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Synthesis 2011(16): 2553-2560  
DOI: 10.1055/s-0030-1260076
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© 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

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