| C-glycosides have been considered as an ideal alternative to O-glycosides due to their excellent metabolic stability.In contrast to the lengthy functional group conversion step in conventional methods,this work develops a strategy for the direct synthesis of C-glycosides using hydroxyl groups,as follows.In the first part,we develop a photocatalytic mediated method for the synthesis of C-glycosides using 1-hydroxy carbohydrates as starting materials.In this reaction,glycosyl radicals were generated from the adducts of 1-hydroxy carbohydrates and Nheterocyclic carbene(NHC),which react with activated olefins to produce Cglycosides.This method is applicable to 1-hydroxy carbohydrates with different protecting groups.Generally,the reactivity of the substrates with electron-absorbing groups is better than that of those with electron-donating groups.The reaction exhibits good α-selectivity,and the α-configuration of the products was determined by twodimensional nuclear magnetic spectroscopy.In the second part of the work,we explored the boundaries of this reaction model using alkyl alcohols as radical precursors and trifluoromethyl olefins as radical acceptors.We successfully demonstrated that the present reaction system is applicable to sugars with hydroxyl groups at any position.In addition,primary,secondary,and tertiary alkyl alcohols are reactive and have a site selectivity of primary > secondary >tertiary,and the present reaction has a single site selectivity for multiple sites with the same chemical environment.The above work provides a new approach for the synthesis of C-glycosides,which is beneficial for related medicinal chemistry and chemical biology studies. |
