Catalytic activity of 1-methylimidazole-based phosphine ligands in the palladium-catalyzed Suzuki coupling reaction

Article abstract of DOI:10.1002/aoc.3249

The catalytic activities of three N-methylimidazole-based phosphine ligands in the Suzuki coupling reaction were tested using PdCl₂ as the catalyst. The results showed all three phosphine ligands exhibited excellent activity towards the Suzuki reaction, and the catalytic activity decreased with increasing number of imidazole groups.

Full text of DOI:10.1002/aoc.3249

Full Paper
Received: 15 October 2014
Revised: 17 October 2014
Accepted: 17 October 2014
Published online in Wiley Online Library: 2 December 2014
(wileyonlinelibrary.com) DOI 10.1002/aoc.3249
Catalytic activity of 1-methylimidazole-based
phosphine ligands in the palladium-catalyzed
Suzuki coupling reaction
Jin Tao Guan*, Xiao Ming Song, Zhi Yong Zhang, Ben Mei Wei
and Zhi Qun Dai
The catalytic activities of three N-methylimidazole-based phosphine ligands in the Suzuki coupling reaction were tested using
PdCl2 as the catalyst. The results showed all three phosphine ligands exhibited excellent activity towards the Suzuki reaction,
and the catalytic activity decreased with increasing number of imidazole groups. Copyright © 2014 John Wiley & Sons, Ltd.
Keywords: 1-methylimidazole; phosphine ligand; Suzuki coupling reaction
Product yields were calculated by GC, using a 6890N Network GC
Introduction
system (Agilent Technologies). 1H NMR and 31P NMR spectra were
The palladium-catalyzed Suzuki cross-coupling reaction of arylboronic
acids and aryl halides is one of the most powerful and straightforward
methods for the formation of C–C bonds in organic synthesis.[1–5] This
method has been widely used for the synthesis of pharmaceuticals,
bioactive compounds, natural products and optical materials, on both
laboratory and industrial scales. Since the first discovery of the Suzuki
cross-coupling reaction,[6] numerous efforts have been made to
increase the reaction efficiency.[4,7,8] In general, the reaction is carried
out in the presence of palladium–phosphine catalysts because they
provide excellent catalytic activity for the coupling reaction.[2,9–13] In
spite of these developments, there is still a need for readily available
ligands which lead to highly active catalyst systems and are easily
tunable and easy to scale up. 1-Substituted imidazole-based
phosphines,[14] notably C2 substituted phosphines, which can be syn-
thesized in one or two reaction steps on multi-gram to kilogram scales
and allow high tenability have attracted increasing interest in catalysis,
such as alkene isomerizations,[15,16] Buchwald–Hartwig aminations,[17]
Heck reactions,[18] hydrosilylation of alkenes,[19] Suzuki reactions,[17,20]
C–H bond activation[21] and hydroxylation of aryl halides.[22] However,
most research has focused on N-arylimidazole; just a few studies
involving N-alkylimidazole[19,23] have been reported. As part of an
ongoing project on palladium-catalyzed reactions,[24,25] we report
herein an investigation of the catalytic activity of three
1-methylimidazole-based phosphines in the Suzuki reaction.
recorded with a Varian Mercury Plus 400MHz spectrometer.
General Procedure for Suzuki Coupling Reaction
A mixture of aryl halide (2 mmol), phenylboronic acid (331.8 mg,
2.5 mmol), base (4 mmol), PdCl2 (1.77 mg, 0.01 mmol), 1a (532.57 mg,
0.02 mmol) and H2O (3 ml) under nitrogen in a pressure tube was
heated to given temperature and maintained for a given time. Then
it was cooled and extracted with diethyl ether (4 × 5.0 ml) and dried
with Na2SO4. After evaporation under reduced pressure, the residue
was purified using silica gel to give the desired product.
Results and Discussion
The three 1-methylimidazole based-phosphines 1a–c were synthe-
sized according to literature procedures, and were characterized
1
using H NMR, 13C NMR and 31P NMR spectroscopy and melting
point measurements. We then embarked on evaluating their activity
in the Suzuki reaction. Bromobenzene and phenylboronic acid were
selected as the model substrates to optimize the reaction conditions.
Our initial investigation was focused on the influence of various ba-
ses and various ligands at 80°C for 0.5 h (Table 1). The results show that
K3PO4 is the most effective base (Table 1, entry 4), the other inorganic
and organic bases being inferior. We also investigated the activities of
ligands in the model reaction using K3PO4 as the base (Table 1, entries
4, 8 and 9). All three ligands exhibit good catalytic activity towards the
reaction. Ligand 1a gives the best yield (Table 1, entry 4), while ligands
Experimental
General
*
Correspondence to: Jin Tao Guan, School of Chemical and Environmental
Engineering, Wuhan Polytechnic University, Wuhan, PR China. Email:
guanjintao@126.com
All reactions were carried out under an atmosphere of highly
purified nitrogen using standard Schlenk or vacuum-line tech-
niques. All solvents were used after degassing with nitrogen.
Phosphine ligands 1a–c[26] (Fig. 1) were prepared according to
literature procedures.
School of Chemical and Environmental Engineering, Wuhan Polytechnic
University, Wuhan, PR China
Appl. Organometal. Chem. 2015, 29, 87–89
Copyright © 2014 John Wiley & Sons, Ltd.

J. T. Guan et al.
Conclusions
In summary, we investigated the activities of 1-methylimidazole-
based phosphine ligands in the Suzuki reaction. The results showed
that the ligand with one 1-methylimidazole substituent gave the
best yield. Thus, ligand 1a utilized in the Pd-catalyzed Suzuki
Figure 1. 1-Methylimidazole-based phosphines.
Table 2. Effect of solvent on the Suzuki coupling reactiona
1b and 1c with two and three 1-methylimidazole substituents, respec-
tively, give slightly lower yields (Table 1, entries 8 and 9). Probably the
overcrowded steric hindrance prevents the oxidative addition. Then,
we investigated the effect of solvent on the model reaction. It is evi-
dent from Table 2 that the reaction gives good yields in strong polar
solvents (Table 2, entries 1, 7, 8 and 12), the best yield being obtained
in ethanol (Table 2, entry 7), which is considered an eco-friendly and
desirable solvent for organic synthesis.[27] In contrast, the commonly
used DMF or 1,4-dioxane give poor yields (Table 2, entries 2 and 5).
Thus the optimized reaction conditions are found to be 0.5 mol% of
PdCl2, 1mol% of 1a, 2 equiv. of K3PO4, in ethanol at 80°C.
Entry
Solvent
H2O
Yield (%)b
1
79
15
26
2
2
DMF
3
Toluene
Acetone
1,4-Dioxane
THF
4
5
4
6
20
96
91
76
2
7
EtOH
The Suzuki reactions of a variety of aryl bromides and aryl chlorides
with phenylboronic acid were studied under the optimized conditions.
The results are summarized in Table 3. The reactions proceed well for
all the substrates examined, and expected products are isolated in
moderate to excellent yields. Alkyl-substituted bromobenzene reacts
with phenylboronic acid to give the corresponding products in
excellent yields (Table 3, entries 2–7), and an obvious decrease is
observed in the case of para-C12H25-bromobenzene and ortho-
methylbromobenzene (Table 3, entries 8 and 9). In the case of
fluorine-containing substrates, the corresponding products are
obtained in excellent yields (Table 3, entries 10–14). However,
moderate yields are obtained for difluorine-substituted substrates
(Table 3, entries 15 and 16). The reaction of 4-bromobiphenyl with
phenylboronic acid gives the desired product in good yield (Table 3,
entry 17). Less active aryl chlorides, such as 4-chloroacetophenone,
also react with phenylboronic acid to give the desired product
when the reaction time is prolonged to 24 h (Table 3, entry 18).
However, a poor yield is obtained for chlorobenzene even
after 24h (Table 3, entry 19). These results also indicate that a
variety of important functional groups can be tolerated under the
reaction conditions.
8
MeOH
9
Isopropanol
Ethyl acetate
Et3N
10
11
12
18
90
Acetonitrile
aReaction conditions: bromobenzene (2 mmol), phenylboronic acid
(2.5 mmol), K3PO4 (4 mmol), PdCl2 (0.01 mmol), 1a (0.02 mmol) and
solvent (3 ml) at 80°C for 0.5 h in a pressure tube.
bGC yields.
Table 3. Suzuki coupling reaction of aryl halides with phenylboronic acida
Entry
R
X
Yield (%)b
1
H
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
99
97
96
94
95
94
93
80
85
96
96
94
90
94
46
40
72
85c
30c
2
4-Methyl
4-Propyl
4-Butyl
4-Pentyl
4-Octyl
4-Decyl
3
4
5
6
Table 1. Effect of base and ligand on the Suzuki coupling reactiona
7
8
4-Dodecyl
2-Methyl
9
10
11
12
13
14
15
16
17
18
19
4-Trifluoromethoxy
4-Fluoro
Entry
Base
NaOH
Ligand
Yield (%)b
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1b
1c
19
13
46
79
50
56
55
68
56
3-Fluoro
K2CO3
2-Fluoro-4-methoxy
2-Fluoro-4-formyl
2,3-Difluoro
3,5-Difluoro
4-Phenyl
Na2CO3
K3PO4
NaHCO3
Et3N
CH3CH2ONa
K3PO4
4-Acetyl
H
K3PO4
aReaction conditions: aryl halide (2 mmol), phenylboronic acid
(2.5 mmol), K3PO4 (4 mmol), PdCl2 (0.5 mol%), 1a (1 mol%) and
EtOH (3 ml) at 80°C for 3 h in a pressure tube.
aReaction conditions: bromobenzene (2 mmol), phenylboronic acid
(2.5 mmol), base (4 mmol), PdCl2 (0.01 mmol), ligand (0.02 mmol)
and H2O (3 ml) at 80°C for 0.5 h in a pressure tube.
bGC yields.
bIsolated yields.
cPdCl2 (1 mol%), 1a (2 mol%), 80°C for 24 h.
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Appl. Organometal. Chem. 2015, 29, 87–89

Suzuki reaction catalyzed by 1-methylimidazole-based phosphine ligands
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Acknowledgements
We gratefully acknowledge financial support from the Foundation
of Hubei Provincial Department of Education (no. Q20111704 and
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