Formation and reactivity of gem-difluoro-substituted pyridinium ylides: Experimental and DFT investigation

Abstract

According to DFT B3LYP/6-31G* calculations the reaction of difluorocarbene with pyridines proceeds reversibly with the formation of thermodynamically unstable intermediates, difluoro-substituted pyridinium ylides, which dissociate to carbene and pyridine with low activation barrier. The equilibrium constant of the reaction increases with increasing electron-withdrawing ability of substituents in the pyridine ring. Difluoroylides were generated from 4-cyano, 4-benzoyl- and 4-ethoxycarbonyl-substituted pyridines under difluorocarbene generation conditions (CF2Br2/Pb/Bu4NBr/CH2Cl2/ultrasound) and trapped with dimethyl maleate or fumaronitrile. 3-Fluoroindolizines were isolated as final products of the reaction which involves dehydrofluorination of the primary cycloadducts followed by dehydrogenation by active MnO2.