Theoretical Investigation of the Mechanism of an Iminium-Enamine Conversion in a Proline-Catalyzed Aldol Reaction Using the ReaxFF Reacting Force Field

In the field of organic synthesis, the development of reactions that enable the creation of asymmetric carbon atoms in a stereoselective way remains a key subject. In 2000, it was recognized that the stereochemical outcome of a reaction can be controlled by the use of a small, organic molecule, e.g., proline, as catalyst. This type of reaction can be referred to as organocatalyzed. Here, we present a theoretical study focusing on the mechanism of the proline-catalyzed self-aldol reaction of propanal. More precisely, we investigate the iminium-enamine conversion leading to the nuceophilic species of the reaction. Along with quantum mechanical calculations, an original reactive force field approach, i.e., ReaxFF, is used to model the reaction with molecular dynamics simulations.
This work is related to our Master Thesis which was awarded by the “Prix du meilleur mémoire” of the Société Royale de Chimie.