Regio- and stereochemical behavior of cyclooctane and cyclodecane derivatives containing CF2 moieties

Abstract

Cyclooctane and cyclodecane are important medium-size rings in organic chemistry, and fluorination can significantly modulate the properties of organic molecules, such as polarity, viscosity, and acidity. In this quantum-chemical study, two CF₂ groups replaced the methylene moieties of the most stable conformations of cyclooctane (boat-chair) and cyclodecane (boat-chair-boat) to evaluate the effect of head, corner, and edge substitution on the energetics of the possible structures, including both constitutional and stereochemical-type isomers. It was found that CF₂ groups prefer to occupy head (at C5) and corner positions of the cyclooctane ring rather than head (at C1) and edge positions, as these latter positions orient the fluorines endo, causing transannular repulsion. However, the 2,7 isomer, which possesses an edge CF₂ group, is remarkably stable due to an unprecedented transannular hydrogen bond between hydrogen at C3 and the CF₂ at C7. Similar findings were obtained for the cyclodecane derivatives, indicating that fluorination is preferable in certain positions due to steric and strain relief, while the transannular hydrogen bond also plays a secondary role as a source of stabilization. Given the CF₂ groups' ability to order the conformation of these medium-size rings, fluorination may be utilized in systems where this property is required, such as in liquid crystals.