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

Abstract

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, abstracts 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 abstraction 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.

Radical-Mediated C–H Functionalization: A Strategy for Access to Modified Cyclodextrins

“…A competitive addition of both nucleophiles to the oxacarbenium ion intermediate may also be considered. 20 Obviously, both products, 2 and 3, derived from the same C5 VII radical intermediate, through an intramolecular 1,8-HAT reaction promoted by the 6 I -O-yl radical. No compounds resulting from abstraction at C1 VII via a 1,6-HAT process were detected.…”

Easy Access to Modified Cyclodextrins by an Intramolecular Radical Approach

“…Preliminary observations made on the X‐ray structure of permethylated β‐CD show that the macrocyclic ring has sufficient inter‐residue flexibility to permit the glycosidic and aglyconic bonds adopt an exo ‐ syn conformation with values of Φ and Ψ similar to those of β‐maltose 13. The analogous situation is obtained over a minimized structure of permethylated β‐CD and therefore, we anticipated that the 1,8‐HAT process between two vicinal units could take place with high regioselectivity 14. If this strategy succeeded, it could provide facile access to modified CDs on their primary face, CDs which are difficult to obtain by conventional methods, and which could show significant deformations in their cavities.…”

1,n‐Hydrogen‐Atom Transfer (HAT) Reactions in Which n≠5: An Updated Inventory

“…A comparative study performed on the analogous C‐ disaccharide pointed to the greater flexibility of the C‐ glycosidic bond and the lack of anomeric effect. No selectivity in intra‐HAT was observed, as shown in Figure 3 109…”

“…No selectivity in intra-HAT was observed, as shown in Figure 3. [109] Selective C5' functionalization was also recorded from nitrogen-centered sulfonamidyl radicals although in slightly lower yields. [110] The photochemically induced 1,8-abstraction of a hydrogen atom from 59.1, performed from the triplet excited state of the benzophenone moiety, was proposed to explain the formation of 59.2.…”