Organocatalytic strategy for hydrophenolation of gem-difluoroalkenes

Gem-difluoroalkenes are an easily accessed fluorinated functional group, and a useful intermediate for elaborating into more complex fluorinated compounds. Currently, most functionalization reactions of gem-difluoroalkenes, with or without a transition metal-based catalyst system, involve the addition or removal of a fluorine atom to generate trifluorinated or monofluorinated products, respectively. In contrast, we present a complementary “fluorine-retentive” reaction that exploits an organocatalytic strategy to add phenols across gem-difluoroalkenes to deliver β,β-difluorophenethyl arylethers. The products are produced in good to moderate yields and selectivities, thus providing a range of compounds that are underrepresented in the synthetic and medicinal chemistry literature.     

Nucleophilic (phenylsulfonyl)difluoromethylation of alkyl halides using PhSO2CF2SiMe3: preparation of gem-difluoroalkenes and trifluoromethyl compounds

Nucleophilic (phenylsulfonyl)difluoromethylation of both alkyl iodides and bromides was successfully accomplished by using CsF/15-crown-5 as an initiating system in DME, and the amount of 15-crown-5 was found to be critical to the yield of the product. The prepared (phenylsulfonyl)difluoromethylated alkanes were converted into gem-difluoroalkenes by a base-mediated 1,2-elimination reaction, and the latter species could be further transformed into trifluoromethyl compounds in the presence of KF/18-crown-6 or TBAF.