Exploring the mechanism of neighboring group assisted glycosylation reactions

Glycosyl donors based on the 2,6-di-O-acyl-3,4-O-isopropylidene-D-galactopyranosyl-(leaving group) structure have been shown experimentally to have a high propensity for giving acyl transfer to the alcohol nucleophile as major side products in the glycosylation reaction. The corresponding cations of these relatively rigid glycosyl donors were investigated by density functional methods. The precursor cations resulting from neighboring group assistance from the 2-O-acyl group were found to be the most stable. The nucleophile methanol most favorably approaches the LUMO of such cations on the former carbonyl carbon. The resulting stable intermediate has a long C-O bond of 2.79 Angstrom. It is suggested that such intermediates can lead to both acyl transfer and beta-glycoside after passing through at least one further transition state.