Facial Selectivity in Mechanical Bond Formation: Axially Chiral Enantiomers and Geometric Isomers from a Simple Prochiral Macrocycle

Gallagher, Peter R.; Savoini, Andrea; Saady, Abed; Maynard, John R. J.; Butler, Patrick W. V.; Tizzard, Graham J.; Goldup, Stephen M.

doi:10.1021/jacs.3c14329

Cited by 3 publications

(6 citation statements)

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“…This is not because the macrocycle preferentially encircles the amine unit; the high chemical shift of triazole protons H h in rotaxanes 11 is consistent with the macrocycle exchanging between the two triazole containing compartments where it engages in a C–H···N H-bond . Instead, and in contrast with MAC rotaxanes, based on a similar prochiral axle, the two co-conformers of rotaxanes 11 are enantiomeric and so the H h pair are enantiotopic and isochronous.…”

Section: Resultsmentioning

confidence: 93%

“…Our simple, first-principles approach has allowed us to unambiguously identify and define all the possible conditional stereogenic units of rotaxanes and catenanes and confirm that, now that a previously overlooked MGI-2 rotaxane stereochemistry has been found, the pantheon of unique stereogenic units is complete. Based on this analysis, methods exist to stereoselectively synthesize all conditional mechanical stereogenic units of [2]catenanes and [2]rotaxanes apart from MGI-2 rotaxanes; although until 2014, chiral stationary phase high-performance liquid chromatography (HPLC) was required to produce enantioenriched samples of mechanically chiral molecules since this time, methodologies for the stereoselective synthesis of MPC ,,, and MAC catenanes and rotaxanes have been disclosed. Similarly, the first stereoselective synthesis of MGI-1 rotaxanes was reported in 2005 using calixarene rings, and since then many examples based on cone-shaped macrocycles, and more recently simple prochiral rings, , have been reported.…”

Section: Resultsmentioning

confidence: 99%

“…Now that all of the mechanical stereogenic units of simple [2]catenanes and [2]rotaxanes have been delineated and concepts developed to allow their stereoselective synthesis, − ,− , it is reasonable to propose that, 62 years after such systems were first discussed, we have finally reached the end of the beginning of the study of mechanical stereochemistry. Such molecules have already been used as the basis of molecular machines, enantioselective sensors and catalysts, and chiroptical switches, work which will only accelerate as methods to synthesize them improve.…”

Section: Discussionmentioning

confidence: 99%

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The Final Stereogenic Unit of [2]Rotaxanes: Type 2 Geometric Isomers

Savoini,

Gallagher,

Saady

et al. 2024

J. Am. Chem. Soc.

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Mechanical stereochemistry arises when the interlocking of stereochemically trivial covalent subcomponents results in a stereochemically complex object. Although this general concept was identified in 1961, the stereochemical description of these molecules is still under development to the extent that new forms of mechanical stereochemistry are still being identified. Here, we present a simple analysis of rotaxane and catenane stereochemistry that allowed us to identify the final missing simple mechanical stereogenic unit, an overlooked form of rotaxane geometric isomerism, and demonstrate its stereoselective synthesis.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Final Stereogenic Unit of [2]Rotaxanes: Type 2 Geometric Isomers

Savoini,

Gallagher,

Saady

et al. 2024

J. Am. Chem. Soc.

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“…Given that the stereoisomers of rotaxanes and catenanes are clearly related by a notional ring opening process, it seems sensible that (i) the method used to assign their absolute stereochemistry should avoid automatic inversion of the stereolabel when this process is considered and (ii) the methods used should require the minimum number of arbitrary rules. We recently fell afoul of these rules; our proposed method for assigning the stereochemistry of axially chiral rotaxanes could not be extended to type 2 rotaxane geometric isomers without causing an inversion of stereolabel compared with the corresponding catenane . To overcome this problem, we have revised our methods for assigning the axial stereogenic unit of rotaxanes and catenanes.…”

Section: Describing Mechanical Stereochemistrymentioning

confidence: 99%

“…We recently fell afoul of these rules; our proposed method for assigning the stereochemistry of axially chiral rotaxanes could not be extended to type 2 rotaxane geometric isomers without causing an inversion of stereolabel compared with the corresponding catenane. 23 To overcome this problem, we have revised our methods for assigning the axial stereogenic unit of rotaxanes and catenanes.…”

Section: Describing Mechanical Stereochemistrymentioning

confidence: 99%

The End of the Beginning of Mechanical Stereochemistry

Goldup

2024

Acc. Chem. Res.

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Conspectus Stereochemistry has played a key role in the development of synthetic chemistry for the simple reason that the function and properties of most molecules, from medicine to materials science, depend on their shape and thus the stereoisomer used. However, despite the potential for rotaxanes and catenanes to display unusual forms of stereochemistry being identified as early as 1961, this aspect of the mechanical bond remained underexplored and underexploited; until 2014 it was only possible to access chiral rotaxanes and catenanes whose stereoisomerism is solely attributable to the mechanical bond using chiral stationary phase high performance liquid chromatography, which limited their production on scale and thus inhibited the investigation of their properties and applications. Furthermore, the stereogenic units of such molecules and analogues were often poorly described, which made it hard to fully articulate both what had been achieved in the field and what problems were left to solve. Relatively recently, methods to access rotaxanes and catenanes that display mechanical stereochemistry selectively have been developed, making these intriguing structures available for study in a range of prototypical applications including catalysis, sensing, and as chiral luminophores. In this Account, we briefly discuss the history of mechanical stereochemistry, beginning in 1961 when the potential for mechanical stereoisomerism was first identified, before defining how mechanical stereochemistry arises from a structural point of view. Building on this, using simple stereochemical arguments, we confirm that the complete set of unique stereogenic units of two-component rotaxanes and catenanes have finally been identified and categorized unambiguously, with the last being identified only in 2024. After pausing to discuss some of the stereochemical curiosities that arise when molecules contain both covalent and mechanical stereogenic units, and the potential for stereoisomerism to arise due to co-conformational movement, we use our stereochemical framework to summarize our efforts to develop conceptually general approaches to [2]catenanes and [2]rotaxanes containing all of the possible mechanical stereogenic units. In particular, we highlight how the nature of a mechanical stereogenic unit affects the available strategies for their stereoselective synthesis. We finish by highlighting recent prototypical chemical applications of interlocked molecules that rely on their mechanical stereochemistry, before discussing future directions and challenges. Taken together, we propose that the transition of such molecules from being hard to make and poorly described, to being available in high stereopurity using clearly articulated methodological and stereochemical concepts suggests that the field is finally maturing. Thus, we are now coming to the end of the beginning of mechanical stereochemistry. The stage is now set for such molecules to play a functional role in a range of areas, indeed in any chemical or physical application wh...

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