Synthesis of Chiral <i>gem</i>-Difluoromethylene Compounds by Enantioselective Ethoxycarbonyldifluoromethylation of MBH Fluorides via Silicon-Assisted C–F Bond Activation

Abstract

The enantioselective ethoxycarbonyldifluoromethylation of Morita–Baylis–Hillman (MBH) fluorides with Me3SiCF2CO2Et under organocatalysis is described. Moderately functionalized chiral gem-difluoromethylene compounds with a stereogenic “C-CF2-C*” unit were synthesized in high yields with high enantioselectivities. The initial C–F bond activation is assisted by the silicon atom via a dual SN2′-SN2′ stepwise pathway. Dynamic kinetic resolution of the MBH-fluorides explained the high yields and high ee’s of the products. The method was extended to the enantioselective introduction of “Het-CF2” units.