Copper-Catalyzed Stereoselective Borylation and Palladium-Catalyzed Stereospecific Cross-Coupling to Give Aryl C-Glycosides

Metabolically stable C-glycosides are an essential family of compounds in bioactive natural products, therapeutic agents, and biological probes. For their application, development of synthetic methods by connecting glycosides and aglycons with strict stereocontrol at the anomeric carbon, as well as with high functional-group compatibility and environmental compatibility is a pivotal issue. Although Suzuki-Miyaura-type C(sp(3))-C(sp(2)) cross-coupling using glycosyl boronates is a potential candidate for the construction of C-glycosides, neither the cross-coupling itself nor the facile synthesis of the coupling precursor, glycosyl boronates, have been achieved to date. Herein, it was succeeded to develop a copper-catalyzed stereoselective one-step borylation of glycosyl bromides to glycosyl boronates and palladium-catalyzed stereospecific cross-coupling of beta-glycosyl borates with aryl bromides to give aryl beta-C-glycosides, in which the beta-configuration of the anomeric carbon of the glycosyl trifluoroborates is stereoretentively transferred to that of the resulting aryl C-glycosides.

Automated summary

Metabolically stable C-glycosides play a crucial role in bioactive natural products, therapeutic agents, and biological probes. The development of synthetic methods for connecting glycosides and aglycons with strict stereocontrol is essential. In this study, a copper-catalyzed one-step borylation of glycosyl bromides to glycosyl boronates and a palladium-catalyzed cross-coupling of β-glycosyl borates with aryl bromides were successfully achieved, resulting in the synthesis of aryl β-C-glycosides.