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Beilstein Journal of Organic Chemistry logoLink to Beilstein Journal of Organic Chemistry
. 2013 Feb 12;9:303–312. doi: 10.3762/bjoc.9.35

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

Ismail Özdemir 1,✉, Nevin Gürbüz 1, Nazan Kaloğlu 1, Öznur Doğan 1, Murat Kaloğlu 1, Christian Bruneau 2, Henri Doucet 2,✉
Editor: Huw M L Davies
PMCID: PMC3596014  PMID: 23504414

Abstract

New Pd–NHC complexes have been synthesized and employed for palladium-catalyzed direct arylation of pyrrole derivatives by using electron-deficient aryl chlorides as coupling partners. The desired coupling products were obtained in moderate to good yields by using 1 mol % of these air-stable palladium complexes. This is an advantage compared to the procedures employing air-sensitive phosphines, which have been previously shown to promote the coupling of aryl chlorides with heteroarenes.

Keywords: aryl chlorides, atom-economy, C–H bond activation, C–H functionalization, carbenes, palladium, pyrroles

Introduction

N-Heterocyclic carbenes (NHC) have emerged as an important class of ligands in the development of homogeneous catalysis [1–9]. Such ligands, which are electronically and sterically tunable, and which generally form thermally stable compounds with different metal ions, are strong σ-donors. These qualities have rendered N-heterocyclic carbene ligands as classical substitutes to phosphines in organometallic catalysis [10–14]. This is especially true for palladium-catalyzed coupling reactions. Pd–NHC catalysts [15] have proven to be excellent alternatives to catalytic systems involving palladium associated to tertiary phosphine ligands [16–19].

The introduction of aryl groups at C2 or C5 positions of pyrroles is an important research area in organic synthesis as such motives are known to be present in several bioactive molecules, such as Atorvastatin, which is used for lowering blood cholesterol, Fendosal, which is an anti-inflammatory agent, or Tanaproget, which is a progesterone-receptor agonist (Figure 1).

Figure 1.

Figure 1

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Examples of pyrrole-containing bioactive compounds.

The palladium-catalyzed direct arylation of various heteroaromatics including pyrroles by a C–H bond activation using aryl halides has met great success in recent years, allowing the synthesis of a wide variety of arylated heteroaromatics in only one step [20–25]. However, there are still limitations for these reactions in terms of aryl halide or heteroaromatic tolerance. Up to now, very few examples of palladium-catalyzed direct arylations of pyrroles by using aryl chlorides have been reported, [26–27]. Daugulis and co-workers recently described the arylation of pyrrole derivatives with a variety of aryl chlorides using 5 mol % of Pd(OAc)2 associated to 10 mol % of Cy2P-o-biphenyl as the catalyst [26]. However, in most cases, such couplings were performed with aryl bromides or iodides [28–39].

The influence of mono- or diphosphines as ligands for the palladium-catalyzed coupling of heteroarenes with aryl halides through a C–H bond activation has been largely explored. On the other hand, the influence of carbene ligands for such couplings remains largely unexplored [40–47]. Quite congested N-heterocyclic carbene–palladium catalysts have been employed by Fagnou and co-workers to promote intramolecular direct arylations of arenes [40]. A few examples of couplings of aryl bromides and iodides employing Pd–NHC complexes have also been reported [41–45]. For example, Sames and co-workers described the use of imidazolylidene carbene ligands for the Pd-catalyzed direct arylation of pyrroles or indoles using bromobenzene and aryl iodides [42]. They observed that an important steric demand on the carbene ligand led to better results. Recently, the use of palladium(II) acetate complexes bearing both a phosphine and a carbene ligand, was reported by Lee and co-workers for the direct arylation of imidazoles with some aryl chlorides [46]. However, to our knowledge, N-heterocyclic carbene ligands have not yet been employed for the palladium-catalyzed direct arylation of pyrroles with aryl chlorides. As carbene ligands have proved to be very useful for several palladium-catalyzed reactions involving aryl chlorides, we decided to explore their potential for the direct 2- or 5-arylation of pyrrole derivatives.

Results and Discussion

First, a range or Pd–NHC complexes employing a variety of carbene ligands was prepared (Scheme 1). The deviations from the accustomed structures of palladium–NHC complexes can be attributed to steric rather than to electronic factors [48]. The use of quite congested carbene ligands has been found to be required for the palladium-catalyzed direct arylation of pyrroles, indoles, benzothiophene [42,45] or arenes [40]. Therefore, we employed carbenes bearing relatively bulky N-substituents. The reaction of Pd(OAc)2 with the corresponding benzimidazolium halides in DMSO at 60–110 °C gave 1–9 in 53–87% yields (Scheme 1). The geometry of these complexes was not defined, as no crystals suitable for X-ray analysis could be obtained.

Scheme 1.

Scheme 1

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Synthesis of Pd–NHC complexes.

Arylation with Pd–NHC complexes

We initially examined the direct 5-arylation of 1-methylpyrrole-2-carboxaldehyde (10) with 4-chlorobenzonitrile (11) using these nine Pd–NHC complexes. We had previously observed that with this pyrrole derivative a high yield of 89% could be obtained in the presence of only 0.5 mol % of a triphosphine associated to Pd(OAc)2 as the catalyst [27]. With complexes 2, 3, 8 and 9, a high conversion of 4-chlorobenzonitrile (11) and good yields of the coupling product 16 were obtained (Table 1, entries 1–9). Then, in order to confirm this trend, 2-chlorobenzonitrile (12) and 4-(trifluoromethyl)chlorobenzene (13) were reacted with 1-methylpyrrole-2-carboxaldehyde (10) by using this library of complexes (Table 1, entries 10–27). Again, complexes 2, 8 and 9 were found to be effective catalysts for this transformation, and led to a high conversion of 2-chlorobenzonitrile (12) to give 17 in 55–60% yield (Table 1, entries 10–18). For 4-(trifluoromethyl)chlorobenzene (13), the best results were obtained with catalysts 2 and 8 to give 18 in 76% and 74% yields, respectively (Table 1, entries 20 and 26). Then, the reactivity of 4-chlorobenzaldehyde (14) and 4-chloroacetophenone (15) was examined by using complexes 2, 8 and 9. For both substrates the best yields of products 19 and 20 of 41% and 50% were obtained with complex 8 (Table 1, entries 28–33).

Table 1.

Direct arylation of 1-methylpyrrole-2-carboxaldehyde (10) with chlorobenzene derivatives.a

graphic file with name Beilstein_J_Org_Chem-09-303-i001.jpg
Entry ArCl Pd–NHC Product Conv. (%)b Yield (%)b
1
2
3
4
5
6
7
8
9		 Inline graphic
11 		1
2
3
4
5
6
7
8
9 		Inline graphic
16 		68
99
99
69
64
46
45
80
74		 57
87
83
61
57
36
37
72
65
10
11
12
13
14
15
16
17
18		 Inline graphic
12 		1
2
3
4
5
6
7
8
9 		Inline graphic
17 		63
78
38
45
32
32
26
65
67		 23
60
11
33
7
5
20
58
55
19
20
21
22
23
24
25
26
27		 Inline graphic
13 		1
2
3
4
5
6
7
8
9 		Inline graphic
18 		100
98
100
100
86
77
100
98
98		 56
76
34
32
8
40
28
74
21
28
29
30		 Inline graphic
14 		2
8
9 		Inline graphic
19 		11
70
74		 2
41
38
31
32
33		 Inline graphic
15 		2
8
9 		Inline graphic
20 		24
73
74		 9
50
47
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aReaction conditions: Pd–NHC (0.01 mmol), aryl chloride (1 mmol), 1-methylpyrrole-2-carboxaldehyde (10, 2 mmol), KOAc (2 mmol), DMAc (3 mL), 20 h, 150 °C. bDetermined by GC and NMR.

The reactivity of 2-acetyl-1-methylpyrrole (21) was similar to 1-methylpyrrole-2-carboxaldehyde (10, Table 2). Complexes 8 and 9 promoted an almost complete conversion of 2- and 4-chlorobenzonitrile, and of 4-(trifluoromethyl)chlorobenzene to give the desired coupling products 22–24 in good yields. On the other hand, low to moderate yields were obtained with complexes 1, 4 and 6.

Table 2.

Direct arylation of 2-acetyl-1-methylpyrrole (21) with chlorobenzene derivatives.a

graphic file with name Beilstein_J_Org_Chem-09-303-i012.jpg
Entry ArCl Pd–NHC Product Conv. (%)b Yield (%)b
1
2
3
4
5
6		 Inline graphic
11 		1
4
6
7
8
9 		Inline graphic
22 		58
64
79
77
98
99		 54
61
45
71
85
85
7
8
9
10		 Inline graphic
12 		1
4
8
9 		Inline graphic
23 		62
71
94
90		 38
59
78
78
11
12
13
14		 Inline graphic
13 		1
4
8
9 		Inline graphic
24 		79
80
92
95		 21
42
77
76
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aReaction conditions: Pd–NHC (0.01 mmol), aryl chloride (1 mmol), 2-acetyl-1-methylpyrrole (2 mmol), KOAc (2 mmol), DMAc (3 mL), 20 h, 150 °C. bDetermined by GC and NMR.

Methyl 1-methylpyrrole-2-carboxylate (25) also reacts with 4-chlorobenzonitrile (11) to give 26 in good yields with catalysts 2, 8 and 9 (Table 3). No significant decarboxylation of the pyrrole derivative was observed in the course of this reaction.

Table 3.

Direct arylation of methyl 1-methylpyrrole-2-carboxylate (25) with 4-chlorobenzonitrile (11).a

graphic file with name Beilstein_J_Org_Chem-09-303-i019.jpg
Entry Pd–NHC Conv. (%)b Yield (%)b
1 1 52 32
2 2 94 78
3 4 58 27
4 5 69 51
5 6 66 47
6 7 61 49
7 8 98 83
8 9 97 81
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aReaction conditions: Pd–NHC (0.01 mmol), 4-chlorobenzonitrile (11, 1 mmol), methyl 1-methylpyrrole-2-carboxylate (25, 2 mmol), KOAc (2 mmol), DMAc (3 mL), 20 h, 150 °C. bDetermined by GC and NMR.

Three aryl chlorides have also been coupled with 1-methylpyrrole (27, Table 4). A large excess of 1-methylpyrrole (27) was employed (4 equiv) in order to avoid the formation of 2,5-diarylated pyrroles. From 2- and 4-chlorobenzonitrile, 28 and 29 were obtained in high yields in the presence of complexes 8 and 9. On the other hand, the formation of several side-products was observed during the coupling of 4-(trifluoromethyl)chlorobenzene (13) with this pyrrole derivative, and 30 was obtained in low yields (Table 4, entries 11–15).

Table 4.

Direct arylation of 1-methylpyrrole (27) with chlorobenzene derivatives.a

graphic file with name Beilstein_J_Org_Chem-09-303-i020.jpg
Entry ArCl Pd–NHC Product Conv. (%)b Yield (%)b
1
2
3
4
5
6		 Inline graphic
11 		1
4
6
7
8
9 		Inline graphic
28 		56
75
44
68
94
96		 50
70
39
63
83
90
7
8
9
10		 Inline graphic
12 		1
4
8
9 		Inline graphic
29 		78
81
94
92		 74
70
88
83
11
12
13
14
15		 Inline graphic
13 		2
3
4
8
9 		Inline graphic
30 		94
91
89
96
97		 31
27
39
29
25
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aReaction conditions: Pd–NHC (0.01 mmol), aryl chloride (1 mmol), 1-methylpyrrole (27, 4 mmol), KOAc (2 mmol), DMAc (3 mL), 20 h, 150 °C. bDetermined by GC and NMR.

Finally, the reactivity of 1-phenylpyrrole (31) with two aryl chlorides was examined (Table 5). Again, good yields in 32 were obtained with complexes 2, 8 and 9 for the coupling with 4-chlorobenzonitrile (11). 4-Chloroacetophenone (15) also gave 33 in good yields with complexes 8 and 9.

Table 5.

Direct arylation of 1-phenylpyrrole (31) with chlorobenzene derivatives.a

graphic file with name Beilstein_J_Org_Chem-09-303-i027.jpg
Entry ArCl Pd–NHC Product Conv. (%)b Yield (%)b
1
2
3
4
5
6
7
8		 Inline graphic
11 		1
2
4
5
6
7
8
9 		Inline graphic
32 		81
90
80
85
86
87
98
98		 71
85
73
79
74
81
89
88
9
10
11		 Inline graphic
15 		2
8
9 		Inline graphic
33 		87
92
99		 55
86
76
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aReaction conditions: Pd–NHC (0.01 mmol), aryl chloride (1 mmol), 1-phenylpyrrole (31, 4 mmol), KOAc (2 mmol), DMAc (3 mL), 20 h, 150 °C. bDetermined by GC and NMR.

Conclusion

In summary, we have demonstrated that the regioselective C2 or C5 direct arylation of a range of pyrrole derivatives using electron-deficient aryl chlorides can be promoted by N-heterocyclic carbene ligands associated to palladium. So far, the reason for the influence of the nature of the carbene ligand on such couplings remains unclear. However, the presence of bulky N-substituents on the benzimidazole ring, such as 3,5-di-tert-butylbenzyl (1–4) or benzhydryl (8), appears to be favorable; whereas, 2-(2-ethoxy)phenoxyethyl substituent (5–7) generally led to lower yields. The presence of a 2-(2-ethyl)-1,3-dioxalane as N-substituent (9) was also found to be profitable. To our knowledge, these are the first examples of direct arylations of pyrroles by using aryl chlorides as the coupling partners and Pd-N-heterocyclic carbene complexes as the catalyst. Finally, as the major by-products are AcOK associated to HBr instead of metallic salts, this procedure is environmentally more attractive than the classical coupling procedures.

Experimental

The reaction of benzimidazolium halide (2 equiv) with Pd(OAc)2 in DMSO according to Scheme 1 led to the formation of the desired complexes of Pd(II) in 53–87% yield. The crude product was recrystallized from a dichloromethane/diethyl ether mixture 1:3 at room temperature, which afforded the corresponding crystals. The new complexes were characterized by 1H NMR, 13C NMR, IR and elemental analysis techniques, which support the proposed structures.

As described in [49], the air and moisture-stable palladium-carbene complexes (1–9) were soluble in halogenated solvents and insoluble in nonpolar solvents. Palladium complexes exhibit a characteristic ν(NCN) band typically at 1407–1477 cm−1. The formation of the Pd–NHC complexes was confirmed by the absence of the 1H NMR resonance signal of the acidic benzimidazolium C2–H. The 13C NMR spectra of Pd–NHC complexes exhibit a resonance signal in the 181.2–183.6 ppm range ascribed to the carbenic carbon atom, which is consistent with the reported values for Pd–NHC complexes [43]. NMR data showed that complexes 2 and 4–7 were cis/trans mixtures.

General procedure for the preparation of the palladium–NHC complexes

As described in [50], to a solution of benzimidazolium salts (10 mmol) in DMSO (5 mL) was added palladium(II) diacetate (5 mmol) under argon, and the resulting mixture was stirred at room temperature for 2 h, then at 60 °C for 4 h, at 80 °C for 2 h and finally at 110 °C for 2 h. Volatiles were removed in vacuo, and the residue was washed twice with THF (5 mL). The complex was crystallized from dichloromethane/diethyl ether 1:3 at room temperature.

Dibromo-bis[1-(3,5-di-tert-butylbenzyl)-3-(2-methoxyethyl)benzimidazol-2-ylidene]palladium(II) (1): Yield: 0.29 g, 87%; mp 172–174 °C; 1H NMR (CDCl3, δ) 1.29 (t, J = 7.0 Hz, 4H, NCH2CH2OCH3), 1.31 (t, J = 7.0 Hz, 4H, NCH2CH2OCH3), 1.33 (s, 36H, NCH2C6H3(C(CH3)3)-3,5), 2.63 (s, 6H, NCH2CH2OCH3), 5.10 (s, 4H, NCH2C6H3(C(CH3)3-3,5)), 6.89–7.6 (m, 14H, NC6H4N and NCH2C6H3(C(CH3)3-3,5)); 13C NMR (CDCl3, δ) 31.5 (NCH2C6H3(C(CH3)3)-3,5), 34.8 (NCH2C6H3(C(CH3)3-3,5)), 35.0 (NCH2CH2OCH3), 41.0 (NCH2C6H3(C(CH3)3)-3,5)), 48.3 (NCH2CH2OCH3), 58.8 (NCH2C6H3(C(CH3)3-3,5)), 111.1, 111.2, 121.7, 122.3, 122.7, 122.9, 134.2, 134.6, 151.1, 151.3 (NC6H4N and NCH2C6H3(C(CH3)3-3,5)), 183.6 (Pd-Ccarbene); IR (cm−1) ν(CN): 1407; Anal. calcd for C50H68N4PdBr2: C, 60.58; H, 6.91; N, 5.65; found: C, 60.47; H, 6.94; N, 5.63.

cis/trans-Dibromo-bis[1-(3,5-di-tert-butylbenzyl)-3-(3,4,5-trimethoxybenzyl)benzimidazol-2-ylidene]palladium(II) (2): Yield: 0.29 g, 87%; mp 160–162 °C; 1H NMR (CDCl3, δ) 1.16, 1.21 (s, 36H, NCH2C6H3(C(CH3)3-3,5), 3.66, 3.80, 3.81, 3.86 (s, 18 H, NCH2C6H2(OCH3)3-3,4,5), 5.32, 5.37 (s, 4H, NCH2C6H3(C(CH3)3-3,5), 5.74, 5.79 (s, 4H, NCH2C6H2(OCH3)3-3,4,5), 6.09–7.39 (m, 18H, NC6H4N, NCH2C6H3(C(CH3)3-3,5 and NCH2C6H2(OCH3)3-3,4,5); 13C NMR (CDCl3, δ) 31.2, 31.3 (NCH2C6H3(C(CH3)3-3,5), 31.4, 31.7, 34.7, 34.8 (NCH2C6H2(OCH3)3-3,4,5), 41.0, 41.1 (NCH2C6H3(C(CH3)3-3,5), 53.2, 53.9 (NCH2C6H3(C(CH3)3-3, 5), 56.3, 56.4 (NCH2C6H2(OCH3)3-3,4,5), 104.4, 104.8, 111.8, 112.4, 121.1, 121.3, 123.4, 129.9, 130.4, 133.1, 133.5, 133.9, 134.3, 134.4, 134.7, 137.7, 151.2, 151.5, 153.5, 153.7 (NC6H4N, NCH2C6H3(C(CH3)3-3,5 and NCH2C6H2(OCH3)3-3,4,5), 181.2 and 182.3 (Pd-Ccarbene); IR (cm−1) ν(CN): 1447; Anal. calcd for C64H80N4O6PdBr2: C, 60.64; H, 6.36; N, 4.42; found: C, 60.57; H, 6.54; N, 4.45.

Dibromo-bis[1,3-bis(3,5-di-tert-butylbenzyl)benzimidazol-2-ylidene]palladium(II) (3): Yield: 0.27 g, 82%; mp 248–250 °C; 1H NMR (CDCl3, δ) 1.18 (s, 72H, NCH2C6H3(C(CH3)3)-3,5), 5.80 (s, 8H, NCH2C6H3(C(CH3)3-3,5), 6.14–7.48 (m, 20H, NC6H4N and NCH2C6H3(C(CH3)3-3,5); 13C NMR (CDCl3, δ) 31.4 (NCH2C6H3(C(CH3)3)-3,5), 41.02 (NCH2C6H3(C(CH3)3)-3,5), 53.9 (NCH2C6H3(C(CH3)3-3,5), 111.6, 112.2, 121.3, 121.5, 122.3, 122.8, 133.4, 134.4, 134.6, 151.1, 151.2 (NC6H4N and NCH2C6H3(C(CH3)3-3,5)), 182.5 (Pd-Ccarbene); IR (cm−1) ν(CN): 1477; Anal. calcd for C74H100N4PdBr2: C, 67.75; H, 7.68; N, 4.27; found: C, 67.72; H, 7.64; N, 4.27.

cis/trans-Dichloro-bis[1-(3,5-di-tert-butylbenzyl)-3-(2,3,4,5,6-pentamethylbenzyl)benzimidazol-2-ylidene]palladium(II) (4): Yield: 0.27 g, 82%; mp 310–312 °C; 1H NMR (CDCl3, δ) 1.27, 1.29 (s, 36 H, NCH2C6H3(C(CH3)3-3,5)), 2.20, 2.23, 2.24, 2.29, 2.30, 2.34 (s, 30H, NCH2C6(CH3)5-2,3,4,5,6), 5.30 and 5.40 (s, 4H, NCH2C6(CH3)5-2,3,4,5,6), 5.53, 5.54 (s, 4H, NCH2C6H3(C(CH3)3-3,5)), 6.04–7.55 (m, 14H, NC6H4N and NCH2C6H3(C(CH3)3-3,5)); 13C NMR (CDCl3, δ) 31.3, 31.4 (NCH2C6H3(C(CH3)3-3,5), 41.0, 41.1 (NCH2C6H3(C(CH3)3-3,5)), 17.1, 17.2, 17.3, 17.6, 17.7, 17.8 (NCH2C6(CH3)5-2,3,4,5,6), 51.2, 51.3 (NCH2C6(CH3)5-2,3,4,5,6), 51.5, 51.6 (NCH2C6H3(C(CH3)3-3,5)), 111.2, 111.4, 111.8, 121.3, 121.5, 122.0, 122.5, 122.7, 122.8, 128.5, 128.6, 132.9, 133.0, 134.3, 134.4, 134.5, 134.6, 134.8, 134.9, 135.1, 151.0, 151.1 (NC6H4N and NCH2C6H3(C(CH3)3-3,5)), 182.4, 182.5 (Pd-Ccarbene); IR (cm−1) ν(CN): 1451; Anal. calcd for C68H84N4PdCl2: C, 71.97; H, 7.46; N, 4.94; found: C, 71.92; H, 7.64; N, 4.97.

cis/trans-Dibromo-bis[1-(2,4,6-trimethylbenzyl)-3-(2-(2-ethoxy)phenoxyethyl)benzimidazol-2-ylidene]palladium(II) (5): Yield: 0.33 g; 81%; mp 238–240 °C; 1H NMR (CDCl3, δ) 1.23, 1.39 (t, J = 7.0 Hz, 6H, NCH2CH2OC6H4(OCH2CH3)-2), 2.29, 2.34, 2.35, 2.36 (s, 18H, NCH2C6H2(CH3)-2,4,6), 3.89, 4.01 (q, J = 7.0 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 4.81, 4.83 (t, J = 5.9 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 5.39, 5.41 (t, J = 5.9, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 6.03, 6.13 (s, 4H, NCH2C6H2(CH3)-2,4,6), 6.80–7.77 (m, 20H, NC6H4N, NCH2CH2OC6H4(OCH2CH3)-2, NCH2C6H2(CH3)-2,4,6); 13C NMR (CDCl3, δ) 15.1, 15.3 (NCH2CH2OC6H4(OCH2CH3)-2), 21.0, 21.1, 21.2, 21.3 (NCH2C6H2(CH3)-2,4,6), 48.0, 48.1 (NCH2CH2OC6H4(OCH2CH3)-2), 50.1, 50.6 (NCH2CH2OC6H4(OCH2CH3)-2), 64.0, 64.1 (NCH2CH2OC6H4(OCH2CH3)-2), 67.8, 67.9 (NCH2C6H2(CH3)-2,4,6), 111.3, 111.5, 112.8, 113.3, 120.7, 120.9, 121.4, 122.9, 128.0, 129.4, 129.6, 134.6, 135.7, 138.4, 138.6, 138.9, 148.0, 148.5, 148.6 (NC6H4NNCH2CH2OC6H4(OCH2CH3)-2, NCH2C6H2(CH3)-2,4,6), 182.2, 182.3 (Pd-Ccarbene); IR (cm−1) ν(CN): 1448; Anal. calcd for C54H60N4O4PdBr2: C, 59.21; H, 5.52; N, 5.12; found: C, 59.27; H, 5.54; N, 5.13.

cis/trans-Dichloro-bis[1-(2-(2-ethoxy)phenoxyethyl)-3-(4-methylbenzyl)benzimidazol-2-ylidene] palladium(II) (6): Yield: 0.32 g, 66%; mp 235–237 °C; 1H NMR (CDCl3, δ) 1.43, 1.45 (t, J = 6.9 Hz, 6H, NCH2CH2OC6H4(OCH2CH3)-2), 2.29, 2.35 (s, 6H, NCH2C6H4(CH3)-4), 3.98, 4.03 (q, J = 7.0 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 4.57, 4.82 (t, J = 5.0 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 5.27, 5.42 (t, J = 5.0 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 5.97, 6.15 (s, 4H, NCH2C6H4(CH3)-4), 6.68–8.56 (m, 24H, NC6H4N, NCH2CH2OC6H4(OCH2CH3)-2, NCH2C6H4(CH3)-4); 13C NMR (CDCl3, δ) 15.0, 15.1 (NCH2CH2OC6H4(OCH2CH3)-2), 21.1, 21.2 (NCH2C6H4(CH3)-4), 48.1, 48.3 (NCH2CH2OC6H4(OCH2CH3)-2), 52.1, 52.2 (NCH2CH2OC6H4(OCH2CH3)-2), 64.0, 64.1 (NCH2CH2OC6H4(OCH2CH3)-2), 68.3, 68.6 (NCH2C6H4(CH3)-4), 110.8, 111.1, 112.2, 112.8, 113.1, 120.7, 120.9, 121.2, 123.0, 123.1, 127.6, 127.7, 127.8, 129.3, 129.5, 132.6, 134.1, 135.6, 137.4, 137.6, 148.0, 148.4, 148.6 (NC6H4NNCH2CH2OC6H4(OCH2CH3)-2, NCH2C6H4(CH3)-4), 182.0, 182.1 (Pd-Ccarbene); IR (cm−1) ν(CN): 1407; Anal. calcd for C50H52N4O4PdCl2: C, 63.19; H, 5.52; N, 5.90; found: C, 63.18; H, 5.50; N, 5.93.

cis/trans-Dichloro-bis[1-(2-(2-ethoxy)phenoxyethyl)-3-(3-methoxybenzyl)benzimidazo-2-ylidene]palladium(II) (7): Yield: 0.22 g, 53%; mp 205–207 °C; 1H NMR (CDCl3, δ) 1.43, 1.45 (t, J = 7.0 Hz, 6H, NCH2CH2OC6H4(OCH2CH3)-2), 3.66, 3.75 (s, 6H, NCH2C6H4(OCH3)-3), 3.97, 4.03 (q, J = 7.0 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2)), 4.60, 4.83 (t, J = 5.6 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 5.29, 5.43 (t, J = 5.7 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 6.01, 6.18 (s, 4H, NCH2C6H4(OCH3)-3), 6.67–7.86 (m, 24H, NC6H4N, NCH2CH2OC6H4(OCH2CH3)-2, NCH2C6H4(OCH3)-3); 13C NMR (CDCl3, δ) 15.0, 15.3 (NCH2CH2OC6H4(OCH2CH3)-2), 48.0, 48.3 (NCH2CH2OC6H4(OCH2CH3)-2), 52.3, 52.4 (NCH2C6H4(OCH3)-3), 55.5, 55.7 (NCH2CH2OC6H4(OCH2CH3)-2), 63.9, 64.0 (NCH2CH2OC6H4(OCH2CH3)-2), 68.3, 68.6 (NCH2C6H4(OCH3)-3), 112.3, 113.1, 114.7, 120.0, 120.7, 120.9, 123.1, 123.2, 129.8, 134.0, 134.1, 135.6, 137.0, 137.3, 148.0, 148.4, 160.0, 160.3 (NC6H4N NCH2CH2OC6H4(OCH2CH3)-2, NCH2C6H4(OCH3)-3), 182.0, 182.2 (Pd-Ccarbene); IR (cm−1) ν(CN): 1444; Anal. calcd for C50H52N4O6PdCl2: C, 61.14; H, 5.34; N, 5.70; found: C, 61.21; H, 5.37; N, 5.73.

Dibromo-bis[1-(3-methylbenzyl)-3-(benzhydryl)]benzimidazol-2-ylidene]palladium(II) (8): Yield: 0.35 g, 60%; mp 230–232 °C; 1H NMR (CDCl3, δ) 2.12 (3-CH3C6H5), 5.72 (s, 2H, (3-CH3)(C6H5)-CH2), 6.74–7.79 (m, 19H, CH(C6H5)2, C6H4 and 3-CH3C6H5); 13C NMR (CDCl3, δ) 21.3 (3-(CH3)(C6H5)), 52.0 (3-(CH3)(C6H5)-CH2), 67.5 (CH(C6H5), 112.4, 123.6, 125.5, 128.6, 128.7, 128.9, 129.1, 133.4, 133.8, 134.9, 135.9, 136.1, 137.6, 138.0, 138.2, 138.4 (3-(CH3)(C6H5), CH(C6H5) and C6H4), 183.5 (Pd-Ccarbene); IR (cm−1) ν(CN): 1412; Anal. calcd for C56H46N4Br2Pd: C, 64.60; H, 4.45; N, 5.38; found: C, 64.58; H, 4.49; N, 5.46.

Dibromo-bis[1-(benzyl)-3-(2-(2-ethyl)-1,3-dioxalane)]benzimidazol-2-ylidene]palladium(II) (9): Yield: 0.31 g, 62%; mp 282–284 °C; 1H NMR (CDCl3, δ) 2.27 (m, 2H, NCH2CH2CH), 3.83 and 3.99 (t, 4H, J = 6.6 Hz, NCH2CH2CHO2CH2CH2), 5.01 (m, 3H, NCH2CH2CH and NCH2CH2CH), 6.01 (s, 2H, (C6H5)-CH2), 7.0–7.92 (m, 9H, (C6H5)CH2 and C6H4); 13C NMR (CDCl3, δ) 33.7 (NCH2CH2CH), 40.8 (NCH2CH2CH), 64.9 (NCH2CH2CHO2CH2CH2), 101.6 (NCH2CH2CHO2CH2CH2), 101.9, 111.3, 112.2, 123.7, 128.3, 128.5, 128.8, 128.9, 133.9, 134.4, 136.6 (C6H5CH2 and C6H4), 181.7 (Pd-Ccarbene); IR (cm−1) ν(CN): 1408; Anal. calcd for C38H40O4N4PdBr2: C, 51.69; H, 4.57; N, 6.35; found: C, 51.60; H, 4.61; N, 6.37.

General Procedure for direct arylations

As described in [47], in a typical experiment, the aryl chloride (1 mmol), heteroaryl derivative (2 or 4 mmol) (see Table 1–5) and KOAc (2 mmol) were introduced in a Schlenk tube, equipped with a magnetic stirring bar. The Pd complex (0.01 mmol, see Table 1–5) and DMAc (3 mL) were added, and the Schlenk tube was purged several times with argon. The Schlenk tube was placed in a preheated oil bath at 150 °C, and the reaction mixture was stirred for 20 h. Then, the reaction mixture was analysed by gas chromatography to determine the conversion of the aryl chloride. The solvent was removed by heating of the reaction vessel under vacuum and the residue was charged directly onto a silica-gel column. The products were eluted by using an appropriate ratio of diethyl ether and pentane.

Acknowledgments

This work was financially supported by the Technological and Scientific Research Council of Turkey TUBİTAK-BOSPHORUS (France) [109T605] and İnönü University Research Fund (İ.Ü. B.A.P: 2010/107).

This article is part of the Thematic Series "C–H Functionalization".

Contributor Information

Ismail Özdemir, Email: iozdemir44@gmail.com.

Henri Doucet, Email: henri.doucet@univ-rennes1.fr.

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