AB-INITIO EXAMINATION OF ANOMERIC EFFECTS IN TETRAHYDROPYRANS, 1,3-DIOXANES, AND GLUCOSE

Axial and equatorial structures of 2-methyl-, 2-hydroxy-, 2-methoxy-, 2-amino-, 2-fluoro-, and 2-chlorotetrahydropyran, of the 2-tetrahydrop yranylammonium cation, of 2-methyl-, 2-hydroxy, and 2-methoxy-1,3-diox ane, and of the corresponding cyclohexanes have been fully optimized a t the HF/6-31G level. NBO analysis of the Hartree-Fock wave functions confirms that the anomeric effects of hydroxy-, methoxy-, fluoro-, an d chloropyrans and of glucose and methyl glucoside are indeed due to h yperconjugation. In cyclohexane, tetrahydropyran, and glucose theoreti cal Delta E values involving the OH and OMe substituents are nearly id entical. The experimentally observed differences of about 1 kcal/mol i n the Delta H-0 and Delta G(0) values of the OH and OMe compounds are very likely due to solvent interactions involving the OH group. In the gas phase, glucose orientates its ring hydroxy groups and the CH2OH g roup differently than in the crystal. The structures observed in the c rystal lead to 7.9 kcal/mol higher energies. This might be rationalize d by the fact that the isolated molecule tries to maximize the number of intramolecular hydrogen bonds. 2-Hydroxy-1,3-dioxane prefers an equ atorial conformation. NBO analysis reveals that the exo-anomeric effec t favoring the equatorial form dominates over the endo-anomeric effect in dioxanes. In contrast, 2-methoxy-1,3-dioxane shows an axial prefer ence which is not due to hyperconjugation. The reverse anomeric effect in 2-aminotetrahydropyran is due to steric repulsions because the axi al conformation with the largest hyperconjugation contribution require s one of the NH2 hydrogens to point above the ring. The equatorial pre ference of NH3+ is a result of steric and other (probably electrostati c) contributions, since hyperconjugation strongly favors: the axial co nformation. For all cases for which the hyperconjugation contributions are overcompensated by the Lewis energies, steric repulsions are also indicated by significant ring distortions. Dipole moments correlate w ith relative energies qualitatively in some cases, but a quantitative relationship cannot be ascertained. Single point calculations with Huz inaga basis sets reveal that at the HF/6-31G level axial-equatorial e nergy differences of all compounds considered in this investigation ar e biased toward axial structures by 0.5-1 kcal/mol. Thus, the 6-31G b asis set fails to reproduce the small equatorial preference of 2-fluor ohexane at the HF as well as at correlated levels.