Chem. Res. Chin. Univ.
doi: 10.1007/s40242-015-4437-3
Bifunctional Salen-Cu(II) Complex as Efficient Catalyst for N-arylation of Imidazoles and Suzuki-Miyaura Coupling Reactions WANG Yi*, GAO Jingyi, ZHAO Mengdan and LI Jiamei College of Chemistry and Engineering, Yunnan Normal University, Kunming 650500, P. R. China Abstract Bifunctional Salen-Cu(II) complex catalyzed cross-coupling reactions of aryl halids with imidazoles or phenylboronic acid reagents have been developed as practical methods for C―N and C―C bond formation. The procedure tolerates aryl halides with various functional groups(such as methoxy, acetyl, nitrile, fluoro and nitro groups) and gives the corresponding coupling products in moderate to high yields. The catalyst remained active after five successive catalytic runs without loss in performance. Keywords Salen-Cu(II) complex; Homogenous catalysis; Cross-coupling; N-arylation
1
Introduction
Transition-metal-catalyzed carbon-heteroatom or carboncarbon cross coupling reactions are essential in organic synthesis[1,2]. Rh-, Ru- and Pd-based noble metal complexes with a large number of phosphorous[3,4], carbene[5―7], oxime[8,9], imine[10―12] and other ligands[13,14] have been reported as catalysts for such couplings. From an academic, industrial, and economic standpoint, the abundant and inexpensive use of copper has led to remarkable progress in the development of copper-catalyzed C―C and C―N bond formation reactions[15―19]. Buchwald et al.[20] and Taillefer et al.[21―23] revealed rate accelerations when arylations were conducted in the presence of certain copper ligands. Many important results have been achieved via the methodology. However, this method still suffers from some limitations. Firstly, the system is only efficient with Cu(I) complexes, such as CuI, CuCl, CuBr and Cu2O, which are unstable under moist air for a long time compared with Cu(II) complexes. Secondly, the high stoichiometric consumption of copper reagent or ligand(usually 20%, molar fraction) and longer reaction time(generally required 24―72 h) remain many disadvantages. And thirdly, these protocols generally obtain good yield preferentially with aryl halides activated by electron-withdrawing or o-carboxylic acid groups. To circumvent these problems, developing new ideal protocols of high solubility, low cytotoxicity and high stability would be of importance. The Salen-Cu(II) complexes are one of the most versatile and thoroughly studied complexes in many catalytic systems[24―27]. The Salen-type Schiff base ligands containing phosphonium groups and their metal complexes are all ionic. The positively charged phosphonium ligand is remarkably
soluble in most organic solvents and stable in air and does not decompose even after several months. Although the bifunctional Salen phosphonium complexes have been applied to some catalytic systems[28,29], there have been no reports of the use of such complexes in Cu-catalyzed aromatic coupling reactions. Thus, we reported the bifunctional Salen-Cu(II) complex containing phosphonium groups at the 5,5-positions of the Salen ligand(Fig.1)[29] and its catalytic activity in the coupling reaction of N- and C-arylations of aryl nucleophilic compounds and aryl halides via a simple experimental procedure.
Fig.1
2 2.1
Structure of bifunctional Salen-Cu(II) complex(1)
Experimental General Information
All the reagents were purchased from commercial suppliers and used without further purification. The bifunctional Salen-Cu(II) complex was synthesized in a yield of 82% according to the reported methods[28,29]. Column chromatography was carried out with silica gel(200―300 mesh). Thin layer chromatography was carried out with Merck silica gel GF254 plates. 1H NMR(400 MHz) and 13C NMR(100 MHz) spectra were recorded in CDCl3. Chemical shifts were reported with tetramethyl silane(TMS) as
——————————— *Corresponding author. E-mail:
[email protected] Received November 19, 2014; accepted December 4, 2014. Supported by the National Natural Science Foundation of China(No.20672054) and the Scientific Research Fund of Yunnan Provincial Department of Education, China(No.22012Z020). © Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH
2
Chem. Res. Chin. Univ.
internal standard.
2.2 Typical Procedure for the Catalysis of N-arylation of Imidazoles Catalyst 1(12 mg, 0.01 mmol), imidazole(1.0 mmol), aryl halide(1.0 mmol), NaOH(80 mg, 2.0 mmol), and dimethyl sulfoxide(DMSO, 3 mL) were added to a sealed tube. The reaction mixture was stirred at 100 °C for 4 h and then cooled to room temperature. After adding 3 mL of H2O, the solution was extracted with ethyl acetate. The organic layer was then dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The N-arylated product was finally obtained by column chromatography on silica gel.
2.3 Typical Catalytic Procedure Miyaura Cross-coupling Reactions
of
Suzuki-
The procedure is the same as the typical procedure for the catalysis of N-arylation of imidazoles except that imidazole was replaced with phenylboronic acid.
3
Results and Discussion
We first focused on the N-arylation of imidazole, since 1-arylimidazoles are important motifs found in a series of medicinally important compounds that have been exploited as key building blocks for the synthesis of N-heterocyclic carbenes[30―32]. As shown in Table 1, among the different bases tested in the catalysis under the same reaction conditions, NaOH gave the best isolated yield of around 96% after reaction for 4 h(Table 1, Entry 1). Other inorganic bases, including Na2CO3, K2CO3 and Cs2CO3 were less effective than NaOH with a longer reaction time of 12 h. However, only a trace Table 1
Screening of reaction conditions for bifunctional Salen-Cu(II) complex catalyzed N-arylation of imidazole with bromobenzenea Solvent
Time/h Temperature/°C Yieldb(%)
Entry
Base
1
NaOH
DMSO
4
100
96
2
KOH
DMSO
4
100
95
3
K2CO3
DMSO
12
100
50
4
Na2CO3
DMSO
12
100
56
5
Cs2CO3
DMSO
12
100
67
6
Et3N
DMSO
24
100
<5
7
Pyridine
DMSO
24
100
<5
8
NaOH
DMF
4
100
87
9
NaOH
Toluene
12
120
78
10
NaOH
Xylene
12
120
80
11
NaOH
THF
12
60
25
12
NaOH
DMSO
2
100
60
13
NaOH
DMSO
6
100
96
14
NaOH
DMSO
4
80
82
15c
NaOH
DMSO
4
100
70
a.
. Reaction conditions:
bromobenzene(1.0 mmol), imidazole(1.0 mmol), base(2.0 mmol), complex 1(0.01 mmol), solvent(3 mL), air atmosphere; b. isolated yield; c. 0.5% (molar fraction) catalyst was used.
amount of product was found when organic bases, such as triethylamine or pyridine, were used(Table 1, Entries 3―7). Solvent is another important factor affecting the catalysis. DMSO was highly efficient for the catalysis, giving the product in a yield of 96%. Further investigation revealed that 4 h was enough for the reaction to go to completion. When the reaction time was decreased to 2 h, the yield dropped to 60%(Table 1, Entry 12). Furthermore, a low temperature slowed the reaction rate. Only a yield of 82% was obtained when the reaction was carried out at 80 °C(Table 1, Entry 14). Reducing the loading of the catalyst to 0.5%(molar fraction) caused the reaction yield to drop to 70%(Table 1, Entry 15). With the optimal reaction conditions in hand, a broader study was undertaken. The coupling reactions of imidazole with substituted aryl iodides and bromides were tested. Generally, the substituted aryl iodides resulted in higher yields compared to the substituted aryl bromides under the same reaction conditions(Table 2, products 2―6). It is satisfying to us that moderate to excellent yields ranged from 85% to 98% were obtained for all the combinations. The weak sensitivity to electron effects is very interesting for electron-rich substrates, which are less straight forward by transition-metal-catalyzed reactions[33,34]. Furthermore, the catalytic system could tolerate a variety of functionalized aryl halides during the reaction, including nitrile, nitro, acetyl and ether groups(Table 2, products 5―7, 10). It is noteworthy that the reaction is highly chemoselective. For example, imidazole could be selectively arylated with aryl halides bearing hydroxyl or amino group in good yields without the formation of diaryl ethers, diarylamines or other coupling side products(Table 2, products 11 and 12), while these functional groups should be protected before catalysis as reported previously[35,36]. We then successfully applied the reaction conditions to the reaction of a variety of imidazole derivatives with aryl bromides, with the results presented in Table 3. We were pleased to find that most of the imidazole derivatives and indole exclusively afforded the corresponding products 13―20 in good to excellent yields(72%―91%) under the optimized reaction conditions. To our delight, the reaction was less sensitive to steric hindrance on the imidazoles compared to Ullmann-type condensations. The sterically hindered 2-methylimidazole and 2-ethyl-4-methylimidazole could undergo the selective N-arylation with 2-bromopyridine to give corresponding 2-(2-methyl-1H-imidazol-1-yl)pyridine(18), and 2-(2-ethyl-4methyl-1H-imidazol-1-yl)pyridine(20) with the yields of 87% and 72%, respectively. With an endeavor to expand the scope of the methodology, we established the protocols based on the use of the new catalytic systems to the reactions of a variety of aryl iodides and aryl bromides with phenylboronic acid with the results presented in Table 4. Irrespective of the substituents, aromatic bromides coupled smoothly with phenylboronic acid to produce the desired products 21―29 in high yields. As can be seen from Table 4, electron-deficient, electron-neutral and electron-rich aryl halides reacted with phenylboronic acid to generate the corresponding cross-coupling products in excellent
WANG Yi et al. Table 2
Table 3
N-arylation of imidazole with different aryl halides catalyzed by complex 1a Product
Yieldb(%)
Entry
Aryl halide
1
X=I, R=H
98
2
X=Br, R=H
96
3
Entry
Bifunctinal Salen-Cu(II) complex catalyzed N-arylation of aryl halides with other imidazolesa
Aryl halide
Het-NH
Product
1
Yieldb(%) 85
2 3
X=I, R=Br
93
4
X=Br, R= Br
80
13 2
86
3 5
X=I, R=CH3
95
6
X=Br, R=CH3
88
14 3
89
4 7
X=I, R=NO2
90
8
X=Br, R=NO2
85
15 4
5
16
9
X=I, R=CN
92
10
X=Br, R=CN
87
5
6 11
X=Br, R=COCH3
12
90
X=Br, R=H
6
91
X=Br, R=CF3
87 18
7
8 13
90 17
7 c
91
79 19
89 8
72
9 20 14
93
X=Br, R=OCH3
a.
.
10 15
X=Br, R=OH
Reaction conditions: aryl bromide(1.0 mmol), imidazole derivative(1.0 mmol), NaOH(2.0 mmol), complex 1(0.01 mmol), DMSO(3 mL) at 100 °C in air; b. isolated yields.
94 11
16
X=Br, R=NH2
87 12
a.
.
Reaction conditions: aryl halide(1.0 mmol), imidazole(1.0 mmol), NaOH(2.0 mmol), complex 1(0.01 mmol), DMSO(3 mL) at 100 °C in air; b. isolated yields; c. the aryl halide is 2-bromopyridine.
yields. One of the major problems in homogeneous catalysis is catalyst’s recycling inability as the catalyst is inseparable from the reaction mixture. Herein, the stability of the bifunctional Salen-Cu(II) complex 1 was studied in repeated coupling
reactions. The 4-bromotoluene and phenylboronic acid were chosen as model substrates for studying catalyst reuse and stability. After the first run of coupling reaction, we checked the substrate complete consumption by recording the 1H NMR spectrum of the reaction mixture after initial workup. Then, we added a fresh batch of substrates(4-bromotoluene and phenylboronic acid) and base without adding any additional catalyst into the reaction vessel. After each 4 h interval, the 1H NMR spectrum indicates a complete consumption of substrates within 4 h for five successive catalytic runs and the average isolated yield of 4-methyl-biphenyl is 92% after five catalytic cycles. This result clearly demonstrates that the catalyst maintains the activity in five consecutive catalytic runs. The reusability study of the catalyst indeed constitutes a challenge of considerable economic and environmental importance.
4
Chem. Res. Chin. Univ. Table 4
Entry
Suzuki-Miyaura cross-coupling reactions catalyzed by bifunctional Salen-Cu(II) complex 1a Aryl halide
Product
1
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Yieldb(%)
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90
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21
1479 2
94
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5588 [9] Alonso D. A., Nájera C., Pacheco M. C., Org. Lett., 2000, 2(13),
92
1823 23 4
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87
24(6), 1075 [12] Cui J., Zhang M., Zhang Y., Inorg. Chem. Commun., 2010, 13, 81
24
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89
Int. Ed., 2002, 41(19), 3668 [14] Dai M., Liang B., Wang C., Chen J., Yang Z., Org. Lett., 2004, 6(2),
25 6
221 [15] Ma D., Cai Q., Acc. Chem. Res., 2008, 41(11), 1450
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91
[18] Suresh P., Pitchuman K., J. Org. Chem., 2008, 73(22), 9121 [19] Jammi S., Sakthivel S., Rout L., Mukherjee T., Mandai S., Mitra R.,
27 8
Saha P., Punniyamurthy T., J. Org. Chem., 2009, 74, 1971
86
[20] Strieter E. R., Bhayana B., Buchwald S. L., J. Am. Chem. Soc., 2009, 131(5), 12898
28
[21] Cristau H. J., Cellier P. P., Spindler J. F., Taillefer M., Eur. J. Org. 9
84
Chem., 2004, 695 [22] Cristau H. J., Cellier, P. P. Spindler J. F., Taillefer M., Chem. Eur. J.,
29
2004, 10(22), 5607 [23] Monnier F., Taillefer M., Angew. Chem. Int. Ed., 2008, 47(17), 3096
a.
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The reactions were carried out via the general procedure(see the experimental section); b. isolated yields.
4
Conclusions
In summary, we developed an efficient and recycled protocol of bifunctional Salen-Cu(II) catalyzed N-arylation of imidazoles and Suzuki-Miyaura cross-coupling reactions with a low catalyst loading(1%, molar fraction) and cheap base even under aerobic conditions. Simple experimental procedure, easily available and synthesis catalyst, and tolerance with diverse functional groups make the present methodology attractive. Further applications of other catalysis to biologically important molecules are still in progress.
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