Dynamic Kinetic Control Enables Nickel-Catalyzed Enantioconvergent C(sp³)-O Coupling

The enantioselective formation of C(sp³)-O bonds from racemic alkyl electrophiles is a longstanding challenge in asymmetric catalysis. Here, we introduce a nickel(II)-catalyzed enantioconvergent S_N2 alkylation of racemic secondary alkyl halides with hydroxamic acids that exploits halide-driven substrate racemization under a dynamic kinetic resolution pathway. The reaction proceeds under mild, air- and moisture-tolerant conditions, tolerates diverse electrophiles, and delivers enantioenriched hydroxamates with high selectivity. Gram-scale synthesis and downstream derivatizations highlight the utility of this protocol, enabling concise access to the Rho-pathway inhibitor (S)-CCG-1423 and a key intermediate for the γ-secretase inhibitor LY411575. This strategy establishes a general platform for late-stage, stereoselective C-O bond formation and provides a versatile route to oxygen-containing motifs relevant to bioactive molecules and drug discovery.