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:

Structurally defined anti-π-allyliridium complexes catalyse Z-retentive asymmetric allylic alkylation of oxindoles

Nature Catalysis volume 5, pages 1089–1097 (2022)Cite this article

Subjects

Abstract

The enantioselective synthesis of chiral Z-olefins is an important but challenging topic in organic chemistry. Iridium-catalysed Z-retentive asymmetric allylic substitution reactions have recently emerged as a promising strategy for trapping thermodynamically less stable anti-π-allyliridium intermediates. However, detailed mechanistic knowledge about this process has remained elusive. Here we report the structural characterization and transformations of the previously assumed putative anti-π-allyliridium intermediates. These complexes are highly efficient catalysts that enable Z-retentive asymmetric allylic alkylation of oxindoles accommodating a wide substrate scope. An iridium catalyst with a different metal-to-ligand ratio from that of a similar catalyst reported in the literature has been found to be crucial for regioselective nucleophilic attack at the less substituted allylic terminus. This simple yet powerful approach lays a solid foundation towards a general platform for the enantioselective synthesis of chiral Z-olefins.

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: Mechanism for transition metal-catalysed asymmetric allylic substitution.
Fig. 2: Synthesis of the π-allyliridium complexes.
Fig. 3: Isomerization of π-allyliridium complexes monitored by 31P NMR spectroscopy.
Fig. 4: Scope of the Ir-catalysed Z-retentive asymmetric allylic substitution.
Fig. 5: Optimized structures of key transition states.

Similar content being viewed by others

Data availability

Detailed experimental procedures, characterizations of new compounds and computational results are provided in the Supplementary Information. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2161348 (K1c-Cl), 2161343 (K1c-Br), 2161345 (K1c-I), 2161346 (K2a-Cl-H), 2161347 (K2a-I-H), 2161354 (K2c-Br-H), 2161350 (K2c-I-H), 2161340 (anti-K2c-Br-Me), 2161342 (anti-K2c-Br-Pr), 2161344 (anti-K2c-Br-Ph), 2161341 (exo-syn-K2c-Br-Me), 2161353 (endo-syn-K2c-Br-Pr), 2161349 (Z-3bA), 2161351 (Z-3a′A) and 2161352 (Z-3uA, structure shown in Supplementary Fig. 20). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. The output files of the theoretical calculations in this work have been deposited at Zenodo (https://doi.org/10.5281/zenodo.6817573). All other data are available from the corresponding authors upon reasonable request.

References

  1. Siau, W.-Y., Zhang, Y. & Zhao, Y. Stereoselective synthesis of Z-alkenes. Top. Curr. Chem. 327, 33–58 (2012).

    Article  CAS  Google Scholar 

  2. Oger, C., Balas, L., Durand, T. & Galano, J.-M. Are alkyne reductions chemo-, regio-, and stereoselective enough to provide pure (Z)-olefins in polyfunctionalized bioactive molecules? Chem. Rev. 113, 1313–1350 (2013).

    Article  CAS  Google Scholar 

  3. Kluwer, A. M. & Elsevier, C. J. in Handbook of Homogeneous Hydrogenation (eds de Vries, J. G. & Elsevier, C. J.) 375–412 (Wiley-VCH, 2007).

  4. Negishi, E.-i. et al. Recent advances in efficient and selective synthesis of di-, tri-, and tetrasubstituted alkenes via Pd-catalyzed alkenylation–carbonyl olefination synergy. Acc. Chem. Res. 41, 1474–1485 (2008).

    Article  CAS  Google Scholar 

  5. Xu, S., Kamada, H., Kim, E. H., Oda, A. & Negishi, E.-i. in Metal-Catalyzed Cross-Coupling Reactions and More (eds de Meijere, A. et al.) 133–278 (Wiley-VCH, 2014).

    Google Scholar 

  6. Armstrong, M. K., Goodstein, M. B. & Lalic, G. Diastereodivergent reductive cross coupling of alkynes through tandem catalysis: Z- and E-selective hydroarylation of terminal alkynes. J. Am. Chem. Soc. 140, 10233–10241 (2018).

    Article  CAS  Google Scholar 

  7. Ogba, O. M., Warner, N. C., O’Leary, D. J. & Grubbs, R. H. Recent advances in ruthenium-based olefin metathesis. Chem. Soc. Rev. 47, 4510–4544 (2018).

    Article  CAS  Google Scholar 

  8. Koh, M. J. et al. High-value alcohols and higher-oxidation-state compounds by catalytic Z-selective cross-metathesis. Nature 517, 181–186 (2015).

    Article  CAS  Google Scholar 

  9. Mu, Y., Nguyen, T. T., Koh, M. J., Schrock, R. R. & Hoveyda, A. H. E- and Z-, di- and tri-substituted alkenyl nitriles through catalytic cross-metathesis. Nat. Chem. 11, 478–487 (2019).

    Article  CAS  Google Scholar 

  10. Nevesely, T., Wienhold, M., Molloy, J. J. & Gilmour, R. Advances in the E → Z isomerization of alkenes using small molecule photocatalysts. Chem. Rev. 122, 2650–2694 (2022).

    Article  CAS  Google Scholar 

  11. Maryanoff, B. E. & Reitz, A. B. The Wittig olefination reaction and modifications involving phosphoryl-stabilized carbanions. Stereochemistry, mechanism, and selected synthetic aspects. Chem. Rev. 89, 863–927 (1989).

    Article  CAS  Google Scholar 

  12. Kazmaier, U. (ed.) Transition Metal Catalyzed Enantioselective Allylic Substitution in Organic Synthesis (Springer, 2012).

  13. Trost, B. M. & Crawley, M. L. Asymmetric transition-metal-catalyzed allylic alkylations: applications in total synthesis. Chem. Rev. 103, 2921–2944 (2003).

    Article  CAS  Google Scholar 

  14. Lu, Z. & Ma, S. Metal-catalyzed enantioselective allylation in asymmetric synthesis. Angew. Chem. Int. Ed. 47, 258–297 (2008).

    Article  CAS  Google Scholar 

  15. Consiglio, G. & Waymouth, R. M. Enantioselective homogeneous catalysis involving transition-metal-allyl intermediates. Chem. Rev. 89, 257–276 (1989).

    Article  CAS  Google Scholar 

  16. Faller, J. W., Thomsen, M. E. & Mattina, M. J. Organometallic conformational equilibriums. X. Steric factors and their mechanistic implications in π-allyl(amine)chloropalladium(II) complexes. J. Am. Chem. Soc. 93, 2642–2653 (1971).

    Article  CAS  Google Scholar 

  17. Gibson, D. H. & Erwin, D. K. Anti to syn isomerization in π-allyliron carbonyl complexes. J. Org. Chem. 86, C31–C33 (1975).

    Article  CAS  Google Scholar 

  18. Tobisch, S. & Taube, R. Density functional (DFT) study of the anti–syn isomerization of the butenyl group in cationic and neutral (butenyl)(butadiene)(monoligand)nickel(II) complexes. Organometallics 18, 3045–3060 (1999).

    Article  CAS  Google Scholar 

  19. Takeuchi, R. & Kashio, M. Iridium complex-catalyzed allylic alkylation of allylic esters and allylic alcohols: unique regio- and stereoselectivity. J. Am. Chem. Soc. 120, 8647–8655 (1998).

    Article  CAS  Google Scholar 

  20. Kazmaier, U. & Zumpe, F. L. Palladium-catalyzed allylic alkylations without isomerization—dream or reality? Angew. Chem. Int. Ed. 39, 802–804 (2000).

    Article  CAS  Google Scholar 

  21. Lin, H.-C. et al. Nucleophile-dependent Z/E- and regioselectivity in the palladium-catalyzed asymmetric allylic C–H alkylation of 1,4-dienes. J. Am. Chem. Soc. 141, 5824–5834 (2019).

    Article  CAS  Google Scholar 

  22. Jette, C. I., Tong, Z. J., Hadt, R. G. & Stoltz, B. M. Copper-catalyzed enantioselective allylic alkylation with a γ-butyrolactone-derived silyl ketene acetal. Angew. Chem. Int. Ed. 59, 2033–2038 (2020).

    Article  CAS  Google Scholar 

  23. Janssen, J. P. & Helmchen, G. First enantioselective alkylations of monosubstituted allylic acetates catalyzed by chiral iridium complexes. Tetrahedron Lett. 38, 8025–8026 (1997).

    Article  CAS  Google Scholar 

  24. Cheng, Q. et al. Iridium-catalyzed asymmetric allylic substitution reactions. Chem. Rev. 119, 1855–1969 (2019).

    Article  CAS  Google Scholar 

  25. Rössler, S. L., Petrone, D. A. & Carreira, E. M. Iridium-catalyzed asymmetric synthesis of functionally rich molecules enabled by (phosphoramidite,olefin) ligands. Acc. Chem. Res. 52, 2657–2672 (2019).

    Article  Google Scholar 

  26. Qu, J. & Helmchen, G. Applications of iridium-catalyzed asymmetric allylic substitution reactions in target-oriented synthesis. Acc. Chem. Res. 50, 2539–2555 (2017).

    Article  CAS  Google Scholar 

  27. Bartels, B. & Helmchen, G. Ir-catalysed allylic substitution: mechanistic aspects and asymmetric synthesis with phosphorus amidites as ligands. Chem. Commun. 741–742 (1999).

  28. Madrahimov, S. T. & Hartwig, J. F. Origins of enantioselectivity during allylic substitution reactions catalyzed by metallacyclic iridium complexes. J. Am. Chem. Soc. 134, 8136–8147 (2012).

    Article  CAS  Google Scholar 

  29. Liu, W.-B., Zheng, C., Zhuo, C.-X., Dai, L.-X. & You, S.-L. Iridium-catalyzed allylic alkylation reaction with N-aryl phosphoramidite ligands: scope and mechanistic studies. J. Am. Chem. Soc. 134, 4812–4821 (2012).

    Article  CAS  Google Scholar 

  30. Jiang, R., Ding, L., Zheng, C. & You, S.-L. Iridium-catalyzed Z-retentive asymmetric allylic substitution reactions. Science 371, 380–386 (2021).

    Article  CAS  Google Scholar 

  31. Ding, L., Song, H., Zheng, C. & You, S.-L. Enantioselective synthesis of medium-sized-ring lactones via iridium-catalyzed Z-retentive asymmetric allylic substitution reaction. J. Am. Chem. Soc. 144, 4770–4775 (2022).

    Article  CAS  Google Scholar 

  32. Rossler, S. L., Krautwald, S. & Carreira, E. M. Study of intermediates in iridium–(phosphoramidite,olefin)-catalyzed enantioselective allylic substitution. J. Am. Chem. Soc. 139, 3603–3606 (2017).

    Article  CAS  Google Scholar 

  33. Wolf, J. & Werner, H. Basic metals. Part 61. Synthesis of [(C5H5)Rh(η3-1-MeC3H4)[P(CHMe2)3]PF6 from (C5H5)Rh(MeC≡CMe)[P(CHMe2)3]. The mechanism of conversion of an alkyne into an allyl ligand via an allene intermediate. Organometallics 6, 1164–1169 (1987).

  34. Appleton, T. G., Clark, H. C. & Manzer, L. E. The trans-influence: its measurement and significance. Coord. Chem. Rev. 10, 335–422 (1973).

    Article  CAS  Google Scholar 

  35. Madrahimov, S. T., Markovic, D. & Hartwig, J. F. The allyl intermediate in regioselective and enantioselective iridium-catalyzed asymmetric allylic substitution reactions. J. Am. Chem. Soc. 131, 7228–7229 (2009).

    Article  CAS  Google Scholar 

  36. Spiess, S., Raskatov, J. A., Gnamm, C., Brodner, K. & Helmchen, G. Ir-catalyzed asymmetric allylic substitutions with (phosphoramidite)Ir complexes—resting states, synthesis, and characterization of catalytically active (π-allyl)Ir complexes. Chem. Eur. J. 15, 11087–11090 (2009).

    Article  CAS  Google Scholar 

  37. Frisch, M. J. et al. Gaussian 16, Revision A.03 (Gaussian Inc., 2016).

  38. Neese, F., Wennmohs, F., Becker, U. & Riplinger, C. The ORCA quantum chemistry program package. J. Chem. Phys. 152, 224108 (2020).

    Article  CAS  Google Scholar 

  39. Lu, T. & Chen, F. Multiwfn: a multifunctional wavefunction analyzer. J. Comput. Chem. 33, 580–592 (2012).

    Article  Google Scholar 

  40. Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the National Key Research and Development Program of China (2021YFA1500100), the National Natural Science Foundation of China (21821002, 22031012, 22171282 and 91856201), the Youth Innovation Promotion Association of the Chinese Academy of Sciences (Y2021075) and the Science and Technology Commission of Shanghai Municipality (19590750400 and 21520780100) for generous financial support. We also thank X. Leng (SIOC) and L. Li (Shanghai Jiao Tong University) for X-ray crystallographic analysis, and R. Leveson-Gower (University of Groningen) for proofreading the manuscript. S.-L.Y. thanks the support of the Tencent Foundation through an XPLORER PRIZE.

Author information

Authors and Affiliations

  1. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    Ru Jiang, Qing-Ru Zhao, Chao Zheng & Shu-Li You

Authors
  1. Ru Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing-Ru Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shu-Li You
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.-L.Y. conceived and supervised the project; R.J. synthesized and characterized the Ir complexes and developed the Ir-catalysed Z-retentive asymmetric allylic substitution reactions; Q.-R.Z. contributed to expanding the scope of the reaction; R.J. and C.Z. performed the electronic structure calculations; C.Z. wrote the manuscript with revisions suggested by all authors.

Corresponding authors

Correspondence to Chao Zheng or Shu-Li You.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Catalysis thanks Liqin Qiu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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 Methods, Figs. 1–21, Tables 1–19, notes and references.

Supplementary Data 1

Cif file for K1c-I.

Supplementary Data 2

Cif file for K1c-Br.

Supplementary Data 3

Cif file for K1c-Cl.

Supplementary Data 4

Cif file for K2a-Cl-H.

Supplementary Data 5

Cif file for K2a-I-H.

Supplementary Data 6

Cif file for K2c-Br-H.

Supplementary Data 7

Cif file for K2c-I-H.

Supplementary Data 8

Cif file for anti-K2c-Br-Me.

Supplementary Data 9

Cif file for anti-K2c-Br-Pr.

Supplementary Data 10

Cif file for anti-K2c-Br-Ph.

Supplementary Data 11

Cif file for exo-syn-K2c-Br-Me.

Supplementary Data 12

Cif file for endo-syn-K2c-Br-Pr.

Supplementary Data 13

Cif file for Z-3bA.

Supplementary Data 13

Cif file for Z-3a′A.

Supplementary Data 13

Cif file for Z-3uA.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, R., Zhao, QR., Zheng, C. et al. Structurally defined anti-π-allyliridium complexes catalyse Z-retentive asymmetric allylic alkylation of oxindoles. Nat Catal 5, 1089–1097 (2022). https://doi.org/10.1038/s41929-022-00879-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41929-022-00879-z

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