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

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

Remote Electronic Effects by Ether Protecting Groups Fine-Tune Glycosyl Donor Reactivity

It was established that <i>para</i>-substituted benzyl ether protecting groups affect the reactivity of glycosyl donors of the thioglycoside type with the <i>N</i>-iodosuccinimide/triflic acid promoter system. Having electron donating <i>p</i>-methoxybenzyl ether (PMB) groups increased the reactivity of the donor in comparison to having electron withdrawing <i>p</i>-chloro (PClB) or <i>p</i>-cyanobenzyl ether (PCNB) protecting groups, which decreased the reactivity of the glycosyl donor relative to the parent benzyl ether (Bn) protected glycosyl donor. These findings were used to perform the first armed-disarmed coupling between two benzylated glucosyl donors by tuning their reactivity. In addition, the present work describes a highly efficient palladium catalyzed multiple cyanation and methoxylation of <i>p</i>-chlorobenzyl protected thioglycosides. The results of this paper regarding both the different electron withdrawing properties of various benzyl ethers and the efficient and multiple protecting group transformations are applicable in general organic chemistry and not restricted to carbohydrate chemistry