Synthesis of gem-Difluorinated Isoxazoles via Palladium-Catalyzed Oxylallylation of Alkynone Oxime Ethers.

Abstract

A novel and reliable palladium-catalyzed oxylallylation of alkynone oxime ethers with fluorine-containing alkenes was accomplished. Using the bulk industrial chemical 3-bromo-3,3-difluoroprop-1-ene as the coupling partner, this synthetic methodology offers the first example for the assembly of structurally diverse gem-difluorinated isoxazole derivatives in moderate to good yields with high atom- and step-economy and excellent functional group compatibility. More importantly, this strategy allows for the direct combination of the isoxazole motifs and gem-difluoroalkene unit, which is not easy to obtain through a general synthetic strategy.