Skip to main content
SpringerLink
Log in

Iron(III)-catalysed carbonyl–olefin metathesis

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon–carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries1. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism2. While the corresponding carbonyl–olefin metathesis reaction can also be used to construct carbon–carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl–olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl–olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Olefination and metathesis reactions for the formation of alkenes.
Figure 2: Initial evaluation of the catalytic carbonyl–olefin metathesis reaction.
Figure 3: Scope of the iron(III)-catalysed carbonyl–olefin metathesis reaction.
Figure 4: Alkene evaluation in the catalytic carbonyl–olefin metathesis reaction.
Figure 5: Mechanistic hypothesis for the iron(III)-chloride-catalysed carbonyl–olefin metathesis reaction.

Similar content being viewed by others

References

  1. Hoveyda, A. H. & Zhugralin, A. R. The remarkable metal-catalysed olefin metathesis reaction. Nature 450, 243–251 (2007)

    Article  CAS  ADS  Google Scholar 

  2. Grubbs, R. H. & Wenzel, A. G. Handbook of Metathesis 2nd edn, Vols 1–3 (Wiley, 2015)

  3. Katz, T. J. & McGinnis, J. The mechanism of the olefin metathesis reaction. J. Am. Chem. Soc. 97, 1592–1594 (1975)

    Article  CAS  Google Scholar 

  4. Grubbs, R. H., Carr, D. D., Hoppin, C. & Burk, P. L. Consideration of the mechanism of the metal catalyzed olefin metathesis reaction. J. Am. Chem. Soc. 98, 3478–3483 (1976)

    Article  CAS  Google Scholar 

  5. Chauvin, Y. Olefin metathesis: the early days. Angew. Chem. Int. Ed. 45, 3740–3747 (2006)

    Article  Google Scholar 

  6. Fürstner, A. Olefin metathesis and beyond. Angew. Chem. Int. Ed. 39, 3012–3043 (2000)

    Article  Google Scholar 

  7. 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 

  8. Petasis, N. A. & Bzowej, E. I. Titanium-mediated carbonyl olefinations. 1. Methylenations of carbonyl compounds with dimethyltitanocene. J. Am. Chem. Soc. 112, 6392–6394 (1990)

    Article  CAS  Google Scholar 

  9. Takeda, T. & Tsubouchi, A. in Modern Carbonyl Olefination (ed. Takeda, T. ) 151–199 (Wiley, 2003)

  10. Jones, G. II, Acquadro, M. A. & Carmody, M. A. Long-chain enals via carbonyl–olefin metathesis. An application in pheromone synthesis. J. Chem. Soc. Chem. Commun. 6, 206–207 (1975)

    Article  Google Scholar 

  11. Pérez-Ruiz, R., Miranda, M. A., Alle, R., Meerholz, K. & Griesbeck, A. G. An efficient carbonyl-alkene metathesis of bicyclic oxetanes: photoinduced electron transfer reduction of the Paternò–Büchi adducts from 2,3-dihydrofuran and aromatic aldehydes. Photochem. Photobiol. Sci. 5, 51–55 (2006)

    Article  Google Scholar 

  12. Valiulin, R. A. & Kutateladze, A. G. Harvesting the strain installed by a Paternò−Büchi step in a synthetically useful way: high-yielding photoprotolytic oxametathesis in polycyclic systems. Org. Lett. 11, 3886–3889 (2009)

    Article  CAS  Google Scholar 

  13. Fu, G. C. & Grubbs, R. H. Synthesis of cycloalkenes via alkylidene-mediated olefin metathesis and carbonyl olefination. J. Am. Chem. Soc. 115, 3800–3801 (1993)

    Article  CAS  Google Scholar 

  14. Stille, J. R., Santarsiero, B. D. & Grubbs, R. H. Rearrangement of bicyclo[2.2.1]heptane ring systems by titanocene alkylidene complexes to bicyclo[3.2.0]heptane enol ethers. Total synthesis of (±)-Δ9(12)-capnellene. J. Org. Chem. 55, 843–862 (1990)

    Article  CAS  Google Scholar 

  15. Iyer, K. & Rainier, J. D. Olefinic ester and diene ring-closing metathesis using a reduced titanium alkylidene. J. Am. Chem. Soc. 129, 12604–12605 (2007)

    Article  CAS  Google Scholar 

  16. Soicke, A., Slavov, N., Neudörfl, J.-M. & Schmalz, H.-G. Metal-free intramolecular carbonyl–olefin metathesis of ortho-prenylaryl ketones. Synlett 17, 2487–2490 (2011)

    Google Scholar 

  17. van Schaik, H.-P., Vijn, R.-J. & Bickelhaupt, F. Acid-catalyzed olefination of benzaldehyde. Angew. Chem. Int. Edn Engl. 33, 1611–1612 (1994)

    Article  Google Scholar 

  18. Bah, J., Franzén, J. & Naidu, V. R. Direct organocatalytic oxo-metathesis, a trans-selective carbocation-catalyzed olefination of aldehydes. Eur. J. Org. Chem. 2015, 1834–1839 (2015)

    Article  Google Scholar 

  19. Jossifov, C., Kalinova, R. & Demonceau, A. Carbonyl olefin metathesis. Chim. Oggi 26, 85–87 (2008)

    CAS  Google Scholar 

  20. Griffith, A. K., Vanos, C. M. & Lambert, T. H. Organocatalytic carbonyl-olefin metathesis. J. Am. Chem. Soc. 134, 18581–18584 (2012)

    Article  CAS  Google Scholar 

  21. Hong, B., Li, H., Wu, J., Zhang, J. & Lei, X. Total syntheses of (−)-huperzine Q and (+)-lycopladines B and C. Angew. Chem. Int. Ed. 54, 1011–1015 (2015)

    Article  CAS  Google Scholar 

  22. Heller, S. T., Kiho, T., Narayan, A. R. H. & Sarpong, R. Protic-solvent-mediated cycloisomerization of quinoline and isoquinoline propargylic alcohols: syntheses of (±)-3-demethoxyerythratidinone and (±)-cocculidine. Angew. Chem. Int. Ed. 52, 11129–11133 (2013)

    Article  CAS  Google Scholar 

  23. Clarke, M. L. & France, M. B. The carbonyl ene reaction. Tetrahedron 64, 9003–9031 (2008)

    Article  CAS  Google Scholar 

  24. Miles, R. B., Davis, C. E. & Coates, R. M. Syn- and anti-selective Prins cyclizations of δ,ε-unsaturated ketones to 1,3-halohydrins with Lewis acids. J. Org. Chem. 71, 1493–1501 (2006)

    Article  CAS  Google Scholar 

  25. Jackson, A. C., Goldman, B. E. & Snider, B. B. Intramolecular and intermolecular Lewis acid catalyzed ene reactions using ketones as enophiles. J. Org. Chem. 49, 3988–3994 (1984)

    Article  CAS  Google Scholar 

  26. Reetz, M. T. Lewis acid induced α-alkylation of carbonyl compounds. Angew. Chem. Int. Edn Engl. 21, 96–108 (1982)

    Article  Google Scholar 

  27. Demole, E., Enggist, P. & Borer, M. C. Applications synthétiques de la cyclisation d’alcools tertiaires γ-éthyléniques en α-bromotétrahydrofurannes sous l’action du N-bromosuccinimide. II. Cyclisation du (±)-nérolidol en diméthyl-2,5-(méthyl-4-pentène-3-yl)-2-cycloheptène-4-one, tétraméthyl-3, 3, 7, 10-oxa-2-tricyclo[5.5.0.01,4]-dodécène-9, β-acoratriène, cédradiène-2,8, épi-2-α-cédrène et α-cédrène. Helv. Chim. Acta 54, 1845–1864 (1971)

    Article  CAS  Google Scholar 

  28. Carless, H. A. J. & Trivedi, H. S. New ring expansion reaction of 2-t-butyloxetans. J. Chem. Soc. Chem. Commun. 382–383 (1979)

  29. Zimmerman, P. M. Automated discovery of chemically reasonable elementary reaction steps. J. Comput. Chem. 34, 1385–1392 (2013)

    Article  CAS  Google Scholar 

  30. Zimmerman, P. M. Reliable transition state searches integrated with the growing string method. J. Chem. Theory Comput. 9, 3043–3050 (2013)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Petroleum Research Fund (PRF#54688-DNI1) and start-up funds provided by the University of Michigan. J.R.L. thanks the National Science Foundation for a predoctoral fellowship. P.M.Z. thanks the Office of Naval Research for support under grant N00014-14-1-0551 and the Petroleum Research Fund (PRF#54267-DNI6). We are grateful to A. Speelman, A. McQuarters and N. Lehnert at the University of Michigan for helpful discussions.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Michigan, Willard Henry Dow Laboratory, 930 North University Avenue, Ann Arbor, 48109, Michigan, USA

    Jacob R. Ludwig, Paul M. Zimmerman, Joseph B. Gianino & Corinna S. Schindler

Authors
  1. Jacob R. Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul M. Zimmerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph B. Gianino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Corinna S. Schindler
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.R.L., J.B.G. and C.S.S. devised the experiments, prepared the starting materials and the products. P.M.Z. conducted the theoretical investigations. J.R.L., J.B.G., P.M.Z. and C.S.S. prepared this manuscript for publication.

Corresponding author

Correspondence to Corinna S. Schindler.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Tables 1-8 and 6 Supplementary Figures. Also included are Supplementary Methods and Materials, Supplementary Results, X-Ray crystallographic data and NMR Spectral data, which contains 1H and 13C NMR data for all new compounds. (PDF 34111 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ludwig, J., Zimmerman, P., Gianino, J. et al. Iron(III)-catalysed carbonyl–olefin metathesis. Nature 533, 374–379 (2016). https://doi.org/10.1038/nature17432

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature17432

  • Springer Nature Limited

This article is cited by

Search

Navigation