Synthesis and pKa values of 2-(3- and 4-pentafluorosulfanylphenyl)-2-fluorocyclopropylamines

Abstract

Starting from 3- and 4-pentafluorosulfanylbenzaldehydes, a series of cis- and trans-2-aryl-2-fluorocyclopropylamines bearing an SF5 group in 3- or 4-position of the aryl ring were synthesized in 7 steps via the corresponding cyclopropanecarboxylic acids. While the pKa values of the carboxylic acids are very little depending on the stereochemistry at the cyclopropane ring and the regiochemistry of the SF5-substituents in the aryl ring, the pKa of the corresponding 2-fluorocyclopropylamines is strongly dependent on the stereochemistry at the three-membered ring due to hyperconjugative effects of the CF and the CN bonds. Again, the regiochemistry of SF5 substitution in the phenyl ring has almost no influence.