Cyclobutyl-Containing Rigid Analogues of Threonine: Synthesis and Physical Chemical Properties

Hitherto unknown <i>cis</i>- and <i>trans</i>-1-amino-3-hydroxy-3-methylcyclobutanecarboxylic acids were synthesized in multigram scale. The obtained compounds can be considered as achiral conformationally restricted analogues of threonine with fixed spatial orientation of functional groups. p<i>K</i>_a values are noticeably different for both amino acids. According to the X-ray data the cyclobutane rings in both compounds are almost planar (the corresponding torsion angles are below 7°)

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

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 p<i>K</i>_a 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

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

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 p<i>K</i>_a 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

“Reported, but Still Unknown.” A Closer Look into 3,4-Bis- and 3,4,5-Tris(trifluoromethyl)pyrazoles

Straightforward practical synthetic approaches to 3,4-bis- and 3,4,5-tris­(trifluoromethyl)­pyrazoles have been developed. The key step of the both syntheses is a transformation of the carboxylic group in a pyrazole core into the trifluoromethyl group by sulfur tetrafluoride. The elaborated synthetic protocols allow gram-scale preparation of the target products. The obtained compounds are comprehensively characterized by means of crystallographic analysis, determination of p<i>K</i>_a values and fluorescence measurements