Protecting-Group-Free and Minimally Protected Glycosylation: Recent Advances Toward Direct Glycosidic Bond Formation

Protecting-group-free glycosylation reduces the steps needed to convert native sugars into glycosides, but selectivity and product isolation remain major limits. This review examines methods published mainly from 2024 to August 2026. It compares donor preparation, activation conditions, linkage scope and stereochemical control. Glycosyl sulfonyl hydrazides can be prepared directly from reducing sugars and used in nickel-mediated arylation or copper-mediated C-, S- and Se-glycosylation. These donors can be isolated in large quantities by crystallization, but coupling often requires chromatography and high catalyst or reagent loadings. Ligand choice can give access to both anomers, although some methods require temporary hydroxyl protection. Photochemical thioglycoside activation, aqueous S-glycosylation and direct anomeric activation provide routes to other products. Selected examples are compared by reaction scale, isolated yield, purification and protection requirements. The comparison shows how simpler donor preparation can shorten a synthesis and why selectivity, reagent use and product isolation still affect method choice.