Role of Bifunctional Catalysts in Desymmetrization and Transamidation

초록

The reaction of carboxamides transamidation1 and meso anhydrides desymmetrization2 catalyzed by bifunctional Bronsted acid/base organocatalyst was investigated and compared theoretically by DFT method. The energy barriers are much lowered by the catalysts. With the bifunctional catalysts, the reaction of anhydrides desymmetrization (Figure 1) proceeds through a 2-step mechanism with the energy barrier lowered to 19.0 kcal/mol and 0.9 kcal/mol. The pyridine moiety in the catalyst works as a Bronsted base to activate methanol substrate, and the nitrogen atom attaches to phosphorus atom working as a Bronsted acid to activate anhydride by hydrogen bonding. The role of enantioselectivity of the catalyst is studied also, and it shows consistent with experimental results. The energy barrier of transamidation reaction (Figure 2) for the overall process without catalyst is very high (47.89 kcal/mol). In the presence of catalyst, the reaction proceeds through a multi-step mechanism and the energy barrier is much lower than the reaction without catalyst. The reaction mechanism in the presence of solvent and high temperature and the comparing of real system and model system are also considered in this study. This shows that L-proline functions as an efficient catalyst. A novel mechanism of dehydration in the process of the reaction is also proposed.