An efficient intermolecular C(aryl)–S bond forming reaction catalyzed by BINAM–copper(II) complex D. J. C. Prasad, Ajay B. Naidu, G. Sekar * Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600 036, India article info Article history: Received 21 October 2008 Revised 23 December 2008 Accepted 9 January 2009 Available online 13 January 2009 Keywords: Ullmann coupling C–S bond formation Copper catalyst Diamine ligand Thioethers abstract A wide range of diaryl thioethers and aryl alkyl thioethers are synthesized from the corresponding aryl iodides and aromatic/aliphatic thiols through Ullmann type intermolecular coupling reactions in the presence of a catalytic amount of easily available BINAM–Cu(OTf) 2 complex. Less reactive aryl bromides have also been shown to react with thiols under identical reaction conditions to give good yields of the thioethers without increasing the reaction temperature and time. Ó 2009 Elsevier Ltd. All rights reserved. C(aryl)–S bond containing molecules constitute a very impor- tant class of organic compounds playing a significant role in a number of chemical, material and pharmaceutical industries. 1 Tra- ditional reaction conditions for the formation of this C–S bond re- quire drastic conditions such as heating the reaction mixture at 200 °C in a polar solvent such as HMPA. Reduction of aryl sulfones or aryl sulfoxides is the alternative method for the synthesis of sul- fides and it requires strong reducing agents such as DIBAL-H or LiAlH 4 . 2 Later on, palladium-catalyzed C(aryl)–sulfur bond forma- tion from the corresponding aryl halides and thiols became the method of choice. 3,4 However, the high cost of palladium salts, high oxophilicity associated with phosphine ligands and tedious multi- step processes involved in the synthesis of these ligands have ren- dered Pd unpopular, particularly for large scale reactions. The use of copper salt is an alternative for expensive palladium for the aryl–sulfur bond formation reaction from corresponding aryl halides and thiols. However, traditional copper-mediated reac- tions suffer from many drawbacks such as high reaction tempera- ture, use of super stoichiometric copper salts, sensitivity to functional groups on the aryl halide and irreproducibility. 5 In fact, only in the last few years considerable efforts have been taken to improve the efficiency of this reaction. They have now started to bear fruit with the use of copper salts with several ligands such as phosphazene, 6 ethylene glycol, 7 neocuproine, 8 N-methyl glycine, 9 oxime-phosphine oxide ligand, 10 tripod ligand, 11 benzotriazole, 12 Cu nanoparticles, 13 1,2-diaminocyclohexane, 14 b-ketoester 15 and L-proline. 16 It is thought that these ligands in- crease the efficiency of the Ullmann reaction by increasing the sol- ubility of the copper salts by preventing their aggregation. However, this advance in the field of Ullmann coupling is not sufficient as most of the reactions still require longer reaction times (more than 24 h), high reaction temperature (more than 110 °C) and in some cases, high catalytic loading. In particular, the coupling of aryl bromides with thiols does not provide the cor- responding sulfides or provides only poor yields. 9,13a,14 The catalyst loading or temperature has to be increased to improve the yields. 9,14 Therefore a mild, economic and efficient catalytic system is still desirable for this C(aryl)–sulfur bond formation. NR 1 R 2 NR 1 R 2 L1: R 1 = H; R 2 = Me L2: R 1 = R 2 = Me L3: R 1 = R 2 = H L4: R 1 = H; R 2 = Bn As part of our ongoing research in copper catalyzed oxidation chem- istry, 17 very recently, we reported a BINAM (1,1 0 -binaphthyl-2,2’- diamine) L3–Cu complex as an efficient catalyst for the synthesis of diaryl ethers and aryl alkyl ethers through Ullmann coupling. 18 Thus, it was a natural extension for us to investigate the BINAM- copper catalyzed Ullmann type of coupling of thiols with aryl ha- lides for the synthesis of important C(aryl)–S bond containing com- pounds (Scheme 1). 0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2009.01.022 * Corresponding author. Tel.: +91 44 2257 4229; fax: +91 44 2257 4202. E-mail address: gsekar@iitm.ac.in (G. Sekar). Tetrahedron Letters 50 (2009) 1411–1415 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet