“On-water” defluorinative cyclization of trifluoromethyl enones with phosphine oxides: synthesis of polysubstituted furans

Abstract

The unique properties at the macroscopic phase boundary between water and insoluble reactants have the potential to enhance reaction rates and selectivity. In this work, a mild, transition-metal-free, and efficient defluorinative cyclization of readily available trifluoromethyl enones with phosphine oxides is developed in a pure water solution, involving a sequence of intermolecular defluorophosphorylation and intramolecular defluoroheterocyclization. A variety of polysubstituted furans featuring C1-fluorine, C2-trifluoromethyl, and C3-phosphoryl groups could be synthesized in good yields with excellent tolerance toward various functional groups. Moreover, these furans could be readily transformed into other structurally valuable furan derivatives. The utilization of water not only serves as an environmentally friendly solvent but also contributes to excellent reaction selectivity and selective C–F bond activation.