Enantioselective N-α C(sp3)-H Functionalization of Amides by Trifunctional Catalytic Systems

The trifunctional catalytic systems (TCS) consisting of bifunctional photocatalysts and transition metals will be designed to achieve the enantioselective N- C(sp3)-H functionalization of amides (ENCHFA). Mechanistically, the bifunctional chiral hydrogen bonding-based aryl ketones will activate the amides to form -amido radicals via HAT and control their reactivity in an enantioselective manner while transition metal will provide another opportunity to active substrates and accomplish the photocatalytic cycle via a radical relay. Combining chiral hydrogen bonding-based aryl ketones with Co catalysis, the protocol will develop the external oxidant-free enantioselective N- C-H alkenylation, arylation and alkoxylation of amides with H2 evolution. Furthermore, the enantioselective N- C-H trifluoromethylation of amides will be relized by merging chiral hydrogen bonding-based aryl ketones with Cu catalysis. The trifunctional catalytic systems will not only enrich the types of enantioselective C-H functionalization of amides, but also reveal the mechanism of trifunctional catalytic systems, as well as provide guidance for designing multiple systems in asymmetric catalysis.