Nickel(II) complex containing N-(4,5-dihydrooxazol-2-yl)benzamide ligands: Highly efficient catalyst for Heck coupling reactions

Article abstract of DOI:10.1002/aoc.3134

Heck reaction catalyzed by Ni(II) containing N-(4,5-dihydrooxazol-2-yl) benzamide has been developed. The coupling of alkenes with aryl iodide or aryl bromide in the presence of potassium carbonate in DMF provides the corresponding products with moderate to good yields. This method possesses obvious advantages such as low-cost catalyst and simple experimental operation.

Full text of DOI:10.1002/aoc.3134

Full Paper
Received: 15 November 2013
Revised: 14 January 2014
Accepted: 5 February 2014
Published online in Wiley Online Library: 30 March 2014
(wileyonlinelibrary.com) DOI 10.1002/aoc.3134
Nickel(II) complex containing N-(4,5-
dihydrooxazol-2-yl)benzamide ligands: highly
efficient catalyst for Heck coupling reactions
Junke Wanga,c*, Yingxiao Zonga,b*, Shenglong Weib and Yi Panc
Heck reaction catalyzed by Ni(II) containing N-(4,5-dihydrooxazol-2-yl) benzamide has been developed. The coupling of
alkenes with aryl iodide or aryl bromide in the presence of potassium carbonate in DMF provides the corresponding products
with moderate to good yields. This method possesses obvious advantages such as low-cost catalyst and simple experimental
operation. 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: nickel(II) complex; Heck reaction; aryl iodides; aryl bromides
Introduction
Experimental
The palladium-catalyzed coupling reaction between an aryl
halide and a terminal alkene, the Mizoroki–Heck reaction, widely
known as the Heck reaction, has become one of the most power-
ful synthetic methodologies for C―C bond formation.[1–3]
This reaction has benefited from a variety of applications in
areas of polymerization processes, pharmaceuticals and ad-
vanced synthesis of natural products.[4–9] Many publications
concerning improvements to the original Heck reaction condi-
tions have appeared in the literature. Although the palladium-
catalyzed reactions display an extraordinary functional group
tolerance and palladium complexes show high catalytic activities,
there is an obvious drawback that the high cost of palladium has
resulted in the exploration of less costly transition metals as
alternatives to palladium systems.
For the Heck coupling reaction, a reaction tube was charged with
aryl halide (4 mmol), olefinic substrate (6 mmol), K2CO3 (5 mmol),
Ni(II) complex (0.02 mmol) and 5 ml DMF. The resulting mixture
was stirred at 100 °C for an appropriate time. Progress of the reaction
was monitored by thin-layer chromatography. Upon completion of
the reaction, the reaction mixture was cooled to room temperature,
diluted with EtOAc (20 ml), and washed with dilute HCl and water.
The combined organic layer was dried over anhydrous Na2SO4
and stripped from the solvent under reduced pressure. The residue
was subjected to column chromatography on silica gel using ethyl
acetate and hexane mixtures to afford the Mizoroki–Heck product
in high purity. All of the Mizoroki–Heck products were known
compounds and were characterized by comparison of their proton
NMR spectra with those appearing in the literature.
In recent years, more importance has been attached to nickel
catalysts. Nickel appears to be most promising for the replace-
ment of palladium as a catalyst for carbon–carbon cross-coupling
reactions,[10] due to its relatively low cost and ability to readily
undergo oxidative addition reactions with C―X bonds. Nickel-
mediated conjugate addition reactions of alkyl halide with alkene
have been reported.[11] However, relatively little effort has been
dedicated to the development of nickel complexes as catalysts
for the Mizoroki–Heck reaction.[12,13,13a),13b),13c),14]
Results and Discussion
In a preliminary experiment, we investigated the cross-coupling
reaction between bromobenzene and t-butyl acrylate by utilizing
nickel(II) N-(4,5-dihydrooxazol-2-yl)benzamide complexes as
*
Correspondence to: Junke Wang and Yingxiao Zong, Key Laboratory of Hexi
Corridor Resources Utilization of Gansu Universities, College of Chemistry and
Chemical Engineering, Hexi University, Zhangye 734000, China. E-mail:
wangjk@hxu.edu.cn; zongyx@hxu.edu.cn
In our previous study,[15] N-(4,5-dihydrooxazol-2-yl)benza-
mide[16] (Fig. 1) was an excellent N,O-bidentate ligand and could
coordinate well with nickel to obtain Ni(II) complex (Fig. 2). The
crystallographic structure of the complex has been confirmed.
Moreover, we have reported the synthesis of N-benzothiazol-2-yl-
amides from 1-benzoyl-3-(2-bromophenyl) thiourea via the forma-
tion of C―S bond employing the ligand and Cu(I) as catalyst
(Scheme 1).[15] In continuation of our work to develop new
catalysts for organic transformations, here we report nickel(II) N-
(4,5-dihydrooxazol-2-yl)benzamide complex to catalyze the
Mizoroki–Heck reaction of aryl bromides with various olefins.
a Key Laboratory of Hexi Corridor Resources Utilization of Gansu Universities,
College of Chemistry and Chemical Engineering, Hexi University, Zhangye
734000, China
b Gansu Engineering Laboratory of Applied Fungus, Hexi University, Zhangye
734000, China
c
School of Chemistry and Chemical Engineering, Nanjing University, Nanjing
210093, China
Appl. Organometal. Chem. 2014, 28, 351–353
Copyright © 2014 John Wiley & Sons, Ltd.

J. Wang et al.
catalyst in the presence of a mild base (Cs2CO3) in DMSO (Table 1,
entry 1). We were pleased to find that the use of this complex
could efficiently catalyze the cross-coupling reaction. In order to
demonstrate the efficiency of the catalyst, a controlled experi-
ment without the catalyst was conducted. It was found that no
cross-coupling product was observed in the absence of the cata-
lyst (Table 1, entry 2).
Figure 1. Molecular structure of N-(4,5-dihydrooxazol-2-yl)benzamide.
To identify the optimal conditions for the Heck reaction, a
series of bases and solvents were screened (Table 1). Initially,
the coupling of t-butyl acrylate with bromobenzene was selected
as a model system. The effects of additives such as organic and
inorganic bases in the coupling reaction were investigated. After
screening Cs2CO3, K2CO3, Na2CO3, K3PO4, CH3COOK, TEA or
CH3COONa as base (Table 1, entries 3–9), we found that in the
presence of K2CO3 the yield of product was up to 95% (Table 1,
entry 3). Therefore, K2CO3 was selected as the base for further
screening reactions. Several solvents were tested for the Heck re-
action. It was difficult for reactions to take place in PhCl or PhCH3
(Table 1, entries 10 and 11). It seemed that solvents also played
an important role in the Heck reaction. Although a lower catalyst
loading (0.5 mol%) could be used to accomplish this reaction,
0.5 mol% Ni(II) complexes was optimal in terms of reaction time
and isolated yield. On the basis of the above experiments, the op-
timized reaction conditions are summarized as follows: 0.5 mol%
Ni(II) complexes, 1 equiv. K2CO3, in DMF.
O
N
N
O
Ni
O
N
N
O
Figure 2. Chemical diagram of the Ni(II) complex.
With the optimal conditions in hand, the scope of the sub-
strates was investigated. As shown in Table 2, all of the aryl bro-
mide can react with alkenes smoothly. In general, for a particular
Scheme 1. Synthesis of N-benzothiazol-2-yl-amides by a copper-cata-
lyzed intramolecular cyclization process.
Table 2. Nickel(II) complex-catalyzed Heck coupling reactiona
Table 1. Optimization of Heck reaction conditionsa
Entry
R1
R2
X
Time Product
(h)
Yield
(%)b
Entry Catalyst (mol%)
Base
Solvent Temp. Time Yield
(%)b
1
2
3
4
5
6
7
8
9
H
―COOtBu
CH3CO ―COOtBu
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
24
24
30
22
24
20
24
24
24
36
36
48
48
20
20
3a
3b
3c
3d
3e
3f
94
95
96
94
93
96
88
78
85
89
75
0
(°C)
(h)
1
2
3
4
5
6
7
8
9
Ni(II) complex (2) Cs2CO3
DMSO
DMSO
DMF
80
80
80
80
80
80
80
80
80
80
80
80
80
80
24
36
24
24
24
24
24
24
24
24
24
24
24
36
96
0
CH3
CN
H
―COOtBu
―COOtBu
―COOCH3
Ni(II) complex (0) Cs2CO3
Ni(II) complex (2) Cs2CO3
Ni(II) complex (2) K2CO3
Ni(II) complex (2) Na2CO3
Ni(II) complex (2) K3PO4
95
95
86
51
25
36
0
DMF
CH3CO ―COOCH3
CH3CO ―C6H5
DMF
3 g
3 h
3i
DMF
H
―C6H5
―C6H5
―C6H5
Ni(II) complex (2) CH3COONa DMF
Cl
Ni(II) complex (2) CH3COOK
Ni(II) complex (2) TEA
DMSO
10 MeO
11
3j
DMSO
PhCl
H
―C6H4―4―CH3 Br
3 k
3 m
3n
3o
3p
10 Ni(II) complex (2) K2CO3
11 Ni(II) complex (2) K2CO3
12 Ni(II) complex (1) K2CO3
13 Ni(II) complex (0.5) K2CO3
14 Ni(II) complex (0.25) K2CO3
0
12 NO2
13 CH3
―COOtBu
―COOtBu
―COOtBu
―C6H5
Cl
Cl
I
PhCH3
DMF
0
0
95
94
82
14
H
96
90
DMF
15 Cl
I
DMF
aReaction conditions: aryl halide (4 mmol), olefin (6 mmol), K2CO3
(5 mmol), Ni(II) complex (0.5 mol %), DMF (5 ml) at 100 °C for the
indicated time.
bIsolated yield after column chromatography based on aryl halide.
aReaction conditions: bromobenzene (4.0 mmol), t-butyl acrylate
(6 mmol), base (2.0 mmol), solvent (5.0 ml).
bIsolated yield after column chromatography based on bromobenzene.
wileyonlinelibrary.com/journal/aoc
Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 351–353

Ni(II) complex-catalyzed Heck coupling reaction
and bromides with various substituted alkenes under
appropriate reaction conditions. More importantly, the
catalyst is inexpensive compared with palladium
catalysts. The application of this new catalyst in organic
synthesis will be expanded. This work is under way in
our laboratory.
Acknowledgments
We are thankful for financial support from Key Laboratory
of Hexi Corridor Resources Utilization of Gansu Universities
(No. XZ1011), Gansu Engineering Laboratory of Applied
Mycology, the National Science Foundation of China
(No. 21262010), the President’s Funds of Hexi University
(No. XZ-2009-9), Jinchuan Group Co., LTD, and the
National Science Foundation of China (No. 21262010).
Figure 3. The proposed mechanism.
References
aryl bromide, the cross-coupled products were obtained in good
to high isolated yields with t-butyl acrylate or methyl acrylate
(Table 2, entries 1–6) as the vinylic substrate. However, compared
with aryl bromide with an electron-deficient group, it took longer
for the aryl bromide with an electron-rich group to complete the
coupling reaction (Table 2, entries 2 and 3). When styrene instead
of t-butyl acrylate or methyl acrylate was used as the olefinic part-
ner, the corresponding product was obtained in a slightly lower
yield (Table 2, entries 7–10). Little effect of the substituted groups
on the styrene ring was observed for the coupling reactions. For
the Mizoroki–Heck coupling reaction, the fact that the more diffi-
cult aryl chlorides can react with olefin is the ultimate objective in
designing the Mizoroki–Heck coupling catalyst. We attempt to
carry out the reaction of 4-nitrochlorobenzene or 4-chlorotoluene
with t-butyl acrylate under the same conditions. However, no
desired products were obtained even after 48 h (Table 2, entries
12 and 13). We also investigated the reaction of iodobenzene
with t-butyl acrylate. It was found that the corresponding prod-
ucts were obtained in somewhat higher yields (Table 2, entry
13). However, in comparison with the aryl bromide, a slightly
shorter time was required to complete the Heck coupling reac-
tion. In order to extend the scope of the material, benzyl chloride
and benzyl bromide as alkyl halides instead of arylbromide were
used; however, the corresponding products were not obtained.
After the investigation of the substrates was completed, the
proposed mechanism could be obtained according to the previ-
ous report (Fig. 3). The oxidative addition reaction of Ni complex
with halogenated hydrocarbon formed aryl Ni complex 1, from
which the ligand halogen broke away to make the alkene coor-
dination with Ni, followed by C C group insertion between the
aryl group and Ni to obtain complex 2. Intramolecular β-H elim-
ination then took place in complex 2 to obtain the coupling
product 3. At the same time, Ni complex 1 can be regenerated
by reductive elimination.
[1] T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581.
[2] R. F. Heck, J. Am. Chem. Soc. 1971, 93, 6896.
[3] R. F. Heck, J. P. Nolley, J. Org. Chem. 1972, 37, 2320.
[4] R. F. Heck, Acc. Chem. Res. 1979, 12, 146.
[5] I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009.
[6] M. Shibasaki, E. M. Vogl, J. Organomet. Chem. 1999, 576, 1.
[7] J. Mo, L. Xu, J. Ruan, S. Liu, J. Xiao, Chem. Commun. 2006, 3591.
[8] W. A. Herrmann, C. Brössmer, K. Öfele, Angew. Chem. Int. Ed. 1995,
34, 1844.
[9] W. A. Herrmann, V. P. W. Böhm, C.-P. Reisinger, J. Organomet. Chem.
1999, 576, 23.
[10] a) S. L. Zultanski, G. C. Fu, J. Am. Chem. Soc. 2013, 135, 624; b) S.
Ge, J. F. Hartwig, Angew. Chem. Int. Ed. 2012, 51, 12837; c) A. R.
Ehle, Q. Zhou, M. P. Watson, Org. Lett. 2012, 14, 1202; d) T. M.
Gosig, J. Kleimark, S. O. N. Lill, S. Korsager, A. T. Lindhardt, P.-O.
Norrby, T. Skrydstrup, J. Am. Chem. Soc. 2012, 134, 443; e) F. Li,
J. J. Hu, L. L. Koh, T. S. A. Hor, Dalton Trans. 2010, 39, 5231; f) Y.
Zhang, G. Song, G. Ma, J. Zhao, C.-L. Pan, X. Li, Organometallics
2009, 28, 3233.
[11] a) P. S. Mawhand, G. P. Yiannikouros, P. S. Belica, P. Madan, J. Org.
Chem. 1995, 60, 6574; b) S. Condon-Gueugnot, E. L. Bonel, J.-Y.
Nédélec, J. Périchon, J. Org. Chem. 1995, 60, 7684.
[12] K. Mitsudo, T. Imura, T. Yamaguchi, H. Tanaka, Tetrahedron Lett.
2008, 49, 7287.
[13] a) S. Tang, C. Liu, A. Lei, Chem. Commun. 2013, 2442; b) E. A. Standley,
T. F. Jamison, J. Am. Chem. Soc. 2013, 135, 1585; c) C. Liu, S. Tang, D. Liu,
J. Yuan, L. Zheng, L. Meng, A. Lei, Angew. Chem. 2012, 124, 3698.
[14] a) K. Inamoto, J.-I. Kuroda, K. Hiroya, Y. Noda, M. Watanabe,
T. Sakamoto, Organometallics 2006, 25, 3095; b) K. Inamoto,
J.-I. Kuroda, T. Danjo, T. Sakamoto, Synlett 2005, 1624; c) P. K.
Suganthy, R. N. Prabhu, V. S. Sridevi, Tetrahedron Lett. 2013, 54, 5695.
[15] J. Jiang, C. Duan, Y. Li, J. Bai, Y. Pan, Anal. Sci. 2006, 20, x119.
[16] J. K. Wang, F. Peng, J. L. Jiang, Z. J. Lu, L. Y. Wang, J. Bai, Y. Pan,
Tetrahedron Lett. 2008, 49, 467.
Supporting Information
Additional supporting information may be found in the online
version of this article at the publisher’s web-site.
Crystallographic data for the Ni(II) complex have been deposited
with Cambridge Crystallographic Centre, CCDC No. 295856.
Copies of this information may be obtained free of charge from
the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(email: deposit@ccdc.cam.ac.uk).
Conclusions
We have developed a new combination of Ni(II) complex
containing N-(4,5-dihydrooxazol-2-yl)benzamide, which proved
to be efficient for the Heck coupling reaction of aryl iodides
Appl. Organometal. Chem. 2014, 28, 351–353
Copyright © 2014 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc