Enabling Access to 3-gem-Difluorovinyl Lactams via Zn-Mediated Sequential Single Electron Reductive Hydrodehalogenation

Abstract

Herein, we describe a direct route for the synthesis of 3-gem-difluorovinyl lactams through Zn-mediated reductive hydrodehalogenation. Importantly, by using inexpensive deuterium oxide (D₂O), the high value-added vicinal dideuterated gem-difluoroalkenes with excellent deuterium (D) incorporation were prepared. Mechanism studies indicated a successive single electron transfer process: the reaction initially undergoes hydrodechlorination to give the intermediate α-trifluoromethylidene lactams, which are then activated by the in-situ generated zinc cations and reduced to the desired product via hydrodefluorination.