Dimeric ortho-palladated complex of 2,3-dimethoxybenzaldehyde oxime catalyzed Suzuki-Miyaura cross-coupling reaction under microwave irradiation

Article abstract of DOI:10.1007/s13738-014-0579-3

Abstract The catalytic activity of dimeric [Pd{C₆H₂(-CH=NOH)-(OMe)₂-2,3}(μ-Cl)]₂ complex as an efficient, air, and moisture-tolerant catalyst was investigated in Suzuki cross-coupling reactions of various aryl halides. The combination of homogenous metal catalyst, microwave irradiation, and microwave-active polar solvents gave high yields of substituted biaryl products in short reaction times.

Full text of DOI:10.1007/s13738-014-0579-3

J IRAN CHEM SOC
DOI 10.1007/s13738-014-0579-3
ORIGINAL PAPER
Dimeric ortho‑palladated complex of 2,3‑dimethoxybenzaldehyde
oxime catalyzed Suzuki–Miyaura cross‑coupling reaction
under microwave irradiation
Abdol‑Reza Hajipour · Fatemeh Rafiee
Received: 7 September 2014 / Accepted: 17 December 2014
© Iranian Chemical Society 2015
Abstract The catalytic activity of dimeric [Pd{C6H2(–
CH=NOH)–(OMe)2-2,3}(µ–Cl)]2 complex as an effi-
cient, air, and moisture-tolerant catalyst was investigated
in Suzuki cross-coupling reactions of various aryl halides.
The combination of homogenous metal catalyst, microwave
irradiation, and microwave-active polar solvents gave high
yields of substituted biaryl products in short reaction times.
of the palladacycle catalysts is due to the slow generation
of low ligated Pd(0) complexes from a stable palladium(II)
pre-catalyst [16].
There are various cross-coupling reactions and among
them the Suzuki–Miyaura coupling of aryl halides with
aryl boronic acids is one of the most versatile and utilized
synthetic method for the construction of symmetric and
unsymmetric biaryls [17–23]. Biaryls are an important
class of organic compounds due to their range of excellent
physical and chemical properties. They present significant
interest for the synthesis of herbicides [24], pharmaceuti-
cals [25], natural products [26], bioactive products [27],
microelectrode array [28], conducting polymers, and liq-
uid crystal materials [29]. The key benefits of the Suzuki–
Miyaura coupling are the mild reaction conditions, the
tolerance of a broad range of functionalities, commercial
availability and easy handling of organoboron reagents, and
removal of the nontoxic boron-containing by-products [30].
Transition metal-catalyzed cross-coupling reactions
typically need long reaction times and an inert atmosphere
to reach completion with traditional heating. Modern tech-
niques are focused on the design of novel methodologies
to modify these chemical transformations using simpler,
faster, and more efficient processes. The use of microwave
irradiation in homogeneous transition metal-catalyzed reac-
tions leads to the reduction of reaction times, production of
high yields and higher selectivity, the decrease of discarded
by-products from thermal side reactions, and increased life-
time of the catalyst [31–33].
Keywords ortho-Palladated catalyst · Palladacycle
complexes · Oxime · Suzuki reaction · Biaryls
Introduction
Transition metal-catalyzed coupling reactions are among
the most potent and convenient tools of modern organic
synthesis [1]. Palladium is used as efficient and active cata-
lyst in these reactions [2–4]. Generally, the combination of
palladium catalysts with various phosphine ligands [5–8]
and also N-heterocyclic carbenes [9–11] results in excellent
yields and high efficiency in cross-coupling reactions, how-
ever, they are usually sensitive to air and moisture or expen-
sive. Palladacycle complexes, with air and moisture stabil-
ity and high catalytic activity have recently been employed
in cross-coupling reactions [12–15]. The high productivity
A.-R. Hajipour (*)
Pharmaceutical Research Laboratory, Department of Chemistry,
Isfahan University of Technology, 84156 Isfahan, Islamic
Republic of Iran
In continuation of our recent investigations on the syn-
thesis of the palladacycle catalysts and application of these
complexes in microwave-assisted cross-coupling reac-
tions [34–39], we now wish to report the synthesis and the
extension of [Pd{C6H2(–CH=NOH)–(OMe)2-2,3}(µ–Cl)]2
homogeneous complex, as a thermally stable and oxygen
e-mail: haji@cc.iut.ac.ir
F. Rafiee
Department of Chemistry, Faculty of Science, Alzahra University,
Vanak, Tehran, Iran
e-mail: f.rafiee@alzahra.ac.ir
1 3

J IRAN CHEM SOC
insensitive catalyst for the cross-coupling reaction of vari-
ous aryl halides with aryl boronic acids and sodium tetrap-
henylborate under microwave irradiation.
H, 3.13; N, 4.35. Found: C, 33.62; H, 3.12; N, 4.30. M.P.
186 °C dec.
1H-NMR (500 MHz): δ 8.72 (s, 1H), 8.46 (s, 1H), 6.91
3
3
(d, J = 8.8 Hz, 1H), 6.85 (d, J = 8.8 Hz, 1H), 3.81 (s,
3H), 3.78 (s, 3H). IR (cm−1): 3,400, 3,000, 1,650, 1,600,
1,560, 1,510, 1,450.
Experimental
Reagents and measurements
General procedure for Suzuki reaction of aryl halides
All melting points were taken on a Gallenkamp melting
apparatus. 1H-NMR spectra were recorded using 400 MHz
in CDCl3 solutions at room temperature (TMS was used
as an internal standard) on a Bruker, Avance 500 instru-
ment (Rheinstetten, Germany) and Varian 400 NMR. FT-IR
spectra were recorded on a spectrophotometer (Jasco-680,
Japan). Spectra of solids were carried out using KBr pel-
lets. Vibrational transition frequencies were reported in a
wave number (cm−1). We used the Milestone microwave
(Microwave Labstation-MLS GmbH-ATC-FO 300) for
synthesis. Furthermore, we used Gas chromatography (GC)
(BEIFIN 3,420 Gas Chromatograph equipped a Varian CP
SIL 5 CB column-30 m, 0.32 mm, 0.25 μm) for examina-
tion of reaction completion and yields. Palladium chloride,
aryl halides and all chemicals were purchased from Merck
and Aldrich and were used as received.
A mixture of the aryl halide (1 mmol), phenylboronic acid
(1.2 mmol) or Ph4BNa (0.25 mmol), K2CO3 (2 mmol),
ortho-palladated oxime catalyst (A) (0.05 mmol %) was
added to ethanol (2 mL) in round-bottom flask equipped
with condenser and placed into the Milestone microwave.
Initially the microwave irradiation of was set at 400 W,
the temperature was ramped from room temperature to the
desired temperature of 60 °C. Once this was reached, the
reaction mixture was held at this temperature until the reac-
tion was completed. The direct control of reaction mixture
temperature carried out with the IR sensors, and software
enables on-line temperature–pressure control by regulation
of microwave power output. The mixture was stirred con-
tinuously during the reaction and monitored by both TLC
and GC. After the reaction was completed, the mixture was
cooled to room temperature and was diluted with n-hexane
and water. The organic phase was dried over MgSO4, fil-
tered and concentrated under reduced pressure using rotary
evaporator. The residue was purified by silica gel column
chromatography. The products were characterized by com-
General procedure for the synthesis of ortho-palladated
oxime complex
1
2,3-Dimethoxybenzaldehyde oxime was synthesized
according to our previous work [40]. For the synthesis of
ortho-palladated oxime complex, to a solution containing
PdCl2 (1 mmol) and 2 mmol LiCl in methanol (40 mL), a
methanol solution of 2,3-dimethoxybenzaldehyde oxime
(1 mmol) and sodium acetate (1 mmol) was added. The
mixture was stirred for 48 h at room temperature. Then the
mixture was filtered and water (30 mL) was added to the
filtrate to give yellow solid. The residue was recrystallized
from dichloromethane to give catalyst (A) (53 %). Elemen-
tal analysis (C18H20N2O6Cl2Pd2); calculated: C, 33.56;
paring their m.p., IR, H, 13C NMR spectra with those
found in the literature [39].
Results and discussion
In this paper, dimeric ortho-palladated complex
[Pd{C6H2(–CH=NOH)–(OMe)2-2,3}(µ–Cl)]2 (A) was
synthesized (Scheme 1) and the efficiency of this catalyst
was investigated in Suzuki reaction of various aryl halides
under microwave irradiation.
Scheme 1 Preparation of
ortho-palladated catalyst (A)
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J IRAN CHEM SOC
Table 1 Optimization of reaction conditions in Suzuki cross-cou-
pling of aryl halides under microwave irradiation
also 4,4′-dimethoxybiphenyl was formed due to homocou-
pling of 4-bromoanisole as by-products. The best results
were obtained in ethanol as the high microwave absorbing
solvent and K2CO3 as base by employing 0.05 mol % of
ortho-palladated complex (A) as the catalyst at 60 °C and
400 W (Table 1, entry 10). As this catalyst is not sensitive
to oxygen, the reactions were carried out under air atmos-
phere. These optimize reaction conditions were applied in
the Suzuki cross-coupling reaction of various aryl halides
under microwave irradiation (Scheme 2).
As is demonstrated in Table 2, the catalyst can be used
for coupling reaction of aryl iodides, bromides and even
less reactive aryl chlorides with aryl boronic acids and
sodium tetraphenylborate in good to excellent yields
(Table 2). Sodium tetraphenylborate, unlike boronic acid
reagents can react with four equivalents of electrophilic
reagents. This phenylating agent is a cheap and easily
available starting material in place of phenylboronic acid.
Therefore, from both economical concerns and increased
environmental awareness, this is an atom economical
reaction.
Entry Base
Solvent Catalyst
(mmol %)
Tempera-
ture (°C)
Conversion
(%)a
1
K2CO3 DMF
K2CO3 DMF
0.1
120
120
120
120
120
130
90
68
72
60
57
80
63
22
29
48
100
91
100
–
2
0.2
0.2
0.2
0.2
0.3
3
Na2CO3 DMF
NaOAc DMF
Cs2CO3 DMF
K2CO3 NMP
4
5
6
7
K2CO3 Dioxane 0.3
K2CO3 THF 0.3
K2CO3 CH3CN 0.4
8
80
9
80
10
11
12
13
K2CO3 EtOH
K2CO3 EtOH
K2CO3 EtOH
0.05
60
0.04
0.1
60
60
–
EtOH
0.05
60
Reaction conditions: 4-bromoanisole (1 mmol), phenylboronic acid
(1.2 mmol) K2CO3 (2 mmol), solvent (2 ml), ortho-palladated cata-
lyst (A), 400 W, 3 min
a
Determined by GC
We examined the electronic and steric effects on the
resulted yields and conversion times of the reactions.
Aryl bromides and iodides substituted with electron-with-
drawing groups are the most suitable substrates for the
Suzuki–Miyaura cross-coupling reaction. Aryl chlorides
are, however, more attractive as starting materials because
of their lower cost and more widely available than their
bromide or iodide counterparts. Due to the strength of the
C–Cl bond compared with C–Br and C–I bonds and their
reluctance towards oxidative addition to Pd(0), required
times for conversion of aryl chlorides to biaryls are longer
(Table 2, entries 21–24). Aryl halides with electron-with-
drawing substituent transformed to the corresponding
coupled products rather than electron-donating substitu-
ent with better conversions and shorter reaction times. The
steric hindrance of the procedure was examined using 2-,
To optimize the reaction conditions, we employed the
coupling reaction of 4-bromoanisole with phenylboronic
acid using catalytic amounts of the ortho-palladated com-
plex (A) to evaluate the effects of the various bases and sol-
vents under microwave irradiation, as shown in Table 1.
The monitoring system for reaction times, tempera-
ture, pressure, and power in microwave reactor allow for
an excellent control of reaction parameters which gener-
ally leads to rapid optimization and more reproducible
reaction conditions. The direct control of reaction mix-
ture temperature; carry out with the IR sensors. At high
temperature in DMF and NMP as solvent, biphenyl was
obtained due to homocoupling of phenylboronic acid and
Scheme 2 Suzuki reaction
of aryl halides using ortho-
palladated catalyst (A)
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J IRAN CHEM SOC
Table 2 Suzuki cross-coupling reaction of various aryl halides under microwave irradiation
Entry
Ar–X
Ar′B(OH)2
Biaryl product
Time (min)
Yield (%)a
1
Ph–I
PhB(OH)2
Ph–Ph
0.5
1
97
95
93
95
94
92
96
95
93
95
92
94
90
93
90
87
91
96
95
90
94
87
73
81
2
p-O2N–C6H4–I
m-O2N–C6H4–I
p-MeO–C6H4–I
p-MeO–C6H4–I
Ph–Br
p-MeO–C6H4–B(OH)2
p-MeO–C6H4–B(OH)2
PhB(OH)2
p-O2N–C6H4–C6H4–p-OMe
m-O2N–C6H4–C6H4–p-OMe
p-MeO–C6H4–Ph
p-MeO–C6H4–Ph
p-MeO–C6H4–Ph
Ph–Ph
3
2
4
3
5
Ph4BNa
3
6
p-MeO–C6H4–B(OH)2
Ph4BNa
2
7
Ph–Br
1
8
p-MeO–C6H4–Br
p-MeO–C6H4–Br
p-NC–C6H4–Br
p-OHC–C6H4–Br
p-NC–C6H4–Br
p-OHC–C6H4–Br
p-MeOC–C6H4–Br
m-MeOC–C6H4–Br
o-MeOC–C6H4–Br
p-MeOC–C6H4–Br
p-Cl–C6H4–Br
m-Cl–C6H4–Br
o-Cl–C6H4–Br
Ph–Cl
PhB(OH)2
p-MeO–C6H4–Ph
p-MeO–C6H4–C6H4–p-OMe
p-NC–C6H4–Ph
4
9
p-MeO–C6H4–B(OH)2
PhB(OH)2
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
3
PhB(OH)2
p-OHC–C6H4–Ph
p-NC–C6H4–Ph
3
Ph4BNa
4
Ph4BNa
p-OHC–C6H4–Ph
p-MeOC–C6H4–C6H4–p-OMe
m-MeOC–C6H4–C6H4–p-OMe
o-MeOC–C6H4–C6H4–p-OMe
p-MeOC–C6H4–Ph
p-Cl–C6H4–Ph
4
p-MeO–C6H4–B(OH)2
p-MeO–C6H4–B(OH)2
p-MeO–C6H4–B(OH)2
PhB(OH)2
5
7
10
6
PhB(OH)2
1
PhB(OH)2
m-Cl–C6H4–Ph
1.5
3
PhB(OH)2
o-Cl–C6H4–Ph
PhB(OH)2
Ph–Ph
5
p-OHC–C6H4–Cl
p-MeOC–C6H4–Cl
p-OHC–C6H4–Cl
PhB(OH)2
p-OHC–C6H4–Ph
p-MeOC–C6H4–Ph
p-OHC–C6H4–Ph
6
PhB(OH)2
8
Ph4BNa
6
Reaction conditions: aryl halide (1 mmol), phenylboronic acid (1.2 mmol) or Ph4BNa (0.25 mmol), K2CO3 (2 mmol), ortho-palladated catalyst
(A) (0.05 mmol %), ethanol (2 ml), 60 ºC, 400 W
a
Isolated yield
3- and 4-bromoacetophenone as hindered substituted aryls
(Table 2, entries 14–16). Increasing the hindrance in vicin-
ity of leaving group can cause to decrease the reaction con-
version. The chemo-selectivity of the procedure was exam-
ined using 2-, 3- and 4-choloro-bromobenzene. In these
reactions Br acted as better leaving group (Table 2, entries
18–20).
was added to the reaction mixture of 4-bromoanisole and
phenylboronic acid under mentioned optimized conditions
and heated the reaction mixture, no catalytic activity was
observed for the catalyst.
Conclusions
Study on palladacycle catalyst cross-couplings showed
that the catalyst role in these reactions probably involve
the palladium nanoparticles and palladacycles behave as a
mere resource for producing nanoparticles Pd(0) [41–43].
Palladacycles decompose to liberate catalytic Pd(0) spe-
cies and show a positive Hg(0) test which was assigned as
probable evidence for catalysis by Pd nanoparticles [44].
To evaluate the proposed mechanism, the mercury drop test
was operated. In the presence of a heterogeneous catalyst,
mercury leads to the amalgamation of the surface of it. In
contrast, Hg(0) cannot have a poisoning effect on homoge-
neous palladium complexes, where the Pd(II) metal cen-
tre is tightly bound to the ligand. When a drop of Hg(0)
In this work, a general protocol was applied for the micro-
wave-promoted Suzuki reaction of various aryl halides
with aryl boronic acids and sodium tetraphenylborate using
ortho-palladated complex of 2,3-dimethoxybenzaldehyde
oxime. The catalytic amounts of this dimeric complex as an
inherent air and moisture resistant catalyst converted vari-
ous aryl halides to the corresponding products in excellent
yields. The combination of homogenous complex as cata-
lyst, microwave irradiation and also high dipole moment
of ethanol as microwave-active polar solvent caused to
increase lifetime of the catalyst, improve the yields of the
reactions and decrease the reaction times.
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J IRAN CHEM SOC
Acknowledgments We gratefully acknowledge the funding support
received for this project from the Isfahan University of Technology
(IUT), IR Iran and Isfahan Science & Technology Town (ISTT), IR,
Iran. Further financial support from the Center of Excellence in Sen-
sor and Green Chemistry Research (IUT) is gratefully acknowledged.
We also gratefully acknowledge the partial financial support received
from the research council of Alzahra University.
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