Palladium-catalysed C−H glycosylation for synthesis of C-aryl glycosides
Nature Catalysis Pub Date : 2019-08-05 , DOI: 10.1038/s41929-019-0324-5
Quanquan Wang, Shuang An, Zhiqiang Deng, Wanjun Zhu, Zeyi Huang, Gang He, Gong Chen
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C-aryl glycosides are widely found in nature and play important roles in drug design. Despite the significant progress made over the past few decades, efficient and stereoselective synthesis of complex C-aryl glycosides remains challenging, lagging far behind the state of the art of the synthesis of O- or N-glycosides. Here, we report a simple and powerful bioinspired strategy for the stereoselective synthesis of C-aryl glycosides via palladium-catalysed ortho-directed C(sp2)−H functionalization of arenes and heteroarenes with easily accessible glycosyl chloride donors. The catalytic palladacycle intermediate generated via C−H palladation provides a soft aryl nucleophile that can react with glycosyl oxocarbenium ion partners with high efficiency and excellent stereocontrol. The method can be applied to a wide range of arene and heteroarene substrates, glycosyl chloride donors and auxiliary groups. It can simplify the synthesis of a variety of complex C-aryl glycosides and offers a tool for late-stage modification of drug molecules.
