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.

Keywords: O-glycoside; cooperative catalysis; electron-deficient pyridinium salts; regioselectivity; thiourea.

Scheme 1

Mechanistic hypothesis for work.

Figure 1

¹H NMR (a) glycosyl donor 1α and (b) a mixture of 1α and 10 mol % 3a in CD₂Cl₂ at room temperature.

Figure 2

¹H NMR (a) glycosyl acceptor 2a, (b) pyridinium salt 3a (in DMSO-d₆) and (c) a mixture of 2a and 3a in 1:1 ratio in CD₂Cl₂ at room temperature.

Figure 3

¹H NMR (a) glycosyl acceptor 2a, (b) pyridinium salt 3a (in DMSO-d₆), (c) aryl thiourea and (d) a mixture of 2a, 3a (10 mol %) and 4 (10 mol %) in CD₂Cl₂ at room temperature.

Scheme 2

Synergistic electron-deficient pyridinium salt/aryl thiourea-catalyzed regioselective O-glycosylation.

Figure 4

Plausible reaction mechanism.