Photoinduced H-Bonding EDA complex-enabled skeletal editing of furans to pyridazines

Skeletal editing enables direct structural reorganization of molecular frameworks, providing a powerful strategy for rapid exploration of chemical space in lead optimization. Herein we report a mild, photoinduced skeletal editing strategy that converts furans into pharmacologically valuable pyridazines without external photocatalysts. Upon photoexcitation, the H-bonding electron donor–acceptor (EDA) complex formed between furan and hexafluoroisopropanol (HFIP) enables activation of molecular oxygen, generating reactive oxygen species that promote oxidative ring opening of furan to a 1,4-dicarbonyl intermediate, which subsequently condenses with hydrazine hydrate to afford pyridazines. The method displays broad substrate scope, tolerates complex and drug-derived motifs, and can be implemented to continuous-flow processing with enhanced efficiency and scalability. Skeletal editing enables direct structural reorganization of molecular frameworks, providing a powerful strategy for rapid exploration of chemical space in lead optimization. Herein the authors report a mild, photoinduced skeletal editing strategy that converts furans into pharmacologically valuable pyridazines without external photocatalysts.