Influence of Protecting Groups on the Reactivity and Selectivity of Glycosylation: Chemistry of the 4,6-O-Benzylidene Protected Mannopyranosyl Donors and Related Species

Abstract

The genesis and development of the 4,6-O-benzylidene acetal method for the preparation of β-mannopyranosides are reviewed. Particular emphasis is placed on the influence of the various protecting groups on stereoselectivity and these effects are interpreted in the framework of a general mechanistic scheme invoking a series of solvent-separated and contact ion pairs in dynamic equilibrium with a covalent α-glycosyl trifluoromethanesulfonate.

Determination of the Influence of Side‐Chain Conformation on Glycosylation Selectivity using Conformationally Restricted Donors

“…As the oxocarbenium ion [21] is in equilibrium with the commonly observed [22] α-glycosyl triflate this stabilization results in a longer lifetime of the oxocarbenium ion and looser ion pairs leading to a reduction in selectivity (Scheme 5). [23] This rationale is consistent with computational work by Woerpel suggesting that pyranosyl oxocarbenium ions are stabilized when the side chain adopts the gg conformation. [7] Furthermore it is in full agreement with kinetic isotope effect measurements [24] and cation clock experiments, [25] both of which indicate a higher degree of S N 1-like character in the formation of 4,6- O -benzylidene–protected α-mannosides than for their β-anomers which are closer to the S N 2 end of the mechanistic spectrum for nucleophilic substitution.…”

Synthesis and Structural Verification of the Xylomannan Antifreeze Substance from the Freeze-Tolerant Alaskan Beetle Upis ceramboides

“…13 With the glycosyl acceptor 5 , itself a thioglycoside, the sulfenyl trap 1-octene was added to the reaction mixture before it was allowed to warm to room temperature to prevent premature activation of the disaccharyl thioglycoside. 7a,14 As anticipated, 11 these reactions were highly β-selective with only a single anomer being isolated in each case. Acidolysis of the reactive trans -fused acetonide in 4 and 5 was then followed by benzoylation to give 6 and 7 , which, on treatment with sodium cyanoborohydride and HCl 15 underwent reductive cleavage of the benzylidene acetal units to give the corresponding 6′- O -benzyl ethers retaining hydroxyl groups at the 4′-position, 8 and 9 (Scheme 1).…”

A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art

“…Because of the widespread use of triflate-containing promoters and the spectroscopic identification of covalent glycosyl triflates, 42,71–72 most discussions in recent years focus on the possibility of the involvement of glycosyl triflates. This is especially the case in the benzylidenedirected β-mannosylation reaction for which α-mannosyl triflates were identified as resting intermediates 60,71–73 and as reactants in S N 2-like displacements. 14,19 It is reasonable to expect that for a given glycosyl oxocarbenium ion, the tightness of ion pairs with counter ions will vary inversely with the stability of the counter ion.…”