New methods of constructing fluorinated organic compounds and their application

This review summarizes several effective synthetic methods of fluorinated organic compounds developed by our group. Two topics have been described in this review. The first topic describes novel fluorinations using diethylaminosulfur trifluoride (DAST). The treatment of tertiary cyclopropyl silyl ethers with DAST caused ring opening and produced allylic fluorides. The reaction of DAST with a tertiary cyclobutanol provided a fluorocyclobutane, a (fluoromethyl)cyclopropane or a homoallylic fluoride. DAST reacted with cyclic ketoximes bearing substituent(s) that can stabilize a carbocation to cause the fluorinative fragmentation which produces fluorinated carbonitrile. The second topic describes the novel syntheses of organic compounds containing the difluoromethylene moiety using fluorinated building blocks. The indium-mediated coupling of aldehydes with 3-bromo-3,3-difluoropropene gives alpha,alpha-difluorohomoallylic alcohols in high yields. alpha,alpha-Difluorohomopropargylic alcohols were also obtained from the indium-mediated coupling of aldehydes with alpha-bromo-alpha,alpha-difluoropropargyl compounds. In the presence of a palladium(0) catalyst, several nucleophiles regioselectively reacted with 3-bromo-3,3-difluoropropene at its gamma-position, and reacted with 1-substituted-3-bromo-3,3-difluoropropenes at their alpha-position. (+)-(R)-1-Amino-2,2-difluorocyclopropane-1-carboxylic acid was synthesized via the lipase-catalyzed asymmetric acetylation of a pro-chiral diol as a key step.