Accessing tetrasubstituted CF2H 1-pyrrolines via electrochemical hydrodefluorination and [3+2] cascade cyclization

Tetrasubstituted difluoromethyl 1-pyrrolines are scarcely reported compared to trifluoromethyl 1-pyrrolines. Herein, we present a novel access to difluoromethyl 1-pyrrolines through electrochemical hydrodefluorination of trifluoromethyl alkenes and [3+2] cascade cyclization. Under mild and sustainable conditions, numerous valuable gem -difluoroalkene synthons were efficiently synthesized from readily available starting materials without the use of any transition-metal catalysts or external reductants. These products can be efficiently transformed into novel tetrasubstituted difluoromethyl 1-pyrrolines via a Zn-catalyzed [3+2] cascade cyclization. This sustainable methodology features excellent atom economy and favourable E-factor metrics. Mechanistic investigations suggested that trace amounts of water in the solvent serve as the hydrogen source during the hydrodefluorination, and a plausible reaction mechanism is proposed. A general and efficient methodology for accessing novel tetrasubstituted difluoromethyl 1-pyrrolines from readily available trifluoromethyl alkenes has been developed via sequential electrochemical hydrodefluorination and [3+2] cascade cyclization. Numerous valuable gem -difluoroalkene synthons were efficiently synthesized under mild and sustainable conditions without the use of any transition-metal catalysts or external reductants. Furthermore, various scarcely reported β -CF 2 H 1-pyrrolines were efficiently prepared in moderate to high yields with excellent diastereoselectivity ( dr > 20:1).