Copper-Catalyzed Deaminative Difluoromethylation

The 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 NH(2)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.