Synthesis of Polycyclic Furan and Chromene Derivatives via Cascade Reactions Enabled by Cleavage of Multiple C(sp3)−F Bonds

Abstract The strong and unreactive C−F bond makes polyfluorocarbons extremely long‐lived and potentially toxic. A successive selective and controllable C( sp 3 )−F functionalization of polyfluoroalkylated ketones with S ‐ and O ‐nucleophiles to enable efficient synthesis of pharmaceutically important fluorine‐ and sulfur‐containing polycyclic furan and chromene derivatives under transition metal‐free conditions is demonstrated here. The combination of C−S/C−O coupling, aromatization, and cyclization cascade contribute to the accurate four/five C( sp 3 )−F bond cleavage at two different sites of perfluoroalkyl chain. The formation of reactive quinoid intermediates and the necessity of using TBAB (tetrabutylammonium bromide) as additive and Cs 2 CO 3 as base were identified by detailed mechanistic studies. magnified image