Stereoselective Assembly of C-oligosaccharides via Modular Difunctionalization of Glycals

Abstract

C-oligosaccharides are found in natural products and drug molecules. Despite the considerable progress made during the last decades, modular and stereoselective synthesis of C-oligosaccharides continues to be challenging and underdeveloped compared to the synthesis technology of O-oligosaccharides. Herein, we have designed a distinct strategy for the stereoselective and efficient synthesis of C-oligosaccharides via palladium-catalyzed nondirected C1-H glycosylation/C2-alkenylation, cyanation, and alkynylation of 2-iodoglycals with glycosyl chloride donors while realizing the difunctionalization of 2-iodoglycals for the first time. The catalysis approach tolerates various functional groups, including derivatives of marketed drugs and natural products. Notably, the obtained C-oligosaccharides can be further transformed into various C-glycosides while fully conserving the stereo-chemistry. Density functional theory (DFT) calculations studies are supportive of a concerted oxidative addition mechanism alkenyl-norbornadiene-palladacycle (ANP) intermediate with an α-mannofuranose chloride and the high stereoselectivity of glycosylation was due to steric hindrance.