Highly Stereoselective Synthesis of Bis-C-ferrocenyl Glycosides via Palladium-Catalyzed Directed C–H Glycosylation

Abstract

Conjugation of carbohydrates to ferrocene scaffolds is of great value in drug design, given the nontoxic and lipophilic nature of ferrocene. However, the efficient and stereoselective synthesis of C-ferrocenyl glycosides remains a challenge. Herein, we developed a Pd-catalyzed stereoselective C–H glycosylation to provide rapid access to sole bis-C-ferrocenyl glycosides in good to high yields (up to 98% yield) with exclusive stereoselectivity. A diverse range of glycosyl chlorides were well tolerated, including d-mannose, d-glucose, l-xylose, l-rhamnose, d-mannofuranose, and d-ribofuranose. Additionally, a mononuclear PdII intermediate was characterized by X-ray single-crystal diffraction, and might participate in the C–H palladation step.

Palladium Catalysis: Dependence of the Efficiency of C−C Bond Formation on Carboxylate Ligand and Alkali Metal Carboxylate or Carboxylic Acid Additive. Part A: the C(sp2)−C(sp2), C(sp2)−C(sp3) and C(sp3)−C(sp3) Bonds

“…At 100 °C, the Pd-catalyzed bisÀ CÀ H glycosylation of ferrocenyl amide depicted in Scheme 36a in the presence of KHCO 3 provided a better yield with addition of catalytic amounts of AcOH than that of other carboxylic acids. [170] Decrease the reaction temperature to 60 °C and use of overstoichiometric of AcOH with K 2 CO 3 instead of KHCO 3 improved the yield to 88%. Interestingly, the use of a 1:1 mixture of KHCO 3 and KOAc under acid-free conditions gave rise to 91% yield.…”