Noncovalent interactions: An emerging focal point in stereoselective catalytic carbohydrate synthesis

Abstract

The incorporation of frontier synthetic concepts into stereoselective carbohydrate synthesis is gaining significant traction. In the last five years, there are increasing reports documenting that the consideration of weak non-covalent interactions (NCIs) constitutes a vital factor in steering the anomeric and site-selectivity, as well as in activating difficult glycosylations. In light of blossoming developments on this front, we present a brief overview of recent case studies that involve the harnessing of hydrogen bonding (HB), halogen bonding (XB), chalcogen bonding (ChB) and π-interactions. These NCIs represent a considerable palette of classical/non-classical weak interactions that is of current interest to the broad synthesis community. Significantly, a close mechanistic analysis often revealed that NCIs were instrumental in dictating the final stereoselectivity outcome of many glycosylation pathways. We are optimistic that by expanding the focal point from purely glycosyl substrate modifications towards tweaking catalytic NCIs at the supramolecular level of chemical glycosylations, this emerging concept offers new levers of stereoselectivity control beyond classical stereoelectronic and steric considerations.