The impact of oxacarbenium ion conformers on the stereochemical outcome of glycosylations

The influence of acceptor nucleophilicity on the glycosylation reaction mechanism

“…Based on the conformational behavior of the donors and the intermediate α-triflates 18α , adopting an 1 C 4 conformation, 48,49 the high reactivity of these donors 50,51 and a large variety of glycosylation reactions, both in solution, 50,52–55 and on fluorous 56 and solid supports, 57 it has been postulated that the selectivity in these glycosylation reactions can be related to the intermediacy of an 4 H 3 oxocarbenium ion-like intermediate. 53,54,58 …”

Do Glycosyl Sulfonium Ions Engage in Neighbouring‐Group Participation? A Study of Oxathiane Glycosyl Donors and the Basis for their Stereoselectivity

“…[44] If the rates of these two addition steps are equal, then the stereoselectivity is governed by the relative abundance of the 3 H 4 and 4 H 3 conformers; however, different steric interactions in the transition states may render the addition steps inequivalent. [10] A Monte Carlo search was used to generate a broad range of conformations for the substituents attached to 3 H 4 and 4 H 3 oxacarbenium ions 46-48. The geometry of each conformer was optimised using DFT calculations (B3LYP/6-31G*).…”

“…[8] To combat this problem, attention has become focused on the underlying mechanistic theory of the glycosylation reaction. [9,10] Traditionally, stereoselectivity in the presence of non-participating protecting groups has been attributed to the kinetic anomeric effect. [11] However, this principle has been challenged; [12] an alternative theory has emerged in the form of the two-conformer hypothesis, [13,14] in which stereoselectivity is determined by the selective addition of nucleophiles to different conformations of an oxacarbenium ion intermediate.…”

Advances in Stereoselective 1,2‐cisGlycosylation using C‐2 Auxiliaries

“…Furthermore, this strategy is also applicable to the synthesis of 2-deoxy-2-amino-glycosides using amine-protecting groups that can performN GP.H owever, care needs to be taken when using an N-acetyl group for NGP as the corresponding glycosyl oxazoline is ac ommonly formed byproduct, but can be avoided by using Lewis acid catalysis. [13] Althoughe xcellent, these methods are stereoselective via different mechanismsr anging from solvente ffects, [14] directed aglycon delivery, [15] steric shielding, [12] S n 2-like displacement of a quasi-stable intermediate, [10a] stabilizationo fa no xocarbenium ion conformation [13,16] and post-glycosylation anomerization. [9] In contrast, the introductiono f1 ,2-cis glycosidic linkages is much more challenging and requires glycosyl donors having a non-assisting functionality at C-2.…”