Sterically Hindered 2,4,6-Tri-tert-butylpyridinium Salts as Single Hydrogen Bond Donors for Highly Stereoselective Glycosylation Reactions of Glycals

Abstract

We demonstrate here that the strained and bulky protonated 2,4,6-tri-tert-butylpyridine salts serve as efficient catalysts for highly stereoselective glycosylations of various glycals. Moreover, the mechanism of action involves an interesting single hydrogen bond mediated protonation of glycals and not via the generally conceived Brønsted acid pathway. The counteranions also play a role in the outcome of the reaction.

A robust and tunable halogen bond organocatalyzed 2-deoxyglycosylation involving quantum tunneling

“…Specifically, we aim to harness and unravel noncovalent mechanisms unique to XB organocatalysis, so that enabling methodologies, which facilitates the preferential construction of challenging bonds over thiourea catalysis in biologically relevant molecules can be developed. In line with this aim, we have identified the biologically relevant 2-deoxyglycosylation as an ideal reaction model for the discovery for unknown XB catalytic mechanisms [46][47][48][49][50][51][52][53][54][55][56][57][58][59] . The unique poly-oxygenated nature of glycosyl substrates and products provides numerous XB acceptor moieties for the in situ catalytic establishment of dynamic noncovalent activations.…”

“…The unique poly-oxygenated nature of glycosyl substrates and products provides numerous XB acceptor moieties for the in situ catalytic establishment of dynamic noncovalent activations. Moreover, the synthetic importance of 2deoxyglycosides as a privileged and biologically useful compound class is well exemplified by the continual intense interest by many different research groups [46][47][48][49][50][51][52][53][54][55][56][57][58][59] , due to its prevalence in glycosidic natural products, such as digitoxin and saccharomicin B (ref. 46 ).…”

Recent Advances in Stereoselective Chemical O-Glycosylation Reactions

“… Ghosh et al (2019 ) further demonstrated that the protonated 2,4,6-tri- tert -butylpyridine salt serves as bulky and strained catalysts for efficient and highly stereoselective glycosylation reactions of various glycals (entry c, I in Scheme 13 ). They have explored the efficacy of the catalyst for a variety of differentially protected glycal donors ( 122 ) and various acceptors generating their corresponding 2-deoxyglycoside 124 , and also extended its applicability in gram-scale synthesizing norbornene–glycoside.…”

Organocatalysis applied to carbohydrates: from roots to current developments

“…Bulky pyridinium salts such as 113 have recently been used for the protonation of diversely protected glycals in non-polar solvents (Scheme 18). 46 In this case, direct protonation of the glycal by the pyridinium salt has been excluded by the authors. Based on the 1 H-NMR study, they have been able to observe the formation of a hydrogen bond between the pyridinium salt and the hydroxyl group of the acceptor.…”