New methods of constructing fluorinated organic compounds and their application

This review summarizes several effective synthetic methods of fluorinated o rganic compounds developed by our group. Two topics have been described in this review. The first topic describes novel fluorinations using diethylami nosulfur trifluoride (DAST). The treatment of tertiary cyclopropyl silyl et hers with DAST caused ring opening and produced allylic fluorides. The reac tion of DAST with a tertiary cyclobutanol provided a fluorocyclobutane, a ( fluoromethyl)cyclopropane or a homoallylic fluoride. DAST reacted with cycl ic ketoximes bearing substituent(s) that can stabilize a carbocation to cau se the fluorinative fragmentation which produces fluorinated carbonitrile. The second topic describes the novel syntheses of organic compounds contain ing the difluoromethylene moiety using fluorinated building blocks. The ind ium-mediated coupling of aldehydes with 3-bromo-3,3-difluoropropene gives a lpha,alpha-difluorohomoallylic alcohols in high yields. alpha,alpha-Difluor ohomopropargylic alcohols were also obtained from the indium-mediated coupl ing of aldehydes with alpha-bromo-alpha,alpha-difluoropropargyl compounds. In the presence of a palladium(0) catalyst, several nucleophiles regioselec tively reacted with 3-bromo-3,3-difluoropropene at its gamma-position, and reacted with 1-substituted-3-bromo-3,3-difluoropropenes at their alpha-posi tion. (+)-(R)-1-Amino-2,2-difluorocyclopropane-1-carboxylic acid was synthe sized via the lipase-catalyzed asymmetric acetylation of a pro-chiral diol as a key step.