Transformations and Tautomeric Equilibrium among Different Intermediates in Proline-Catalyzed Reactions of Aldehydes or Ketones

Abstract

The enamines, iminium ions, and oxazolidinones are thought to be the key intermediates in the proline-catalyzed reactions of aldehydes or ketones, but there is an extensive controversy about their roles. Here, the corresponding transition states connecting any two of the three kinds of species are located at the ωB97XD/6-311++G** level of theory. The calculations demonstrate that the oxazolidinones are the predominant species in both the gas phase and solvents; there exists tautomeric equilibrium among these species and the equilibriums are controlled by the employed solvents and temperature in the reaction. These results demonstrate that the concentration and role of the mentioned species are controlled by the employed solvent and temperature. A new reaction pathway is presented herein for the transformation between iminium ions and oxazolidinones through iminium ion-water complex and oxazolidinone-water complex. The calculations demonstrate that the rate-limiting step in proline-catalyzed Mannich reaction between acetaldehyde/keteones and N-Boc imines is the formation of the C—C bond rather than the intermediates tautomerization. These calculations rationalize the available experimental observations and can be valuable in optimizing the experimental conditions of asymmetric organic-catalyzed reactions of aldehydes or ketones.