Base-Controlled Regioselective Synthesis of α-Fluoro-Allylnitriles and -Acrylonitriles from Alkenylsulfonium Salts and Cyanofluoromethyl Phosphonate

Abstract

Achieving high regio- and stereoselectivity in alkenes synthesis remains a formidable challenge in synthetic chemistry. Herein, we report a tunable C–C coupling strategy for the divergent synthesis of multisubstituted alkenes from alkenylsulfonium salts and cyanofluoromethyl phosphonate. The choice between t-BuOK and DBU as the base selectively furnishes either α-fluoro allylnitriles or the corresponding isomerized α-fluoro acrylonitriles. Remarkably, under DBU-promoted conditions, a one-pot incorporation of alcohols drives a tandem transesterification process, delivering diversified α-fluoro acrylonitriles with high regio- and stereocontrol. Furthermore, the synthetic utility of this method is further demonstrated by the late-stage modification of complex bioactive molecules and versatile product transformations.