Nontraditional Synthesis of Disaccharides via Acyclic Vinylic Ether Intermediates: Catalytic C-O Cross-Coupling as the Enabling Link

J Org Chem. 2024 Nov 26. doi: 10.1021/acs.joc.4c02176. Online ahead of print.

Abstract

We describe complementary methods for synthesizing acyclic vinylic ethers from two carbohydrate-derived synthons. We compare a nonstereoselective olefination approach with a stereoselective catalytic C-O cross-coupling method, preparing 1,2-disubstituted vinylic ethers with complexity on both sides of the ether linkage. Upon epoxidation/in situ oxacyclization of acyclic vinylic ethers, we synthesized disaccharides with α-d-galacto-, α-d-talo-, β-d-allo-, and α-d-altropyranoside stereochemistry, from d-lyxose and d-ribose precursors. Stereoselective CuI/CyDMEDA-catalyzed C-O cross-couplings offer considerable potential for broadly implementing this nontraditional strategy for glycoside synthesis.