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The reaction of common acyl-metal species (acyl anion) with aldehydes to furnish acyloins has received much less attention and specifically was restricted to using preformed stoichiometric acyl-metal reagents. Moreover, the (catalytic) enantioselective variants remain unexplored, and the asymmetric synthesis of chiral acyloins has met significant challenges in organic synthesis. Here, we uncover the highly enantioselective coupling of acid chlorides with α-bromobenzoates by nickel catalysis for producing enantioenriched protected α-hydroxy ketones (acyloins,60 examples) with high enantioselectivities (up to 99% ee). The successful execution of this enantioselective coupling protocol enables the formation of a key ketyl radical from α-bromoalkyl benzoate in situ generated from corresponding aldehyde and acyl bromide, which finally is captured by chiral acyl-Ni species catalytically in situ formed from acyl chlorides, thus avoiding the use of preformed acyl-metal reagents. The synthetic utility of this chemistry is demonstrated in the downstream synthetic elaboration toward a diverse set of synthetically valuable chiral building blocks and biologically active compounds.

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.