Fluoroalkyl-Substituted Cyclopropane Derivatives: Synthesis and Physicochemical Properties

A series of all 12 cis- and trans-cyclopropanecarboxylic acids and cyclopropylamines bearing CH2F, CHF2, and CF3 substituents were synthesized by different methods on a multigram scale. Dissociation constants (pKa) and log P values were measured for the obtained compounds or their derivatives to evaluate the influence of the type and relative position of fluoroalkyl substituents on the acidity and lipophilicity of monofunctionalized cyclopropanes. An analysis of the selected products by X-ray crystallography was carried out to obtain a better insight into the observed differences in physicochemical properties.