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Synthesis 2011(16): 2553-2560  
DOI: 10.1055/s-0030-1260076
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart ˙ New York

Pd-Catalysed Direct 5-Arylation of 1-Methylpyrazole with Aryl Bromides

Anissa Beladhriaa,b, Kassem Beydounb, Hamed Ben Ammar*a, Ridha Ben Salemc, Henri Doucet*b
a Laboratoire Laboratoire de Chimie Organique Appliquée, (99 UR 12-13), Université de Gabès, Faculté des Sciences de Gabès, 6072 Gabès, Tunisia
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;
c Laboratoire de Chimie Organique Physique (99 UR 12-13) , Université de Sfax, Faculté des Sciences de Sfax, Route de la Soukra km 4, 3038 Sfax, Tunisia
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Publication History

Received 25 February 2011
Publication Date:
17 June 2011 (online)

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Abstract

1-Methylpyrazole was found to be a suitable partner for palladium-catalysed direct arylation through C-H activation/functionalisation using aryl bromides. The reaction conditions and the nature of the catalyst were found to have a determining influence on the selectivity. The use of an excess of pyrazole (4 equiv), and only 0.5-1 mol% palladium(II) acetate as the catalyst, potassium acetate as the base and DMAc as the solvent, promotes the 5-arylation in moderate to high selectivities and yields. A wide variety of aryl and heteroaryl bromide derivatives have been successfully employed. Their electronic and steric properties also have an influence on the regioselectivities and yields of the coupling products. Both electron-poor and electron-rich aryl bromides gave satisfactory results, although, very congested products were obtained with lower regio­selectivities.

Key words

arylation - coupling - palladium - pyrazoles - regioselectivity

    References

  • For examples of palladium-catalysed cross-coupling with heteroaromatic compounds, see:
  • 1a Li JJ. Gribble GW. Palladium in Heterocyclic Chemistry   Pergamon; Amsterdam: 2000. 
  • 1b Doucet H. Santelli M. Synlett  2006,  2001 
  • For the synthesis of 5-arylpyrazoles using Suzuki reaction, see:
  • 2a Gerard A.-L. Bouillon A. Mahatsekake C. Collot V. Rault S. Tetrahedron Lett.  2006,  47:  4665 
    Search in Google Scholar
  • 2b Kudo N. Perseghini M. Fu GC. Angew. Chem. Int. Ed.  2006,  45:  1282 
    Search in Google Scholar
  • 2c Gerard A.-L. Mahatsekake C. Collot V. Rault S. Tetrahedron Lett.  2007,  48:  4123 
    Search in Google Scholar
  • 2d McLaughlin M. Marcantonio K. Chen C.-y. Davies IW. J. Org. Chem.  2008,  73:  4309 
    Search in Google Scholar
  • For the synthesis of 5-arylpyrazoles using the Negishi reaction, see:
  • 3a Yagi K. Ogura T. Numata A. Ishii S. Arai K. Heterocycles  1997,  45:  1463 
    Search in Google Scholar
  • 3b Kristensen J. Begtrup M. Vedso P. Synthesis  1998,  1604 
  • 3c Pawlas J. Vedso P. Jakobsen P. Huusfeldt PO. Begtrup M.
    J. Org. Chem.  2000,  65:  9001 
    Search in Google Scholar
  • 3d Fray MJ. Allen P. Bradley PR. Challenger CE. Closier M. Evans TJ. Lewis ML. Mathias JP. Nichols CL. Po-Ba YM. Snow H. Stefaniak MH. Vuong HV. Heterocycles  2006,  67:  489 
    Search in Google Scholar
  • 4 For the synthesis of 5-arylpyrazoles using the Stille reaction, see: Whitlock GA. Conlon K. McMurray G. Roberts LR. Stobie A. Thurlow RJ. Bioorg. Med. Chem. Lett.  2008,  18:  2930 
    CrossrefSearch in Google Scholar
  • 5 For examples of 5-arylations of pyrazoles using magnesium derivatives, see: Despotopoulou C. Klier L. Knochel P. Org. Lett.  2009,  11:  3326 
    CrossrefPubMedSearch 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 Campeau L.-C. Stuart DR. Fagnou K. Aldrichimica Acta  2007,  40:  35 
    Search in Google Scholar
  • 7d Seregin IV. Gevorgyan V. Chem. Soc. Rev.  2007,  36:  1173 
    Search in Google Scholar
  • 7e Li B.-J. Yang S.-D. Shi Z.-J. Synlett  2008,  949 
  • 7f Ackermann L. Vicente R. Kapdi A. Angew. Chem. Int. Ed.  2009,  48:  9792 
    Search in Google Scholar
  • 7g Bellina F. Rossi R. Tetrahedron  2009,  65:  10269 
    Search in Google Scholar
  • 7h Roger J. Gottumukkala AL. Doucet H. ChemCatChem  2010,  2:  20 
    Search in Google Scholar
  • For recent examples of palladium-catalysed 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 Amaladass P. Clement JA. Mohanakrishnan AK. Tetrahedron  2007,  63:  10363 
    Search in Google Scholar
  • 8d Derridj F. Gottumukkala AL. Djebbar S. Doucet H. Eur. J. Inorg. Chem.  2008,  2550 
  • 8e Nakano M. Tsurugi H. Satoh T. Miura M. Org. Lett.  2008,  10:  1851 
    Search in Google Scholar
  • 8f Roger J. Po˛gan F. Doucet H. Green Chem.  2009,  11:  425 
    Search in Google Scholar
  • 8g Liegault B. Petrov I. Gorelsky SI. Fagnou K. J. Org. Chem.  2010,  75:  1047 
    Search in Google Scholar
  • 8h Derridj F. Roger J. Djebbar S. Doucet H. Org. Lett.  2010,  12:  4320 
    Search in Google Scholar
  • For recent examples of palladium-catalysed direct arylations of furans, see:
  • 9a Parisien M. Valette D. Fagnou K.
    J. Org. Chem.  2005,  70:  7578 
    Search in Google Scholar
  • 9b Lindahl K.-F. Carroll A. Quinn RJ. Ripper JA. Tetrahedron Lett.  2006,  47:  7493 
    Search in Google Scholar
  • 9c Beccalli EM. Broggini G. Martinelli M. Sottocornola S. Synthesis  2008,  136 
  • 9d Gottumukkala AL. Doucet H. Adv. Synth. Catal.  2008,  350:  2183 
    Search in Google Scholar
  • 9e Liégaut B. Lapointe D. Caron L. Vlassova A. Fagnou K. J. Org. Chem.  2009,  74:  1826 
    Search in Google Scholar
  • 9f Dong JJ. Roger J. Pozgan F. Doucet H. Green Chem.  2009,  11:  1832 
    Search in Google Scholar
  • For recent examples of palladium-catalysed direct arylations of pyrroles or indoles, see:
  • 10a Bellina F. Cauteruccio S. Rossi R. Eur. J. Org. Chem.  2006,  1379 
  • 10b Wang X. Gribkov DV. Sames D. J. Org. Chem.  2007,  72:  1476 
    Search in Google Scholar
  • 10c Lebrasseur N. Larrosa I. J. Am. Chem. Soc.  2008,  130:  2926 
    Search in Google Scholar
  • 10d Roger J. Doucet H. Adv. Synth. Catal.  2009,  351:  1977 
    Search in Google Scholar
  • 10e Fall Y. Doucet H. Santelli M. ChemSusChem  2009,  2:  153 
    Search in Google Scholar
  • 10f Jafarpour F. Rahiminejadan S. Hazrati H. J. Org. Chem.  2010,  75:  3109 
    Search in Google Scholar
  • For recent examples of palladium-catalysed direct arylations of thiazoles, see:
  • 11a Gottumukkala AL. Doucet H. Eur. J. Inorg. Chem.  2007,  3629 
  • 11b 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
  • 11c Martin T. Verrier C. Hoarau C. Marsais F. Org. Lett.  2008,  10:  2909 
    Search in Google Scholar
  • 11d Roger J. Po˛gan F. Doucet H. J. Org. Chem.  2009,  74:  1179 
    Search in Google Scholar
  • 11e Roy D. Mom S. Beaupérin M. Doucet H. Hierso J.-C. Angew. Chem. Int. Ed.  2010,  49:  6650 
    Search in Google Scholar
  • For recent examples of palladium-catalysed direct arylations of oxazoles, see:
  • 12a Hoarau C. Du Fou de Kerdaniel A. Bracq N. Grandclaudon P. Couture A. Marsais F. Tetrahedron Lett.  2005,  46:  8573 
    Search in Google Scholar
  • 12b Turner GL. Morris JA. Greaney MF. Angew. Chem. Int. Ed.  2007,  46:  7996 
    Search in Google Scholar
  • 12c Roger J. Doucet H. Org. Biomol. Chem.  2008,  6:  169 
    Search in Google Scholar
  • 12d Ohnmacht SA. Mamone P. Culshaw AJ. Greaney MF. Chem. Commun.  2008,  1241 
  • 12e Besselievre F. Mahuteau-Betzer F. Grierson DS. Piguel S. J. Org. Chem.  2008,  73:  3278 
    Search in Google Scholar
  • 12f Verrier C. Hoarau C. Marsais F. Org. Biomol. Chem.  2009,  7:  647 
    Search in Google Scholar
  • For recent examples of palladium-catalysed direct arylations of imidazoles, see:
  • 13a Bellina F. Cauteruccio S. Mannina L. Rossi R. Viel S. Eur. J. Org. Chem.  2006,  693 
  • 13b Cerna I. Pohl R. Klepetarova B. Hocek M. Org. Lett.  2006,  8:  5389 
    Search in Google Scholar
  • 13c Bellina F. Calandri C. Cauteruccio S. Rossi R. Tetrahedron  2007,  63:  1970 
    Search in Google Scholar
  • 13d Bellina F. Cauteruccio S. Di Flore A. Rossi R. Eur. J. Org. Chem.  2008,  5436 
  • 13e Bellina F. Cauteruccio S. Di Flore A. Marchietti C. Rossi R. Tetrahedron  2008,  64:  6060 
    Search in Google Scholar
  • 13f Roger J. Doucet H. Tetrahedron  2009,  65:  9772 
    Search in Google Scholar
  • For recent examples of palladium-catalysed direct arylations of triazoles, see:
  • 14a Chuprakov S. Chernyak N. Dudnik AS. Gevorgyan V. Org. Lett.  2007,  9:  2333 
    Search in Google Scholar
  • 14b Iwasaki M. Yorimitsu H. Oshima K. Chem. Asian J.  2007,  2:  1430 
    Search in Google Scholar
  • 14c Ackermann L. Vincente R. Born R. Adv. Synth. Catal.  2008,  350:  741 
    Search in Google Scholar
  • 15 For examples of palladium-catalysed direct arylations of indazoles, see: Ohnmacht SA. Culshaw AJ. Greaney MF. Org. Lett.  2010,  12:  224 
    CrossrefPubMedSearch in Google Scholar
  • 16 For an example of palladium-catalysed 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
  • For examples of palladium-catalysed direct 4-arylations of pyrazoles, see:
  • 17a Kumar S. Ila H. Junjappa H. J. Org. Chem.  2009,  74:  7046 
    Search in Google Scholar
  • 17b Fall Y. Doucet H. Santelli M. Synthesis  2010,  127 
  • 18 Goikhman R. Jacques TL. Sames D. J. Am. Chem. Soc.  2009,  131:  3042 
    CrossrefSearch in Google Scholar
  • 19 For examples of direct 5-arylations of 4-substituted pyrazoles, see: Mateos C. Mendiola J. Carpintero M. Minguez JM. Org. Lett.  2010,  12:  4924 
    CrossrefSearch in Google Scholar
  • 20 Tanaka A. Terasawa T. Hagihara H. Sakuma Y. Ishibe N. Sawada M. Takasugi H. Tanaka H. J. Med. Chem.  1998,  41:  2390 
    CrossrefSearch in Google Scholar
  • 21 Grimmett MR. Lim KHR. Weavers RT. Aust. J. Chem.  1979,  32:  2203 
    CrossrefSearch in Google Scholar