Hydrogen Atom Transfer Experiments Provide Chemical Evidence for the Conformational Differences between C- and O-Disaccharides

The glycopyran‐6‐O‐yl radical promoted hydrogen atom transfer reaction (HAT) between the two pyranose units of α‐D‐Manp‐(1→4)‐α‐D‐Glcp and α‐D‐Manp‐(1→4a)‐4a‐carba‐α‐D‐Glcp disaccharides provides supporting chemical evidence for the conformational differences between O‐ and C‐glycosyl compounds. In the O‐disaccharide the 6‐alkoxyl radical, generated under oxidative or reductive conditions, s exclusively the hydrogen at C‐5′ via a completely regioselective 1,8‐HAT reaction. This may be attributable to the conformational restriction of the glycosidic and aglyconic bonds due principally to steric and stereoelectronic effects. On the contrary, very little regioselectivity is observed in the homologous C‐disaccharide and a mixture of compounds generated by 1,5‐, 1,6‐, and 1,8‐HAT processes where the ion occurs at hydrogen atoms positioned at C‐4a, C‐1′, and C‐5′, respectively, has been obtained. This study has been extended to simpler O‐ and C‐glycosides, where the aglycon was a straight n‐alkyl alcohol tether of five atoms; in general, all of the results obtained are shown to be consistent with a major conformational flexibility of the C‐glycosidic bond. Long‐range hydrogen atom transfer (HAT) reactions promoted by alkoxyl radicals serve to highlight the conformational differences between O‐ and C‐disaccharides. In O‐disaccharides the 6‐O‐yl radical s exclusively the hydrogen at C‐5′ viaa 1,8‐HAT reaction. On the contrary, very little regioselectivity is observed in C‐disaccharides and the ion of the hydrogen at C‐1′, via a 1,6‐HAT reaction, competes favourably.