Theoretical investigation on enantioselective Biginelli reaction catalyzed by natural tartaric acid

摘要

In this study, enantioselective Biginelli reaction of aldehyde, β-ketoester, and urea catalyzed by natural (2R, 3R)-tartaric acid has been investigated using density functional theory calculations. The results indicate that the most favorable pathway involves a protonated imine from aldehyde and urea in the first step. Tartaric acid forms H-bonds network with substrates enhancing the electrophilicity of protonated imine and the nucleophilicity of β-ketoester. (R)-3,4-Dihydropyrimidin-2-(1H)-ones is preferable for the reaction. The solvent effect is discussed in the prediction of enantiomeric excess (ee) values in ethanol and water.