Synthesis and Physical-Chemical Properties of cis- and trans-1-Amino-3-fluoro-3-methylcyclobutanecarboxylic Acids

• Published in: European journal of organic chemistry Vol. 2016; no. 28; pp. 4782 - 4786
• Main Authors: Chernykh, Anton V., Feskov, Illia O., Chernykh, Alla V., Kondratov, Ivan S., Tolmachova, Nataliya, Radchenko, Dmytro S., Daniliuc, Constantin G., Haufe, Günter
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 01.10.2016; Wiley; Wiley Subscription Services, Inc
• Subjects: Acids; Amino acids; Chemistry; Chemistry, Organic; Cyclobutane; Diastereoisomers; Fluorine; Physical Sciences; Science & Technology; X-ray diffraction; ASYMMETRIC-SYNTHESIS; TRIFLUOROMETHYL; Fluorine; STABILITY; Diastereoisomers; X-ray diffraction; Amino acids; INHIBITION; PEPTIDES; F-19 NMR; Cyclobutane; STEREOSELECTIVE-SYNTHESIS; PET; FLUORINATED AMINO-ACIDS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201600953

Hitherto unknown cis‐ and trans‐1‐amino‐3‐fluoro‐3‐methylcyclobutanecarboxylic acids were synthesized as pure diastereomers starting from diisopropyl 3‐oxocyclobutane‐1,1‐dicarboxylate. While pKa values of the carboxylic acid functions are the same for both stereoisomers (pKa = 2.80), the values for the amino groups are slightly different (8.46 or 8.77, respectively) presumably because of different interactions with the fluorine atoms. Fluorinated as well as sterically constrained analogues of natural α‐amino acids attract widespread attention. This work combines both aspects and provides synthesis and physical‐chemical data of the title compounds, which are most interesting for organic and medicinal chemists working on drug design.