Non-traditional synthesis of disaccharides via acyclic vinylic ether intermediates: Catalytic C-O cross-coupling as the enabling link

We describe complementary methods for synthesizing acyclic vinylic ethers from two carbohydrate-derived synthons. We compare a non-stereoselective modified Julia olefination approach with a newer, stereoselective catalytic C-O cross-coupling method, preparing 1,2-disubstituted vinylic ethers with structural and stereochemical complexity on both sides of the ether linkage. Upon epoxidation / in situ oxacyclization of acyclic vinylic ether products, we have synthesized disaccharides with alpha-D-galacto-, alpha-D-talo-, beta-D-allo-, and alpha-D-altropyranoside stereochemistry arising from D-lyxose and D-ribose precursors. The stereoselective CuI/CyDMEDA-catalyzed C-O cross-coupling method offers considerable potential for broadly implementing this non-traditional strategy for glycoside synthesis.