An efficient Pd-NHC catalyst system in situ generated from Na2PdCl4 and PEG-functionalized imidazolium salts for Mizoroki-Heck reactions in water

Article abstract of DOI:10.3762/bjoc.13.168

Three PEG-functionalized imidazolium salts L1-L3 were designed and prepared from commercially available materials via a simple method. Their corresponding water soluble Pd-NHC catalysts, in situ generated from the imidazolium salts L1-L3 and Na₂PdCl₄ in water, showed impressive catalytic activity for aqueous Mizoroki-Heck reactions. The kinetic study revealed that the Pd catalyst derived from the imidazolium salt L1, bearing a pyridine-2-methyl substituent at the N3 atom of the imidazole ring, showed the best catalytic activity. Under the optimal conditions, a wide range of substituted alkenes were achieved in good to excellent yields from various aryl bromides and alkenes with the catalyst TON of up to 10,000.

Full text of DOI:10.3762/bjoc.13.168

An efficient Pd–NHC catalyst system in situ generated from
Na2PdCl4 and PEG-functionalized imidazolium salts for
Mizoroki–Heck reactions in water
Nan Sun*, Meng Chen, Liqun Jin, Wei Zhao, Baoxiang Hu, Zhenlu Shen and Xinquan Hu*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 1735–1744.
College of Chemical Engineering, Zhejiang University of Technology,
Hangzhou 310032, China
doi:10.3762/bjoc.13.168
Received: 07 June 2017
Accepted: 03 August 2017
Published: 21 August 2017
Email:
Nan Sun* - sunnan@zjut.edu.cn; Xinquan Hu* - xinquan@zjut.edu.cn
*
Corresponding author
Associate Editor: B. Stoltz
Keywords:
© 2017 Sun et al.; licensee Beilstein-Institut.
License and terms: see end of document.
aqueous homogeneous catalysis; Mizoroki–Heck reaction; Na2PdCl4;
PEG-functionalized imidazolium salts
Abstract
Three PEG-functionalized imidazolium salts L1–L3 were designed and prepared from commercially available materials via a
simple method. Their corresponding water soluble Pd–NHC catalysts, in situ generated from the imidazolium salts L1–L3 and
Na2PdCl4 in water, showed impressive catalytic activity for aqueous Mizoroki–Heck reactions. The kinetic study revealed that the
Pd catalyst derived from the imidazolium salt L1, bearing a pyridine-2-methyl substituent at the N3 atom of the imidazole ring,
showed the best catalytic activity. Under the optimal conditions, a wide range of substituted alkenes were achieved in good to
excellent yields from various aryl bromides and alkenes with the catalyst TON of up to 10,000.
Introduction
Nowadays, both increasing environmental concerns and drastic hazardous waste treatment issues. Thus, great efforts have been
commercial competition are the driving forces to develop more put into reducing or eliminating those organic solvents by
sustainable and economic processes for important chemicals replacing them with more environmentally acceptable alterna-
syntheses in both academic and industrial fields [1,2]. In fine tives [3]. It is beyond doubt that water is a preferred choice
chemical industries, organic solvents still dominate in modern because of its abundance, non-toxicity, non-flammability, as
synthetic processes since they are capable of dissolving a wide well as minimum environmental impacts. In addition, using
range of organic compounds and controlling the reaction selec- water as medium often leads to exceptional chemical reactivity
tivity and rate. However, they are often volatile, toxic, flam- and selectivity owing to its unique physicochemical properties
mable and expensive as well as might introduce a bulk of [4-6].
1735

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
The palladium-catalyzed cross-coupling reactions to form few examples were reported for Mizoroki–Heck reactions
C–C bonds are very powerful synthetic tools in modern organic [45,51,53,57]. Previous research by Rösch and other groups
synthesis [7]. With their increasing applications in the synthesis disclosed that introducing a hemilable donor group (such as N,
of pharmaceuticals, natural products and functional materials O, S etc.) on the NHC rings was favorable for the palladium-
[
8-10], moving these useful transformations to occurring in catalyzed Mizoroki–Heck cross-coupling reactions [64,65].
aqueous media became more and more attractive [11]. Despite These electron-donating groups could provide a flexible envi-
there are several strategies for palladium-catalyzed cross-cou- ronment for the Pd center and thus favoring the complexation
pling reactions in water, such as microwave heating [12], ultra- and the migratory insertion of an alkene. Cavell reported that a
sonic irradiation [13,14] and ligand-free methodology [15,16], pyridine functionalized Pd–NHC complex showed outstanding
the more efficient and preferable one is the use of water-soluble catalytic activity in Mizoroki–Heck reactions with DMF as sol-
ligated palladium catalysts. This approach not only enhances vent [66].
the water solubility of the catalyst, but also facilitates the
recovery of the catalyst by separating the aqueous phase and With this regards, we herein report the development of a new
subsequently for the potential reuse of catalyst [17]. Initially, poly(ethylene glycol, PEG) and pyridine bi-functionalized
such catalysts have been obtained through modifying tradi- imidazolium salt L1 (Figure 1), which was employed as a water
tional palladium–phosphine catalysts by grafting various hydro- soluble NHC ligand precursor for an in situ generated Pd–NHC
philic substituents on phosphine ligands [18-27]. However, catalyst for Mizoroki–Heck reactions in water. Meanwhile, two
most of these phosphine ligands are air sensitive and required analogues, phenyl (L2) and naphthyl (L3) functionalized imida-
tedious work to preparation. In addition, the easy dissociation of zolium salts were synthesized and their catalytic activities in
common P–Pd bonds under aqueous reaction conditions often aqueous Mizoroki–Heck reactions were also studied.
restricted the reuse of the catalyst and led to undesired residues.
Therefore, in recent years, efforts have been turned to the devel- Results and Discussion
opment of water-soluble non-phosphine ligands [28-34]. In this PEGs are a kind of highly water soluble polymers from the po-
context, N-heterocyclic carbenes (NHCs) have been recognized lymerization of ethylene oxide [67]. Owing to their significant
as the preferable candidates [35,36]. In contrast to common advantages, including widely commercial availability, biocom-
phosphine- and nitrogen-based ligands, NHCs exhibit stronger patibility, chemical and thermal stability and ease to be derived,
σ-donating and weaker π-accepting properties, which make the PEGs have been widely used as phase-transfer catalysts (PTC)
corresponding Pd–NHC complexes more air and water stable. or in the preparation of water soluble ligands for aqueous
Furthermore, the convenient functionalization of the N atom of organic reactions during the past decades [68,69]. More
the NHC ring allows for the possible incorporation of water recently, several PEG-functionalized azolium salts have been
soluble moieties, thus providing more opportunities for water synthesized as water soluble NHC precursors for aqueous
soluble catalyst design [37-39].
Pd-catalyzed cross-coupling reactions [56-59,70]. Fujihara also
pointed out that the flexible linear long-chain structure of PEGs
Since the pioneering report of a sulfonate-functionalized NHC could wrap and stabilize the metal center and thus significantly
ligand by Shaughnessy [40], a number of water-soluble NHC enhanced the catalytic efficiency [70]. Therefore, we chose
ligands, functionalized with sulfonate- [41-46], carboxylate- PEG as functionalization group to prepare water soluble cata-
[
47-52], polyether- [53-59] and other hydrophilic groups [60- lysts.
3], have been developed and used in the aqueous Pd-catalyzed
6
cross-coupling reactions. Among them, most of them were The PEG-functionalized imidazolium salts L1–L3 were pre-
contributed to Suzuki–Miyaura reactions and only a very pared via a three-step reaction sequence as depicted in
Figure 1: Structures of imidazolium salts L1–L3.
1736

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
Scheme 1. Firstly, the commercially available MeO-PEG1900- with NaOH as base, the yields of 3aa were increased from 68%
OH was reacted with MsCl using pyridine as base in CH2Cl2 to to 88% and 78%, respectively, after the addition of 2.0 equiva-
form MeO-PEG1900-OMs, which was then treated with sodium lents of EtOH and t-BuOH, inferring that EtOH and t-BuOH
imidazole in THF to form the imidazole-functionalized PEG could facilitate the reaction. However, both of them were infe-
(
MeO-PEG1900-Im). The resulted MeO-PEG1900-Im was heated rior to the reactions using NaOEt and NaOt-Bu as the base
with various organic bromides (2-(bromomethyl)pyridine, directly (entries 9 and 10, Table 1). Furthermore, it was
benzyl bromide and 1-(bromomethyl)naphthalene) to generate found that N2 atmospheric conditions were crucial for the
the corresponding imidazolium salts L1–L3 under solvent-free reaction and a nearly quantitative GC yield was resulted with
conditions. All imidazolium salts were water-soluble and air- 0.05–0.1 mol % catalyst loadings (entries 11 and 12, Table 1).
stable. The resulted salts L1–L3 were characterized by Further decreasing the catalyst loading to 0.01 mol % resulted
1
H NMR, 13C NMR and MALDI–TOF–MS analyses (see Sup- in a 89% GC yield of the coupling product 3aa (entry 13,
porting Information File 1).
Table 1). Additionally, increasing the molar ratio of L1 and
Na2PdCl4 to 1.5 did not obviously affect the yield (entry 14,
The catalytic performance of the synthesized imidazolium salts Table 1). However, without L1, the GC yield of 3aa was
as NHC precursors for Pd-catalyzed Mizoroki–Heck reactions dramatically decreased to 25%, which hinted that L1 played a
in water was investigated. A model reaction was carried out by crucial role in this transformation (entry 15, Table 1). We also
using 4-bromoacetophenone (1a) and styrene (2a) as the sub- attempted to carry out the reaction at lower reaction tempera-
strates, water as solvent and Na2PdCl4/L1 as the catalyst. The ture; however, much lower conversion was found (entry 16,
mixture of Na2PdCl4, L1 and base in water were preheated at Table 1). Moreover, a blank experiment showed that no reac-
6
0 °C for 30 min before the addition of substrates [41]. The tion occurred without Na2PdCl4 (entry 17, Table 1). To confirm
effect of base was first explored. As the selected experimental that Na2PdCl4 and L1 in situ generated the Pd–NHC species,
results illustrated in Table 1, almost no reaction was observed we treated Na2PdCl4, L1 and NaOEt in D2O at 60 °C for
without base at 100 °C for 12 h (entry 1, Table 1). The reaction 30 min, and then performed NMR analyses. The 1H NMR spec-
could be obviously promoted by a wide range of common trum clearly showed that the proton signal of the 2-position
bases, such as Et3N, NaHCO3, Na2CO3, K2CO3, NaOH, NaOEt (9.41 ppm) of the imidazolium salt L1 disappeared. Two down-
and NaOt-Bu. The best result was obtained with NaOEt as the field signals at 180.9 and 170.9 ppm appeared in the 13C NMR
base. With 2.0 equivalents of NaOEt, the desired coupling prod- spectrum, which is similar to the reported 13C NMR analysis for
uct 3aa was achieved in 97% GC yield (entry 7, Table 1). Em- Pd–NHC species [66]. It is strongly suggested that a Pd–NHC
ploying NaOt-Bu could also provide an excellent yield (91%, complex was formed from deprotonation of L1 under the reac-
entry 8, Table 1). Weaker bases, such as Et3N and NaHCO3, led tion conditions. However, the exact structure of this complex is
to lower yields (entries 2 and 3, Table 1). The performance of not clear yet.
NaOEt and NaOt-Bu was obviously better than that of NaOH.
To clarify that this improvement might be due to the generation With the preliminary reaction conditions in hand, we then
of EtOH and t-BuOH from the hydrolysis of NaOEt and further compared the catalytic performance of those Pd-com-
NaOt-Bu in water, we then studied the effect of EtOH and plexes derived from phenyl and naphthyl analogues L2 and L3
t-BuOH on the reaction. In contrast to the reaction in neat water with that of pyridine functionalized NHC precursor L1.
Scheme 1: The synthetic route for the preparation of imidazolium salts L1–L3.
1737

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
Table 1: Optimizing the reaction conditions of the Mizoroki–Heck reaction.a
Entry
Base
Pd:L1 (Pd mol %)
Yieldb (%)
1
2
3
4
5
6
7
8
9
–
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.1%)
1:1 (0.05%)
1:1 (0.01%)
1:1.5 (0.01%)
1:0 (0.05%)
1:1 (0.05%)
–
trace
23
Et3N
NaHCO3
20
Na2CO3
66
K2CO3
57
NaOH
68
NaOEt
97
NaOt-Bu
91
NaOH + EtOH (2.0 equiv)
88
1
1
1
1
1
1
1
1
0
NaOH + t-BuOH (2.0 equiv)
78
1c
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
>99
>99
89
2c
3c
4c
88
5c
25
6c,d
7c,e
46
n.r.
aReaction conditions: 4-bromoacetophenone (1a, 1.0 mmol), styrene (2a, 1.2 mmol), base (2.0 mmol), Na2PdCl4 (0.001 mmol, 0.1% aqueous solu-
tion), L1 (0.001 mmol, 1% aqueous solution), 1.5 mL H2O, 100 °C, 12 h. The mixture of L1, Na2PdCl4 and base in water was preheated in water at
60 °C for 30 min before adding substrates 1a and 2a. bGC yields were determined by using the area normalization method and calculated based
on 1a. cPurged with N2. dCarried out at 90 °C. eWithout Na2PdCl4, L1 (0.1 mol %).
A kinetic study of the coupling between 4-bromoacetophenone
(
1a) and styrene (2a) was performed in the presence of
0
1
.01 mol % of Na2PdCl4/L and 2.0 equivalents of NaOEt at
00 °C in water and all the three reactions preceded for 24 h. As
shown in Figure 2, the reaction using Na2PdCl4/L1 as the cata-
lyst had a relatively shorter induction period and a higher cata-
lytic activity than those of Na2PdCl4/L2 and Na2PdCl4/L3.
After 24 h, a 100% conversion of 1a was observed in the
Na2PdCl4/L1 catalytic system, a conversion of 87% in
Na2PdCl4/L2 and 77% in Na2PdCl4/L3. This result might be at-
tributed to the side-arm pyridine group acting as a hemilable
coordination site and thus enhanced the catalytic activity of the
palladium complex in Mizoroki–Heck reactions. Furthermore,
the TON of the coupling of 4-bromoacetophenone (1a) and
styrene (2a) with Na2PdCl4/L1 as the catalyst was calculated to
be 10,000, which is much higher than for previously reported
catalytic systems under aqueous conditions.
Figure 2: Kinetic profiles of Mizoroki–Heck reactions in water,
Na2PdCl4/L1 (square), L2 (circle), and L3 (triangle). Reaction condi-
tions: 4-bromoacetophenone (1a, 1.0 mmol), styrene (2a, 1.2 mmol),
NaOEt (2.0 mmol), 0.01 mol % Na2PdCl4, Pd/L = 1:1 (molar ratio),
1.5 mL H2O, 100 °C.
After obtaining the optimal conditions, we then started to
explore the substrate scope of the newly developed catalytic (entries 1–12). Under the optimized reaction conditions
system for Mizoroki–Heck reactions in water. First, a variety of (0.05 mol % Na2PdCl4 and L1, 100 °C, 2.0 equivalents of
para-substituted phenyl bromides 1a–l were tested to couple NaOEt for 12 h), the coupling reactions of aryl bromides 1a–c
with styrene (2a) and the results were summarized in Table 2 with strongly electron-withdrawing substituents (COCH3, CHO
1738

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
Table 2: Mizoroki–Heck reactions between substituted aryl bromides and styrene.a
Entry
Ar–Br 1 (R)
Product 3
Pd/L1 (mol %)
T (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
1a (R = COCH3)
1b (R = CHO)
1c(R = NO2)
1d (R = CF3)
1e (R = F)
3aa
3ba
3ca
3da
3ea
3fa
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.1
100
100
100
120
120
120
120
120
120
120
100
100
96
98
95
94
87
90
87
76
88
53
87
65
1f (R = Cl)
1g (R = Br)
3ga
3ha
3ia
1h (R = H)
1i (R = CH3)
1j (R = OCH3)
1k (R = NH2)
1l (R = OH)
0.1
1
1
1
0
3ja
0.1
1
3ka
3la
0.05
0.05
2c
13
14
15
1m (3-COCH3)
1n (3-CHO)
1o (3-CH3)
3ma
3na
3oa
0.05
0.05
0.1
100
100
120
91
89
77
16
17
18
1p (2-COCH3)
1q (2-CHO)
1r (2-CH3)
3pa
3qa
3ra
0.05
0.05
0.1
100
100
120
<10
51
73
19
20
21
0.1
120
120
120
84
97
86
1
s
3
sa
0.05
0.05
1
t
3
ta
1u
3ua
aReaction conditions: Ar–Br 1 (1.0 mmol), styrene (2a, 1.2 mmol), NaOEt (2.0 mmol), Na2PdCl4 (0.05–0.1 mol %, 0.1% aqueous solution), L1
0.05–0.1 mol %, 1% aqueous solution), 1.5 mL H2O, 100 °C, 12 h, purged with N2. The mixture of L1, Na2PdCl4 and base in water was preheated in
water at 60 °C for 30 min before adding substrates 1 and 2a. bIsolated yields. c3.0 Equivalents of NaOEt was used.
(
1739

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
and NO2) proceeded smoothly and the desired coupling One of the important advantages of using water-soluble cata-
products 3aa–ca were obtained in almost quantitative yields lysts for reactions in water is the easy isolation of products by
(
(
entries 1–3, Table 2). However, higher reaction temperature extraction with a water immiscible solvent, while retaining the
120 °C) was necessary for the coupling of aryl bromides 1d–g catalyst in the aqueous phase for recovery and potential reuse.
with moderate electron-withdrawing substituents (CF3, F, Cl Therefore, the recyclability of the Na2PdCl4/L1 catalytic system
and Br) and their coupling products 3da–ga could be still ob- for Mizoroki–Heck reactions in water was examined by using
tained in good to excellent yields (87–94%, entries 4–7, the coupling of 4-bromoacetophenone (1a) and styrene (2a)
Table 2). It was not surprising that substrates of aryl bromides under the optimal conditions as a model reaction. After each
1
h–j with electron-donating substituents (H, CH3 and OCH3) cycle, the yielded coupling product was extracted with MTBE.
showed rather difficulties for the completion of the reaction. Then, fresh 4-bromoacetophenone, styrene and base were added
With slightly adjusting the reaction conditions (higher reaction into the catalyst-containing aqueous phase for further reaction.
temperature (120 °C) and higher catalyst loading (0.1 mol %), The results in Figure 3 show that the conversion of 4-bromo-
reasonable yields of coupling products 3ha–ja could be ob- acetophenone was 85% for first recycle and 56% for second
tained (entries 8–10, Table 2). It should be pointed out that in recycle, while the selectivity of (E)-4-acetylstilbene (3aa) was
the reaction of 1,4-dibromobenzene (1g), only mono-olefinated unchanged (>99%), which revealed that the catalytic system
product 3ga was formed and not a trace of any di-olefinated still remained certain catalytic activity.
product was detected. We also found that amino and hydroxy
substituted aryl bromides 1k and 1l exhibited high reactivity in
the present aqueous catalytic systems (entries 11 and 12 vs
entries 1–3, Table 2). It might be attributed to the hydrogen
bonding action between amino or hydroxy groups and water
and thus activated these two substrates. Then, the reactivity of
meta- or ortho-substituted phenyl bromides 1m–r were exam-
ined (entries 13–18, Table 2). Compared with para-substituted
analogues 1a, 1b and 1i, the meta-substituted phenyl bromides
1
m, 1n and 1o showed slightly lower reactivities under the
same reaction conditions (entries 13–15 vs entries 1, 2, 9,
Table 2). Nevertheless, the steric hindrance of phenyl bromides
with a substituent at the ortho-position obviously stagnated the
coupling reaction and the yields of the corresponding coupling
products 1pa, 1qa and 1ra were much lower than their para-
and meta-substituted analogues (entries 16–18, Table 2).
Besides the substituted phenyl bromides, 2-bromonaphthalene
Figure 3: Reusability of the Na2PdCl4/L1 catalytic system for the cata-
lytic Mizoroki–Heck coupling reaction of 4-bromoacetophene (1a) and
styrene (2a).
(
(
1s) and some N-heteroaromatic bromides (3-bromopyridine
1t) and 3-bromoquinoline (1u)) could smoothly couple with 2a
to afford the corresponding coupling products 3sa, 3ta and 3ua Conclusion
in good to excellent yields (84, 97 and 86%, respectively, In summary, we have developed three PEG-functionalized
entries 19–21, Table 2).
imidazolium salts L1–L3 from commercially available MeO-
PEG1900-OH, imidazole, and various arylmethyl bromides
The scope of alkenes was also investigated to couple with (2-bromomethylpyridine for L1, benzyl bromide for L2 and
-bromoacetophenone in water (Table 3). These alkenes 1-bromomethylnaphthalene for L3). It was shown that these
included para-substituted styrenes 2b–d (OCH3, CH3 and Cl), imidazolium salts L1–L3 could be utilized as water soluble
-vinylnaphthalene (2e), acrylic acid (2f), 4-vinylpyridine (2g), NHC ligand precursors in combination with Na2PdCl4 to form
4
2
as well as an internal alkene ((E)-stilbene, (2h)). To our delight, in situ the corresponding Pd–NHC catalysts for Mizoroki–Heck
all these tested alkenes smoothly transformed into the corre- reactions in water without any organic co-solvent or phase
sponding products 3ab–ah in excellent yields (85–97%) with transfer reagent. The results indicate that L1 bearing a side-
0
.05–0.1 mol % of Na2PdCl4/L1 at 100 or 120 °C (Table 3). It armed pyridine at N3-position of the imidazole ring exhibited
is noteworthy that a trace amount of 1,1-disubstituted ethylene the best catalytic activity in Mizoroki–Heck reactions, in which
isomers and/or Z-isomers in coupling products were also ob- the pyridine group might serve as a hemilable donating func-
served in some cases. However, the selectivity of E-isomers tional group in the catalytic process. For the coupling of
were always over 99% according to GC analyses.
4-bromoacetophenone and styrene, the TON of Na2PdCl4/L1
1740

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
Table 3: Mizoroki–Heck reactions between 4-bromoacetophenone and various alkenes.a
Entry
1
Alkene 2
Product 3
Pd/L1 (mol %)
T (°C)
Yieldb (%)
97
0.05
100
2
2
2
b
c
d
3
3
3
ab
ac
ad
2
3
4
0.05
0.05
100
100
95
93
0.05
0.1
100
120
120
96
89
85
2e
3ae
5c
2
f
3
af
6
0.1
2g
3ag
7
0.05
120
93
2h
3ah
aReaction conditions: 4-bromoacetophenone (1a, 1.0 mmol), alkenes 2 (1.2 mmol), NaOEt (2.0 mmol), Na2PdCl4 (0.05–0.1 mol %, 0.1% aqueous
solution), L1 (0.05–0.1 mol %, 0.1% aqueous solution), 1.5 mL H2O, 100 °C, 12 h, purged with N2. The mixture of L1, Na2PdCl4 and base in water
was preheated in water at 60 °C for 30 min before adding substrates 1a and 2. bIsolated yields. c3.0 Equivalents of NaOEt was used.
catalytic system reached up to 10,000. Under the optimal condi- provides an efficient, practical and environmental benign
tions, large amounts of substituted alkenes were obtained in method for the construction of various alkene derivatives.
good to excellent yields using the Na2PdCl4/L1 catalyst system
Experimental
with only a 0.05–0.1 mol % palladium loading. To the best of
our knowledge, the catalyst loading in the current report for General
aqueous Mizoroki–Heck couplings of aryl bromides is much All chemicals were reagent grade and used as purchased. Mono-
lower than other previously reported counterparts. Moreover, methylated PEG1900 (MeO-PEG1900-OH) was obtained from
imidazolium salt L1 was conveniently synthesized from com- Meryer Chem. Tech. Co. Ltd, China. All proton and 13C nuclear
mercially available materials. This newly developed protocol magnetic resonance (NMR) spectra were recorded on Bruker
1741

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
AVANCE III 500 MHz spectrometer in deuterated solvents Hz, 2H, NCH2), 3.58–3.42 (m, 196H, CH2 of PEG chain), 3.30
with tetramethylsilane (TMS) as internal standard. Mass spec- (s, 3H, PEG-OCH3); 13C NMR (CDCl3) δ 136.8, 128.2, 118.8,
trometry data (MALDI–TOF) of the three imidazolium salts 71.2–69.8 (CPEG), 58.2, 46.3.
L1–L3 were collected on a Bruker ultrafleXtreme mass spec-
trometer. Low-resolution mass analyses were performed on a Synthesis of imidazolium salts L1, L2 and L3
Thermo Trace ISQ GC–MS instrument in EI mode (70 eV) or a A mixture of MeO-PEG1900-Im (3.9 g, 2 mmol) and the corre-
Thermo Scientific ITQ 1100TM mass spectrometer in ESI sponding organic bromide (2.4 mmol) was heated in a sealed
mode. High-resolution mass spectra were recorded in the EI tube at 100 oC for 24 h. The resulting imidazolium salts was
mode on a Waters GCT Premier TOF mass spectrometer with isolated by precipitation with MTBE.
an Agilent 6890 gas chromatography using a DB-XLB column
(
30 m × 0.25 mm (i.d.), 0.25 μm). Melting points (uncorrected) Imidazolium salt L1. Yield: 3.9 g (92%), pale brown solid;
were determined on a Büchi M-565 apparatus. Gas chromatog- 1H NMR (DMSO-d6) δ 9.41 (s, 1H, CHimid), 8.56 (d, J = 4.2
raphy (GC) analyses were performed on Shimadzu GC-20A Hz, 1H, CHpyri), 7.92–7.88 (m, 1H, CHpyri), 7.84 (s, 2H,
instrument with FID detector using a RTX-5 capillary column CHpyri), 7.53 (d, J = 7.8 Hz, 1H, CHimid), 7.41 (d, J = 7.1 Hz,
(
30 m × 0.32 mm (i.d.), 0.25 μm). Flash column chromatogra- 1H, CHimid), 5.64 (s, 2H, CHbenzyl), 4.43 (t, J = 4.7 Hz, 2H,
phy was performed on silica gel (200–300 mesh) with petro- OCH2), 3.81 (t, J = 4.7 Hz, 2H, NCH2), 3.66–3.42 (m, 196H,
leum ether/ethyl acetate as eluent. De-ionized water was used in CH2 of PEG chain), 3.24 (s, 3H, PEG-OCH3); 13C NMR
all reactions.
(CDCl3) δ 153.7, 149.6, 137.6, 137.3, 123.7, 123.0, 122.9,
22.7, 71.2–68.3 (CPEG), 58.1, 53.0, 49.0; MALDI–TOF–MS
1
Preparation of PEG-functionalized
m/z: [Mn=49 − Br]+ calcd for C110H212N3O50, 2375.4; found,
imidazolium salts L1, L2 and L3
2375.8.
Synthesis of MeO-PEG1900-OMs
MeO-PEG1900-OH (38.0 g , 0.02 mol) and pyridine (3.16 g, Imidazolium salt L2. Yield: 3.9 g (92%), pale white solid;
.04 mol) were dissolved in 50 mL of dry DCM at an ice-water 1H NMR (DMSO-d6) δ 9.28 (s, 1H, CHimid), 7.85–7.80 (m, 2H,
0
bath and under N2 atmosphere, followed by adding dropwise a CHAr), 7.44–7.40 (m, 5H, CHAr), 5.46 (s, 2H, CHbenzyl), 4.38
solution of methanesulfonyl chloride (MsCl, 4.58 g, 0.04 mol) (t, J = 4.6 Hz, 2H, OCH2), 3.79 (t, J = 4.6 Hz, 2H, NCH2),
in 200 mL of dry DCM. After completion of addition, the mix- 3.51–3.42 (m, 196H, CH2 of PEG chain), 3.24 (s, 3H, PEG-
ture was stirred at room temperature for 24 h. The reaction was OCH3); 13C NMR (DMSO-d6) δ 136.6, 135.0, 128.9, 128.7,
quenched with 100 mL of ice-water and the pH was adjusted to 128.4, 123.1, 122.2, 71.34–68.2 (CPEG), 58.0, 51.7, 49.0;
7
with a 20% aqueous NaOH solution. The organic layer was MALDI–TOF–MS m/z: [Mn=49 − Br]+ calcd for
separated, washed with water, dried with Na2SO4 and filtered. C111H213N2O50, 2374.4; found, 2374.8.
After removal of the solvent under vacuum, the residual was
precipitated with methyl tert-butyl ether (MTBE) to afford Imidazolium salt L3. Yield: 3.8 g (88%), pale white solid;
3
8.3 g (97%) of MeO-PEG1900-OMs as a white solid. 1H NMR 1H NMR (DMSO-d6) δ 9.28 (s, 1H, CHimid), 8.15 (d, J = 8.0
(
CDCl3) δ 4.34–4.32 (m, 2H, CH2OMs), 3.74–3.44 (m, 198H, Hz, 1H, CHAr), 8.04–8.03 (m, 2H, CHAr), 7.84 (s, 1H, CHAr),
CH2 of PEG chain), 3.33 (s, 3H, PEG-OCH3), 3.04 (s, 3H, 7.80 (s, 1H, CHAr), 7.64–7.57 (m, 3H, CHAr), 7.52 (d, J = 6.9
SO2CH3); 13C NMR (CDCl3) δ 71.9–68.2 (CPEG), 60.7, 58.2, Hz, 1H, CHimid), 5.98 (s, 2H, CHbenzyl), 4.36 (t, J = 2.4 Hz, 2H,
3
6.8.
OCH2), 3.76 (t, J = 4.7 Hz, 2H, NCH2), 3.51–3.41 (m, 196H,
CH2 of PEG chain), 3.24 (s, 3H, PEG-OCH3); 13C NMR
(DMSO-d6) δ 136.7, 133.5, 130.5, 130.2, 129.7, 128.9, 127.8,
Synthesis of MeO-PEG1900-Im
To a solution of imidazole (0.89 g, 13 mmol) in 120 mL of dry 127.2, 126.4, 125.6, 123.02, 122.97, 122.5, 71.3–68.1 (CPEG),
THF at room temperature under N2 atmosphere was added NaH 58.0, 49.8, 49.0; MALDI–TOF–MS m/z: [Mn=49 − Br]+ calcd
(
60% dispersion in mineral oil, 0.8 g, 20 mmol). The mixture for C115H215N2O50, 2424.4; found, 2424.9.
was then heated to 40 °C for 1 h to ensure the completion of
H2 releasing. After that, MeO-PEG1900-OMs (19.7 g, 10 mmol) General procedure for Mizoroki–Heck reactions in
was added and the mixture was refluxed for 24 h. Then, the re- water
sulting suspension was filtered off and the filtrate was concen- To a 10 mL tube, Na2PdCl4 (0.1% aqueous solution,
trated under vacuum. Precipitation with MTBE afforded 18.2 g 0.05–0.1 mol %), imidazolium salts L1–L3 (1% aqueous solu-
(
(
93%) of MeO-PEG1900-Im as a light yellow solid. 1H NMR tion, 0.05–0.1 mol %), NaOEt (2.0 mmol) and 1.5 mL water
CDCl3) δ 7.50 (s, 1H, CHimid), 6.96 (s, 1H, CHimid), 6.95 (s, were successively added, followed by preheating at 60 °C for
1
H, CHimid), 4.05 (t, J = 5.2 Hz, 2H, OCH2), 3.68 (t, J = 5.2 30 min. Then, aryl bromide (1.0 mmol) and styrene (1.2 mmol)
1742

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
1
1
1
6.Basu, B.; Biswas, K.; Kundu, S.; Ghosh, S. Green Chem. 2010, 12,
were added, purged with N2, sealed and heated at 100 °C. After
2 h, the solution was extracted with MTBE (5 mL × 2) and the
1734–1738. doi:10.1039/c0gc00122h
1
7.Shaughnessy, K. H. Chem. Rev. 2009, 109, 643–710.
doi:10.1021/cr800403r
organic layers combined, dried over anhydrous Na2SO4, and
concentrated under vacuum. Finally, the resulted residual were
purified by flash chromatography on silica to afford the desired
cross-coupling alkene products. The purity of the obtained
products was confirmed by NMR and the yields were based on
aryl bromides.
8.Casalnuovo, A. L.; Calabrese, J. C. J. Am. Chem. Soc. 1990, 112,
4324–4330. doi:10.1021/ja00167a032
19.Genet, J. P.; Blart, E.; Savignac, M. Synlett 1992, 715–717.
doi:10.1055/s-1992-21465
2
0.Bumagin, N. A.; Bykov, V. V.; Sukhomlinova, L. I.; Tolstaya, T. P.;
Beletskaya, I. P. J. Organomet. Chem. 1995, 486, 259–262.
doi:10.1016/0022-328X(94)05056-H
2
2
2
1.Genet, J. P.; Savignac, M. J. Organomet. Chem. 1999, 576, 305–317.
Supporting Information
doi:10.1016/S0022-328X(98)01088-2
2.Uozumi, Y.; Kimura, T. Synlett 2002, 2045–2048.
doi:10.1055/s-2002-35605
Supporting Information File 1
Characterization data of Mizoroki–Heck products and
copies of NMR spectra.
3.Amengual, R.; Genin, E.; Michelet, V.; Savignac, M.; Genet, J. P.
Adv. Synth. Catal. 2002, 344, 393–398.
[
http://www.beilstein-journals.org/bjoc/content/
doi:10.1002/1615-4169(200206)344:3/4<393::AID-ADSC393>3.0.CO;2
-K
supplementary/1860-5397-13-168-S1.pdf]
2
2
2
4.Moore, L. R.; Shaughnessy, K. H. Org. Lett. 2004, 6, 225–228.
doi:10.1021/ol0360288
5.DeVasher, R. B.; Moore, L. R.; Shaughnessy, K. H. J. Org. Chem.
Acknowledgements
2004, 69, 7919–7927. doi:10.1021/jo048910c
This work was supported by the National Natural Science Foun-
dations of China (21473160). We also thank for the support
from “Zhejiang Key Course of Chemical Engineering and Tech-
nology” and “Zhejiang Key Laboratory of Green Pesticides and
Cleaner Production Technology of Zhejiang Province” of the
Zhejiang University of Technology.
6.Shaughnessy, K. H. Eur. J. Org. Chem. 2006, 1827–1835.
doi:10.1002/ejoc.200500972
27.Jeffery, T. Tetrahedron Lett. 1994, 35, 3051–3054.
doi:10.1016/S0040-4039(00)76825-0
2
8.Azoui, H.; Baczko, K.; Cassel, S.; Larpent, C. Green Chem. 2008, 10,
197–1203. doi:10.1039/b804828b
1
2
9.Pawar, S. S.; Dekhane, D. V.; Shingare, M. S.; Thore, S. N.
Tetrahedron Lett. 2008, 49, 4252–4255.
References
doi:10.1016/j.tetlet.2008.04.148
1.
Anastas, P.; Eghbali, N. Chem. Soc. Rev. 2010, 39, 301–312.
30.Zhang, G.; Luan, Y.; Han, X.; Wang, Y.; Wen, X.; Ding, C.; Gao, J.
Green Chem. 2013, 15, 2081–2085. doi:10.1039/c3gc40645h
31.Nehra, P.; Khungar, B.; Pericherla, K.; Sivasubramanian, S. C.;
Kumar, A. Green Chem. 2014, 16, 4266–4271.
doi:10.1039/B918763B
2.
Sheldon, R. A. Chem. Soc. Rev. 2012, 41, 1437–1451.
doi:10.1039/C1CS15219J
3
.
.
Sheldon, R. A. Green Chem. 2005, 7, 267–278. doi:10.1039/b418069k
Li, C.-J.; Chan, T.-H. Organic reactions in aqueous media; Wiley-VCH:
New York, 1997.
doi:10.1039/C4GC00525B
4
32.Potier, J.; Menuel, S.; Rousseau, J.; Tumkevicius, S.; Hapiot, F.;
Monflier, E. Appl. Catal., A 2014, 479, 1–8.
5
6
7
8
9
1
.
.
.
.
.
Butler, R. N.; Coyne, A. G. Chem. Rev. 2010, 110, 6302–6337.
doi:10.1021/cr100162c
doi:10.1016/j.apcata.2014.04.021
33.Khan, R. I.; Pitchumani, K. Green Chem. 2016, 18, 5518–5528.
doi:10.1039/C6GC01326K
Simon, M.-O.; Li, C.-J. Chem. Soc. Rev. 2012, 41, 1415–1427.
doi:10.1039/C1CS15222J
34.Waheed, M.; Ahmed, N. Tetrahedron Lett. 2016, 57, 3785–3789.
doi:10.1016/j.tetlet.2016.07.028
de Meijere, A.; Diederich, F. Metal-catalyzed cross-coupling reactions,
2
nd ed.; Wiley-VCH: Weinheim, 2008. doi:10.1002/9783527619535
Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005,
4, 4442–4489. doi:10.1002/anie.200500368
35.Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290–1309.
doi:10.1002/1521-3773(20020415)41:8<1290::AID-ANIE1290>3.0.CO;
2-Y
4
Torborg, C.; Beller, M. Adv. Synth. Catal. 2009, 351, 3027–3043.
36.Kantchev, E. A. B.; O'Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed.
2007, 46, 2768–2813. doi:10.1002/anie.200601663
37.Velazquez, H. D.; Verpoort, F. Chem. Soc. Rev. 2012, 41, 7032–7060.
doi:10.1039/c2cs35102a
doi:10.1002/adsc.200900587
0.Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177–2250.
doi:10.1021/cr100346g
1
1.Li, C.-J. Chem. Rev. 2005, 105, 3095–3166. doi:10.1021/cr030009u
2.Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563–2591.
doi:10.1021/cr0509410
38.Schaper, L.-A.; Hock, S. J.; Herrmann, W. A.; Kühn, F. E.
Angew. Chem., Int. Ed. 2013, 52, 270–289.
1
doi:10.1002/anie.201205119
1
1
1
3.Poláčková, V.; Hut'ka, M.; Toma, Š. Ultrason. Sonochem. 2005, 12,
39.Levin, E.; Ivry, E.; Diesendruck, C. E.; Lemcoff, N. G. Chem. Rev.
2015, 115, 4607–4692. doi:10.1021/cr400640e
99–102. doi:10.1016/j.ultsonch.2004.05.011
4.Zhang, Z.; Zha, Z.; Gan, C.; Pan, C.; Zhou, Y.; Wang, Z.; Zhou, M.-M.
J. Org. Chem. 2006, 71, 4339–4342. doi:10.1021/jo060372b
40.Moore, L. R.; Cooks, S. M.; Anderson, M. S.; Schanz, H.-J.;
Griffin, S. T.; Rogers, R. D.; Kirk, M. C.; Shaughnessy, K. H.
Organometallics 2006, 25, 5151–5158. doi:10.1021/om060552b
5.Bumagin, N. A.; More, P. G.; Beletskaya, I. P. J. Organomet. Chem.
1989, 371, 397–401. doi:10.1016/0022-328X(89)85235-0
1743

Beilstein J. Org. Chem. 2017, 13, 1735–1744.
4
4
4
4
4
4
1.Fleckenstein, C.; Roy, S.; Leuthäußer, S.; Plenio, H. Chem. Commun.
68.Bergbreiter, D. E. Chem. Rev. 2002, 102, 3345–3383.
2007, 2870–2872. doi:10.1039/B703658B
doi:10.1021/cr010343v
2.Roy, S.; Plenio, H. Adv. Synth. Catal. 2010, 352, 1014–1022.
doi:10.1002/adsc.200900886
69.Bergbreiter, D. E.; Tian, J.; Hongfa, C. Chem. Rev. 2009, 109,
530–582. doi:10.1021/cr8004235
3.Türkmen, H.; Pelit, L.; Çetinkaya, B. J. Mol. Catal. A: Chem. 2011, 348,
70.Fujihara, T.; Yoshikawa, T.; Satou, M.; Ohta, H.; Terao, J.; Tsuji, Y.
Chem. Commun. 2015, 51, 17382–17385. doi:10.1039/C5CC07588B
8
8–93. doi:10.1016/j.molcata.2011.08.008
4.Godoy, F.; Segarra, C.; Poyatos, M.; Peris, E. Organometallics 2011,
0, 684–688. doi:10.1021/om100960t
5.Yuan, D.; Teng, Q.; Huynh, H. V. Organometallics 2014, 33,
794–1800. doi:10.1021/om500140g
3
1
License and Terms
6.Zhong, R.; Pöthig, A.; Feng, Y.; Riener, K.; Herrmann, W. A.;
Kühn, F. E. Green Chem. 2014, 16, 4955–4962.
doi:10.1039/C4GC00986J
This is an Open Access article under the terms of the
Creative Commons Attribution License
4
7.Churruca, F.; SanMartin, R.; Inés, B.; Tellitu, I.; Domínguez, E.
Adv. Synth. Catal. 2006, 348, 1836–1840.
(http://creativecommons.org/licenses/by/4.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
doi:10.1002/adsc.200606173
4
8.Inés, B.; SanMartin, R.; Jesús Moure, M.; Domínguez, E.
Adv. Synth. Catal. 2009, 351, 2124–2132.
doi:10.1002/adsc.200900345
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
4
5
5
5
5
9.Türkmen, H.; Can, R.; Çetinkaya, B. Dalton Trans. 2009, 7039–7044.
doi:10.1039/b907032j
(
http://www.beilstein-journals.org/bjoc)
0.Tu, T.; Feng, X.; Wang, Z.; Liu, X. Dalton Trans. 2010, 39,
10598–10600. doi:10.1039/c0dt01083a
1.Wang, Z.; Feng, X.; Fang, W.; Tu, T. Synlett 2011, 951–954.
doi:10.1055/s-0030-1259723
The definitive version of this article is the electronic one
which can be found at:
2.Li, L.; Wang, J.; Zhou, C.; Wang, R.; Hong, M. Green Chem. 2011, 13,
doi:10.3762/bjoc.13.168
2071–2077. doi:10.1039/c1gc15312a
3.Gülcemal, S.; Kahraman, S.; Daran, J.-C.; Çetinkaya, E.; Çetinkaya, B.
J. Organomet. Chem. 2009, 694, 3580–3589.
doi:10.1016/j.jorganchem.2009.07.010
5
5
5
5
5
4.Zhang, X.; Qiu, Y.; Rao, B.; Luo, M. Organometallics 2009, 28,
3093–3099. doi:10.1021/om8011695
5.Karimi, B.; Akhavan, P. F. Chem. Commun. 2011, 47, 7686–7688.
doi:10.1039/c1cc00017a
6.Liu, N.; Liu, C.; Jin, Z. Green Chem. 2012, 14, 592–597.
doi:10.1039/c2gc16486h
7.Liu, Y.; Wang, Y.; Long, E. Transition Met. Chem. 2014, 39, 11–15.
doi:10.1007/s11243-013-9765-x
8.Shi, J.-c.; Yu, H.; Jiang, D.; Yu, M.; Huang, Y.; Nong, L.; Zhang, Q.;
Jin, Z. Catal. Lett. 2014, 144, 158–164.
doi:10.1007/s10562-013-1126-z
5
6
6
6
6
6
6
6
6
9.Zhou, Z.; Zhao, Y.; Zhen, H.; Lin, Z.; Ling, Q. Appl. Organomet. Chem.
2
016, 30, 924–931. doi:10.1002/aoc.3522
0.Yang, C.-C.; Lin, P.-S.; Liu, F.-C.; Lin, I. J. B. Organometallics 2010,
9, 5959–5971. doi:10.1021/om100751r
2
1.Luo, F.-T.; Lo, H.-K. J. Organomet. Chem. 2011, 696, 1262–1265.
doi:10.1016/j.jorganchem.2010.11.002
2.Zhou, Z.; Qiu, J.; Xie, L.; Du, F.; Xu, G.; Xie, Y.; Ling, Q. Catal. Lett.
2014, 144, 1911–1918. doi:10.1007/s10562-014-1323-4
3.Meise, M.; Haag, R. ChemSusChem 2008, 1, 637–642.
doi:10.1002/cssc.200800042
4.Albert, K.; Gisdakis, P.; Rösch, N. Organometallics 1998, 17,
1608–1616. doi:10.1021/om9709190
5.Normand, A. T.; Cavell, K. J. Eur. J. Inorg. Chem. 2008, 2781–2800.
doi:10.1002/ejic.200800323
6.McGuinness, D. S.; Cavell, K. J. Organometallics 2000, 19, 741–748.
doi:10.1021/om990776c
7.Chen, J.; Spear, S. K.; Huddleston, J. G.; Rogers, R. D. Green Chem.
2005, 7, 64–82. doi:10.1039/b413546f
1744