Remote C(sp3)–H cyanation and deuteration of amides via photoredox catalysis

Abstract

Selective functionalization of remote C(sp³)–H bonds represents a major challenge in organic synthesis. We report a unified visible-light photoredox catalytic strategy for remote C(sp³)–H cyanation and deuteration of amides. Key to this approach is the in situ generation of aryl radicals from ortho-iodobenzoyl-derived amides, which triggers intramolecular 1,5-hydrogen atom transfer to form α-carbon radicals. These intermediates undergo divergent trapping to afford α-cyano- or α-deuterated amides. The cyanation protocol features broad substrate scope, good to excellent yields, and late-stage functionalization capability. The deuteration protocol, using D₂O, delivers α-deuterated amides with high deuterium incorporation and functional group tolerance. Mechanistic studies support a pathway involving aryl radical-mediated 1,5-HAT. This strategy offers an efficient and general route to valuable α-functionalized amide derivatives from readily available precursors.