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

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.