Interpretation of anomeric effect in 2-hydroxytetrahydropyrans based on extensive bond interactions

Abstract

Recently, exchange repulsion and electron delocalization have been a focus of attention as the origin of the anomeric effect. However, the details of these interactions remain unclear. In this study, to elucidate what exchange repulsion and electron delocalization contribute to anomer stabilities of 2-hydroxytetrahydropyran (2-hydroxy-THP), the electronic structures of the anomers were investigated using bond model analysis. The vicinal bond interactions around the anomeric carbon make the equatorial configuration of the hydroxy group more stable than the axial configuration. Exchange repulsions contribute much to this relative stability of the equatorial configuration. However, exchange repulsion and electron delocalization due to 1,3-diaxial interactions and other interactions involving lone pair electrons of oxygen make the axial configuration more stable overall than the equatorial configuration. The anomeric effect in glucose can also be explained in a manner similar to that in 2-hydroxy-THP. Additionally, interactions between the vicinal hydroxy groups contribute to the stabilization of the axial configuration.