Recently, the research team led by Zhu Feng at the Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, has achieved significant research progress. The related findings have been published in CCS Chemistry under the title: "Photoinduced Cobalt-Catalyzed Reductive Addition of Glycosyl C-Aldehydes: Stereoselective Synthesis of C-Hydroxymethine Glycosides".

Article abstract:

C-Glycosides are widely recognized for their natural abundance and numerous biological activities. Hydroxyme-thine C-glycosides, a relatively underdeveloped subclass of alkyl C-glycosides, inherit the metabolic stability of C-glycosides while retaining the functional versatility of O-glycosides, making them highly appealing for drug design and medicinal chemistry. However, the development of a green, mild, and highly stereoselective method for constructing the -CH(OH)- moiety in hydroxymethine C-glycosides has remained a significant challenge. Herein, we report a photoinduced cobalt-catalyzed asymmetric reductive couplings of glycosyl C-aldehydes and aryl iodides, enabling the efficient synthesis of hydroxymethine C-glycosides in good yields with excellent stereoselectivity (58 examples, up to 99% yield and >20:1 d.r.). This method demonstrates broad functional group tolerance, wide substrate scope, and outstanding diastereos electivity. Remarkably, a simple switch in the chiral ligand's stereoconfiguration allows access to two diastereomers with high efficiency, facilitating rapidconstruction of a sugar library. The synthetic utility of this approach is highlighted by the preparation of diverseanalogs of natural products and pharmaceuticals. Preliminary density functional theory (DFT) calculations provide mechanistic insights into the origins and variations of stereoselectivity. This asymmetric metallaphotoredox strategy offers a versatile platform for hydroxymethine C-glycoside synthesis, advancing the development of sugar-based therapeutic and diagnostic reagents while enriching C(sp3)-glycoside libraries.