Application of dimeric orthopalladated complex in Suzuki-Miyaura cross coupling reaction under microwave irradiation and conventional heating

Article abstract of DOI:10.1016/j.ica.2011.01.050

The Suzuki-Miyaura reaction of various aryl halides using [Pd{C ₆H₂(CH₂CH₂NH₂)-(OMe) ₂,3,4} (μ-Br)]₂ have been investigated. This orthopalladated complex is an efficient, stable and non-sensitive to air and moisture catalyst for the hetrocoupling reaction in DMF as the reaction solvent at 130 °C. The combination of dimeric complex as homogenous catalyst and microwave irradiation can be very useful and efficient methods in organic synthesis, so the application of microwave irradiation have been investigated using homogenous dimeric complex [Pd{C₆H₂(CH ₂CH₂NH₂)-(OMe)₂,3,4} (μ-Br)] ₂. Application of dimeric complex as catalyst caused to produce the desired coupling products and the using of microwave irradiation improving the yields of the reactions and shortening the reaction times.

Full text of DOI:10.1016/j.ica.2011.01.050

Inorganica Chimica Acta 370 (2011) 531–535
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Note
Application of dimeric orthopalladated complex in Suzuki–Miyaura cross
coupling reaction under microwave irradiation and conventional heating
Abdol R. Hajipour a,b, , Kazem Karami b, Azadeh Pirisedigh b
⇑
a Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison, 53706-1532 WI, USA
b Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The Suzuki–Miyaura reaction of various aryl halides using [Pd{C6H2(CH2CH2NH2)–(OMe)2,3,4} (l-Br)]2
Received 27 February 2010
Received in revised form 8 November 2010
Accepted 18 January 2011
Available online 28 January 2011
have been investigated. This orthopalladated complex is an efficient, stable and non-sensitive to air
and moisture catalyst for the hetrocoupling reaction in DMF as the reaction solvent at 130 °C. The com-
bination of dimeric complex as homogenous catalyst and microwave irradiation can be very useful and
efficient methods in organic synthesis, so the application of microwave irradiation have been investigated
using homogenous dimeric complex [Pd{C6H2(CH2CH2NH2)–(OMe)2,3,4} (l-Br)]2. Application of dimeric
Keywords:
complex as catalyst caused to produce the desired coupling products and the using of microwave irradi-
ation improving the yields of the reactions and shortening the reaction times.
Ó 2011 Elsevier B.V. All rights reserved.
Orthopalladate
C–C bond formation
Catalyst
Suzuki reaction
1. Introduction
One negative aspect of the Suzuki reaction is long reaction time,
especially with satirically hindered coupling partners [26]. Modern
In modern synthetic chemistry the transition metals have been
employed as efficient catalysts for C–C bond formation [1,2] and
for this purpose the palladium catalysts are more efficient [3,4].
There are various cross coupling reactions and among them the Su-
zuki–Miyaura cross-coupling of aryl halides with aryl boronic acids
is one of the most useful method for synthesis of biaryl and hetero
biaryl derivatives [5–9]. Biaryls are basic intermediates in organic
synthesis and as functional groups in many natural products com-
pounds, bioactive products, and liquid crystal materials [10,11].
The special benefits of the Suzuki–Miyaura coupling are straight-
forward synthesize of the wide tolerance compounds with vast
functional groups under normal conditions [12], commercial avail-
ability of organoboron reagents, easy handling of these materials
[13]. In 1981, the application of Pd(PPh3)4 in Suzuki reaction has
been reported for the first time [14] and recently, N-heterocyclic
carbenes (NHC) have been applied as potentially effective ligands
for Suzuki reactions [15–18], however they are usually either air/
moisture sensitive or expensive [19]. The new palladacycles com-
plexes as active and more air inert catalytic candidates have re-
cently been employed in Suzuki reaction [20,21]. In many cases,
these compounds are dimeric chloro-bridged ortho-palladated
complexes [22–25].
techniques are focused on the design of new methodologies with
ability to modify the known chemical transformations using sim-
pler, faster, more inexpensive and in general, more efficient pro-
cesses [27]. Microwave (MW) as
a non-conventional energy
source has become very popular and useful technology in organic
chemistry [28], microwave irradiation has recently reported as a
potential method for improving the reaction yields in shorter reac-
tion times [28] under clean and green chemistry conditions [29].
The microwave-promoted Suzuki–Miyaura couplings were initially
reported in 1996 [30]. The combination of immobilized homoge-
nous catalysts and microwave irradiation can be very useful and
is an efficient methods for modification of known procedure in or-
ganic synthesis [27].
In conjunction of our pervious works on the synthesis and
application of palladacycle complexes [31–33], herein we report
the application of homogeneous homoveratrylamine Pd(II) pre-
catalyst A (Scheme 1) in Suzuki–Miyaura cross coupling reaction
of various aryl halides under microwave irradiation and conven-
tional heating conditions.
2. Results and discussion
Initially the affinity of catalyst A was tried for Suzuki–Miyaura
coupling of various arylhalides with phenylboronic acid via
conventional heating under air conditions (Scheme 1).
⇑
Corresponding author at: Pharmaceutical Research Laboratory, Department of
Chemistry, Isfahan University of Technology, Isfahan 84156, Iran.
E-mail address: haji@cc.iut.ac.ir (A.R. Hajipour).
0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2011.01.050

532
A.R. Hajipour et al. / Inorganica Chimica Acta 370 (2011) 531–535
irradiation did improve the yields of the reactions and shortening
1
2
A:
2
Ar1
Ar2
the reaction times from hours to minutes (Tables 2 and 3). As is
exhibited in Tables 2 and 3 a wide range of aryl halides were trans-
formed to the corresponding coupled products in good to excellent
yields and short reaction times. The palladacycle complex A was
entirely stable and thus the reactions could be carried out without
using inert atmosphere.
2
3
NH2
MeO
Pd
Br
OMe
2
Scheme 1. The Suzuki cross-coupling reaction.
In palladium catalyzed carbon–carbon bond formation reac-
tions, it is commonly believed that better conversions are achieved
for aryl halides with electron-withdrawing rather than electron
donating substituent [34]. The electron deficient aryl bromides
were transformed efficiently to the coupling products with 100%
conversion in short reaction times (Table 3, entries 7–9, 11). 2-Bro-
moacetophenone produced corresponding coupling compound
with 60% conversion (Table 3, entry 10) which may be attributed
to the electronic and steric nature. Aryl iodide was examined in
this reaction and the desired coupling product was obtained in
excellent yield (Table 3, entries 1). The aryl iodide with electron
donating substituent was examined and 90% conversion was
As demonstrated in Table 1, the corresponding coupled prod-
ucts were obtained using various amounts of catalyst A in the pres-
ence of K2CO3 as base [31,32] in different solvents.
According to the obtained results, DMF as solvent and K2CO3 as
base gave the best results. As is demonstrated in Tables 2 and 3, the
catalysts can be used for cross-coupling reaction of aryl iodides,
bromides and even less reactive aryl chlorides under both conven-
tional heating and microwave irradiation conditions. However, aryl
chlorides were reacted more slowly in comparison to the iodides
and bromides derivatives. Longer reaction times were required
under conventional heating (Table 2) and assistance of microwave
Table 1
Optimization of reaction condition on Suzuki reaction of different arylhalides with phenylboronic acid under reflux condition in oil bath.
Entry
1
Ar–X
Base
Catalyst (mol%)
1
Solvent
NMP
Temperature (°C)
Time (h)
24
Conversion (%)
90
K2CO3
150
I
I
2
3
K2CO3
K2CO3
1
THF
THF
80
80
1
95
20
0.5
24
I
I
I
I
MeO
MeO
MeO
MeO
NC
4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0.5
1
DMF
130
130
130
130
80
4
60
5
DMF
1.5
1
100
100
20
6
2
DMF
7
1
DMF
6
Br
8
1
1,4-dioxane
methanol
methanol
1
10
I
I
MeO
MeO
9
1
80
3
100
0
10
1
80
5
Br
11
K2CO3
1
methanol
80
5
40
Br
NC

A.R. Hajipour et al. / Inorganica Chimica Acta 370 (2011) 531–535
533
Table 2
Table 2 (continued)
Suzuki reaction of aryl halides with phenylboronic acid using catalyst
A under
conventional heating conditions using an oil bath.a
Entry Ar1–X
Ar2
Time
(h)
Conversion Yielda
(%)
(%)
Entry Ar1–X
1
Ar2
Ph
Time
(h)
Conversion Yielda
(%)
(%)
16
3,4-MeO
C6H3
10
85
82
Br
4
100
88
I
2
Ph
12
95
86
I
17
1-Naph
10
80
75
Br
Br
MeO
3
Ph
Ph
3
98
70
92
60
Br
Br
4
5
10
18
3,4-MeO
C6H3
10
85
75
Ph
10
65
53
Br
a
Reaction condition: aryl bromide; 1 mmol, phenylboronic acid; 1.2 mmol,
K2CO3; 1 mmol, catalyst; 3 0.01 mmol, temperature; 130 °C.
6
Ph
Ph
5
9
100
100
92
80
Cl
Br
observed (Table 3, entry 2). These results prompt us to extend the
optional process to less reactive and non-expensive aryl chlorides.
Chlorobenzene did not transform to the coupling product (Table 3,
entry 13), however 4-chlorobenzaldehyde changed to desired
product with 100% conversion (Table 2, entry 14). 1-Bromo-3-chlo-
robenzene led to the formation of only one product which is due to
the chemo-selectivity of this method (Table 2, entry 6). Trying to
apply 2-bromopyridine as an efficient substrate was not successful
(Table 2, entry 12). We also tried the coupling reaction for more
steric hindrance arylhalides and arylboranes with high yield and
in short reaction time Tables 2 and 3, entries 15–18).
7
Br
OHC
8
Ph
10
10
100
100
87
80
Br
NC
9
A mechanistic description of the Suzuki reaction has been pre-
sented in Scheme 2. Initially, Pd(II) converts to Pd(0) [35], followed
by the oxidative addition of aryl halide to Pd(0) to form aryl palla-
dium (II) intermediate 1. Phenylboronic acid which is activated by
K2CO3 reacts with intermediate 1. After transmetallation reaction,
the intermediate 2 obtains. Finally, reductive elimination of inter-
mediate 2 produces the desired coupling products. Several study in
palladacycle catalyst cross-coupling indicated that the catalyst role
in these chemistry is probably involve the palladium nanoparticles
and palladacycles behave as a mere resource for producing nano-
particles Pd(0) [36–38]. To evaluate the suggested mechanism,
the mercury drop test was employed, since mercury leads to the
amalgamation of the surface of a heterogeneous catalyst. In con-
trast, Hg(0) is not expected to have a poisoning effect on homoge-
neous palladium complexes, where the Pd(II) metal center is
tightly bound to the ligand [36,37]. When a drop of Hg(0) was
added to the reaction mixtures of bromobenzene under mentioned
optimized conditions at t = 0 min and heated the reaction mixture
using microwave irradiation, no catalytic activity was observed for
the catalyst.
H3COC
H3COC
10
11
Br
Ph
Ph
13
13
100
60
90
50
COCH3
Br
12
Ph
15
0
1
N
Br
Cl
13
14
Ph
Ph
15
10
0
0
95
90
Cl
OHC
15
4-MeOC6H4 12
80
75
Br
3. Experimental
3.1. General
1H NMR spectra were recorded using 500 and 400 MHz in CDCl3
solutions at room temperature (TMS was used as an internal

534
A.R. Hajipour et al. / Inorganica Chimica Acta 370 (2011) 531–535
Table 3
Table 3 (continued)
Suzuki reaction of aryl halides with phenylboronic acid using catalyst
A under
Entry Ar1–X
Ar2
Time
Conversion Yielda
microwave irradiation.a
(min)
(%)
(%)
Entry Ar1–X
1
Ar2
Ph
Time
(min)
Conversion Yielda
16
3,4-MeO
C6H3
20
80
78
Br
(%)
(%)
2
100
90
I
17
1-Naph
20
87
80
2
Ph
15
90
85
Br
Br
I
MeO
3
Ph
Ph
2
100
70
95
60
Br
Br
18
3,4-MeO
C6H3
20
95
85
4
5
15
Ph
15
60
45
Br
a
Reaction condition: aryl bromide; 1 mmol, phenylboronic acid; 1.2 mmol,
K2CO3; 1 mmol, catalyst; 3 0.01 mmol, temperature; 130 °C.
6
Ph
Ph
2
100
100
90
85
Cl
Br
7
15
Br
NH
2
Pd
Br
MeO
OHC
8
Ph
15
15
100
100
90
85
Br
OMe
2
(3)
NC
9
H3COC
H3COC
ArX
Ar-Ph
10
11
Br
Ph
Ph
15
15
100
60
90
50
PdL
2
Pd(0)
Reductive
Elimination
Oxidative
Addition
COCH3
Br
L
L
12
Ph
20
0
0
Ar
Pd
X
Ar
Pd
L
Ph
(1)
N
Br
Cl
(2)
13
14
Ph
Ph
20
20
0
0
L
Transmetallation
PhB(OH)3K + KHCO3
100
90
Cl
B(OH)
OHC
+K CO3
2
15
4-MeOC6H4 15
88
85
Br
B(OH)4K + KHCO3
PhB(OH)2+ K2CO3+ H2O
Scheme 2. Proposed mechanism for Suzuki reaction.

A.R. Hajipour et al. / Inorganica Chimica Acta 370 (2011) 531–535
535
standard) on a Bruker, Avance 500 instrument (Rheinstetten,
4. Conclusions
Germany) and Varian 400 NMR. The FT-IR adsorption spectra were
recorded on a Jasco-680 (Jasco, Japan) FT-IR spectrophotometer
with KBr pellets. Vibration bands were reported as wave number
(per centimeter). Homoveratrylamine, aryl halides, phenylboronic
acid, solvents and palladium acetate were bought from Merck
and Aldrich and used as received.
In this work, we used ortho-palladated complex of homoverat-
rylamine as an efficient catalyst for the Suzuki reaction of various
aryl halides. This catalyst was stable under heating conditions
without using inert atmosphere due to its inherent air and mois-
ture resistances. A general protocol was applied for the palla-
dium-catalyzed Suzuki reaction of electron-rich and electron-
poor aryl halides using phenylboronic acid. The catalytic amounts
of this catalyst converted various aryl bromides and iodides to the
corresponding products in good yields. Moreover, the aryl chlo-
rides with electron withdrawing group were converted to the cor-
responding products in excellent yields.
3.2. Synthesis of palladacycle complex (A)
[Pd{C6H2(CH2CH2NH2)–(OMe)2,3,4} (l-Br)]2 (A) was prepared
using our reported method [31,32].
Acknowledgments
3.3. General procedure for the Suzuki reaction of aryl halides with
phenylboronic acid
We gratefully acknowledge the funding support received for
this project from the Isfahan University of Technology (IUT), IR
Iran. Further financial support from Center of Excellence in Sensor
Research and Green Chemistry (IUT) is gratefully acknowledged.
A mixture of the appropriate aryl halide (1 mmol), phenylbo-
ronic acid (1.2 mmol), palladium pre-catalyst A (1 mmol%), K2CO3
(1 mmol) was added to DMF (2 mL) in round-bottom flask
equipped with condenser and placed into the Milestone Micro-
wave or an oil bath. Initially the microwave irradiation of was
set at 500 W, the temperature was ramped from room temperature
to the desired temperature of 130 °C. Once this was reached, the
reaction mixture was held at this temperature until the reaction
was completed. During this time, the power was modulated auto-
matically to keep the reaction mixture at 130 °C. The mixture was
stirred continuously during the reaction. After the reaction was
completed (monitored by TLC), the mixture was cooled to room
temperature and the reaction mixture was poured into a separat-
ing funnel and water (30 mL) and n-hexane (30 mL) were added.
The organic phase was dried over CaCl2, filtered, and the solvent
was evaporated. The residue was purified by silica gel column
chromatography (n-hexane:EtOAc, 90:10) or recrystallization.
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