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Radical Reactions of Alkyl 2-Bromo-2,2-difluoroacetates with Vinyl Ethers: “Omitted” Examples and Application for the Synthesis of 3,3-Difluoro-GABA

Author:
Kondratov, Ivan S., Bugera, Maksym Ya., Tolmachova, Nataliya A., Posternak, Ganna G., Daniliuc, Constantin G., Haufe, Günter
Source:
Journal of organic chemistry 2015 v.80 no.24 pp. 12258-12264
ISSN:
1520-6904
Subject:
acidification, alcohols, alkenes, benzene, ethers, fluorine, free radicals, organic chemistry
Abstract:
Addition reactions of perfluoroalkyl radicals to ordinary or polyfluorinated alkenes have been frequently used to synthesize perfluoroalkylated organic compounds. Here ethyl/methyl 2-bromo-2,2-difluoroacetate, diethyl (bromodifluoromethyl)phosphonate, [(bromodifluoromethyl)sulfonyl]benzene, and ethyl 2-bromo-2-fluoroacetate were involved in Na₂S₂O₄-mediated radical additions to vinyl ethers in the presence of alcohols to give difluoro or monofluoroacetyl-substituted acetals or corresponding difluoromethylphosphonate- and (difluoromethylphenyl)sulfonyl-substituted alkyl acetals. This methodology has also been applied as a key step in the synthesis of hitherto unknown 3,3-difluoro-GABA, completing the series of isomeric difluoro GABAs. Comparison of the pKₐ values of 3-fluoro- and 3,3-difluoro-GABA with that of the fluorine free parent compound showed that introduction of each fluorine lead to acidification of both the amino and the carboxyl functions by approximately one unit.
Agid:
5504974