Stereoselectivity in the epoxidation of carbohydrate-based oxepines

The facial selectivity in the DMDO epoxidation of carbohydrate-based oxepines derived from glucose, galactose, and mannose has been determined by product analysis and density functional theory (DFT, B3LYP/6-31+G**//B3LYP/6-31G*) calculations. Oxepines 3 and 4, derived from d-galactose and d-mannose, largely favor alpha- over beta-epoxidation. The results reported here, along with selectivities in the DMDO-mediated epoxidation of d-xylose-based oxepine 1 and d-glucose-based oxepines 2 and 5 reported earlier, support a model in which electronic effects, guided by the stereochemistry of the oxygens on the oxepine ring, largely determine the stereoselectivity of epoxidation. Other contributing factors included conformational issues in the oxepine's transition state relative to the reactant, the asynchronicity in bond formation of the epoxide, and the overall steric bulk on the alpha- and beta-faces of the oxepine. Considered together, these factors should generally predict facial selectivity in the DMDO-epoxidation of cyclic enol ethers.