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
SN2 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.