Nitrogen-Oxidized Tröger's Base Macrocyclic Arenes: Unprecedented Enantioselective Recognition in Water

Angew Chem Int Ed Engl. 2024 Oct 10:e202416975. doi: 10.1002/anie.202416975. Online ahead of print.

Abstract

Achieving high enantioselectivity with synthetic receptors, particularly in water, remains a significant challenge despite the success seen in natural biological systems. In this study, we introduce a facile synthesis of Tröger's base (TB)-containing macrocyclic arenes (TBn), where TB units are linked via methylene bridges, providing the macrocycles with a rigid framework. Oxidation of enantiopure TBn yields corresponding chiral nitrogen oxides (TBnNO) with excellent water solubility, attributed to the high polarity of the N-O bond, surpassing the pH limitations of traditional ion-functionalized approaches. Remarkably, TBnNO exhibits exceptional enantioselective recognition toward a wide range of chiral guests in aqueous solution, achieving enantioselectivities as high as 41.0. The underlying mechanism involves a combination of hydrophobic interactions and steric effects caused by rigid chiral cavities. These findings highlight the potential of nitrogen-oxidized macrocycles as a transformative tool for supramolecular application in water.

Keywords: Enantioselective Recognition ·Host-Guest Chemistry ·Tröger's base; macrocyclic arene ·Nitrogen-oxidized·.