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

Catalytic radical C(sp3)–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(sp3)–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.