Synthesis of a Mechanically Planar Chiral Rotaxane Ligand for Enantioselective Catalysis

Andrew W Heard,Stephen M Goldup

doi:10.1016/j.chempr.2020.02.006

Abstract

SummaryRotaxanes are interlocked molecules in which a molecular ring is trapped on a dumbbell-shaped axle because of its inability to escape over the bulky end groups, resulting in a so-called mechanical bond. Interlocked molecules have mainly been studied as components of molecular machines, but the crowded, flexible environment created by threading one molecule through another has also been explored in catalysis and sensing. However, so far, the applications of one of the most intriguing properties of interlocked molecules, their ability to display stereogenic units that do not rely on the stereochemistry of their covalent subunits, termed “mechanical chirality,” have yet to be properly explored, and prototypical demonstration of the applications of mechanically chiral rotaxanes remain scarce. Here, we describe a mechanically planar chiral rotaxane-based Au complex that mediates a cyclopropanation reaction with stereoselectivities that are comparable with the best conventional covalent catalyst reported for this reaction.

Highlights

Building on our recent effort to improve access to mechanically chiral molecules through the use of chiral derivatizing units[38,39] and auxiliaries,[40] here we demonstrate the first example of enantioselective catalysis with a mechanically planar chiral rotaxane, one of the simplest conditional mechanical stereogenic units, which arises when an achiral macrocycle with Cnh point group symmetry encircles an achiral axle with Cnv point group symmetry.[6,9,10]
Conclusions the first enantiopure mechanically planar chiral rotaxane was reported over two decades ago,[15] this is, to our knowledge, the first time that this stereogenic unit has been applied in catalysis
The stereoselectivities observed in this cyclopropanation reaction are lower than those reported when pivloate esters, which are not tolerated by [Au(6)(Cl)], were employed with the best covalent catalysts (76% to 94% ee),[41] clearly demonstrating that challenges remain to be overcome for mechanically chiral rotaxanes to become useful tools in organic synthesis

Summary

Introduction

Interlocked molecules such as rotaxanes, in which a dumbbell-shaped axle is threaded through a macrocycle, and catenanes, in which two or more macrocycles are held together in a manner akin to links in a chain,[1] are most commonly investigated as components of molecular machines,[2] building on the pioneering work of Stoddart and Sauvage, who were awarded the Nobel Prize for their efforts in 2016.3–5 In contrast, one of the most intriguing structural properties of interlocked molecules, their ability to display enantiotopic stereogenic elements that do not rely on covalent stereochemistry,[6] has received much less attention, despite the possibility of such enantiomerism being discussed early in the development of the field.[7,8] Such ‘‘mechanical’’ stereogenic units can arise because of desymmetrization of one of the covalent subunits by the relative position of the other (co-conformational chirality), the combination of subunits with appropriate symmetry properties (conditional mechanical chirality), or the unconditional topology of the mechanical bond itself (Figure 1A).[6,9,10]The relative paucity of even prototypical applications of mechanically chiral molecules is at least in part because enantiopure samples were historically hard to synthesize, with the pioneering work carried out by Vogtle, Okamoto, and Sauvage,[15,16] requiring the use of chiral stationary phase high-performance liquid chromatography (HPLC) to separate the enantiomeric products from a racemic mixture. Building on our recent effort to improve access to mechanically chiral molecules through the use of chiral derivatizing units[38,39] and auxiliaries,[40] here we demonstrate the first example of enantioselective catalysis with a mechanically planar chiral rotaxane, one of the simplest conditional mechanical stereogenic units, which arises when an achiral macrocycle with Cnh point group symmetry encircles an achiral axle with Cnv point group symmetry.[6,9,10] Our rotaxane catalyst, whose structure was not designed or optimized, displays enantioselectivities in an AuI-mediated cyclopropanation reaction comparable to the best reported covalent catalyst.[41] Our results suggest that mechanical stereochemistry has untapped potential in the development of new enantioselective catalytic systems.

Results

Conclusion