Remote C(sp3)–H acylation of amides under photoredox cooperative N-heterocyclic carbene/palladium catalysis

Abstract

Direct acylation of amides at C(sp³)–H sites from aldehydes is one of the most convenient methods to access highly valuable keto-amides; yet it remains challenging and less developed. Herein, we report a photoredox cooperative NHC/Pd-catalyzed method that enables C(sp³)–H acylation for the quick construction of keto-amide derivatives from readily available amides and aldehydes. This work demonstrates the generation of ketyl radicals from aldehydes under NHC/Pd catalysis and alkyl radicals via 1,5-hydrogen atom transfer from aryl radicals under photoredox/Pd catalysis, thus providing two- and three-component reactions for the synthesis of α- and γ-keto-amides through radical–radical coupling reactions. This work shows good compatibility with a large variety of functional groups, as demonstrated by more than 75 examples, including complex bioactive compounds. Mechanistic studies including several control reactions shed light on the mechanism of this photoredox cooperative NHC/Pd-catalyzed reaction.