Harnessing Cooperative Hydrogen-Atom Transfer and Nitrene-Primed Radical–Polar Crossover for Asymmetric C–H Amidation of α-Amino Carbonyls

Catalytic radical C(sp 3 )–N coupling via C–H bond cleavage and nitrene transfer has become a major focus in catalysis over the past few decades. However, asymmetric C(sp 3 )–N coupling in this context is mostly limited to the intramolecular amination of benzylic or allylic C–H bonds, which is attributed to limited mechanistic pathways. Described herein is copper-catalyzed enantioselective and intermolecular α C–H amidation of α-amino carbonyls with dioxazolones (amidating reagent), affording otherwise hard-to-access chiral aminals. The coupling proceeds under dioxazolone-dependent conditions with possible photoredox assistance and is peptide-compatible. Mechanistic studies of the amidation reaction with methyldioxazolone reveal a radical-polar crossover pathway primed by dual nitrenes as an amidating reagent and a supporting ligand, and the C–N formation occurs via nitrene-primed umpolung rather than through the conventional hydrogen-atom transfer-radical rebound pathway.