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.
The possibility of deoxofluorination of β-keto esters using SF4 was investigated. The scope and limitation of the reaction were determined. The efficient method for the synthesis of β,β-difluorocarboxylic acids was elaborated based on the reaction. The set of mentioned acids, being the perspective building blocks for medicinal chemistry, were synthesized on multigram scale. The safety of SF4 use was discussed. The described method does not improve upon the safety of using SF4, but practical recommendations for working with the reagent are proposed. Despite the hazards of using toxic SF4, a significant increase of efficacy in the synthesis of medicinal-chemistry-relevant building blocks, based on the reaction, in comparison with earlier described approaches is shown.
Diverse trifluoromethyl-substituted
compounds were synthesized
by deoxofluorination of cinnamic and (hetero)aromatic carboxylic acids
with sulfur tetrafluoride. The obtained products were used as starting
materials in the preparation of novel fluorinated amino acids, anilines,
and aliphatic amines - valuable building blocks for medicinal chemistry
and agrochemistry.
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