Promotion of Metal-Free Catalytic Coupling of Fluorinated Halogenated Hydrocarbons By a Base for the Synthesis of Difluoromethyl Heterocyclic Amines

Abstract

The selective functionalization of difluoromethyl groups (−CF₂) is a promising approach and an attractive synthetic route for accessing fluorine-containing moieties with medicinal benefits. Here, we report a case of a C−N coupling reaction between bromodifluoropropene with heterocyclic amines, such as indole, pyrrole, and imidazole, promoted by an alkali without the use of transition metal catalysis. This reaction differs from existing methods in that it does not undergo a difluoromethylation isomerization reaction but directly retains the structure of the terminal olefin. This chemical conversion process has a wide substrate range, good functional group tolerance, and an ideal reaction conversion rate, making it an effective new method for the difluoropropenation of heterocyclic amines.