Stereoelectronic Factors in the Stereoselective Epoxidation of Glycals and 4-Deoxypentenosides

• Published in: Journal of organic chemistry Vol. 76; no. 8; pp. 2532 - 2547
• Main Authors: Alberch, Laura, Cheng, Gang, Seo, Seung-Kee, Li, Xuehua, Boulineau, Fabien P, Wei, Alexander
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.04.2011; Amer Chemical Soc
• Subjects: Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Carbon - chemistry; Chemical reactivity; Chemistry; Chemistry, Organic; Electrons; Epoxy Compounds - chemistry; Exact sciences and technology; Glycosides - chemical synthesis; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Organic chemistry; Oxygen - chemistry; Physical Sciences; Preparations and properties; Reactivity and mechanisms; Science & Technology; Stereoisomerism; ROUTE; ETHERS; HYDRIDE REDUCTIVE REARRANGEMENT; ACETALS; CLEAVAGE; REGIOSELECTIVITY; DERIVATIVES; SELECTIVITY; Molecular orbital; Frontier orbital; Molecular structure; Isostere; Pyran derivatives; Theoretical study; Glycal; Oside; Stereochemistry; Oxygen heterocycle; Unsaturated compound; Stereoselectivity; Anomer; Steric effect; Epoxidation; Density functional method; Electronic effect; Chemical reactivity; Organic peroxide
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/jo102382r

Glycals and 4-deoxypentenosides (4-DPs), unsaturated pyranosides with similar structures and reactivity profiles, can exhibit a high degree of stereoselectivity upon epoxidation with dimethyldioxirane (DMDO). In most cases, the glycals and their corresponding 4-DP isosteres share the same facioselectivity, implying that the pyran substituents are largely responsible for the stereodirecting effect. Fully substituted dihydropyrans are subject to a “majority rule”, in which the epoxidation is directed toward the face opposite to two of the three groups. Removing one of the substituents has a variable effect on the epoxidation outcome, depending on its position and also on the relative stereochemistry of the remaining two groups. Overall, we observe that the greatest loss in facioselectivity for glycals and 4-DPs is caused by removal of the C3 oxygen, followed by the C5/anomeric substituent, and least of all by the C4/C2 oxygen. DFT calculations based on polarized-π frontier molecular orbital (PPFMO) theory support a stereoelectronic role for the oxygen substituents in 4-DP facioselectivity, but less clearly so in the case of glycals. We conclude that the anomeric oxygen in 4-DPs contributes toward a stereoelectronic bias in facioselectivity whereas the C5 alkoxymethyl in glycals imparts a steric bias, which at times can compete with the stereodirecting effects from the other oxygen substituents.