3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents

Abstract

The selective synthesis of fluorinated organic molecules continues to be of major importance for the development of bioactive compounds (agrochemicals and pharmaceuticals) as well as unique materials. Among the established synthetic toolbox for incorporation of fluorine-containing units, efficient and general reagents for introducing -CF₂- groups have been largely neglected. Here, we present the synthesis of 3,3-difluoropropen-1-yl ammonium salts (DFPAs) as stable, and scalable gem-difluoromethylation reagents, which allow for the direct reaction with a wide range of fascinating nucleophiles. DFPAs smoothly react with N-, O-, S-, Se-, and C-nucleophiles under mild conditions without necessity of metal catalysts with exclusive regioselectivity. In this way, the presented reagents also permit the straightforward preparation of many analogues of existing pharmaceuticals.