Asymmetric Suzuki Cross-Couplings of Activated Secondary Alkyl Electrophiles: Arylations of Racemic α-Chloroamides

A nickel-catalyzed stereoconvergent method for the enantioselective Suzuki arylation of racemic α-chloroamides has been developed. This process provides a unique example of an asymmetric arylation of an α-haloamide, an enantioselective arylation of an α-chlorocarbonyl compound, and an asymmetric Suzuki reaction with an activated alkyl electrophile or an arylboron reagent. The method is also applicable to the corresponding enantioselective cross-coupling of α-bromoamides. The coupling products can be transformed without racemization into enantioenriched α-arylcarboxylic acids and primary alcohols. A modest kinetic resolution of the α-chloroamide was observed; a mechanistic study indicated that the selectivity may reflect discrimination by the chiral catalyst of the two enantiomeric α-chloroamides in an irreversible oxidative-addition process.