Direct deoxygenative arylation of saccharides via phosphorus-assisted C-OH bond activation.

Abstract

Aryl C-glycosides are privileged scaffolds in drug discovery, biochemical research, and materials science. Established methods for their synthesis typically involve radical cross-coupling of saccharides. However, the glycosyl donors required in these methods encounter longstanding challenges, including instability and the need for prefunctionalization at the anomeric position. Herein, we report a highly efficient radical cross-coupling approach in which the native hydroxyl group on saccharides is activated in situ by a phosphorus reagent, enabling C - C bond formation with aryl iodides to afford a broad range of aryl C-glycosides. A combination of Zn and I₂ is developed for initiating the key β-scission step. Importantly, the glycosyl donors are bench-stable and readily available, addressing the issues associated with previous donors. Furthermore, this method offers an attractive strategy for the direct synthesis of drug-sugar conjugates and therapeutic agents. Mechanistic experiments and density functional theory (DFT) calculations provide strong support for the proposed reaction mechanism.