Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

Abstract

The glycosylation of O-glycosyl trichloroacetimidate donors using a synergistic catalytic system of electron-deficient pyridinium salts/aryl thiourea derivatives at room temperature is demonstrated. The acidity of the adduct formed by the 1,2-addition of alcohol to the electron-deficient pyridinium salt is increased in the presence of an aryl thiourea derivative as an hydrogen-bonding cocatalyst. This transformation occurs under mild reaction conditions with a wide range of O-glycosyl trichloroacetimidate donors and glycosyl acceptors to afford the corresponding O-glycosides in moderate to good yields with predictable selectivity. In addition, the optimized method is also utilized for the regioselective O-glycosylation by using a partially protected acceptor.

Stereoselective O‐Glycosylations by Pyrylium Salt Organocatalysis**

“…Chemie Forschungsartikel selectivity and yield and furthermore gave high b-selectivity using the standard procedure in Et 2 Oa sw ell as when using MeCN as the solvent. Lastly,a4,6-deprotected glycosyl nucleophile was glycosylated regioselectively with exclusive formation of the desired b-linked disaccharide (18)i nb oth MeCN and in toluene.Asimilar preference for the 6-OH of the 4,6-diol has been reported by Kumar and co-workers [48] using pyridinium catalysts,a lbeit with lower b-selectivity.…”

“…Many pyrylium salts are commercially available and have gained interest in the scientific community as organic dyes [39, 40] and photoredox catalysts, [41–43] and were recently introduced as catalysts for Katritzky‐like C−N bond activations [44–46] by Cornella and co‐workers. In addition, structurally related pyridinium salts have previously been utilized in glycosylation chemistry [47–49] . However, to the best of our knowledge, pyrylium salts have not previously been used in glycosylation chemistry.…”

Recent Developments in Stereoselective Chemical Glycosylation

“…Later, Shaw et al . described a glycosylation catalyzed by pyridinium bromide‐thiourea combination that is very similar to Schmidt's system …”

Organocatalysis applied to carbohydrates: from roots to current developments

“…Electron-deficient pyridinium salts were found to be acidic enough, in the presence of the thiourea 37 to activate trichloroacetimidates (gluco-, galacto-, manno-). 31 Besides few exceptions, the α/β selectivity remained moderate, often in favor of the α-glycoside.…”

“…As already mentioned, pyridinium salts exhibit similar anion binding properties to thioureas. 31 Therefore they can also be used for the activation of glycals. Such electrondeficient salts (as 106) readily undergo 1,2-addition of the alcohol facilitating the protonation of the glycal (Scheme 17).…”