CuI/L (L¼pyridine-functionalized 1,3-diketones) catalyzed CeN coupling reactions of aryl halides with NH-containing heterocycles Zhenxing Xi, Fenghui Liu, Yongbo Zhou, Wanzhi Chen * Department of Chemistry, Zhejiang University, Xixi Campus, Hangzhou 310028, PR China Received 5 December 2007; received in revised form 22 February 2008; accepted 26 February 2008 Available online 29 February 2008 Abstract An efficient copper-catalyzed N-arylation and N-heteroarylation reactions of imidazole, pyrrole, indole, pyrazole, and perimidine with aryl or heteroaryl halides using pyridine-functionalized 1,3-diketone as ligands have been investigated. The ligands bearing pyridyl and 1,3-diketone moieties, which may form chelated Cu(I) species, are inexpensive and readily available. The combination of CuI and 1,3-di(pyridin-2-yl)pro- pane-1,3-dione is very efficient for CeN coupling reactions to afford various N-arylated products in good to excellent yields. Ó 2008 Elsevier Ltd. All rights reserved. Keywords: Copper; Pyridine-functionalized diones; CeN coupling; Heterocycles 1. Introduction Metal-catalyzed Ullmann-type CeN coupling reaction rep- resents one of the most efficient method to form various CeN bond containing compounds that have important biological, pharmaceutical, or material properties. 1 Traditional Cu-cata- lyzed Ullmann reactions require the use of stoichiometric amounts of copper, harsh reaction conditions, strong bases and often use of toxic polar solvents such as hexamethylphos- phoramide (HMPA), and thus limited their large scale applica- tions in industry. One of the most significant achievement in this field is the development of palladium-catalyzed cross-coupling reactions, which have become the major synthetic protocol for the construction of arylecarbon bonds. 2 The palladium-cata- lyzed cross-coupling reactions may also be applied to the for- mation of C-heteroatom such as CeN, CeO, CeS bonds. 3 The BuchwaldeHartwig amination has been widely used for the preparation of aryl amines by the reactions of aryl halides and primary or secondary amines, amides, sulfonamides, im- ines, and heterocyclic compounds containing NeH bonds. 4 Al- though the reactions catalyzed by the palladium catalysts with bulky phosphine ligands can be performed at mild conditions, the phosphine ligands are normally not easily available, air-sen- sitive, and expensive. 5 Despite some limitations of copper catalysts and the success of palladium-catalyzed reactions, cop- per-based protocols still attract a great attention recently since copper is much cheaper, and make the reactions of choice in large and industrial scale applications. Especially, copper-based Ullmann-type reactions are often successful where palladium- based procedures have failed. Recently, milder Ullmann-type methodologies for the N-arylation of anilines, 6 imidazoles, 7 amides, 8 nitrogen containing heterocycles, 9 and hydrazides 10 as well as the preparation of diaryl ethers 11 have been reported. The copper-catalyzed aryl amination has already proved to be a general method to form carbonenitrogen bonds, and the re- cent achievements point toward the development of even milder reaction conditions and greater functional group compatibility. Various types of ligands and catalytic systems have been developed. It has been found that some bidentate N,N-, N,O-, O,O-, or N,S-ligand such as amino acids, 12 diols and triols, 13 di- ketones, 14 ketone-esters, 15 amino-alcohols, 16 diamines, 6b,8,9,17 diimines, 6a,7,10,18 imine-amine, 19 diethylsalicylamide, 20 ami- noarenethiolate, 21 pyrrolidine-2-phosphonic acid phenyl mono- ester, 22 etc. are efficient ligands for the copper-catalyzed Ullmann arylation reactions. The high catalytic activities of * Corresponding author. Tel./fax: þ86 571 88273314. E-mail address: chenwzz@zju.edu.cn (W. Chen). 0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2008.02.082 Available online at www.sciencedirect.com Tetrahedron 64 (2008) 4254e4259 www.elsevier.com/locate/tet