A highly efficient catalytic system for cross-coupling of aryl chlorides and bromides with malononitrile anion by palladium carbene complexes

Article abstract of DOI:10.1039/b302890a

Six imidazolium chlorides (1-6) as precursors of 1,3-diaryl substituted N-heterocyclic carbene ligands were synthesized and evaluated in palladium-catalyzed cross-coupling reactions of aryl chlorides and bromides with malononitrile in the presence of NaH.

Full text of DOI:10.1039/b302890a

A highly efficient catalytic system for cross-coupling of aryl chlorides
and bromides with malononitrile anion by palladium carbene complexes†
Chengwei Gao, Xiaochun Tao, Yanlong Qian and Jiling Huang*
Laboratory of Organometallic Chemistry, East China University of Science and Technology, Shanghai
200237, P. R. China. E-mail: qianling@online.sh.cn; Fax: 86-21-5428 2375; Tel: 86-21-5428 2375
Received (in Cambridge, UK) 12th March 2003, Accepted 7th May 2003
First published as an Advance Article on the web 20th May 2003
Six imidazolium chlorides (1–6) as precursors of 1,3-diaryl
substituted N-heterocyclic carbene ligands were synthesized
and evaluated in palladium-catalyzed cross-coupling reac-
tions of aryl chlorides and bromides with malononitrile in
the presence of NaH. Among them, 1,3-bis(2,4,6-triethylphe-
nyl)imidazolium chloride (5) and 1,3-bis(2,4,6-triisopropyl-
phenyl)imidazolium chloride (6) are novel. The catalytic
system combining Pd(0) with imidazolium salts 4, 5 and 6
with bulky aryl groups in pyridine is found to be superior
over others and afforded a-arylmalononitriles in high yields
when employing a wide variety of substrates.
situ from the imidazolium salts. To explore the effect of
substituent groups of the carbene ligands on the catalytic C–C
bond formation processes, six imidazolium salts with different
substituents have been prepared (Scheme 2). Among them,
1,3-bis(2,4,6-triethylphenyl)imidazolium chloride (5) and
1,3-bis(2,4,6-triisopropylphenyl)imidazolium chloride (6) are
novel. We wondered if the catalytic arylation could be
performed with the help of palladium complexes bearing the N-
heterocyclic carbene ligands in a suitable solvent.
As part of an effort to develop high-throughput synthetic
methods for a-arylmalononitriles by palladium-catalyzed cross-
coupling with a number of precursors of the carbene ligands
(Scheme 2), we found that the bulky substituted N-heterocyclic
carbene ligands could effectively promote the reactions of the
palladium-catalyzed coupling of bromobenzene with malononi-
trile when the reaction is performed in pyridine (Scheme 3 and
Table 1). The imidazolium salts 4 and 5 showed excellent
catalytic activity in a high yield of 91% (Table 1, entries 6 and
7), and the imidazolium salt 6 (entry 8) also showed high yield
of 78%. For others only moderate yields of phenylmalononitrile
(entries 2–4) were obtained. In the absence of imidazolium
salts, the product was not detected in the reaction (entries 1 and
9).
Palladium-catalyzed cross-coupling reactions of aryl halides or
halide equivalents with various nucleophiles have been shown
to be highly effective and practical approaches for the formation
of C–C bonds.1 There has been much interest recently in the
application of N-heterocyclic carbenes as ligands (Scheme 1) in
organic synthesis and coordination chemistry.2 N-Heterocyclic
carbene complexes have been successfully used in a wide range
of catalytic reactions.2,3 Obviously, because of their stability
and ease of preparation, imidazolium salts, as precursors to
form N-heterocyclic carbenes are especially suitable and
economic for high throughput approaches.
It is known that arylmalononitriles as well as a-aryl-b-
cyanoacetates are important intermediates in the preparation of
useful organic compounds like bioactive materials,4 hetero-
cyclic compounds5 and organic conducting materials.6 How-
ever, under basic conditions the reactions of aryl halides with
active methylene compounds are difficult and give no con-
densation products. Suzuki et al.7 and Miura et al.8 reported a
synthetic route to arylmalononitriles by catalytic coupling of
aryl iodides with malononitrile anion in the presence of
As to the catalytic coupling of chlorobenzene, the activity of
the catalytic system was somewhat lower than that for
bromobenzene. By increasing the moles of palladium(0)
complex and imidazolium salt as well as moderately extending
the reaction time, the satisfactory results for the coupling were
also obtained in yields of 70–75% for imidazolium salts 4, 5 and
6 (Table 1, entries 14–16). As shown in Table 1, the activity of
the imidazolium chlorides in the palladium-catalyzed coupling
of bromobenzene and chlorobenzene was in the following
order: 4 ≈ 5 > 6 ì 3 > 2 > 1. In addition, our work has
showed that the palladium N-heterocyclic carbene complex
could smoothly realize cross-coupling of aryl iodides with
malononitrile in tetrahydrofuran as solvent and gave ar-
ylmalonontriles in satisfactory yields.12 But under similar
copper(
) iodide, respectively. Uno et al.9 reported another
I
synthetic preparation of arylmalononitriles by Pd(PPh3)2Cl2
from aryl iodides. In addition, Yamanaka et al.10 reported
Pd(PPh3)4 catalysed coupling of bromobenzene and N-hetero-
aryl bromides with malononitrile anion in moderate yields.
Recently Cristau et al. reported the arylation of iodobenzene
with malononitrile anion catalyzed by 20 mol% of nickel(0)
complexes in 70% yield.11 Evidently, the use of aryl chlorides
or aryl bromides as substrates has proved difficult but would
economically benefit a number of industrial processes.
We wish here to report the palladium-catalyzed C–C
coupling of normally less active aryl halides with malononitrile
in the presence of sodium hydride using a catalytic system of
Pd(0) and bulky nucleophilic carbenes as ligands, generated in
Scheme 2 Imidazolium salts used.
Scheme 1 Preparation of N-heterocyclic carbenes from imidazolium
salts.
† Electronic supplementary information (ESI) available: experimental
details. See http://www.rsc.org/suppdata/cc/b3/b302890a/
Scheme 3
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CHEM. COMMUN., 2003, 1444–1445
This journal is © The Royal Society of Chemistry 2003

Table 1 Cross-coupling of bromobenzene and chlorobenzene with
malononitrile using Pd(dba)2 and imidazolium salts (1–6) in pyridine
Table 2 Cross-coupling of halides with malononitrile catalyzed by the
catalytic system of Pd(dba)2–imidazolium salts in pyridine
Imidazolium
salt
Isolated yields
(%)
Imidazolium
salt
Yield
(%)
Entry
X
Time/h
Entry
Ar
X
Time/h
1
2
3
4
5a
6
7
8
9
10
11
12
13a
14
15
16
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
None
1
2
3
4
4
5
6
12
10
10
10
12
10
10
10
16
14
14
14
16
14
14
14
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
2-Me–C6H4
2-Me–C6H4
2-Me–C6H4
4-Me–C6H4
4-Me–C6H4
4-Me–C6H4
2-MeO–C6H4
2-MeO–C6H4
2-MeO–C6H4
4-MeO–C6H4
4-MeO–C6H4
4-MeO–C6H4
4-F–C6H4
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
4
5
6
4
5
6
4
5
6
4
5
6
4
5
6
4
5
4
5
4
5
4
5
4
5
4
5
4
5
10
10
10
10
10
10
10
10
10
14
14
14
12
12
12
10
10
16
16
14
14
14
14
14
14
14
14
14
14
91
91
88
94
92
90
85
91
90
65
64
60
75
75
70
85
94
51
50
73
71
45
45
85
86
77
70
90
94
26
30
35
45
91
91
78
0
None
1
2
3
4
4
5
6
Trace
3
4
15
75
73
70
4-F–C6H4
4-F–C6H4
1-Naphthyl
1-Naphthyl
2-Me–C6H4
2-Me–C6H4
4-Me–C6H4
4-Me–C6H4
2-MeO–C6H4
2-MeO–C6H4
1-Naphthyl
1-Naphthyl
4-F3C–C6H4
4-F3C–C6H4–
4-Ph–C6H4
4-Ph–C6H4
a Refluxed in THF as solvent.
reaction conditions, the coupling only gave 45% yield for
bromobenzene, and 15% for chlorobenzene, respectively (Table
1, entry 5 and 13). Obviously, pyridine, as solvent, is not only
high efficient, but also has high recovery ( > 90%) after
distillation. Therefore, the high activity of this catalytic system
presumably results from the combination of strong electron-
donating ability with steric demands of the N-heterocyclic
carbene ligands as well as the effect of the solvents.
The coupling results of a number of aryl bromides and aryl
chlorides (Scheme 4) with malononitrile anion using the bulky
substituted imidazolium salts (4, 5 and 6) and Pd(0) as catalytic
systems are listed in Table 2. It can be seen from Table 2 that the
imidazolium chlorides 4 and 5 have similar high activity.
Because of its steric effects, the activity of the imidazolium
chloride 6 is a little bit lower.
As seen from Table 2, the bromine atom in the aryl bromides
could be smoothly substituted by a malononitrile group with
high efficiency, and the corresponding coupling products were
obtained in good yields of 64–94% (entries 1–17). For the
methoxybromobenzene substrates, when the methoxy group is
in the ortho-position, good coupling yields of 85–91% are
obtained (entries 7–9), while in the para-position the yields
decrease to 60–65% (entries 10–12). Generally, with imidazo-
lium salts 4, 5 and 6, most aryl bromides have high reaction
rates and higher coupling yields.
However when using aryl chlorides instead of aryl bromides
under the above conditions, the reaction became somewhat
difficult. When the amounts of Pd(dba)2 and imidazolium salts
are increased up to 50% with appropriate reaction time, the
coupling with aryl chlorides could be performed with good
results. For most aryl chlorides, the catalytic cross-coupling can
also proceed under these conditions; all substrates gave yields
from 45% to 94% (Table 2, entries 18–29). The 4A-biphenyl
chloride as substrate showed high activity and gave yields of
90% and 94% for imidazolium salts 4 and 5 (entries 28 and 29),
respectively. The steric and electronic effects of the substituent
groups on the aromatic rings were also observed in this case.
The electron-donating group, methoxy, in 2-methoxyphenyl
chlorides led to a sharp decrease in the yields (entries 22 and
23). Generally, the electron-withdrawing groups on aryl
chloride rings could promote the activity of the coupling
(entries 26 and 27).
Notes and references
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Scheme 4
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