Nontraditional 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 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.