Abstract

Whereas highly practical chemical methods for the synthesis of polypeptides and polynucleotides are well established and in common use, glycan synthesis remains a challenging endeavor largely reserved for specialists in sugar chemistry. Glycosylation reactions are fundamentally challenging relative to peptide and nucleotide couplings, which involve non-stereogenic linkages that are not strongly affected by the identity of the specific reacting partners. Carbohydrate couplings engage highly variable, stereochemically complex, and densely functionalized reacting partners, while generating a new stereocenter in the glycosidic linkage. Glycosylation methods that can be applied easily and broadly would be greatly enabling to research concerning the role of sugars in biological chemistry and medicine. Recent developments in transition-metal catalysis and organocatalysis have enabled selective glycosylation reactions with catalyst-controlled stereo- and site selectivity, making headway toward the longstanding goal of achieving generality in chemical glycosylation. This chapter highlights seminal examples of catalyst control in glycosylation, focusing on cases wherein catalyst structure and electronics play a demonstrated role in the stereochemical outcome of a glycosylation reaction.