Synthesis of α,α-Difluoro-Functionalized Ketones

摘要

In the presence of a catalytic amount of tetrakis(triphenylphosphine) palladium [Pd(PPh_3)_4], 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℃. 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(PPh_3)_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(PPh_3)_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-difluoro ketones 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-difluoro-functionalized ketones.