Tetrakis(dimethylamino)ethylene as a useful reductant of some bromodifluoromethyl heterocycles.: Application to the synthesis of new gem-difluorinated heteroarylated compounds

The cyclic voltammetry of the reductive cleavage of some bromodifluoromethyl heterocycles and of the oxidation of the tetrakis(dimethylamino)ethylene was investigated in N,N-dimethylformamide and acetonitrile, at an inert electrode. The systematic investigation of the kinetics of the electrochemical reduction of this series of bromodifluoromethyl compounds provides clear evidence of a concerted electron-transfer-bond-breaking mechanism. Application of the theory of the dissociative electron transfer allowed the estimation of the carbon-halogen bond dissociation energy and the standard potential of the reaction. On the basis of the electrochemical experiments, the tetrakis(dimethylamino)ethylene (TDAE) was found to be an effective reductant of the 2-(bromodifluoromethyl)benzoxazole (1) and of the 5-(bromodifluoromethyl)-3-phenyl-1,2,4-oxadiazole (4). A stepwise electron transfer with a difluoromethyl radical as intermediate is assumed to take place in this reaction. Under mild conditions, the generated difluoromethyl heterocyclic anion was efficiently trapped with aromatic and heterocyclic aldehydes 7-17 and ketones 18 and 19. In this way, the corresponding beta,beta-difluoro-alpha-heteroarylated alcohols 20-38 were obtained in moderate to good yields and the compounds 20, 21, and 23-27 were tested against the HIV-1 virus.