Synthesis of α-Halo-α,α-difluoromethyl Ketones by a Trifluoroacetate Release/Halogenation Protocol

Abstract

Three series of α-halo-α,α-difluoromethyl ketones are prepared from highly α-fluorinated gem-diols by exploiting the facile release of trifluoroacetate, followed by immediate trapping of the liberated α,α-difluoroenolate with an electrophilic chlorine, bromine, or iodine source. The products are typically isolated in good yields, even in the case of sensitive, α-iodo-α,α-difluoromethyl ketones. Also, we demonstrate that an α-iodo-α,α-difluoromethyl ketone will participate in a copper-promoted reaction to forge a new carbon-carbon bond.