Stereoselectivity of Galactosylation Reactions In Vacuo

Abstract

Controlling the stereoselective outcome of glycosidic bond formation remains a major challenge in chemical synthesis. This process typically proceeds along a complex SN1-SN2 mechanistic continuum. In solution, the key contributions to these mechanisms are difficult to determine due to influence by structural and environmental variables, such as solvents, counterions or temperature. To isolate the intrinsic factors driving steroselectivity in glycosylations, we investigate the reactions for the monosaccharide galactose in the gas phase. We perform ion–molecule galactosylation reactions in complete isolation inside an ion trap of a mass spectrometer and directly probe the stereochemistry of the formed products using mass-resolved ultraviolet cold ion spectroscopy. The results show that α-selectivity is significantly weaker in the gas phase than in solution, and that the product stereochemistry might be influenced by the nucleophile’s electron density rather than its overall nucleophilic strength.