Palladium catalysis enables cross-coupling-like SN2-glycosylation of phenols

• 成果类型: Article
• 署名作者: Deng, Li-Fan; Wang, Yingwei; Xu, Shiyang; Shen, Ao; Zhu, Hangping; Zhang, Siyu; Zhang, Xia; Niu, Dawen
• 署名单位: Sichuan University; Sichuan University; Sichuan University; Sichuan University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11470
• DOI: 10.1126/science.adk1111
• 发表日期: 2023-11-24
• 页码: 928-935
• 关键词: o-glycosylation; derivatives

摘要

Despite their importance in life and material sciences, the efficient construction of stereo-defined glycosides remains a challenge. Studies of carbohydrate functions would be advanced if glycosylation methods were as reliable and modular as palladium (Pd)-catalyzed cross-coupling. However, Pd-catalysis excels in forming sp(2)-hybridized carbon centers whereas glycosylation mostly builds sp(3)-hybridized C-O linkages. We report a glycosylation platform through Pd-catalyzed S(N)2 displacement from phenols toward bench-stable, aryl-iodide-containing glycosyl sulfides. The key Pd(II) oxidative addition intermediate diverges from an arylating agent (Csp(2) electrophile) to a glycosylating agent (Csp(3) electrophile). This method inherits many merits of cross-coupling reactions, including operational simplicity and functional group tolerance. It preserves the S(N)2 mechanism for various substrates and is amenable to late-stage glycosylation of commercial drugs and natural products.