Factors influencing stereoselectivity of sulfur oxidation: substituent effects on the oxidation of 5-thioglycopyranose derivatives

Abstract

Various 5-thioglycopyranose derivatives, including 5-thiogalactopyranose, 5-thiomannopyranose, and 1-substituted-5-thioglucopyranose derivatives, were oxidized to the sulfoxides with m-chloroperoxybenzoic acid (MCPBA) and 2-benzenesulfonyl-3-( m-nitrophenyl)-oxaziridine (BSNPO) in order to probe the origin of the reversal stereoselectivity observed in the MCPBA oxidation of the 1- O-methyl and 1- O-acetyl derivatives of 5-thio-α-D-glucopyranose. Analyses, using σ p values, of the stereoselectivity in the oxidation of 1- O-( p-substituted benzoyl)-5-thio-α-D-glucose derivatives suggested that electronic effects of the anomeric substituents significantly affect the stereoselectivity and that the electron-donating and electron-withdrawing substituents tend to afford more and less of axial/equatorial ratios of the sulfoxides, respectively. The analyses, using multisubstituent parameters, of the oxidation of 1-substituted-5-thio-α-D-glucopyranose derivatives gave insight into the substituent effect on the stereoselectivity; that is, both the electronegativity effect and the resonance effect are involved, and steric repulsion between the anomeric substituent and the oxidant contributes especially in the case of the oxidation with the bulky BSNPO. It was shown from competition experiments, however, that the oxidation rates depend solely on the inductive effect (or electronegativity effect) of the anomeric substituent. From the extended Hückel orbital calculation on the model compounds and the regioselectivities in the oxidation of α- and β-1,5-dithioglucopyranoside derivatives, it was suggested that the oxidation rate is governed, in the same manner as anomeric effect, by the interaction between the sulfur lone pair and the antibonding orbital of the glycosidic bond. From these results, asymmetry of electron density on the sulfur lone pair orbital was proposed to be the origin of the stereoselectivity.