Synthesis of Polycyclic Furan and Chromene Derivatives via Cascade Reactions Enabled by Cleavage of Multiple C(sp(3))-F Bonds

摘要

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 withS- andO-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 Cs2CO3 as base were identified by detailed mechanistic studies.