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

The strong and unreactive C−F bond makes polyfluorocarbons extremely long-lived and potentially toxic. A successive selective and controllable C(sp³)−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(sp³)−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 Cs₂CO₃ as base were identified by detailed mechanistic studies. (Figure presented.).