Organocatalytic Strategy for Hydrophenolation of Gem-Difluoroalkenes

Tetrahedron. 2019 Aug 9;75(32):4325-4336. doi: 10.1016/j.tet.2019.04.016. Epub 2019 Apr 9.

Abstract

Gem-difluoroalkenes are an easily accessed fluorinated functional group, and a useful intermediate for elaborating into more complex fluorinated compounds. Currently, most functionalization reactions of gem-difluoroalkenes, with or without a transition metal-based catalyst system, involve the addition or removal of a fluorine atom to generate trifluorinated or monofluorinated products, respectively. In contrast, we present a complementary "fluorine-retentive" reaction that exploits an organocatalytic strategy to add phenols across gem-difluoroalkenes to deliver β,β-difluorophenethyl arylethers. The products are produced in good to moderate yields and selectivities, thus providing a range of compounds that are underrepresented in the synthetic and medicinal chemistry literature.