Cu(OAc)2 catalyzed Sonogashira cross-coupling reaction in amines

Chinese Chemical Letters 18 (2007) 13–16 www.elsevier.com/locate/cclet

Cu(OAc)2 catalyzed Sonogashira cross-coupling reaction in amines Sheng Mei Guo, Chen Liang Deng, Jin Heng Li * Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China Received 15 May 2006

Abstract A simple Cu(OAc)2 catalyzed Sonogashira coupling protocol is presented. It was found that the couplings of a variety of aryl halides with terminal alkynes were conducted smoothly to afford the corresponding desired products in moderate to excellent yields, using Cu(OAc)2 as the catalyst and Et3N as the solvent. # 2006 Jin Heng Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Cu(OAc)2; Sonogashira cross-coupling reaction; Aryl halide; Alkyne

Alkynes are interest for synthetic, pharmaceutical and material chemists [1,2]. The Sonogashira cross-coupling reaction has been proved as a powerful tool for the synthesis of alkynes [2–6]. Since its invention, much attention has been focused on the development of the efficient and selective palladium catalytic systems (often palladium combined with a ligand) [2–5]. However, most of these catalytic systems are considerably expensive. Therefore, development of cheaper metals as catalysts [2,5,6] is the need for solution of this problem. In recent years, CuI, Cu(phen)(PPh3)Br and copper nanoclusters have been employed in the Sonogashira cross-coupling reaction [6]. Okuro et al. first demonstrated the copper catalyzed Sonogashira reaction, but the scope was limited to aryl iodides [6a]. Even 1.10phenanthraline was used as a ligand in the Sonogashira coupling reaction catalyzed by Cu(phen)(PPh3)Br or [Cu(phen)(PPh3)2]NO3 catalyzed [6b–d]. Ma and Liu [6e] discovered that CuI combined with N,N-dimethyl-glycine as the catalytic system could couple the deactivated aryl bromides. Wang et al. have also observed that the CuI/ ethylene diamine catalytic system was effective for the couplings of aryl iodides and bromides [6f]. In 2004, Rothenberg and co-workers [6g] have reported that the Sonogashira reaction of aromatic iodides and activated aromatic bromides catalyzed by copper nanoclusters gave the satisfactory results in ligand-free conditions. In view of economy and environment, the development of more active copper catalytic systems is still challenging for direct couplings of a large range of aryl halides with alkynes. Here, we report a simple Sonogashira coupling protocol catalyzed by a catalytic amount of Cu(OAc)2, using Et3N as the solvent (Scheme 1). In the earlier reports, terminal alkynes could undergo oxidative homocoupling reaction readily in the presence of Cu(OAc)2, in air [7]. As shown in Table 1, however, we found that Cu(OAc)2 was not an effective catalyst for the

* Corresponding author. E-mail address: [email protected] (J.H. Li). 1001-8417/$ – see front matter # 2006 Jin Heng Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2006.11.019

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S.M. Guo et al. / Chinese Chemical Letters 18 (2007) 13–16

Scheme 1.

Table 1 Copper catalyzed Sonogashira cross-coupling reaction of 1-iodo-4-methylbenzene 1a with phenylacetylene 2a [8]a

Entry

b

1 2c 3d 4 5 6 7 8 9 10 11 12 13 14 15e 16f a b c d e f

Copper (mol.%)

Cu(OAc)2 (50) Cu(OAc)2 (50) Cu(OAc)2 (50) Cu(OAc)2 (10) Cu(OAc)2 (50) Cu(OAc)2 (50) Cu(OAc)2 (50) Cu(OAc)2 (50) Cu(OAc)2 (50) Cu(OAc)2 (50) CuO (50) CuCl2 (50) CuI (50) Cu2O (50) Cu(OAc)2 (50) Cu(OAc)2 (50)

Solvent

Et3N Et3N Et3N Et3N Et3N 1-Methylpiperidine Dicyclohexylamine Pyridine Et3N/DMF (5:2) Et3N/H2O (5:2) Et3N Et3N Et3N Et3N Et3N Et3N

Isolated yield (%) 3

4b

29 33 18 92 21 30 68 31 62 12 Trace 69 Trace Trace 43 32

– – – 7 84 69 36 64 29 80 7 39 15 Trace 20 47

Reaction conditions: 1a (0.5 mmol), 2a (0.8 mmol), copper and solvent (3 mL) at 140–150 8C in argon for 24 h. Without 1a. Without 1a in air. Without 1a in air at room temperature. At 120 8C. 2a (0.65 mmol).

homocoupling of phenylacetylene 2a, using Et3N as the medium (entries 1–3). The yield of homocoupling product 3 was only 33%, when 2a reacted with Cu(OAc)2 (50 mol.%) and Et3N (3 mL) in air at 140–150 8C (entry 2). The results encouraged us to employ Cu(OAc)2 as a catalyst for the Sonogashira cross-coupling reaction. The loading of Cu(OAc)2 played a crucial role in the selectivity between the oxidative homocoupling reaction and the Sonogashira reaction. Treatment of 1-iodo-4-methylbenzene 1a with 2a, Cu(OAc)2 (10 mol.%), Et3N (3 mL) in argon at 140– 150 8C afforded the corresponding coupling product 4 in a rather low yield together with a 92% yield of 3 (entry 4), whereas the yield of the target product 4 was enhanced sharply to 84% when 50 mol.% of Cu(OAc)2 was added (entry 5). A series of other solvents, such as 1-methylpiperidine, dicyclohexylamine, pyridine and Et3N/DMF were less effective than Et3N (entries 5–9). However, the identical results to those of entry 5 were observed, when the reaction was performed in aqueous Et3N (entry 10). We have also investigated a set of copper catalysts including CuI, the reported effective catalyst, the results indicated that they were inferior to Cu(OAc)2 (entries 5 and 11–14). Finally, the effects of both the reaction temperature and the amount of alkyne 2a were also evaluated (entries 15 and 16). When the reaction was conducted either at 120 8C or in the presence of 0.65 mmol of 2a, the yield of 4 was decreased. With the optimized reaction conditions in hand [9], we then attempt to extend the scope of the substrates (Table 2). We were delighted to find that a variety of aryl iodides 1a–g and an activated bromide 1h were coupled with alkynes smoothly to afford the corresponding coupled products in moderate to excellent yields in the presence of Cu(OAc)2 (50 mol.%) and Et3N (3 mL) at 140–150 8C for 24 h (entries 1–11). For example, the coupling of 1a with 2b gave the corresponding products in an 83% yield (entry 1), but the substrate 2c bearing an unprotected hydroxyl group was

S.M. Guo et al. / Chinese Chemical Letters 18 (2007) 13–16

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Table 2 The Sonogashira cross-couplings of ArX 1 with alkynes 2 catalyzed by Cu(OAc)2a Entry

ArX 1

1 2 3 4 5 6 7 8 9 10 11 12

p-CH3C6H4I p-CH3C6H4I p-NO2C6H4I p-NO2C6H4I o-NO2C6H4I p-CH3COC6H4I C6H5I o-CH3C6H4I p-MeOC6H4I p-NO2C6H4Br p-NO2C6H4Br C6H5Br

a b

Yield (%)b

Alkyne 2 1a 1a 1b 1b 1c 1d 1e 1f 1g 1h 1h 1e

n-C8H17CBBCH HCBBCCH2OH C6H5CBBCH n-C8H17CBBCH C6H5CBBCH C6H5CBBCH C6H5CBBCH C6H5CBBCH C6H5CBBCH C6H5CBBCH n-C8H17CBBCH C6H5CBBCH

2b 2c 2a 2b 2a 2a 2a 2a 2a 2a 2b 2a

83 Trace 100 81 87 98 65 55 64 66 61 Trace

5 6 7 8 9 10 11 12 13 7 8 11

Reaction conditions: 1 (0.5 mmol), 2 (0.8 mmol), Cu(OAc)2 (50 mol.%) and Et3N (3 mL) at 140–150 8C in argon for 24 h. Isolated yield.

unsuccessful for this reaction (entry 2). Other iodides 1b–g coupled with alkynes 2a or 2b also underwent smoothly to provide the desired products in moderate to excellent yields (entries 3–9). The efficiency of the catalytic system was reduced to some extent for the couplings of aryl bromides (entries 10–12). Satisfactory yields were still achieved from the reaction between the activated bromide 1h and 2a or 2b (entries 10 and 11). Unfortunately, only trace amount of the target product 11 was isolated, when another less active bromide 1i was coupled with 2a under the same reaction conditions (entry 12). In summary, a simple Cu(OAc)2 catalyzed Sonogashira cross-coupling protocol has been developed. Compared with the earlier reports, several advantages of the present protocol were established including: (1) the reaction could be carried out in either Et3N or aqueous Et3N, which was employed as both the solvent and the base for the reaction. (2) Cu(OAc)2 is an effective catalyst for the Sonogashira cross-coupling, but not for the oxidative homocoupling under the current conditions. Further efforts to extend the application of this catalytic system in other transformations are underway. Acknowledgements The authors thank Fok Ying Dong Education Foundation (No. 101012), the Key Project of Chinese Ministry of Education (No. 206102), Scientific Research Fund of Hunan Provincial Education Department (No. 05B038) and the NNSF of China (Nos. 20572020 and 20202002) for financial support. References [1] (a) H.G. Viehe, Chemistry of Acetylene, Marcel Dekker, New York, 1969; (b) F. Bohlmann, F.T. Burkhart, C. Zero, Naturally Occurring Acetylenes, Academic Press, London/New York, 1973; (c) F. Alonso, I.P. Beletskaya, M. Yus, Chem. Rev. 104 (2004) 3079. [2] For reviews, see: (a) F. Diederich, P.J. Stang, Metal-catalyzed Cross-coupling Reactions, Wiley-VCH, Weinheim, 1998; (b) N. Miyaura, Cross-coupling Reaction, Springer, Berlin, 2002; (c) J. Hassan, M. Sevignon, C. Gozzi, et al. Chem. Rev. 102 (2002) 1359; (d) I.P. Beletskaya, A.V. Cheprakov, Coord. Chem. Rev. 248 (2004) 2337; (e) A. de Meijere, F. Diederich, Metal-catalyzed Cross-coupling Reactions, Wiley-VCH, Weinheim, 2004. [3] (a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 44 (1975) 4467; (b) H.A. Dieck, R.F. Heck, J. Organomet. Chem. 93 (1975) 259; (c) L. Cassar, J. Organomet. Chem. 93 (1975) 253. [4] For recent selected papers on palladium catalysts, see: (a) J. Cheng, Y. Sun, F. Wang, et al. J. Org. Chem. 69 (2004) 5428; (b) M. Feuerstein, H. Doucet, M. Santelli, Tetrahedron Lett. 45 (2004) 8443; (c) G. Adjabeng, T. Brenstrum, C.S. Frampton, et al. J. Org. Chem. 69 (2004) 5082;

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S.M. Guo et al. / Chinese Chemical Letters 18 (2007) 13–16 (d) A. Arques, D. Aunon, P. Molina, Tetrahedron Lett. 45 (2004) 4337; (e) R.A. Gossage, H.A. Jenkins, P.N. Yadav, Tetrahedron Lett. 45 (2004) 7689; (f) S. Urgaonkar, J.G. Verkade, J. Org. Chem. 69 (2004) 5752; (g) S.U. Son, Y. Jang, J. Park, et al. J. Am. Chem. Soc. 126 (2004) 5026; (h) J.H. Li, X.D. Zhang, Y.X. Xie, Synthesis (2005) 804; (i) B. Liang, M. Dai, J. Chen, et al. J. Org. Chem. 70 (2005) 391; (j) J.H. Li, Y. Liang, Y.X. Xie, J. Org. Chem. 70 (2005) 4393; (k) J.H. Li, X.D. Zhang, Y.X. Xie, Synthesis (2005) 804; (l) C. Yi, R. Hua, J. Org. Chem. 71 (2006) 2535; (m) Y. Liang, Y.X. Xie, J.H. Li, J. Org. Chem. 71 (2006) 379; (n) A. Cwik, Z. Hell, F. Figueras, Tetrahedron Lett. 47 (2006) 3023. For the selected paper on nickel catalysts, see: L. Wang, P. Li, Y. Zhang, Chem. Commun. (2004) 514 (and references cited therein). For the papers on copper catalysts, see: (a) K. Okuro, M. Furuune, M. Enna, et al. J. Org. Chem. 58 (1993) 4716; (b) R.K. Gujadhur, C.G. Bates, D. Venkataraman, Org. Lett. 3 (2001) 4315; (c) P. Saejueng, C.G. Bates, D. Venkataraman, Synthesis (2005) 1706; (d) S. Cacchi, G. Fabrizi, L.M. Parisi, Org. Lett. 5 (2003) 3841; (e) D. Ma, F. Liu, Chem. Commun. (2004) 1934; (f) Y.F. Wang, W. Deng, L. Liu, et al. Chin. Chem. Lett. 16 (2005) 1197; (g) M.B. Thathagar, J. Beckers, G. Rothenberg, Green Chem. 6 (2004) 215. For a review on the Cu(OAc)2-mediated homocouplings of alkynes under oxygen, see: P. Siemsen, R.C. Livingston, F. Diederich, Angew. Chem. Int. Ef. 39 (2000) 2632. Typical procedure for the copper catalyzed Sonogashira cross-coupling reaction: Cu(OAc)2 (50 mol.%) was added to a mixture of aryl halide 1 (0.5 mmol), alkyne 2 (0.80 mmol) and Et3N (3 mL) in a Schlenk tube (by syringe). Then the mixture was stirred in Ar at 140–150 8C for 24 h until the starting material was completely consumed (monitored by TLC). The mixture was filtered and concentrated, the residue was purified by flash column chromatography eluted with hexane or hexane/ethyl acetate to afford the desired products.