Tetrakis(dimethylamino)ethylene as a Useful Reductant of Some Bromodifluoromethyl Heterocycles. Application to the Synthesis of New gem-Difluorinated Heteroarylated Compounds

• Published in: Journal of organic chemistry 1998-08, Vol.63 (16), p.5385-5394
• Main Authors: Burkholder, Conrad, Dolbier, William R, Médebielle, Maurice
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo980201+

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 β,β-difluoro-α-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.