THE ANOMERIC AND EXOANOMERIC EFFECTS OF A HYDROXYL GROUP AND THE STEREOCHEMISTRY OF THE HEMIACETAL LINKAGE

The conformational properties and the anomeric and exo-anomeric effect s of the hydroxyl group linked to the anomeric carbon in aldopyranoses have been studied with ab initio methods using 2-hydroxytetrahydropyr an (1) as a model. The potential of rotation around the hemiacetal ano meric C-O bond has been calculated with the 6-31G and 6-311 + + G**// 6-31G basis sets. The ab initio geometry and energy of the conformers have been determined by gradient optimization at various levels of th e Hartree-Fock and density functional theory (DFT). Vibrational freque ncies were calculated at the 6-31G level and used to evaluate zero-po int energies, thermal energies, and entropies for minima. Solvent effe cts on the stability of conformers were estimated using the continuum model. At all levels of theory, and contrary to the result on 2-methox ytetrahydropyran (2), three minima were found on the rotation curves a round the C1-O1 bond for both anomers of 1. Variations in calculated v alence geometries for compounds display structural changes distinctive for the anomeric and exo-anomeric effects. The calculations predict t he axial form of 1 as the preferred anomer in vacuum. Solvent effects change the equilibrium and the equatorial form is favored in aqueous s olution. The calculated energy differences are in agreement with the e xperimental data on 2-hydroxytetrahydropyran. The magnitude of the ano meric effect for the hydroxyl group was estimated to be 2.0 kcal/mol. The hydroxyl group in the axial and equatorial position exhibits the e xo-anomeric effect of 2.3 and 2.9 kcal/mol, respectively. (C) 1998 Els evier Science Ltd. All rights reserved.