General and Modular Access to Enantioenriched α-Trifluoromethyl Ketones via Nickel-Catalyzed Reductive Trifluoroalkylation

The development of new catalytic enantioselective access to stereogenic CF_(3)-containingmolecules is of great interest for expediting the discovery of lead compounds that remain challenging.Specifically,enantioselective synthesis of valuable ketones featuring stereogenicα-CF_(3) has rarely been reported.We devise a general and modular approach to facilely access enantioenrichedα-CF_(3) ketones via nickel-catalyzed reductive cross-coupling of readily available acid chlorides and racemicα-CF_(3) alkyl bromides in an enantioconvergent fashion under mild conditions.This protocol features neighboring directing group-free,high chemoselectivity,excellent functional group tolerance,facile scale-up,and notable amenability to straightforward downstream elaboration toward pharmaceutically useful enantioenrichedβ-trifluoromethylated secondary and tertiary alcohols,thus constituting a reliable,direct,practical,and efficient synthetic alternative to furnish enantiopureα-CF_(3) carbonyls.Interestingly,an appropriate choice of the phosphine ligand as coligand plays an important role in high efficiency and asymmetric induction.Mechanistic studies suggest a radical chain pathway.