Solvent microstructure effect on reaction stereochemistry; ring opening of chalcone oxides

Abstract

The stereochemistry and kinetics of acid-catalysed ring-opening reactions of epoxides are reported. Predominant inversion is found in the usual hydroxylic solvents. As the nucleophilicity of the solvent diminishes and acidity increases, the stereochemistry changes to predominant retention. Electron-donating substituents also tend to favour retention. In mixed solvents, the solvent microstructure is altered, leading to net retention for nucleophiles such as methanol. The exception is dioxane–methanol, which gives enhanced inversion. Molecular mechanics calculations indicate an electrostatic preference for the retention route, but a steric preference for inversion. The activation parameters indicate a negative entropy for both inversion and retention paths. Possible reasons are discussed for the entropy of the retention route being in the range normally found for A2 reactions.