N-heterocyclic carbene-palladium(II)-1-methylimidazole complex catalyzed Mizoroki-Heck reaction of aryl chlorides with styrenes

Article abstract of DOI:10.3762/bjoc.8.222

A well-defined N-heterocyclic carbene-palladium(II)-1-methylimidazole [NHC-Pd(II)-Im] complex 1 was found to be an effective catalyst for the Mizoroki-Heck reaction of a variety of aryl chlorides with styrenes. Both activated and deactivated aryl chlorides work well to give the corresponding coupling products in good to excellent yields by using tetrabutylammonium bromide (TBAB) as the ionic liquid.

Full text of DOI:10.3762/bjoc.8.222

N-Heterocyclic carbene–palladium(II)-1-methyl-
imidazole complex catalyzed Mizoroki–Heck reaction
of aryl chlorides with styrenes
Ting-Ting Gao, Ai-Ping Jin and Li-Xiong Shao*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 1916–1919.
College of Chemistry and Materials Engineering, Wenzhou University,
Chashan University Town, Zhejiang Province 325035, People’s
Republic of China
doi:10.3762/bjoc.8.222
Received: 15 September 2012
Accepted: 24 October 2012
Published: 12 November 2012
Email:
Li-Xiong Shao* - Shaolix@wzu.edu.cn
Associate Editor: K. Itami
* Corresponding author
© 2012 Gao et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
aryl chloride; Mizoroki–Heck reaction; N-heterocyclic carbene;
palladium complex; synthetic method
Abstract
A well-defined N-heterocyclic carbene–palladium(II)-1-methylimidazole [NHC-Pd(II)-Im] complex 1 was found to be an effective
catalyst for the Mizoroki–Heck reaction of a variety of aryl chlorides with styrenes. Both activated and deactivated aryl chlorides
work well to give the corresponding coupling products in good to excellent yields by using tetrabutylammonium bromide (TBAB)
as the ionic liquid.
Introduction
The palladium-catalyzed reaction between organic halides and tors than traditional phosphine ligands, which can then increase
alkenes, the Mizoroki–Heck reaction, is one of the most versa- the catalytic activity of the metal centre and the stability of the
tile methods for the formation of carbon–carbon bonds [1-7]. NHC–metal complexes, have attracted growing attention in the
Usually, in order to achieve the highest efficiency of the palla- metal-catalyzed carbon–carbon and carbon–heteroatom bond-
dium-catalyzed Mizoroki–Heck reaction, toxic, air-sensitive formation reactions during the past two decades [10-15]. Conse-
and expensive phosphine ligands are introduced to facilitate the quently, since the seminal papers reported by Herrmann and
corresponding transformations [8,9]. In order to overcome the co-workers [16,17], the NHC–Pd complexes have become a
drawbacks associated with the phosphine ligands, the develop- strong challenge to the phosphine–metal complexes in the
ment of alternative stable, inexpensive and easily available Mizoroki–Heck reaction. Among the electrophiles participating
phosphine-free ligands is still in great demand.
in the NHC–Pd-complex-catalyzed Mizoroki–Heck reaction,
organic iodides and bromides, which can be easily activated by
In the meantime, N-heterocyclic carbenes (NHCs), possessing the metal centre, are usually used as good partners [18-25]. In
the advantages of being stronger σ-donors and weaker π-accep- contrast to the common electrophiles such as organic iodides
1916

Beilstein J. Org. Chem. 2012, 8, 1916–1919.
and bromides, organic chlorides are the most attractive in the interest to carrying out the reaction between chlorobenzene (2a)
Mizoroki–Heck reaction toward industrial applications due to and styrene (3a) in the presence of NHC-Pd(II)-Im 1 using
their lower cost and the widest availability [26-28]. However, TBAB as the solvent at 140 °C (Table 1). As can be seen from
organic chlorides, especially the deactivated ones, are generally Table 1, all reactions took place smoothly under air to give the
unreactive in the NHC–Pd-complex-catalyzed Mizoroki-Heck desired coupling product 4a in low to excellent yields within
reaction [29-31]. Furthermore, synthetic routes for the above 12 h in the presence of any of the bases tested. To our pleasure,
mentioned NHC–Pd complexes that showed good catalytic the best result can be achieved when Cs2CO3 was used as the
activity toward activated aryl chlorides, are all lengthy [32-36]. base (Table 1, entry 1) [45].
Therefore, although the progress has been achieved for the
NHC–Pd-complex-catalyzed Mizoroki–Heck reaction of aryl
Table 1: Optimization for the NHC-Pd(II)-Im complex 1 catalyzed reac-
chlorides, the drive to develop easily available and widely
applicable complexes with broad substrate scope, is still a
current topic of interest.
tion of chlorobenzene (2a) with styrene (3a).
Recently, we have demonstrated that the well-defined N-hetero-
cyclic carbene–palladium(II)-1-methylimidazole [NHC-Pd(II)-
Im] complex 1 (Figure 1), which can be easily prepared from
commercially available PdCl2, IPr.HCl [1,3-bis(2,6-
diisopropylphenyl)imidazolium chloride], and 1-methylimida-
zole in a one-step procedure in high yield, was an effective cata-
lyst in C–C and C–N bond-formation reactions [37-44]. In our
continuing investigations on the further applications of this
complex in organic synthesis, we found that complex 1 was an
active catalyst for the Mizoroki–Heck reaction of aryl chlorides,
including both activated and deactivated aryl chlorides, with
styrenes performed under air. Herein, we wish to report these
results in detail.
Entrya
Base
Yield (%)b
1
2
3
4
5
6
7
8
9
10
Cs2CO3
NaOH
94
54
67
80
22
52
34
15
44
85
KOH
NaHCO3
KHCO3
Na2CO3
K2CO3
KOt-Bu
NaOt-Bu
LiOt-Bu
aAll reactions were carried out by using 2a (0.75 mmol), 3a (0.9 mmol),
base (2.0 equiv), 1 (1.0 mol %), TBAB (2.0 g) at 140 °C for 12 h.
bIsolated yields.
The optimal reaction conditions (Table 1, entry 1) were then
applied to a variety of aryl chlorides and styrenes to investigate
the generality (Table 2). As can be seen from Table 2, most
reactions proceeded well to give products 4 in good to high
yields. For instance, in the first round, the reactions between
various aryl chlorides 2 and styrene (3a) were examined
(Table 2, entries 1–7). It seems that all of the activated and
Figure 1: NHC-Pd(II)-Im complex 1.
Results and Discussion
Initially, the model reaction between chlorobenzene (2a) deactivated aryl chlorides work well under the optimal condi-
(0.75 mmol) and styrene (3a) (0.90 mmol) was carried out in tions to give the products 4b, 4c, 4e, 4f and 4g in good to high
common polar solvents, such as N,N-dimethylformamide, N,N- yields (Table 2, entries 1, 2, 4, 5 and 6). 2-Methylphenyl chlo-
dimethylacetamide and dimethylsulfoxide, in the presence of ride (2d) gave product 4d in a slightly lower yield (71%) prob-
different inorganic bases and NHC-Pd(II)-Im complex 1 ably due to its steric hindrance (Table 2, entry 3). The reaction
(1.0 mol %) at 150 °C for 24 h. To our disappointment, almost between 2-chlorothiophene (2h) and styrene (3a) also gave pro-
no desired product 4a was observed in all cases. It was reported duct 4h in 63% yield (Table 2, entry 7). In a second round, the
that tetrabutylammonium bromide (TBAB), as a simple ionic reactions between chlorobenzene (2a) and various styrenes 3
liquid, possessing the advantages of low price and easy avail- were also investigated (Table 2, entries 8–13). It also seems that
ability, can facilitate the NHC–Pd-complex-catalyzed the electronic effect of the substituents on the styrenes did not
Mizoroki–Heck reaction [29-31,33]. Thus, we then turned our affect the reactions, and all reactions took place smoothly to
1917

Beilstein J. Org. Chem. 2012, 8, 1916–1919.
give products 4 in good yields (Table 2, entries 8–12). The reac- the solvent to facilitate the reaction [46-48]. Compared to the
tion between chlorobenzene (2a) and 2,4-dimethylstyrene (3g) previously reported NHC–Pd(II) complexes used in the
only gave product 4l in 67% yield, which may also be due to the Mizoroki–Heck reaction with aryl chlorides as the substrates,
steric effect. In addition, acceptable yields can be achieved from the method reported in this paper possesses the advantages of
the reactions of 2-chlorothiophene (2h) with 4-fluorostyrene easy availability of the catalyst and broader substrate applicabil-
(3b) and 4-methylstyrene (3c), respectively (Table 2, entries 19 ity.
and 20).
Supporting Information
Table 2: NHC-Pd(II)-Im complex 1 catalyzed Mizoroki–Heck reactions
of aryl chlorides 2 with styrenes 3.
Supporting Information File 1
General procedure for the NHC-Pd(II)-Im complex 1
catalyzed Mizoroki–Heck reaction, characterization data
and copies of spectra.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-222-S1.pdf]
Entrya
2 (R1)
3 (R2)
Yield (%)b
Acknowledgements
1
2b (3-MeO)
3a (H)
3a
4b, 85
4c, 94
4d, 71
4e, 91
4f, 80
4g, 89
4h, 63
4e, 81
4f, 85
4i, 83
4j, 81
4k, 80
Financial support from the Natural Science Foundation of
Zhejiang Province (No. LY12B02012) is greatly appreciated.
Ting-Ting Gao thanks the Science and Technology Department
of Zhejiang Province (Xinmiao Programme) for financial
support (No. 2011R424043).
2
2c (3-Me)
3
2d (2-Me)
3a
4
2e (4-F)
3a
5
2f (4-Me)
3a
6
2g (4-NO2)
3a
7c
8
2h
3a
2a (H)
2a
3b (4-F)
3c (4-Me)
3d (4-MeO)
3e (3-F)
3f (4-t-Bu)
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