Mechanism of Acid-Catalyzed Anomerization of Methyl D-Glucopyranosides

Article abstract of DOI:10.1021/jo00356a010

The anomerization of methyl D-glucopyranosides catalyzed by D2SO4 in Me2SO/CD3OD solvent was monitored by proton magnetic resonance and by changes in optical rotation.The rate of anomerization was found to be zero order in methanol, yet methanol (or a similar nucleophilic species) was required to effect anomerization.It has been shown that the solvent plays a dominant role in controlling the stereochemistry of reactions at the anomeric carbon; however, the transition-state interactions must be between solvent cage molecules and substrate and are thus solvational forces rather than a more direct nucleophilic participation inside the solvent cage.Evidence is presented supporting the notion that glucoside hydroxyls orient solvent cage molecules to assist attaining a suitable transition-state structure.