Nitrogen-containing heterocycles are the most common structural units in numerous natural products, drugs, and bioactive compounds. Among them, functionalized tetrahydropyridine derivatives are widely present in many alkaloids, biologically active molecules and drug molecules. Consequently, the synthesis of this class of nitrogen heterocyclic compounds has attracted widespread attention from chemists. Despite many known powerful methods, some of the existing protocols still require use of expensive transition metal catalysts or harsh reaction conditions, thus limiting their extensive application. Herein, we report an efficient and practical method for synthesis of functionalized 1,2,3,6-tetrahydropyridine derivatives by visible-light-induced nitrogen radical-mediated addition/cyclization of vinylcyclopropanes. This process involves controlled generation of sulfonamidyl radicals from N-aminopyridinium salts to trigger the addition/cyclization reaction with vinylcyclopropanes. This work not only enriches the reaction scope of photogenerated nitrogen radicals, but also provides a new approach for the construction of 1,2,3,6-tetrahydropyridines. Notably, the N-aminopyridine salts in this reaction act as a bifunctional reagent, both as a nitrogen radical precursors and a nitrogen nucleophilic reagents. Vinylcyclopropanes serve as versatile four-atom coupling partners, undergoing radical addition followed by ring-opening and cyclization. This work significantly expands synthetic approaches for heterocyclic construction by demonstrating a novel reaction mechanism for visible-light-catalyzed nitrogen radical generation, providing a direct and modular synthetic pathway for tetrahydropyridine core structures. After extensive condition screening, the optimal conditions for this reaction were determined as follows: 10-phenylphenothiazine (Ph-PTZ) as the photocatalyst and 1,2-dichloroethane (DCE) as the solvent under irradiation of 390 nm purple LEDs. Subsequently, the substrate scope of N-aminopyridine salts and vinylcyclopropanes was examined, leading to the synthesis of 42 examples of 1,2,3,6-tetrahydropyridine analogs in up to 77% isolated yield. In addition, this method can be scaled up to the gram scale while the product undergoes various transformations of functional groups. Finally, a possible reaction mechanism was proposed for the reaction based on free radical trapping experiments and fluorescence quenching experiments.

Key words: photoredox catalysis, sulfonamidyl radicals, N-aminopyridine salts, vinylcyclopropanes, bifunctional reagents, tetrahydropyridines