Pathology

Organic chemistry

Combinatorial chemistry

Reactivity (psychology)

Sulfone

Electrophile

Monosaccharide

Radical

Catalysis

Chemistry

Alternative medicine

Glycosyl

Medicine

Nature Synthesis

Identifying a general bench-stable precursor of multifunctional sugar residues that is also amenable to further activation under mild conditions remains a great challenge in carbohydrate chemistry. Here, we show that heteroaryl glycosyl sulfones undergo desulfonylative cross-coupling with electrophiles in the presence of a Hantzsch ester and a weak base under visible light illumination at ambient temperature. Illumination was found to initiate the reactivity of an in situ-generated Hantzsch ester–base complex, triggering single-electron transfer steps that activate sulfones and afford glycosyl radicals, which are readily utilized for a range of stereocontrolled carbon–carbon and carbon–sulfur bond formations. Importantly, the heteroaryl glycosyl sulfones can be synthesized on a multi-gram scale. Furthermore, this catalyst- and transition metal-free approach enables sulfone donors of various monosaccharides and glycans to be transformed to synthetically valuable glycosides with high stereochemical purity and broad functional group tolerance. This method overcomes previous limitations in scope, scalability and donor instability.                                                                                                        Developing a bench-stable glycosyl donor of multifunctional sugar residues that can be activated under mild conditions is a challenge in carbohydrate chemistry. Now, stable glycosyl sulfones are used in a photoinduced method for desulfonylative cross-coupling to prepare a range of C- and S-glycosides.

Visible light activation enables desulfonylative cross-coupling of glycosyl sulfones