Effect of 2‑<i>O</i>‑Benzoyl para-Substituents on Glycosylation Rates

Abstract

From a series of competition experiments, we have explored the degree to which various para-substituents (CN, Br, H, OMe, pyrrolidino) of a 2-<i>O</i>-benzoyl functionalized glucosyl donor of the thioglycoside type affect the rate of glycosylation under <i>N</i>-iodosuccinimide/triflic acid activation. As expected, electron-withdrawing groups were found to decrease the rate of glycosylation, whereas electron-donating groups resulted in the opposite outcome, underscoring the influence on the reaction rate exerted by a participating group. On this basis, a Hammett linear free-energy relationship was established (<i>R</i>² = 0.979, ρ = 0.6), offering fundamental insight into the magnitude of anchimeric assistance in glycosylation chemistry