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

Conjugation of carbohydrates to ferrocenescaffolds isof greatvalue in drug design, given the nontoxic and lipophilic nature offerrocene. However, the efficient and stereoselective synthesis of C-ferrocenyl glycosides remains a challenge. Herein, wedeveloped a Pd-catalyzed stereoselective C-H glycosylationto provide rapid access to sole bis-C-ferrocenylglycosides in good to high yields (up to 98% yield) with exclusivestereoselectivity. A diverse range of glycosyl chlorides were welltolerated, including d-mannose, d-glucose, l-xylose, l-rhamnose, d-mannofuranose, and d-ribofuranose. Additionally, a mononuclear Pd-II intermediatewas characterized by X-ray single-crystal diffraction, and might participatein the C-H palladation step.

Automated summary

Efficient and stereoselective synthesis of C-ferrocenyl glycosides was achieved through Pd-catalyzed stereoselective C-H glycosylation, providing rapid access to sole bis-C-ferrocenylglycosides in good to high yields (up to 98% yield) with exclusive stereoselectivity. A diverse range of glycosyl chlorides were well tolerated.