Tailoring Unstrained Pyrrolidines via Reductive C–N Bond Cleavage with Lewis Acid and Photoredox Catalysis

Skeletal remodeling of unstrained azacycles such as pyrrolidine remains a formidable challenge in synthetic chemistry. To achieve such remodeling, continuous development of the cleavage of inert C–N bonds is essential. In this study, we introduce an effective strategy for the reductive cleavage of C–N bond in N-benzoyl pyrrolidine, leveraging a combination of Lewis acid and photoredox catalysis. This method involves single-electron transfer to the amide, followed by site-selective cleavage at C2–N bond. Cyclic voltammetry and NMR studies demonstrated that the Lewis acid is crucial for promoting the single-electron transfer from the photoredox catalyst to the amide carbonyl group. This protocol is widely applicable to various pyrrolidine-containing molecules and enables inert C–N bond cleavage including C–C bond formation via intermolecular radical addition. Furthermore, the current protocol successfully converts pyrrolidines to aziridines, lactones, and tetrahydrofurans, demonstrating the potential to expand synthetic strategies in skeletal remodeling.