Synthesis of γ-(Electron-withdrawing group)-Substituted α,α-Difluoro Ketones by UV-Initiated Addition of Iododifluoromethyl Ketones with Electron-Deficient Alkenes

Article abstract of DOI:10.1021/jo00126a032

Under UV irradiation (254 nm), iododifluoromethyl phenyl, alkyl, and chlorodifluoromethyl ketones were reacted with a series of alkyl acrylates (CH2=CHCO2R', R': Et, n-Bu, t-Bu, and Me), N,N-dimethylacrylamide, acrylonitrile, and vinyl methyl ketone in the absence of solvent at ambient temperature.High yields of the corresponding 1:1 addition products were obtained when 1 reacted with ethyl acrylates (50-79percent).The reaction of 1a with n-butyl acrylate gave a similar 1:1 adduct (51percent).However, an addition-reduction product, PhC(O)CF2CH2CH2CO2H, was isolated in 44percent yield when tert-butyl acrylate was reacted wit 1a.More interestingly, both 1:1 and 1:2 adducts were formed in a 1.3:1 ratio when 1a was reacted with methyl acrylate under similar conditions, which indicated that the ester group exhibited an important effect on reaction selectivity.In the reaction with 1a, ethyl and methyl acrylates also displayed significantly higher reactivity than that of n- or tert-butyl acrylates. 1 also reacted with N,N-dimethylacrylamide to afford high yields of the 1:1 adducts.However, telomeric products were obtained in the reaction of 1a with acrylonitrile, and the 1:1 and pure 1:2 addition products were isolated in low yield.The reaction of acrylonitrile with alkyl-substituted iododifluoromethyl ketone, 1b, gave only the reduced product, n-C4H9C(O)CF2H, under similar conditions.With vinyl methyl ketone, the reaction of 1a produced an addition-reduction product, PhC(O)CF2CH2CH2C(O)Me, in 50percent yield.The reactivity of RC(O)CF2I (1) varied with the substituted R groups in the reaction with ethyl acrylate and N,N-dimethylacrylamide: R, ClCF2 > Ph > n-C4H9 > n-C6H13.Correspondingly, the reaction of 1a with ethyl acrylate generated a polymer in the presence of a catalytic amount of tetrakis(triphenylphosphine)palladium.Treatment of the adducts with zinc in the presence of a catalytic amount of NiCl2*6H2O in moist THF afforded the corresponding γ-(electron-withdrawing group)-substituted α,α-difluoro ketones in high yields.