Photoredox‐Catalyzed 1,2,2‐Trifunctionalization of Alkenes with 1,7‐Enynes and α‐Bromocarbonyls

Comprehensive Summary

Cyclopenta[ c ]quinoline derivatives represent privileged structural motifs that exhibit remarkable potential biological activities, which have prompted considerable interest in developing green, efficient and general synthetic strategies for constructing this scaffold. Despite significant advances, the currently available methods for the rapid assembly of cyclopenta[ c ]quinoline frameworks are predominantly limited to two‐component reactions, and the development of multicomponent strategies that enable rapid diversification and complexity generation remains highly desirable. Herein, we report a novel visible‐light photoredox‐catalyzed three‐component 1,2,2‐trifunctionalization of alkenes with 1,7‐enynes and α‐bromocarbonyls, enabling rapid and efficient synthesis of structurally diverse cyclopenta[ c ]quinoline derivatives with excellent functional group tolerance. Notably, this strategy represents a rare example of 1,5‐hydrogen atom transfer‐enabled 1,2,2‐trifunctionalization of alkenes. This mild and transition metal‐free protocol operates under ambient conditions with visible light as the sole energy source and allows simultaneous construction of four C–C bonds in one pot, offering a step‐economical and atom‐efficient approach to complex polycyclic architectures. The reaction exhibits a broad substrate scope across all three coupling partners, including various substituted 1,7‐enynes, cyclic and acyclic enamides, unactivated alkenes, and diverse activated alkyl bromides, delivering the desired products in up to 94% yield. Moreover, the synthetic utility of this method is highlighted by gram‐scale synthesis and facile downstream transformations of the products. Mechanistic studies, including radical‐trapping experiments, radical clock studies, Stern‐Volmer fluorescence quenching analysis, and light on/off experiments, indicate that the reaction proceeds through a sequential cascade process involving reductive C–Br bond cleavage, sequential difunctionalization of alkenes, 1,5‐hydrogen atom transfer, and intramolecular cyclization.