biphenyl-based phosphine system in the Ullmann homocoupling of aryl bromides

Journal of Organometallic Chemistry 696 (2011) 2966e2970

Contents lists available at ScienceDirect

Journal of Organometallic Chemistry journal homepage: www.elsevier.com/locate/jorganchem

Investigation of the catalytic activity of a Pd/biphenyl-based phosphine system in the Ullmann homocoupling of aryl bromides Shirin Nadri a, Ehsan Azadi a, Ali Ataei a, Mohammad Joshaghani a, b, *, Ezzat Rafiee a, b a b

Chemistry Faculty, Razi University, Kermanshah 67149, Iran Kermanshah Oil Refining Company, Kermanshah, Iran

a r t i c l e i n f o

a b s t r a c t

Article history: Received 14 February 2011 Received in revised form 27 April 2011 Accepted 28 April 2011

We described Ullmann homocoupling promoted by a Pd/biphenyl-based phosphine system using DMF as solvent. Using Hammett equation it is found that the rate determining step of the reaction depends on the electronic nature of substituents of aryl bromides. Increase the rate of reaction with decreasing the electron donating of the substituent from NH2 to H suggesting an oxidative addition step as the rate determining step. Decrease the rate of reaction with increasing the electron-withdrawing ability of the substituent from H to NO2 indicating a reductive elimination step as the rate determining step. Ó 2011 Published by Elsevier B.V.

Keywords: CeC coupling reaction Ullmann reaction Palladium Biphenyl-based phosphine Hammett correlation

1. Introduction The Ullmann reaction has evolved considerably from its original guise as the homocoupling of aryl halides in the presence of an excess of copper powder at elevated temperatures [1]. Improvements to this method have emerged in recent years with palladium-catalyzed systems under milder conditions which allow easy access to biaryls from relatively simple substrates [2e5]. There are several reaction mechanisms for homocoupling. One of the well-recognized mechanisms for Ullmann reaction [6,7] (Scheme 1, abbreviated as 0/2/4) involves consecutive oxidative addition steps of aryl halide on Pd(0) and Pd(II) species, respectively. The resulting Pd(IV) species is very unstable and readily undergoes reductive elimination to form Pd(II) species. A terminal reducing agent is required to regenerate Pd(0) from Pd(II) in the terminal reduction step and to complete the catalytic cycle. Several types of reductants have been reported such as zinc powder [8], tertiary amines [6], hydrazine [9], molecular hydrogen [10], hydroquinone [11]. The main characteristic of this mechanism is the change of palladium oxidation state between zero, two and four.

* Corresponding author. Chemistry Faculty, Razi University, Kermanshah 67149, Iran. Tel./fax: þ98 831 4274559. E-mail address: [email protected] (M. Joshaghani). 0022-328X/$ e see front matter Ó 2011 Published by Elsevier B.V. doi:10.1016/j.jorganchem.2011.04.032

In addition to above mechanism, another reaction mechanism (abbreviated as 0/2) has already been proposed [12] in which, an oxidative addition of aryl halide on Pd(0) takes place, followed by disproportionation to afford intermediate ArePdeAr and PdX2. The resulting bisarylpalladium(II) will be subjected to reductive elimination to yield the coupling product together with Pd(0) precursor. PdX2 can be reduced using a terminal reducing agent such as amines. Despite of these outstanding characteristics, the reports on the mechanistic details about this homocoupling reaction are relatively rare [13,14]. For example it is not clear which step is the rate determining step of the overall reaction. Since such details are key information in catalyst designing, and emanating from our interest in palladium-catalyzed CeC coupling reactions [15e20] we decided to investigate the Ullmann homocoupling reactions of aryl bromides since this reaction is a oneecomponent reaction and does not need any pseudo-conditioning pre-treatment. Among a series of mechanistic tools, Hammett’ linear free energy relationship (LFER) is more useful for one-component reactions and its constants sR and r are measure of the effects of chemical structure on reactivity of compounds. With this in mind, we used palladium acetate as a catalyst and a synthesized biphenyl-based phosphine [15,16] in the Ullmann homocoupling reaction (Scheme 2). Mild reaction conditions, low catalyst loadings and short reaction times are only some reported advantages of this class of phosphines in the Pd-catalyzed crosscoupling reactions [21e28]. In fact, a suitable balance of structural,

S. Nadri et al. / Journal of Organometallic Chemistry 696 (2011) 2966e2970

steric and electronic properties, made them as one of the most effective classes of phosphine ligands identified so far for such reactions.

Pd(II) Initial reduction

Pd(0)

Terminal reduction

2. Material and methods

First oxidative addition

4

1

Ar X

2.1. General information

Ar Pd(II)X

Pd(II)X2

All reactions were performed under an atmosphere of dry nitrogen. All chemicals were purchased commercially from Fluka and/or Merck companies that were used without further purification. The biphenyl-based phosphine was prepared according to our previous work [15,16]. 1 H (200 MHz), 13C (100 MHz) and 31P (81 MHz) NMR spectra were recorded on a Bruker Avance Spectrometer. Elemental analysis was performed using CHN Herause rapid model. Gas chromatography was performed on a Varian CP-3800 (column: CP-Sil 8 CB fused silica capillary column). Thin layer chromatography on precoated silica gel Fluorescent 254 nm (0.2 mm) on aluminum plates were used for monitoring the reactions. The cross coupling products were characterized by their 1H NMR spectra or GC analysis.

2

3 Reductive elimination

Ar Ar

Second oxidative addition

Pd(IV)X2

Ar Ar

Ar X

Scheme 1. General catalytic cycle for the Pd(0)-catalyzed homocoupling of aryl halides.

2

Br

Pd(OAc)2 Biphenyl-based phosphine

R

2967

R

R

2.2. General procedure for palladium-catalyzed homocoupling of aryl bromides

PPh2 Phosphine:

A mixture of palladium acetate (0.2 mol%), biphenyl-based phosphine (0.4 mol%), aryl bromide (5 mmol) and NEt3 (7.5 mmol) in DMF (10 ml) was stirred under nitrogen atmosphere at 100  C for appropriate time. The reaction mixture was then cooled to room temperature. After extraction with water and ether, the combined organic layer was dried over MgSO4. The solvent was evaporated and the crude product was characterized by 1H NMR spectroscopy.

Me Scheme 2. Homocoupling of aryl bromides catalyzed by palladium.

Table 1 Initial optimizations for homocoupling reaction of bromobenzene.a

2

Br

[Cat.] Base, Solvent,100 oC

Entry

Pd(OAc)2 (mol%)

Phosphine:Pd

Base

Solvent

Yieldb (%)

TONb

1 2 3 4 5 6 7 8 9 10 11 12 13c 14 15 16d 17 18d 19 20e 21f

0.001 0.01 0.1 0.2 0.3 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2

1:1 1:1 1:1 1:1 1:1 0:1 2:1 3:1 2:1 2:1 2:1 2:1 2:1 2:1 2:1 2:1 2:1 2:1 2:1 2:1 2:1

NEt3 NEt3 NEt3 NEt3 NEt3 NEt3 NEt3 NEt3 No base NaOH NaOAc K2CO3 K2CO3 NEt3 NEt3 NEt3 NEt3 NEt3 NEt3 NEt3 NEt3

DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF Toluene 1,4-Dioxane THF CH3NO2 CH3CN DMSO DMF DMF

0 0 21 58 63 0 (22) 100 41 0 (<5) 44 (65) 65 (73) 67 (82) 91 (100) 0 (<5) 0 (<5) 0 (13) 39 (85) 12 (41) 33 (76) (12) (29)

0 0 210 290 210 0 (110) 500 205 0 (<25) 220 (325) 325 (365) 335 (410) 455 (500) 0 (<25) 0 (<25) 0 (65) 195 (425) 60 (205) 165 (380) (60) (145)

a b c d e f

Reaction conditions: bromobenzene (5 mmol), base (7.5 mmol), solvent (10 ml), 100  C, 5 h, under N2. GC yield. The numbers in parentheses are yields and TON after 24 h. In the presence of isopropanol. 60  C. Room temperature. Bath temperature (75  C).

2968

S. Nadri et al. / Journal of Organometallic Chemistry 696 (2011) 2966e2970

3. Results and discussion 3.1. Initial optimization Initial optimizations for homocoupling reaction of bromobenzene were carried out to find the optimum catalyst loading, phosphine:Pd mole ratio, base and solvent (Table 1). As the results show, the yield of reaction increases significantly with increasing the catalyst loading till 0.2 mol% Pd(OAc)2 and then increases smoothly with higher catalyst loading (Table 1, entries 1e5). The 0.2 mol% catalyst was selected according economically point of view. The influence of the phosphine:Pd mole ratio on the outcome of the reaction (yield and turnover number [TON]) was investigated using different mole ratios 0:1, 1:1, 2:1 and 3:1 (Table 1, entries 4, 6e8). Phosphine-free reaction led to the biphenyl product with low yield even after 24 h (Table 1, entry 6). An effortless interpretation is exist which suggests the phosphine facilitates the homocoupling reactions by promoting the initial reduction of the Pd(OAc)2 to Pd(0). However, other factors should also be considered. For examples, it has been reported that biphenyl-based phosphines contribute in the stabilization of the intermediates by avoiding the catalyst degradation through the formation of p-interactions with the aryl ring [29e33]. As a result, it may be concluded that

significant influence of the phosphine is due to its steric-electronic effects on palladium center. A 2:1 phosphine:Pd mole ratio appears to provide the active catalyst (Table 1, entry 7). This mole ratio is in consistent with our results regarding Suzuki [16] and Heck [18] cross-couplings using the same phosphine. Using a higher mole ratio (Table 1, entry 8) gave low yield which may be due to decrease of rate of oxidative addition step by formation of a bis-phosphine Pd complex and blocking of free coordination sites on the Pd species. We paid attention to the effects of base in homocoupling reactions. Indeed, the base is necessary for terminal reduction and without base, the catalytic cycle is not completed. A among a series of bases, NEt3 was selected as a base of choice (Table 1, entry 7). Its more efficiency is probably due to its solubility in most organic solvents as well as its high reducing ability. Low conversion was achieved using K2CO3 (Table 1, entry 12). This feature may be interpreted by the fact that in the presence of an inorganic base, DMF decomposes into the carbon monoxide and dimethylamine; the latter could reduce aryl halides in the presence of Pd (0) catalysts [34]. Panvela et al. [35] reported that a reductive reagent such as isopropanol could promote the homocoupling of aryl halides using inorganic bases such as K2CO3. In our system addition of isopropanol to the reaction mixture using K2CO3 as base could really

Table 2 The Ullmann homocoupling of various aryl bromides.a

2

Br

R

Entry

Aryl bromides

Pd(OAc)2 / Phosphine Et3N, DMF, 100 oC

R

R

Yieldb

sp

krelc

TONb

100

0

1

500

1

Br

2

Br

CH3

59 (74)

0.17

0.59

295 (370)

3

Br

OCH3

27 (53)

0.27

0.27

135 (265)

4

Br

COCH3

18 (39)

0.5

0.18

90 (195)

5

Br

NO2

5 (28)

0.78

0.05

25 (140)

6

Br

NH2

10 (24)

0.66

0.1

50 (120)

<5 (73)

e

e

<25 (365)

<5

e

e

<25

Br 7

8 a b c d

d

Br

Reaction condition: aryl bromide (5 mmol), Pd(OAc)2 (0.2 mol%), phosphine (0.4 mol%), NEt3 (7.5 mmol), DMF (10 ml), 100  C, 5 h, N2. The results in parentheses is conversion after 24 h. krel is equal with (kR/kH), that kH is related to homocoupling reaction of bromobenzene and para-substituent is H. The number in parentheses is from the Pd(OAc)2 (5 mol%), phosphine (10 mol%).

S. Nadri et al. / Journal of Organometallic Chemistry 696 (2011) 2966e2970

Fig. 1. LFER for the Ullmann homocoupling reactions of various aryl bromides.

increase the yield of the desired biphenyl (Table 1, entry 13), but it was still less efficient than NEt3. Examination of entry 9 of Table 1 shows that no reductive homocoupling product (biphenyl) was formed in the absence of base, indicating that the base is essential for achieving the palladium-catalyzed reductive homocoupling of aromatic halides in DMF solution. In the next stage, the effect of solvent was investigated. As shown in Table 1, the reaction rate is greatly affected by the kind of solvent used. Among the commonly used organic solvents, the best results were obtained with DMF (Table 1, entry 7) and in some extent with CH3NO2 and DMSO (Table 1, entries 17, 19). DMF has an important advantage which made them as a unique solvent. Its water solubility makes the product extraction and purification very easy. The effect of temperature was finally examined and it is found that the reaction temperature has a great effect; the reaction being very slow below 100  C (Table 1, entries 20e21). Thus, temperature of 100  C was the optimal one in this study. 3.2. The Ullmann homocoupling reactions Using the optimized reaction conditions, we explored the general applicability of Pdephosphine system with different aryl

2969

bromides containing electron-withdrawing or donating substituents in the Ullmann homocoupling reaction (Table 2). Regardless 4-bromotoluene which has acceptable conversion and coupling yield (Table 2, entry 2), both electron-rich and electron-deficient studied aryl bromides had low to negligible conversions and yields. 1-bromo-4-nitrobenzene gave significant conversion but very low yield (Table 2, entry 5) after 24 h which may be due its activity toward dehalogenation [36]. Similarly, 4-brommoaniline had excellent conversion but negligible yield (Table 2, entry 6) because of substrates like amines strongly inhibit or prevent formation of biaryls by providing alternative reaction pathways [37e39]. Thus amines are arylated at N-atoms affording triarylamines [37]. Table 2 shows that 1-bromonaphthalene and 4-bromobiphenyl were inactive substrates for this reaction (entries 7, 8). It seems that steric factor is mostly responsible for the decreased yield in these cases. In the case of 1-bromonaphthalene increasing catalyst loading to 5 mol% gave 73% yield indicating the efficiency of the high catalyst loading (Table 2, entry 7). 3.3. Mechanistic study by Hammett correlation As briefly discussed in the introduction, there are several mechanisms for the Ullmann coupling, among them, the 0/2/4 and 0/2 mechanisms are most common. In order to investigate which of them is responsible in our reaction condition; competitive reaction using equimolar amounts of 4-iodobenzene and 4-bromoanisole was performed. If a 0/2/4 mechanism accounts the Ullmann reactions, the coupling product should be mainly biphenyl formed from the homocoupling of iodobenzene. While, in a 0/2 mechanism, both homo and cross coupling products should be observed [6]. In our preliminary tests, no cross coupling product was observed indicating a 0/2/4 mechanism should be responsible. After determination of the reaction mechanism, we should concentrated on a question arouse, which step in the overall reaction is likely to be the slow and hence rate-limiting one? Among two consecutive oxidative addition steps, the first one is

Fig. 2. LFER for the Ullmann homocoupling reactions in other catalytic systems, (a) Cat: Pd(dppf)Cl2, in DMSO see Ref. [41] (b) Cat: Pd(dppf)Cl2, in 3-Pentanol; see Ref. [42] (c) Cat: PdCl2/EDTA/ascorbic acid in watereethanol, see Ref. [43].

2970

S. Nadri et al. / Journal of Organometallic Chemistry 696 (2011) 2966e2970

unlikely to be since oxidative addition for more electron-rich Pd(0) is faster than Pd(II). In addition, more steric crowding about Pd(II) decrease more the rate of second oxidative addition respect to Pd(0). The terminal reduction step is unlikely to be rds as well since it is independent to aryl halide. This leaves steps (2) and (3) as possible candidates for the rate determining step. Using Hammett correlation we are capable to undertake mechanistic studies. If only one of these steps (2 or 3) is the rate determining step for all aryl bromides, independent of electron-withdrawing or electrondonating properties of substituents, a straight line should be expected in the Hammett plot. As shown in Table 2, both electron-donating and electronwithdrawing substituents reduce the reaction yield. This behavior may be interpreted by considering different rate determining step in the catalytic cycle. In this context, to evaluate the above substituent effects we have attempted to correlate the data reported in Table 2 with s substituent constant in terms of Hammett’s equation:

Log krel ¼ Log ðkR =kH Þ ¼ rsp where kR and kH are related to homocoupling reaction of substituted and unsubstituted bromobenzenes, respectively. sp is the substituent constant [40] and r is the reaction constant; the later could be obtained from the slope of the plot of Log krel against sp. A Hammett plot of the Log krel (derived from the corresponding TON) versus sp is clearly composed of two straight lines, one on the left with r ¼ þ1.52, and the other on the right with r ¼ 1.65 (Fig. 1). In the left side of the plot (with r ¼ þ1.52), decreasing the electron donating of the substituent (from NH2 with sp ¼ 0.6 to H with sp ¼ 0) increases the rate of coupling reaction. This behavior is in agreement with that expected for the second oxidative addition step (step 2) as the rate-limiting step. In the right side of the plot (with r ¼ 1.65) however, increasing the electron-withdrawing ability of the substituent has opposite effect; decreases the rate of coupling reaction. These results are more consisting by choosing the reductive elimination step (step 3) as probable rate-limiting step. On the other word, increasing the electron-withdrawing ability of the substituent increases the rate of oxidative addition to the extent where the oxidative addition become fast than the reductive elimination and hence the reductive elimination become the rate determining step. Therefore, there is a point (or narrow band) where the rate of reductive elimination (step 3) catches up with the rate of second oxidative addition (step 2). In such point, it is not clear to decide what step is the rate-limiting step. In our case study, this point was unsubstituted bromobenzene but for LFER study on literature results [41e43] revealed that different substituents may be the choice depends on the electron density of metal center (Fig. 2). 4. Conclusions In summary, the results presented in this paper show that Pd/biphenyl-based phosphine system is capable of catalyzing homocoupling of aryl bromides. More prominently, Hammett study on our results as well as literature results shows that electronic properties of aryl bromide affect on the rate of the Ullmann reaction. Depending on the nature of substituent, the rate determining step may be either oxidative addition step or reductive elimination step. Electron-withdrawing groups prompt the oxidative addition. Therefore, increase the rate of reaction with decreasing the electron donating of the substituent from NH2 to H suggesting an oxidative addition step as the rate determining step. Decrease the rate of reaction with

increasing the electron-withdrawing ability of the substituent from H to NO2 indicating a reductive elimination step as the rate determining step. In the case of bromobenzene, the rate of oxidative addition and reductive elimination steps are comparable and it is not clear to decide what step is the rate-limiting step. Acknowledgments The authors thank the Razi University Research Council and Kermanshah Oil Refining Company for support of this work. References [1] F. Ullmann, J. Bielecki, Chem. Ber 34 (1901) 2174e2178. [2] W.M. Seganish, M.E. Mowery, S. Riggleman, P. DeShong, Tetrahedron 61 (2005) 2117e2121. [3] J. Hassan, C. Hathroubi, C. Gozzi, M. Lemaire, Tetrahedron Lett. 41 (2000) 8791e8794. [4] M. Kuroboshi, Y. Waki, H. Tanaka, J. Org. Chem 68 (2003) 3938e3942. [5] M. Catellani, E. Motti, S. Baratta, Org. Lett. 3 (2001) 3611e3614. [6] J. Hassan, C. Hathroubi, C. Gozzi, M. Lemaire, Tetrahedron 57 (2001) 7845e7855. [7] I. Cepanec, M. Litvi c, J. Udikovi c, I. Pogoreli c, M. Lovric, Tetrahedron 63 (2007) 5614e5621. [8] A.S. Kende, L.S. Libeskind, D.M. Braitsch, Tetrahedron Lett. 16 (1975) 3375e3378. [9] R. Nakajima, Y. Shintani, T. Hara, Bull. Chem. Soc. Jpn. 53 (1980) 1767e1768. [10] S. Mukhopadhyay, G. Rothenberg, H. Wiener, Y. Sasson, Tetrahedron 55 (1999) 14763e14768. [11] D.D. Hennings, T. Iwama, V.H. Rawal, Org. Lett. 1 (1999) 1205e1208. [12] M. Kotora, T. Takahashi, in: E.-I. Negishi (Ed.), Handbook of Organopalladium Chemistry for Organic Synthesis, vol. 1, Wiley-Interscience, New York, 2002, pp. 973e993. [13] C. Amatore, E. CarrC, A. Jutand, H. Tanaka, Q. Ren, S. Torii, Chem. Eur. J. 2 (1996) 957e966. [14] S. Mukhopadhyay, G. Rothenberg, D. Gitis, H. Wiener, Y. Sasson, J. Chem. Soc., Perkin Trans. 2 (1999) 2481e2484. [15] M. Joshaghani, E. Faramarzi, E. Rafiee, M. Daryanavard, J. Xiao, C. Baillie, J. Mol. Catal. A: Chem. 273 (2007) 310e315. [16] M. Joshaghani, M. Daryanavard, E. Rafiee, J. Xiao, C. Baillie, Tetrahedron Lett. 48 (2007) 2025e2027. [17] M. Joshaghani, M. Daryanavard, E. Rafiee, Sh Nadri, J. Organomet. Chem 693 (2008) 3135e3140. [18] Sh Nadri, M. Joshaghani, E. Rafiee, Appl. Catal. A: Gen. 362 (2009) 163e168. [19] Sh. Nadri, M. Joshaghani, E. Rafiee, Tetrahedron Lett. 50 (2009) 5470e5473. [20] Sh. Nadri, M. Joshaghani, E. Rafiee, Organometallics 28 (2009) 6281e6287. [21] T.E. Barder, S.D. Walker, J.R. Martinelli, S.L. Buchwald, J. Am. Chem. Soc. 127 (2005) 4685e4696. [22] K.L. Billingsley, K.W. Anderson, S.L. Buchwald, Angew. Chem. Ind. Ed. 45 (2006) 3484e3488. [23] J.E. Milne, S.L. Buchwald, J. Am. Chem. Soc. 126 (2004) 13028e13032. [24] J.P. Wolfe, H. Tomori, J.P. Sadighi, J.J. Yin, S.L. Buchwald, J. Org. Chem 65 (2002) 1158e1174. [25] D.W. Old, J.P. Wolfe, S.L. Buchwald, J. Am. Chem. Soc. 120 (1998) 9722e9723. [26] J.P. Wolfe, S.L. Buchwald, Angew. Chem. Ind. Ed. 38 (1999) 2413e2416. [27] A.V. Vorogushin, X.H. Huang, S.L. Buchwald, J. Am. Chem. Soc. 127 (2005) 8146e8149. [28] C.H. Burgos, T.E. Barder, X.H. Huang, S.L. Buchwald, Angew. Chem. Ind. Ed. 45 (2006) 4321e4326. [29] J. Yin, M.P. Rainka, X.-X. Zhang, S.L. Buchwald, J. Am. Chem Soc. 124 (2002) 1162e1163. [30] S.D. Walker, T.E. Barder, J.R. Martinelli, S.L. Buchwald, Angew. Chem. Int. Ed. 43 (2004) 1871e1876. [31] T.E. Barder, J. Am. Chem. Soc. 128 (2006) 898e904. [32] T.E. Barder, S.L. Buchwald, J. Am. Chem. Soc. 129 (2007) 12003e12010. [33] T.E. Barder, M.R. Biscoe, S.L. Buchwald, Organometallics 26 (2007) 2183e2192. [34] A.M. Zawisza, J. Muzart, Tetrahedron Lett. 48 (2007) 6738e6742. [35] V. Panvela, J. Hassan, L. Lavenot, C. Gozzi, M. Lemaire, Tetrahedron Lett. 39 (1998) 2559e2560. [36] K. Abiraj, G.R. Srinivasa, D. Channe Gowda, Tetrahedron Lett. 45 (2004) 2081e2084. [37] S. Gauthier, J.M.J. Frechet, Synthesis (1987) 383e385. [38] A.R. deLera, R. Suau, L. Castedo, J. Heterocycl. Chem. 24 (1987) 313e319. [39] A.J. Pearson, M.V. Chelliah, J. Org. Chem. 63 (1998) 3087e3098. [40] C. Hansch, A. Leo, R.W. Taft, Chem. Rev. 91 (1991) 165e195. [41] Ch. Qi, X. Sun, C. Lu, J. Yang, Y. Du, H. Wu, X.-M. Zhang, J. Organomet. Chem. 694 (2009) 2912e2916. [42] M. Zeng, Y. Du, L. Shao, Ch. Qi, X.-M. Zhang, J. Org. Chem. 75 (2010) 2556e2563. [43] R.N. Ram, V. Singh, Tetrahedron Lett. 47 (2006) 7625e7628.