New mechanistic approach in the enamine-based asymmetric organocatalysis

Abstract

During the course of my research in asymmetric organocatalysis, inversion of enantioselectivity was observed in the asymmetric aldol reactions of acetone with different aldehydes catalyzed by amphiphilic proline derivatives in aqueous media by varying only achiral components. It was not possible to explain the explored dual stereocontrol with the existing models, therefore I proposed a new mechanism for asymmetric aldol reactions catalyzed by l-amino acid derivatives in aqueous media and explained the explored phenomenon of inversion of enantioselectivity with different structures of micelle-stabilized transition state described as a metal-free version of the Zimmerman-Traxler model with explicit participation of a water molecule. Contrary to the existing models, according to the proposed mechanism, the formation of new bonds proceeds directly in the transition state stabilized by a water molecule, without the additional step of product iminium ion hydrolysis. The proposed mechanism has universal character, it is consistent with experimental results and general theoretical conceptions, and it is applicable to all enamine-based asymmetric organocatalytic reactions carried out not only in aqueous, but in organic media as well, because the initial step of catalytic cycle, which involves the formation of an enamine from the carbonyl compound and proline (derivative), liberates one water molecule.