Selective C–N\nBond Cleavage in Unstrained Pyrrolidines\nEnabled by Lewis Acid and Photoredox Catalysis

Cleavage of inert\nC–N bonds in unstrained azacycles\nsuch\nas pyrrolidine remains a formidable challenge in synthetic chemistry.\nTo address this, we introduce an effective strategy for the reductive\ncleavage of the C–N bond in <i>N</i>-benzoyl pyrrolidine,\nleveraging a combination of Lewis acid and photoredox catalysis. This\nmethod involves single-electron transfer to the amide, followed by\nsite-selective cleavage at the C2–N bond. Cyclic voltammetry\nand NMR studies demonstrated that the Lewis acid is crucial for promoting\nthe single-electron transfer from the photoredox catalyst to the amide\ncarbonyl group. This protocol is widely applicable to various pyrrolidine-containing\nmolecules and enables inert C–N bond cleavage including C–C\nbond formation via intermolecular radical addition. Furthermore, the\ncurrent protocol successfully converts pyrrolidines to aziridines,\nγ-lactones, and tetrahydrofurans, showcasing its potential of\nthe inert C–N bond cleavage for expanding synthetic strategies.