Catalyst-Controlled Chemoselective β-Mannosylation of Phenols Via Attractive Noncovalent Interactions

We report the development of chemo- and stereoselective phenolic β-mannosylations catalyzed by precisely tuned bis-thiourea H-bond donors. β-Mannosylation of phenols is demonstrated to occur selectively in the presence of primary and secondary alcohols as well as thiols and thiophenols. Kinetic and computational studies support a mechanism of nucleophile activation promoted by general base-catalysis and enhanced by aromatic interactions between the catalyst and the phenolic substrate. The reactions obey Michaelis-Menten kinetics, and selectivity for glycosylation of phenols over aliphatic alcohols can be ascribed to a combination of stronger binding of the nucleophile to the catalyst and higher reaction rate of the bound complex. In contrast, selectivity of phenols over more acidic thiophenols is achieved exclusively through preferential binding to the catalyst.