Self-Photocatalyzed Difluoromethylation-Cyclization and Controllable Hydrodefluorination: Access to Medium-Sized Monofluoro- N -heterocycles

Abstract

Molecular editing enabling precision hydrodefluorination remains a highly challenging endeavor owing to the high C–F bond energy and the possibility of exhaustive defluorination. At present, the established strategy for hydrodefluorination is mainly dedicated to specific C–F bonds, including trifluoromethylarenes, trifluoroacetates, and amides. Herein, we present an energy-mediated self-photocatalyzed intramolecular difluoromethylation-cyclization and controllable hydrodefluorination protocol to medium-sized monofluoro-N-heterocycles. Broad substrate scope and functional group compatibility, biologically active molecule modification (Erlotinib, Norethisterone, Norgestrel, Norquetiapine, Desloratadine, Melatonin, Vortioxetine, and Ethynyl Estradiol), large-scale synthesis, and diverse derivatization highlight the utility of this catalytic strategy.