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Mechanically axially chiral catenanes and noncanonical mechanically axially chiral rotaxanes

Abstract

Chirality typically arises in molecules because of a rigidly chiral arrangement of covalently bonded atoms. Less generally appreciated is that chirality can arise when molecules are threaded through one another to create a mechanical bond. For example, when two macrocycles with chemically distinct faces are joined to form a catenane, the structure is chiral, although the rings themselves are not. However, enantiopure mechanically axially chiral catenanes in which the mechanical bond provides the sole source of stereochemistry have not been reported. Here we re-examine the symmetry properties of these molecules and in doing so identify a straightforward route to access them from simple chiral building blocks. Our analysis also led us to identify an analogous but previously unremarked upon rotaxane stereogenic unit, which also yielded to our co-conformational auxiliary approach. With methods to access mechanically axially chiral molecules in hand, their properties and applications can now be explored.

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Fig. 1: Schematic depictions of the mechanical stereogenic units of chiral catenanes and rotaxanes (stereolabels are arbitrary).
Fig. 2: Proposed co-conformational auxiliary approach for the synthesis of axially chiral catenanes.
Fig. 3: Synthesis and analysis of enantiopure axially chiral catenane 6.
Fig. 4: Synthesis of mechanically axially chiral rotaxane 10.
Fig. 5: Assignment and further analysis of the mechanical axial stereogenic unit.

Data availability

All characterization data for novel compounds (NMR, MS, CD, HPLC) are available through the University of Southampton data repository (https://doi.org/10.5258/SOTON/D2185). Crystallographic data have been uploaded to the CCDC and are available under accession nos. 2109976 (rac-(Sma,Rco-c)-3), 2115463 (rac-6), 2109991 (rac-S15) and 2109992 ((Rma,Rco-c)-9).

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Acknowledgements

S.M.G. thanks the ERC (agreement no. 724987) and the Royal Society for a Wolfson Research Fellowship (RSWF\FT\180010). P.B. thanks the University of Southampton for a Presidential Scholarship. P.G. thanks the University of Southampton for funding.

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Authors and Affiliations

Authors

Contributions

J.R.J.M. and P.G. contributed equally. Both have the right to place themselves as first author on their CVs. J.R.J.M. and S.M.G. developed the co-conformational auxiliary concept. J.R.J.M. synthesized 3 and 5 and collected SCXRD diffraction data for a reduced product of catenane 5. P.G. synthesized 9 and 10, determined the stereochemistry of rotaxanes 9, and managed the preparation of manuscript graphics. D.L. optimized the synthesis and purification of 3 and 5, synthesized 6 and determined the stereochemistry of catenanes 3. P.B. collected the X-ray diffraction data of 3, 6 and 9 and fully refined all SCXRD data. D.L. and P.G. managed the preparation of the Supplementary Information. S.M.G. directed the research. All authors contributed to the analysis of the results and the writing of the manuscript.

Corresponding author

Correspondence to Stephen M. Goldup.

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Supplementary information

Supplementary Information

Experimental procedures and analytical data for compounds 110 and S1S21 and elaborated discussions of manuscript content.

Supplementary Data 1

Crystallographic data for catenane rac-(Sma,Rco-c)-3; (CCDC reference, 2109976)

Supplementary Data 2

Crystallographic data for catenane rac-6; (CCDC reference, 2115463)

Supplementary Data 3

Crystallographic data for catenane rac-S15; (CCDC reference, 2109991)

Supplementary Data 4

Crystallographic data for rotaxane (Rma,Rco-c)-9; (CCDC reference, 2109992)

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Maynard, J.R.J., Gallagher, P., Lozano, D. et al. Mechanically axially chiral catenanes and noncanonical mechanically axially chiral rotaxanes. Nat. Chem. (2022). https://doi.org/10.1038/s41557-022-00973-6

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