Palladium-Catalyzed O - and N -Glycosylation with Glycosyl Chlorides

Abstract

Despite the significant progress in carbohydrate chemistry, there remains a pressing need for efficient and practical glycosylation methods using simple glycosyl donors and with high atom economy. Herein, a new protocol for glycosylation with glycosyl chloride donors under palladium-catalyzed conditions is developed. Pd II complex serves as a Lewis acid to promote the activation of glycosyl chloride for the formation of oxocarbenium ion intermediate. This new method is operationally simple, robust, and enables efficient synthesis of both Oand N-glycosides with a broad substrate scope. In particular, it offers an easy access to a range of N-ribonucleoside analogs.

Synthesis and Glycosidation of Anomeric Halides: Evolution from Early Studies to Modern Methods of the 21st Century

“…Very recently, Chen and co-workers developed a new protocol to activate glycosyl chloride donors to synthesize O -glycosides using palladium­(II) reagents . On the basis of their previous work of palladium-catalyzed C -aryl glycoside synthesis, the authors established that palladium acetate can serve as a Lewis acid that will interact with the chloride leaving group thereby activating the anomeric C–Cl bond .…”

Chemical and chemoenzymatic stereoselective synthesis of β-nucleosides and their analogues

“…In 2020, Chen and He developed a palladium-catalyzed glycosylation by employing glycosyl chloride 61 as the donor (Scheme 13). 24 The easily prepared glycosyl chloride donor 61 was more stable than the corresponding bromide and iodide donors, leading to tolerance for high reaction temperatures. The reaction of thymine with the d -ribofuranose chloride donor 61 in the presence of BSA, Pd(OAc) 2 , and K 2 CO 3 in CHCl 3 at 110 °C for 24 h gave nucleoside 62 with 75% yield and excellent β-selectivity (β only).…”

Stereoselective O-Glycosylation of Glycals with Arylboronic Acids Using Air as the Oxygen Source

“…Manifold chemical approaches for synthesizing O -glycosides have been developed successfully in the last few decades, typically requiring anhydrous and inert atmosphere-protected reaction conditions . Glycosylation approaches conventionally employing saturated glycosyl donors with an anomeric leaving group, activated by stoichiometric activators or catalytic promoters, achieved stereoselectivities, generally relying on the design and preparation of the glycosyl donors (Scheme a) . With the development of transition-metal catalysis, the unsaturated glycosyl donors (glycals) demonstrated great potential for stereoselective glycosylation .…”