Nickel-Catalyzed Enantioconvergent S N 2 O -Alkylation through Halide-Enabled Dynamic Kinetic Resolution

Abstract

Metal-catalyzed enantioselective construction of C(sp 3 )–O bonds from racemic alkyl electrophiles has attracted considerable attention, yet existing approaches typically proceed through organometallic or radical intermediates. Here, we highlight a halide-enabled dynamic kinetic resolution platform that integrates rapid substrate racemization with nickel-catalyzed enantioselective O -alkylation. Bromide ions generated in situ continuously promote reversible S N 2 exchange between substrate enantiomers, providing a self-sustained racemization process without external racemization catalysts or additional energy input. Combined with ligand-controlled outer-sphere S N 2 substitution, this strategy affords a broad range of enantioenriched hydroxamates in high yields and excellent enantioselectivities under mild, air- and moisture-tolerant conditions. Mechanistic studies support a halide-driven dynamic kinetic resolution coupled with an outer-sphere Ni(II)-mediated substitution pathway, providing a general strategy for asymmetric C(sp 3 )–O bond formation.