Stereospecific and Stereoselective Suzuki–Miyaura Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 542

137

134 135

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Taking advantage of the radical pathway observed for the aforementioned
Ni-catalyzed processes, Fu and co-workers were able to develop methods for
the stereoconvergent cross-coupling of racemic secondary alkyl halides to
organoboron nucleophiles using a chiral ligand. As shown in eqn (11.36),
primary alkylboranes were coupled to a series of racemic secondary alkyl
halides in the presence of [Ni(COD) 2 ] and chiral diamine ligands. Initially,
homobenzylic secondary bromides were coupled to alkylboranes in high
yield and enantioselectivity with a Ni-chiral diamine ligand catalyst sys-
tem. 103 This advance was followed shortly thereafter by the asymmetric
arylation of racemic b-chloroamides. 104 Notably, the precise conditions
(solvent, additive) vary from substrate to substrate and can have a significant
impact on the reaction outcome.

(11 : 36)

(11 : 37)

A possible mechanism for the Ni-catalyzed alkyl Suzuki reaction is provided
in Scheme 11.15. The reaction is believed to occur via aNi I -Ni III manifold,
with the oxidative addition occurring by a radical mechanism. 105-108 Com-
petition studies have demonstrated that oxidative addition is likely not rate
limiting in the case of cyclohexyl iodides or bromides, whereas it is likely rate
limiting for cyclohexyl chlorides. 101 Interestingly, in the case of a-chloro-
amides as coupling partners, modest enantioenrichment was observed in
unreacted starting material,

leading the authors to suggest that the