Ab initio molecular orbital calculation of carbohydrate model compounds .6. The gauche effect and conformations of the hydroxymethyl and methoxymethyl groups

Conformational properties and the gauche effect of the two functional groups, hydroxymethyl and methoxymethyl, in hexopyranosides have been studied with nb initio methods using the methyl 2,3,4-trideoxy-alpha-D-glycero-hexopyranoside (1), methyl 2,3,4-trideoxy-beta-D-glycero-hexopyranoside (2), methyl 6-O-methyl-2,3,4-trideoxy-alpha-D-glycero-hexopyranoside (3), and methyl 6-O-methyl-2,3,4-trideoxy-beta-D-glycero-hexopyranoside (4) as models. The geometry of the conformers around the C5-C6 bond for the methyl 2,3,4-trideoxy-D-glycero-hexopyranosides was determined by gradient optimization at the SCF level using the 6-31G*, 6-31+G*, and 6-311++G** basis sets. The optimized geometries were used to calculate the energy of the gauche-trans (gt), trans-gauche (tg), and gauche-gauche (gg) conformers with the 6-31G*:, 6-31+G* 6-31fG**, 6-31G**, 6-311G*, and 6-311++G** basis sets, Electron correlation effects were accounted for at the second-order Moller-Plesset perturbation (MP2) level using the 6-31G* basis set and using the adiabatic connection method (ACM) of density functional theory (DFT) using standard 6-31G*, dzvp, and cc-pvtz basis sets. Solvent effects on the stability of conformers were evaluated using a continuum model. At all levels of theory, 1 and 2 prefer the gauche over the trans conformers around the C5-C6 bond. This preference is due to internal hydrogen bonding which is possible in the gg(sc) and gt(-sc) conformers. Solvent effects decrease this preference by similar to 0.9 kcal/mol. Methylation of the oxygen of the C6 hydroxyl completely reversed the relative energy of conformers, such that in 3 and 4, the trans conformer is favored. The trans preference is decreased by solvent which stabilized the gauche conformers by 0.7-1.3 kcal/mol with respect to the trans. These results suggest that the gauche preference of the hydroxymethyl group in 1 and 2, is due to the presence of hydrogen bonding and not due to the gauche effect.