Electrochemically induced free-radical tandem cyclisation of chlorodifluoromethylated ketones Application to the synthesis of gem-difluorinated heterocycles

The synthesis of a series of chlorodiffuoromethylated ketones 1-6 is presented and the cyclic voltammetry of the reductive cleavage of these ketones was investigated, in N,N-dimethylformamide (DMF), at an inert electrode. Indirect electrochemical reduction (by means of an electrogenerated anion radical) in acetonitrile (CH3CN) or in N,N-dimethylformamide (DMF), of the naphthalene-derived chlorodifluoroacetylated compounds 1 and 2 in the presence of the olefinic substrates 7-10, yields new gem-difluoro heterocyclic compounds 11-16 after intramolecular cyclisation of a gamma,gamma -difluoroalkyl radical. Aromatic nucleophilic substitution of alpha,alpha -difluoroketones 12 and 13, in anhydrous dimethylsulfoxide, with several tetramethylammonium salts of imidazole as nucleophiles, proceeds under mild conditions to give the corresponding nitrogen-nitrogen exchanged products 17-23 in moderate to good yields. (C) 2001 Elsevier Science B.V. All rights reserved.