Visible-Light-Induced Selenium-Mediated Cascade Cyclization of 2-Isocyanobenzonitriles with Secondary Amines to Access Indole-Fused Polycyclics

Abstract

The development of green and sustainable synthetic methodologies for constructing indole-fused polycyclic frameworks is of paramount importance in modern chemistry. Herein, we present an efficient and environmentally benign visible-light-induced selenium-mediated cascade cyclization of 2-isocyanobenzonitriles with secondary amines. This methodlogy enables the switchable construction of indolo[2,3-b]quinoxalines and imidazo[4,5-b]indoles by the formation of one C−C bond, two C−N bonds, and two rings in a single step. Mechanistic investigations indicated that the generated selenourea form an intramolecular EDA complex with the assistance of base, which undergo single-electron transfer under visible light. An imidoyl radical, generated via aerobic oxidative deselenization, initiates a free-radical cascade cyclization, leading to the desired fused heterocycles. This protocol exemplifies the principles of green chemistry by featuring high atom economy, ambient temperature operation, photocatalyst- and metal-free and broad substrate scope. Furthermore, Se is efficiently recovered and recycled using vitamin C, reducing waste and enhancing sustainability.