Efficient imidazolium salts for palladium-catalyzed Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions

Article abstract of DOI:10.1016/j.cclet.2013.03.025

The system, Pd(OAc)₂/imidazolium salts (L₂), was found as an efficient catalyst in the Heck coupling reaction of olefins with aryl halides and Suzuki reactions of various aryl halides with aryl boronic acids under aerobic condition. This catalytic system demonstrates great tolerance to a wide range of groups on all substrates of aryl halides, alkenes and aryl boronic acids.

Full text of DOI:10.1016/j.cclet.2013.03.025

Chinese Chemical Letters 24 (2013) 433–436
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Chinese Chemical Letters
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Original article
Efficient imidazolium salts for palladium-catalyzed Mizoroki–Heck and
Suzuki–Miyaura cross-coupling reactions
b,
a
Mojtaba Amini a, , Mojtaba Bagherzadeh , Sadegh Rostamnia
*
*
a Department of Chemistry, Faculty of Science, University of Maragheh, Maragheh, P.O. Box 55181-83111731, Iran
b Chemistry Department, Sharif University of Technology, Tehran, P.O. Box 11155-3615, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
The system, Pd(OAc)2/imidazolium salts (L2), was found as an efficient catalyst in the Heck coupling
reaction of olefins with aryl halides and Suzuki reactions of various aryl halides with aryl boronic acids
under aerobic condition. This catalytic system demonstrates great tolerance to a wide range of groups on
all substrates of aryl halides, alkenes and aryl boronic acids.
Received 5 January 2013
Received in revised form 8 February 2013
Accepted 8 March 2013
Available online 12 April 2013
ß 2013 Mojtaba Amini, Mojtaba Bagherzadeh. Published by Elsevier B.V. on behalf of Chinese Chemical
Society. All rights reserved.
Keywords:
Imidazolium salt
Heck coupling reaction
Suzuki coupling reaction
Pd(OAc)2
1. Introduction
2. Experimental
Palladium-catalyzed formation of the carbon–carbon bond
has become an extremely powerful tool in modern organic
chemistry [1–4]. Among them, the Suzuki–Miyaura and Mizor-
oki–Heck coupling reactions have emerged as two of the most
important reactions, and in the last ten years have witnessed an
exponential growth in the application of Pd-catalyzed Heck and
Suzuki reactions in target-oriented organic synthesis [5–8].
N-Heterocyclic carbenes (NHCs) derived by deprotonation of
imidazolium salts are often considered phosphine mimics and
have consequently received a great deal of attention as alternatives
to phosphine based ligands in Pd-catalyzed chemistry [9–11]. A
2.1. Preparation of 4,5-dibromo-1,3-bis(2,4,6-trimethylphenyl)
imidazolium chloride (L4)
In a Schlenk flask under argon, to a THF suspension (20 mL)
of 1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride (1 g,
2.93 mmol), solid potassium tert-butoxide (0.35 g, 3.12 mmol)
was added in a single portion. The mixture was stirred for 45 min
at room temperature, and volatiles were removed under
vacuum. After addition of THF (20 mL) and stirring for 5 min,
the reaction mixture was filtered under argon, and carbon
tetrabromide (2.42 g, 5.86 mmol) in THF (10 mL) was added
dropwise to solution, over a period of ca. 30 min. The resulting
brown solution was stirred for 4 h. Subsequent removal of
volatiles in vacuo gave a dark brown residue that was extracted
into toluene (10 mL) and then a solution of HCl in dioxane (4 mol/
L) was added, and the resulting white precipitate was collected.
combination of their powerful s-donating and weak p-accepting
characteristics make them the ligands of choice for many catalytic
systems, thus leading to the preparation of organometallic
catalysts of enormous utility in organic synthesis [12–14].
Therefore, herein, we report the use of easily prepared, oxygen,
moisture, and thermally stable imidazolium salts (L1–4) as ligands
for Pd(II)-catalyzed Heck and Suzuki coupling reactions of aryl
iodides, bromides, and chlorides (Scheme 1).
Yield 351 mg (29%). 1H NMR (500 MHz, DMSO-d6):
o-CH3), 2.39 (s, 6H, p-CH3), 7.27 (s, 4H, Ar–H), 10.13 (s, 1H,
HNCN); 1H NMR (500 MHz, CDCl3):
2.20 (s, 6H, p-CH3), 2.54 (s,
12H, o-CH3), 6.82 (s, 4H, Ar–H), 10.16 (s, 1H, HNCN); 13C NMR
(125 MHz, DMSO-d6): 16.9, 20.7, 113.1, 129.3, 129.6, 135.1,
d 2.13 (s, 12H,
d
d
140.5, 141.7; Elemental analysis calcd. for C21H23Br2ClN2: C
50.58, H 4.65, N 5.62; found C 50.55, H 4.59, N 5.67; ESI-MS
(C21H23Br2Cl1N2) (m/z): 497.4 [M]+.
* Corresponding authors.
E-mail addresses: mamini@maragheh.ac.ir (M. Amini),
bagherzadeh@sharif.edu (M. Bagherzadeh).
1001-8417/$ – see front matter ß 2013 Mojtaba Amini, Mojtaba Bagherzadeh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.03.025

[
M. Amini et al. / Chinese Chemical Letters 24 (2013) 433–436
N
N
+
N
N
+
Cl -
Cl -
L1
L2
Cl
Br
Br
Cl
N
N
+
N
N
+
Cl -
Cl -
L3
L4
Scheme 1. The imidazolium salts (L1–4) used as ligands for Pd(II)-catalyzed Heck and Suzuki coupling reactions.
2.2. General procedure for the Heck reactions
affords the corresponding imidazolium salt L4 as a white
precipitate which can be isolated and stored in the air for several
months. The L4 was fully characterized by spectroscopy (1H NMR,
13C NMR, and ESI-mass spectrometry) and by elemental analysis.
Elemental analysis of L4 fully agreed with experimental analysis.
All Heck reactions were carried out in air. A mixture of aryl
halide (1.0 mmol), olefins (1.2 mmol), K2CO3 (2 mmol), Pd(OAc)2
(0.5 mol%), and imidazolium salt L2 (1.0 mol%) in DMF (3 mL) was
allowed to react in a sealed tube at 80 8C. The reaction mixtures
was added to brine (15 mL) and extracted three times with diethyl
ether (3 Â 15 mL). The further purification of the product was
achieved by flash chromatography on a silica gel column using
hexane/ethyl acetate (5/1).
The 1H NMR spectrum of L4 in DMSO-d6 shows resonances at
d
2.13, 2.39, and 7.27 for the p- and o-methyl and the aromatic ring
proton of the phenyl groups, respectively. Also the imidazolium
proton of L4 resonates at
d 10.13 in DMSO-d6. The ESI mass
spectrum of L4 shows a molecular ion peak at m/z 497.4 [M]+.
To investigate the reactivity of (L1–4) as ligand, we first
employed 4-acetylbromobenzene and n-butyl acrylate as the
standard substrates. Their coupling reactions were carried out
under a variety of palladium sources, bases and solvents. The
results are summarized in Table 1. In a comparative study, we
applied these salts in conjunction with Pd(OAc)2 as pre-catalyst for
the Heck coupling reaction of 4-acetylbromobenzene and n-butyl
acrylate in DMF as solvent at 80 8C. Results (Table 1, entries 1–4)
show that all four salts (L1–4) are very efficient and suitable ligands
for the Heck coupling reaction with Pd(II) as pre-catalyst. On the
basis of higher yields for L2 compared to others, this salt was
selected as the ligand of choice for this reaction.
2.3. General procedure for the Suzuki reactions
All Suzuki reactions were carried out in air. A mixture of aryl
halide (1.0 mmol), aryl boronic acid (1.2 mmol), KOH (2 mmol),
Pd(OAc)2 (0.5 mol%) and imidazolium salt L2 (1.0 mol%) in mixture
of H2O/i-PrOH (3 mL) (1/1, v/v) was allowed to react in a sealed
tube at 80 8C. The reaction mixtures was added to brine (15 mL)
and extracted three times with diethyl ether (3 Â 15 mL). The
further purification of the product was achieved by flash
chromatography on a silica gel column using hexane/ethyl acetate
(5/1, v/v).
We then examined the effect of bases and among the tested
bases, K2CO3 was the most effective base for the coupled product in
presence of L2 (Table 1, entry 8), while other bases, such as NaOAc,
Na2CO3 and K3PO4 gave yields of 11%, 51% and 37%, respectively
(Table 1, entries 5–7). Replacement of inorganic bases by the
organic base Et3N afforded low product yields (Table 1, entry 9).
The next step was to optimize the conditions to select the best
solvent from the commonly used ones. Solvents N,N-dimethylfor-
mamide (DMF) and N,N-dimethylacetamide (DMAc) were found to
3. Results and discussion
The ligands (L1–L3) were prepared according to the
literature [15,16]. The new imidazolium salt, 4,5-dibromo-1,3-
bis(2,4,6-trimethylphenyl)imidazolium chloride (L4), was readily
prepared via a one-step synthesis. Deprotonation of 1,3-bis(2,4,6-
trimethylphenyl)imidazolium chloride (L1) with t-BuOK in THF
following addition of CBr4 and then a solution of HCl in dioxane
Table 1
The optimized reaction conditions for Pd-catalyzed Mizoroki–Heck reactions.a
Entry
Ligand
Base
Solvent
Pd source
Yield (%)b
Entry
Ligand
Base
Solvent
Pd source
Yield (%)b
1
2
3
4
5
6
7
8
9
L1
L2
L3
L4
L2
L2
L2
L2
L2
K2CO3
K2CO3
K2CO3
K2CO3
NaOAc
Na2CO3
K3PO4
K2CO3
Et3N
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
87
10
11
12
13
14
15
16
17
18
L2
L2
L2
L2
L2
L2
L2
L2
L2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMAc
H2O/DMF
H2O
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
95
81
21
41
63
69
79
85
71
96
93
91
i-PrOH
Toluene
Dioxane
DMF
11
51
37
96
DMF
Pd(CH3CN)2Cl2
K2PdCl4
Trace
DMF
a
Reaction conditions: 1.0 mmol of 4-acetylbromobenzene, 1.2 mmol of n-butyl acrylate, 2 mmol of base, 0.5 mol% Pd salt, 1.0 mol% imidazolium salt (L1–4), 80 8C, 2 h, 3 mL
solvent.
b
Isolated yield.

M. Amini et al. / Chinese Chemical Letters 24 (2013) 433–436
435
Table 2
Heck reaction between aryl halides and olefins.a
Entry
ArX
Olefin
Yield (%)b
Entry
ArX
Olefin
Yield (%)b
1
2
3
4
5
6
7
8
9
PhI
PhCH5CH2
98
97
97
98
98
96
95
96
90
10
11
12
13
14
15
16
17
18
4-MeCO–PhBr
4-MeCO–PhBr
4-MeO–PhBr
4-MeO–PhBr
2-MeO–PhBr
PhBr
PhCH5CH2
94
96
81
83
72
55
49
46
17
PhI
H2C5CH–COOBu
H2C5CH–COOMe
H2C5CH–COOEt
4-Me–PhCH5CH2
4-MeO–PhCH5CH2
H2C5CH–COOBu
PhCH5CH2
H2C5CH–COOBu
H2C5CH–COOBu
PhCH5CH2
PhI
PhI
PhI
H2C5CH–COOBu
H2C5CH–COOBu
PhCH5CH2
PhI
4-MeO–PhI
4-MeO–PhI
2-MeO–PhI
4-MeCO–PhCl
4-MeCO–PhCl
PhCl
H2C5CH–COOBu
H2C5CH–COOBu
H2C5CH–COOBu
a
Reaction conditions: 1.0 mmol of aryl halide, 1.2 mmol of olfins, 2 mmol of K2CO3, 0.5 mol% Pd(OAc)2, 1.0 mol% imidazolium salt L2, 80 8C, 3 mL DMF.
Isolated yield.
b
Table 3
The optimized reaction condition for Pd-catalyzed Suzuki reaction.a
Entry
Base
Solvent
Yield (%)b
Entry
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMF
71
65
53
47
31
21
87
8
9
K2CO3
KOH
H2O/i-PrOH
H2O/i-PrOH
H2O/i-PrOH
H2O/i-PrOH
H2O/i-PrOH
H2O/i-PrOH
84
97
69
42
75
63
DMAc
H2O
10
11
12
13
Na2CO3
K3PO4
NaOAc
Et3N
i-PrOH
Toluene
Dioxane
H2O/DMF
a
Reaction conditions: 1.0 mmol of 4-acetylbromobenzene, 1.2 mmol of phenylboronic acid, 2 mmol of bases, 0.5 mol% Pd(OAc)2, 1.0 mol% imidazolium salt L2, 80 8C, 3 mL
solvent.
b
Isolated yield.
be of similar activity and more active than the other solvents,
such as dioxane, toluene, H2O, i-PrOH and a mixture of H2O/DMF
(2/1, v/v) in presence of K2CO3 as base catalyzed by Pd(OAc)2/L2 at
80 8C for 2 h (Table 1, entries 10–15). Then we carried out
screening of palladium salts for better performance of the reaction
and other palladium sources, including Pd(OAc)2, proved to be less
effective in the reaction of 4-MeCO-PhBr and n-butyl acrylate
(Table 1, entries 16–18).
substrates to optimize the reaction conditions (Table 3). The
solvents, such as DMF, DMAc, H2O, i-PrOH, dioxane and toluene,
gave low to moderate yields ranging from 21% to 71% as illustrated
in Table 3 (entries 1–6). However, when we adopted the organic/
aqueous co-solvent, satisfactory results were obtained and a
mixture of H2O/i-PrOH (1/1, v/v) was found to be the best of choice
(Table 3, entry 8). The merit of the co-solvent is attributed to the
good solubility of the organic reactants and the inorganic bases.
Among the tested bases, KOH is the best choice as compared to the
other bases in a mixture of H2O/i-PrOH (1/1, v/v) as solvent. The
activity toward cross-coupled product was decreased when K2CO3
was replaced with Na2CO3, K3PO4, NaOAc, and Et3N (Table 3,
entries 10–13).
On the basis of the optimized conditions, we next carried out
the Heck coupling reactions with a variety of aryl halides and
alkene derivatives (Table 2). The coupling reactions of olefins and
aryl iodides showed excellent yields (Table 2, entries 1–6). In the
case of iodoanisole derivatives, sterically hindered 2-iodoanisole
showed a slightly lower yield than 4-iodoanisole (Table 2, entries
7–9). Next, a variety of aryl bromides was employed as coupling
partner with n-butyl acrylate and styrene in the Heck reaction
using the Pd(OAc)2/L2 catalytic system. Aryl bromides having an
electron withdrawing substituent gave the coupled product in
good yields, and aryl bromides containing an electron donating
group produced the corresponding coupled product in moderate
yields (Table 2, entries 10–13). Among the bromoanisole
derivatives, 2-bromoanisole exhibited the lowest yield (Table 2,
entry 14). The coupling reactions of n-butyl acrylate with electron
neutral aryl bromide, bromobenzene, gave the desired coupled
product in 55% yield (Table 2, entry 15). We also tried the coupling
reaction using aryl chlorides and found that the coupling of 4-
acetylchlorobenzene with styrene and n-butyl acrylate resulted in
moderate yields (Table 2, entries 16, 17). Unfortunately, the
catalytic system Pd(OAc)2/L2 showed no activity for the Heck
coupling reaction of chlorobenzene and trace amounts of coupling
product was observed (Table 2, entry 18). The Heck coupling
reaction of olefins with aryl halides showed the desired E-isomeric
products as the only product.
Table 4
Suzuki–Miyaura cross-coupling reaction of aryl halides with aryl boronic acids.a
[TD$INLINE]
X
R2
Pd(OAc)2/ L2
+
H2O/ i-PrOH, KOH,
R2
80 0C, 2 h
R1
R1
B(OH)2
Entry
R1
X
R2
Yield (%)b
1
2
3
4
5
6
7
8
H
Br
Br
Br
Br
Br
Br
Cl
Cl
H
95
97
71
90
73
94
67
48
4-COCH3
H
H
2-CH3O
4-CH3O
2-CH3O
4-CH3O
H
H
4-COCH3
4-COCH3
4-COCH3
H
H
Further, we investigated the Suzuki coupling reaction using the
imidazolium salt L2 as the ligand and Pd (OAc)2 as the catalyst. We
initially investigated the effect of bases and solvents on Suzuki
reaction using 4-acetylbromobenzene and phenylboronic acid as
a
Reaction conditions: 1.0 mmol of aryl halides, 1.2 mmol of aryl boronic acids,
2 mmol of KOH, 0.5 mol% Pd(OAc)2, 1.0 mol% imidazolium salt L2, 80 8C, 3 mL
mixture of H2O/i-PrOH (1:1, v/v).
b
Isolated yield.

436
M. Amini et al. / Chinese Chemical Letters 24 (2013) 433–436
References
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M. Amini thanks the Research Council of University of
Maragheh for financially support of this work and M.B. thanks
the Sharif University of Technology for funding of this work.