Molecular Diversity

, Volume 7, Issue 2–4, pp 107–114 | Cite as

A rapid microwave protocol for Heck vinylation of aryl chlorides under air

  • Gopal K. Datta
  • Karl S. A. Vallin
  • Mats Larhed


In modern high-throughput chemistry, the overall workflow is a crucial factor and much work is devoted to speeding up the process of chemistry development. Since automated microwave-based synthesizers are known to streamline the compound production and to accelerate slow organic transformations, this technology was implemented for Heck reactions with sluggish aryl chlorides. Furthermore, homogeneous palladium-catalyzed Heck vinylations of aryl chlorides can be performed under air under optimized conditions. Based on this finding, controlled microwave heating was utilized to accelerate model reactions down to 30 min employing a mixture of ionic liquid and 1,4-dioxane as solvent.

aryl chloride Heck reaction ionic liquid microwave heating palladium catalysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bräse, S., Köbberling, J. and Griebenow, N., Handbook of Organopalladium Chemistry for Organic Synthesis, E.-i. Negishi (ed.), Wiley-Interscience, New York, 2002, Vol. 2, pp. 3117–3131.Google Scholar
  2. 2.
    Kappe, C. O., High-speed combinatorial synthesis utilizing microwave irradiation, Curr. Opin. Chem. Bio., 6 (2002) 314–320.Google Scholar
  3. 3.
    Larhed, M. and Hallberg, A., Microwave-assisted high-speed chemistry: A new technique in drug discovery, Drug Discov. Today, 6 (2001) 406–416.Google Scholar
  4. 4.
    Lidström, P., Tierney, J., Wathey, B. and Westman. J., Microwave assisted organic synthesis – A review, Tetrahedron, 57 (2001) 9225–9283.Google Scholar
  5. 5.
    Lew, A., Krutzik, P. O., Hart, M. E. and Chamberlin, A. R., Increasing rates of reaction: Microwave-assisted organic synthesis for combinatorial chemistry, J. Comb. Chem., 4 (2002) 95–105.Google Scholar
  6. 6.
    Larhed, M., Moberg, C. and Hallberg, A., Microwave-accelerated homogeneous catalysis in organic chemistry, Acc. Chem. Res., 35 (2002) 717–727.Google Scholar
  7. 7.
    Vallin, K. S. A., Emilsson, P., Larhed, M. and Hallberg, A., High-speed Heck reactions in ionic liquid with controlled microwave heating, J. Org. Chem., 67 (2002) 6243–6246.Google Scholar
  8. 8.
    Littke, A. F. and Fu, G. C., Palladium-catalyzed coupling reactions of aryl chlorides, Angew. Chem. Int. Ed., 41 (2002) 4176–4211.Google Scholar
  9. 9.
    For the first report of a microwave-heated palladium-catalyzed reaction with an aryl chloride, see: Fürstner, A. and Seidel, G., Microwave-assisted synthesis of pinacol boronates from aryl chlorides catalyzed by a palladium/imidazolium salt system, Org. Lett., 4 (2002) 541–543.Google Scholar
  10. 10.
    For heterogeneous microwave promoted Heck arylations of aryl chlorides, see: Choudary, M. B., Madhi, S., Chowdari, S. N., Kantam, L. M. and Sreedhar, B., Layered double hydroxide supported nanopalladium catalyst for Heck-, Suzuki-, Sonogashira-, and Stille-type coupling reactions of chloroarenes, J. Am. Chem. Soc., 124 (2002) 14127–14136.Google Scholar
  11. 11.
    Netherton, M. R. and Fu, G. C., Air-stable trialkylphosphonium salts: simple, practical, and versatile replacements for air-sensitive trialkylphosphines. applications in stoichiometric and catalytic processes, Org. Lett., 3 (2001) 4295–4298.Google Scholar
  12. 12.
    Heck, R. F., Nolley, J. P., Palladium-catalyzed vinylic hydrogen substitution reactions with aryl, benzyl, and styryl halides, J. Org. Chem., 37 (1972) 2320–2322.Google Scholar
  13. 13.
    De Meijere, A. and Meyer, F. E., Fine feathers make fine birds: The Heck reaction in modern garb, Angew. Chem. Int. Ed. Engl., 23/24 (1994) 2379–2411.Google Scholar
  14. 14.
    Beletskaya, I. P. and Cheprakov, A. V., The Heck reaction as a sharpening stone of palladium catalysis, Chem. Rev., 100 (2000) 3009–3066.Google Scholar
  15. 15.
    Larhed, M. and Hallberg, A., Handbook of Organopalladium Chemistry for Organic Synthesis, E.-i. Negishi (ed.), Wiley-Interscience, New York, 2002, Vol. 1, pp. 1133–1178.Google Scholar
  16. 16.
    Welton, T., Room-temperature ionic liquids. Solvents for synthesis and catalysis, Chem. Rev., 99 (1999) 2071–2083.Google Scholar
  17. 17.
    Wasserscheid, P. and Keim, W., Ionic liquids – New ‘solutions’ for transition metal catalysis, Angew. Chem. Int. Ed., 39 (2000) 3773–3789.Google Scholar
  18. 18.
    Sheldon, R., Catalytic reactions in ionic liquids, Chem. Commun., (2001) 2399–2407.Google Scholar
  19. 19.
    Ley, S. V., Leach, A. G. and Storer, R. I., A polymer-supported thionating reagent, J. Chem. Soc., Perkin Trans. 1, (2001) 358–361.Google Scholar
  20. 20.
    Van der Eycken, E., Appukkuttan, P., De Borggraeve, W., Dehaen, W., Dallinger, D. and Kappe, C. O., High-speed microwave-promoted hetero-Diels-Alder reactions of 2(1H)-pyrazinones in ionic liquid doped solvents, J. Org. Chem., 67 (2002) 7904–7907.Google Scholar
  21. 21.
    Carmichael, A. J., Earle, M. J., Holbrey, J. D., McCormac, P. B. and Seddon, K. R., The Heck reaction in ionic liquids: A multiphasic catalyst system, Org. Lett., 1 (1999) 997–1000.Google Scholar
  22. 22.
    Selvakumar, K., Zapf, A., Beller, M., New palladium carbene catalysts for the Heck reaction of aryl chlorides in ionic liquids, Org. Lett., 4 (2002) 3031–3033.Google Scholar
  23. 23.
    Herrmann, W. A., Bohm, V. P.W. and Reisinger, C. P., Application of palladacycles in Heck type reactions, J. Organomet. Chem., 576 (1999) 23–41.Google Scholar
  24. 24.
    Leadbeater, N. E. and Torenius, H. M., A study of the ionic liquid mediated microwave heating of organic solvents, J.Org. Chem., 67 (2002) 3145–3148.Google Scholar
  25. 25.
    Herrmann, W. A. and Kocher, C., N-heterocyclic carbenes, Angew. Chem. Int. Ed. Engl., 36 (1997) 2163–2187.Google Scholar
  26. 26.
    McGuinness, D. S., Cavell, K. J., Skelton, B. W. and White, A. H., Zerovalent palladium and nickel complexes of heterocyclic carbenes: Oxidative addition of organic halides, carbon-carbon coupling processes, and the Heck reaction, Organometallics, 18 (1999) 1596–1605.Google Scholar
  27. 27.
    Feuerstein, M., Doucet, H. and Santelli, M., Efficient Heck vinylation of aryl halides catalyzed by a new air-stable palladium-tetraphosphine complex, J. Org. Chem., 66 (2001) 5923–5925.Google Scholar
  28. 28.
    Calo, V., Nacci, A., Monopoli, A., Lopez, L. and Di Cosmo, A., Heck reaction of β-substituted acrylates in ionic liquids catalyzed by a Pd-benzothiazole carbene complex, Tetrahedron, 57 (2001) 6071–6077.Google Scholar
  29. 29.
    Feuerstein, M., Doucet, H. and Santelli, M., Palladium/tetraphosphine catalysed heck reaction with orthosubstituted aryl bromides, Synlett., 12 (2001) 1980–1982.Google Scholar
  30. 30.
    Montgomery, G. J., McKeown, P., McGown, A. T. and Robins, D. J., Synthesis and antiproliferative activity of unsaturated quinoline derivatives, Anti-Cancer Drug Design, 15 (2000) 171–181.Google Scholar
  31. 31.
    Dupont, J., Monteiro, A. L., Pozebon, D. and Gruber, S. A., On the use of phosphine-free PdCl 2 (SEt2)2 complex as catalyst precursor for the Heck reaction, Tetrahedron Lett., 42 (2001) 7345–7348.Google Scholar
  32. 32.
    Beller, M., Hartmut, F., Klaus, K., Reisinger, C. P. and Herrmann, W. A., First palladium-catalyzed Heck reactions with efficient colloidal catalyst systems, J. Organomet. Chem., 520 (1996) 257–259.Google Scholar
  33. 33.
    Gooben, L. J. and Paetzold, J., Pd-catalyzed decarbonylative olefination of aryl esters: Towards a waste-free Heck reaction, Angew. Chem. Int. Ed., 41 (2002) 1237–1241.Google Scholar
  34. 34.
    Huddleston, J. G., Willauer, H. D., Swatloski, R. P., Visser, A. E. and Rogers, R. D., Room temperature ionic liquids as novel media for ‘clean’ liquid-liquid extraction, Chem. Commun., (1998) 1765–1766.Google Scholar
  35. 35.
    Lucas, P., El Mehdi, N., Ho, H. A., Belanger, D. and Breau, L., Expedient synthesis of symmetric aryl ketones and of ambient-temperature molten salts of imidazole, Synthesis, 9 (2000) 1253–1258.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Gopal K. Datta
    • 1
  • Karl S. A. Vallin
    • 1
  • Mats Larhed
    • 1
  1. 1.Department of Organic Pharmaceutical Chemistry, Biomedical CentreUppsala UniversityUppsalaSweden

Personalised recommendations