Affiliation:
1. Enamine Ltd. (http://www.enamine.net) Winston Churchill Street 78 Kyїv 02094 Ukraine
2. Taras Shevchenko National University of Kyiv Volodymyrska Street 60 Kyїv 01601 Ukraine
3. Institute of Organic Chemistry National Academy of Sciences of Ukraine Akademik Kukhar Street 5 Kyїv 02094 Ukraine
Abstract
AbstractMultigram synthesis of 3‐fluorinated cyclobutane building blocks has been disclosed. The proposed synthetic schemes were based on nucleophilic fluorination and eventually led to 3‐fluorocyclocutanecarboxylic acid as a key target compound and intermediate. Further functional group transformations provided monofluorinated cyclobutane‐derived alcohols, amines, bromides, thiols, sulfonyl chlorides, etc. Furthermore, the synthesis of diastereopure cis‐ and trans‐isomeric 2‐ and 3‐fluorocyclobutanecarboxylic acids and amines was also performed. In both cases, diastereomer separation was used to obtain pure stereoisomers. The effect of the fluorine position and relative spatial orientation on the physicochemical properties of the corresponding monoflurinated derivatives was studied by measurements of pKa and logP values.