Synthesis of α,α-Difluoro-Functionalized Ketones

Article abstract of DOI:10.1021/jo00122a044

In the presence of a catalytic amount of tetrakis(triphenylphosphine)palladium , iododifluoromethyl alkyl and phenyl ketones 1 react with alkenes to give the corresponding α,α-difluoro-γ-iodo ketones in high yields at room temperature either neat or in hexane at 60 deg C.A variety of functional groups, such as alkyl, trimethylsilyl, hydroxy, epoxy, ketone, and ester, are tolerated under the reaction conditions.The reaction can be completely suppressed by a radical inhibitor, di-tert-butyl nitroxide or hydroquinone.A ring closure reaction occurs when 1 reacts with diethyl diallylmalonate in the presence of a catalytic amount of Pd(PPh3)4.Under UV irradiation, the reaction of 1 with diallyl ether gives a tetrahydrofuran derivative.All these results are consistent with a radical chain mechanism initiated by single electron transfer from Pd(PPh3)4 to 1.In the presence of a catalytic amount of nickel dichloride hexahydrate, the iodine in the 1:1 addition adducts is readily reduced by zinc in moist THF under mild conditions to give the corresponding α,α-difluoro ketones in high yields.A one-pot addition-reduction reaction has been developed for the synthesis of α,α-difluoroketones without the isolation of the 1:1 addition adducts, which provides a new, efficient, and practical method for the preparation of a variety of α,α-difluorofunctionalized ketones.