Catalytic Asymmetric α-Alkylation of Ketones with Unactivated Alkyl Halides.

Abstract

A catalytic, enantioselective method for direct α-alkylation of ketones with unactivated alkyl halides is realized by employing an α-enolizable ketone in a nickel-catalyzed C(sp3)-C(sp3) cross-coupling reaction. The key to the success is attributed to a unique bimetallic ligand. A variety of acyclic ketones and unactivated alkyl iodides can serve as suitable substrates under mild conditions to generate chiral ketones with α-quaternary carbon stereocenters in high yields with good enantioselectivities. A range of transformations based on the ketone moiety are also demonstrated to show the potential application of this method. Preliminary mechanistic studies support a dinickel-catalyzed cross-coupling mechanism.