Photocatalytic deoxygenative functionalization of the anomeric position of carbohydrates

In recent decades, photocatalysis has gained significant traction, as light-driven activation of substrates enables unconventional pathways, in particular radical chemistry, under mild conditions. This approach has proven especially powerful in carbohydrate chemistry, where it has addressed longstanding challenges in functionalization, unlocking novel reactivities and streamlining the synthesis of high-value intermediates. Inspired by MacMillan’s work on metallaphotoredox deoxygenative arylation of alcohols, we developed an α-aryl glycoside synthesis via in situ generation of glycosyl radicals. This is achieved through N-heterocyclic carbene activation and subsequent homolytic cleavage of the hydroxy group and a cross-coupling with aryl bromides of the newly formed radical, using a dual catalytic system involving a nickel species and a donor-acceptor cyanoarene photocatalyst, replacing the iridium catalyst of the original protocol. Additionally, inspired by Wendlandt and co-workers’ approach to sugar epimerization, we further adapted the method by incorporating a synergistic HAT-photocatalytic step. This enabled hydroxy-to-hydrogen substitution, a formal deoxygenation which may potentially represent an alternative to the stannane-based Barton-McCombie reaction. The reaction proved effective on both sugar and general alcohol substrates.