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Synthesis 2010(1): 127-135  
DOI: 10.1055/s-0029-1217075
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Palladium-Catalyzed Direct Arylation of Pyrazole Derivatives: A Green Access to 4-Arylpyrazoles

Yacoub Falla, Henri Doucet*b, Maurice Santelli*a
a Laboratoire de Synthèse Organique (Equipe Chirosciences, Associée au CNRS, UMR 6263), Faculté des Sciences de Saint Jérôme, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
e-Mail: m.santelli@univ-cezanne.fr;
b Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes ‘Catalyse et Organometalliques’, Campus de Beaulieu, 35042 Rennes, France
Fax: +33(2)23236939; e-Mail: henri.doucet@univ-rennes1.fr;
Further Information

Publication History

Received 3 September 2009
Publication Date:
22 October 2009 (online)

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Abstract

1,3,5-Trisubstituted pyrazoles were found to be suitable partners for palladium-catalyzed direct arylation via C-H activation/functionalization using aryl bromides. The reaction conditions and the catalyst have a determining influence on the yields. The system using palladium(II) acetate as the catalyst, potassium acetate as the base, and N,N-dimethylacetamide as the solvent promotes selective 4-arylations in moderate to high yields. Several aryl and heteroaryl bromide derivatives have been employed successfully; their electronic properties have a decisive influence on the yields of coupling products. Electron-poor aryl bromides gave satisfactory results, whereas the electron-rich ones gave lower yields.

Key words

pyrazoles - palladium catalysis - C-H arylation - aryl bromide

    References

  • 1 For examples of palladium cross-coupling with heteroaromatic compounds, see: Li JJ. Gribble GW. Palladium in Heterocyclic Chemistry   Pergamon; Amsterdam: 2000. 
  • For the synthesis of 4-arylpyrazoles using the Suzuki reaction, see:
  • 2a Walker SD. Barder TE. Martinelli JR. Buchwald SL. Angew. Chem. Int. Ed.  2004,  43:  1871 
    Search in Google Scholar
  • 2b Liu B. Moffett KK. Joseph RW. Dorsey BD. Tetrahedron Lett.  2005,  46:  1779 
    Search in Google Scholar
  • 2c Lory PMJ. Agarkov A. Gilbertson SR. Synlett  2006,  3045 
  • 2d Kudo N. Perseghini M. Fu GC. Angew. Chem. Int. Ed.  2006,  45:  1282 
    Search in Google Scholar
  • 2e Guram AS. King AO. Allen JG. Wang X. Schenkel LB. Chan J. Bunel EE. Faul MM. Larsen RD. Martinelli MJ. Reider PJ. Org. Lett.  2006,  8:  1787 
    Search in Google Scholar
  • 2f Li H.-y. Wang Y. McMillen WT. Chatterjee A. Toth JE. Mundla SR. Voss M. Boyer RD. Sawyer JS. Tetrahedron  2007,  63:  11763 
    Search in Google Scholar
  • 2g Browne DL. Helm MD. Plant A. Harrity JPA. Angew. Chem. Int. Ed.  2007,  46:  8656 
    Search in Google Scholar
  • 2h Nolt MB. Zhao Z. Wolkenberg SE. Tetrahedron Lett.  2008,  49:  3137 
    Search in Google Scholar
  • For the synthesis of 4-arylpyrazoles using the Negishi reaction, see:
  • 3a Balle T. Andersen K. Vedso P. Synthesis  2002,  1509 
  • 3b Milne JE. Buchwald SL. J. Am. Chem. Soc.  2004,  126:  13028 
    Search in Google Scholar
  • For the synthesis of 4-arylpyrazoles using the Kumada reaction, see:
  • 4a Felding J. Kristensen J. Bjerregaard T. Sander L. Vedso P. Begtrup M. J. Org. Chem.  1999,  64:  4196 
    Search in Google Scholar
  • 4b Ichikawa H. Ohno Y. Usami Y. Arimoto M. Heterocycles  2006,  68:  2247 
    Search in Google Scholar
  • For the synthesis of 4-arylpyrazoles using the Stille reaction, see:
  • 5a Elguero J. Jaramillo C. Pardo C. Synthesis  1997,  563 
  • 5b Jeon S.-L. Choi JH. Kim BT. Jeong IH. J. Fluorine Chem.  2007,  128:  1191 
    Search in Google Scholar
  • 6 Ohta A. Akita Y. Ohkuwa T. Chiba M. Fukunaga R. Miyafuji A. Nakata T. Tani N. Aoyagi Y. Heterocycles  1990,  31:  1951 
    CrossrefSearch in Google Scholar
  • 7a Alberico D. Scott ME. Lautens M. Chem. Rev.  2007,  107:  174 
    Search in Google Scholar
  • 7b Satoh T. Miura M. Chem. Lett.  2007,  36:  200 
    Search in Google Scholar
  • 7c Doucet H. Hierso JC. Curr. Opin. Drug Discovery Devel.  2007,  10:  672 
    Search in Google Scholar
  • 7d Campeau L.-C. Stuart DR. Fagnou K. Aldrichimica Acta  2007,  40:  35 
    Search in Google Scholar
  • 7e Seregin IV. Gevorgyan V. Chem. Soc. Rev.  2007,  36:  1173 
    Search in Google Scholar
  • 7f Li B.-J. Yang S.-D. Shi Z.-J. Synlett  2008,  949 
  • For recent examples of direct arylations of thiophenes, see:
  • 8a David E. Pellet-Rostaing S. Lemaire M. Tetrahedron  2007,  63:  8999 
    Search in Google Scholar
  • 8b Chiong HA. Daugulis O. Org. Lett.  2007,  9:  1449 
    Search in Google Scholar
  • 8c Battace A. Lemhadri M. Zair T. Doucet H. Santelli M. Adv. Synth. Catal.  2007,  349:  2507 
    Search in Google Scholar
  • 8d Amaladass P. Clement JA. Mohanakrishnan AK. Tetrahedron  2007,  63:  10363 
    Search in Google Scholar
  • 8e Derridj F. Gottumukkala AL. Djebbar S. Doucet H. Eur. J. Inorg. Chem.  2008,  2550 
  • 8f Nakano M. Tsurugi H. Satoh T. Miura M. Org. Lett.  2008,  10:  1851 
    Search in Google Scholar
  • 8g Roger J. Po˛gan F. Doucet H. Green Chem.  2009,  11:  425 
    Search in Google Scholar
  • For recent examples of direct arylations of pyrroles or indoles, see:
  • 9a Bellina F. Cauteruccio S. Rossi R. Eur. J. Org. Chem.  2006,  1379 
  • 9b Wang X. Gribkov DV. Sames D. J. Org. Chem.  2007,  72:  1476 
    Search in Google Scholar
  • 9c Lebrasseur N. Larrosa I. J. Am. Chem. Soc.  2008,  130:  2926 
    Search in Google Scholar
  • For recent examples of direct arylations of thiazoles, see:
  • 10a Gottumukkala AL. Doucet H. Eur. J. Inorg. Chem.  2007,  3629 
  • 10b Campeau L.-C. Bertrand-Laperle M. Leclerc J.-P. Villemure E. Gorelsky S. Fagnou K. J. Am. Chem. Soc.  2008,  130:  3276 
    Search in Google Scholar
  • 10c Martin T. Verrier C. Hoarau C. Marsais F. Org. Lett.  2008,  10:  2909 
    Search in Google Scholar
  • 10d Roger J. Po˛gan F. Doucet H. J. Org. Chem.  2009,  74:  1179 
    Search in Google Scholar
  • For recent examples of direct arylations of oxazoles, see:
  • 11a Hoarau C. Du Fou de Kerdaniel A. Bracq N. Grandclaudon P. Couture A. Marsais F. Tetrahedron Lett.  2005,  46:  8573 
    Search in Google Scholar
  • 11b Turner GL. Morris JA. Greaney MF. Angew. Chem. Int. Ed.  2007,  46:  7996 
    Search in Google Scholar
  • 11c Derridj F. Djebbar S. Benali-Baitich O. Doucet H. J. Organomet. Chem.  2008,  693:  135 
    Search in Google Scholar
  • 11d Roger J. Doucet H. Org. Biomol. Chem.  2008,  6:  169 
    Search in Google Scholar
  • 11e Ohnmacht SA. Mamone P. Culshaw AJ. Greaney MF. Chem. Commun.  2008,  1241 
  • 11f Besselievre F. Mahuteau-Betzer F. Grierson DS. Piguel S. J. Org. Chem.  2008,  73:  3278 
    Search in Google Scholar
  • 11g Verrier C. Hoarau C. Marsais F. Org. Biomol. Chem.  2009,  7:  647 
    Search in Google Scholar
  • For recent examples of direct arylations of imidazoles, see:
  • 12a Bellina F. Cauteruccio S. Mannina L. Rossi R. Viel S. Eur. J. Org. Chem.  2006,  693 
  • 12b Cerna I. Pohl R. Klepetarova B. Hocek M. Org. Lett.  2006,  8:  5389 
    Search in Google Scholar
  • 12c Bellina F. Calandri C. Cauteruccio S. Rossi R. Tetrahedron  2007,  63:  1970 
    Search in Google Scholar
  • 12d Bellina F. Cauteruccio S. Di Flore A. Rossi R. Eur. J. Org. Chem.  2008,  5436 
  • 12e Bellina F. Cauteruccio S. Di Flore A. Marchietti C. Rossi R. Tetrahedron  2008,  64:  6060 
    Search in Google Scholar
  • For recent examples of direct arylations of triazoles, see:
  • 13a Chuprakov S. Chernyak N. Dudnik AS. Gevorgyan V. Org. Lett.  2007,  9:  2333 
    Search in Google Scholar
  • 13b Iwasaki M. Yorimitsu H. Oshima K. Chem. Asian J.  2007,  2:  1430 
    Search in Google Scholar
  • 13c Ackermann L. Vincente R. Born R. Adv. Synth. Catal.  2008,  350:  741 
    Search in Google Scholar
  • For recent examples of direct arylations of furans, see:
  • 14a Parisien M. Valette D. Fagnou K. J. Org. Chem.  2005,  70:  7578 
    Search in Google Scholar
  • 14b Lindahl K.-F. Carroll A. Quinn RJ. Ripper JA. Tetrahedron Lett.  2006,  47:  7493 
    Search in Google Scholar
  • 14c Battace A. Lemhadri M. Zair T. Doucet H. Santelli M. Organometallics  2007,  26:  472 
    Search in Google Scholar
  • 14d Beccalli EM. Broggini G. Martinelli M. Sottocornola S. Synthesis  2008,  136 
  • 14e Po˛gan F. Roger J. Doucet H. ChemSusChem  2008,  1:  404 
    Search in Google Scholar
  • 14f Liégaut B. Lapointe D. Caron L. Vlassova A. Fagnou K. J. Org. Chem.  2009,  74:  1826 
    Search in Google Scholar
  • For recent examples of direct regioselective 4-arylations of heteroaromatics, see:
  • 15a Gottumukkala AL. Doucet H. Adv. Synth. Catal.  2008,  350:  2183 
    Search in Google Scholar
  • 15b Fall Y. Doucet H. Santelli M. ChemSusChem  2009,  2:  153 
    Search in Google Scholar
  • 15c Dong JJ. Roger J. Doucet H. Tetrahedron Lett.  2009,  50:  2778 
    Search in Google Scholar
  • 16 For an example of the direct 3-arylation of a pyrazole, see: Brnardic EJ. Garbaccio RM. Fraley ME. Tasber ES. Steen JT. Arrington KL. Dudkin VY. Hartman GD. Stirdivant SM. Drakas BA. Rickert K. Walsh ES. Hamilton K. Buser CA. Hardwick J. Tao W. Beck SC. Mao X. Lobell RB. Sepp-Lorenzino L. Yan Y. Ikuta M. Munshi SK. Kuo LC. Kreatsoulas C. Bioorg. Med. Chem. Lett.  2007,  17:  5989 
    CrossrefSearch in Google Scholar
  • 17 For examples of direct 4-arylations of pyrazoles, see: Goikhman R. Jacques TL. Sames D. J. Am. Chem. Soc.  2009,  131:  3042 
    CrossrefSearch in Google Scholar
  • 18 Blaszykowski C. Aktoudianakis E. Alberico D. Bressy C. Hulcoop DG. Jafarpour F. Joushaghani A. Laleu B. Lautens M. J. Org. Chem.  2008,  73:  1888 
    CrossrefSearch in Google Scholar
  • 19a Lee KY. Gowrisankar SK. Jae N. Tetrahedron Lett.  2005,  46:  5387 
    Search in Google Scholar
  • 19b Krebs AW. Franken E. Mueller M. Colberg H. Cholcha W. Wilken J. Ohrenberg J. Albrecht R. Weiss E. Tetrahedron Lett.  1992,  33:  5947 
    Search in Google Scholar