Bidentate phosphines as ligands in the palladium-catalyzed intramolecular arylation: the intermolecular base-assisted proton abstraction mechanism Sergio Pascual a , Paula de Mendoza a , Ataualpa A.C. Braga a , Feliu Maseras a,b, * , Antonio M. Echavarren a,c, * a Institute of Chemical Research of Catalonia (ICIQ), Av. Pa € ısos Catalans 16, 43007 Tarragona, Spain b Unitat de Quı ´mica Fı ´sica, Universitat Auto `noma de Barcelona, 08193 Bellaterra, Catalonia, Spain c Departamento de Quı ´mica Orga ´nica, Universidad Auto ´noma de Madrid, Cantoblanco, 28049 Madrid, Spain Received 1 September 2007; received in revised form 10 October 2007; accepted 13 November 2007 Available online 17 January 2008 Abstract The palladium-catalyzed arylation of aryl bromides can be carried out in the presence of bidentate phosphines, such as dppm, dppe, dppf, and Xantphos under mild conditions. The experimental results and the DFT calculations fully support for this reaction a mechanism proceeding by an intermolecular proton abstraction. Ó 2008 Elsevier Ltd. All rights reserved. Keywords: Palladium; Arylation; Phosphines; DFT calculations 1. Introduction The arylation of arenes catalyzed by palladium is a useful alternative to methods based on cross-coupling reactions 1 for the construction of biaryls and more complex polyarenes. 2 Al- though much of the effort has been focused on the intramolec- ular arylation of substrates 1 to form carbo- and heterocycles 2 (Scheme 1), 2e4 significant progress has been done recently in the intermolecular version of this reaction. 5,6 Recent mechanistic work does not support earlier proposals based on an electrophilic aromatic substitution (S E Ar) 7,8 for the palladium-catalyzed arylation reaction. Thus, intramolecu- lar isotope effects k H /k D ¼3.5e4 have been determined in dif- ferent processes. 4a,9 We have also reported examples in which the arylation proceeded at position ortho or para to electron- withdrawing NO 2 groups. 10 Determining the details of this arylation is important to de- velop milder reaction conditions. In addition, similar mecha- nisms are probably followed in other reactions that proceed via palladacycles. 3d,11e13,14e18 We have recently studied the effect of substituents on the arylation process on systems 3, which led to mixtures of 4 and 5 after aromatization of the ini- tially formed 9-aryl-9,10-dihydrophenanthrenes using DDQ (Scheme 2). 19 Electron-withdrawing substituents X, such as fluorine, chlorine, and trifluoromethyl, favor formation of products 4. This directing effect is particularly strong at the ortho position to the CeH bond being cleaved. Electronega- tive methoxy groups that are electron-releasing in electrophilic 1: X = Cl, Br, I, OTf Z = CH 2 , (CH 2 ) 2 , NHR, O, etc [Pd(0)L n ] Z X Z 2 base, DMF or DMA, Δ Scheme 1. * Corresponding authors. Institute of Chemical Research of Catalonia (ICIQ), Av. Pa € ısos Catalans 16, 43007 Tarragona, Spain. Tel.: þ34 97 7920 218; fax: þ34 97 7920 225 (A.M.E.). E-mail addresses: fmaseras@iciq.es (F. Maseras), aechavarren@iciq.es (A.M. Echavarren). 0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2008.01.056 Available online at www.sciencedirect.com Tetrahedron 64 (2008) 6021e6029 www.elsevier.com/locate/tet