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.

  • Protocol
  • Published:

Thermal and high pressure intramolecular Diels–Alder reaction of vinylsulfonamides

Nature Protocols volume 1, pages 3076–3087 (2006)Cite this article

Abstract

Vinylsulfonamides with a furan, carbocyclic, semicyclic or acyclic 1,3-diene moiety are synthetized via a domino elimination–amidation reaction of 2-chloroethanesulfonyl chloride. Intramolecular Diels–Alder reaction of these vinylsulfonamides with thermal (toluene, 110 °C) or high pressure (dichloromethane, 13 kbar) activation provides efficient access to a range of γ- and δ-sultams following a 2–3 d long synthetic procedure. Enantiopure sultams are readily obtained from N-1-phenylethyl substituted vinylsulfonamides.

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

Figure 1
Figure 2: Intramolecular Diels–Alder reaction of vinylsulfonamides containing an acyclic or semicyclic 1,3-diene moiety to give γ-sultams.
Figure 3: IMDA of furan-containing vinylsulfonamides with an (S)-(–)-1-phenylethyl unit.
Figure 4: Reactions using vinylsulfonamides with carbocyclic or acyclic 1,3-diene moieties and an (S)-(–)-1-phenylethyl unit to give δ-sultams.
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9: GC integration of the reaction mixture 3k–6k.

Similar content being viewed by others

References

  1. Buglass, A.J. & Tillett, J.G. Sultones and sultams. in The Chemistry of Sulphonic Acids, Esters and Their Derivatives (eds. Patai, S. & Rappoport, Z.) 789–878 (Wiley, New York, 1991).

    Chapter  Google Scholar 

  2. Zhang, H.-K., Chan, W.-H., Lee, A.W.M., Wong, W.-Y. & Xia, P.-F. Synthesis of chiral sultams and their application as chiral auxiliaries in an asymmetric Diels-Alder reaction. Tetrahedron Asymmetry 16, 761–771 (2005).

    Article  CAS  Google Scholar 

  3. Hanessian, S., Sailes, H. & Therrien, E. Synthesis of functionally diverse bicyclic sulfonamides as constrained proline analogues and application to the design of potential thrombin inhibitors. Tetrahedron 59, 7047–7056 (2003).

    Article  CAS  Google Scholar 

  4. Zhuang, L. et al. Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected Cells. J. Med. Chem. 46, 453–456 (2003).

    Article  CAS  Google Scholar 

  5. Inagaki, M. et al. Novel antiarthritic agents with 1,2-isothiazolidine-1,1-dioxide (γ-sultam) skeleton: cytokine suppressive dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase. J. Med. Chem. 43, 2040–2048 (2000).

    Article  CAS  Google Scholar 

  6. Miller, R.A. et al. A practical and efficient preparation of the releasable naphthosultam side chain of a novel anti-MRSA carbapenem. J. Org. Chem. 65, 1399–1406 (2000).

    Article  CAS  Google Scholar 

  7. Rogachev, V.O., Filimonov, V.D., Fröhlich, R., Kataeva, O. & Metz, P. Stereoselective synthesis of γ- and δ-sultams by intramolecular Diels-Alder reaction of vinylsulfonamides possessing an acyclic or carbocyclic 1,3-diene moiety. Heterocycles 67, 589–595 (2006).

    Article  CAS  Google Scholar 

  8. Rogatchov, V.O. et al. Preparation of enantiopure sultams by intramolecular Diels-Alder reaction of furan-containing vinylsulfonamides. Tetrahedron Lett. 43, 4753–4756 (2002).

    Article  CAS  Google Scholar 

  9. Greig, I.R., Tozer, M.J. & Wright, P.T. Synthesis of cyclic sulfonamides through intramolecular Diels-Alder reactions. Org. Lett. 3, 369–371 (2001).

    Article  CAS  Google Scholar 

  10. Plietker, B., Seng, D., Fröhlich, R. & Metz, P. High pressure intramolecular Diels-Alder reactions of vinylsulfonates and vinylsulfonamides. Tetrahedron 56, 873–879 (2000).

    Article  CAS  Google Scholar 

  11. Brosius, A.D., Overman, L.E. & Schwink, L. Total synthesis of (+)-Aloperine. Use of a nitrogen-bound silicon tether in an intramolecular Diels-Alder Reaction. J. Am. Chem. Soc. 121, 700–709 (1999).

    Article  CAS  Google Scholar 

  12. Metz, P., Seng, D., Fröhlich, R. & Wibbeling, B. Intramolecular Diels-Alder reactions of vinylsulfonamides. Synlett 741–742 (1996).

  13. Lee, J., Zhong, Y.-L., Reamer, R.A. & Askin, D. Practical synthesis of sultams via sulfonamide dianion alkylation: application to the synthesis of chiral sultams. Org. Lett. 5, 4175–4177 (2003).

    Article  CAS  Google Scholar 

  14. Ueda, M. et al. Indium-mediated tandem radical addition-cyclization-trap reactions in aqueous media. Org. Lett. 5, 3835–3838 (2003).

    Article  CAS  Google Scholar 

  15. McReynolds, M.D., Dougherty, J.M. & Hanson, P.R. Synthesis of phosphorus and sulfur heterocycles via ring-closing olefin metathesis. Chem. Rev. 104, 2239–2258 (2004).

    Article  CAS  Google Scholar 

  16. Karsch, S., Freitag, D., Schwab, P. & Metz, P. Ring closing metathesis in the synthesis of sultones and sultams. Synthesis 1696–1712 (2004).

  17. Freitag, D., Schwab, P. & Metz, P. A concise synthesis of β-lactam-sulfonamide hybrids. Tetrahedron Lett. 45, 3589–3592 (2004).

    Article  CAS  Google Scholar 

  18. Merten, S., Fröhlich, R., Kataeva, O. & Metz, P. Synthesis of sultams by intramolecular heck reaction. Adv. Synth. Catal. 347, 754–758 (2005).

    Article  CAS  Google Scholar 

  19. Zhang, S.-J. et al. Diastereoselective epoxidation of N-enoylsultams with different chiral sultams as auxiliaries. Chin. J. Chem. 24, 681–688 (2006).

    Article  CAS  Google Scholar 

  20. Rehn, S., Ofial, A.R. & Mayr, H. Synthesis of allylamines from alkynes and iminium ions. Synthesis 1790–1796 (2003).

  21. Rondestvedt, C.S. Unsaturated sulfonic acids. IV. Preparation and properties of α-bromoalkenesulfonyl chlorides. J. Am. Chem. Soc. 76, 1926–1929 (1954).

    Article  CAS  Google Scholar 

  22. Wurche, F. & Klärner, F.G. The effect of pressure on organic reactions: basic principles and mechanistic applications. J. Prakt. Chem. 342, 609–636 (2000).

    Article  Google Scholar 

  23. Tietze, L.F., Henrich, M., Niklaus, A. & Buback, M. The effect of high pressure on the diastereoselectivity of intermolecular all-carbon Diels-Alder reactions. Chem. Eur. J. 5, 297–304 (1999).

    Article  CAS  Google Scholar 

  24. Zylber, J., Tubul, A. & Brun, P. Asymmetric synthesis of methyl N-(1-phenylethyl)-3-aza-10-oxatricyclo[5.2.1.01,5]-4-oxodec-8-ene-6-carboxylate by an intramolecular Diels-Alder reaction. Tetrahedron Asymmetry 6, 377–380 (1995).

    Article  CAS  Google Scholar 

  25. Jung, M.E. & Miller, S.J. Preparation of N-alkadienyl N-E-2-arylethenylcarbamates via sulfoxide elimination in a synthetic approach to lycorine. Heterocycles 30, 839–853 (1990).

    Article  CAS  Google Scholar 

  26. Alcaide, B. et al. Anomalous behavior in some nucleophilic ring opening of furyl-2-oxirane. Heterocycles 31, 1997–2002 (1990).

    Article  CAS  Google Scholar 

  27. Bovenschulte, E., Metz, P. & Henkel, G. Intramolecular Diels Alder reactions of vinylsulfonic acid esters. Angew. Chem. Int. Ed. Engl. 28, 202–203 (1989).

    Article  Google Scholar 

  28. Metz, P., Fleischer, M. & Fröhlich, R. Intramolecular Diels-Alder reaction of vinylsulfonates derived from hydroxyalkyl substituted 1,3-dienes and oxidative desulfurization of the resultant sultones. Tetrahedron 51, 711–732 (1995).

    Article  CAS  Google Scholar 

  29. Metz, P., Fleischer, M. & Fröhlich, R. Vinylsulfonyl chloride, a ketene equivalent for the intramolecular Diels-Alder reaction. Synlett 985–987 (1992).

  30. Sellén, M., Bäckvall, J.-E. & Helquist, P. Synthesis of substituted cyclic 1,3-dienes via selective 1,4-elimination of benzenesulfinic acid from allylic phenyl sulfones. J. Org. Chem. 56, 835–839 (1991).

    Article  Google Scholar 

  31. Bäckvall, J.-E. & Andersson, P.G. Stereocontrolled oxaspirocyclization of conjugated dienes via palladium catalysis. J. Org. Chem. 56, 2274–2276 (1991).

    Article  Google Scholar 

  32. Jurczak, J. & Gryko, D.T. Organic synthesis at high pressure. in Chemistry Under Extreme or Non-Classical Conditions (eds. van Eldik, R. & Hubbard, C.D.) 163–188 (Wiley, New York, and Spektrum, Heidelberg, Germany, 1996).

    Google Scholar 

  33. Matsumoto, K. & Acheson, R.M (eds.) Organic Synthesis at High Pressure 456pp. (Wiley, New York, 1991).

    Google Scholar 

Download references

Acknowledgements

Financial support of this work by the Deutsche Forschungsgemeinschaft (grants ME 776/15-2 and 436 RUS 17/90/04), the Russian Foundation for Basic Research (grants 00-03-32812 and 02-03-06577), the Ministry of Science and Education of Russia (grants 15134 and 399) and the Bundesministerium für Bildung und Forschung (grant RUS 02/044) is gratefully acknowledged. We thank Prof. Dr. H. Mayr, Ludwig-Maximilians-Universität München, for samples of dienylamines 1b and 1c, and V.O.R. thanks the Deutsche Akademische Austauschdienst for a research stipend.

Author information

Authors and Affiliations

  1. Department of Organic Chemistry, Tomsk Polytechnic University, Prospekt Lenina 30, Tomsk, 634050, Russia

    Victor O Rogachev

  2. Department of Chemistry, Technische Universität Dresden, Bergstraße 66, Dresden, D-01069, Germany

    Peter Metz

Authors
  1. Victor O Rogachev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Metz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victor O Rogachev.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rogachev, V., Metz, P. Thermal and high pressure intramolecular Diels–Alder reaction of vinylsulfonamides. Nat Protoc 1, 3076–3087 (2006). https://doi.org/10.1038/nprot.2006.463

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2006.463

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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