Proton Transfer and Hydrogen Bonding in Glycosylation Reactions

What is it about?

The glycosylation reaction is the central chemical reaction in glycoscience. To date, sufficient mechanistic details to design high yielding stereospecific glycosylation reactions are not known. At a simple level of understanding the reaction resembles nucleophilic displacement reactions in which proton transfer plays little or no role since it happens after the transition state. However, experimental and computational evidence suggests that in some cases proton transfer and its precursor hydrogen bonding can play a role in glycosylation reactions. This evidence is reviewed and an hypothesis is made that the reactions that are SN2 like have early proton transfer whereas reactions that are SN1 like have late proton transfer. Several ideas on how to exploit these mechanistic details to allow for stereospecific glycosylation reactions are presented.

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Why is it important?

This work is aimed at graduate students and postdoctoral fellows who might decide to take up this synthetic challenge and experimentally test the ideas presented in this review.

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