A simple method for the synthesis of N -difluoromethylated pyridines and 4-pyridones/quinolones by using BrCF 2 COOEt as the difluoromethylation reagent.

We describe a novel transition metal-free method for the synthesis of N -difluoromethylated pyridines and 4-pyridones/quinolones by using readily available ethyl bromodifluoroacetate as a fluorine source. The formation of N -difluoromethylated pyridines involves a two-step process in which N -alkylation by ethyl bromodifluoroacetate is followed by in situ hydrolysis of the ester and decarboxylation. Besides optimizing the N -difluoromethylation conditions and assessing the influence of steric and electronic effects on the outcome of the reaction, we have synthesized the N -difluoromethylated analogues of two fluorophores and demonstrated that their spectroscopic properties can be improved through replacement of N -CH 3 group by N -CF 2 H.