An Auxiliary Approach for the Stereoselective Synthesis of Topologically Chiral Catenanes

Mathieu Denis,James E.M Lewis,Florian Modicom,Stephen M Goldup

doi:10.1016/j.chempr.2019.03.008

Abstract

SummaryCatenanes, molecules in which two rings are threaded through one another like links in a chain, can form as two structures related like an object and its mirror image but otherwise identical if the individual rings lack bilateral symmetry. These structures are described as “topologically chiral” because, unlike most chiral molecules, it is not possible to convert one mirror-image form to the other under the rules of mathematical topology. Although intriguing and discussed as early as 1961, to date all methods of accessing molecules containing only this topological stereogenic element require the separation of the mirror-image forms via chiral stationary phase high-performance liquid chromatography, which has limited their investigation to date. Here, we present a simple method that uses a readily available source of chiral information to allow the stereoselective synthesis of topologically chiral catenanes.

Highlights

Chiral molecules occupy a special place in synthetic chemistry because of their ubiquity in biological systems and emerging applications in materials science.[1]
The examples of enantiopure catenanes in which the mechanical bond provides the only fixed stereogenic unit all make use of PCSP-HPLC to separate the enantiomeric products.[14,15]. This has prevented their investigation in enantioselective catalysis and sensing and materials science, even as examples of chiral interlocked molecules based on covalent stereogenic units[15,16,17,18,19] and other chirotopic mechanical stereogenic elements[20,21] have begun to show promise in these areas.[8]
We selected this methodology to demonstrate our proposed chiral auxiliary approach to topologically chiral catenanes because diastereomeric small crowded molecules, in which the topological and covalent elements of stereochemistry are held in close proximity and interact strongly, are a priori more likely to be separable

Summary

INTRODUCTION

Chiral molecules occupy a special place in synthetic chemistry because of their ubiquity in biological systems and emerging applications in materials science.[1]. The examples of enantiopure catenanes in which the mechanical bond provides the only fixed stereogenic unit all make use of PCSP-HPLC to separate the enantiomeric products.[14,15] This has prevented their investigation in enantioselective catalysis and sensing and materials science, even as examples of chiral interlocked molecules based on covalent stereogenic units[15,16,17,18,19] and other chirotopic mechanical stereogenic elements[20,21] have begun to show promise in these areas.[8]. Rise to two possible interlocked products that differ only in the configuration of the mechanical bond These diastereomers can be separated, at least in principle, by simple chemical means (e.g., silica gel chromatography) because they are no longer related as object and mirror image and have distinct physical properties. Once they are separated, ‘‘deleting’’ the covalent stereogenic unit from the catenanes would give rise to the separated mirror-image catenanes as single isomers, completely circumventing the need for enantiomer separation

RESULTS AND DISCUSSION

Conclusions

13. For a recent example see

24. This is directly analogous to the same approach in covalent systems