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Received: 12 January 2012 Revised: 5 April 2012 Accepted: 7 April 2012 Published online in Wiley Online Library

(wileyonlinelibrary.com) DOI 10.1002/aoc.2871

Bi(III)-catalyzed C-S cross-coupling reactionPayal Malik and Debashis Chakraborty*

A direct synthetic route for the C-S coupling of aryl halides with thiophenols is described. This method is tolerant to electron-withdrawing and electron-donating functional groups and also to the presence of functional groups in the ortho position of

the aryl iodide or thiophenol. Aryl iodides are coupled with thiophenols without affecting the other functionalities presentin the aryl ring. These reactions follow second-order kinetics. Copyright © 2012 John Wiley & Sons, Ltd.

Supporting information may be found in the online version of this article.

Keywords: C-S cross-coupling reaction; Bi2O3; aryl halide; thiophenol; water

* Correspondence to: Debashis Chakraborty, Department of Chemistry, IndianInstitute of Technology Madras, Chennai-600 036, Tamil Nadu, India. E-mail:dchakraborty@iitm.ac.in

Department of Chemistry, Indian Institute of Technology Madras, Chennai-600036, Tamil Nadu, India

Introduction

Cross-couplings catalyzed by transition metals historically relyon a reactive electrophile into which a transition metal inserts,and a reactive nucleophile that transfers an organic fragmentto the transition metal center. Reductive elimination finallydelivers the product.[1–5] Over time, milder and more selectiveconditions for cross-coupling reactions have been developed.Since the development of metal-catalyzed cross-couplingreactions in 1970s, numerous efforts have been made to makecross-coupling reactions more reliable and applicable.[6–8] Inthe last decade, transition metal-catalyzed C-S coupling ofdiaryl disulfides with aryl halides, boronic acid, aryl silane andaryl bismuthane have been reported.[9–11] The C-S bond isimportant in numerous compounds with biological and pharma-ceutical impact as well as for precursors required for thedevelopment of molecular materials, making several methodsfor its formation indispensable.[12–20] The traditional methodsfor C-S bond formation often employ harsh conditions. Thecoupling of thiolates with aryl halides takes place in hexamethyl-phosphoramide at 200�C. The reduction of sulfoxides andsulfones is carried out with strong reducing agents like DIBAL-Hand LiAlH4.

[21,22] To overcome such drawbacks, considerableresearch on the development of catalytic systems for the C-Scross-coupling of thiols with aryl halides have been developed.For industries, these reactions are attractive because the costand environmental impact of the process (E factor) are relativelylow. Palladium-,[23–36] copper-,[37–60] nickel-,[61–67] cobalt-,[68]

and iron-based [69–72] catalytic systems have been reported forthis purpose. The high cost and air sensitivity of palladium cata-lyst systems and tedious procedures for the preparation ofligands restrict their applications in large-scale processes. Al-though useful methods are currently available, the requirementof high temperatures or specially designed phosphine ligandshas prompted a search for new methods. Hence there is a needfor improved procedures for this important reaction in organicchemistry. Recently, bismuth salts have been employed for vari-ous organic transformations owing to its benign nature.[73–79]

Our continued interest in green chemistry research promptedus to explore the capability of bismuth compounds in catalyzingvarious organic reactions.[80,81]

Appl. Organometal. Chem. (2012)

Results and Discussion

C-S Cross-Coupling Reaction

The onset of investigations began with a search for the optimalconditions required for the C-S coupling between various aryliodides and thiophenols. The reactions were performed in thepresence of various Bi(III) compounds, solvents, ligands and bases(Table 1). The optimization results reveal that the 10 mol%Bi2O3 and N,N-dimethylethane-1,2-diamine with 1 equiv. KOHin water were the best reaction conditions. In fact, the prod-uct yield was reduced drastically when less than 10 mol%Bi2O3 was used.

The results shown in Table 2 indicate that the coupling ofthiophenols with aryl bromides or iodides was successful, leadingto the desired product in excellent yield. In summary, this protocolis tolerant to electron-withdrawing and electron-donating functionalgroups and also to the presence of a functional group in the orthoposition of the aryl iodide or thiophenol. The coupling reaction ischemoselective. Aryl iodides coupled with thiophenols withoutaffecting fluoro, chloro, bromo and amino groups present in the arylring. In general the reactions using aryl bromides are slower ascompared to the corresponding iodides and aryl chlorides werefound to be unreactive under the same reaction conditions.

The work-up for these coupling reactions involves extraction ofthe aqueous reaction mixture with ethyl acetate, and subsequentremoval of solvent followed by flash chromatography of thecrude product. We are pleased to disclose that the aqueousphase containing Bi2O3 can be recycled repeatedly without muchloss in activity of the reaction or yield (Table 3). We do not isolatethe Bi2O3 from the aqueous suspension, which is used repeatedlyfor subsequent cycles. The requisite amount of KOH was addedalong with the starting materials.

Copyright © 2012 John Wiley & Sons, Ltd.

Table 1. Optimization of reaction conditionsa

Entry Catalyst Ligand Solvent Base Time (h)b Yield (%)c

1 Bi2O3 1 H2O KOH 34 64

2 Bi2O3 2 H2O KOH 39 53

3 Bi2O3 3 H2O KOH 30 81

4 Bi2O3 4 H2O KOH 21 90

5 Bi2O3 5 H2O KOH 24 85

6 Bi2O3 6 H2O KOH 44 50

7 Bi2O3 7 H2O KOH 30 45

8 Bi2O3 4 DMSO KOH 30 60

9 Bi2O3 4 DMF KOH 32 69

10 Bi2O3 4 Toluene KOH 35 40

11 Bi2O3 4 CH3CN KOH 40 30

12 BiCl3 4 H2O KOH 33 60

13 BiBr3 4 H2O KOH 42 58

14 Bi(NO3)3.5H2O 4 H2O KOH 50 50

15 Bi2O3 4 H2O K3PO4 26 82

16 Bi2O3 4 H2O Cs2CO3 30 75

17 Bi2O3 4 H2O Na2CO3 34 71

18 Bi2O3 4 H2O K2CO3 31 69

19 Bi2O3 4 H2O NaHCO3 35 50

20 Bi2O3 4 H2O NaOH 28 60

21 Bi2O3 (5 mol%) 4 H2O KOH 48 38

a4-Methylbenzenethiol (1 mmol) and phenyl iodide (1.2 mmol) were used.bMonitored using TLC until all the thiophenol was found consumed.cIsolated yield after column chromatography of the crude product.

P. Malik and D. Chakraborty

The kinetics for the coupling reaction of 2,4-dimethylbenze-nethiol with phenyl iodide was investigated. High-performanceliquid chromatography (HPLC) was used to determine the variousstarting materials and products present as a function of time. Theconcentration of thiophenol decreases steadily, while that of theproduct increases (see supporting information). We have calcu-lated the rate of such reactions. The van’t Hoff differential methodwas used to determine the order (n) and rate constant (k) (Fig. 1).The rate of the reaction at different concentrations can be

estimated by evaluating the slope of the tangent at each pointon the curve corresponding to that of 2,4-dimethylbenzenethiol.With these data, log10(rate) versus log10(concentration) is plotted.The order (n) and rate constant (k) are given by the slope of theline and its intercept on the log10(rate) axis. From Fig. 1, it is clearthat this reaction proceeds with second-order kinetics (n=2.01)and the rate constant k=0.1068 L mol�1 h�1.The proposed catalytic cycle (Scheme 1) for this coupling

reaction involves the coordination of the ligand to Bi2O3. Thenext step involves the coordination of the aryl bromide or iodideto this complex, followed by attack of the thiolate anion. This is

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accompanied by elimination of the product and the ligand catalystcomplex is set free to participate in the subsequent cycle. Thismechanism is in accordance with reports available in the literature.

We have concluded from inductively coupled plasma massspectrometric studies performed on Bi2O3 that this catalysis isnot a result of impurities (see supporting information). Trace Cu(II) or Fe(III) was introduced into the reaction mixture in theabsence of Bi2O3. The reaction mixture was stirred for 21 h. HPLCanalysis of the crude after work-up revealed the presence ofthe expected product in trace quantities. These studies suggestthat the contribution of product formation due to the presenceof Cu(II) or Fe(III) impurities is negligible.

Conclusions

A simple and efficient procedure is described for C-S bond forma-tion by cross-coupling of thiophenols with aryl bromides andiodides by using a combination of Bi2O3 and N,N-dimethylethane-1,2-diamine in water. These reactions do not require an inert

ohn Wiley & Sons, Ltd. Appl. Organometal. Chem. (2012)

Table 2. Bi2O3 catalyzed C-S cross-coupling reaction of thiophenols with aryl halidesa

Entry Thiophenol Halide Product Time (h)b Yield (%)c Characterization (ref.)d

1 27 84 [82]

2 22 87 [84]

3 20 88 [85]

4 26 84 [82]

5 29 85 [82]

6 17 92 [84]

7 30 85 [84]

8 18 88 [85]

9 17 86 [84]

10 29 85 [86]

11 21 90 [54]

12 30 88 [84]

13 28 90 [83]

14 35 85 [72]

15 31 87 [82]

16 40 78 [72]

17 52 60 [86]

18 27 82 [86]

aReactions of thiophenol (1 mmol) and aryl halide (1.2 mmol) with 10 mol% Bi2O3, 10 mol% N,N-dimethylethane-1,2-diamine and 1 equiv. KOH wereperformed in H2O at 100�C.

bMonitored with TLC.cIsolated yield after column chromatography of the crude product.dReference for authenticated product characterization.

Bi(III) catalyzed C-S grouping

atmosphere and can be performed at moderate temperatures,resulting in products in high yield and purity.

Experimental

Typical Procedure for the Coupling of Thiophenoland Aryl Halide

To a stirred aqueous (2.5 ml) suspension of thiophenol (1 mmol),Bi2O3 (46 mg, 10 mol %), N,N-dimethylethane-1,2-diamine

Appl. Organometal. Chem. (2012) Copyright © 2012 John W

(0.011 ml, 10 mol%) and KOH (56 mg, 1 equiv.), aryl halide(1.2 mmol) were added. The reaction mixture was heated toreflux and monitored using thin-layer chromatography (TLC) pe-riodically until all thiophenol was found consumed. The reactionmixture was extracted repeatedly with ethyl acetate. All thevolatile organics were removed under reduced pressure. Thecrude product was purified using flash column chromatography.The characterization data matched very well with the literature(Table 2).

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Scheme 1. Proposed catalytic cycle for C-S coupling using Bi2O3

-2.0 -1.5 -1.0 -0.5-6.0

-5.5

-5.0

-4.5

-4.0

-3.5

-3.0

-2.5

-2.0

Y = -0.9713 + 2.0142 XR=0.9998

log 10

(ra

te)

log10

C

Figure 1. Van’t Hoff differential plot for the reaction of 2,4-dimethylben-zenethiol with phenyl iodide using 10 mol% Bi2O3, 1 equiv. KOH and10 mol% N,N-dimethylethane-1,2-diamine in water under reflux

Table 3. Results for the coupling of iodobenzene and 4-methylbenzenethiol in different cyclesa

Cycle Time (h)b Yield (%)c

1 21 90

2 21 90

3 21 90

4 21 89

5 21 89

aReactions of thiophenol (1 mmol) and aryl halide (1.2 mmol)with 10 mol% Bi2O3, 10 mol% N,N-dimethylethane-1,2-diamine and1 equiv. KOH were performed in H2O at 100�C.

bMonitored with TLC.cIsolated yield after column chromatography of the crude product.

P. Malik and D. Chakraborty

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Acknowledgments

The authors thank the Department of Science and Technology,New Delhi, for financial support.

References

[1] S. E. Denmark, J. H.-C. Liu, Angew. Chem. Int. Ed. 2010, 49, 2978.[2] A. Rodolph, M. Lautens, Angew. Chem. Int. Ed. 2009, 48, 2656.[3] J. B. Johnson, T. Rovis, Angew. Chem. Int. Ed. 2008, 47, 840.[4] G. A. Molander, N. Ellis, Acc. Chem. Res. 2007, 40, 275.[5] A. C. Frisch, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 674.[6] A. de Meijere, F. Diederich, Metal-Catalyzed Cross-Coupling Reactions,

Wiley-VCH, Weinheim, 2004.[7] N. Miyaura, Cross-Coupling Reactions: A Practical Guide, Springer,

Berlin, 2002.[8] F. Diederich, P. J. Stang, Metal-Catalyzed Cross-Coupling Reactions,

Weinheim, Wiley-VCH, 1998.[9] S. V. Ley, A. W. Thomas, Angew. Chem. Int. Ed. 2003, 42, 5400.

[10] S. Yasuike, M. Nishioka, N. Kakusawa, J. Kurita, Tetrahedron Lett.2011, 52, 6403.

[11] S. E. Denmark, M. H. Ober, Adv. Synth. Catal. 2004, 246, 1703.[12] J.-P. Corbet, G. Mignani, Chem. Rev. 2006, 106, 2651.[13] I. P. Beletskaya, A. V. Cheprakov, Coord. Chem. Rev. 2004, 248, 2337.[14] J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev.

2002, 102, 1359.[15] D. J. Procter, J. Chem. Soc. Perkin Trans. 2001, 1, 335.[16] C. G. Frost, P. Mendonca, J. Chem. Soc. Perkin Trans 1998, 1, 2615.[17] J. P. Wolfe, S. Wagaw, J.-F. Marcoux, S. L. Buchwald, Acc. Chem. Res.

1998, 31, 805.[18] C. M. Rayner, Contemp. Org. Synth. 1996, 3, 499.[19] D. N. Jones in Comprehensive Organic Chemistry, Vol. 3 (Eds.: D. H.

Barton, D. W. Ollis), Pergamon, New York, 1979.[20] J. V. Wangelin in Transition Metals for Organic Synthesis, Vol. 1 (Eds:

M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004.[21] J. A. Van Bierbeek, M. Gingras, Tetrahedron Lett. 1998, 39, 6283.[22] T. Yamamoto, Y. Sekine, Can. J. Chem. 1984, 62, 1544.[23] M. A. Fernández Rodríguez, Q. Shen, J. F. Hartwig, J. Am. Chem. Soc.

2006, 128, 2180.[24] R. S. Barbikri, C. R. Bellato, A. K. C. Dias, A. C. Massabni, Catal. Lett.

2006, 109, 171.[25] C. Mispelaere-Canivet, J.-F. Spindler, S. Perrio, P. Beslin, Tetrahedron

2005, 61, 5253.[26] T. Itoh, T. Mase, Org. Lett. 2004, 6, 4587.[27] M. Murata, S. L. Buchwald, Tetrahedron 2004, 60, 7397.[28] G. Y. Li, Angew. Chem. Int. Ed. 2001, 40, 1513.[29] M. A. Fernández-Rodríguez, J. F. Hartwig, Chem. Eur. J. 2010, 16,

2355.[30] C. S. Bryan, J. A. Braunger, M. Lautens, Angew. Chem. Int. Ed. 2009, 48,

7064.[31] U. Schopfer, A. Schlapbach, Tetrahedron 2001, 57, 3069.[32] Z. Jiang, J. She, X. Lin, Adv. Synth. Catal. 2009, 351, 2558.[33] J.-Y. Lee, P. H. Lee, J. Org. Chem. 2008, 73, 7413.[34] C. C. Eichman, J. P. Stambuli, J. Org. Chem. 2009, 74, 4005.[35] C.-F. Fu, Y.-H. Liu, S.-M. Peng, S.-T. Liu, Tetrahedron 2010, 66, 2119.[36] M. A. Fernandez-Rodriguez, J. F. Hartwig, Chem. Eur. J. 2006, 12,

7782.[37] Y.-J. Chen, H.-H. Chen, Org. Lett. 2006, 8, 5609.[38] D. Zhu, L. Xu, F. Wu, B. S. Wan, Tetrahedron Lett. 2006, 47, 5781.[39] C. G. Bates, P. Saejueng, M. Q. Doherty, D. Venkataraman, Org. Lett.

2004, 6, 5005.[40] W. Deng, Y. Zou, Y.-F. Wang, L. Liu, Q.-X. Guo, Synlett 2004, 1254.[41] Y.-J. Wu, H. He, Synlett 2003, 1789.[42] C. G. Bates, R. K. Gujadhur, D. Venkataraman, Org. Lett. 2002, 4, 2803.[43] F. Y. Kwong, S. L. Buchwald, Org. Lett. 2002, 4, 3517.[44] C. Savarin, J. Srogl, L. S. Liebeskind, Org. Lett. 2002, 4, 4309.[45] C. Palomo, M. Oiarbide, R. Lopez, E. Gomez-Bengoa, Tetrahedron Lett.

2000, 41, 1283.[46] E. P. S. Herradura, K. A. Pendola, R. K. Guy, Org. Lett. 2000, 2, 2019.[47] Y.-B. Huang, C.-T. Yang, J. Yi, X.-J. Deng, Y. Fu, L. Liu, J. Org. Chem.

2011, 76, 800.[48] D. J. C. Prasad, G. Sekar, Org. Lett. 2011, 13, 1008.

ohn Wiley & Sons, Ltd. Appl. Organometal. Chem. (2012)

Bi(III) catalyzed C-S grouping

[49] C.-K. Chen, Y.-W. Chen, C.-H. Lin, H.-P. Lin, C.-F. Lee, Chem. Commun.2010, 46, 282.

[50] Y.-S. Feng, Y.-Y. Li, L. Tang, W. Wu, H.-J. Xu, Tetrahedron Lett. 2010, 51,2489.

[51] D. J. C. Prasad, G. Sekar, Synthesis 2010, 79.[52] L. Rout, T. K. Sen, T. Punniyamurthy, Angew. Chem. Int. Ed. 2007, 46,

5583.[53] X. Lv, W. Bao, J. Org. Chem. 2007, 72, 3863.[54] L. Rout, P. Saha, S. Jammi, T. Punniyamurthy, Eur. J. Org. Chem. 2008,

640.[55] S. Bhadra, B. Sreedhar, B. C. Ranu, Adv. Synth. Catal. 2009, 351, 2369.[56] E. Sperotto, G. P. M. van Klink, J. G. de Vries, G. Koten, J. Org. Chem.

2008, 73, 5625.[57] C. Gonzalez-Arellano, R. Luque, D. J. Macquarrie, Chem. Commun.

2009, 1410.[58] Z. Duan, S. Ranjit, P. Zhang, X. Liu, Chem. Eur. J. 2009, 3666.[59] S. Ranjit, R. Lee, D. Heryadi, C. Shen, J.-E. Wu, P. Zhang, K.-W. Huang,

X. Liu, J. Org. Chem. 2011, 76, 8999.[60] S. Ranjit, Z. Duan, P. Zhang, X. Liu, Org. Lett. 2010, 12, 4134.[61] C. Millois, P. Diaz, Org. Lett. 2000, 2, 1705.[62] V. Percec, J.-Y. Bae, D. H. Hill, J. Org. Chem. 1995, 60, 6895.[63] J. Zhang, C. M. Medley, J. A. Krause, H. Guan, Organometallics 2010,

29, 6393.[64] S. Jammi, P. Barua, L. Rout, P. Saha, T. Punniyamurthy, Tetrahedron

Lett. 2008, 49, 1484.[65] H. J. Cristau, B. Chabaud, A. Chêne, H. Christol, Synthesis 1981, 892.[66] K. Takagi, Chem. Lett. 1987, 2221.[67] N. Taniguchi, J. Org. Chem. 2004, 69, 6904.[68] Y.-C. Wong, T. T. Jayanth, C.-H. Cheng, Org. Lett. 2006, 8, 5613.

Appl. Organometal. Chem. (2012) Copyright © 2012 John W

[69] J. Mao, G. Xie, M. Wu, J. Guo, S. Ji, Adv. Synth. Catal. 2008, 350,2477.

[70] V. K. Akkilagunta, V. P. Reddy, K. R. Rao, Synlett 2010, 1260.[71] W.-Y. Wu, J.-C. Wang, F.-Y. Tsai, Green Chem. 2009, 11, 326.[72] X.-L. Fang, R.-Y. Tang, X.-G. Zhang, J.-H. Li, Synthesis 2011, 1099.[73] Y. Matano, T. Ikegami in Organobismuth Chemistry (Eds: H. Suzuki,

Y. Matano), Elsevier, New York, 2001.[74] H. Kamisaki, T. Nanjo, C. Tsukano, Y. Takemoto, Chem. Eur. J. 2011,

17, 626.[75] K. Komeyama, N. Saigo, M. Miyagi, K. Takaki, Angew. Chem. Int. Ed.

2009, 48, 9875.[76] H. R. Kricheldorf, Chem. Rev. 2009, 109, 5579.[77] V. Liautard, V. Desvergnes, K. Itoh, H.-W. Liu, O. R. Martin, J. Org.

Chem. 2008, 73, 3103.[78] H. H. Jung, J. R. Seiders, P. E. Floreancig, Angew. Chem. Int. Ed. 2007,

46, 8464.[79] P. A. Evans, J. Cui, S. J. Gharpure, R. G. Hinkle, J. Am. Chem. Soc. 2003,

125, 11456.[80] P. Malik, D. Chakraborty, Synthesis 2011, 277.[81] D. Chakraborty, R. R. Gowda, P. Malik, Tetrahedron Lett. 2009, 50, 6553.[82] S. P. Lohmann, B. J. Burke, M. D. Smith, J. P. Attfield, H. Tanaka,

K. Kaneko, S. V. Ley, Synlett 2005, 1291.[83] S. Zhang, P. Qian, M. Zhang, M. Hu, J. Cheng, J. Org. Chem. 2010,

75, 6732.[84] M. A. Fernandez-Rodriguez, J. F. Hartwig, J. Org. Chem. 2009, 74, 1663.[85] Y. Li, C. Nie, H. Wang, X. Li, F. Verpoort, C. Duan, Eur. J. Org. Chem.

2011, 7331.[86] P. Buranaprasertsuk, J. W. W. Chang, W. Chavasiri, P. W. H. Chan,

Tetrahedron Lett. 2008, 49, 2023.

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