Synergistic catalysis: Unlocking site-selective functionalization of carbohydrate hydroxyl groups for advanced glycoscience

Abstract

Selective functionalization of carbohydrate hydroxyl groups is challenging due to their abundance and similar reactivity. Synergistic catalysis—using multiple catalysts to activate different substrates—offers a promising solution, outperforming traditional single-catalyst approaches. This review presents recent advances in synergistic systems employing transition metals, chiral ligands, and organoboron compounds to achieve regio-, stereo-, and enantioselective transformations. These methods enable the construction of glycosidic linkages and carbohydrate mimics with potential biological activity. The role of non-covalent interactions, dynamic kinetic resolution, and computational tools in guiding selectivity is also discussed. Emphasis is placed on reaction efficiency, sustainability, and scalability, alongside persistent challenges such as hydroxyl differentiation, catalyst compatibility, and system optimization. Future directions include developing novel catalytic platforms, integrating computational design, and adopting greener methodologies to expand access to carbohydrate-based molecules with valuable functional properties.