Enantioselective Access to Chiral γ‑Ketoamides via Photoredox Catalyzed Carbamoyl Radical Addition/Asymmetric Protonation

Herein, we report a method for the enantioselective synthesis
of
β-chiral amides through photoredox-catalyzed carbamoyl radical
addition to α,β-unsaturated ketones, followed by enantioselective
protonation. The combination of photoredox catalysis with chiral Brønsted
acid catalysis enables the generation of carbamoyl radicals under
mild conditions and achieves stereocontrol in the protonation step.
This dual catalytic system offers a direct and efficient approach
to access synthetically valuable β-chiral γ-ketoamides,
delivering products with high enantioselectivities and broad functional
group tolerance. Mechanistic investigations support a sequential process
involving photoinduced radical conjugate addition, single-electron
reduction, and enantioselective protonation. This strategy expands
the utility of carbamoyl radicals in asymmetric synthesis and contributes
to the development of radical-based enantioselective methodologies.