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

The synthesis of a series of chlorodifluoromethylated 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 γ,γ-difluoroalkyl radical. Aromatic nucleophilic substitution of α,α-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.