ca01 only detailed ToC 1..24

1.1.4 Nickel–Alkene Complexes 65
Scheme 59 Applications of Nickel-Catalyzed Conjugate Additions in Total Synthesis [128–130]
O
O
O
O
O
O
Me 2Zn, LiBr
Ni(acac) 2 1, Et2O
78%
1. Me2Zn, Ni(acac)2 1
2. TMSCl, Et 3N
O
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
Ac
(1R ∗ ,2R ∗ ,3R ∗ )-75 58%
+
Ph
O
O
O
Ac
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