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

Anissa Beladhria; Kassem Beydoun; Hamed Ben Ammar; Ridha Ben Salem; Henri Doucet

doi:10.1055/s-0030-1260076

SPECIALTOPIC

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

Anissa Beladhria^a,b, Kassem Beydoun^b, Hamed Ben Ammar*^a, Ridha Ben Salem^c, 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

Abstract

All articles of this category

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

Full Text

References

For examples of palladium-catalysed cross-coupling with heteroaromatic compounds, see:

<A NAME="RC22411ST-1A">1a</A> Li JJ. Gribble GW. Palladium in Heterocyclic Chemistry Pergamon; Amsterdam: 2000.

<A NAME="RC22411ST-1B">1b</A> Doucet H. Santelli M. Synlett 2006, 2001

For the synthesis of 5-arylpyrazoles using Suzuki reaction, see:

<A NAME="RC22411ST-2A">2a</A> Gerard A.-L. Bouillon A. Mahatsekake C. Collot V. Rault S. Tetrahedron Lett. 2006, 47: 4665

<A NAME="RC22411ST-2B">2b</A> Kudo N. Perseghini M. Fu GC. Angew. Chem. Int. Ed. 2006, 45: 1282

<A NAME="RC22411ST-2C">2c</A> Gerard A.-L. Mahatsekake C. Collot V. Rault S. Tetrahedron Lett. 2007, 48: 4123

<A NAME="RC22411ST-2D">2d</A> McLaughlin M. Marcantonio K. Chen C.-y. Davies IW. J. Org. Chem. 2008, 73: 4309

For the synthesis of 5-arylpyrazoles using the Negishi reaction, see:

<A NAME="RC22411ST-3A">3a</A> Yagi K. Ogura T. Numata A. Ishii S. Arai K. Heterocycles 1997, 45: 1463

<A NAME="RC22411ST-3B">3b</A> Kristensen J. Begtrup M. Vedso P. Synthesis 1998, 1604

<A NAME="RC22411ST-3C">3c</A> Pawlas J. Vedso P. Jakobsen P. Huusfeldt PO. Begtrup M.
J. Org. Chem. 2000, 65: 9001

<A NAME="RC22411ST-3D">3d</A> 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

<A NAME="RC22411ST-4">4</A> 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

<A NAME="RC22411ST-5">5</A> For examples of 5-arylations of pyrazoles using magnesium derivatives, see: Despotopoulou C. Klier L. Knochel P. Org. Lett. 2009, 11: 3326

<A NAME="RC22411ST-6">6</A> Ohta A. Akita Y. Ohkuwa T. Chiba M. Fukunaga R. Miyafuji A. Nakata T. Tani N. Aoyagi Y. Heterocycles 1990, 31: 1951

<A NAME="RC22411ST-7A">7a</A> Alberico D. Scott ME. Lautens M. Chem. Rev. 2007, 107: 174

<A NAME="RC22411ST-7B">7b</A> Satoh T. Miura M. Chem. Lett. 2007, 36: 200

<A NAME="RC22411ST-7C">7c</A> Campeau L.-C. Stuart DR. Fagnou K. Aldrichimica Acta 2007, 40: 35

<A NAME="RC22411ST-7D">7d</A> Seregin IV. Gevorgyan V. Chem. Soc. Rev. 2007, 36: 1173

<A NAME="RC22411ST-7E">7e</A> Li B.-J. Yang S.-D. Shi Z.-J. Synlett 2008, 949

<A NAME="RC22411ST-7F">7f</A> Ackermann L. Vicente R. Kapdi A. Angew. Chem. Int. Ed. 2009, 48: 9792

<A NAME="RC22411ST-7G">7g</A> Bellina F. Rossi R. Tetrahedron 2009, 65: 10269

<A NAME="RC22411ST-7H">7h</A> Roger J. Gottumukkala AL. Doucet H. ChemCatChem 2010, 2: 20

For recent examples of palladium-catalysed direct arylations of thiophenes, see:

<A NAME="RC22411ST-8A">8a</A> David E. Pellet-Rostaing S. Lemaire M. Tetrahedron 2007, 63: 8999

<A NAME="RC22411ST-8B">8b</A> Chiong HA. Daugulis O. Org. Lett. 2007, 9: 1449

<A NAME="RC22411ST-8C">8c</A> Amaladass P. Clement JA. Mohanakrishnan AK. Tetrahedron 2007, 63: 10363

<A NAME="RC22411ST-8D">8d</A> Derridj F. Gottumukkala AL. Djebbar S. Doucet H. Eur. J. Inorg. Chem. 2008, 2550

<A NAME="RC22411ST-8E">8e</A> Nakano M. Tsurugi H. Satoh T. Miura M. Org. Lett. 2008, 10: 1851

<A NAME="RC22411ST-8F">8f</A> Roger J. Po˛gan F. Doucet H. Green Chem. 2009, 11: 425

<A NAME="RC22411ST-8G">8g</A> Liegault B. Petrov I. Gorelsky SI. Fagnou K. J. Org. Chem. 2010, 75: 1047

<A NAME="RC22411ST-8H">8h</A> Derridj F. Roger J. Djebbar S. Doucet H. Org. Lett. 2010, 12: 4320

For recent examples of palladium-catalysed direct arylations of furans, see:

<A NAME="RC22411ST-9A">9a</A> Parisien M. Valette D. Fagnou K.
J. Org. Chem. 2005, 70: 7578

<A NAME="RC22411ST-9B">9b</A> Lindahl K.-F. Carroll A. Quinn RJ. Ripper JA. Tetrahedron Lett. 2006, 47: 7493

<A NAME="RC22411ST-9C">9c</A> Beccalli EM. Broggini G. Martinelli M. Sottocornola S. Synthesis 2008, 136

<A NAME="RC22411ST-9D">9d</A> Gottumukkala AL. Doucet H. Adv. Synth. Catal. 2008, 350: 2183

<A NAME="RC22411ST-9E">9e</A> Liégaut B. Lapointe D. Caron L. Vlassova A. Fagnou K. J. Org. Chem. 2009, 74: 1826

<A NAME="RC22411ST-9F">9f</A> Dong JJ. Roger J. Pozgan F. Doucet H. Green Chem. 2009, 11: 1832

For recent examples of palladium-catalysed direct arylations of pyrroles or indoles, see:

<A NAME="RC22411ST-10A">10a</A> Bellina F. Cauteruccio S. Rossi R. Eur. J. Org. Chem. 2006, 1379

<A NAME="RC22411ST-10B">10b</A> Wang X. Gribkov DV. Sames D. J. Org. Chem. 2007, 72: 1476

<A NAME="RC22411ST-10C">10c</A> Lebrasseur N. Larrosa I. J. Am. Chem. Soc. 2008, 130: 2926

<A NAME="RC22411ST-10D">10d</A> Roger J. Doucet H. Adv. Synth. Catal. 2009, 351: 1977

<A NAME="RC22411ST-10E">10e</A> Fall Y. Doucet H. Santelli M. ChemSusChem 2009, 2: 153

<A NAME="RC22411ST-10F">10f</A> Jafarpour F. Rahiminejadan S. Hazrati H. J. Org. Chem. 2010, 75: 3109

For recent examples of palladium-catalysed direct arylations of thiazoles, see:

<A NAME="RC22411ST-11A">11a</A> Gottumukkala AL. Doucet H. Eur. J. Inorg. Chem. 2007, 3629

<A NAME="RC22411ST-11B">11b</A> Campeau L.-C. Bertrand-Laperle M. Leclerc J.-P. Villemure E. Gorelsky S. Fagnou K. J. Am. Chem. Soc. 2008, 130: 3276

<A NAME="RC22411ST-11C">11c</A> Martin T. Verrier C. Hoarau C. Marsais F. Org. Lett. 2008, 10: 2909

<A NAME="RC22411ST-11D">11d</A> Roger J. Po˛gan F. Doucet H. J. Org. Chem. 2009, 74: 1179

<A NAME="RC22411ST-11E">11e</A> Roy D. Mom S. Beaupérin M. Doucet H. Hierso J.-C. Angew. Chem. Int. Ed. 2010, 49: 6650

For recent examples of palladium-catalysed direct arylations of oxazoles, see:

<A NAME="RC22411ST-12A">12a</A> Hoarau C. Du Fou de Kerdaniel A. Bracq N. Grandclaudon P. Couture A. Marsais F. Tetrahedron Lett. 2005, 46: 8573

<A NAME="RC22411ST-12B">12b</A> Turner GL. Morris JA. Greaney MF. Angew. Chem. Int. Ed. 2007, 46: 7996

<A NAME="RC22411ST-12C">12c</A> Roger J. Doucet H. Org. Biomol. Chem. 2008, 6: 169

<A NAME="RC22411ST-12D">12d</A> Ohnmacht SA. Mamone P. Culshaw AJ. Greaney MF. Chem. Commun. 2008, 1241

<A NAME="RC22411ST-12E">12e</A> Besselievre F. Mahuteau-Betzer F. Grierson DS. Piguel S. J. Org. Chem. 2008, 73: 3278

<A NAME="RC22411ST-12F">12f</A> Verrier C. Hoarau C. Marsais F. Org. Biomol. Chem. 2009, 7: 647

For recent examples of palladium-catalysed direct arylations of imidazoles, see:

<A NAME="RC22411ST-13A">13a</A> Bellina F. Cauteruccio S. Mannina L. Rossi R. Viel S. Eur. J. Org. Chem. 2006, 693

<A NAME="RC22411ST-13B">13b</A> Cerna I. Pohl R. Klepetarova B. Hocek M. Org. Lett. 2006, 8: 5389

<A NAME="RC22411ST-13C">13c</A> Bellina F. Calandri C. Cauteruccio S. Rossi R. Tetrahedron 2007, 63: 1970

<A NAME="RC22411ST-13D">13d</A> Bellina F. Cauteruccio S. Di Flore A. Rossi R. Eur. J. Org. Chem. 2008, 5436

<A NAME="RC22411ST-13E">13e</A> Bellina F. Cauteruccio S. Di Flore A. Marchietti C. Rossi R. Tetrahedron 2008, 64: 6060

<A NAME="RC22411ST-13F">13f</A> Roger J. Doucet H. Tetrahedron 2009, 65: 9772

For recent examples of palladium-catalysed direct arylations of triazoles, see:

<A NAME="RC22411ST-14A">14a</A> Chuprakov S. Chernyak N. Dudnik AS. Gevorgyan V. Org. Lett. 2007, 9: 2333

<A NAME="RC22411ST-14B">14b</A> Iwasaki M. Yorimitsu H. Oshima K. Chem. Asian J. 2007, 2: 1430

<A NAME="RC22411ST-14C">14c</A> Ackermann L. Vincente R. Born R. Adv. Synth. Catal. 2008, 350: 741

<A NAME="RC22411ST-15">15</A> For examples of palladium-catalysed direct arylations of indazoles, see: Ohnmacht SA. Culshaw AJ. Greaney MF. Org. Lett. 2010, 12: 224

<A NAME="RC22411ST-16">16</A> 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

For examples of palladium-catalysed direct 4-arylations of pyrazoles, see:

<A NAME="RC22411ST-17A">17a</A> Kumar S. Ila H. Junjappa H. J. Org. Chem. 2009, 74: 7046

<A NAME="RC22411ST-17B">17b</A> Fall Y. Doucet H. Santelli M. Synthesis 2010, 127

<A NAME="RC22411ST-18">18</A> Goikhman R. Jacques TL. Sames D. J. Am. Chem. Soc. 2009, 131: 3042

<A NAME="RC22411ST-19">19</A> For examples of direct 5-arylations of 4-substituted pyrazoles, see: Mateos C. Mendiola J. Carpintero M. Minguez JM. Org. Lett. 2010, 12: 4924

<A NAME="RC22411ST-20">20</A> Tanaka A. Terasawa T. Hagihara H. Sakuma Y. Ishibe N. Sawada M. Takasugi H. Tanaka H. J. Med. Chem. 1998, 41: 2390

<A NAME="RC22411ST-21">21</A> Grimmett MR. Lim KHR. Weavers RT. Aust. J. Chem. 1979, 32: 2203