The Cu-Free Sonogashira Reaction Mechanism

Part of the Springer Theses book series (Springer Theses)


The palladium-catalyzed Sonogashira reaction is one of the most important and widely used methods for preparing arylacetylenes and conjugated enynes, [1, 2, 3, 4, 5, 6] which are precursors for natural products, pharmaceuticals, and materials with specialized optical and electronic properties [7, 8, 9, 10, 11, 12]. The purpose of the work reported in this chapter was to weigh up the reaction mechanisms proposed in the literature and possible alternative pathways using a general model of the typical Pd-catalyzed copper-free Sonogashira reaction. To this aim, the Gibbs energy profiles of the different mechanistic proposals were computed by means of DFT calculations. Additionally, the effect of the electronic nature of the alkyne’s substituents over all the reaction pathways was also analyzed. This was examined for a set of substituents combining theoretical calculations and experiments. This work was carried out in collaboration with the experimental group of Prof. Carmen N\(\acute{\mathrm{a}}\)jera at the Universidad de Alicante.


Energy Barrier Ionic Mechanism Phosphine Ligand Anionic Mechanism Reductive Elimination 
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  1. 1.
    Sonogashira, K.: J. Organomet. Chem. 653, 46 (2002)CrossRefGoogle Scholar
  2. 2.
    Negishi, E.-I., Anastasia, L.: Chem. Rev. 2003, 103 (1979)Google Scholar
  3. 3.
    Tykwinski, R.R.: Angew. Chem. Int. Ed. 42, 1566 (2003)CrossRefGoogle Scholar
  4. 4.
    Chinchilla, R., Nãijera, C.: Chem. Rev. 107, 874 (2007)CrossRefGoogle Scholar
  5. 5.
    Chinchilla, R., Nãijera, C.: Chem. Soc. Rev. 40, 5084 (2011)CrossRefGoogle Scholar
  6. 6.
    Bunz, U.H.F.: Chem. Rev. 100, 1605 (2000)CrossRefGoogle Scholar
  7. 7.
    Nicolaou, K.C., Bulger, P.G., Sarlah, D.: Angew. Chem. Int. Ed. 44, 4442 (2005)CrossRefGoogle Scholar
  8. 8.
    Müller, T.J., D’Souza, D.M.: Pure Appl. Chem. 80, 609 (2008)CrossRefGoogle Scholar
  9. 9.
    Schiedel, M.S., Briehn, C.A., Bäuerle, P.: J. Organomet. Chem. 653, 200 (2002)CrossRefGoogle Scholar
  10. 10.
    Hortholary, C., Coudret, C.: J. Org. Chem. 68, 2167 (2003)CrossRefGoogle Scholar
  11. 11.
    Zapf, A., Beller, M.: Top. Catal. 19, 101 (2002)CrossRefGoogle Scholar
  12. 12.
    Torborg, C., Beller, M.: Adv. Synth. Catal. 351, 3027 (2009)CrossRefGoogle Scholar
  13. 13.
    Dieck, H.A., Heck, F.R.: J. Organomet. Chem. 93, 259 (1975)CrossRefGoogle Scholar
  14. 14.
    Cassar, L.: J. Organomet. Chem. 93, 253 (1975)CrossRefGoogle Scholar
  15. 15.
    Kotora, M., Takahashi, T.: In: Negishi, E.-I., de Meijere, A. (eds.) Handbook of Organopalladium Chemistry for Organic Synthesis, p. 973. Wiley-Interscience, New York (2002)CrossRefGoogle Scholar
  16. 16.
    Bräse, S., de Meijere, A.: In: Negishi, E.-I., de Meijere, A. (eds.) Handbook of Organopalladium Chemistry for Organic Synthesis, p. 1133. Wiley-Interscience, New York (2002)Google Scholar
  17. 17.
    Sonogashira, K., Tohda, Y., Hagihara, N.: Tetrahedron Lett. 16, 4467 (1975)Google Scholar
  18. 18.
    Ljungdahl, T., Pettersson, K., Albinsson, B., Mårtensson, J.: J. Org. Chem. 71, 1677 (2006)CrossRefGoogle Scholar
  19. 19.
    Gelman, D., Buchwald, S.L.: Angew. Chem. Int. Ed. 42, 5993 (2003)CrossRefGoogle Scholar
  20. 20.
    Siemsen, P., Livingston, R.C., Diederich, F.: Angew. Chem. Int. Ed. 39, 2633 (2000)CrossRefGoogle Scholar
  21. 21.
    Fukuyama, T., Shinmen, M., Nishitani, S., Sato, M., Ryu, I.: Org. Lett. 4, 1691 (2002)CrossRefGoogle Scholar
  22. 22.
    Soheili, A., Albaneze-Walker, J., Murry, J.A., Dormer, P.G., Hughes, D.L.: Org. Lett. 5, 4191 (2003)CrossRefGoogle Scholar
  23. 23.
    NÃijera, C., Gil-Moltó, J., Karlström, S., Falvello, L.R.: Org. Lett. 5, 1451 (2003)Google Scholar
  24. 24.
    Rau, S., Lamm, K., Görls, H., Schöffel, J., Walther, D.: J. Organomet. Chem. 689, 3582 (2004)CrossRefGoogle Scholar
  25. 25.
    Li, J.-H., Zhang, X.-D., Xie, Y.-X.: Eur. J. Org. Chem. 2005, 4256 (2005)Google Scholar
  26. 26.
    Gil-Moltó, J., Nãijera, C.: Eur. J. Org. Chem. 19, 4073 (2005)Google Scholar
  27. 27.
    Yi, C., Hua, R.: Catal. Commun. 7, 377 (2006)CrossRefGoogle Scholar
  28. 28.
    de Lima, G.P., Antunes, O.A.C.: Tetrahedron Lett. 49, 2506 (2008)CrossRefGoogle Scholar
  29. 29.
    Komãiromi, A., Tolnai, G., Novãik, Z.: Tetrahedron Lett. 49, 7294 (2008)CrossRefGoogle Scholar
  30. 30.
    Alonso, D.A., Nãijera, C., Pacheco, M.C.: Tetrahedron Lett. 43, 9365 (2002)CrossRefGoogle Scholar
  31. 31.
    Cheng, J., Sun, Y.-H., Wang, F., Guo, M.-J., Xu, J.-H., Pan, Y., Zhang, Z.-G.: J. Org. Chem. 69, 5428 (2004)CrossRefGoogle Scholar
  32. 32.
    Ruiz, J., Cutillas, N., López, F., López, G., Bautista, D.: Organometallics 25, 5768 (2006)CrossRefGoogle Scholar
  33. 33.
    Komãiromi, A., Novãik, Z.: Chem. Commun. 40, 4968 (2008)Google Scholar
  34. 34.
    John, A., Shaikh, M.M., Ghosh, P.: Dalton Trans. 47, 10581 (2009)Google Scholar
  35. 35.
    Torborg, C., Huang, J., Schulz, T., Schäffner, B., Zapf, A., Spannenberg, A., Börner, A., Beller, M.: Chem. Eur. J. 15, 1329 (2009)CrossRefGoogle Scholar
  36. 36.
    Liang, B., Dai, M.-J., Chen, J.-H., Yang, Z.: J. Org. Chem. 70, 391 (2005)CrossRefGoogle Scholar
  37. 37.
    Li, J.-H., Liang, Y., Xie, Y.-X.: J. Org. Chem. 70, 4393 (2005)CrossRefGoogle Scholar
  38. 38.
    Carpita, A., Ribecai, A.: Tetrahedron Lett. 50, 204 (2009)CrossRefGoogle Scholar
  39. 39.
    Urgaonkar, S., Verkade, J.G.: J. Org. Chem. 69, 5752 (2004)CrossRefGoogle Scholar
  40. 40.
    Liang, Y., Xie, Y.-X., Li, J.-H.: J. Org. Chem. 71, 379 (2006)CrossRefGoogle Scholar
  41. 41.
    Amatore, C., Bensalem, S., Ghalem, S., Jutand, A., Medjour, Y.: Eur. J. Org. Chem. 2004, 366 (2004)Google Scholar
  42. 42.
    Tougerti, A., Negri, S., Jutand, A.: Chem. Eur. J. 13, 666 (2007)CrossRefGoogle Scholar
  43. 43.
    Ljungdahl, T., Bennur, T., Dallas, A., Emtenas, H., Mårtensson, J.: Organometallics 27, 2490 (2008)CrossRefGoogle Scholar
  44. 44.
    Chen, L.-P., Hong, S.-G., Hou, H.-Q.: Chin. J. Struct. Chem. 27, 1404 (2008)Google Scholar
  45. 45.
    Sikk, L., Tammiku-Taul, J., Burk, P.: Organometallics 30, 5656 (2011)CrossRefGoogle Scholar
  46. 46.
    Garcã-a-Melchor, M., Pacheco, M.C., Nãijera, C., Lledós, A., Ujaque, G.: ACS Catal. 2, 135 (2012)Google Scholar
  47. 47.
    Becke, A.D.: J. Chem. Phys. 98, 5648 (1993)CrossRefGoogle Scholar
  48. 48.
    Lee, C., Yang, W., Parr, R.G.: Phys. Rev. B 37, 785 (1988)CrossRefGoogle Scholar
  49. 49.
    Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Montgomery, J.A. Jr., Vreven, T., Kudin, K.N., Burant, J.C., Millam, J.M., Iyengar, S.S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J.E., Hratchian, H.P., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Ayala, P.Y., Morokuma, K., Voth, G.A., Salvador, P., Dannenberg, J.J., Zakrzewski, V.G., Dapprich, S., Daniels, A.D., Strain, M.C., Farkas, O., Malick, D.K., Rabuck, A.D., Raghavachari, K., Foresman, J.B., Ortiz, J.V., Cui, Q., Baboul, A.G., Clifford, S., Cioslowski, J., Stefanov, B.B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R.L., Fox, D.J., Keith, T., Al-Laham, M.A. Peng, C.Y., Nanayakkara, A., Challacombe, M., Gill, P.M.W., Johnson, B., Chen, W., Wong, M.W. Gonzalez, C., Pople, J.A.: Gaussian 03, Revision E.01, Gaussian, Inc., Wallingford (2004)Google Scholar
  50. 50.
    Andrae, D., Häussermann, U., Dolg, M., Stoll, H., Preuss, H.: Theor. Chim. Acta. 77, 123 (1990)CrossRefGoogle Scholar
  51. 51.
    Ehlers, A.W., Bohme, M., Dapprich, S., Gobbi, A., Hollwarth, A., Jonas, V., Kohler, K.F., Stegmann, R., Veldkamp, A., Frenking, G.: Chem. Phys. Lett. 208, 111 (1993)CrossRefGoogle Scholar
  52. 52.
    Hollwarth, A., Bohme, M., Dapprich, S., Ehlers, A.W., Gobbi, A., Jonas, V., Kohler, K.F., Stegmann, R., Veldkamp, A., Frenking, G.: Chem. Phys. Lett. 208, 237 (1993)CrossRefGoogle Scholar
  53. 53.
    Check, C.E., Faust, T.O., Bailey, J.M., Wright, B.J., Gilbert, T.M., Sunderlin, L.S.: J. Phys. Chem. A 105, 8111 (2001)CrossRefGoogle Scholar
  54. 54.
    Braga, A.A.C., Ujaque, G., Maseras, F.: Organometallics 25, 3647 (2006)CrossRefGoogle Scholar
  55. 55.
    Nova, A., Ujaque, G., Maseras, F., Lledós, A., Espinet, P.: J. Am. Chem. Soc. 128, 14571 (2006)CrossRefGoogle Scholar
  56. 56.
    Álvarez, R., Pérez, M., Faza, O.N., de Lera, A.R.: Organometallics 27, 3378 (2008)Google Scholar
  57. 57.
    Ariafard, A., Yates, B.F.: J. Am. Chem. Soc. 131, 13981 (2009)CrossRefGoogle Scholar
  58. 58.
    Pérez-RodrÃ-guez, M., Braga, A.A.C., GarcÃ-a-Melchor, M., Pérez-Temprano, M.H., Casares, J.A., Ujaque, G., de Lera, A.R., Álvarez, R., Maseras, F., Espinet, P.: J. Am. Chem. Soc. 131, 3650 (2009)Google Scholar
  59. 59.
    Pérez-RodrÃ-guez, M., Braga, A.A.C., de Lera, A.R., Maseras, F., Álvarez, R., Espinet, P.: Organometallics 29, 4983 (2010)Google Scholar
  60. 60.
    Thaler, T., Haag, B., Gavryushin, A., Schober, K., Hartmann, E., Gschwind, R.M., Zipse, H., Mayer, P., Knochel, P.: Nature Chem. 2, 125 (2010)CrossRefGoogle Scholar
  61. 61.
    Martin, R.L., Hay, P.J., Pratt, L.R.: J. Phys. Chem. A 102, 3565 (1998)CrossRefGoogle Scholar
  62. 62.
    Miertus, S., Scrocco, E., Tomasi, J.: J. Chem. Phys. 55, 117 (1981)Google Scholar
  63. 63.
    Besora, M., Braga, A.A.C., Ujaque, G., Maseras, F., Lledós, A.: Theor. Chem. Acc. 128, 639 (2011)CrossRefGoogle Scholar
  64. 64.
    Casado, A.L., Espinet, P.: Organometallics 17, 954 (1998)CrossRefGoogle Scholar
  65. 65.
    GarcÃ-a-Melchor, M., Fuentes, B., Lledós, A., Casares, J.A., Ujaque, G., Espinet, P.: J. Am. Chem. Soc. 133, 13519 (2011)CrossRefGoogle Scholar
  66. 66.
    Kozuch, S., Shaik, S.: J. Am. Chem. Soc. 128, 3355 (2006)CrossRefGoogle Scholar
  67. 67.
    Kozuch, S., Shaik, S.: J. Phys. Chem. A 112, 6032 (2008)CrossRefGoogle Scholar
  68. 68.
    Uhe, A., Kozuch, S., Shaik, S.: J. Comput. Chem. 32, 978 (2011)CrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Department of ChemistryAutonomous University of BarcelonaCerdanyola del VallèsSpain

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