Copper‐Catalyzed Deaminative Difluoromethylation

Abstract

AbstractThe difluoromethyl group (CF2H) is considered to be a lipophilic and metabolically stable bioisostere of an amino (NH2) group. Therefore, methods that can rapidly convert an NH2 group into a CF2H group would be of great value to medicinal chemistry. We report herein an efficient Cu‐catalyzed approach for the conversion of alkyl pyridinium salts, which can be readily synthesized from the corresponding alkyl amines, to their alkyl difluoromethane analogues. This method tolerates a broad range of functional groups and can be applied to the late‐stage modification of complex amino‐containing pharmaceuticals.