A new organocatalytic glycosylation method exploiting the lactol functionality has been disclosed. The catalytic generation of glycosyl oxacarbenium ions from lactols under forcible conditions via weakly Brønsted-acidic, readily available secondary amine salts affects the diastereoselective glycosylation of 2-deoxypyranoses and furanoses. This operationally simple iminium catalyzed activation of 2-deoxy hemi-acetals is a potential alternative to the existing cumbersome methods that need specialized handling. The mechanisms for this unique transformation and kinetic/thermodynamic effects have been discussed based on both experimental evidence and theoretical studies.

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.

The conjugate acid of the bulky base 2,4,6-tri-tert-butylpyridine, under mild conditions, catalyzes the synthesis of silylprotected 2-deoxy-hemiacetals and their dimerized products from glycals at varying concentrations of water. The criticality of the concentration of water in the reaction outcome is indicative of a unique mechanistic pathway for the bulky pyridine salt and not via the general Brønsted acid mechanism. The various silyl-protected hemiacetals thus synthesized were successfully utilized in the stereoselective synthesis of both α and β glycosides.

The reaction of secondary amine salts with 2‐deoxy‐ribofuranoses under forcible conditions leads to the putative furanosyl oxocarbenium ion that is trapped with various alcohols to provide 2‐deoxy‐ribofuranosides. The observed anomeric selectivities range from an equimolar mixture to complete α‐selectivity in the case of bulky sugar acceptors. Owing to the mechanism and temperature of the transformation, the generated oxocarbenium ion shows little or no facial preference towards the nucleophilic attack of non‐carbohydrate acceptors and leads to a mixture of anomers in the case of benzyl and acetyl protected donors. However, the conformationally less flexible tetraisopropylsilyl protected donor reacted with both sugar and non‐sugar acceptors in a stereoselective fashion. Besides, the glycosylation with 2‐cyanoethanol gave the product with unexpected beta‐selectivity presumably due to nitrile effect. The operationally simple organocatalytic protocol provides easy access to otherwise difficult 2‐deoxy‐ribofuranosides/disaccharides.

Amines are used as additives to facilitate or increase the host−guest chemistry between the thiourea and the anions of Bronsted acids. However, we here demonstrate, for the first time, the synergistic effect of the combination of DMAP/HCl/ Schreiner's thiourea in catalyzing dehydrative glycosylation. The variations in the electronic effects of the cationic Bronsted acid part (the protonated DMAP) in the presence of chloride binding Schreiner's thiourea have been discussed using NMR and X-ray crystallographic techniques.