A General and Modular Access to Enantioenriched α Trifluoromethyl Ketones via Nickel-Catalyzed Reductive Cross-Coupling

The development of new catalytic enantioselective access to CF3-containing stereogenicity is of great interest for the expediting discovery of lead compounds yet remains challenging. We devised a general and modular approach to facilely access enantioenriched α-CF3 ketones via nickel-catalyzed reductive cross-coupling of readily available acid chlorides and racemic α-CF3 alkyl bromides in an enantioconvergent fashion under mild conditions. This protocol featured neighboring directing group-free, high chemoselectivity, excellent functional group tolerance, facile scale-up, and notable amenability to straightforward downstream elaboration toward molecule complexity, thus constituting a reliable, direct, practical, and efficient synthetic alternative to furnish enantiopure α-CF3 carbonyls. Interestingly, an appropriate choice of the phosphine ligand as co-ligand plays an important role in high efficiency and asymmetric induction. Mechanistic studies suggest a radical chain pathway.