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

Abstract

An overview of recent advances in glycosylation with particular emphasis on mechanism is presented. The mounting evidence for both the existence of glycosyl oxocarbenium ions as fleeting intermediates in some reactions, and the crucial role of the associated in counter ion in others is discussed. The extremes of the SN1 and SN2 manifolds for the glycosylation reaction are bridged by a continuum of mechanisms in which it appears likely that most examples are located.

Blue Light Photocatalytic Glycosylation without Electrophilic Additives

“…There is a steadily increasing body of kinetic evidence 28–37 that a variety of stereoselective glycosylation reactions proceed by associative reaction pathways rather than by dissociatively free glycosyl oxocarbenium ions that have only been observed in super acidic media. 22,23,38,39 In such classical glycosylation reactions, the associative pathways are more prevalent with more reactive acceptor alcohols, 40–43 consistent with the observed pattern in Table 2. The hexafluorophosphate counterion is not considered to intervene directly in the reaction mechanism except for providing charge stabilization consistent with studies on the influence of a variety of counterions on the stereoselectivity of glycosylation reactions.…”

“…The hexafluorophosphate counterion is not considered to intervene directly in the reaction mechanism except for providing charge stabilization consistent with studies on the influence of a variety of counterions on the stereoselectivity of glycosylation reactions. 38,44 The part of the reaction manifold that affords substitution with overall retention of configuration is best interpreted as taking place via solvent-separated ion triplets rather than via equilibration of the donor configuration followed by concerted displacement as no evidence was found for donor anomerization in these reactions. The root cause of the observed acceleration of reaction rate by the 4 Å MS is presumably associated with their basic character 45 and the relative acidity 46 of the hydroxylamine Tempol.…”

Synthesis and intramolecular glycosylation of sialyl mono-esters of o-xylylene glycol. The importance of donor configuration and nitrogen protecting groups on cyclization yield and selectivity; isolation and characterization of a N-sialyl acetamide indicative of participation by acetonitrile

“…Possibilities for such competing pathways include the collapse of the activated thioglycosides 16 and 18 to oxocarbenium-type intermediates, most likely stabilized in the form of glycosyl triflates, 33–35 and equilibrated glycosyl disulfonium ions such as suggested by Ellervik and coworkers in the activation of sialyl thioglycosides by interhalogen compounds and silver triflate. 36 …”

Metal-free and VOC-free O-glycosylation in supercritical CO2

“…The α-anomer could directly arise from the trapping of the oxonium intermediate. 21 Alternatively, its formation could also be explained by the trapping of the acetoxonium ion to give the β anomer followed by a HBr-promoted anomerization process. 22 To address the origin of the α/β stereoselectivity, the reaction of donor 1 with acceptor a was performed in the presence of excess lutidine as an acid scavenger.…”