American Chemical Society
ja9b07022_si_001.pdf (14.37 MB)

Matching Glycosyl Donor Reactivity to Sulfonate Leaving Group Ability Permits SN2 Glycosylations

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journal contribution
posted on 2019-10-09, 16:03 authored by Ming-Hua Zhuo, David J. Wilbur, Eugene E. Kwan, Clay S. Bennett
Here we demonstrate that highly β-selective glycosylation reactions can be achieved when the electronics of a sulfonyl chloride activator and the reactivity of a glycosyl donor hemiacetal are matched. While these reactions are compatible with the acid- and base-sensitive protecting groups that are commonly used in oligosaccharide synthesis, these protecting groups are not relied upon to control selectivity. Instead, β-selectivity arises from the stereoinversion of an α-glycosyl arylsulfonate in an SN2-like mechanism. Our mechanistic proposal is supported by NMR studies, kinetic isotope effect (KIE) measurements, and DFT calculations.