Stereoelectronic Effects in Glycosylation Reactions

(Stereo)electronic effects dictate the outcome of a glycosylation reaction. This article documents how these effects impact the properties, reactivity, and structure of the donor, reactive intermediates, and acceptor glycosides. It is discussed how the reactivity of carbohydrate donors can be tuned through the protection groups, allowing the development of reactivity-based one-pot glycosylation strategies. The activation of the donor glycoside leads to the formation of an array of reactive intermediates, which have glycosyl cation-like characteristics. We will cover the stability, selectivity, and shape of these reactive intermediates. Finally, the reactivity of carbohydrate acceptors is examined. Similar to the reactivity of glycosyl donors, the nucleophilicity of carbohydrate hydroxyl groups can be modulated by the choice of protecting groups. The increasing insight in the complete spectrum of (stereo)electronic effects at play in the glycosylation reaction will eventually enable us to fully understand and predict the outcome of glycosylation reactions.