Photoinduced-Atom Transfer Radical Cyclization of 1,5-Enenitriles with Thiosulfonates for the Synthesis of γ-Lactams Bearing Sulfonyl and N-Sulfenyliminyl Groups

1,5-Enenitriles are versatile substrates in cascade radical addition and cyclization reactions for the construction of heterocyclic frameworks bearing new functional groups. However, the reaction process usually generates cyclic iminyl intermediates that could undergo hydrolysis to form ketones, resulting in the loss of the nitrogen atom with low atom economy. The direct capture of iminyl radicals by another radical species to afford nitrogen-retaining products remains a significant challenge which has not been well explored. In this work, we report a fac-Ir(ppy)₃-catalyzed atom transfer radical cyclization of 1,5-enenitriles with thiosulfonates for the synthesis of γ-lactams bearing sulfonyl and N-sulfenyliminyl groups. It is the first application of using thiosulfonates as dual-functional reagents for simultaneous formation of C–S and N–S bonds through a photoinduced cascade radical reaction process. The reactions of 1,5-enenitriles and thiosulfonates were conducted in dioxane under mild conditions using Cs₂CO₃ as a base to form targeted products in moderate to good yields. The photoinduced reaction process first generates sulfonyl and thiyl radicals from thiosulfonates, followed by the addition of sulfonyl radicals to enenitriles, 5-exo-dig cyclization for the formation of iminyl radicals, and finally trapping of the iminyl radicals by thiyl radicals to form difunctionalized γ-lactams. This protocol features a photoinduced reaction process under oxidant-free conditions, having a broad substrate scope and easy scalability, 100% atom economy, and representing a sustainable alternative to the conventional methods in making functionalized imines. Mechanistic studies suggest it has an energy transfer (EnT) pathway for thiosulfonate activation to generate initial radicals, while a base is used in neutralizing acidic byproducts for a better conversion. The effort to extend the reaction scope for selenosulfonates was not successful due to the formation of unstable N-selanylimines that could be readily hydrolyzed to pyrrolidine-2,4-diones. Overall, this work introduces a new synthetic utility of thiosulfonates in atom transfer radical cyclization with 1,5-enenitriles for the generation of iminyl radicals as key intermediates, which are captured by thiyl radicals to form N-sulfenylimines. (Figure presented.).