Visible-Light-Driven Radical Cascade Cyclization of 4-(N-Alkyl-Nacrylamido)coumarins: Access to Difluoroalkylated 4,5-Fused Coumarins and Coumarin[4,3-b]pyridinones

Abstract

An efficient and practical visible-light-driven cascade difluoroalkylation/cyclization of 4-(N-alkyl-N-acrylamido)coumarins has been developed using readily accessible bromodifluoromethylphosphonium bromide ([Ph₃PCF₂H]⁺Br^-) as a difluoromethyl radical precursor. This protocol enables the rapid construction of a wide range of difluoroalkylated 4,5fused polycyclic coumarin derivatives under mild, additive-and base-free conditions. Moreover, an alternative photoredox-catalyzed intramolecular radical cyclization of 4-(N-alkyl-N-acrylamido)coumarins has been established, providing efficient access to structurally diverse coumarin [4,3-b]pyridinone derivatives. Both transformations proceed smoothly at room temperature, exhibiting broad substrate scope, excellent regioselectivity, and good functional group tolerance. Preliminary mechanistic investigations indicate that the two pathways operate through distinct radical processes involving single electron transfer (SET) and energy transfer (EnT), respectively.