Palladium catalysis enables cross-coupling–like S <sub>N</sub> 2-glycosylation of phenols
Li‐Fan Deng, Yingwei Wang, Shiyang Xu, Ao Shen, Hangping Zhu, Siyu Zhang, Xia Zhang, Dawen Niu
Abstract
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.