Abstract

In light of fundamental challenges of green organocatalysis, possible mechanisms of asymmetric aldol reactions catalyzed by amphipathic proline derivatives in aqueous media are considered to explain the dual stereocontrol stimulated by varying only achiral components. At the suitable reaction conditions in aqueous media (catalyst type and concentration, ionic strength, temperature, etc.) Amphipathic L-hydroxyproline derivative organocatalysts can form micelles, which function as nanoreactors with localization of hydrophobic species in the core, thus allowing the reagents to concentrate at the interface, where the enamine-based asymmetric aldol reaction takes place. The proposed different micellar transition states explain the explored dual stereocontrol stimulated by changing the pH of aqueous solution. In these structures the concerted bond reorganization is mediated with explicit participation of a water molecule, which is the sixth member of the stereoselectivity determining chair-like ring.

Keywords: Aldol reaction; Critical micelle concentration; Transition state; Dual stereocontrol; Nanoreactor; Asymmetric organocatalysis; Enantioselectivity; Zwitterionic amino acid