Anion-Assisted Glycosylation of Galactose: A Computational Study

Glycosylation reactions and their chemistry are a field of significant contemporary importance. In this paper, a β-selective glycosylation reaction assisted by 2,6-di-tert-butylpyridinium tetrafluoroborate was experimentally performed, and its mechanism was computationally explained. Calculations showed that the first step of the reaction - substitution - goes through an S_N2 mechanism and is the rate-determining step. Conformational analysis and transition state modeling showed that the substitution is catalyzed by the BF₄^- anion, while the cation does not participate. iPrOH and trichloroacetamide (TCA) present in solution can significantly decrease the energy of the substitution step. This knowledge has then been applied to two saccharide glycosylation reactions described previously by other research groups, where the calculated reaction barriers were found to be too high for the experimental conditions given. Taking activators into account in the system in both cases allowed us to find transition states with significantly lower energy, which better correspond to stated experimental conditions.