Kondratov Ivan S, Bugera Maksym Ya, Tolmachova Nataliya A, Posternak Ganna G, Daniliuc Constantin G, Haufe Günter
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine , Murmanska Str. 1, Kyiv, 02660, Ukraine.
Enamine Ltd , Chervonotkatska Str. 78, Kyiv, 02094, Ukraine.
J Org Chem. 2015 Dec 18;80(24):12258-64. doi: 10.1021/acs.joc.5b02171. Epub 2015 Nov 25.
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.
全氟烷基自由基与普通烯烃或多氟烯烃的加成反应经常用于合成全氟烷基化有机化合物。在此，2-溴-2,2-二氟乙酸乙酯/甲酯、（溴二氟甲基）膦酸二乙酯、[（溴二氟甲基）磺酰基]苯和2-溴-2-氟乙酸乙酯在醇存在下参与了Na2S2O4介导的对乙烯基醚的自由基加成反应，得到二氟或单氟乙酰基取代的缩醛或相应的二氟甲基膦酸酯和（二氟甲基苯基）磺酰基取代的烷基缩醛。该方法还被用作合成迄今未知的3,3-二氟-GABA的关键步骤，从而完成了一系列异构二氟GABA的合成。3-氟-GABA和3,3-二氟-GABA与无氟母体化合物的pKa值比较表明，每个氟的引入导致氨基和羧基官能团的酸性均增加约一个单位。
