A simple method for the synthesis ofN-difluoromethylated pyridines and 4-pyridones/quinolones by using BrCF2COOEt as the difluoromethylation reagent

We describe a novel transition metal-free method for the synthesis ofN-difluoromethylated pyridines and 4-pyridones/quinolones by using readily available ethyl bromodifluoroacetate as a fluorine source. The formation ofN-difluoromethylated pyridines involves a two-step process in whichN-alkylation by ethyl bromodifluoroacetate is followed byin situhydrolysis of the ester and decarboxylation. Besides optimizing theN-difluoromethylation conditions and assessing the influence of steric and electronic effects on the outcome of the reaction, we have synthesized theN-difluoromethylated analogues of two fluorophores and demonstrated that their spectroscopic properties can be improved through replacement ofN-CH(3)group byN-CF2H.