, while other alkyls require photolytic or radiolytic conditions.

The addition of ligands such as ethylenediamine or saturated tetraaza macrocycles makes

the process more favorable for both thermodynamic and kinetic reasons.

Scheme 24 One-Electron Oxidative Addition of Alkyl Halides [110]

[Cr(OH2)6] 2+

− [CrX(OH2)5] 2+

R1X R1• [Cr(OH2)6] 2+

[CrR 1 (OH 2) 5] 2+

Reduction of Chloroform with Chromium(II) Perchlorate: [111]

H 2O (1 L) was freed of oxygen and then shaken with CHCl 3 (10 mL). A 0.2 M soln of chromium(II)

perchlorate (500 mL) was added in an atmosphere of N 2 and the soln allowed to

stand for 2 or 3 h at rt. The grayish-red soln gave no precipitate with AgNO 3 soln at rt. A

portion (100 mL) of this soln was placed on a column (15 cm ” 2 cm) of Dowex 50-X4 (200–

400 mesh) in the hydrogen form and the column was eluted with 1 M HClO 4 at the rate of

1–2 drops •s –1 . A green fraction (100 mL) was soon eluted, followed by a colorless soln

(150 mL), and then by a red fraction (110 mL). The green and red fractions were identified

as containing [Cr(H 2O) 5Cl] 2+ and [Cr(H 2O) 5(CHCl 2)] 2+ , respectively, by UV–vis spectroscopy

and quantitative analysis with AgClO 4 and KMnO 4.

2.6.4.2.2 Variation 2:

Two-Electron Oxidative Additions

Electron-rich metal complexes containing at least one electron pair in a metal-based orbital

may undergo a classical two-electron oxidative addition of alkyl halides, making a

new metal-alkyl bond (Scheme 25). This synthetic strategy is thus generally limited to

systems supported by electron-donating ancillary ligands. No synthetically useful examples

of this type of reactivity have been described for noncarbonyl-containing group 6 organometallic

species where the halide ion is incorporated in the coordination sphere of

the metal. However, there are examples of two-electron oxidative addition reactions of alkyl

halides where the halide remains as an outer sphere counterion, as in the preparation

of 62. [102]

2.6.4 Metal–s-Alkyl and –s-Aryl Non-homoleptic Complexes 115

Scheme 25 Two-Electron Oxidative Addition of an Alkyl Halide [102]

W(Cp ∗ ) 2(

O)

MeI, toluene

rt, 12 h

77%

[WMe(Cp ∗ ) 2(

62

O)] + I −

Methyloxobis(ç 5 -pentamethylcyclopentadienyl)tungsten(VI) Iodide (62): [102]

A soln of [W(Cp*) 2(=O)] (150 mg, 0.32 mmol) in toluene (3 mL) was treated with MeI

(0.2 mL, 3.2 mmol) and the mixture was stirred. After ca. 5 min a yellow microcrystalline

deposit started to form. The stirring was continued for 12 h. The mixture was filtered and

the solid was washed with pentane (3 ” 2 mL) and dried in vacuo to give yellow crystals of

62; yield: 150 mg (77%); IR (Nujol) í~ max: [W(=O)] 868 (s) cm –1 ; 1 H NMR (CDCl 3, ä): 2.13 (s,

15H, C 5Me 5), 1.07 (s, 3H, WMe).

2.6.4.3 Method 3:

By Oxidative Addition of Alkanes and Arenes

Alkanes and arenes may be able to add oxidatively to a suitable metal complex, forming

an alkyl (or aryl) hydride product (Scheme 26). Arenes are more suitable than alkanes for

this methodology, for both kinetic and thermodynamic reasons. The metal complex must

be quite electron-rich to accomplish this process. Sufficiently reactive metal substrates

are usually generated in situ from more stable precursors by either a thermal or a photochemical

dissociation or reductive elimination process. For example, the tungstenocene

leading to product 63 is generated by photolytic reductive elimination of dihydrogen

from bis(ç 5 -cyclopentadienyl)dihydridotungsten(IV). [112] Tungstenocene may also be generated

by thermal alkane elimination from a dicyclopentadienyl–alkyl–hydride system.

[113] The product of the oxidative addition step may further evolve to afford more stable

alkyl or aryl products, as is the case for the synthesis of compound 64.

Scheme 26 Oxidative Addition of Alkanes and Arenes [112,114]

W(Cp) 2H 2

ON

hν, benzene

− H2 W

CH2But CH2But Me4Si (neat)

70 oC, 2.5 d

W

benzene

>80%

W

ON CHBu t

Me4Si

90%

H

(Cp) 2W

Ph

63

ON

W

CH2TMS CH2But (2,2-Dimethylpropyl)nitrosyl(ç 5 -pentamethylcyclopentadienyl)[(trimethylsilyl)methyl]tungsten(II)

(64); Typical Procedure: [114]

In a glovebox an ampule (Teflon stopcock) was charged with [W(CH 2t-Bu) 2Cp*(NO)]

(0.048 g, 0.098 mmol) and Me 4Si (1 mL). The resulting wine-red mixture was stirred and

heated at 708C for 2.5 d, during which time it changed to a darker red soln. The organic

volatiles were removed under reduced pressure. The remaining dark wine-red solid was

redissolved in pentane and filtered through Celite. The resulting soln was stored for several

days to provide 64 as maroon crystals; yield: 0.045 g (90%); 1 H NMR (benzene-d 6, ä):

1.54 (s, 15H, C 5Me 5), 1.35 (s, 9H, t-Bu), 0.38 (s, 9H, TMS).

64

for references see p 135

116 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

2.6.4.4 Method 4:

By Protonation of Carbene and Carbyne Ligands

Under suitable conditions, carbene and carbyne ligands can take up protons to generate

alkyl derivatives. The proton source must be of low acidity to avoid further protonolysis

of the alkyl product. This methodology is of rather limited synthetic utility. Two examples

are shown in Scheme 27. [115,116] The formation of 65 involves loss of the pyridine ligand

and proton transfer from the silanol to the carbene ligand, while even more extensive

changes accompany the protonation of the carbyne ligand to give alkyl complex 66.

Intramolecular proton transfer from other ligands (e.g., other alkyl groups) is also possible.

[65,66]

Scheme 27 Protonation of Carbene and Carbyne Ligands [115,116]

ON

Mo

CHBut py

W( CR 1 )(OBu t ) 3

R 1 = t-Bu, TMS

Ph3SiOH, benzene

rt, 90 min

75%

Et4NOH, THF

62−82%

ON

Mo

CH2But OSiPh3 65

[Et 4N][W(CH 2R 1 )O 3]

ç 5 -Cyclopentadienyl(2,2-dimethylpropyl)nitrosyl(triphenylsilanolato)molybdenum(II)

(65); Typical Procedure: [115]

In a glovebox, [Mo(=CHt-Bu)Cp(pyridine)(NO)] (102 mg, 0.30 mmol) and Ph 3SiOH (83 mg,

1.0 equiv) were weighed into the reaction vessel. Benzene (20 mL) was vacuum-transferred

onto the solids. The mixture was then warmed to rt and stirred for 1.5 h. Over the

course of the reaction a color change from amber to dark red-brown occurred. The solvent

was removed from the final mixture in vacuo, and the residue was extracted with Et 2O

(2 ” 25 mL). The extracts were filtered through Celite and the filtrate was concentrated under

reduced pressure to incipient precipitation. Well-defined red blocks formed overnight

and were isolated by cannulation; yield: 121 mg (75%); IR (Nujol) í~ max: (NO) 1607

(vs) cm –1 ; 1 H NMR (benzene-d 6, ä): 3.79 (d, 1H, CHH, J HH = 9.9 Hz), 0.99 (d, 1H, CHH,

J HH = 9.9 Hz).

Applications of Product Subclass 4 in Organic Synthesis

Alkylchromium(III) compounds are involved in the large-scale commercial polymerization

of ethene and propene. Well-defined complexes that mimic the activity and selectivities

of the commercial catalyst have been obtained. [117] An application of group 6 alkyl

and aryl complexes that has been successfully applied to organic synthesis is the addition

reaction to carbonyl compounds (see Sections 2.6.4.5 and 2.6.4.6). Other chromium-based

systems have been developed for single-electron-transfer chemistry, [118] oxidation of alkanes

via hydrogen atom abstraction, [119] and asymmetric ring opening of meso-epoxides.

[120] Although these latter systems are of interest for synthetic organic chemistry,

they do not involve the formation of direct Cr-C bonds, and consequently these applications

are not treated here. [121]

2.6.4 Metal–s-Alkyl and –s-Aryl Non-homoleptic Complexes 117

2.6.4.5 Method 5:

Addition of Organochromium(III) Compounds to Carbonyl Compounds

Under certain circumstances, organochromium(III) compounds transfer their alkyl or

aryl groups to aldehydes and, less frequently, to ketones. The particular selectivity and

tolerance of this reaction make it particularly useful in organic synthesis. The use of these

chromium reagents may be advantageous for use with acid-sensitive substrates, because

of their reduced Lewis acidity relative to other transfer reagents [e.g., trichloromethyltitanium(IV)

or alkyltriisopropoxotitanium(IV)].

2.6.4.5.1 Variation 1:

Reaction of Organochromium(III) Compounds Prepared

from Organochromium(III) Chloride by Transmetalation

The organochromium(III) compound may be either isolated before the addition to the carbonyl

compound or prepared in situ, as shown in Scheme 28. Triphenyltris(tetrahydrofuran)chromium(III)

is able to react with ketones, viz. pentan-3-one (67) and cyclohexanone.

[122] On the other hand, chlorodialkyl and dichloroalkyl derivatives are highly

aldehyde selective, while alkylpentaaquachromium(III) is unreactive. The alkyldichlorochromium(III)

reagent is particularly useful as it can be readily generated in situ by transmetalation

from chromium(III) chloride and a Grignard reagent; see the formation of

68. [123] These reagents are able to transfer the alkyl group to the organic substrate even

in an alcoholic medium or in the presence of water. [124] Dichloro[(trimethylsilyl)methyl]chromium(III)

allows an aldehyde-selective alkenation process after acid hydrolysis. [125]

This procedure has been more recently supplanted by those described in the following

variations.

Scheme 28 Reaction of Organochromium(III) Complexes with Carbonyl Compounds [122,123]

( )5

O

Cr(Ph)3(THF) 3

THF, −30 to 20 o C

Ph

67 70%

O

H

R 1 = Me, Pr, Bu, Bn

1. CrR1Cl2(THF) 3, THF, −60 oC 2. H2O 65−85%

OH

+

OH

H

( ) 5

R1 68

Ph OH HO

Reaction of Triphenyltris(tetrahydrofuran)chromium(III) with Pentan-3-one (67): [122]

A briskly stirred suspension of [CrPh 3(THF) 3] [from CrCl 3(THF) 3 (16 g, 43 mmol) suspended

in THF (500 mL) and PhMgBr (129 mmol)] in THF at –30 8C was treated dropwise with freshly

distilled pentan-3-one (67; 20 mL, 190 mmol). The mixture was then allowed to warm

up to rt. After 2 h at 208C the solvent was removed by distillation under reduced pressure

and the product hydrolyzed with H 2O and filtered, both residue and filtrate being washed

with Et 2O. The dried ethereal layer was evaporated and the residue (21.2 g) separated by

distillation. The volatile component, bp 57–62 8C/0.01 Torr (14.9 g, 90 mmol, 70% relative

to PhMgBr) was shown to be 3-phenylpentan-3-ol by a direct comparison of its IR spectrum

with that of an authentic specimen. The semicrystalline residue (5.87 g) was chromatographed

to give traces of oily products and 3-ethyl-4-methyl-5-phenylheptane-3,5diol;

yield: 5.36 g (17% relative to PhMgBr); mp 90–92 8C (hexane).

17%

Et

for references see p 135

118 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

2.6.4.5.2 Variation 2:

Reaction of Organochromium(III) Compounds Prepared

from Chromium(II) Chloride by Oxidative Addition

(The Nozaki–Hiyama–Kishi Procedure)

This methodology was pioneered by Hiyama [126] and refined by Kishi [127] and Nozaki. [128]

The organochromium reagent is readily formed from chromium(II) salts upon one-electron

oxidative addition (Section 2.6.4.2.1) of a wide range of substrates including allyl,

propargyl, alkenyl, and aryl halides, alkenyl trifluoromethanesulfonates, and allyl sulfonates

and phosphates. The most convenient chromium(II) salt is the anhydrous chloride,

which can either be purchased or prepared in situ from chromium(III) chloride and various

reducing agents. The performance of the chromium(II) chloride reagent in forming

the Cr-C bond is enhanced by the addition of a catalytic amount of nickel(II) chloride.

[127,128]

The alkylchromium(III) species are highly aldehyde selective, e.g. the formation of 69

in Scheme 29. [126] The most important feature, however, is the unparalleled compatibility

with a wide array of functional groups in both reaction partners. In addition, the method

features useful stereoselectivities. Substituted allyl reagents lead to the homoallyl alcohols.

If the allyl reagent is ª-monosubstituted, the anti-alcohol is favored independent of

whether the starting halide is E or Z configured; see the synthesis of 70 where the antiproduct

is obtained in 100% selectivity. [129] Alkenyl halides or trifluoromethanesulfonates

react with complete retention of their double-bond geometry, e.g. the synthesis of 71. [128]

These useful features have made chromium-induced inter- or intramolecular C-C bond

formations a frequent key step in the total synthesis of molecules of utmost complexity,

[130] including the total synthesis of brevetoxin B. [131]

Scheme 29 The Nozaki–Hiyama–Kishi Reaction [126,128,129]

OHC

PhCHO +

Ph

OTf

O

Br

+ PhCHO

+

Br

CrCl3/LiAlH4 THF, rt

87% Ph

CrCl2, NiCl2 (cat.)

DMF, 25 oC 92%

CrCl 2 (1.2 equiv), THF

3,3,6-Trimethylhepta-1,5-dien-4-ol; Typical Procedure: [126]

CrCl 3 (4.28 g, 27 mmol) was reduced with LiAlH 4 (513 mg, 13.5 mmol) in THF (20 mL). After

stirring at rt for 10 min, 3-methylbut-2-enal (0.56 g, 6.1 mmol) and subsequently 1-bromo-

3-methylbut-2-ene (2.01 g, 13.5 mmol) in THF (10 mL) were added dropwise over 20 min.

Stirring for 3 h, followed by workup and distillation (97–100 8C/4 Torr, Kugelrohr), gave

the product as an oil; yield: 0.90 g (88%).

Ph

OH

70

HO

71

66%

Ph

OH

69

2.6.4 Metal–s-Alkyl and –s-Aryl Non-homoleptic Complexes 119

2.6.4.5.3 Variation 3:

Catalytic Nozaki–Hiyama–Kishi Reaction (The Fürstner Procedure)

The examples outlined in Section 2.6.4.5.2 are stoichiometric in chromium(II) chloride

and generally employ a large excess of this reagent. As shown in Scheme 30, reaction of

the organic halide with two equivalents of chromium(II) halide yields the desired organochromium

species 72 and one equivalent of chromium(III) halide. The nucleophile then

adds to the aldehyde with formation of a chromium alkoxide species. The high stability of

the oxygen-chromium(III) bond serves as the thermodynamic sink; the alcohol product

is recovered by hydrolysis in the stoichiometric process. The use of halosilane, however,

forces an exchange by virtue of the higher oxophilicity of silicon, producing an additional

equivalent of chromium(III) halide. At this point the reaction can be made catalytic in

chromium by simply using a reagent capable of reducing chromium(III) to chromium(II),

e.g. metallic manganese. This modification does not compromise the scope, practicability,

efficiency, and chemo- and diastereoselectivity of the C-C bond formation. [130,132,133] In

addition, it reduces the consumption of the rather high-cost and toxic chromium reagent

and paves the way for potential applications in enantioselective syntheses using chromium

catalysts with chiral ancillary ligands. [134 ]

Scheme 30 The Catalytic Nozaki–Hiyama–Kishi Reaction

R 1 X

2 CrX 2

MnX 2

CrX 3

Mn

CrX 3

CrR1X2 72

OTMS

R 1 R 2

OCrX 2

R 1 R 2

TMSX

R 2 CHO

2-Butyl-1-(4-methoxyphenyl)prop-2-en-1-ol: Typical Procedure: [130]

A soln of 4-methoxybenzaldehyde (340 mg, 2.5 mmol), 2-[(trifluoromethyl)sulfonyloxy]hex-1-ene

(1.06 g, 4.6 mmol), and TMSCl (0.75 mL, 6.0 mmol) in DMF (1.5 mL) and DME

(5 mL) was dropped into a suspension of Mn powder (230 mg, 4.2 mmol), CrCl 2 (46 mg,

0.38 mmol), and NiCl 2 (10 mg, 0.07 mmol) in DME (5 mL) at 508C. After being stirred for

5 h at that temperature, the mixture was quenched with H 2O (15 mL) and extracted with

EtOAc (3 ” 50 mL), and the combined organic layers were washed with brine. Aq TBAF

(75% w/w) was added, and the soln was stirred at rt until TLC showed complete desilylation

of the crude product. Standard workup followed by flash chromatography (hexane/

EtOAc 15:1) afforded the product as a colorless syrup; yield: 420 mg (76%).

2.6.4.6 Method 6:

Additive–Reductive Carbonyl Dimerization

In this reaction an alkyl group R 3 is transferred from a suitable metal–alkyl complex to

the electrophilic carbon of a carbonyl substrate 73 (Scheme 31), resulting in the deoxygenation

and dimerization to product 74 in a single step. [135] The substrate 73 can be an

aromatic aldehyde or ketone, a conjugated enone, or a benzoic acid derivative. The alkyl

transfer reagents [R 3 M] are tungsten(V) compounds formulated as dialkyldipropoxo(ìpropoxo)tungsten(V)

dimers 75. They are obtained in situ by alkylation of the correspond-

for references see p 135

120 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

ing dichloro dimers with lithium or Grignard reagents and they are not isolated in view of

their extreme thermolability. A large variety of alkyl groups, (trimethylsilyl)methyl, and

phenyl have been used as R 3 , including ones where the â-hydrogen elimination process is

possible. [60] The procedure consists of the addition of the carbonyl substrate to 75 in tetrahydrofuran

at –788C, followed by warming to reflux and room-temperature base hydrolysis.

Various substituents (e.g., methoxy, dimethylamino, fluoro, chloro, and hydroxy)

on phenyl groups are tolerated (e.g., see synthesis of 76), but the nitro and ethoxycarbonyl

groups are not. [135] For R 3 = Me, the carbonyl group must be conjugated with an unsaturated

group, otherwise the monomeric carbinol is obtained. With R 3 = Ph, however,

even saturated ketones yield the additive–reductive carbonyl dimerization product. Rearrangement

products can also be obtained, depending on the substituents linked to the

carbonyl group; see, for example, the reaction of 2-furaldehyde (77). [60]

Scheme 31 Additive–Reductive Carbonyl Dimerization [60,135]

2

Me 2N

O

R 1 R 2

O

77

73

CHO

2 [R3 + M]

O

H

R1 2(PrO) 2W W(OPr) 2R

O

1 Pr

O

2

Pr 75

R 1 = Me 82%

Pr

O

Me2(PrO) 2W W(OPr) 2Me2 O

Pr

75 R 1 = Me

R 1

R

74

2

R3 R2 R3 O

Me2N

43%

O

+

76

O O

1,2-Bis[4-(dimethylamino)phenyl]-1,2-dimethylethane (76); Typical Procedure: [135]

[W 2Cl 4(ì-OPr) 4(OPr) 4] (2.2 g, 2.50 mmol) was dissolved in THF (100 mL) at –788C, followed

by treatment with 1.5 M MeLi in Et 2O (4 equiv), resulting in a color change to dark green.

After 30 min, the Gilman test indicated the absence of MeLi. To this soln was added a THF

soln (25 mL) of 4-(dimethylamino)benzaldehyde (2.50 mmol). After stirring for 15 min at

–78 8C, the mixture was slowly warmed and refluxed for 3 h. The mixture was then hydrolyzed

with 2 M NaOH (100 mL) at 20 8C. Et 2O (50 mL) and petroleum ether were added and

the mixture was stirred until dissolution of the amorphous hydrolysis product occurred.

The organic phase was removed and the aqueous phase was extracted with Et 2O

(2 ” 100 mL). The combined organic phases were washed with H 2O and dried (Na 2SO 4).

The solvents were removed by rotary evaporation, leaving a crude material which was

identified (by GC in comparison with authentic samples) as a mixture of the title compound

76; yield: 82% and 1-[4-(dimethylamino)phenyl]ethanol; yield: 4%.

2.6.5 Product Subclass 5:

Metallacyclic Complexes

In many respects, the synthetic methods and reactivity of metallacyclic complexes parallel

those of analogous dialkyl complexes. Metallacyclobutanes and metallacyclopentanes,

on the other hand, display unique features. They may easily transform into, or be pre-

30%

NMe2

2.6.5 Metallacyclic Complexes 121

pared from, carbene–alkene and dialkene isomers, respectively (Scheme 32). The cyclic

forms tend to be more stable for the heavier metal, with differences in stability of three

orders of magnitude being reported for congeneric molybdenum and tungsten compounds.

[8]

Scheme 32 Transformations of Metallacyclobutanes and Metallacyclopentanes

M

Metallacyclobutane complexes are involved as intermediates in alkene metathesis reactions

catalyzed by alkylidene complexes and their use is equivalent to that of the carbene

complexes in this particular organic application (see Section 2.6.1). Chromacyclopentane

complexes are invoked as intermediates in the catalytic trimerization of ethene to hex-1ene.

[136] This catalytic process takes place with good selectivity (74%), but has not yet found

application for the oligomerization of other alkenes nor for cross-oligomerization

processes.

Synthesis of Product Subclass 5

2.6.5.1 Method 1:

By Transmetalation

This method is not as common as those described below for the preparation of group 6

metallacyclic derivatives. Dilithium and di-Grignard reagents have been used, as exemplified

by the syntheses of 78, 79, and 80 (see Scheme 33). [104,137] The synthesis of metallacycles

with large ring sizes suffers from the competitive formation of oligomers and from âhydrogen

elimination processes.

Scheme 33 Metallacycles by Transmetalation [104,137]

Bu

Cr N

tN But Br

N Br

N

Me2 Cr

Cl

Et 2O, −30 o C

Li

CH(TMS)Li(TMEDA)

64%

THF, −20 o C

77%

Li

Bu

Cr

tN ButN N

Me 2

TMS

78

Cr

79

for references see p 135

122 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

N

Me2 Cr

Cl

ClMg

THF, −30 o C

49%

Butane-1,4-diyl(ç 5 -pentamethylcyclopentadienyl)(trimethylphosphine)chromium(III);

Typical Procedure: [137]

[CrCp*Cl 2(THF)] (100 mLof a 0.085 M THF soln, 8.5 mmol) was treated with Me 3P(1mL,

9.88 mmol) and cooled to –508C. 1,4-Dilithiobutane (35 mLof a 0.277 M soln in Et 2O) was

added slowly and the mixture was stirred at –358C. The mixture was evaporated to dryness

and the residue was extracted with pentane (2 ” 150 mL) at –208C. The extract was

filtered, cooled to –788C, and the resulting blood-red crystals isolated and dried under

high vacuum; yield: 2.06 g (76%).

2.6.5.2 Method 2:

By Reductive Coupling of Alkenes

This method is specific for metallacyclopentanes. The alkene-coupling process is favored

by metal reduction. A typical synthetic strategy is the in situ reduction of a metal halide

precursor in the presence of the alkene; see, for example, the synthesis of 79 in Scheme

34. [137] An alkylidene precursor may also lead to a metallacycle with elimination of the carbene

ligand as in the synthesis of 81, representing a deactivation pathway for alkene metathesis

catalysts. [138] The two alkenes may be generated in situ in the coordination sphere

by rearrangement processes, such as intramolecular hydrogen transfer from an alkyl–vinyl

precursor. [139]

MgCl

N

Me 2

Scheme 34 Metallacyclopentanes by Reductive Coupling of Alkenes [137,138]

N

Me2 TMS

N

Cr

Cl

Ph

N

W

CH2But CH2But N

TMS

THF, −30 o Mg, H2C CH2 (excess)

C

90%

H2C CH2

(excess), 80 o C

TMS

N

Me 2

Cr

79

Ph

N

W CH2 N

TMS

Cr

80

TMS

N

Ph

N

W

N

TMS

81

Butane-1,4-diyl(ç 5 -pentamethylcyclopentadienyl)(trimethylphosphine)chromium(III);

Typical Procedure: [137]

The compound described in the experimental procedure in Section 2.6.5.1 can also be prepared

in 68% yield by reacting [CrCp*Cl 2(THF)] with active Mg and Me 3PinanEt 2O soln

saturated with ethene at –78 to –108C.

2.6.6 Complexes with Triply Bonded Heteroelement Ligands 123

2.6.5.3 Method 3:

By Addition of Alkenes to Carbene Complexes

This method is specific for metallacyclobutane complexes. For stability reasons this method

has been mostly applied to the preparation of high oxidation state tungstacyclobutane

derivatives. Given the equilibrium shown in Scheme 32, the use of excess alkene may result

in further exchange processes. The preparation of 82 in Scheme 35 is a two-step process

involving the elimination of 3,3-dimethylbut-1-ene. [29]

Scheme 35 Metallacyclobutanes by Alkene Addition to Carbene Complexes [29]

Pr i

Pri N

W

ButHC OCMe(CF OCMe(CF3) 2

3) 2

(excess)

TMS

pentane, rt, 2 h

ca. quant

Pr i

N

OCMe(CF3) 2

W TMS

TMS

OCMe(CF3) 2

82

1,2-Bis(trimethylsilyl)propane-1,3-diyl(2,6-diisopropylphenylimido)bis(1,1,1,3,3,3-hexafluoro-2-methylpropan-2-olato)tungsten(VI)

(82); Typical Procedure: [29]

Trimethyl(vinyl)silane (124 ìL) was added to a soln of [W(=CHt-Bu)(=NC 6H 3-2,6-iPr 2){OC-

Me(CF 3) 2} 2] (212 mg) in pentane (15 mL). The solvent was removed in vacuo after 2 h to

give a light yellow product that was recrystallized from pentane to give light yellow crystals.

The yield of the crude product was essentially quantitative.

2.6.6 Product Subclass 6:

Complexes with Triply Bonded Heteroelement Ligands

The only known examples are nitride complexes, whereas terminal phosphide and arsenide

complexes are known only without metal-carbon bonds. The lone pair on the nitride

ligand retains sufficient Lewis basicity for coordination. Consequently, electronically

unsaturated derivatives yield polymeric or oligomeric structures where nitrido groups

bridge two metal centers symmetrically or asymmetrically. [140,141] Mononuclear complexes

with terminal nitrido ligands are only found when the Lewis acidity of the metal

center is suppressed by ð-donation from other ligands, e.g. amido ligands as in bis(diisopropylamido)[(dimethylphenylsilyl)methyl]nitridochromium(VI).

[142] In addition, oligonuclear

structures where the nitrogen atom forms bonds of lower order with more metal atoms

may be preferred to a triply bonded mononuclear structure.

Almost all organometallic nitride complexes have been obtained by adding the organic

group(s) to inorganic substrates that already contain the M”N function. An example

is the synthesis of compound 57 shown in Scheme 23. [103] A large number of methods for

assembling a metal-nitrogen triple bond in inorganic compounds are outlined in a review.

[143] Some of these methods are also of potential applicability to organometallic substrates

and are, therefore, briefly mentioned here (Scheme 36).

The exchange of three halides with a nitride can be accomplished by use of the

[Hg 2N] + ion, tris(trimethylsilyl)amine, or ammonia, with elimination of mercury(II) salts,

trimethylsilyl halide, or hydrogen halide, respectively. In the latter case, excess ammonia

is needed to neutralize the acid. The ammonolysis of trialkyl or alkyl–carbene complexes

has been used successfully to prepare organometallic nitride complexes of group 4 and 5

metals (see Sections 2.8–2.11) and could potentially be used for group 6 metals as well.

Ammonolysis of a carbyne complex would appear to have the same potential.

Nitride complexes are also obtained by exchange of a halide with groups capable of

readily eliminating a stable byproduct while leaving a nitrogen atom bonded to the met-

for references see p 135

124 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

al, with concomitant metal oxidation. Azide is the ubiquitous ligand with these characteristics,

leading to the expulsion of dinitrogen. It can be administered either as a hydrophilic

alkali metal salt or as the lipophilic trimethylsilyl derivative. The reaction between

trichloro(ç 5 -pentamethylcyclopentadienyl)molybdenum(IV) dimer and trimethylsilyl

azide generates dichloro(ç 5 -pentamethylcyclopentadienyl)nitridomolybdenum(VI)

which, however, further evolves to more complex products. [140] An alternative to the

azide reagent is the deprotonated 9,10-dihydro-9,10-epiminoanthracene, [144] leading to

the elimination of anthracene.

Other nitride compounds have been obtained by oxidation of coordinated ammonia

ligands. The deoxygenation of a nitrosyl ligand is of potentially wide applicability. The

oxygen-abstracting agent is an oxophilic metal complex such as trimesityl(tetrahydrofuran)vanadium(III).

[145] Nitride compounds are also the byproducts of the addition of nitriles

to triply bonded molybdenum and tungsten compounds (see Section 2.6.2.2). The

splitting of the dinitrogen triple bond by a metal complex is a more recent achievement

[146] but is so far limited to a sterically protected triamidomolybdenum system. [147]

Other methods include the use of nitrogen trichloride, trithiazyl chloride, or aryl azide

reagents. [143,148] Splitting of nitrous oxide (N 2O) provides mixtures of nitrido and nitrosyl

products. [148]

Scheme 36 Methods for Assembling the M”N Function in Inorganic Compounds

of Group 6 Metals

X

[M] X

X

[M] R1 R1 R1 CH2R

[M]

1

CHR1 − 3X −

[M] NO

[N 3− ]

− 3R1 NH3

H

NH3

− 2R1 Me

− [O]

[M] N

− 3e −

− 3H +

[M] NH 3

[M] + 1/2 N N

− N 2

[M] N 3

[M]

− N

N3 −

N

[M] X

Phosphide and arsenide complexes have also been synthesized for the first time in nonorganometallic

complexes. [149,150] Organometallic derivatives have yet to be reported.

2.6.7 Product Subclass 7:

Complexes with Doubly Bonded Heteroelement Ligands

The vast majority of examples in this subclass are oxo and imido derivatives. A fair number

of sulfido derivatives are also known, whereas selenido and tellurido derivatives and

compounds containing a double bond to phosphorus (phosphinidene complexes) are fewer.

The relative small number of derivatives with phosphorus and the chalcogenides may

be attributed to the weakness of the ð-interaction. The bonds between the aforementioned

groups and a transition metal are considered double according to valency; however,

these bonds are often relatively short and strong in electronically unsaturated systems,

especially for oxo and imido ligands, because of the participation of an additional

ligand lone pair to the bonding.

In many cases a mononuclear structure with a terminal, doubly bonded heteroelement

ligand may be unfavorable with respect to the alternative dinuclear structure where

the ligand adopts a bridging, singly bonded conformation (Scheme 37). Facile interconversion

of the two forms may occur, leading to analogous synthetic strategies and reactivity.

−

2.6.7 Complexes with Doubly Bonded Heteroelement Ligands 125

For this reason, bridged dinuclear compounds are also included in this section, although

emphasis is placed on the terminally bonded derivatives. The mononuclear structure is

favored by a sterically encumbering coordination sphere, whereas electronic configurations

that allow the formation of metal-metal bonds lead preferentially to dinuclear

structures. First-row heteroelement-containing ligands (oxo, imido) are found terminally

bonded more frequently than their heavier congeners because of their superior ð-bonding

ability.

As seen for the triply bonded heteroelement derivatives, the most common synthetic

method for the present subclass consists of the introduction of the organic fragment into

an inorganic substrate that already contains the desired doubly bonded heteroelement ligand.

This is especially true for the oxo compounds, as metal oxides or oxometalate precursors

are readily available and inexpensive starting materials. The methods discussed

in this section are those leading to the assembly of the metal-heteroatom double bond

starting from substrates that already contain hydrocarbyl ligands.

Scheme 37 Monomer–Dimer Dichotomy for Doubly Bonded Heteroelement Ligands

2 [M] E [M]

E

[M]

Synthesis of Product Subclass 7

2.6.7.1 Method 1:

From Complexes Containing Singly Bonded Heteroelement Ligands

Singly bonded heteroelement ligands that contain a hydrogen substituent may be deprotonated

by either an internal or an external base and transformed into doubly bonded ligands.

In many cases the singly bonded hydrogen-bearing ligand is formed in situ by

ligand exchange from a halide or alkoxide precursor. This is the case for the reaction between

dichlorobis(ç 5 -pentamethylcyclopentadienyl)tungsten(IV) and potassium hydroxide,

leading to the oxo derivative 83 by spontaneous elimination of water; see Scheme

38. [102] In this case the proton scavenger is a coordinated base (OH) and the conjugate

acid is expelled. In high oxidation state systems, halides may be sufficiently good bases

leading to the expulsion of the hydrogen halide, as in the hydrolysis of tetrabromo(ç 5 -cyclopentadienyl)molybdenum(V).

[151] An intramolecular hydrogen transfer to a carbyne ligand

furnishes the oxo–alkyl derivative 66 (Scheme 27).

For the synthesis of 84, aminolysis of tungsten-methyl bonds yields an imido and an

amido ligand in a first step. An external base, however, is necessary to produce the second

imido ligand, as neither the residual methyl ligand nor excess aniline is sufficiently basic

to carry out the last deprotonation. [152] Imido derivatives have also been obtained from trimethylsilylamido

derivatives, the elimination of the trimethylsilyl group (a proton equivalent)

being favored by the presence of chloro, alkoxo, or oxo ligands. An external base

may also serve as a catalyst for the intramolecular proton transfer to another ligand, as

shown in the triethylamine-catalyzed isomerization of the amido–carbyne complexes 20

to the imido–carbene complexes 21 (Scheme 7). [8,17,29]

A reverse strategy involves rearrangement from a precursor complex that contains

the proton on the metal center and the base on the heteroatom ligand, as in the synthesis

of the phosphinidene complex 85. [153] Ligand exchange from halide precursors with lithium

disulfide has provided access to sulfido derivatives, occasionally involving metal oxidation,

as in the formation of (ç 5 -pentamethylcyclopentadienyl)trisulfidotungstate(VI)

86. [154] The same transformation can also be performed, although in lower yield, using hydrogen

sulfide in the presence of triethylamine. [155]

for references see p 135

126 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Scheme 38 Syntheses from Complexes Containing Singly Bonded

Heteroelement Ligands [102,152–154]

W(Cp ∗ ) 2Cl 2

M(Cp) 2HLi

WMe 4

KOH (2 equiv)

THF, H2O R 1 PCl 2

+

PF 6 −

M = Mo, W; R 1 = 2,4,6-t-Bu 3C 6H 2

WCp ∗ Cl 4

1. Li2S2, THF, rt, 1 h

2. Ph4PBr, MeCN

61%

(Cp ∗ OH

) 2W

OH

PhNH2 (2 equiv)

CH2Cl2, rt, 2.5 h

87%

H

(Cp) 2M

PR1Cl − HCl

[Ph4P][WCp ∗ S3] 86

− H2O 36%

W

Me NPh

NHPh

Et3N, CH2Cl2 rt, 15 min

94%

W(Cp ∗ ) 2( O)

83

+

(Cp) 2M P

R1 85

PF 6 −

Me

W

NPh

84

tert-Butylammonium Trioxo(ç 5 -pentamethylcyclopentadienyl)tungstate(VI): [155]

An excess of t-BuNH 2 (0.08 mL, 0.76 mmol) and H 2O (0.04 mL, 2.2 mmol) was added to a

CH 2Cl 2 soln (25 mL) of [WCp*Cl(=O) 2] (140 mg, 0.36 mmol). The soln was stirred for 1 h,

dried (MgSO 4), and filtered through a pad of Celite. The solvent volume was reduced to

2–3 mLand hexane was added to induce precipitation of [WCp*(=O) 3][t-BuNH 3], which

was isolated; yield: 137 mg (86%).

2.6.7.2 Method 2:

From Other Complexes Containing Doubly Bonded Heteroelement Ligands

Compounds containing a metal-heteroatom double bond may be obtained from analogous

derivatives by exchanging the heteroelement ligand. This strategy is especially useful

for preparing imido and sulfido derivatives from more easily available oxo compounds.

In most cases, this method is used for the preparation of inorganic materials

that are subsequently converted into organometallic compounds via metathetical reactions

(see Section 2.6.1.5). [25] The new function (X) can be administered as either the diprotic

acid (H 2X) or the cumulene (O=C=X).

The use of the acid presents potential problems in the presence of sensitive hydrocarbyl

ligands. For particular systems, especially high oxidation state molybdenum and

tungsten compounds, the metal-carbon bonds are sufficiently covalent and resist protonolysis.

This is illustrated in the oxygen/sulfur exchange leading to products 87 in

Scheme 39. [156] The relative strengths of the metal-heteroelement double bonds are

against the exchange of oxygen by sulfur, whereas the weaker acidity of water vs hydrogen

sulfide favors the exchange. Concerning the oxo/imido exchange, the acidity criteri-

2.6.7 Complexes with Doubly Bonded Heteroelement Ligands 127

on favors the conversion of imido ligands into oxo ligands, especially when the amine byproduct

is further consumed by protonation in an acidic medium. [152] The synthetically

more useful reverse exchange is favored by trapping water with the chlorotrimethylsilane/triethylamine

combination, leading to hexamethyldisiloxane and triethylammonium

chloride. [25] This reaction could in fact involve the in situ conversion of the primary

amine into a bis(trimethylsilyl)amine which subsequently carries out the exchange process.

The direct use of a trimethylsilyl-substituted amine has also led to satisfactory results.

[157]

The use of cumulenes has practical synthetic use only for the conversion of oxo into

imido derivatives by the use of isocyanates. Formation of carbon dioxide provides the necessary

driving force to the reaction. An example is the synthesis of compound 88, where

the incompleteness of the second step limits the yield. [158] A problem of this synthesis is

the potential cycloaddition of the imido product with excess isocyanate, leading to metalated

ureas.

Scheme 39 Syntheses from Other Complexes Containing Doubly Bonded

Heteroelement Ligands [156,158]

H2S, CS2

M = W; R 87

1 = Me 77%

M = W; R1 = CH2TMS 40%

M = Mo; R1 MCp

− H2O

= CH2TMS 77%

∗ R1 ( O) 2 MCp ∗ R1 ( O)( S)

W

R 1 O

O

R2NCO, hexane

140 oC, 1 week

52%

W

R 1 NR 2

O

R2NCO, hexane

125 oC, 20 d

23%

W

R1 NR2 NR2 88

Oxo(ç 5 -pentamethylcyclopentadienyl)sulfido[(trimethylsilyl)methyl]molybdenum(VI)

(87, M = Mo; R 1 =CH 2TMS); Typical Procedure: [156]

A soln of [Mo(CH 2TMS)Cp*(=O) 2] (25 mg, 0.071 mmol) in CS 2 (10 mL) saturated with H 2S

was incubated at rt for 3 d, during which time the color of the soln changed from tinted

yellow to red. The solvent was removed with a stream of N 2. The red residue was spotted

on a 0.25-mm-thick silica gel TLC plate and then developed with Et 2O. The red band was

collected to give [Mo(CH 2TMS)Cp*(=O)(=S)]; yield: 20.2 mg (77%). X-ray crystallographic

quality, dark red crystals were grown from a saturated soln in hexane at –208C.

2.6.7.3 Method 3:

From Complexes Containing Triply Bonded Heteroelement Ligands

This method is restricted to the transformation of terminal nitrides to imide compounds.

A rare example of the application of this method to organometallic substrates is the protonation

of tris(2,2-dimethylpropyl)nitridomolybdenum(VI) to afford the imido complexes

89 (Scheme 40). [103,159]

for references see p 135

128 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Scheme 40 Synthesis from a Complex Containing a

Triply Bonded Heteroelement Ligand [159]

Mo(CH2Bu t )3( N)

X = F, Cl, Br, I, OPh, OSiPh 3

HX, THF

40−85%

H

N

Bu t H2C Mo

X

89

CH2Bu t

CH 2Bu t

Tris(2,2-dimethylpropyl)imido(triphenylsilanolato)molybdenum(VI) (89, X = OSiPh 3);

Typical Procedure: [159]

[Mo(CH 2t-Bu) 3(”N)] (1.0 mmol) and triphenylsilanol (1.0 mmol) were placed in a Schlenk

tube under argon and dissolved in THF (30 mL). The mixture was stirred at 60 8C for 48 h.

Removal of the solvent under reduced pressure and extraction of the residue with hexane

(5 mL) afforded [Mo(CH 2t-Bu) 3(=NH)(OSiPh 3)] as a white powder. Recrystallization from

hexane at 08C gave white crystals; yield: 240 mg (40%); IR (Nujol) í~ max:(N-H) 3371 cm –1 .

2.6.7.4 Method 4:

By Oxidative Processes

The most useful oxidizing agents for the preparation of organometallic oxo compounds

have been nitrogen oxides such as trimethylamine oxide, nitrous oxide, and nitric oxide,

allowing the preparation of compounds that cannot be accessed by other methods, although

the oxidations are often accompanied by the formation of other products. [160] For

selected systems, oxidation of a low-valent precursor with the heteroelement itself in its

natural state (e.g., O 2,S 8) is sufficiently clean to be synthetically useful for the preparation

of oxo and sulfido complexes. This is especially true for ç 5 -cyclopentadienyl and ç 5 -pentamethylcyclopentadienyl

systems. The synthesis of 90 (Scheme 41), involving exhaustive

decarbonylation, represents a typical example. [161] Photochemical activation of the carbonyl

precursor is necessary in some cases. [162] Occasionally, elemental oxygen can be replaced

by hydrogen peroxide, as, for example, in the synthesis of 91, but this requires the

use of a strict stoichiometric ratio to avoid further conversion into peroxo analogues. [163]

Hydrogen sulfide also leads to oxidation, with expulsion of dihydrogen, in the synthesis

of compound 92. [164] The synthetic utility of the oxidation with a diazene to yield a bis(imido)

product has only been illustrated for inorganic target systems. [165]

Scheme 41 Oxidative Processes [161,163,164]

{MCp(CO) 2} 2

MCp(NO)R 1 2

R 1 = Me, CH 2TMS; M = Mo, W

Me 3P

H

Me 3P

PMe3 PMe2

Mo

PMe 3

air, CHCl3 or benzene, rt

M = Mo 69%

M = W 14%

30% aq H2O2, rt, 1 h

ca. 10−50%

H2S, pentane, −78 o C

− H 2

60%

(CpMO2)O 90

MCpO 2R 1

91

Me3P

S

Mo

PMe3 Me3P S

PMe3 92

2.6.7 Complexes with Doubly Bonded Heteroelement Ligands 129

Chlorodioxo(ç 5 -pentamethylcyclopentadienyl)molybdenum(VI): [162]

In a drybox, a 100-mLglass ampule (Teflon stopcock) was charged with a soln of

[MoCp*Cl(CO) 3] (0.980 g, 2.79 mmol) in toluene (50 mL). O 2 was bubbled through the soln

via a 24-gauge syringe needle at a rate of approximately 2 bubbles •s –1 while the soln was

irradiated with a 450-W medium-pressure Hg immersion lamp at 58C. The reaction was

monitored by IR spectroscopy and was stopped after 90 min when the absorbances due

to the carbonyl ligands of the starting material at 1700–2000 cm –1 had disappeared.

During the reaction the soln turned from a red-orange to an amber shade with some

blue solids precipitated on the walls of the reaction vessel. The toluene was removed under

vacuum, leaving a brown solid. The solid was taken up in toluene in the drybox and

the resulting soln filtered through a medium-porosity sintered-glass frit to remove insoluble

blue impurities. Recrystallization (toluene/hexane) afforded [MoCp*Cl(=O) 2] as a yellow

solid; yield: 0.508 g (61%); IR (benzene-d 6) í~ max: (Mo=O) 920 (s), 890 (s) cm –1 ; 1 HNMR

(benzene-d 6, ä): 1.63 (s, C 5Me 5).

ç 5 -Cyclopentadienyldioxo[(trimethylsilyl)methyl]tungsten (91,R 1 =CH 2TMS; M = W);

Typical Procedure: [163]

To a stirred, purple soln of [W(CH 2TMS) 2Cp(NO)] (1.20 g, 2.65 mmol) in Et 2O (50 mL) was

added a 30% by weight aq soln of H 2O 2 (0.22 mL, 2.8 mmol of H 2O 2). The initial purple color

of the mixture faded over the course of 1 h to pale yellow. An IR spectrum of the final yellow

soln was devoid of absorptions due to the nitrosyl reactant. Volatiles were removed

from the final mixture under reduced pressure to obtain a sticky yellow solid which was

dried at 208C/0.005 Torr for 2 h. Recrystallization of the resulting pale yellow solid from

Et 2O/hexanes (1:1) at –208C afforded [W(CH 2TMS)Cp(=O) 2] as a white microcrystalline solid;

yield: 0.50 g (51%); IR (benzene-d 6) í~ max: (W=O) 948 (s), 907 (s) cm –1 ; 1 H NMR (benzened

6, ä): 5.69 (s, 5H, Cp), 0.88 (s, 2H, CH 2), 0.28 (s, 9H, TMS).

Applications of Product Subclass 7 in Organic Synthesis

2.6.7.5 Method 5:

Catalytic Epoxidation of Alkenes

High oxidation state molybdenum oxo complexes are well-established catalysts for the

epoxidation of alkenes by alkyl hydroperoxides, such as in the production of 2-methyloxirane

(Halcon process). Chlorodioxo(ç 5 -pentamethylcyclopentadienyl)molybdenum(VI)

provides an organometallic example of a catalytically active system. The epoxidation reaction

is stereoselective, as shown by the selective formation of trans- and cis-1,2-diphenyloxirane

from the respective E- and Z-alkenes, and can be applied to highly substituted

alkenes; see Scheme 42. [162] Studies on this system have shown that the degradation of the

catalyst involves oxidative poisoning to an unreactive peroxo complex. [162]

Scheme 42 Catalytic Epoxidation of Alkenes [162]

+

Bu t OOH

MCpO2Cl (cat.)

benzene, 25

72%

oC O O

1,2-Epoxycyclooctane; Typical Procedure: [162]

In a drybox, a soln of [MoCp*ClO 2] (0.101 g, 0.338 mmol) in benzene (5 mL) was placed into

a 50-mLbomb. Cyclooctene (1.77 mL, 13.6 mmol) was added via a syringe. Outside the drybox,

3 M t-BuOOH in 2,2,4-trimethylpentane (11.3 mL, 34 mmol) was added. The bomb

was heated to 608C for 3 h. The soln was then diluted to a total volume of 150 mLwith

benzene. The organic layer was washed with H 2O (6 ” 100 mL) to remove excess hydroper-

for references see p 135

130 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

oxide, and then washed with sat. NaCl soln (100 mL) and dried (MgSO 4). The benzene was

removed under vacuum, and the crude product was purified by flash chromatography

(silica gel, EtOAc/hexane 1:9), to give 1,2-epoxycyclooctane; yield: 1.37 g (80%); >95%

pure by 1 H NMR spectroscopy. The epoxide was identified by comparison of its 1 HNMR

spectrum and GC retention time with those of an authentic sample.

2.6.8 Product Subclass 8:

Complexes with Singly Bonded Heteroelement Ligands

The most important examples of this class are the halides, alkoxides, and amides, but derivatives

with phosphorus, sulfur, selenium, and tellurium donors are also synthetically

useful. Most hydrocarbyl functionalities are accessible from halide and alkoxide precursors.

Synthesis of Product Subclass 8

2.6.8.1 Method 1:

By Oxidative Addition of Compounds with Single Bonds

between Heteroelements

The most practical synthetic route to halide derivatives is the oxidation of lower-valent

carbonyl precursors either directly with the halogens or with other stoichiometric

halogen sources such as phosphorus pentachloride or pentabromide, or iodobenzene dichloride.

(ç 5 -Cyclopentadienyl)- and (ç 5 -pentamethylcyclopentadienyl)dicarbonylnitrosylchromium(I)

are oxidized by iodine to the chromium(II) products 93, [166,167] while the analogous

molybdenum and tungsten precursors react with a range of halogen sources to

afford the dihalo derivatives such as 94 (Scheme 43). [168] The synthesis of tetrachloro(ç 5 -

pentamethylcyclopentadienyl)molybdenum(V) (95) requires easily available starting materials,

[27,169] while the alternative transmetalation from MCl 5 and cyclopentadienyl sources

is precluded by competing reductive pathways. This oxidative procedure has also been

used to access arylsulfido derivatives by use of disulfide reagents, as shown by the synthesis

of 96. [170]

Scheme 43 Oxidative Addition [166–170]

Cr(η 5 -C 5R 1 5)(NO)(CO) 2 + I 2

MCp ∗ (NO)(CO) 2 + PCl 5

{MoCp ∗ (CO) 3} 2 + PhΙCl 2

Me2Si

N

Me2Si PPh2 CrMe

PPh2 + 1/2 PhSSPh

MeCN, rt

R1 = H 88%

R1 = Me 62%

MCp ∗ Et2O, −20

Cl2(NO) oC M = Mo 90%

M = W 83% 94

CH2Cl2, rt

82%

toluene, 0 oC 66%

{Cr(η5-C5R1 5)(µ-I)(NO)} 2

93

MoCp ∗ Cl4 95

Me2Si PPh2 Me

N Cr

Me

SPh

2Si PPh2 96

2.6.8 Complexes with Singly Bonded Heteroelement Ligands 131

1-[(Diphenylphosphino-kP)methyl]-N-{[(diphenylphosphino-kP)methyl]dimethylsilyl}-

1,1-dimethylsilanamido-k,N](phenylsulfido)methylchromium(III) (96): [170]

To a red-brown soln of [CrMe{N(SiMe 2CH 2PPh 2) 2}] (0.16 g, 0.27 mmol) in toluene (10 mL)

cooled to 08C was added a soln of PhSSPh (0.03 g, 0.14 mmol) in toluene (5 mL). Immediately,

the soln changed to a dark purple color. After the mixture was stirred for 1 h at 0 8C,

the soln was warmed to rt and the solvent was removed almost to dryness. The residue

was quickly dissolved in hexane (1 mL) and filtered through Celite, and the solvent was

removed in vacuo. Recrystallization from hexanes/toluene (1 mL: 3 drops) in a –408C

freezer yielded a thick oil, which upon agitation gave 96 as purple crystals; yield: 0.12 g

(66%).

2.6.8.2 Method 2:

By Transmetalation

Compounds that already contain a single bond between the metal and a heteroatom ligand

may exchange the latter upon treatment with a suitable salt of the desired new

ligand. The ubiquitous substrates are the halides, especially the chlorides which are easily

accessible by oxidative procedures (Section 2.6.8.1 above) or from inorganic halide precursors.

One example is the synthesis of 20 in Scheme 7. Like the alkylating agents discussed

previously (Sections 2.6.3.1 and 2.6.4.1), some salts are potential reducing agents,

especially alkyl and aryl sulfides, phosphides, and amides. The reaction of precursor 97

(Scheme 44) with a variety of lithium salts always affords the metathesis product in

good yield when X 1 = alkoxo or amido. [171,172] When X 1 = chloro, 5% of reduction is afforded

by the 4-tolylamide salt with the molybdenum system, while the diphenylphosphido reagent

yields exclusively reduction products for both molybdenum and tungsten. [173]

Scheme 44 Transmetalation [171–173]

M

Cl NO

X1 97

+ LiX 2

25−82%

M = Mo, W; X 1 = Cl, NHt-Bu, Ot-Bu; X 2 = NHt-Bu, Ot-Bu, PPh 2

M

X 2 NO

X 1

Bis(2,6-diisopropylphenolato)(2,6-diisopropylphenylimido)(2,2-dimethylpropylidene)tungsten;

Typical Procedure: [17]

The lithium salt of 2,6-diisopropylphenoxide (1.60 g, 6.19 mmol) was added to [W(=CHt-

Bu)Cl 2(=NC 6H 3-2,6-iPr 2)(DME)] (1.82 g, 3.09 mmol) in Et 2O (50 mL) at –40 8C. The soln was

warmed to 258C and stirred for 45 min. The mixture was filtered, and the filtrates were

concentrated to afford an orange solid. Recrystallization of this material from a minimum

of pentane afforded the product as a bright yellow solid in two crops; yield: 1.74 g (72%).

2.6.8.3 Method 3:

From ó-Alkyl Complexes

Protonolysis of the typically polar bond between a group 6 metal and a hydrocarbyl ligand

is usually considered to be an unwanted decomposition reaction. When metal-heteroatom

bonds are desired, however, selective alkane-elimination reactions can sometimes offer

significant advantages, such as ready availability and stability of the protonated

source of the desired ligand (such as carboxylic acids, alcohols, or amines) and the absence

of inorganic salts as byproducts (the resulting alkane is normally easily removed

for references see p 135

132 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

in vacuo). The synthesis of 84 proceeds via the protonolysis of the tungsten-methyl bond

with aniline to form an arylamide ligand (Scheme 38), [152] and Scheme 45 illustrates related

examples involving benzoic acid and ammonium chloride (98 and 99, respectively).

[174,175] Hydrocarbyl groups other than ó-alkyls may also be used as precursors for this

reaction, as demonstrated by the reaction of chromocene with tert-butyl alcohol to give

100. [176]

Scheme 45 Syntheses from ó-Alkyl Complexes [174–176]

W(Me)2(Cp) 2

W(Me) 2(Cp) 2

Cr(Cp) 2 + Bu t OH

+ PhCO2H

+ NH 4Cl

petroleum ether

60 oC 90%

THF, 56 oC 61%

toluene, 110 oC 84%

WMe(Cp) 2Cl

99

{CrCp(OBut )} 2

100

WMe(Cp)2(O2CPh)

(Benzoato-O)bis(ç 5 -cyclopentadienyl)methyltungsten(IV) (98); Typical Procedure: [174]

The compound [W(Me) 2(Cp) 2] (0.52 g, 1.52 mmol) in petroleum ether (bp 100–1208C,

25 mL) was treated with benzoic acid (0.19 g, 1.51 mmol) and the mixture was warmed to

608C. Methane was evolved and the soln turned red. After 1 h the soln was filtered and

slowly concentrated under reduced pressure. Red-brown crystals separated which were

collected by filtration, washed with petroleum ether (2 ” 15 mL), and finally recrystallized

(petroleum ether/Et 2O 2:1); yield: 0.61 g (90%).

2.6.8.4 Method 4:

FromCarbene or Carbyne Complexes

Addition of the conjugate acid of the desired ligand to a metal–carbene or –carbyne compound

results in protonation of the hydrocarbyl ligand (see also Sections 2.6.1.4 and

2.6.4.4), transforming it into an alkyl or carbene ligand with formation of a new metalheteroatom

bond. Examples are the preparations of compound 19 (Scheme 7) and compound

65 (Scheme 27). The reaction of the carbene substrate 101 with tert-butyl alcohol

produces product 102 (Scheme 46) which, upon heating, eliminates alkane and affords a

new carbene compound in an overall process which resembles the protonolysis of an alkyl

complex (Section 2.6.8.3). [19] The same reaction of 101 with triphenylsilanol at low

temperatures leads to the protonolysis product directly.

Scheme 46 Synthesis from a Carbene Complex [19]

NMe2

CH2TMS

W

CHTMS

N

Ph

101

+ ButOH pentane

NMe2

CH2TMS

W CH2TMS

98

Bu N

Ph

tO 102

2.6.9 Miscellaneous Complexes 133

ç 5 -Cyclopentadienyl(2,2-dimethylpropyl)nitrosyl(triphenylsilanolato)molybdenum(II)

(65); Typical Procedure: [115]

See Section 2.6.4.4.

2.6.8.5 Method 5:

From Complexes Containing Doubly Bonded Heteroelement Ligands

Like the synthesis of alkyl compounds by selective protonation of carbene groups (Section

2.6.8.4), ligands with metal-heteroatom single bonds may be obtained from oxo or

imido complexes via a single-proton-transfer reaction, as illustrated for 103 in Scheme

47. Alternatively, the metal-heteroatom bond may be protonated twice, with the external

acid (HX) providing the M-X bond of the final product, as in the synthesis of 104. The

replacement of an oxo or imido ligand with two singly bonded ligands may induce other

modifications in the molecule, notably Æ-hydrogen elimination from an alkyl group,

transforming it into a carbene ligand (see Section 2.6.1.1.3).

Scheme 47 Syntheses from Complexes Containing Doubly Bonded

Heteroelement Ligands [102,152]

W(Cp ∗ ) 2( O) + HBF 4 OEt 2

WMeCp ∗ (

NPh) 2

+

TfOH

Et2O 50%

Et2O 80%

[W(Cp ∗ ) 2(OH)] + BF 4 −

103

WMeCp ∗ (OTf) 2(

104

Hydroxobis(pentamethylcyclopentadienyl)tungsten(IV) Tetrafluoroborate (103): [102]

A soln of [W(Cp*) 2(=O)] (120 mg, 0.26 mmol) in Et 2O (10 mL) was treated with HBF 4 • OEt 2

(excess) at –78 8C. The mixture was warmed to rt and the product was deposited as a white

solid which was isolated by filtration; yield: 75 mg (50%); IR (Nujol) í~ max: (WO-H) 3340 (s,

br) cm –1 ; 1 H NMR (benzene-d 6, ä): 1.88 (s, C 5Me 5).

2.6.9 Product Subclass 9:

Miscellaneous Complexes

Synthesis of Product Subclass 9

2.6.9.1 Method 1:

Allylidene Complexes from Cyclopropenes

Ring-opening reactions of 3,3-disubstituted cyclopropenes yield allylidene complexes, a

synthetic route of particular utility for the generation of ruthenium-based alkene metathesis

catalysts. [47] This methodology has been extended to tungsten allylidene compounds

using tungsten(IV) oxo [177] or imido [178] precursors (Scheme 48). These reactions proceed

via initial formation of the ç 2 -cyclopropene adduct 105, followed by ring opening. Metathesis

of the chloride ligands with electron-withdrawing alkoxide groups furnishes alkene

metathesis catalysts 106 (see Section 2.6.1.5).

NPh)

for references see p 135

134 Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands

Scheme 48 Allylidene Complexes from Cyclopropenes [177,178]

E

X3P

Cl W PX3 Cl

PX3 E = O, NC6H3-2,6-iPr2

Ph Ph

benzene

PX3 = PMePh2, PEt2Ph, P(OMe)3

OR 1 = OCMe(CF3)2

E

X3P

Cl W

Cl PX3 Ph LiOR 1 (2 equiv)

Ph

R 1 O

105 106

Dichloro(2,6-diisopropylphenylimido)(3,3-diphenylallylidene)bis(trimethyl phosphite-

P)tungsten (105, E=NC 6H 3-2,6-iPr 2; X = OMe); Typical Procedure: [178]

A soln of 3,3-diphenylcyclopropene (1.84 g, 9.55 mmol) in benzene (30 mL) was added via

cannula to a soln of [WCl 2(=NC 6H 3-2,6-iPr 2){P(OMe) 3} 3] (7.12 g, 8.88 mmol) in benzene

(60 mL), and the mixture was then stirred for 2 h at 808C. The solvent was removed in vacuo,

and the resulting orange oil was left under dynamic vacuum for an additional 12 h.

The product was then dissolved in THF (95 mL), and the resulting orange soln was filtered.

After all but THF (10 mL) had been removed in vacuo, addition of pentane (150 mL) yielded

an orange powder; yield: 5.50 g (72%); 1 H NMR (90 MHz, toluene-d 8, ä): 12.85 (dt, 1H,

J HH = 12.75, J HP = 6.37, H Æ ), 10.23 (dt, 1H, J HH = 12.75, J HP = 2.45, H â ), 3.65 [t, 18H, P(OMe) 3].

E

W

PX 3

Ph

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141

Science of Synthesis

Houben–Weyl Methods of Molecular Transformations

Sample Contribution

Category Organometallics

Volume 4 Compounds of Group 15 (As, Sb, Bi)

and Silicon Compounds

Product Subclass 4.4.27 Æ-Haloalkylsilanes

Written by N. J. Lawrence

142

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Science of Synthesis : Houben–Weyl methods

of molecular transformations /

ed. board: D. Bellus … Managing ed. G. F. Herrmann. –

Stuttgart ; New York : Thieme

Früher u.d. T.: Methoden der organischen Chemie

Category 1. Organometallics

Vol. 4: Compounds of group 15 (As, Sb, Bi) and silicon

compounds / vol. ed. I. Fleming. Responsible member

of the ed. Board S. V. Ley.

Authors H. Adolfsson .... – 2002

Library of Congress Cataloging in Publication Data

Science of synthesis : Houben–Weyl methods of

molecular transformations.

p. cm.

Includes bibliographical references and index.

Contents: category 1. Organometallics. v. 4. Compounds

of group 15 (As, Sb, Bi) and silicon compounds

/ volume editor, I. Fleming

ISBN 3-13-112171-8 – ISBN 0-86577-943-0 (v. 4)

1. Organic compounds–Synthesis. I. Title: Houben–

Weyl methods of molecular transformations.

QD262 .S35 2000

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00-061560

British Library Cataloguing in Publication Data

Science of Synthesis : Houben–Weyl methods

of molecular transformation

Category 1: Organometallics:

Vol. 4: Compounds of group 15 (As, Sb, Bi) and silicon

compounds. – (Houben–Weyl methods

of organic chemistry)

1. Organometallic compounds – Synthesis

I. Fleming, I., II. Adolfsson, H.

547.2

ISBN 3-13-112171-8

(Georg Thieme Verlag, Stuttgart)

ISBN 0-86577-943-0

(Thieme New York)

Date of publication: December 19, 2001

143

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144

Biographical Sketch

Nicholas Lawrence was born in 1963 in Chichester, West Sussex, UK.

He graduated in Natural Sciences from Cambridge University in 1985.

He remained at Cambridge to work with Professor Ian Fleming, FRS,

gaining his Ph.D. in 1989, having investigated synthetic organosilicon

chemistry and the synthesis of the pancreatic lipase inhibitor tetrahydrolipstatin

(Orlistat). This was followed by postdoctoral research

at Leicester University, UK, with Dr. Paul Jenkins, involving synthetic

routes towards paclitaxel. He was appointed as a lecturer at UMIST in

1991 and Senior Lecturer in organic chemistry in 1997. He was appointed

to a University Senior Research Fellowship at Cardiff University in 2000. His research

interests include the development of new synthetic methods and the synthesis,

design, and isolation (from medicinal herbs) of potential anticancer drugs. His fascination

for organosilicon chemistry continues in the study of synthetic applications of polysiloxanes.

4.4.27 Product Subclass 27: Æ-Haloalkylsilanes

N. J. Lawrence

4.4.27 Product Subclass 27: Æ-Haloalkylsilanes ................................. 146

145

Synthesis of Product Subclass 27 .......................................... 147

4.4.27.1 Method 1: Direct Halogenation of Alkylsilanes ........................ 147

4.4.27.1.1 Variation 1: Chlorination of Alkylsilanes ................................ 148

4.4.27.1.2 Variation 2: Bromination of Alkylsilanes ................................ 148

4.4.27.2 Method 2: Substitution of Æ-Hydroxyalkylsilanes ...................... 149

4.4.27.2.1 Variation 1: Substitution with Chloride Using Thionyl Chloride ........... 150

4.4.27.2.2 Variation 2: Chlorination of Æ-Hydroxyalkylsilanes with

Triphenylphosphine and Carbon Tetrachloride .............. 151

4.4.27.2.3 Variation 3: Iodination of Æ-Hydroxyalkylsilanes with

Methyl(triphenoxy)phosphonium Iodide .................... 151

4.4.27.3 Method 3: Haloalkylation of Halosilanes .............................. 152

4.4.27.4 Method 4: Reaction of Halosilanes with Diazomethane ................ 153

4.4.27.5 Method 5: Nucleophilic Substitution of Halo(haloalkyl)silanes .......... 154

4.4.27.6 Method 6: Alkylation of Æ-Haloalkylsilanes ............................ 155

Applications of Product Subclass 27 in Organic Synthesis ................... 155

146

4.4.27 Product Subclass 27:

Æ-Haloalkylsilanes

N. J. Lawrence

General Introduction

Æ-Haloalkylsilanes are primarily used in organic synthesis to prepare Æ-metalated silanes,

which react with a variety of electrophiles. The nucleophilic substitution of the halogen

atom provides a second important mode of reaction. The general patterns of reactivity

and synthetic importance of Æ-haloalkylsilanes are revealed in the reviews of the use of

the structurally simple examples of the class, such as (chloromethyl)trimethylsilane, [1,2]

(chloromethyl)(isopropoxy)dimethylsilane, [3] and (1-chloroethyl)trimethylsilane. [4] By far

the most commonly encountered examples of the class are Æ-bromo- and Æ-chloroalkylsilanes.

The use of iodides, such as (iodomethyl)trimethylsilane, [5] is less common and

fluorides rare with one important exception, trimethyl(trifluoromethyl)silane (Ruppert s

reagent). Some of the most important applications of Æ-haloalkylsilanes are discussed in

Applications of Product Subclass 27.

The general approaches to the synthesis of Æ-haloalkylsilanes are illustrated in

Scheme 1. Arguably the most important route (via disconnections a) involves the combination

of an alkylsilane and the halogen. Often this is achieved using a radical reaction

(a 1 ). Several Æ-bromo- and chloroalkylsilanes are prepared in this manner. The incorporation

of a good leaving group at the Æ-position of the alkylsilane allows nucleophilic substitution

using a halide (a 3 ). Fluorides and iodides, in addition to chlorides and bromides,

can be accessed using this method. The reaction of an electrophilic halogenating agent

with an Æ-silyl anion is another method to form Æ-haloalkylsilanes (a 2 ). Alkylation of the

anion derived from a chloromethyl- or bromomethylsilane is an effective way of

achieving the synthesis of Æ-haloalkylsilanes via disconnection b. Some simple halosilanes

also bearing Æ-haloalkyl groups are transformed via reaction with nucleophiles to

other Æ-haloalkylsilanes (disconnection c). Silylation of a carbenoid-type haloalkyl anion

also offers a versatile method (disconnection d). The following methods (1–6) illustrate

these approaches in more detail.

4.4.27 Æ-Haloalkylsilanes 147

Scheme 1 General Approaches to Æ-Haloalkylsilanes

R

2 R

Si

1

R1 +

a2 a3 b

R3 Si

X

R2 R1 R1 (R3 Si X

R

)

2

R1 R1 −

+ R3 Si

R2 R1 R1 c d

a

−

b

X = F, Cl, Br, I

−

d

c

R 3

X

Si

(R2 ) −

R1 R1 +

X

a 1

R

Si

2

R1 R1 • + X

R 3

R

Si

2

R1 R1 + + X−

R 3

+ X+

SAFETY: The Æ-haloalkylsilyl group does not bestow any great toxicity upon a molecule,

and as such Æ-haloalkylsilanes do not require any special handling techniques. However,

since they can function as alkylating agents in a synthetic sense, the more-reactive compounds,

such as Æ-iodoalkylsilanes, should be treated with care. Æ-Haloalkylsilanes are

stable at room temperature and can be purified by standard techniques; Æ-iodoalkylsilanes

should be protected from sunlight.

Æ-Haloalkylsilanes have no special spectroscopic properties. However, representative

NMR shifts [6–8] and coupling data for the series of (halomethyl)trimethylsilanes are

summarized in Table 1. The analysis of Æ-fluoroalkylsilanes via 19 F NMR clearly presents

an additional method of characterization.

Table 1 NMR Spectroscopic Data of (Halomethyl)trimethylsilanes [6–8]

1 H(ä) 13 C(ä) d 29 Si (ä)

Me3SiCH2F 0.15, 4.4a 80.0b –1.8c Me3SiCH2Cl 0.11, 2.72 30.3 3.5

Me3SiCH2Br 0.13, 2.42 17.4 2.3

Me3SiCH2I 0.03, 1.93 –11.9 2.3

a2 J(H -F) 47 Hz.

b1 J(F -C) 124 Hz.

c2 J(F -Si) 27 Hz.

d Methylene signal.

Synthesis of Product Subclass 27

4.4.27.1 Method 1:

Direct Halogenation of Alkylsilanes

The direct halogenation of alkylsilanes, via the radical substitution of a hydrogen atom at

the Æ-carbon, sometimes gives Æ-haloalkylsilanes in acceptable yields. This approach has

been used mostly for the preparation of simple derivatives. [9–11] The reaction is considerably

less selective for silanes of higher complexity, unless the radical generated at the Æ-

for references see p 159

148 Science of Synthesis 4.4 Silicon Compounds

position is stabilized. It is therefore not surprising that the method has found use for the

preparation of Æ-aryl-Æ-haloalkylsilanes. There are no examples of the synthesis of Æ-iodoalkylsilanes

by direct combination of a silane with iodine. There is one example of the

synthesis of Æ-fluoromethylsilanes from the reaction of tetramethylsilane and fluorine. [12]

This is unlikely to be a useful method with any general applicability. However, the Grignard

reagents derived from chloromethyl-substituted silanes react with the electrophilic

fluorinating agent N-fluoropyridinium triflate to give fluoromethyl-substituted silanes. [13]

4.4.27.1.1 Variation 1:

Chlorination of Alkylsilanes

There are many reports of the chlorination of simple alkylsilanes. For example, the transformation

of tetramethylsilane (1) into (chloromethyl)trimethylsilane (2) is effected by

the action of chlorine under photochemical conditions. [14] The yield of the reaction in carbon

tetrachloride is not high, in common with other examples of this type of reaction.

However, significantly higher yields are obtained when the photochemical reaction is performed

in the gas phase. [15] The reaction has been used for the synthesis of (Æ-chloroethyl)triethylsilane

from tetraethylsilane. [16] The radical chlorination of alkylsilanes is also

effected by sulfuryl chloride in the presence of a peroxide initiator (usually dibenzoyl peroxide).

The reaction is mostly limited to tetraalkylsilanes and triarylalkylsilanes or those

only bearing a methyl group. [17] Disilanes also undergo the reaction (e.g., 3 fi 4) (Scheme

2). The reaction of trihaloalkylsilanes [14] and dihaloalkylsilanes [18] is complicated by substitution

at other positions in the alkyl chain. Indeed, trichloroalkylsilanes undergo substitution

preferentially at the â-position. As expected for a radical reaction, an Æ-aryl group

accelerates the reaction and allows selective Æ-chlorination of benzylic silanes. [14,19]

Scheme 2 Chlorination of Alkylsilanes [11,14]

Me4Si Cl2, hν

74%

Me3Si Cl

1 2

Cl

Me2Si SiMe2

SO2Cl2, (PhCO)2O2

23%

Cl Si

Cl

3 4

Cl

Me SiMe2 Cl

1,2-Dichloro-1-(chloromethyl)-1,2,2-trimethyldisilane (4); Typical Procedure: [11]

1,2-Dichloro-1,1,2,2-tetramethyldisilane (3; 40 g, 214 mmol) and benzoyl peroxide (0.1 g)

were placed in a 100-mL three-necked flask equipped with a reflux condenser and pressure-equalizing

dropping funnel. The mixture was heated to 80–85 8C and SO 2Cl 2 (43.5 g,

320 mmol) added dropwise through the funnel over a period of 30 min. The mixture was

heated for a further 3 h. Additional SO 2Cl 2 (20 g, 150 mmol) was added and the mixture

was heated for another 5 h. After flash distillation, fractionation through a short column

packed with glass helices gave, in addition to unchanged starting material 3 (yield: 14 g;

bp 68–69 8C/50 Torr), the Æ-chlorodisilane 4; yield: 11 g (23%); bp 84–858C/20 Torr.

4.4.27.1.2 Variation 2:

Bromination of Alkylsilanes

The bromination of alkylsilanes has not found widespread use as a general route to Æ-bromoalkylsilanes.

A rare example is the efficient bromination of (isopropyl)trimethylsilane

(5 fi 6). [20] The related bromination of (isopropyl)dimethylsilane clearly shows that a hy-

4.4.27 Æ-Haloalkylsilanes 149

drosilyl group is oxidized to silyl bromide under the same conditions (7 fi 8) (Scheme

3). [21] Difluorosilanes undergo the reaction without complication. [22] An Æ-methoxymethyl

group is cleanly transformed into a Æ-bromo-Æ-methoxymethyl group. [23,24] The bromination

of benzyltrialkylsilanes is synthetically useful. [25–28] Numerous reports detail the efficient

reaction of bromine or N-bromosuccinimide and a benzylsilane (e.g., 9 fi 10) under

irradiation or in the presence of an appropriate radical initiator. This is often 2,2¢-azobisisobutyronitrile

or benzoyl peroxide. The reaction can sometimes be complicated by

competing dibromination; [19] an excess of N-bromosuccinimide has been used deliberately

in the preparation of the Æ,Æ-dibromosilane 11. [29,30]

Scheme 3 Bromination of Alkylsilanes [19–21,28]

R

Me2Si

1

5 R 1 = Me

7 R 1 = H

Br2, 60 o C

R

Me2Si 1

Br

6 R 1 = Me 64% (from 5)

8 R 1 = Br 55% (from 7)

Me3Si Ph

NBS, CCl4

reflux, 10 h

Me3Si Ph

Br

9 10 60%

O

12

NPr i 2

SiMe 3

NBS, (PhCO 2)O 2, CCl 4

reflux, 10 h

79%

+

Me 3Si Ph

Br

11 21%

O

NPri 2

Br

2-[Bromo(trimethylsilyl)methyl]-N,N-diisopropylbenzamide (13); Typical Procedure: [28]

N,N-Diisopropyl-2-[(trimethylsilyl)methyl]benzamide (12; 1.14 g, 3.9 mmol) in CCl 4

(200 mL) (CAUTION) was added to NBS (1.01 g, 5.0 mmol) and benzoyl peroxide (10 mg).

The mixture was heated under reflux and irradiated by a UV sun lamp for 90 min. The

mixture was cooled to rt and the succinimide removed by filtration through Celite. The

filtrate was concentrated under reduced pressure to give a crude oil. The crude product

was purified by chromatography (silica gel) to give the Æ-bromosilane 13 as a white solid

after recrystallization (pentane); yield: 1.14 g (79%); mp 89–90 8C.

4.4.27.2 Method 2:

Substitution of Æ-Hydroxyalkylsilanes

Æ-Haloalkylsilanes are most conveniently prepared by the nucleophilic substitution by

halide of an Æ-nucleofuge, often derived from a hydroxy group. In very general terms,

the method is applicable to the synthesis of Æ-fluoro- and Æ-iodoalkylsilanes, in addition

to the more common Æ-chloro- and Æ-bromoalkylsilanes. The method is mostly limited by

the availability of the silyl electrophile. Æ-Silyl alcohols (see Section 4.4.28) are often used

as the source of this electrophile, which is formed in situ by a variety of methods (Sections

4.4.27.2.1–4.4.27.2.3). However, other derivatives are sometimes used. For example, (fluoromethyl)trimethylsilane

(15) has been prepared in 38% yield by the reaction of the

tosylate 14 [derived from (hydroxymethyl)trimethylsilane] with dry potassium fluoride

in diethylene glycol. [31] A small amount (ca. 10%) of the ethylsilane 16 (see Applications

13

SiMe 3

Br

for references see p 159

150 Science of Synthesis 4.4 Silicon Compounds

of Product Subclass 27) is also produced (Scheme 4). The reaction of (trimethylsilyl)methyl

trifluoromethanesulfonate with sodium iodide is a good method for the synthesis of

(iodomethyl)trimethylsilane. [32] A siloxy group has been used as the leaving group in the

synthesis of 9-chloro-3-methoxy-9-(trimethylsilyl)fluorene derivatives. [33] Æ-Alkoxymethylsilanes

can be transformed into Æ-bromomethyl- and Æ-iodomethylsilanes by the action of

triphenylphosphine/bromine and potassium iodide/phosphoric acid, respectively. [34] A

more widely used, and related, reaction involves the ring opening of Æ,â-epoxysilanes

(see Section 4.4.29) by halide. In this way, Æ-halo-â-hydroxyalkylsilanes are obtained

with high regioselectivity by treatment of the epoxide with hydrochloric, [35] hydrobromic,

[36] and hydriodic acids (e.g., 17 fi 18) [37] or tetrafluorosilane/water/diethylisopropylamine.

[38] The silyl group accelerates the substitution at the Æ-position, even when it

is more sterically hindered than the â-position.

Scheme 4 Æ-Haloalkylsilanes by Nucleophilic Substitution of a Hydroxy-Derived

Leaving Group and Ring Opening of an Æ,â-Epoxysilane by Halide Ion [31,37]

Me3Si OTs

14

17

SiMe3

O

KF, (HOCH 2CH 2) 2O

aq HI

70%

18

Me3Si F + Me3Si F

15 38% 16 10%

SiMe3

4.4.27.2.1 Variation 1:

Substitution with Chloride Using Thionyl Chloride

Early examples of the substitution of Æ-hydroxysilanes with chloride employ thionyl chloride

as the reagent. [39] The transformation is achieved simply by mixing the alcohol with

thionyl chloride in diethyl ether (19 fi 20, Scheme 5). A benzylsilyl group is not cleaved

by the hydrochloric acid produced under these conditions. The reaction has not seen

many applications, probably because the yields are not generally high. This has prompted

the development of other methods (Sections 4.4.27.2.2 and 4.4.27.2.3).

Scheme 5 Æ-Chloroalkylsilanes from Æ-Hydroxyalkylsilanes and Thionyl Chloride [39]

OH

19

SiMe3

SOCl2, Et2O, 0 oC to rt

78%

(1-Chloropropyl)trimethylsilane (20); Typical Procedure: [39]

(1-Hydroxypropyl)trimethylsilane (19; 0.75 g, 5.8 mmol) in dry Et 2O (5 mL) was added

dropwise at 0 8C to a stirred soln of SOCl 2 (0.76 g, 6.4 mmol) in dry Et 2O (5 mL). The resulting

soln was stirred at 08C for 20 min and at 258C for a further 20 min and then heated

under reflux for 1 h. Evaporation produced the Æ-chloropropylsilane 20 as a crude light

brown oil; yield: 0.68 g (78%).

I

OH

Cl

20

SiMe3

4.4.27 Æ-Haloalkylsilanes 151

4.4.27.2.2 Variation 2:

Chlorination of Æ-Hydroxyalkylsilanes with

Triphenylphosphine and Carbon Tetrachloride

Significant improvements to the method were accomplished by Barrett and co-workers.

They found that conversion of Æ-hydroxyalkylsilanes 21 {prepared by the addition of [(dimethyl)(phenyl)silyl]lithium

to aldehydes} [40] into the Æ-chloroalkylsilanes 22 is effected

by reaction with carbon tetrachloride and triphenylphosphine without complication

(Scheme 6). The Grignard reagent derived from 22 proved to be excellent for the synthesis

of Æ-ketosilanes, used in the synthesis of alkenes via the Peterson reaction (see Applications

of Product Subclass 27). The reaction and subsequent purification of 22 is not complicated

by competing Brook rearrangement. Æ-Bromoalkylsilanes can be prepared in a

similar fashion from Æ-hydroxyalkylsilanes by treatment with carbon tetrabromide and

triphenylphosphine, [41] phosphorus tribromide, [42] or dibromotriphenylphosphorane. [43]

Scheme 6 Æ-Chloroalkylsilanes from Æ-Hydroxysilanes with

Carbon Tetrachloride and Triphenylphosphine [40]

OH

R 1 SiMe 2Ph

21

CCl 4, Ph 3P

Cl

R 1 SiMe 2Ph

22 R1 = (CH2)4Me 85%

R1 = (CH2) 6Me 87%

R1 = Cy 82%

R1 = Ph 65%

(1-Chlorohexyl)dimethylphenylsilane [22, R 1 =(CH 2) 4Me]; Typical Procedure: [40]

A soln of the Æ-hydroxysilane 21 [R 1 =(CH 2) 4Me; 18.77 g, 80 mmol] and Ph 3P (27 g,

100 mmol) in THF (300 mL) and CCl 4 (50 mL) (CAUTION) was heated under reflux for 6 h

in a flask under an atmosphere of argon. After cooling the solvent was removed by vacuum

distillation. The residue was extracted with hexanes (3 ” 300 mL). Evaporation and

chromatography (silica gel, hexanes) of the residue gave the Æ-chlorosilane 22 as a colorless

oil; yield: 17.2 g (85%).

4.4.27.2.3 Variation 3:

Iodination of Æ-Hydroxyalkylsilanes with

Methyl(triphenoxy)phosphonium Iodide

Barrett and co-workers also found that Æ-iodoalkylsilanes can be prepared by reaction

with methyl(triphenoxy)phosphonium iodide (e.g., 23 fi 24, Scheme 7). [44] These compounds

are of limited synthetic value in the Peterson reaction, since iodine/metal exchange

is difficult. Nevertheless the method for their preparation is a rare and potentially

important one.

Scheme 7 Æ-Iodoalkylsilanes from Æ-Hydroxyalkylsilanes [44]

( ) 4

23

OH

SiMe3

(PhO)3PMeI

96%

(1-Iodohexyl)trimethylsilane [24,R=(CH 2) 4Me]; Typical Procedure: [44]

DMF (20 mL) was added to the crude alcohol 23 [R = (CH 2) 4Me; 5 mmol] under dry N 2.To

this soln was added (PhO) 3PMeI (3.39 g, 7.5 mmol) and the mixture stirred for 12 h in the

dark. MeOH (2 mL) and sat. aq Na 2S 2O 3 (1 mL) were added successively. The resulting mix-

( ) 4

24

I

SiMe 3

for references see p 159

152 Science of Synthesis 4.4 Silicon Compounds

ture was extracted with Et 2O (3 ” 30 mL). The combined Et 2O extracts were washed with

sat. aq NH 4Cl and brine, dried (MgSO 4), and evaporated. The residue was purified by flash

chromatography (silica gel, hexanes) followed by Kugelrohr distillation (1108C, 0.7 Torr)

to give the stable Æ-iodoalkylsilane 24; yield 1.36 g (96%).

4.4.27.3 Method 3:

Haloalkylation of Halosilanes

The haloalkylation of chlorosilanes by the reaction of a (Æ-haloalkyl)metal species is a useful

and reasonably general method for the preparation of Æ-haloalkylsilanes (disconnection

d, Scheme 1). Generally, the (chloroalkyl)lithium reagents are prepared in situ by the

deprotonation of the corresponding alkyl halide. [45] For example, (chloromethyl)lithium

is conveniently prepared in situ by the treatment of bromochloromethane with butyllithium

at temperatures between –70 and –60 8C, in the presence of the chlorosilane

(25 fi 26). [45] Under these conditions butyllithium does not react with the chlorosilane.

The method is applicable to the synthesis of a wide variety of silanes including disilanes

and allylsilanes. Bromomethyl and iodomethyl derivatives can be prepared with increasing

difficulty by the use of dibromomethane and diiodomethane. 3-Haloprop-1-enes react

in the same way with chlorotrimethylsilane and lithium dicyclohexylamide efficiently

producing Æ-haloallylsilanes (allyl bromide fi 27, Scheme 8). [46] (Halomethyl)aryl compounds

react in the same way when lithium diisopropylamide is used as the base. [47–49]

Several heterocyclic derivatives have been prepared by this method. [Chloro(pyridin-3yl)methyl]lithium

[prepared from lithium diisopropylamide and 3-(chloromethyl)pyridine]

reacts well with chlorotrimethylsilane. [50] Similar processes can be used to silylate

the lithio derivatives of 4-(chloromethyl)pyridine, [51] 4-(fluoromethyl)pyridine, [51] and 2-

(chloromethyl)benzothiazole. [52] (Dihalomethyl)trialkylsilanes are prepared efficiently

from dihalomethanes, lithium diisopropylamide, and chlorosilanes. [53] Deprotonation of

trihalomethanes with butyllithium at low temperature, followed by reaction with chlorosilanes,

generates trihalomethylsilanes. [54] Similar processes can be effected by formation

of the Grignard reagent derived from polybromo- or polyiodomethane. [55] 1-Bromo-1-(trimethylsilyl)cyclopropanes

[56] can be prepared by the treatment of 1,1-dibromocyclopropanes,

magnesium, and chlorotrimethylsilane under ultrasonic irradiation. [57]

Scheme 8 Reaction of Halosilanes with (Æ-Haloalkyl)lithium Reagents [45,46,60]

Cl

Me2Si

Br

Bu t

O

BrCH2Cl, BuLi

THF, −60 oC 71%

Me2Si

25 26

O

28

F

1. Cy2NLi, TMSCl, −60 oC 2. H + /H2O

55%

71%

Cl

Me3Si

Br

27

1. LDA (4 equiv), TMSCl (6 equiv), −78 oC 2. H + /H2O

Bu

O

t O

F

SiMe3 29

4.4.27 Æ-Haloalkylsilanes 153

In general, the approach works when electron-withdrawing groups are present at the Æposition.

For example, Æ-haloesters are easily deprotonated with lithium diisopropylamide

and silylated to give Æ-haloalkylsilanes. [58,59] The reactions are often complicated

by competing O-silylation. An excess of both lithium diisopropylamide and chlorosilane

ensures a good yield of tert-butyl Æ-fluoro-Æ-(trimethylsilyl)acetate (29) from tert-butyl Æfluoroacetate

(28). [60]

The treatment of silyl ethers of type 30 yields Æ-chloroalkylsilanes effectively by an

in situ method of (Æ-haloalkyl)metal formation (Scheme 9). In this case the silyl group undergoes

intramolecular transfer from the nearby silyl ether group. [61] Elimination of hydrochloric

acid from the Æ-chloroalkylsilane 31 is a competing reaction producing

alkenylsilanes as byproducts.

Scheme 9 Intramolecular Reaction of a Silyl Ether with a (Haloalkyl)lithium Species [61]

O

SiMe 2Bu t

Cl

1. BuLi, t-BuOK, −70 oC, 10 min

2. H2O 72%

OH

30 31

SiMe 2Bu t

Allyl(chloromethyl)dimethylsilane (26); Typical Procedure: [45]

Allyl(chloro)dimethylsilane (25; 9.7 g, 70 mmol), BrCH 2Cl (9.3 g, 70 mmol) and dry THF

(150 mL) were added to a 500-mL three-necked flask equipped with a magnetic stirrer

bar, N 2 inlet tube, and thermometer. The mixture was cooled to –70 8C and 1.6 M BuLi in

hexanes (45 mL, 70 mmol) added down the cold wall of the flask via a syringe over 40 min.

During the addition the temperature of the mixture was maintained between –70 and

–60 8C. The soln was then warmed to rt and H 2O (50 mL) was added. The mixture was extracted

with hexanes (3 ” 100 mL). The combined extracts were dried (CaCl 2) and evaporated

under reduced pressure. The residue was distilled to give the Æ-chloromethylsilane 26;

yield: 7.6 g (71%); bp 778C/80 Torr.

4.4.27.4 Method 4:

Reaction of Halosilanes with Diazomethane

Halosilanes react with diazoalkanes to form Æ-haloalkylsilanes (32 fi 33, Scheme 10). The

reaction is facilitated by copper powder or copper(II) salts. [62–64] Fluorosilanes are the least

reactive of the halides in this type of reaction and effectively do not react in this manner.

The reaction is most efficient with di-, tri-, and tetrachlorosilanes. The reaction between

tetrachlorosilane and diazomethane is violent at room temperature, but can be controlled

at low temperature. In polyhalosilanes, the introduction of one halomethyl group

generally retards the introduction of another. Nevertheless, the method is useful for the

synthesis of dichloro[bis(chloromethyl)]silane from trichloro(chloromethyl)silane. [65]

Bromosilanes are more reactive than chlorosilanes. The method is applicable to halodisilanes.

[66] The reaction of iodotrimethylsilane or trimethylsilyl trifluoromethanesulfonate

with diazomethane does not require catalysis, whereas that of bromotrimethylsilane proceeds

conveniently in the presence of zinc dibromide. [67]

Scheme 10 Reaction of Halosilanes with Diazomethane [64]

CH2N2, Cu, Et2O, −60

45%

32 33

o HSiCl3 C

Cl

H

Cl

Si Cl

Cl

for references see p 159

154 Science of Synthesis 4.4 Silicon Compounds

Dichloro(chloromethyl)silane (33): [64]

CAUTION: Diazomethane is highly toxic and irritating. It is also a detonator and appropriate

safety precautions should be taken when using this reagent (e.g., special glassware, use of a blast

shield, etc.). For further details on the safe handling of diazomethane see refs [68,69] .

Trichlorosilane (32; 40 g, 0.296 mol) in anhyd Et 2O (100 mL) in a 1-L three-necked flask

equipped with a mechanical stirrer, a Y-joint holding a thermometer and a drying tube

filled with Drierite, and a dropping funnel was cooled to –608C and Cu powder (0.5 g)

added. A cold soln of CH 2N 2 (0.194 mol) in Et 2O (350 mL) was added slowly through the

dropping funnel, with vigorous stirring of the mixture. N 2 evolution began immediately.

After the addition was complete the mixture was stirred for 2 h between –65 to –608C

under dry N 2. The mixture was allowed to warm to rt and stirred for a further 2 h. The

Et 2O was removed by distillation through an 18-inch column packed with glass helixes.

Another preparation of the same scale was performed and the residues combined and

fractionally distilled to give dichloro(chloromethyl)silane (33); yield: 40 g (45% based on

32); bp 97.0–97.4 8C/773 Torr.

4.4.27.5 Method 5:

Nucleophilic Substitution of Halo(haloalkyl)silanes

Substitution at silicon of silanes already bearing bromomethyl or chloromethyl groups is

a common process for preparing Æ-halomethylsilanes. The principle reason for the popularity

of the method is the availability of chloro(chloromethyl)dimethylsilane and (bromomethyl)(chloro)dimethylsilane.

[70] Nevertheless the reaction does work well with other

halo(Æ-haloalkyl)silanes. [14,71] Addition of Grignard [14,72] and organolithium reagents occurs

without the complication of substitution of the halogen at the Æ-position (e.g.,

34 fi 35, Scheme 11). The method has been used to prepare Æ-halomethyl-substituted vinylsilanes

from vinyl Grignard [73] and vinyllithum reagents. [74] Allyl, [75] alkynyl, [76] aryl, [77]

and benzyl organometallic reagents also work well. Reaction of (bromomethyl)(chloro)dimethylsilane

with alcohols and triethylamine [and sometimes 4-(dimethylamino)pyridine]

is commonly used to prepare (bromomethyl)silyl ethers for radical cyclization.

Scheme 11 Reaction of an Alkynyllithium Reagent with

Chloro(chloromethyl)dimethylsilane [76]

( ) 5

1. BuLi

2. ClMe2Si

90%

Cl

( ) 5 SiMe2 Cl

34 35

(Chloromethyl)(dimethyl)oct-1-ynylsilane (35); Typical Procedure: [76]

1.5 M BuLi in hexanes (37.3 mL, 55.9 mmol) was added at –788C to oct-1-yne (34; 6.15 g,

55.9 mmol) in THF (60 mL). The mixture was allowed to warm to 08C and stirred for 1 h,

and then at rt for a further 15 min. The mixture was cooled to –788C. Chloro(chloromethyl)dimethylsilane

(8.0 g, 55.9 mmol) in THF (20 mL) was added dropwise to the mixture

over 1 h. The resulting mixture was stirred overnight at –788C. The mixture was allowed

to warm to rt and sat. aq NH 4Cl (50 mL) was added and the mixture extracted with EtOAc

(2 ” 100 mL). The organic extracts were washed with brine, dried (Na 2SO 4), and evaporated

under reduced pressure. The residue was distilled to give (chloromethyl)(dimethyl)oct-1ynylsilane

(35) as an oil; yield: 10.9 g (90%); bp 54–57 8C/3 Torr.

4.4.27 Æ-Haloalkylsilanes 155

4.4.27.6 Method 6:

Alkylation of Æ-Haloalkylsilanes

Æ-Haloalkylsilanes are deprotonated to provide an anion that reacts readily with haloalkanes

(disconnection b, Scheme 1). The carbanion derived from (chloromethyl)trimethylsilane

is stable at low temperature (decomposing slowly over 1 h at –408C) and reacts

with a variety of electrophiles. Similar stability is evident for other members of the product

class (36 fi 37, Scheme 12). Æ-Haloalkylsilanes are most commonly deprotonated

with sec-butyllithium at –788C in the presence of N,N,N¢,N¢-tetramethylethylenediamine

(TMEDA). [78–80] Under these conditions Æ-elimination is not a competing reaction.

Scheme 12 Alkylation of (Chloromethyl)silanes [78]

PhMe2Si

Cl

1. s-BuLi, TMEDA, −78 oC 2. MeI

66%

PhMe 2Si

36 37

(1-Chloroethyl)(dimethyl)phenylsilane (37); Typical Procedure: [78]

1.4 M s-BuLi in cyclohexane/isopentane (92:8) (164 mL, 0.230 mol) was added dropwise

over 1.5 h to (chloromethyl)(dimethyl)phenylsilane (36; 40.0 g, 0.217 mol) in THF

(260 mL) at –788C. TMEDA (24.1 g, 0.21 mol) was added dropwise to the resulting mixture

over 20 min, maintaining the temperature at –788C. The soln was stirred for 1 h at –788C

and then allowed to warm to –558C. MeI (41.2 g, 0.29 mol) in THF (70 mL) was added dropwise

over 1 h, and the mixture stirred for a further 40 min at –408C and then 16 h at rt.

The mixture was added carefully to cold sat. aq NH 4Cl (700 mL) and extracted with Et 2O

(3 ” 350 mL). The combined organic extracts were washed with H 2O, dried (Na 2SO 4), and

evaporated under reduced pressure. The residue was distilled to give the silane 37 as an

oil; yield: 28.3 g (66%); bp 768C/6 Torr.

Applications of Product Subclass 27 in Organic Synthesis

The Grignard reagents derived from Æ-haloalkylsilanes have found widespread use in organic

synthesis. Perhaps the most common application of (chloromethyl)trimethylsilane

[14] is as a methylenating agent in the Peterson reaction. [81] In this reaction addition

of the Grignard reagent 38 to carbonyl compounds generates an alcohol 39, from which

an alkene 40 is produced by base-catalyzed elimination (Scheme 13). The process offers a

useful alternative to the Wittig reaction. The Grignard reagents derived from Æ-haloalkylsilanes

are particularly useful for preparing â-ketosilanes, which are themselves useful in

the stereoselective version of the Peterson alkenation reaction. [82] For example, the Grignard

reagent derived from (Æ-chloroalkyl)(dimethyl)phenylsilane 22 reacts with acyl chlorides

[with copper(I) catalysis] to give the ketone 41. Reaction of this ketone with an organometallic

reagent (R 3 M) followed by potassium hydride or 4-toluenesulfonic acid

yields either stereoisomer of the trisubstituted alkene (Scheme 13). A related process has

shown that (iodomethyl)trimethylsilane generates alkenes directly from ketones by the

use of samarium(II) trifluoromethanesulfonate. [83] (Æ-Silylalkyl)lithiums are produced

from Æ-haloalkylsilanes via transmetalation by reaction with an alkyllithium [42] or by direct

reaction with lithium metal. [19,84]

Cl

for references see p 159

156 Science of Synthesis 4.4 Silicon Compounds

Scheme 13 Æ-Haloalkylsilanes in the Peterson Reaction [81,82]

Me3Si

R 1

Cl

MgCl

1. R 1 COR 2

2. H + /H2O

R

Me3Si 1

HO R2 38 39

SiMe2Ph

1. Mg, Et 2O

2. CuBr SMe 2

3. R 2 COCl

R 1

22 41

SiMe 2Ph

O

R 2

KH

1. R 3 M

2. KH

1. R 3 M

2. TsOH

The Grignard reagents of (chloroalkyl)(isopropoxy)dimethylsilane (42, R 1 = O-iPr) and

(chloroalkyl)(dimethyl)phenylsilane (43, R 1 = Ph) provide excellent hydroxyalkyl anion

equivalents, which react with electrophiles such as aldehydes, imines, [80] ketones and epoxides

to give the adducts 44 and 45, respectively (Scheme 14). The hydroxyalkyl group

46 is revealed using the standard silyl-to-hydroxy protocols.

Scheme 14 Hydroxymethylation with Æ-Haloalkylsilanes [80]

R 1 Me2Si Cl

R 2

42 R 1 = O-iPr; R 2 = alkyl

43 R 1 = Ph; R 2 = alkyl

1. Mg, THF

2. E +

R 1 Me2Si E

R 2

44 R 1 = O-iPr; R 2 = alkyl

45 R 1 = Ph; R 2 = alkyl

R 1

for 44: H2O2, F − , base

for 45: KBr, NaOAc

AcOOH

R 1

40

R 2

R 3

R 2

R 3

HO E

Æ-Haloalkylsilanes readily undergo halogen substitution (e.g., 47 fi 48) by a wide range of

nucleophiles such as iodide, [85] ammonia, azide, [86] amines, [87] diethyl phosphonacetate, [88]

and phosphorus ylides [89] (Scheme 15). The use of iodide and fluoride as nucleophiles provides

a useful method for the preparation of Æ-iodo- and Æ-fluoroalkylsilanes from Æ-bromo-

and Æ-chloroalkylsilanes. Fluoromethyl-substituted silanes are prepared in moderate

yield by the reaction of the corresponding chloromethyl compound with cesium fluoride

in the presence of 18-crown-6. [90] A variation of the substitution reaction is the nucleophile-induced

1,2-transfer of a group bound to the silicon atom (e.g., 49 fi 50), which

can interfere sometimes with the direct displacement (e.g., 47 fi 48).

Scheme 15 Halide Substitution in Æ-Haloalkylsilanes [85–90]

R 1 3Si Cl

R 2

47 R 2 = alkyl

R 1 3Si Cl

R 2

49 R 2 = alkyl

Nu −

R 1 3Si Nu

48

R 2

NuR 1 2Si R 1

50

R 2

R2 46

4.4.27 Æ-Haloalkylsilanes 157

Æ-Haloalkylsilanes are deprotonated with lithium diisopropylamide or alkyllithium reagents

[55,91] to generate an organolithium reagent which reacts readily with electrophiles

such as aldehydes and ketones (Scheme 16). This reaction is incorporated into a useful

protocol for the homologation of ketones and aldehydes, by acid-catalyzed transformation

of the first formed Æ,â-epoxysilanes 51 (see Section 4.4.29). [79,92] The reaction does

not work well with aldehydes or ketones that are either hindered or readily enolizable.

Other electrophiles are compatible with the process. For example, the use of haloalkanes

or deuterium oxide provides chain-extended Æ-haloalkylsilanes and Æ-halo-Æ-deuteroalkylsilanes,

respectively. [93]

Scheme 16 Alkylation of Æ-Haloalkylsilanes [79,92]

Me 3Si

Cl

1. s-BuLi, TMEDA

2. R 1 COR 2

Me3Si

51

O

R 2

R 1

aq H 2SO 4, MeOH

R 1 R 2

O H

Silyl ethers incorporating an Æ-haloalkylsilyl moiety have been used to generate Æ-silyl

radicals for radical cyclization (Scheme 17). Recent progress in the radical cyclization of

(allyloxy)(bromomethyl)silanes, pioneered by Stork [94] and Nishiyama, [95] is summarized

in an excellent review. [96] The initial product 53 of the reaction of silyl ether 52 is oxidatively

cleaved to give a diol 54. Alternatively, treatment of 53 with potassium tert-butoxide

in dimethyl sulfoxide gives the methyl-substituted alcohol 55. [97] Exceptional levels of

stereocontrol are obtained in the acyclic series (e.g., 56 fi 57). [95] The reaction is usually

performed with silyl ethers possessing a bromomethyl group as (bromomethyl)halo(dimethyl)silanes

are commercially available. Nevertheless, Æ-alkyl-Æ-bromosilanes undergo

the same type of reaction. [43] The use of intramolecular radical traps facilitates tandem

radical cyclizations in a similar fashion. [98,99] (Chloromethyl)silanes and (bromomethyl)silanes

are reduced under similar radical conditions to the corresponding trialkylmethylsilanes.

[7,39,100]

Scheme 17 Radical Cyclization of (Allyloxy)(bromomethyl)silanes [94–97]

O

Me2Si Br

52

OBu t

O

Me2Si Bu3SnH, AIBN

benzene, reflux

53

OBu t

DMF, KF, H 2O2

t-BuOK, DMSO

HO

H

HO

54 88%

HO

H

55 66%

OBu t

for references see p 159

158 Science of Synthesis 4.4 Silicon Compounds

Me 2Si

O

Br

Bu3SnH, AIBN

Ph O

benzene, reflux

Me2Si DMF, KF

H2O2 Ph HO Ph

56 57

Finally, no consideration of the chemistry of Æ-haloalkylsilanes would be complete without

mention of Ruppert s reagent [101,102] (58). In the presence of a source of fluoride (usually

tetrabutylammonium fluoride), the reagent will deliver a trifluoromethyl group to carbonyl

groups of aldehydes and ketones, [103,104] esters, [105] and a variety of other functional

groups (Scheme 18). The exceptional versatility of the reagent is revealed in an excellent

review from Prakash and Yudin. [102]

Scheme 18 Trifluoromethylation of Carbonyl Compounds with Ruppert s Reagent [101–104]

R 1

O

R 2

F3CSiMe3 58

TBAF (cat.)

HO CF 3

R 1

R 2

References 159

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163

Science of Synthesis

Houben–Weyl Methods of Molecular Transformations

Sample Contribution

Category Organometallics

Volume 5 Compounds of Group 14 (Ge, Sn, Pb)

Product Subclass 5.1.22 Aryl- and Heteroarylgermanes

Written by A. C. Spivey and C. M. Diaper

164

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Science of synthesis : Houben–Weyl methods of

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Includes bibliographical references and index.

Contents: category 1. Organometallics. v. 5. Compounds

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ISBN 3-13-112181-5 – ISBN 0-86577-944-9 (v. 5)

1. Organic compounds–Synthesis. I. Title: Houben–

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Category 1: Organometallics:

Vol. 5: Compounds of group 14 (Ge, Sn, Pb). –

(Houben–Weyl methods of organic chemistry)

1. Organometallic compounds – Synthesis

I. Maloney, M., II. Clark, A.

547' .05

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Date of publication: December 23, 2002

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166

Biographical Sketches

Alan Spivey received his BSc in chemistry in 1988 from the University

of Nottingham, UK and his DPhil in 1991 from the University of Oxford

under the guidance of Prof. Sir Jack Baldwin. After postdoctoral work

at the UniversitØ de Gen›ve, Switzerland with the late Prof. Wolfgang

Oppolzer, and at the University of Cambridge with Prof. Sir Alan Battersby,

he moved to a lectureship at the University of Sheffield. In January

2003 he moved to Imperial College London as a reader. Research

in his group is focused on the development of new catalysts for asymmetric

acylation, new linkers for solid phase organic synthesis, chemical

aspects of signal transduction, and total synthesis of bioactive natural products.

Chris Diaper received his BSc in chemistry in 1996 from the University

of Bradford, UK and his PhD in 2000 from the University of Sheffield

under the supervision of Dr Alan Spivey. After postdoctoral work at

the University of Nottingham with Prof. Gerry Pattenden he moved to

his current position as a postdoctoral fellow at the University of Alberta,

Canada working with Prof. John Vederas. His research interests include

the development of germanium based linkers for solid-phase

synthesis, the total synthesis of marine natural products and mechanistic

aspects of the diaminopimelate (DAP)biosynthetic pathway.

5.1.22 Product Subclass 22: Aryl- and Heteroarylgermanes

A. C. Spivey and C. M. Diaper

5.1.22 Product Subclass 22: Aryl- and Heteroarylgermanes ..................... 168

Synthesis of Product Subclass 22 .......................................... 170

5.1.22.1 Method 1:From Halogermanes by Substitution with Arylmetals ............. 170

5.1.22.1.1 Variation 1:Using Preformed Arylmetals ................................... 170

5.1.22.1.2 Variation 2:Using Barbier-Type Reactions .................................. 171

5.1.22.2 Method 2:From Aryl Halides by Palladium(0)-Mediated Coupling

with Digermanes ......................................................... 171

5.1.22.3 Method 3:From Aryl Halides by Insertion of Dichlorogermylene ............. 172

5.1.22.4 Method 4:Heteroarylgermanes by Cycloaddition ........................... 173

Applications of Product Subclass 22 in Organic Synthesis ................... 174

5.1.22.5 Method 5:Arylgermanes as Linkers for Solid-Phase Synthesis ............... 174

167

168

5.1.22 Product Subclass 22:

Aryl- and Heteroarylgermanes

A. C. Spivey and C. M. Diaper

General Introduction

Previously published information regarding aryl- and heteroarylgermanes can be found

in Comprehensive Organic Functional Group Transformations, [1] The Chemistry of Organic Germanium,

Tin and Lead Compounds, [2] Houben–Weyl, Vol. 13/6, and The Organic Compounds of

Germanium. [3]

Arylgermanes are thermally stable and amenable to purification by chromatographic

techniques. In addition to spectroscopic studies, [4] reports dealing with the structural

properties of germatriptycenes, [5] germametallocyclophanes, [6] tri-, [7] and tetrasubstituted

arylgermanes have appeared, [8] focusing on the geometry and bonding of the sterically

congested ligands around germanium. In addition, germanium congeners of triphenylmethyl

radicals, [9] cations [10,11] (e.g., tropylium-type ions) [12] have been investigated. The

photochemistry of arylgermanes has also been investigated. [13–15]

A number of hypervalent derivatives of germanium have been synthesized. These include

triarylgermanes with heteroatom functionality at the ortho position on the aromatic

ring, [16–18] and germatranes. [19] Arylgermatranes such as 1 participate in Stille-type crosscoupling

reactions giving, for example, biphenyl 2, presumably because hypervalent germanium

is particularly susceptible to transmetalation with palladium(II)intermediates

(Scheme 1). [20] In addition, aryl(trifuryl)germanes undergo fluoride-mediated Stille-type

couplings, presumably via the hypervalent germanium species [ArGe(OH) 3F] – . [79] Chelation

to germanium has also been used to stabilize thermodynamically highly reactive

metallogermane, [21] germene, [22,23] germacumulene, [24] and germylene [25] derivatives. Sterically

demanding aromatics are also commonly used to stabilize these reactive functionalities

kinetically. 2,4-Di-tert-butyl-6-[(dimethylamino)methyl]phenyl (Mamx) groups combine

both these features, facilitating isolation of germylene structures such as 3. [26]

Scheme 1 Intramolecular Chelation Involving Arylgermanes [20,26]

N

Ge

Ph

1

+ 4-TolBr

Bu t

Pd2(dba) 3, (2-Tol) 3P

THF, 120 oC NMe 2

GeR 1

95%

3 R 1 = Ot-Bu, O-iPr, OEt, OMe, C CPh, C CH, t-Bu, Bu, Me

Although silane-based polymers are well-documented, [27] the corresponding germaniumbased

materials have only recently been subjected to detailed investigation. This interest

is a consequence of the physical properties of these materials common to the group 14

based polymers, namely their electroluminescence and conductivity when doped, typi-

Ph

2

4-Tol

5.1.22 Aryl- and Heteroarylgermanes 169

cally with antimony(V)fluoride. [28] As with related polymers, these materials are susceptible

to photodegradation. [29]

A number of methods have been utilized successfully to synthesize polymeric aryland

heteroarylgermanes. These include Wurtz coupling, [30] coupling of Grignard reagents

with dihalogermanes, [31] treatment of organolithiums with dichlorogermylene–dioxane

complex, [28] zirconium-mediated dehydrogenative coupling [32] and ruthenium-mediated

demethanative coupling. [33]

The reactivity of heteroarylgermanes [34] has been investigated only to a limited extent.

Cycloadditions involving furans 4 (Scheme 2) [35,36] and thiophene 1,1-dioxides [37]

have been reported. In these examples, the presence of germanium does not affect the expected

course of the reactions. Although the electrophilic chemistry of arylgermanes has

been well-documented, [38–43] the reactivity of heteroarylgermanes in this respect remains

to be established except in the case of furylgermanes 4 (Scheme 2). [44]

Scheme 2 Reactions of Furylgermanes [44]

O

Br

Cl

GeMe3

F 3C

chloramine-T

O

NBS

TFAA

GeMe3

O

4

Br

Br2 •dioxane

GeMe3

Br Br

O

CCl2, MeOH

Cl

Me3C +

O

MeO O GeMe3 GeMe 3

Redistribution reactions between aryl- and halogermanes can readily be achieved using

Lewis acid catalysis and microwave irradiation. [45] This process requires strict stoichiometric

control and often results in complex mixtures, detracting from its use as a preparative

technique. Attempts to synthesize arylgermanes from simple aromatics by direct Friedel–

Crafts germylation, [45] or high temperature condensation with trichlorogermane [46] generally

result only in low yields of the desired products. In contrast, polyfluorinated arenes

readily react with halogermanes in the presence of tris(diethylamino)phosphine to give

the corresponding polyfluoroarylgermanes in moderate to good yields. [47]

SAFETY: Appropriate safety precautions and procedures should be taken when handling

and disposing of germanium compounds. For further information about the toxicity

of organogermanium compounds please see Section 5.1.

Bu t

for references see p 175

170 Science of Synthesis 5.1 Germanium Compounds

Synthesis of Product Subclass 22

5.1.22.1 Method 1:

From Halogermanes by Substitution with Arylmetals

Ge-C bonds are usually formed by reaction of halogermanes with organometallics. This

process generally provides the most efficient and convenient entry into this class of compound,

and remains the standard method for their synthesis where applicable.

5.1.22.1.1 Variation1:

Using Preformed Arylmetals

The use of preformed aryl Grignard reagents 5 and organolithium reagents (e.g., those

generated from 7 and butyllithium)with halogermanes is the most common method for

the introduction of aromatic ligands around germanium (Scheme 3). [1] Attempts to effect

selectively monoarylation of polyhalogenated germanium substrates can be achieved

using stoichiometric quantities of reagent, [48] although this process can be substrate dependent.

[49] Synthesis of fully arylated germanes using a large excess of Grignard reagent

requires forcing conditions, otherwise the reaction stops at the triarylated stage when

employing hindered aromatics. [1] Moreover, a total absence of free magnesium from the

reaction mixture is required under thermal conditions to avoid the competitive formation

of hexaaryldigermanes. [3] Use of organolithium reagents is often found to be inferior

to the use of the corresponding Grignard reagents, [1] but can give superior results in

specific cases. [49] Pyrrolyl-, furyl-, and thienylgermanes 8 are synthesized predominantly

using organolithium precursors due to their ease of preparation by selective deprotonation

at the 2-position using alkyllithiums (Scheme 3). [34,50,51]

Scheme 3 Use of Preformed Organometallics in the Synthesis of Aryland

Heteroarylgermanes [1,34,50,51]

R 1

5

MgX

X = Cl, Br; R 1 = alkyl, aryl; R 2 = Me, Et, Ph

R 1

Y

7

Y = O, NMe, S; R 1 = alkyl, aryl; R 2 = Me, Et

R 2 nGeX4−n

50−95%

1. BuLi

2. R2 3GeX

40−80%

R 1

Y

8

6

GeR 2 3

GeR 2 nX 3−n

(Chloromethyl)methylphenyl(2-tolyl)germane [6, R 1 = 2-Me; GeR 2 nX 3–n = Ge(CH 2Cl)MePh];

Typical Procedure: [52]

CAUTION: Inhalation, ingestion, or absorption of iodomethane (MeI) through the skin may be

fatal. It affects the central nervous system, causes irritation to the skin, eyes, and respiratory

tract, and is a suspected carcinogen. Appropriate safety precautions and procedures should be

taken during all stages of its handling and disposal.

2-Tolylmagnesium bromide prepared from 2-bromotoluene (13.5 g, 79 mmol)and Mg

(2.1 g, 87 mmol)in Et 2O (80 mL)was added to a mixture of dichloro(chloromethyl)phenylgermane

(21.3 g, 79 mmol)in Et 2O (50 mL)at 0 8C with stirring. The mixture was stirred at

rt for 3 h. The Grignard reagent prepared from MeI (13.3 g, 87 mmol)and Mg (2.3 g,

95 mmol)in Et 2O (70 mL)was added to the mixture at 0 8C with stirring. The mixture was

5.1.22 Aryl- and Heteroarylgermanes 171

stirred at rt for 3 h, and then refluxed for 1 h. Aq 3 M HCl (40 mL)was added to the mixture

at 0 8C. The organic layer was separated and the aqueous layer extracted with Et 2O

(2 ” 30 mL). The combined organic layer and extracts were dried (Na 2SO 4), and evaporated.

Distillation of the residue gave the product as a colorless oil; yield: 17.2 g (71%); bp 141 8C/

0.18 Torr.

5.1.22.1.2 Variation2:

Using Barbier-Type Reactions

Attempts to synthesize monoarylgermanes using stoichiometric quantities of tetraethoxygermane

or germanium(IV)halides with aryl halides and magnesium metal (Barbier conditions)generally

result in poor yields, often due to low selectivity. [4] This can be improved

in some instances by switching to copper, with the best results being achieved

using germanium(IV)chloride and aryl bromides under forcing conditions. [53] Synthesis

using Barbier conditions under thermal conditions are also plagued by competitive formation

of hexaphenyldigermanes, although yields can be improved using hexacoordinate

tris(benzene-1,2-diolato)germanates in place of germanium(IV) halides when preparing

tetraarylgermanes. [54] Although Wurtz–Fittig coupling using sodium (or lithium)has

been used in the synthesis of tetraarylgermanes, [55] treatment with zinc also results in

modest conversion of germanium(IV)iodide to tetraphenylgermane. [56]

Ultrasound has been used successfully to induce Barbier reactions involving trialkylhalogermanes,

[36] and gives superior yields and avoids digermane side products often observed

under thermal conditions. [57]

Scheme 4 Synthesis of Arylgermanes Using Barbier Conditions [36]

R 1

9

X

R 2 3GeX, Mg, BrCH 2CH 2Br, ))), rt

X = Br; R 1 = 4-CH CH 2; R 2 = Et 74%

R 1

10

GeR 2 3

4-(Triethylgermyl)styrene (10,R 1 = 4-CH=CH 2;R 2 = Et); Typical Procedure: [57]

A Schlenk tube containing Mg turnings (0.60 g, 25 mmol), 1,2-dibromoethane (0.54 mL,

6.22 mmol), Et 3GeBr (3.0 g, 12.5 mmol), and 4-bromostyrene (9, X = Br; R 1 = 4-CH=CH 2;

2.28 g, 12.5 mmol)in THF (25 mL)was placed in a commercial ultrasonic cleaning bath

(Branson B1200 E1, working frequency: 47 kHz)and sonicated for 2 h. The mixture was

washed with brine (20 mL)and extracted with Et 2O (2 ” 20 mL). The organic layers were

dried (MgSO 4), the solvents removed in vacuo, and the residue purified by column chromatography

(silica gel, petroleum ether/Et 2O 95:5)to give the product as an oil; yield: 2.4 g

(74%); 1 H NMR (CDCl 3, ä): 0.9–1.2 (m, 15H), 2.24 (dd, J = 2, 11 Hz, 1H), 5.79 (dd, J = 2, 11 Hz,

1H), 6.73 (dd, J = 11, 17.5 Hz, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H); 13 CNMR

(CDCl 3, ä): 4.4, 9.0, 113.8, 125.9, 134.6, 137.3, 140.1.

5.1.22.2 Method 2:

From Aryl Halides by Palladium(0)-Mediated Coupling with Digermanes

Initial studies carried out by Eaborn demonstrated that hexaalkyldigermanes, like other

group 14 metal analogues, [58] undergo palladium(0)-mediated coupling with aryl bromides,

albeit in low-to-modest yields due to competing formation of the corresponding

biaryl derivatives. [59] This problem was resolved by the use of aryl iodides such as iodobenzene

(11)and 1,2-dichloro-1,1,2,2-tetramethyldigermane, [60] which resulted in excellent

yields of the desired germylated aromatics, in this case iododimethylphenylgermane

(12)and chlorodimethylphenylgermane (13)(Scheme 5). [61] This method is also suitable

for references see p 175

172 Science of Synthesis 5.1 Germanium Compounds

for the synthesis of derivatives such as bis(halodimethylgermyl)thiophene 15 synthesized

from 2,5-dibromothiophene (14), [30] which can be difficult to synthesize using conventional

organometallic procedures due to their tendency to participate in oligomerization

i.e. reaction of 16 to give 17 (Scheme 5). [62] The major drawback with this methodology is

the availability of 1,2-dichloro-1,1,2,2-tetramethyldigermane, [63] which is currently not

commercially available and requires synthesis before use.

Scheme 5 Palladium(0)-Mediated Coupling of Digermanes with Aryl Halides [30,61,62]

PhI

(Me2ClGe)2, Pd(PPh3)4

benzene, 120 o C

Ph I

Ge

Me2 11 12 31%

Br

S

16

+

Ph Ge Cl

Me2 13 68%

S

Br

(Me2ClGe)2, Pd(PPh3)4,

benzene, 120

X = Br, Cl 56% after treatment with MeLi to give X = Me

14 15

oC X

Ge

Me2 S

1. BuLi, TMEDA

2. (Me2ClGe) 2

80%

Me2Ge

S

GeMe2 S S

S

Me 2Ge GeMe 2

Iododimethylphenylgermane (12) and Chlorodimethylphenylgermane (13);

Typical Procedure: [61]

A soln of iodobenzene (11; 82 mg, 0.4 mmol)in benzene (0.8 mL)(CAUTION: carcinogen!)

was treated with 1,2-dichloro-1,1,2,2-tetramethyldigermane (0.4 mmol)in the presence of

Pd(PPh 3) 4 (23 mg, 0.02 mmol)at 1208C for 5 h. Purification by fractional distillation led to

the isolation of 12; yield: 38 mg (31%)and 13; yield: 59 mg (68%)(yields calculated by GC).

5.1.22.3 Method 3:

From Aryl Halides by Insertion of Dichlorogermylene

Insertion of germylenes into aryl carbon–halogen bonds of simple aromatics generally

proceeds in moderate yield using elevated temperatures (>150 8C)and sealed reaction vessels.

[64,65] A modification of this procedure involving the use of the most readily accessible

dichlorogermylene source, dichlorogermylene–dioxane complex, [66] and catalytic quantities

of anhydrous aluminum trichloride allows these reactions to be conducted under relatively

mild conditions (~80 8C, atmospheric pressure)giving insertion in excellent yields

(Scheme 6). [4] The tolerance of this methodology towards other functionalities however

remains to be established.

Scheme 6 Germylene Insertion into Aromatic Halides [4]

R 1

18

Br

GeCl2 dioxane

AlCl3, 80 oC R 1 = 4-Me 98%; (19/20) 64:32

17

R 1

19

GeCl 3

+

R 1

20

X

Ge

Me2 GeBr 3

5.1.22 Aryl- and Heteroarylgermanes 173

Trichloro(4-tolyl)germane (19,R 1 = 4-Me) and Tribromo(4-tolyl)germane (20,R 1 = 4-Me);

Typical Procedure: [4]

A mixture of 4-bromotoluene (250 mL), GeCl 2 •dioxane (10 g, 43.2 mmol), and anhyd AlCl 3

(0.29 g, 2.17 mmol)was heated to 808C for 24 h with continuous stirring. After the mixture

was cooled to rt, it was filtered, the dioxane removed in vacuo, and the unreacted 4bromotoluene

removed by vacuum distillation (43 8C/5”10 –4 Torr)to leave the product as

a white solid; yield: 13.33 g (98%); ratio 19/20 64:32 (by GC/MS).

5.1.22.4 Method 4:

Heteroarylgermanes by Cycloaddition

Cycloaddition reactions involving alkynylgermanes (Section 5.1.20)are generally analogous

to those observed using nonmetalated alkynes. Hence, nitrogen-based heterocycles

such as pyrazoles 22, triazoles 23, and pyridazines 24 can be readily accessed in high yield

by treatment of alkynylgermanes 21 with diazomethane, [67] azides, [68] or tetrazines, [69] respectively

(Scheme 7).

Scheme 7 Nitrogen Heterocycles from Alkynylgermanes by Cycloaddition [67–70]

R 2

21

GeR 1 3

CH 2N 2

R3N3 R1 = Me, Et;

R3 R

= Na, Ph, 4-Tol, 4-O2NC6H4

32−84%

2 = CH NR4 N N

N N

R1 = Me; R2 = H 80%

R1 = Me; R2 = GeMe3 93%

R 1 3Ge R 2

22

N

H

R 1 3Ge R 2

R 2

23

24

GeR 1 3

4-(Trimethylgermyl)pyridazine (24, R 1 = Me; R 2 = H); Typical Procedure: [70]

Tetrazine (82.0 mg, 1.0 mmol)and (ethynyl)trimethylgermane (21,R 1 =Me;R 2 = H; 300 mg,

1.80 mmol, contains approx. 20% THF)in MeCN were heated to reflux for 90 min. The

resulting pale yellow soln was concentrated in vacuo. The residual brown liquid was

purified by column chromatography (silica gel, Et 2O)to afford the product as colorless

oil (which turned yellow quite rapidly in air); yield: 158 mg (80%); 1 H NMR (CDCl 3, ä):

0.45 (s, 9H), 7.50 (dd, J = 4.9, 1.8 Hz, 1H), 9.06 (dd, J = 4.9, 1.4 Hz, 1H), 9.17 (dd, J = 1.8,

1.4 Hz, 1H); 13 C NMR (CDCl 3, ä): –2.43, 131.29, 142.43, 150.64, 154.98.

N N

NR 3

for references see p 175

174 Science of Synthesis 5.1 Germanium Compounds

Applications of Product Subclass 22 in Organic Synthesis

5.1.22.5 Method 5:

Arylgermanes as Linkers for Solid-Phase Synthesis

Group 14 metals have been utilized as key functional elements in a number of linker

strategies for solid-phase organic synthesis. [71] Arylsilane linkers have been shown to be

stable towards a relatively wide range of reaction conditions and can be cleaved via ipsoprotodesilylation

with acid to liberate aromatics from the resin in a traceless fashion. [72]

Cleavage with concomitant diversification has also been achieved via ipso-halodesilylation

using bromine and iodine chloride to liberate aryl bromides and iodides, respectively.

[73] However, one limitation to the use of arylsilane linkers for solid-phase organic synthesis

is the necessity for harsh conditions (e.g., neat HF)when cleaving electron-deficient

aromatics. One tactic that addresses this problems involves increasing the susceptibility

towards electrophilic ipso-demetalation by exchanging silicon for germanium (Scheme

8). [74] This is as a result of the increasing â-effect observed down the periodic group (i.e.,

Si < Ge < Sn)in the rate-determining electrophilic ipso-addition step. [10,38,75–77] Treatment

of the arylgermanium linkers 25 with halogen sources also permits diversification at the

point of cleavage giving 26, [78] and these linkers have been used to synthesize chemical

libraries based on benzodiazapines [74] and pyrazoles. [49]

Scheme 8 Arylgermanes as Diversification Linkers for Solid-Phase Organic Synthesis [78]

R 1

25

E = H, Br, Cl, I

Me2 Ge

E +

R 1

26

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Abbreviations

Chemical

Name Used in Text Abbreviation Used

in Tables and on Arrow

in Schemes

Abbreviation Used

in Experimental

Procedures

(R)-1-amino-2-(methoxymethyl)pyrrolidine RAMP RAMP

(S)-1-amino-2-(methoxymethyl)pyrrolidine SAMP SAMP

ammonium cerium(IV) nitrate CAN CAN

2,2¢-azobisisobutyronitrile AIBN AIBN

barbituric acid BBA BBA

benzyltriethylammonium bromide TEBAB benzyltriethylammonium

bromide

benzyltriethylammonium chloride TEBAC benzyltriethylammonium

chloride

N,O-bis(trimethylsilyl)acetamide BSA BSA

9-borabicyclo[3.3.1]nonane 9-BBNH 9-BBNH

borane–methyl sulfide complex BMS BMS

N-bromosuccinimide NBS NBS

tert-butyldimethylsilyl chloride TBDMSCl TBDMSCl

tert-butyl peroxybenzoate TBPB tert-butyl peroxybenzoate

10-camphorsulfonic acid CSA CSA

chlorosulfonyl isocyanate CSI chlorosulfonyl isocyanate

3-chloroperoxybenzoic acid MCPBA MCPBA

N-chlorosuccinimide NCS NCS

chlorotrimethylsilane TMSCl TMSCl

1,4-diazabicyclo[2.2.2]octane DABCO DABCO

1,5-diazabicyclo[4.3.0]non-5-ene DBN DBN

1,8-diazabicyclo[5.4.0]undec-7-ene DBU DBU

dibenzoyl peroxide DBPO dibenzoyl peroxide

dibenzylideneacetone dba dba

di-tert-butyl azodicarboxylate DBAD di-tert-butyl azodicarboxylate

2,3-dichloro-5,6-dicyanobenzo-

1,4-quinone

DDQ DDQ

dichloromethyl methyl ether DCME DCME

dicyclohexylcarbodiimide DCC DCC

N,N-diethylaminosulfur trifluoride DAST DAST

diethyl azodicarboxylate DEAD DEAD

diethyl tartrate DET DET

2,2¢-dihydroxy-1,1¢-binaphthyllithium

aluminum hydride

BINAL-H BINAL-H

diisobutylaluminum hydride DIBAL-H DIBAL-H

177

178 Abbreviations

Chemical (cont.)

Name Used in Text Abbreviation Used

in Tables and on Arrow

in Schemes

Abbreviation Used

in Experimental

Procedures

diisopropyl tartrate DIPT DIPT

1,2-dimethoxyethane DME DME

dimethylacetamide DMA DMA

dimethyl acetylenedicarboxylate DMAD DMAD

2-(dimethylamino)ethanol Me2N(CH2) 2OH 2-(dimethylamino)ethanol

4-(dimethylamino)pyridine DMAP DMAP

dimethylformamide DMF DMF

dimethyl sulfide DMS DMS

dimethyl sulfoxide DMSO DMSO

di-tert-butyl peroxide DTBP DTBP

1,3-dimethyl-3,4,5,6-tetrahydropyrimidin-2(1H)-one

DMPU DMPU

ethyl diazoacetate EDA EDA

ethylenediaminetetraacetic acid edta edta

hexamethylphosphoric triamide HMPA HMPA

hexamethylphosphorus triamide HMPT HMPT

iodomethane MeI MeI

N-iodosuccinimide NIS NIS

lithium diisopropylamide LDA LDA

lithium hexamethyldisilazanide LiHMDS LiHMDS

lithium isopropylcyclohexylamide LICA LICA

lithium 2,2,6,6-tetramethylpiperidide LTMP LTMP

lutidine lut lut

methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide)

MAD MAD

methyl ethyl ketone MEK methyl ethyl ketone

methylmaleimide NMM NMM

4-methylmorpholine N-oxide NMO NMO

1-methylpyrrolidin-2-one NMP NMP

methyl vinyl ketone MVK methyl vinyl ketone

petroleum ether PEa petroleum ether

N-phenylmaleimide NPM NPM

polyphosphoric acid PPA PPA

polyphosphate ester PPE polyphosphate ester

potassium hexamethyldisilazanide KHMDS KHMDS

pyridine pyridineb pyridine

pyridinium chlorochromate PCC PCC

pyridinium dichromate PDC PDC

pyridinium 4-toluenesulfonate PPTS PPTS

a Used to save space; abbreviation must be defined in a footnote.

b pyused on arrow in schemes.

Chemical (cont.)

Abbreviations 179

Name Used in Text Abbreviation Used

in Tables and on Arrow

in Schemes

Abbreviation Used

in Experimental

Procedures

sodium bis(2-methoxyethoxy)aluminum hydride Red-Al Red-Al

tetrabutylammonium bromide TBAB TBAB

tetrabutylammonium chloride TBACl TBACl

tetrabutylammonium fluoride TBAF TBAF

tetrabutylammonium iodide TBAI TBAI

tetracyanoethene TCNE tetracyanoethene

tetrahydrofuran THF THF

tetrahydropyran THP THP

2,2,6,6-tetramethylpiperidine TMP TMP

trimethylamine N-oxide TMANO trimethylamine N-oxide

N,N,N¢,N¢-tetramethylethylenediamine TMEDA TMEDA

tosylmethyl isocyanide TosMIC TosMIC

triethylbenzylammonium bromide TEBAB TEBAB

triethylbenzylammonium chloride TEBAC TEBAC

trifluoroacetic acid TFA TFA

trifluoroacetic anhydride TFAA TFAA

trimethylsilyl cyanide TMSCN TMSCN

Ligands

acetylacetonato acac

2,2¢-bipyridyl bipy

1,2-bis(dimethylphosphino)ethane DMPE

2,3-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene NORPHOS

2,2¢-bis(diphenylphosphino)-1,1¢-binaphthyl BINAP

1,2-bis(diphenylphosphino)ethane dppe (not diphos)

1,1¢-bis(diphenylphosphino)ferrocene dppf

bis(diphenylphosphino)methane dppm

1,3-bis(diphenylphosphino)propane dppp

1,4-bis(diphenylphosphino)butane dppb

2,3-bis(diphenylphosphino)butane Chiraphos

bis(salicylidene)ethylenediamine salen

cyclooctadiene cod

cyclooctatetraene cot

cyclooctatriene cte

ç 5 -cyclopentadienyl Cp

dibenzylideneacetone dba

6,6-dimethylcyclohexadienyl dmch

2,4-dimethylpentadienyl dmpd

ethylenediaminetetraacetic acid edta

isopinocamphenyl Ipc

180 Abbreviations

Ligands (cont.)

2,3-O-isopropylidene-2,3-hydroxy-1,4bis(diphenylphosphino)butane

Diop

norbornadiene (bicyclo[2.2.1]hepta-2,5-diene) nbd

ç 5 -pentamethylcyclopentadienyl Cp*

Radicals

acetyl Ac

aryl Ar

benzotriazol-1-yl Bt

benzoyl Bz

benzyl Bn

benzyloxycarbonyl Cbz

benzyloxymethyl BOM

9-borabicyclo[3.3.1]nonyl 9-BBN

tert-butoxycarbonyl Boc

butyl Bu

sec-butyl s-Bu

tert-butyl t-Bu

tert-butyldimethylsilyl TBDMS

tert-butyldiphenylsilyl TBDPS

cyclohexyl Cy

3,4-dimethoxybenzyl DMB

ethyl Et

ferrocenyl Fc

9-fluorenylmethoxycarbonyl Fmoc

isobutyl iBu

mesityl Mes

mesyl Ms

4-methoxybenzyl PMB

(2-methoxyethoxy)methyl MEM

methoxymethyl MOM

methyl Me

4-nitrobenzyl PNB

phenyl Ph

phthaloyl Phth

phthalimido NPhth

propyl Pr

isopropyl iPr

tetrahydropyranyl THP

tolyl Tol

tosyl Ts

triethylsilyl TES

triflyl, trifluoromethanesulfonyl Tf

triisopropylsilyl TIPS

trimethylsilyl TMS

2-(trimethylsilyl)ethoxymethyl SEM

trityl [triphenylmethyl] Tr

Abbreviations 181

General

absolute abs

anhydrous anhyd

aqueous aq

boiling point bp

catalyst no abbreviation

catalytic cat.

chemical shift ä

circular dichroism CD

column chromatographyno abbreviation

concentrated concd

configuration (in tables) Config

coupling constant J

dayd

density d

decomposed dec

degrees Celsius 8C

diastereomeric ratio dr

dilute dil

electron-donating group EDG

electron-withdrawing group EWG

electrophile E +

enantiomeric excess ee

enantiomeric ratio er

equation eq

equivalent(s) equiv

flash-vacuum pyrolysis FVP

gas chromatographyGC

gas chromatography-mass spectrometry GC/MS

gas–liquid chromatographyGLC

gram g

highest occupied molecular orbital HOMO

high-performance liquid chromatographyHPLC

hour(s) h

infrared IR

in situ in situ

in vacuo in vacuo

lethal dosage, e.g. to 50% of animals tested LD 50

liquid liq

liter L

lowest unoccupied molecular orbital LUMO

mass spectrometryMS

medium-pressure liquid chromatographyMPLC

melting point mp

milliliter mL

millimole(s) mmol

millimoles per liter mM

minute(s) min

mole(s) mol

nuclear magnetic resonance NMR

nucleophile Nu –

optical purityop

phase-transfer catalysis PTC

proton NMR

1H NMR

182 Abbreviations

General (cont.)

quantitative quant

reference (in tables) Ref

retention factor (for TLC) R f

retention time (chromatography) t R

room temperature rt

saturated sat.

solution soln

temperature (in tables) Temp (8C)

thin layer chromatography TLC

ultraviolet UV

volume (literature) Vol.

via via

vide infra vide infra

vide supra vide supra

yield (in tables) Yield (%)

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