Predicting the catalytic activity of azolium-based halogen bond donors: an experimentally-verified theoretical study

Abstract

This report demonstrates the successful application of electrostatic surface potential distribution analysis for evaluating the relative catalytic activity of a series of azolium-based halogen bond donors. A strong correlation (<i>R</i>² > 0.97) was observed between the positive electrostatic potential of the σ-hole on the halogen atom and the Gibbs free energy of activation of the model reactions (<i>i.e.</i>, halogen abstraction and carbonyl activation). The predictive ability of the applied approach was confirmed experimentally. It was also determined that the catalytic activity of azolium-based halogen bond donors was generally governed by the structure of the azolium cycle, whereas the substituents on the heterocycle had a limited impact on the activity. Ultimately, this study highlighted four of the most promising azolium halogen bond donors, which are expected to exhibit high catalytic activity.