Influence of acyl groups on glucopyranoside reactivity in Lewis acid promoted anomerisation

Using Neighboring-Group Participation for Acyclic Stereocontrol in Diastereoselective Substitution Reactions of Acetals

“…This acceleration likely reflects stabilization of the developing positive charge by neighboring-group participation, considering that the magnitude of the acceleration is similar to that observed for carbohydrates. 5,26 As the donating ability of the acyl group increased, 5 the rate of ionization increased, which is consistent with participation of the carbonyl group (eq 1). The similar rates of hydrolysis of acetals bearing alkyl and aryl groups (i.e., 4a and 4d) indicate that the generation of the cationic intermediates in these reactions is dominated by the donation of electrons from the acyloxy group.…”

“…Using a pivaloate ester as the participating group in combination with strong nucleophiles produced substitution products with diastereoselectivities of ≥90:10.N eighboring-group participation is a widely used approach to control stereochemistry in substitution reactions of carbohydrate compounds. 1−3 Most commonly, acyloxy groups, namely, the acetate, benzoate, and pivaloate esters, 1,4,5 are used to favor the 1,2-trans products with high selectivity. 1,4,6 Neighboring-group participation has not emerged as a useful approach for controlling stereochemistry in reactions involving acyclic acetals, however.…”

“…Neighboring-group participation is a widely used approach to control stereochemistry in substitution reactions of carbohydrate compounds. − Most commonly, acyloxy groups, namely, the acetate, benzoate, and pivaloate esters, ,, are used to favor the 1,2- trans products with high selectivity. ,, Neighboring-group participation has not emerged as a useful approach for controlling stereochemistry in reactions involving acyclic acetals, however. − The use of neighboring-group participation to control stereochemistry in acyclic systems, as illustrated in eq , would be significant because it would provide access to the products expected from nucleophilic additions to α-alkoxy aldehydes that would be governed by the Felkin–Anh or related − stereochemical models. Such transformations, however, often give products with modest diastereoselectivity. ,,− …”

Lewis acid promoted anomerisation of alkyl O- and S-xylo-, arabino- and fucopyranosides

“…Butyl O-and S-glycosides, which are acetylated or benzoylated (Chart 1), were first synthesised (Scheme 2) so that reactivity and stereoselectivity comparisons could be compared with glycosides studied previously. 4,21 Acetyl and benzoyl groups were chosen as protecting groups as they are stable to SnCl4 and TiCl4 and they influence reactivity and stereoselectivity.…”

“…3 From work on glucopyranosides, which are conformationally rigid, there is a benefit from having a benzoyl group at C-2, compared to an acetyl group. 21 This may indicate there is a role for the 2-O-benzoyl group in stabilising a carbocation intermediate, generated during the course of the reaction, through resonance. Benzoyl groups may normally be expected to reduce reactivity towards anomerisation through inductive or field effects as they are more electron withdrawing than acetates (pKa benzoic acid = 4.20 vs pKa acetic acid = 4.76).…”