Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Dynamic self-correcting nucleophilic aromatic substitution

Nature Chemistry volume 10, pages 1023–1030 (2018)Cite this article

Subjects

Abstract

Dynamic covalent chemistry, with its ability to correct synthetic dead-ends, allows for the synthesis of elaborate extended network materials in high yields. However, the limited number of reactions amenable to dynamic covalent chemistry necessarily confines the scope and functionality of materials synthesized. Here, we explore the dynamic and self-correcting nature of nucleophilic aromatic substitution (SNAr), using ortho-aryldithiols and ortho-aryldifluorides that condense to produce redox-active thianthrene units. We demonstrate the facile construction of two-, three- and four-point junctions by reaction between a dithiol nucleophile and three different model electrophiles that produces molecules with two, three and four thianthrene moieties, respectively, in excellent yields. The regioselectivity observed is driven by thermodynamics; other connections form under kinetic control. We also show that the same chemistry can be extended to the synthesis of novel ladder macrocycles and porous polymer networks with Brunauer–Emmett–Teller surface area of up to 813 m2 g−1.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Reactions between a dithiol or tetrathiol nucleophile and three different model electrophiles.
Fig. 2: Dynamic, self-correcting SNAr reaction.
Fig. 3: Facile exchange of dithiol nucleophiles.
Fig. 4: Synthesis of ladder macrocycle 15.
Fig. 5: Model reaction, synthesis and characterization of porous ladder polymer network 19.
Fig. 6: Model reaction, synthesis and characterization of porous ladder polymer network 20.

Similar content being viewed by others

References

  1. Rowan, S. J., Cantrill, S. J., Cousins, G. R. L., Sanders, J. K. M. & Stoddart, J. F. Dynamic covalent chemistry. Angew. Chem. Int. Ed. 41, 898–952 (2002).

    Article  Google Scholar 

  2. Yu, C., Jin, Y. & Zhang, W. Dynamic Covalent Chemistry: Principles, Reactions, and Applications (Wiley-VCH, Weinheim, 2017).

    Chapter  Google Scholar 

  3. Jin, Y., Wang, Q., Taynton, P. & Zhang, W. Dynamic covalent chemistry approaches toward macrocycles, molecular cages, and polymers. Acc. Chem. Res. 47, 1575–1586 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Mastalerz, M. Shape-persistent organic cage compounds by dynamic covalent bond formation. Angew. Chem. Int. Ed. 49, 5042–5053 (2010).

    Article  CAS  Google Scholar 

  5. Zou, W., Dong, J., Luo, Y., Zhao, Q. & Xie, T. Dynamic covalent polymer networks: from old chemistry to modern day innovations. Adv. Mater. 29, 1606100 (2017).

    Article  CAS  Google Scholar 

  6. Belowich, M. E. & Stoddart, J. F. Dynamic imine chemistry. Chem. Soc. Rev. 41, 2003–2024 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Cromwell, O. R., Chung, J. & Guan, Z. Malleable and self-healing covalent polymer networks through tunable dynamic boronic ester bonds. J. Am. Chem. Soc. 137, 6492–6495 (2015).

    Article  CAS  PubMed  Google Scholar 

  8. Bapat, A. P., Roy, D., Ray, J. G., Savin, D. A. & Sumerlin, B. S. Dynamic-covalent macromolecular stars with boronic ester linkages. J. Am. Chem. Soc. 133, 19832–19838 (2011).

    Article  CAS  PubMed  Google Scholar 

  9. Black, S. P., Sanders, J. K. M. & Stefankiewicz, A. R. Disulfide exchange: exposing supramolecular reactivity through dynamic covalent chemistry. Chem. Soc. Rev. 43, 1861–1872 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Lu, Y.-X., Tournilhac, F., Leibler, L. & Guan, Z. Making insoluble polymer networks malleable via olefin metathesis. J. Am. Chem. Soc 134, 8424–8427 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. Wang, Q. et al. Dynamic covalent synthesis of aryleneethynylene cages through alkyne metathesis: dimer, tetramer, or interlocked complex? Chem. Sci. 7, 3370–3376 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jin, Y., Yu, C., Denman, R. J. & Zhang, W. Recent advances in dynamic covalent chemistry. Chem. Soc. Rev. 42, 6634–6654 (2013).

    Article  CAS  PubMed  Google Scholar 

  13. Guo, Q.-H., Fu, Z.-D., Zhao, L. & Wang, M.-X. Synthesis, structure, and properties of O6-corona[3]arene[3]tetrazines. Angew. Chem. Int. Ed. 53, 13548–13552 (2014).

    Article  CAS  Google Scholar 

  14. Fu, Z.-D., Guo, Q.-H., Zhao, L., Wang, D.-X. & Wang, M.-X. Synthesis and structure of corona[6](het)arenes containing mixed bridge units. Org. Lett. 18, 2668–2671 (2016).

    Article  CAS  PubMed  Google Scholar 

  15. Wackerly, J. W., Zhang, M., Nodder, S. T., Carlin, S. M. & Katz, J. L. Single step synthesis of acetylene-substituted oxacalix[4]arenes. Org. Lett. 16, 2920–2922 (2014).

    Article  CAS  PubMed  Google Scholar 

  16. Jayakannan, M. & Ramakrishnan, S. Recent developments in polyether synthesis. Macromol. Rapid Commun. 22, 1463–1473 (2001).

    Article  CAS  Google Scholar 

  17. Long, T. M. & Swager, T. M. Molecular design of free volume as a route to low-κ dielectric materials. J. Am. Chem. Soc. 125, 14113–14119 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. Katz, J. L., Selby, K. J. & Conry, R. R. Single-step synthesis of D3h-symmetric bicyclooxacalixarenes. Org. Lett. 7, 3505–3507 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Alsbaiee, A. et al. Rapid removal of organic micropollutants from water by a porous β-cyclodextrin polymer. Nature 529, 190–194 (2016).

    Article  CAS  PubMed  Google Scholar 

  20. Xiao, L. et al. β-Cyclodextrin polymer network sequesters perfluorooctanoic acid at environmentally relevant concentrations. J. Am. Chem. Soc. 139, 7689–7692 (2017).

    Article  CAS  PubMed  Google Scholar 

  21. Wu, Z.-C., Guo, Q.-H. & Wang, M.-X. Corona[5]arenes accessed by a macrocycle-to-macrocycle transformation route and a one-pot three-component reaction. Angew. Chem. Int. Ed. 56, 7151–7155 (2017).

    Article  CAS  Google Scholar 

  22. Ben-Haida, A. et al. Ring-closing depolymerisation of aromatic polyethers. Chem. Commun. 1533–1534 (1997).

  23. Joule, J. A. Thianthrenes in Advances in Heterocyclic Chemistry Vol. 48 (Academic, New York, 1990).

    Google Scholar 

  24. Ding, Y., Zhang, C., Zhang, L., Zhou, Y. & Yu, G. Molecular engineering of organic electroactive materials for redox flow batteries. Chem. Soc. Rev. 47, 69–103 (2018).

    Article  CAS  PubMed  Google Scholar 

  25. Bunnett, J. F. & Zahler, R. E. Aromatic nucleophilic substitution reactions. Chem. Rev. 49, 273–412 (1951).

    Article  CAS  Google Scholar 

  26. Makhseed, S., Ibrahim, F. & Samuel, J. Phthalimide based polymers of intrinsic microporosity. Polymer 53, 2964–2972 (2012).

    Article  CAS  Google Scholar 

  27. Hargreaves, M. K., Pritchard, J. G. & Dave, H. R. Cyclic carboxylic monoimides. Chem. Rev. 70, 439–469 (1970).

    Article  CAS  Google Scholar 

  28. McKeown, N. B. & Budd, P. M. Polymers of intrinsic microporosity (PIMs): organic materials for membrane separations, heterogeneous catalysis and hydrogen storage. Chem. Soc. Rev. 35, 675–683 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Mayor, M. & Lehn, J.-M. Potassium cryptate of a macrobicyclic ligand featuring a reducible hexakis(phenylthio)benzene electron-acceptor site. Helv. Chim. Acta 80, 2277–2285 (1997).

    Article  CAS  Google Scholar 

  30. Wu, H. et al. Tuning for visible fluorescence and near-infrared phosphorescence on a unimolecular mechanically sensitive platform via adjustable CH−π interaction. ACS Appl. Mater. Interfaces 9, 3865–3872 (2017).

    Article  CAS  PubMed  Google Scholar 

  31. Spokoyny, A. M. et al. A perfluoroaryl-cysteine SNAr chemistry approach to unprotected peptide stapling.J. Am. Chem. Soc. 135, 5946–5949 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sing, K. S. W. et al. Reporting data for gas/solid systems with special reference to the determination of surface area and porosity. IUPAC 57, 603–619 (1985).

    CAS  Google Scholar 

  33. Pandey, P. et al. A ‘click-based’ porous organic polymer from tetrahedral building blocks. J. Mater. Chem. 21, 1700–1703 (2011).

    Article  CAS  Google Scholar 

  34. Chakraborty, S., Colon, Y. J., Snurr, R. Q. & Nguyen, S. T. Hierarchically porous organic polymers: highly enhanced gas uptake and transport through templated synthesis. Chem. Sci. 6, 384–389 (2015).

    Article  CAS  PubMed  Google Scholar 

  35. Wilson, A., Gasparini, G. & Matile, S. Functional systems with orthogonal dynamic covalent bonds. Chem. Soc. Rev. 43, 1948–1962 (2014).

    Article  CAS  PubMed  Google Scholar 

  36. Lascano, S. et al. The third orthogonal dynamic covalent bond. Chem. Sci. 7, 4720–4724 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by an Abdul Latif Jameel World Water and Food Security Lab (J-WAFS) Seed Grant. W.J.O. is indebted to the Agency for Science, Technology and Research (A*STAR), Singapore, for a graduate scholarship. The authors thank M. He for discussions and XPS measurements, B. Yoon for SEM measurements, R. Cook and A. Leshinsky for MALDI measurements, R. G. Griffin and D. Banks for ssNMR measurements, and I. Jeon for X-ray diffraction measurements.

Author information

Authors and Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA

    Wen Jie Ong & Timothy M. Swager

Authors
  1. Wen Jie Ong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy M. Swager
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W.J.O. performed all of the experiments. Both authors designed the experiments, analysed the data, and wrote the manuscript.

Corresponding author

Correspondence to Timothy M. Swager.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figures 1–22; Cyclic voltammetry; Characterization of compounds 19 and 20; Experimental Procedures; NMR spectra

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ong, W.J., Swager, T.M. Dynamic self-correcting nucleophilic aromatic substitution. Nature Chem 10, 1023–1030 (2018). https://doi.org/10.1038/s41557-018-0122-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41557-018-0122-8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing