A Voltage-Controlled Strategy for Modular Shono-Type Amination

Shono-type oxidation to generate functionalized heterocycles is a powerful method for late-stage diversification of relevant pharmacophores; how-ever, development beyond oxygen-based nucleophiles remains underdeveloped. The limited scope can often be ascribed to constant current electrolysis resulting in potential drifts that oxidize a desired nucleophilic partner. Herein, we report a voltage-controlled strategy to selectively oxidize a broad scope of substrates, enabling modular C–N bond formation from protected amine nucleophiles. We implement an electroanalytically-guided workflow using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) to identify oxidation potentials across a range of heterocyclic substrates. Controlled potential electrolysis (CPE) selectively generates -functionalized C–N products in moderate to good yields using carbamate-, sulfonamide-, and benzamide-derived nucleophiles. The importance of voltage control is further exemplified in two cases: (1) change in selectivity at different potentials with a morpholine substrate and (2) analysis of reaction outcomes between Celecoxib and an N-Boc or N-Ns-pyrrolidine substrate; the latter requires a potential more anodic than Celecoxib and does not yield desired product. Lastly, sequential voltage-controlled C–N and C–O functionalization of a model substrate generates difunctionalized pyrrolidines further broadening the utility of this reaction.