ca01 only detailed ToC 1..24

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