PEG-modified N-heterocyclic carbene ligands for highly efficient and recyclable Pd-catalyzed Heck reaction in water

Article abstract of DOI:10.1007/s11243-013-9765-x

A water-soluble and air-stable Pd(OAc)₂/mPEG _n MeImI system was found to be a highly efficient and reusable catalyst for the coupling of aryl halides and styrene in neat water using K₂CO₃ as base. After extraction, the catalytic system could be reused several times with only a slight decrease in its activity.

Full text of DOI:10.1007/s11243-013-9765-x

Transition Met Chem (2014) 39:11–15
DOI 10.1007/s11243-013-9765-x
PEG-modified N-heterocyclic carbene ligands for highly efficient
and recyclable Pd-catalyzed Heck reaction in water
Yulan Liu
•
Yan Wang Ensheng Long
•
Received: 1 August 2013 / Accepted: 26 September 2013 / Published online: 6 November 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract A water-soluble and air-stable Pd(OAc)2/
mPEG MeImI system was found to be a highly efficient
organic products by simple purification, leading to the pos-
sibility of reuse of the catalyst [16, 17].
n
and reusable catalyst for the coupling of aryl halides and
styrene in neat water using K CO as base. After extrac-
More recently, poly(ethylene glycol) (PEG) has been
successfully used as an alternative reaction medium [18–
21]. Neutral water-soluble ligand substituents such as
poly(ethylene glycol) (PEG) are an attractive alternative to
ionic substituents. To date, there are only a few examples
of PEG-modified NHC ligands used in transition metal-
catalyzed organic reactions [22–26].
2
3
tion, the catalytic system could be reused several times
with only a slight decrease in its activity.
Introduction
Zhang and coworkers reported that Pd(OAc) in PEG-
2
The field of N-heterocyclic carbenes (NHCs) as ligands in
transition metal chemistry remained dormant until Arduengo
et al. [1] published initial reports in 1991 that ignited a rap-
idly growing research field. In this initial report, it was shown
that palladium NHC complexes are excellent catalysts for a
number of Heck reactions, exemplifying high catalyst
activity and a remarkably long catalyst lifetime [2–7]. The
combination of metal catalysis and water has led in recent
years to the development of a huge number of new and
greener synthetic methodologies [8–11]. The most popular
strategy for obtaining a water-soluble catalyst is to modify
the ligand with a water-soluble functional group, including
sulfonate [12, 13], ammonium [14], carboxylate [12], and
polyoxyethylene moieties [15]. The water-soluble catalytic
system may be easily separated from the water-insoluble
functionalized imidazolium salts constituted a highly effi-
cient and recyclable catalytic system for the Heck reaction
of aryl bromides and activated aryl chlorides in the absence
of ligands, but they used them as reaction medium also
[27]. In the PEG-supported imidazolium salts, PEG not
only remarkably diluted the solvent, but also constituted a
bulky imidazolium salt, which possibly results in the active
NHC-palladium catalyst in situ.
Herein, we describe the results of our research into the
development of Pd(OAc) /mPEG MeImI as an efficient
2
n
and recyclable catalyst for the Heck reaction of aryl bro-
mides and aryl chlorides in water (Scheme 1).
Experimental
General considerations
Electronic supplementary material The online version of this
article (doi:10.1007/s11243-013-9765-x) contains supplementary
material, which is available to authorized users.
All chemicals employed in the synthesis were analytical
grade, obtained commercially, and used as received with-
out further purification. Solvents were dried with standard
Y. Liu (&) Á Y. Wang Á E. Long (&)
College of Architecture and Environment, Sichuan University,
Chengdu 610207, Peoples Republic of China
e-mail: 625901300@qq.com
1
methods and freshly distilled prior to use. NMR spectra ( H
1
3
400 MHz, C 100 MHz) were performed on a Bruker
Avance III 400 MHz spectrometer. The NMR studies were
carried out in high-quality 5-mm NMR tubes. Signals are
E. Long
e-mail: Longes2@163.com
123

1
2
Transition Met Chem (2014) 39:11–15
R'
Me
OTs
NaI
Me
N
I
X
O
O
n
n
[
Pd]
N
Me
N
R'
TsCl
Water
Reflux
R
R
1
I
,2-product
Me
OH
Me
N
Me
O
O
Scheme 2 Heck cross-coupling reaction of aryl halides and styrene
n
n
=
7,
mPEG MeImI
n = 7, mPEG350
n = 16, mPEG750
1, n
7
(mPEG MeImI, n = 7, n = 16) were prepared by a mod-
n
2, n = 16, mPEG16MeImI
ification of the literature method [28].
Scheme 1 Synthesis of PEG-functionalized NHC ligands
mPEG MeImI and mPEG16MeImI
7
Typical procedure for the Heck cross-coupling of aryl
halides with styrene
quoted in parts per million as d downfield from TMS as an
internal standard. Coupling constants (J values) are given
in Hertz. NMR multiplicities are abbreviated as follows:
s = singlet, d = doublet, t = triplet, m = multiplet signal.
GC–MS analyses were carried out on an Agilent 6,890 GC
with 5,973 mass spectral detectors, using an AT.SE-30
column of 50 m length, 0.32 mm diameter, and 0.5 lm
film thicknesses. The PEG-modified NHC ligands
The appropriate amounts of mPEG MeImI, base, and metal
n
precursor were added to the required water (3.0 mL). The
mixture was stirred for 5 min; then, the aryl halide
(0.5 mmol) and styrene (0.75 mmol) were added, and the
mixture was vigorously stirred in a sealed tube at 373 K.
The course of the reaction was monitored by GC–MS
analysis, and yields were calculated against the aryl
halides. On completion of the reaction, the aqueous solu-
Table 1 Optimization of the reaction conditions
tion wass mixed with Et O (3.0 mL), followed by extrac-
2
a
tion with Et O (3 9 3.0 mL). The organic fraction was
2
Entry
Precat (mol %)
Pd(OAc) , 1.0
T (K)
Base
Yield (%)
dried over anhydrous MgSO and then filtered, and the
4
1
2
3
4
5
6
7
8
9
2
373
373
373
373
373
373
373
373
373
373
373
373
373
373
373
298
413
413
373
373
373
373
373
2
K CO
2
K CO
2
K CO
3
3
3
36
solvent was evaporated. Further purification of the product
was achieved by flash chromatography on a silica gel
column. Products were characterized by NMR-spectros-
copy, which was consistent with the literature data.
Pd/1 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:1, 1.0
Pd/2 = 1:2, 1.0
Pd/2 = 1:3, 1.0
Pd/2 = 1:4, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 0.05
Pd/2 = 1:5, 0.5
Pd/2 = 1:5, 0.1
Pd/2 = 1:5, 0.01
Pd/2 = 1:5, 1.0
Pd/2 = 1:5, 1.0
77
97
NaOH
72
t-BuONa
68
1.
(E)-4-Methoxystilbene[19] (Table 3, entries 1, 6, and
2)
Na
LiCl
Et
Cs
KOH
2
CO
3
50
1
21
2.
3.
4.
5.
6.
(E)-4-Methylstilbene[20] (Table 3, entries 2 and 4)
(E)-Stilbene[27] (Table 3, entries 3, 8, and 11)
(E)-2-Methylstilbene[1] (Table 3, entry 5)
3
N
46
2
CO
3
85
10
11
12
13
14
15
16
17
18
19
20
21
22
23
70
(E)-4-Nitrostilbene[1] (Table 3, entries 7 and 10)
(E)-4-Acetylstilbene[28] (Table 3, entry 9)
K
K
K
K
K
K
K
K
K
K
K
3
2
2
2
2
2
2
2
2
2
2
PO
4
82
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
66
3
3
3
3
3
3
3
3
3
78
82
Table 2 Reusability of the catalyst in the Heck reaction
88
a
b
Run
Conversion
Yield (%)
Trace
98
1
2
3
4
5
99
97
96
92
91
96
94
93
90
88
90
96
78
48
NaOAc
None
30
Reaction conditions: 4-bromotoluene (0.5 mmol), styrene
Trace
(
(
a
2 2 3
0.75 mmol), catalyst (Pd(OAc) :2 = 1:5, 0.5 mol %), K CO
1.0 mmol), water (3.0 mL), 373 K, 3 h
Reaction conditions: 4-bromotoluene (0.5 mmol), styrene (0.75 mmol),
catalyst Pd(OAc) /mPEG MeImI, base (1.0 mmol), water (3.0 mL), 3 h
Measured by GC–MS
2
n
a
b
Measured by GC–MS
Isolated yield
1
23

Transition Met Chem (2014) 39:11–15
13
Table 3 Heck reactions of aryl halides and styrene
a
Entry
1
Aryl halide
p-MeOC
Product
Time (h)/temp (K)
1 h/373 K
Yield (%)
6
4
H I
97
MeO
2
3
4
5
p-MeC
6
H
4
I
1 h/373 K
1 h/373 K
3 h/373 K
3 h/373 K
98
Me
6
C H
5
I
95
96
92
p-MeC
6
H
H
4
Br
Br
Me
o-MeC
6
4
Me
6
7
8
p-MeOC
6
H
4
Br
3 h/373 K
3 h/373 K
3 h/373 K
94
97
MeO
NO2
2 6 4
p-NO C H Br
6
C H
5
Br
93
c
9
p-CH COC
3
6
H
4
Cl
6 h/373 K
6 h/373 K
24 h/393 K
90
MeCO
c
1
1
0
1
2
p-NO C
H
6 4
Cl
91
52
NO2
c
6 5
C H Cl
c
38
1
2
p-MeOC
6 4
H Cl
24 h/393 K
MeO
Reaction conditions: aryl halides (0.5 mmol), styrene (0.75 mmol), catalyst (Pd(OAc)
(
2 2 3
:2 = 1:5, 0. 5 mol %), K CO (1.0 mmol), water
3.0 mL), 373 K
a
Measured by GC–MS
b
Catalyst 1.0 mol %
Results and discussion
the best results for this reaction, and other bases such as
Na CO , LiCl, and triethylamine (Et N) were not suitable
2
3
3
The Heck reaction was carried out in water by the reaction
of 4-bromotoluene with styrene in the presence of various
bases (Table 1, entries 2–11). We found that K CO gave
(Table 1, entries 6–8) (Scheme 2).
The catalyst formed with mPEG MeImI appears to be
1
6
more efficient than the one with mPEG MeImI because of
7
2
3
123

1
4
Transition Met Chem (2014) 39:11–15
their different PEG chain lengths (Table 1, entries 1 and 2).
Several Pd/ligand mole ratios were also examined
Conclusion
(
Table 1, entries 3, 12–15), and Pd/mPEG MeImI = 1:5
6
In summary, the in situ-generated Pd(OAc) /2 (1:5) com-
2
1
was selected as the optimal reaction condition. Since this
imidazoline salt can play a dual role both as reaction
medium and also through the PEG group that it bears, as a
potential complexing agent in the Heck reactions [28].
The reaction temperature is one of the important factors
to control the reaction process [29]. In consequence, an
optimum of the reaction temperature in the Heck reactions
might be observed (Table 1, entries 3, 16, and 17), and
plex represents an efficient and reusable catalyst system for
the Heck coupling reactions of aryl iodides, bromides, and
activated aryl chlorides in water. However, Pd(OAc) /2
2
was not a good catalyst for the Heck reaction of unacti-
vated aryl chlorides in our system. The reusability of PEG-
modified NHCs ligands with Pd can also be regarded as
offering strong practical advantages for Heck reactions.
Further studies of its applicability in other C–C bond
forming reactions are currently under investigation.
3
73 K was selected as the optimal reaction temperature.
Various catalyst concentrations were also tested (Table 1,
entries 19–21), and 1.0 mol % gave the best result.
Acknowledgments Financial support for this work was provided by
the National Natural Science Foundation of China (No. 51178282).
The dual property (both as reaction medium and com-
plexing agent) offers the potential for recycling of the
imidazoline salt together with its corresponding catalytic
Pd complex, which should thus eliminate wastage both of
the ligand and also of the Pd compound [28]. The reus-
ability of the catalytic system was tested in the Heck
reaction of styrene and 4-bromotoluene using K CO as the
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