Active palladium catalyst supported by bulky diimine ligand catalyzed Suzuki-Miyaura coupling reaction in water under phosphane-free and low catalyst loading conditions

Article abstract of DOI:10.1002/aoc.3110

A new catalytic system based on palladium and bulky diimine ligand for Suzuki-Miyaura coupling reaction of aryl iodides, bromides and chlorides in neat water is described. The desired biphenyl products were obtained in high to excellent yields for aryl iodides and bromides in the presence of low catalyst loading. Air-stable catalyst has been recycled for the reaction of iodobenzene with phenylboronic acid for five consecutive runs. Copyright

Full text of DOI:10.1002/aoc.3110

Full Paper
Received: 8 October 2013
Revised: 10 November 2013
Accepted: 11 November 2013
Published online in Wiley Online Library: 6 February 2014
(wileyonlinelibrary.com) DOI 10.1002/aoc.3110
Active palladium catalyst supported by bulky
diimine ligand catalyzed Suzuki–Miyaura
coupling reaction in water under phosphane-
free and low catalyst loading conditions†
Mohammad Gholinejada*, Vahid Karimkhanib,c and Il Kimc
A new catalytic system based on palladium and bulky diimine ligand for Suzuki–Miyaura coupling reaction of aryl iodides,
bromides and chlorides in neat water is described. The desired biphenyl products were obtained in high to excellent yields
for aryl iodides and bromides in the presence of low catalyst loading. Air-stable catalyst has been recycled for the reaction
of iodobenzene with phenylboronic acid for five consecutive runs. Copyright © 2014 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: Suzuki; palladium; bulky diimine; supported; water
as a cheap and safe solvent instead of expensive, flammable and toxic
Introduction
organic solvents reduces environmental damage caused by organic
solvents.[33] Thus in recent years there has been growing interest in
Palladium-catalyzed cross-coupling reactions have become a key
the development of the Suzuki–Miyaura coupling reaction in water.[34]
and powerful tool in organic synthesis for the formation of
carbon–carbon bonds.[1,2] Among the different types of palladium-cata-
lyzed reaction, the Suzuki–Miyaura reaction, which is the reaction be-
Experimental
tween aryl halides and arylboronic acids, represents possibly the most
important and widely used one.[3–7] Over recent years, the Suzuki–
General
1H NMR spectra were recorded at 250 and 400 MHz and 13C NMR
Miyaura reaction has had an important impact on industry and aca-
demic laboratories in the synthesis, for example, of pharmaceuticals,
spectra were recorded at 62.9 and 100 MHz in CDCl3 using
fine chemicals and polymers, and the total synthesis of natural prod-
tetramethylsilane (TMS) as internal standard. Organic solvents were
ucts.[1–7] Palladium-catalyzed carbon–carbon and carbon–heteroatom
purified by known procedures and stored over molecular sieves
bond formation reactions have been traditionally performed using
(4Å). All reagents used in this study were purchased from Aldrich
and Merck Chemical and used without further purification.
palladium catalysts in the presence of various phosphane ligands.[8-18]
These ligands suffer from issues such as difficulty of synthesis, and poor
thermal and air stability. Moreover, most phosphane ligands are
expensive, not easily available, unrecoverable, and also toxic, giving rise
to particular environmental and economic concerns, especially when
large-scale operations are under consideration. To avoid these
drawbacks, there is a growing interest in using phosphane-free and
eco-friendly ligands such as diazabutadienes,[19] oximes,[20–24] N-
heterocyclic carbenes[25–30] and amine-bridged (bis)phenol ligands[31]
in the presence of palladium pre-catalysts.
Previous findings reveal that the bulky electron-rich ligands show
high activity in different palladium-catalyzed coupling reactions by
stabilizing Pd(0) intermediates and avoiding precipitation of the metal
in homogeneous catalysis.[32] The electron richness imparted to the
palladium by the ligand assists the cleavage of the Ar-X bond in the
oxidative addition step, while the steric bulk of the ligand promotes
reductive elimination of the desired coupling product.
Catalyst Synthesis
Primary ligand (Scheme 1, compound 1)
Ligands and catalysts were synthesized following a procedure
reported in the literature,[35] which will briefly be explained in
the following paragraphs.
*
Correspondence to: Mohammad Gholinejad, Department of Chemistry,
Institute for Advanced Studies in Basic Sciences (IASBS), Gava zang, PO
Box 45195–1159, Zanjan 45137–66731, Iran. Email: gholinejad@iasbs.ac.ir
†
This paper is dedicated to Professor Nasser Iranpoor on the occasion of his 60th
birthday.
a Department of Chemistry, Institute for Advanced Studies in Basic Sciences
(IASBS), Zanjan 45137-66731, Iran
Today, environmental consciousness encourages the chemical
community to search for more environmentally sustainable chemical
processes for chemical syntheses. For this purpose, the use of new
heterogeneous recyclable catalysts and of less toxic materials as solvents
and reagents are two important challenging subjects. The use of water
b Department of Polymer Engineering and Color Technology, Amirkabir Univer-
sity of Technology, PO Box 15875-4413, Tehran, Iran
c
WCU Center for Synthetic Polymer Bioconjugate Hybrid Materials, Department of
Polymer Science and Engineering, Pusan National University, Pusan 609-735, Korea
Appl. Organometal. Chem. 2014, 28, 221–224
Copyright © 2014 John Wiley & Sons, Ltd.

M. Gholinejad et al.
4,4′-((4-methoxyphenyl)methylene)bis(2,6-dimethylaniline) was
prepared by reacting 2,6-dimethylaniline with p-methoxybenzaldehyde.
2,6-Dimethylaniline was heated to 130 °C under an inert
atmosphere to which p-methoxybenzaldehyde dissolved in
concentrated HCl and THF were added over a period of 1 h.
The reaction mixture was refluxed for 24 h. After cooling to room
temperature, it was basified with aqueous NaOH and extracted
with CHCl3. The combined organic layers were washed with wa-
ter and brine, respectively. The solution was dried over MgSO4
and pentane was added to precipitate the product, which was
then purified through recrystallization twice in CHCl3 using
pentane to obtain the product as a pure creamy white crystalline
powder.
purification of the product was achieved by flash chromatog-
raphy using hexane–EtOAc to give the desired biphenyl
compound.
Results and Discussion
Recently, different bidendate α-diimine ligands coordinated to nickel
were used as an active catalyst in ethylene polymerization.[35]
Condensations of bulky ortho-substituted anilines bearing
remote push–pull substituents with acenaphthenequinone, in
the presence of nickel pre-catalysts, give nickel catalyst
precursors for which the polymerization activity varied with
substituents on the catalyst. In the present work, we report the
synthesis of the palladium complex 4 catalyst (Fig. 1) and its
performance in the Suzuki–Miyaura coupling reaction of
structurally different aryl halides under low loading of catalyst
in water as an eco-friendly medium. Catalyst synthesis steps
were characterized by 1H NMR, mass, TGA and FT-IR analysis
(see supporting information). TGA of compound 4 showed three
steps of weight losses. The first weight loss occurred between
25 and 100°C, with an observed weight loss of 3.3% corresponding
to the loss of acetonitrile ligand. The second and third weight losses
Synthesis of ligand (N,N’-(acenaphthylene-1,2-diylidene)bis(4-((4-
amino-3,5-dimethylphenyl)(4-methoxyphenyl)methyl)-2,6-
dimethylaniline)) (Scheme 1, compound 2)
To a methanol solution of 4,4′-((4-methoxyphenyl)methylene)
bis(2,6-dimethylaniline), acenaphthenequinone (AQN) in 2:1
ratio and a catalytic amount of formic acid were added. The
reaction mixture was stirred overnight at 50 °C. After the
reaction, methanol was removed under vacuum with a rotary
evaporator and the resulting product was purified via column
chromatography (ethyl acetate–hexane, silica
gel). The solvent was evaporated to obtain
O
the product, which was then dried at 50 °C
under vacuum.
NH2
CHO
OMe
Me
Me
HCl, THF
Palladium complex synthesis (scheme 1,compound 4)
+
reflux, 24h
The Pd–diimine catalyst used in this study,
[(ArN-C(AQN)-(AQN)C-NAr)Pd(CH3)(N-CMe)]SbF6
(Ar-4,4′-((4-methoxyphenyl)methylene)bis(2,6-
dimethylaniline)), was synthesized following a
similar procedure reported in the literature,[36]
which will briefly be explained in the
following. Under an inert atmosphere, (COD)
PdClMe and diimine ligand were dissolved in
a 1:1 ratio in diethyl ether. The reaction was
run for 24 h at room temperature. The air-stable
orange precipitate formed was recovered by fil-
tration, washed with 3 × 25 ml diethyl ether and
dried under vacuum. For synthesizing the final
catalyst, AgSbF6 was added to the acetonitrile
solution of [(ArN-C(AQN) - (AQN)C-NAr)Pd(CH3)
(Cl) in a 1:1 ratio at room temperature, resulting
in immediate precipitation of AgCl. This mixture
was allowed to stir overnight. AgCl was re-
moved via filtration and the solvent was
evaporated.
H2N
NH2
1
O
O
MeOH,HCO2H
reflux, 24 h
N
N
+
1
O
O
NH2
H2N
2
O
O
Et2O
24h, r.t.
Pd
2
+
N
N
Cl
Pd
Cl
NH2
O
H2N
3
-
SbF6
General Experimental Procedure for the
Suzuki–Miyaura Reaction
O
Palladium catalyst (0.8 mol%, 10 mg), aryl
halide (1 mmol), arylboronic acid (1.5 mmol),
potassium carbonate (1.5 mmol) and distilled
water (2 ml) were added to a 5 ml flask. The
mixture was stirred for an appropriate reaction
time at 100 °C and the progress of the reaction
was monitored by GC. After completion of the
reaction, the aqueous layer was extracted with
ethyl acetate or hexane (5 × 1 ml). Further
r.t.
-
3+ CH3CN + AgSbF6
N
N
N
+
Pd
C
NH2
H2N
Me
4
Figure 1. Synthesis steps of palladium catalyst.
wileyonlinelibrary.com/journal/aoc
Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 221–224

Suzuki reactions catalyzed by Pd supported by bulky diimine ligand
occurred between 100 and 275 °C and between 275 and 375 °C and
may be related to the loss of methyl and 1,2-dihydroacenaphthylene.
In order to find optimized reaction conditions for the
Suzuki–Miyaura coupling reaction, less reactive 4-bromoanisole
was selected as a model compound and its coupling reaction
with phenylboronic acid was studied under different reaction
conditions. Our initial investigation focused on the effect of
various solvents and using different bases (Table 1).
Table 2. Effect of different reaction temperatures on the reaction of
4-bromoanisole and phenylboronic acid in the presence of catalyst
using K2CO3 as a base in water within 15 h
Cat. (0.8 mol%)
Br
K2CO3, H2O (2 mL)
15 h
Ph-B(OH)
+
2
The results indicated that in the presence of catalyst, using water
as a solvent and K2CO3 as a base, the best reaction yield was
obtained under heterogeneous conditions. However, to ensure
that the temperature was optimal, the reaction was performed at
different reaction temperatures (Table 2).
OMe
OMe
Entry
Temperature (°C)
Yield (%)
1
2
3
4
50
60
42
64
73
88
Using the optimized reaction conditions, we attempted to
apply the catalyst to Suzuki–Miyaura coupling reactions of
structurally different aryl halides with arylboronic acids (Table 3).
The results of Table 3 indicated that, using this protocol, the reac-
tion of aryl iodides proceeded smoothly to produce the desired
biphenyl compounds in high to excellent yields (entries 1–4). Also,
the reaction of aryl bromides with arylboronic acids proceeded well
and afforded the corresponding biphenyl products in high to
excellent yields (entries 5–15). Reactions of 5-bromopyrimidine
and 3-bromothiophene as heterocyclic aryl bromides with
phenylboronic acid performed well and afforded the desired
products in 94% and 89% isolated yields, respectively. In addition,
we studied reaction of 4-chlorotoluene, 4-chloronitrobenzene and
4-chlorobenzonitril under optimized reaction conditions. The
desired biphenyls were isolated in 48%, 58% and 65% isolated
yields, respectively, after 24h.
80
100
Table 3. Reaction of different aryl halides with arylboronic acids in
the presence of the catalyst in water
Cat. (0.8 mol%)
X
K2CO3, H2O (2 mL)
100 °C
Ph-B(OH)
+
2
R
R
Since the palladium precursors are expensive and also there are
typically strict guidelines to limit the levels of palladium impurity in
the drug product, separation of the palladium catalyst is highly
attractive from economic and environmental viewpoints. Finally,
we studied the recycling of the catalyst for the reaction of
Entry
R(X)
Ar-B(OH)2 Time Product Isolated
(h)
yield (%)
1
H(I)
Ph
Ph
2
5
1a
1b
1c
94
92
93
90
85
88
86
86
92
90
82
85
92
86
85
88
48
65
58
2
p-Me(I)
p-Me(I)
p-OMe(I)
H(Br)
3
4-Me-C6H4
5
4
Ph
7
1d
1a
1d
1e
1b
1f
Table 1. Effect of different solvents and bases
5
Ph
16
15
16
20
3
6
p-OMe(Br)
p-OMe(Br)
p-Me(Br)
p-CN(Br)
p-CN(Br)
p-NO2(Br)
p-NO2(Br)
p-Ph(Br)
Ph
7
4-Me-C6H4
Cat. (0.8 mol%)
8
Ph
Br
K2CO3, H2O (2 mL)
9
Ph
100 °C, 15 h
Ph-B(OH)
+
2
10
11
12
13
14
15
15
16
17
18
4-Me-C6H4
3
1 g
1 h
1i
Ph
6
OMe
OMe
4-Me-C6H4
6
Ph
Ph
Ph
Ph
Ph
Ph
Ph
20
24
15
10
24
24
24
1j
2-Bromothiophene
2-Bromopyridine
5-Bromopyrimidine
p-Me(Cl)
1 k
1 l
Entry
Solvent
DMF
Base
Et3N
Yield (%)
1
22
40
46
34
72
25
76
88
29
54
42
43
62
70
1 m
1b
1f
2
DMF
KOH
3
DMF
K2CO3
Et3N
p-CN(Cl)
4
Toluene
Toluene
H2O
p-NO2(Cl)
1 h
5
K2CO3
Et3N
6
iodobenzene (5mmol) with phenylboronic acid (7.5mmol). For this
purpose, the heterogeneous solid catalyst was separated by
centrifugation from the reaction mixture and was charged into
another batch of the reaction for five runs (Table 4).
Finally, in order to gain information about the active catalytic
species at 100 °C, we studied the hot filtration test for the
reaction of 4-bromoanisole and phenylboronic acid. The reaction
mixture was filtered after 2 h at the reaction temperature (49%
GC yield after 2 h) and allowed the filtrate to react. GC analysis
7
H2O
KOH
8
H2O
K2CO3
DBU
9
H2O
10
11
12
13
14
Dioxane
Dioxane
Dioxane
DMF-H2O
DMF-H2O
Et3N
KOH
K2CO3
Et3N
K2CO3
Appl. Organometal. Chem. 2014, 28, 221–224
Copyright © 2014 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

M. Gholinejad et al.
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In this article we studied the catalytic activity of bulky diimine
palladium complex in Suzuki–Miyaura coupling reactions of
structurally different aryl halides in water. In the presence of
low catalyst loading, aryl iodides and bromides reacted efficiently
and gave the desired biphenyl products in high to excellent
yields. Reactions of less reactive aryl chlorides were sluggish
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Grant No. R32-2008-000-10174-0) and the Fusion Research Program
for Green Technologies through the National Research Foundation
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Supporting Information
Additional supporting information may be found in the online
version of this article at the publisher’ web-site.
wileyonlinelibrary.com/journal/aoc
Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 221–224