Photochemical [1,3]-Silyl Migration Meets Organocatalysis: A Metal-Free Route to Enantioenriched α‑Hydroxy Amides

Chiral α-hydroxy amide derivatives are privileged structural motifs in pharmaceuticals and bioactive molecules, yet their catalytic asymmetric synthesis remains challenging, particularly under transition metal-free conditions. Herein, we report the successful merger of photochemical [1,3]-silyl migration (Brook rearrangement) with the organocatalytic asymmetric addition reaction of ketenes, establishing a metal-free paradigm for the enantioselective synthesis of α-hydroxy amides. The success of this process hinges on the transient generation of siloxyketenes from α-ketoacylsilanes. This transformation features mild reaction conditions, a broad substrate scope, good functional group tolerance, and facile scalability. The method highlights the formal synthesis of the AAK1 inhibitor and BMS-270394. Mechanistic studies, including DFT calculations, provide critical insights into the reaction pathway and stereochemical outcomes.