Halogen-bond-assisted radical activation of glycosyl donors enables mild and stereoconvergent 1,2-cis-glycosylation

The chemistry of carbohydrates has a history of over 100 years, but simple, stereoselective and efficient glycosylation methods remain highly needed to facilitate the studies of sugars in various disciplines. Here we report a strategy for 1,2-cis-glycosylation without using metals, strong (Lewis) acids, elaborate catalysts or labile substrates. Our method operates by a unique mechanism: it activates glycosyl donors through a radical cascade rather than the conventional acid-promoted, ionic process. As elucidated by computational and experimental studies, the ally! glycosyl sulfones (as donors) form halogen bond complexes with perfluoroalkyl iodides, which-merely by visible light irradiation-fragment via radical intermediates to give the electrophilic glycosyl iodides. In situ trapping by various nucleophiles affords, in a stereoconvergent manner, the challenging 1,2-cis-glycosides. This metal- and acid-free reaction shows remarkable tolerance to functional groups. The high stereoselectivity holds for a broad array of donors. This study suggests that the simple C2-alkoxy group can serve as an effective directing group for building 1,2-cis-glycosidic bonds.

Automated summary

The chemistry of carbohydrates has a long history, and a simple, stereoselective and efficient glycosylation method is still needed for studying sugars. This study presents a strategy for 1,2-cis-glycosylation without using metals or strong acids. The method activates glycosyl donors through a radical cascade, resulting in the formation of 1,2-cis-glycosides with high stereoselectivity. The reaction shows remarkable tolerance to functional groups and is applicable to a broad range of donors.