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

Article abstract of DOI:10.3762/bjoc.9.35

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

Full text of 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 Gürbüz1, Nazan Kaloğlu1, Öznur Doğan1,
Murat Kaloğlu1, Christian Bruneau2 and Henri Doucet*2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 303–312.
1Chemistry Department, Faculty Science and Arts, İnönü University,
44280 Malatya, Türkiye and 2Institut Sciences Chimiques de Rennes,
UMR 6226 CNRS-Université de Rennes "Organometalliques, Material
and Catalysis", Campus de Beaulieu, 35042 Rennes, France. Fax:
+33 (0)2-23-23-69-39; Tel: +33 (0)2-23-23-63-84
doi:10.3762/bjoc.9.35
Received: 18 October 2012
Accepted: 16 January 2013
Published: 12 February 2013
Email:
This article is part of the Thematic Series "C–H Functionalization".
Guest Editor: H. M. L. Davies
Ismail Özdemir* - iozdemir44@gmail.com; Henri Doucet* -
henri.doucet@univ-rennes1.fr
* Corresponding author
© 2013 Özdemir et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
aryl chlorides; atom-economy; C–H bond activation; C–H
functionalization; carbenes; palladium; pyrroles
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-sensi-
tive phosphines, which have been previously shown to promote the coupling of aryl chlorides with heteroarenes.
Introduction
N-Heterocyclic carbenes (NHC) have emerged as an important tions. Pd–NHC catalysts [15] have proven to be excellent alter-
class of ligands in the development of homogeneous catalysis natives to catalytic systems involving palladium associated to
[1-9]. Such ligands, which are electronically and sterically tertiary phosphine ligands [16-19].
tunable, and which generally form thermally stable compounds
with different metal ions, are strong σ-donors. These qualities The introduction of aryl groups at C2 or C5 positions of
have rendered N-heterocyclic carbene ligands as classical pyrroles is an important research area in organic synthesis
substitutes to phosphines in organometallic catalysis [10-14]. as such motives are known to be present in several bioactive
This is especially true for palladium-catalyzed coupling reac- molecules, such as Atorvastatin, which is used for lowering
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Beilstein J. Org. Chem. 2013, 9, 303–312.
blood cholesterol, Fendosal, which is an anti-inflammatory knowledge, N-heterocyclic carbene ligands have not yet been
agent, or Tanaproget, which is a progesterone-receptor employed for the palladium-catalyzed direct arylation of
agonist (Figure 1).
pyrroles with aryl chlorides. As carbene ligands have proved to
be very useful for several palladium-catalyzed reactions
The palladium-catalyzed direct arylation of various heteroaro- involving aryl chlorides, we decided to explore their potential
matics including pyrroles by a C–H bond activation using aryl for the direct 2- or 5-arylation of pyrrole derivatives.
halides has met great success in recent years, allowing the syn-
thesis of a wide variety of arylated heteroaromatics in only one Results and Discussion
step [20-25]. However, there are still limitations for these reac- First, a range or Pd–NHC complexes employing a variety of
tions in terms of aryl halide or heteroaromatic tolerance. Up to carbene ligands was prepared (Scheme 1). The deviations from
now, very few examples of palladium-catalyzed direct aryla- the accustomed structures of palladium–NHC complexes can be
tions of pyrroles by using aryl chlorides have been reported, attributed to steric rather than to electronic factors [48]. The use
[26,27]. Daugulis and co-workers recently described the aryl- of quite congested carbene ligands has been found to be
ation of pyrrole derivatives with a variety of aryl chlorides required for the palladium-catalyzed direct arylation of pyrroles,
using 5 mol % of Pd(OAc)2 associated to 10 mol % of Cy2P-o- indoles, benzothiophene [42,45] or arenes [40]. Therefore, we
biphenyl as the catalyst [26]. However, in most cases, such employed carbenes bearing relatively bulky N-substituents. The
couplings were performed with aryl bromides or iodides [28- reaction of Pd(OAc)2 with the corresponding benzimidazolium
39].
halides in DMSO at 60–110 °C gave 1–9 in 53–87% yields
(Scheme 1). The geometry of these complexes was not defined,
The influence of mono- or diphosphines as ligands for the palla- as no crystals suitable for X-ray analysis could be obtained.
dium-catalyzed coupling of heteroarenes with aryl halides
through a C–H bond activation has been largely explored. On Arylation with Pd–NHC complexes
the other hand, the influence of carbene ligands for such We initially examined the direct 5-arylation of 1-methylpyrrole-
couplings remains largely unexplored [40-47]. Quite congested 2-carboxaldehyde (10) with 4-chlorobenzonitrile (11) using
N-heterocyclic carbene–palladium catalysts have been these nine Pd–NHC complexes. We had previously observed
employed by Fagnou and co-workers to promote intramolec- that with this pyrrole derivative a high yield of 89% could be
ular direct arylations of arenes [40]. A few examples of obtained in the presence of only 0.5 mol % of a triphosphine
couplings of aryl bromides and iodides employing Pd–NHC associated to Pd(OAc)2 as the catalyst [27]. With complexes 2,
complexes have also been reported [41-45]. For example, 3, 8 and 9, a high conversion of 4-chlorobenzonitrile (11) and
Sames and co-workers described the use of imidazolylidene good yields of the coupling product 16 were obtained (Table 1,
carbene ligands for the Pd-catalyzed direct arylation of pyrroles entries 1–9). Then, in order to confirm this trend, 2-chloroben-
or indoles using bromobenzene and aryl iodides [42]. They zonitrile (12) and 4-(trifluoromethyl)chlorobenzene (13) were
observed that an important steric demand on the carbene ligand reacted with 1-methylpyrrole-2-carboxaldehyde (10) by using
led to better results. Recently, the use of palladium(II) acetate this library of complexes (Table 1, entries 10–27). Again,
complexes bearing both a phosphine and a carbene ligand, was complexes 2, 8 and 9 were found to be effective catalysts for
reported by Lee and co-workers for the direct arylation of this transformation, and led to a high conversion of
imidazoles with some aryl chlorides [46]. However, to our 2-chlorobenzonitrile (12) to give 17 in 55–60% yield (Table 1,
Figure 1: Examples of pyrrole-containing bioactive compounds.
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Beilstein J. Org. Chem. 2013, 9, 303–312.
Scheme 1: Synthesis of Pd–NHC complexes.
entries 10–18). For 4-(trifluoromethyl)chlorobenzene (13), the to give the desired coupling products 22–24 in good yields. On
best results were obtained with catalysts 2 and 8 to give 18 in the other hand, low to moderate yields were obtained with
76% and 74% yields, respectively (Table 1, entries 20 and 26). complexes 1, 4 and 6.
Then, the reactivity of 4-chlorobenzaldehyde (14) and
4-chloroacetophenone (15) was examined by using complexes Methyl 1-methylpyrrole-2-carboxylate (25) also reacts with
2, 8 and 9. For both substrates the best yields of products 19 and 4-chlorobenzonitrile (11) to give 26 in good yields with cata-
20 of 41% and 50% were obtained with complex 8 (Table 1, lysts 2, 8 and 9 (Table 3). No significant decarboxylation of the
entries 28–33).
pyrrole derivative was observed in the course of this reaction.
The reactivity of 2-acetyl-1-methylpyrrole (21) was similar to Three aryl chlorides have also been coupled with 1-methylpyr-
1-methylpyrrole-2-carboxaldehyde (10, Table 2). Complexes 8 role (27, Table 4). A large excess of 1-methylpyrrole (27) was
and 9 promoted an almost complete conversion of 2- and employed (4 equiv) in order to avoid the formation of 2,5-diary-
4-chlorobenzonitrile, and of 4-(trifluoromethyl)chlorobenzene lated pyrroles. From 2- and 4-chlorobenzonitrile, 28 and 29
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Beilstein J. Org. Chem. 2013, 9, 303–312.
Table 1: Direct arylation of 1-methylpyrrole-2-carboxaldehyde (10) with chlorobenzene derivatives.a
Entry
ArCl
Pd–NHC
Product
Conv. (%)b
Yield (%)b
1
2
3
4
5
6
7
8
9
1
2
3
4
5
6
7
8
9
68
99
99
69
64
46
45
80
74
57
87
83
61
57
36
37
72
65
11
16
10
11
12
13
14
15
16
17
18
1
2
3
4
5
6
7
8
9
63
78
38
45
32
32
26
65
67
23
60
11
33
7
5
20
58
55
12
17
19
20
21
22
23
24
25
26
27
1
2
3
4
5
6
7
8
9
100
98
100
100
86
77
100
98
56
76
34
32
8
40
28
74
21
13
18
98
28
29
30
2
8
9
11
70
74
2
41
38
14
15
19
20
31
32
33
2
8
9
24
73
74
9
50
47
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.
were obtained in high yields in the presence of complexes 8 and 4-chlorobenzonitrile (11). 4-Chloroacetophenone (15) also gave
9. On the other hand, the formation of several side-products was 33 in good yields with complexes 8 and 9.
observed during the coupling of 4-(trifluoromethyl)chloroben-
zene (13) with this pyrrole derivative, and 30 was obtained in Conclusion
low yields (Table 4, entries 11–15).
In summary, we have demonstrated that the regioselective C2 or
C5 direct arylation of a range of pyrrole derivatives using elec-
Finally, the reactivity of 1-phenylpyrrole (31) with two aryl tron-deficient aryl chlorides can be promoted by N-heterocyclic
chlorides was examined (Table 5). Again, good yields in 32 carbene ligands associated to palladium. So far, the reason for
were obtained with complexes 2, 8 and 9 for the coupling with the influence of the nature of the carbene ligand on such
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Table 2: Direct arylation of 2-acetyl-1-methylpyrrole (21) with chlorobenzene derivatives.a
Entry
ArCl
Pd–NHC
Product
Conv. (%)b
Yield (%)b
1
2
3
4
5
6
1
4
6
7
8
9
58
64
79
77
98
99
54
61
45
71
85
85
11
22
7
8
9
1
4
8
9
62
71
94
90
38
59
78
78
10
12
13
23
24
11
12
13
14
1
4
8
9
79
80
92
95
21
42
77
76
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.
Table 3: Direct arylation of methyl 1-methylpyrrole-2-carboxylate (25) with 4-chlorobenzonitrile (11).a
Entry
Pd–NHC
Conv. (%)b
Yield (%)b
1
2
3
4
5
6
7
8
1
2
4
5
6
7
8
9
52
94
58
69
66
61
98
97
32
78
27
51
47
49
83
81
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.
couplings remains unclear. However, the presence of bulky knowledge, these are the first examples of direct arylations of
N-substituents on the benzimidazole ring, such as 3,5-di-tert- pyrroles by using aryl chlorides as the coupling partners and
butylbenzyl (1–4) or benzhydryl (8), appears to be favorable; Pd-N-heterocyclic carbene complexes as the catalyst. Finally, as
whereas, 2-(2-ethoxy)phenoxyethyl substituent (5–7) generally the major by-products are AcOK associated to HBr instead of
led to lower yields. The presence of a 2-(2-ethyl)-1,3-dioxalane metallic salts, this procedure is environmentally more attractive
as N-substituent (9) was also found to be profitable. To our than the classical coupling procedures.
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Table 4: Direct arylation of 1-methylpyrrole (27) with chlorobenzene derivatives.a
Entry
ArCl
Pd–NHC
Product
Conv. (%)b
Yield (%)b
1
2
3
4
5
6
1
4
6
7
8
9
56
75
44
68
94
96
50
70
39
63
83
90
11
28
7
8
9
1
4
8
9
78
81
94
92
74
70
88
83
10
12
13
29
30
11
12
13
14
15
2
3
4
8
9
94
91
89
96
97
31
27
39
29
25
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.
Table 5: Direct arylation of 1-phenylpyrrole (31) with chlorobenzene derivatives.a
Entry
ArCl
Pd–NHC
Product
Conv. (%)b
Yield (%)b
1
2
3
4
5
6
7
8
1
2
4
5
6
7
8
9
81
90
80
85
86
87
98
98
71
85
73
79
74
81
89
88
11
32
9
10
11
2
8
9
87
92
99
55
86
76
15
33
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.
Experimental
tion of the desired complexes of Pd(II) in 53–87% yield. The
The reaction of benzimidazolium halide (2 equiv) with crude product was recrystallized from a dichloromethane/
Pd(OAc)2 in DMSO according to Scheme 1 led to the forma- diethyl ether mixture 1:3 at room temperature, which afforded
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Beilstein J. Org. Chem. 2013, 9, 303–312.
the corresponding crystals. The new complexes were character- 13C NMR (CDCl3, δ) 31.2, 31.3 (NCH2C6H3(C(CH3)3-3,5),
ized by 1H NMR, 13C NMR, IR and elemental analysis tech- 31.4, 31.7, 34.7, 34.8 (NCH2C6H2(OCH3)3-3,4,5), 41.0, 41.1
niques, which support the proposed structures.
(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,
As described in [49], the air and moisture-stable palladium- 112.4, 121.1, 121.3, 123.4, 129.9, 130.4, 133.1, 133.5, 133.9,
carbene complexes (1–9) were soluble in halogenated solvents 134.3, 134.4, 134.7, 137.7, 151.2, 151.5, 153.5, 153.7
and insoluble in nonpolar solvents. Palladium complexes ex- (NC6H4N, NCH2C6H3(C(CH3)3-3,5 and NCH2C6H2(OCH3)3-
hibit a characteristic ν(NCN) band typically at 1407–1477 cm−1. 3,4,5), 181.2 and 182.3 (Pd-Ccarbene); IR (cm−1) ν(CN): 1447;
The formation of the Pd–NHC complexes was confirmed by the Anal. calcd for C64H80N4O6PdBr2: C, 60.64; H, 6.36; N, 4.42;
absence of the 1H NMR resonance signal of the acidic benzimi- found: C, 60.57; H, 6.54; N, 4.45.
dazolium C2–H. The 13C NMR spectra of Pd–NHC complexes
exhibit a resonance signal in the 181.2–183.6 ppm range Dibromo-bis[1,3-bis(3,5-di-tert-butylbenzyl)benzimidazol-2-
ascribed to the carbenic carbon atom, which is consistent with ylidene]palladium(II) (3): Yield: 0.27 g, 82%; mp
the reported values for Pd–NHC complexes [43]. NMR data 248–250 °C; 1H NMR (CDCl3, δ) 1.18 (s, 72H,
showed that complexes 2 and 4–7 were cis/trans mixtures.
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-
General procedure for the preparation of the
palladium–NHC complexes
As described in [50], to a solution of benzimidazolium salts 3,5), 111.6, 112.2, 121.3, 121.5, 122.3, 122.8, 133.4, 134.4,
(10 mmol) in DMSO (5 mL) was added palladium(II) diacetate 134.6, 151.1, 151.2 (NC6H4N and NCH2C6H3(C(CH3)3-3,5)),
(5 mmol) under argon, and the resulting mixture was stirred at 182.5 (Pd-Ccarbene); IR (cm−1) ν(CN): 1477; Anal. calcd for
room temperature for 2 h, then at 60 °C for 4 h, at 80 °C for 2 h C74H100N4PdBr2: C, 67.75; H, 7.68; N, 4.27; found: C, 67.72;
and finally at 110 °C for 2 h. Volatiles were removed in vacuo, H, 7.64; N, 4.27.
and the residue was washed twice with THF (5 mL). The com-
plex was crystallized from dichloromethane/diethyl ether 1:3 at cis/trans-Dichloro-bis[1-(3,5-di-tert-butylbenzyl)-3-(2,3,4,5,6-
room temperature.
pentamethylbenzyl)benzimidazol-2-ylidene]palladium(II)
(4): Yield: 0.27 g, 82%; mp 310–312 °C; 1H NMR (CDCl3, δ)
Dibromo-bis[1-(3,5-di-tert-butylbenzyl)-3-(2-methoxy- 1.27, 1.29 (s, 36 H, NCH2C6H3(C(CH3)3-3,5)), 2.20, 2.23, 2.24,
ethyl)benzimidazol-2-ylidene]palladium(II) (1): Yield: 0.29 2.29, 2.30, 2.34 (s, 30H, NCH2C6(CH3)5-2,3,4,5,6), 5.30 and
g, 87%; mp 172–174 °C; 1H NMR (CDCl3, δ) 1.29 (t, J = 7.0 5.40 (s, 4H, NCH2C6(CH3)5-2,3,4,5,6), 5.53, 5.54 (s, 4H,
Hz, 4H, NCH2CH2OCH3), 1.31 (t, J = 7.0 Hz, 4H, NCH2CH2- NCH2C6H3(C(CH3)3-3,5)), 6.04–7.55 (m, 14H, NC6H4N and
OCH3), 1.33 (s, 36H, NCH2C6H3(C(CH3)3)-3,5), 2.63 (s, 6H, NCH2C6H3(C(CH3)3-3,5)); 13C NMR (CDCl3, δ) 31.3, 31.4
NCH2CH2OCH3), 5.10 (s, 4H, NCH2C6H3(C(CH3)3-3,5)), (NCH2C6H3(C(CH3)3-3,5), 41.0, 41.1 (NCH2C6H3(C(CH3)3-
6.89–7.6 (m, 14H, NC6H4N and NCH2C6H3(C(CH3)3-3,5)); 3,5)), 17.1, 17.2, 17.3, 17.6, 17.7, 17.8 (NCH2C6(CH3)5-
13C NMR (CDCl3, δ) 31.5 (NCH2C6H3(C(CH3)3)-3,5), 34.8 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)), 35.0 (NCH2CH2OCH3), 41.0 (NCH2C6H3(C(CH3)3-3,5)), 111.2, 111.4, 111.8, 121.3, 121.5,
(NCH2C6H3(C(CH3)3)-3,5)), 48.3 (NCH2CH2OCH3), 58.8 122.0, 122.5, 122.7, 122.8, 128.5, 128.6, 132.9, 133.0, 134.3,
(NCH2C6H3(C(CH3)3-3,5)), 111.1, 111.2, 121.7, 122.3, 122.7, 134.4, 134.5, 134.6, 134.8, 134.9, 135.1, 151.0, 151.1 (NC6H4N
122.9, 134.2, 134.6, 151.1, 151.3 (NC6H4N and NCH2C6H3- and NCH2C6H3(C(CH3)3-3,5)), 182.4, 182.5 (Pd-Ccarbene); IR
(C(CH3)3-3,5)), 183.6 (Pd-Ccarbene); IR (cm−1) ν(CN): 1407; (cm−1) ν(CN): 1451; Anal. calcd for C68H84N4PdCl2: C, 71.97;
Anal. calcd for C50H68N4PdBr2: C, 60.58; H, 6.91; N, 5.65; H, 7.46; N, 4.94; found: C, 71.92; H, 7.64; N, 4.97.
found: C, 60.47; H, 6.94; N, 5.63.
cis/trans-Dibromo-bis[1-(2,4,6-trimethylbenzyl)-3-(2-(2-eth-
cis/trans-Dibromo-bis[1-(3,5-di-tert-butylbenzyl)-3-(3,4,5- oxy)phenoxyethyl)benzimidazol-2-ylidene]palladium(II) (5):
trimethoxybenzyl)benzimidazol-2-ylidene]palladium(II) (2): Yield: 0.33 g; 81%; mp 238–240 °C; 1H NMR (CDCl3, δ) 1.23,
Yield: 0.29 g, 87%; mp 160–162 °C; 1H NMR (CDCl3, δ) 1.16, 1.39 (t, J = 7.0 Hz, 6H, NCH2CH2OC6H4(OCH2CH3)-2), 2.29,
1.21 (s, 36H, NCH2C6H3(C(CH3)3-3,5), 3.66, 3.80, 3.81, 3.86 2.34, 2.35, 2.36 (s, 18H, NCH2C6H2(CH3)-2,4,6), 3.89, 4.01 (q,
(s, 18 H, NCH2C6H2(OCH3)3-3,4,5), 5.32, 5.37 (s, 4H, J = 7.0 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 4.81, 4.83 (t,
N C H 2 C 6 H 3 ( C ( C H 3 ) 3 - 3 , 5 ) , 5 . 7 4 , 5 . 7 9 ( s , 4 H , J = 5.9 Hz, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 5.39, 5.41 (t,
NCH2C6H2(OCH3)3-3,4,5), 6.09–7.39 (m, 18H, NC6H4N, J = 5.9, 4H, NCH2CH2OC6H4(OCH2CH3)-2), 6.03, 6.13 (s, 4H,
NCH2C6H3(C(CH3)3-3,5 and NCH2C6H2(OCH3)3-3,4,5); NCH2C6H2(CH3)-2,4,6), 6.80–7.77 (m, 20H, NC6H4N,
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Beilstein J. Org. Chem. 2013, 9, 303–312.
NCH2CH2-OC6H4(OCH2CH3)-2, NCH2C6H2(CH3)-2,4,6); 134.1, 135.6, 137.0, 137.3, 148.0, 148.4, 160.0, 160.3 (NC6H4N
13C NMR (CDCl3, δ) 15.1, 15.3 (NCH2CH2OC6H4- NCH2CH2O-C6H4(OCH2CH3)-2, NCH2C6H4(OCH3)-3),
(OCH2CH3)-2), 21.0, 21.1, 21.2, 21.3 (NCH2C6H2(CH3)- 182.0, 182.2 (Pd-Ccarbene); IR (cm−1) ν(CN): 1444; Anal. calcd
2,4,6), 48.0, 48.1 (NCH2CH2OC6H4(OCH2CH3)-2), 50.1, 50.6 for C50H52N4O6PdCl2: C, 61.14; H, 5.34; N, 5.70; found: C,
(NCH2CH2O-C6H4(OCH2CH3)-2), 64.0, 64.1 (NCH2CH2O- 61.21; H, 5.37; N, 5.73.
C6H4(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, Dibromo-bis[1-(3-methylbenzyl)-3-(benzhydryl)]benzimi-
129.4, 129.6, 134.6, 135.7, 138.4, 138.6, 138.9, 148.0, 148.5, dazol-2-ylidene]palladium(II) (8): Yield: 0.35 g, 60%; mp
148. 6 (NC6 H4 NNCH2 CH2 -OC6 H4 (OCH2 CH3 )-2, 230–232 °C; 1H NMR (CDCl3, δ) 2.12 (3-CH3C6H5), 5.72 (s,
NCH2C6H2(CH3)-2,4,6), 182.2, 182.3 (Pd-Ccarbene); IR (cm−1) 2H, (3-CH3)(C6H5)-CH2), 6.74–7.79 (m, 19H, CH(C6H5)2,
ν(CN): 1448; Anal. calcd for C54H60N4O4PdBr2: C, 59.21; H, C6H4 and 3-CH3C6H5); 13C NMR (CDCl3, δ) 21.3
5.52; N, 5.12; found: C, 59.27; H, 5.54; N, 5.13.
(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,
cis/trans-Dichloro-bis[1-(2-(2-ethoxy)phenoxyethyl)-3-(4- 134.9, 135.9, 136.1, 137.6, 138.0, 138.2, 138.4 (3-(CH3)(C6H5),
methylbenzyl)benzimidazol-2-ylidene] palladium(II) (6): CH(C6H5) and C6H4), 183.5 (Pd-Ccarbene); IR (cm−1) ν(CN):
Yield: 0.32 g, 66%; mp 235–237 °C; 1H NMR (CDCl3, δ) 1.43, 1412; Anal. calcd for C56H46N4Br2Pd: C, 64.60; H, 4.45; N,
1.45 (t, J = 6.9 Hz, 6H, NCH2CH2OC6H4(OCH2CH3)-2), 2.29, 5.38; found: C, 64.58; H, 4.49; N, 5.46.
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, Dibromo-bis[1-(benzyl)-3-(2-(2-ethyl)-1,3-dioxalane)]benz-
NCH2CH2OC6H4(OCH2CH3)-2), 5.27, 5.42 (t, J = 5.0 Hz, 4H, imidazol-2-ylidene]palladium(II) (9): Yield: 0.31 g, 62%; mp
NCH2CH2OC6H4(OCH2CH3)-2), 5.97, 6.15 (s, 4H, 282–284 °C; 1H NMR (CDCl3, δ) 2.27 (m, 2H, NCH2CH2CH),
NCH2C6H4(CH3)-4), 6.68–8.56 (m, 24H, NC6H4N, 3.83 and 3.99 (t, 4H, J = 6.6 Hz, NCH2CH2CHO2CH2CH2),
NCH2CH2O-C6H4(OCH2CH3)-2, NCH2C6H4(CH3)-4); 5.01 (m, 3H, NCH2CH2CH and NCH2CH2CH), 6.01 (s, 2H,
13C NMR (CDCl3, δ) 15.0, 15.1 (NCH2CH2OC6H4- (C6H5)-CH2), 7.0–7.92 (m, 9H, (C6H5)CH2 and C6H4);
(OCH2CH3)-2), 21.1, 21.2 (NCH2C6H4(CH3)-4), 48.1, 48.3 13C NMR (CDCl3, δ) 33.7 (NCH2CH2CH), 40.8
(NCH2CH2OC6H4(OCH2CH3)-2), 52.1, 52.2 (NCH2CH2O- (NCH2CH2CH), 64.9 (NCH2CH2CHO2CH2CH2), 101.6
C6H4(OCH2CH3)-2), 64.0, 64.1 (NCH2CH2OC6H4- (NCH2CH2CHO2CH2CH2), 101.9, 111.3, 112.2, 123.7, 128.3,
(OCH2CH3)-2), 68.3, 68.6 (NCH2C6H4(CH3)-4), 110.8, 111.1, 128.5, 128.8, 128.9, 133.9, 134.4, 136.6 (C6H5CH2 and C6H4),
112.2, 112.8, 113.1, 120.7, 120.9, 121.2, 123.0, 123.1, 127.6, 181.7 (Pd-Ccarbene); IR (cm−1) ν(CN): 1408; Anal. calcd for
127.7, 127.8, 129.3, 129.5, 132.6, 134.1, 135.6, 137.4, 137.6, C38H40O4N4PdBr2: C, 51.69; H, 4.57; N, 6.35; found: C, 51.60;
148.0, 148.4, 148.6 (NC6H4NNCH2CH2O-C6H4(OCH2CH3)-2, H, 4.61; N, 6.37.
NCH2C6H4(CH3)-4), 182.0, 182.1 (Pd-Ccarbene); IR (cm−1)
ν(CN): 1407; Anal. calcd for C50H52N4O4PdCl2: C, 63.19; H, General Procedure for direct arylations
5.52; N, 5.90; found: C, 63.18; H, 5.50; N, 5.93.
As described in [47], in a typical experiment, the aryl chloride
(1 mmol), heteroaryl derivative (2 or 4 mmol) (see Table 1–5)
cis/trans-Dichloro-bis[1-(2-(2-ethoxy)phenoxyethyl)-3-(3- and KOAc (2 mmol) were introduced in a Schlenk tube,
methoxybenzyl)benzimidazo-2-ylidene]palladium(II) (7): equipped with a magnetic stirring bar. The Pd complex
Yield: 0.22 g, 53%; mp 205–207 °C; 1H NMR (CDCl3, δ) 1.43, (0.01 mmol, see Table 1–5) and DMAc (3 mL) were added, and
1.45 (t, J = 7.0 Hz, 6H, NCH2CH2OC6H4(OCH2CH3)-2), 3.66, the Schlenk tube was purged several times with argon. The
3.75 (s, 6H, NCH2C6H4(OCH3)-3), 3.97, 4.03 (q, J = 7.0 Hz, Schlenk tube was placed in a preheated oil bath at 150 °C, and
4H, NCH2CH2OC6H4(OCH2CH3)-2)), 4.60, 4.83 (t, J = 5.6 Hz, the reaction mixture was stirred for 20 h. Then, the reaction
4H, NCH2CH2OC6H4(OCH2CH3)-2), 5.29, 5.43 (t, J = 5.7 Hz, mixture was analysed by gas chromatography to determine the
4H, NCH2CH2OC6H4(OCH2CH3)-2), 6.01, 6.18 (s, 4H, conversion of the aryl chloride. The solvent was removed by
NCH2C6H4(OCH3)-3), 6.67–7.86 (m, 24H, NC6H4N, heating of the reaction vessel under vacuum and the residue was
NCH2CH2O-C6H4(OCH2CH3)-2, NCH2C6H4(OCH3)-3); charged directly onto a silica-gel column. The products were
13C NMR (CDCl3, δ) 15.0, 15.3 (NCH2CH2OC6H4- eluted by using an appropriate ratio of diethyl ether and
(OCH2CH3)-2), 48.0, 48.3 (NCH2CH2OC6H4(OCH2CH3)-2), pentane.
52.3, 52.4 (NCH2C6H4(OCH3)-3), 55.5, 55.7 (NCH2CH2O-
C6H4(OCH2CH3)-2), 63.9, 64.0 (NCH2CH2OC6H4- Acknowledgements
(OCH2CH3)-2), 68.3, 68.6 (NCH2C6H4(OCH3)-3), 112.3, This work was financially supported by the Technological and
113.1, 114.7, 120.0, 120.7, 120.9, 123.1, 123.2, 129.8, 134.0, Scientific Research Council of Turkey TUBİTAK-
310

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