Synthesis and catalytic activity of pyrazolyl-functionalized N-heterocyclic carbene palladium complexes

Article abstract of DOI:10.1007/s11243-013-9784-7

Three pyrazolyl-functionalized N-heterocyclic carbene (NHC) palladium complexes based on 1-[2-(pyrazol-1-yl)phenyl]imidazole have been synthesized and characterized by physico-chemical and spectroscopic methods, and the structures of two of the complexes have been confirmed by single-crystal X-ray diffraction. The pyrazolyl-functionalized NHCs act as chelating N,C-bidentate ligands in these three complexes. Catalytic tests have proved that these complexes exhibit highly effective catalytic activity for the Suzuki-Miyaura and Mizoroki-Heck coupling reactions in water or aqueous/organic media under air. The substituents on the pyrazolyl ring exert different influences on the catalytic activity of the complexes in these coupling reactions.

Full text of DOI:10.1007/s11243-013-9784-7

Transition Met Chem (2014) 39:151–157
DOI 10.1007/s11243-013-9784-7
Synthesis and catalytic activity of pyrazolyl-functionalized
N-heterocyclic carbene palladium complexes
•
•
•
Cai-Hong Cheng Jia-Ru Xu Hai-Bin Song
Liang-Fu Tang
Received: 16 October 2013 / Accepted: 12 November 2013 / Published online: 26 November 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract Three pyrazolyl-functionalized N-heterocyclic
carbene (NHC) palladium complexes based on 1-[2-(pyr-
azol-1-yl)phenyl]imidazole have been synthesized and
characterized by physico-chemical and spectroscopic
methods, and the structures of two of the complexes have
been confirmed by single-crystal X-ray diffraction.
The pyrazolyl-functionalized NHCs act as chelating
N,C-bidentate ligands in these three complexes. Catalytic tests
have proved that these complexes exhibit highly effective
catalytic activity for the Suzuki–Miyaura and Mizoroki–
Heck coupling reactions in water or aqueous/organic media
under air. The substituents on the pyrazolyl ring exert dif-
ferent influences on the catalytic activity of the complexes in
these coupling reactions.
family of nitrogen-functionalized NHCs, pyrazolyl-func-
tionalized NHCs [12–17] have attracted considerable atten-
tion owing to the coordination versatility of pyrazole-based
ligands and the catalytic activity of their complexes [18–20].
Moreover, the electronic and steric effects of pyrazole-based
ligands can be easily fine-tuned by changing the substituents
on the pyrazolyl ring [20, 21]. The pyrazolyl group is intro-
duced to the NHCs via two general approaches; as a pendant
substituent attached to the side-arm of NHCs by the alkyl
linker [12–17] and as a bridge between two NHCs [22–24].
Examples of the pyrazolyl group attached to NHCs by an aryl
linkerareverylimited [25–27]. Our recentinvestigationshave
indicated that NHCs based on 1-[2-(pyrazol-1-yl)phenyl]-
imidazole exhibit versatile coordination modes in their silver
complexes [27], and these silver complexes possess highly
effective catalytic activity, which inspires us to exploit other
transition metal complexes of these pyrazolyl-functionalized
NHCs. As an extension of this work, we herein report the
synthesis of their palladium complexes. These palladium
complexes showed highly efficient catalytic activity for the
carbon–carbon coupling reactions under air atmosphere.
Introduction
N-Heterocyclic carbenes (NHCs) and their transition metal
complexes have become ubiquitous in coordination and
organometallic chemistry [1–4], since the isolation of the first
isolable NHC [5]. Recent investigations demonstrated that
NHCs with additional donor functionalities can provide rel-
atively stable and efficient catalysts or catalyst precursors
throughthereversiblecoordination/dissociationprocessofthe
donorfunctionsfromthemetalcenters.Thus,variousclassical
donor-functionalized NHC ligands, such as N-, P-, O-, and
S-functionalized NHCs [6–11], have been synthesized and
used in a large number of catalytic transformations. In the
Experimental
NMR (1H and 13C) were recorded on a Bruker 400 spec-
trometer, and the chemical shifts were reported in ppm
with respect to the reference (internal SiMe4 for 1H and 13
C
NMR spectra). The assignments were confirmed by stan-
dard Bruker gradient enhanced HMBC and HMQC pulse
sequences. Element analyses were carried out on an Ele-
mentar Vairo EL analyzer. Melting points were measured
with an X-4 digital micro melting-point apparatus and were
uncorrected. 1-[2-(3,5-dimethylpyrazol-1-yl)phenyl]imidazole
(DPI) [27], N-[2-(pyrazol-1-yl)phenyl]-N0-benzylimidazolium
C.-H. Cheng ꢀ J.-R. Xu ꢀ H.-B. Song ꢀ L.-F. Tang (&)
State Key Laboratory of Elemento-Organic Chemistry,
Department of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China
e-mail: lftang@nankai.edu.cn
123

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Transition Met Chem (2014) 39:151–157
chloride (PBCl) [27], and N-[2-(3,5-dimethylpyrazol-1-
yl)phenyl]-N0-benzylimidazolium chloride (DPBCl) [27]
were prepared according to the published methods.
134.6 (C6H4), 136.9 (C6H5), 145.0 (C5 of pyrazole), 152.0
(C3 of pyrazole), 152.4 (Ccarbene). Anal. Calcd for
C21H20Cl2N4Pd: C, 49.9; H, 4.0; N, 11.1. Found: C, 50.0;
H, 3.9; N, 11.1.
Synthesis of N-[2-(pyrazol-1-yl)phenyl]-N0-
benzylimidazol-2-ylidene palladium chloride (1)
Synthesis of N-[2-(3,5-dimethylpyrazol-1-yl)phenyl]-
N0-isopropylimidazolium iodide
A mixture of PBCl (0.50 g, 1.5 mmol) and Ag2O (0.35 g,
1.5 mmol) in CH2Cl2 (20 mL) was stirred for 24 h at room
temperature in the absence of light. Then, Pd(CH3CN)2Cl2
(0.39 g, 1.5 mmol) was added. The reaction mixture was
continuously stirred for 24 h. The solvent was removed
under reduced pressure, and the residue was purified by
column chromatography on silica using ethanol/dichloro-
methane (1/20 v/v) as the eluent. The yellow eluate was
concentrated to dryness to give a slightly yellow solid
A mixture of DPI (0.47 g, 2 mmol) and isopropyl iodide
(0.24 mL, 2.4 mmol) in CH3CN (5 mL) was stirred and
heated at reflux for 24 h. After cooling to room tempera-
ture, ethyl acetate (10 mL) was added. A yellow precipitate
was formed, which was filtered off and washed with dried
ethyl ether to give a yellow solid. Yield: 0.80 g (98 %);
1
m.p. 184–186 °C. H NMR (400 MHz, CDCl3): d 1.63 (d,
J = 6.7 Hz, 6H, CH(CH3)2), 2.08 (s, 3H, 5-CH3), 2.18 (s,
3H, 3-CH3), 5.26 (septet, J = 6.7 Hz, 1H, CH(CH3)2), 5.97
(s, 1H, H4 of pyrazole), 7.07 and 7.68 (s, s, br, br, 1H, 1H,
protons of imidazole), 7.48–7.54 (m, 1H), 7.69–7.72 (m,
2H) and 8.11–8.13 (m, 1H) (C6H4), 10.29 (s, 1H, proton of
imidazolium). 13C NMR (100 MHz, CDCl3): d 11.5 (5-CH3),
13.4 (3-CH3), 23.1 (CH(CH3)2), 53.7 (CH(CH3)2), 107.2
(C4 of pyrazole), 119.9 and 122.7 (carbons of imidazole),
126.8 and 129.4 (ortho-carbons of C6H4), 131.0 and 131.4
(meta-carbons of C6H4), 131.5 and 133.5 (C6H4), 141.8
(C5 of pyrazole), 150.6 (C3 of pyrazole). Anal. Calcd for
C17H21IN4: C, 50.0; H, 5.2; N, 13.7. Found: C, 50.5; H, 4.8;
N, 13.5.
1
sample of 1. Yield: 0.43 g (60 %); m.p. 195–197 °C. H
NMR (400 MHz, DMSO-d6): d 5.39 (d, J = 14.6 Hz, 1H,
CH2), 6.05 (d, J = 14.6 Hz, 1H, CH2), 6.69 (s, br, 1H, H4
of pyrazole), 7.36–7.44 (m, 3H, meta- and para-protons of
C6H5), 7.56 (d, J = 7.2 Hz, 2H, ortho-protons of C6H5),
7.67 (s, br, 1H, H3 of pyrazole), 7.75–7.87 (m, 4H, protons
of C6H4 and imidazole), 7.93 (d, J = 4.0 Hz, 2H, C6H4),
8.39 (s, br, 1H, H5 of pyrazole). 13C NMR (100 MHz,
DMSO-d6): d 53.0 (CH2), 109.2 (C4 of pyrazole), 124.0
and 124.1 (carbons of imidazole), 127.6 and 128.7 (ortho-
carbons of C6H4), 128.2 (para-carbon of C6H5), 128.3
(ortho-carbons of C6H5), 128.8 (meta-carbons of C6H5),
130.6 and 131.7 (meta-carbons of C6H4), 132.7 and 132.9
(C6H4), 136.6 (C5 of pyrazole), 136.8 (C6H5), 145.0 (C3 of
pyrazole),
151.7
(Ccarbene).
Anal.
Calcd
for
Synthesis of N-[2-(3,5-dimethylpyrazol-1-yl)phenyl]-
N0-isopropylimidazol-2-ylidene palladium iodide
acetate (3)
C19H16Cl2N4Pd: C, 47.8; H, 3.4; N, 11.7. Found: C, 47.5;
H, 3.4; N, 11.6.
Synthesis of N-[2-(3,5-dimethylpyrazol-1-yl)phenyl]-
N0-benzylimidazol-2-ylidene palladium chloride (2)
A mixture of N-[2-(3,5-dimethylpyrazol-1-yl)phenyl]-N0-
isopropylimidazolium iodide (0.41 g, 1 mmol) and
Pd(OAc)2 (0.22 g, 1 mmol) in CH2Cl2 (20 mL) was stirred
at room temperature for 24 h. The reaction mixture was
filtered. The filtrate was concentrated to dryness and
washed with dried ethyl ether to give a yellow solid sample
This compound was obtained similarly using DPBCl
instead of PBCl as described above for 1 as a slightly
yellow solid. Yield: 46 %; m.p. 272–274 °C. 1H NMR
(400 MHz, DMSO-d6): d 2.06 (s, 3H, 5-CH3), 2.14 (s, 3H,
3-CH3), 5.42 (d, J = 15.4 Hz, 1H, CH2), 6.03 (d,
J = 15.4 Hz, 1H, CH2), 6.29 (s, 1H, H4 of pyrazole),
7.07–7.16 (m, 2H, meta-protons of C6H5), 7.33–7.37 (m,
2H, ortho-protons of C6H5), 7.39 (d, J = 2.0 Hz, 1H, para-
proton of C6H5), 7.69 and 7.85 (d, d, J = 2.0 Hz, 1H, 1H,
protons of imidazole), 7.81–7.84 and 7.90–7.94 (m, m, 2H,
2H, C6H4). 13C NMR (100 MHz, DMSO-d6): d 12.4 (3-
CH3), 14.0 (5-CH3), 52.5 (CH2), 108.8 (C4 of pyrazole),
123.7 and 124.3 (carbons of imidazole), 126.9 (meta-car-
bons of C6H5), 127.7 and 129.5 (ortho-carbons of C6H4),
127.9 (para-carbon of C6H5), 128.8 (ortho-carbons of
C6H5), 130.1 and 131.7 (meta-carbons of C6H4), 131.2 and
1
of 3. Yield: 0.49 g (86 %); m.p. 134–136 °C. H NMR
(400 MHz, CDCl3):
d
1.41 (d, J = 6.4 Hz, 3H,
CH(CH3)2), 1.51 (d, J = 6.4 Hz, 3H, CH(CH3)2), 1.82 (s,
3H, 5-CH3), 2.04 (s, 3H, 3-CH3), 2.14 (s, 3H, COCH3),
5.69–5.77 (m, 1H, CH(CH3)2), 6.03 (s, 1H, H4 of pyra-
zole), 7.04 and 7.17 (s, s, br, br, 1H, 1H, protons of
imidazole), 7.61–7.76 (m, 4H, C6H4). 13C NMR
(100 MHz, CDCl3): d 12.9 (5-CH3), 13.8 (COCH3), 14.1
(3-CH3), 21.5 and 24.2 (CH(CH3)2), 31.6 (CH(CH3)2),
108.7 (C4 of pyrazole), 118.8 and 122.9 (carbons of
imidazole), 127.1, 130.2, 130.3 and 131.3 (ortho- and
meta-carbons of C6H4), 132.8 and 135.0 (C6H4), 143.5
(C5 of pyrazole), 151.0 (C3 of pyrazole), 152.4 (Ccarbene).
123

Transition Met Chem (2014) 39:151–157
153
Anal. Calcd for C21.95H28.93Cl2I1.02N4O3.95Pd: C, 36.7; H,
4.1; N, 7.8. Found: C, 36.6; H, 3.7; N, 7.5.
Table 1 Crystal data and refinement parameters for complexes 1 and 3
Complex
Formula
1
3.CH3CO2H.CH2Cl2
C19H16Cl2N4Pd
C21.95H28.93Cl2I1.02
N4O3.95Pd
Crystal structure determinations
Formula weight
477.66
719.32
Crystals of 1 and 3 suitable for X-ray analyses were obtained
by slow diffusion of hexane into their CH2Cl2 solutions at
4 °C. The C(1), C(10), C(13)–C(19), N(1) and N(4) atoms in
1 were found to be disordered. Satisfactory results were
obtained when these atoms were given occupancy factors of
0.598, and C(1)0, C(10)0, C(13)0–C(19)0, N(1)0 and N(4)0
atoms were given occupancy factors of 0.402. The geometry
of disordered groups was restricted, and isotropic displace-
ment parameters for all disordered atoms were used. Crystals
of 3 contained one CH3CO2H and one CH2Cl2 molecules.
The acetate position was partly replaced by iodide (2.4 %) in
this complex. All intensity data were collected on a Rigaku
Saturn CCD detector at 113(2) K. Semi-empirical absorption
corrections were applied using the CrystalClear program
[28]. The structures were solved by direct methods and dif-
ference Fourier map using SHELXS of the SHELXTL
package and refined with SHELXL [29] by full-matrix least-
squares on F2. A summary of the fundamental crystal data for
1 and 3 is listed in Table 1.
Crystal size (mm)
0.24 9 0.22 9 0.18 0.20 9 0.18 9 0.12
˚
k (MoKa) (A)
0.71073
Triclinic
P¯ı
0.71073
Monoclinic
P21/n
Crystal system
Space group
˚
a (A)
9.397(3)
14.846(4)
15.915(5)
65.95(1)
89.59(2)
74.01(1)
1,935.1(10)
4
8.403(2)
22.464(6)
15.206(4)
90
˚
b (A)
˚
c (A)
a (o)
b (o)
c (o)
94.722(5)
90
3
˚
V (A)
2,860.6(14)
4
Z
Dc (g.cm-3
F(000)
)
1.640
1.670
952
1,418
l (mm-1
)
1.245
1.974
h Range (°)
No. of measured
reflections
1.41–29.11
26,838
1.62–27.89
29,171
No. of unique
reflections (Rint
10,300 (0.0399)
6,923
6,744 (0.0436)
5,831
)
General procedure for the catalytic Suzuki–Miyaura
reaction
No. of observed
reflections with
(I [ 2r(I))
No. of parameters
In a typical experiment, the mixture of PhB(OH)2 (0.15 g,
1.2 mmol), ArX (1 mmol), Cs2CO3 (0.66 g, 2.0 mmol) and
NHC–Pd complex (n mol%) was charged into a reaction
tube (10 mL) with 2 mL of mixed solvent of isopropyl
alcohol and water (1/1 v/v) or pure water. After the reac-
tion mixture was stirred at 80 °C for a given time, water
(10 mL) was added. The reaction mixture was extracted
with ethyl ether (3 9 10 mL). The organic phases were
combined and dried over anhydrous Na2SO4. The solvent
was removed under reduced pressure, and the residue was
purified by column chromatography on silica using hexane
as the eluent to give the corresponding diphenyl deriva-
tives. When ArX was 4-bromoacetophenone, ethyl acetate
was used as the eluent. The products were confirmed by
comparison with NMR spectroscopic data in the literature.
405
318
GOF
1.052
1.034
Residuals R1, wR2
0.0505, 0.1170
0.0546, 0.1594
solvent was removed under reduced pressure, and the res-
idue was purified by column chromatography on silica
using ethyl acetate/hexane as the eluent to give the corre-
sponding trans-1,2-diarylethene, which was confirmed by
comparison with NMR spectroscopic data in literature.
Results and discussion
Synthesis and characterization of NHC–Pd complexes
General procedure for the catalytic Mizoroki–Heck
reaction
The pyrazolyl-functionalized NHC–Pd complexes (1) and
(2) were easily obtained by the carbene transfer reaction of
the corresponding NHC–Ag complexes with Pd(CH3-
CN)2Cl2 (Scheme 1), while complex 3 was obtained by the
direct reaction of the imidazolium salt with Pd(OAc)2.
Complexes 1–3 were stable to air and moisture, and they
were soluble in chlorinated solvents. These three
In a typical experiment, a mixture of ArX (1 mmol), sty-
rene (0.14 mL, 1.2 mmol), K2CO3 (0.28 g, 2.0 mmol) and
NHC–Pd complex (n mol%) was charged into a reaction
tube (10 mL) with 2 mL of mixed solvent of DMF and
water (3/1 v/v). Then, the reaction mixture was stirred at
120 °C for 24 h. After cooling to room temperature, the
123

154
Transition Met Chem (2014) 39:151–157
Scheme 1 Synthesis of pyrazolyl-functionalized NHC–Pd complexes
complexes have been characterized by elemental analyses
and NMR spectroscopy.
Compared with the spectra of their imidazolium salt
1
precursors, a notable change in the H NMR spectra of
these three complexes was the disappearance of the char-
acteristic proton signal of imidazolium, indicating the
formation of NHC–Pd complexes along with the deproto-
nation of the acidic hydrogen. In addition, an obvious
carbene carbon signal was observed around 152 ppm in
their 13C NMR spectra, which is similar to those of
reported NHC–Pd complexes [30, 31]. The 1H NMR
spectra of 1 and 2 indicated the methylene protons of the
benzyl group were nonequivalent, and an AB system was
observed at room temperature. At the same time, two sets
of 1H and 13C NMR signals corresponding to the isopropyl
methyl groups were observed in complex 3. These results
suggest the presence of large steric repulsion in these three
complexes, possibly owing to the chelating coordination of
the NHC ligands, which prevents the free rotation of
substituents.
Fig. 1 Molecular structure of 1. The thermal ellipsoids are drawn
˚
at the 30 % probability level. Selected bond distances (A) and
angles (°): Pd(1)–C(10) 1.979(4), Pd(1)–N(1) 2.004(4), Pd(1)–Cl(1)
2.336(1), Pd(1)–Cl(2) 2.321(1) and C(10)–Pd(1)–N(1) 86.4(2),
C(10)–Pd(1)–Cl(2) 89.9(1), C(10)–Pd(1)–Cl(1) 176.0(1), N(1)–
Pd(1)–Cl(1) 89.6(1), Cl(1)–Pd(1)–Cl(2) 94.07(4), N(4)–C(13)–C(14)
113.9(5)
slightly distorted square-planar coordination geometry. The
deviation of the palladium atom from the square plane is
˚
only 0.0040 A in 1 and 0.0252 A in 3, respectively. The
˚
˚
Pd–C and Pd–N bond distances are 1.979(4) A and 2.004(4)
˚
˚
A in 1, respectively, similar to the Pd–C (1.956(5) A) and
˚
Pd–N (2.037(5) A) bond distances in 3. These values are
comparable to those of other known pyrazolyl-functional-
ized NHC–Pd complexes, such as those in LPdCl2 (Pd–C
˚
˚
1.970(4) A and Pd–N 2.042(3) A, L = 3-butyl-1-(pyra-
zolylmethyl)imidazol-2-ylidene) [16] and L02Pd2Br2 (av.
0
˚
˚
Pd–C 1.965 A and av. Pd–N 2.097 A, L = N-[bis(3,5-
dimethylpyrazol-1-yl)methyl]phenyl-N0-benzylimidazol-2-
ylidene) [26].
Crystal structures of 1 and 3
The molecular structures of 1 and 3 have been further
confirmed by X-ray structural analyses. The X-ray crystal
structure of complex 1 consists of two crystallographically
independent molecules with similar structural parameters.
One of them is presented in Fig. 1. The crystal structure of
complex 3 is shown in Fig. 2. The pyrazolyl-functionalized
NHCs act as [N,C] chelating bidentate ligands through the
carbene carbon and pyrazolyl nitrogen atoms coordinating
to the palladium atom in these two complexes, resulting in
a seven-membered metallocycle with boat-like conforma-
tion. The palladium atom exhibits a four-coordinate
The dihedral angles between the phenyl plane with
pyrazolyl and imidazolyl planes are significantly different
in these two complexes, possibly owing to the different
substituents in the third position of the imidazolyl ring and
the different anions in the palladium atom. The dihedral
angle between the phenyl plane and the pyrazolyl plane is
52.7° in 1, smaller than the corresponding dihedral angle in
3 (58.7°), while the dihedral angle between the phenyl
plane and the imidazolyl plane is 126.4° in 1, larger than
that in 3 (123.8°). In addition, the electronegative oxygen is
123

Transition Met Chem (2014) 39:151–157
155
Table 2 Catalytic activity of NHC–Pd complexes in the Suzuki–
Miyaura reaction
Entry
ArX
Cat.
n
t/h
Yield (%)a,b
1c
2c
3c
C6H5Br
1
2
3
1
2
3
2
3
1
2
1
2
1
2
1
2
3
1
2
1
2
3
1
2
3
1
2
3
1
2
3
0.01
0.01
0.1
1
99
98
99
97
96
97
94
88
90
97
83
86
96
95
99
84
87
99
82
98
96
90
98
99
92
88
93
90
69
68
36
C6H5Br
1
C6H5Br
12
1
4
C6H5Br
0.01
0.01
0.1
5
C6H5Br
1
6
C6H5Br
12
12
12
2
7
o-CH3OC6H4Br
o-CH3OC6H4Br
o-C2H5C6H4Br
o-C2H5C6H4Br
o-ClC6H4Br
0.01
0.01
0.1
8
9
10
11
12
13
14
15
16
17
18c
19c
20
21
22
23
24
25c
26c
27c
28
29
30
31
a
0.1
2
0.1
24
24
24
24
12
12
12
4
o-ClC6H4Br
0.1
m-CH3OC6H4Br
m-CH3OC6H4Br
m-FC6H4Br
0.1
Fig. 2 Molecular structure of 3. The thermal ellipsoids are drawn at
the 30 % probability level. The uncoordinated solvents and the part
incorporation of iodide have been deleted for clarity. Selected bond
0.1
0.005
0.005
0.1
˚
distances (A) and angles (°): Pd(1)–I(1) 2.5759(7), Pd(1)–C(14)
m-FC6H4Br
1.956(5), Pd(1)–N(1) 2.037(5), Pd(1)–O(1) 2.083(4), C(18)–O(1)
1.308(10), C(18)–O(2) 1.246(12) and C(14)–Pd(1)–N(1) 85.4(2),
C(14)–Pd(1)–O(1) 174.9(2), C(14)–Pd(1)–I(1) 90.7(2), N(1)–Pd(1)–
I(1) 175.7(1), C(16)–C(15)–C(17) 113.5(6), O(1)–C(18)–O(2)
121.2(8), O(2)–C(18)–C(19) 123.0(8)
m-FC6H4Br
m-FC6H4Br
0.005
0.01
0.1
m-FC6H4Br
10
12
12
12
12
12
12
10
12
12
24
24
24
p-BrC6H4COCH3
p-BrC6H4COCH3
p-BrC6H4COCH3
p-BrC6H4COCH3
p-BrC6H4COCH3
p-BrC6H4COCH3
1-bromonaphthalene
1-bromonaphthalene
1-bromonaphthalene
2-bromopyridine
2-bromopyridine
2-bromopyridine
0.1
trans to the carbene carbon atom in 3, like those in other
pyrazolyl-functionalized NHC–Pd complexes [14]. The
angle C(14)–Pd(1)–O(1) is 174.9(2)° in 3. It is worth not-
ing that some angles around the C(13) atom in 1 (such as
the angle N(4)–C(13)–C(14) of 113.9(5)°) and the C(15)
atom in 3 (such as the angle C(16)–C(15)–C(17) of
113.5(6)°) markedly deviate from the tetrahedral geometry
of the sp3 hybridized carbon atom, which reflects the pre-
sence of the steric repulsion between the benzyl in 1 and
isopropyl in 3 with other substituents in these complexes,
as also indicated by their NMR spectra.
0.1
0.1
0.1
0.1
0.01
0.01
0.01
0.1
0.1
0.1
Isolated yield
b
c
The catalytic activity of complexes 1–3
Average of two runs
Water as the solvent
Palladium-catalyzed cross-coupling reaction has become
an extremely powerful tool for the formation of carbon–
carbon and carbon–heteroatom bonds. NHC–Pd complexes
have been successfully applied in this area [32, 33], since
Herrmann and co-works reported well-defined NHC–Pd
complexes as efficient catalysts in the Heck reaction [4].
Additionally, NHC–metal complexes for catalysis in
aqueous media have received considerable attention
because water is an attractive benign solvent [34]. Some
cross-coupling reactions catalyzed by NHC–Pd complexes
have been successfully performed in water in recent years
[31, 34–38]. Herein, our studies showed that complexes
1–3 exhibited highly effective catalytic activities in the
Suzuki–Miyaura (Table 2) and Mizoroki–Heck (Table 3)
coupling reactions in water or aqueous/organic media
under air atmosphere.
The initial cross-coupling reaction between PhBr and
PhB(OH)2 was performed in pure water using Cs2CO3 as
the base at 80 °C. The corresponding coupled product was
obtained in excellent isolated yield when 0.01 mol% of 1
or 2 as well as 0.1 mol% of 3 was used as the catalyst
123

156
Transition Met Chem (2014) 39:151–157
catalyst for the reaction of m-FC6H4Br (Table 2, entry 15).
Furthermore, the coupling reaction proceeded significantly
faster upon using pure water as the solvent (Table 2,
entry 18) [25]. The cross-coupling reactions of other
substituted aryl bromides could give moderate to good
yields, upon prolonging the reaction time or increasing the
loading amount of catalysts. The data of Table 2 revealed
that complexes 1 and 2 possess higher catalytic activity
than complex 3. In most cases, no obvious catalytic activity
difference was observed between 1 and 2, indicating that
the substituents on the pyrazolyl ring have slight influences
on the catalytic activities of the complexes. This is dif-
ferent from that in pyridyl-supported tridentate pyrazolyl-
functionalized NHC–Pd complexes, in which the catalytic
activity was obviously decreased by the substituents on the
pyrazolyl ring [25]. Under the present conditions, these
complexes showed relatively low catalytic activity for the
coupling reaction of 2-bromopyridine (Table 2, entries
29–31).
Table 3 Catalytic activity of NHC–Pd complexes in the Mizoroki–
Heck reaction
Entry
ArX
Cat.
n
Yield (%)a,b
1
C6H5Br
1
2
3
1
2
3
1
2
3
1
2
1
2
3
1
2
3
1
2
3
1
2
1
2
3
1
2
3
1
2
3
2
0.5
0.5
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
67
89
75
74
95
89
95
57
79
99
99
92
80
85
99
96
85
92
86
99
84
40
95
95
97
44
23
29
85
45
52
99
2
C6H5Br
3
C6H5Br
4
o-CH3OC6H4Br
o-CH3OC6H4Br
o-CH3OC6H4Br
o-C2H5C6H4Br
o-C2H5C6H4Br
o-C2H5C6H4Br
m-FC6H4Br
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
a
m-FC6H4Br
m-CH3OC6H4Br
m-CH3OC6H4Br
m-CH3OC6H4Br
m-BrC6H4CHO
m-BrC6H4CHO
m-BrC6H4CHO
p-BrC6H4COCH3
p-BrC6H4COCH3
p-BrC6H4COCH3
2,4,6-Me3C6H2Br
2,4,6-Me3C6H2Br
1-bromonaphthalene
1-bromonaphthalene
1-bromonaphthalene
2-bromopyridine
2-bromopyridine
2-bromopyridine
2-bromothiophene
2-bromothiophene
2-bromothiophene
C6H5I
Complexes 1–3 also showed good catalytic activity for
the Heck reaction between aryl halides and styrene
(Table 3). Moderate to excellent yields were obtained
when 0.5 mol% of complex was used as the catalyst
(Table 3, entries 1–3, 18–24 and 32). All tested aryl halides
gave satisfactory yields when the loading amount of cata-
lyst was increased to 1.0 mol% (Table 3, entries 4–17 and
25). It can be observed from Table 3 that complex 1 shows
higher catalytic activity than complex 2 in most cases,
suggesting that the substituents on the pyrazolyl ring
decrease the catalytic activity of complex 2, presumably as
a result of steric and electronic effects of the substituents
influencing the coordination/dissociation process of the
pyrazolyl nitrogen to the palladium center [14]. Table 3
also reveals that the catalytic activity of complex 3 is
comparable to that of complexes 1 and 2 in the Heck
reaction. For example, essentially quantitative product
yield was obtained for the coupling of 4-bromoacetophe-
none when 0.5 mol% of complex 3 was used as the catalyst
(Table 3, entry 20), which may be the result of the acetato
ligand stabilizing active species in the Heck reaction [39,
40]. In addition, for heteroaryl bromides (Table 3, entries
26–31), the yields still need to be further improved.
Isolated yield
b
Average of two runs
(Table 2, entries 1–3). This cross-coupling reaction could
also proceed smoothly to give the expected product in the
co-solvent of isopropyl alcohol and water (1/1 v/v)
(Table 2, entries 4–6). Taking into account the solubility of
the catalysts and substrates, other cross-coupling reactions
of aryl halide with PhB(OH)2 were carried out in the co-
solvent of isopropyl alcohol and water (Table 2, entries
7–17, 20–24 and 28–31). Almost quantitative yield was
obtained when only 0.005 mol% of 1 was used as the
Conclusion
In a summary, three pyrazolyl-functionalized NHC–Pd
complexes have been synthesized. The pyrazolyl-func-
tionalized NHCs act as chelating N,C-bidentate ligands in
these complexes. These complexes exhibit highly effective
catalytic activities in the Suzuki–Miyaura and Mizoroki–
Heck coupling reactions in water or aqueous/organic media
under air atmosphere. Additionally, the substituents on the
123

Transition Met Chem (2014) 39:151–157
157
12. Lee HM, Chiu PL, Hu CH, Lai CL, Chou YC (2005) J Organomet
Chem 690:403
13. Messerle BA, Page MJ, Turner P (2006) Dalton Trans 3927
14. Wang R, Twamley B, Shreeve JM (2006) J Org Chem 71:426
15. Chiu PL, Chen CY, Lee CC, Hsieh MH, Chuang CH, Lee HM
(2006) Inorg Chem 45:2520
pyrazolyl ring have no obvious influence on the catalytic
activity of complexes in the Suzuki–Miyaura reaction,
while these substituents decrease the catalytic activity of
the complex in the Mizoroki–Heck reaction in most cases.
Further studies on the structure–activity relationships of
such catalysts are currently in progress.
16. Wang R, Zeng Z, Twamley B, Piekarski MM, Shreeve JM (2007)
Eur J Org Chem 655
17. Page MJ, Wagler J, Messerle BA (2009) Dalton Trans 7029
18. Ojwach SO, Darkwa J (2010) Inorg Chim Acta 363:1947
19. Viciano-Chumillas M, Tanase S, de Jongh LJ, Reedijk J (2010)
Eur J Inorg Chem 3403
Supplementary material
20. Halcrow MA (2009) Dalton Trans 2059
CCDC 959855 for 1 and 959856 for 3 contain the sup-
plementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
21. Guerrero M, Pons J, Ros J (2010) J Organomet Chem 695:1957
22. Scheele UJ, John M, Dechert S, Meyer F (2008) Eur J Inorg
Chem 373
23. Jeon SJ, Waymouth RM (2008) Dalton Trans 437
24. Zhou Y, Chen W (2007) Organometallics 26:2742
25. Zeng F, Yu Z (2006) J Org Chem 71:5274
26. Li Q, Xie YF, Sun BC, Yang J, Song HB, Tang LF (2013)
J Organomet Chem 745–746:106
Acknowledgments This work is supported by the National Natural
Science Foundation of China (No. 20972075) and NFFTBS
(No. J1103306).
27. Cheng CH, Chen DF, Song HB, Tang LF (2013) J Organomet
Chem 726:1
28. CrystalStructure 3.7.0 and Crystalclear 1.36: Crystal Structure
Analysis Package, Rigaku and Rigaku/MSC (2000) TX
29. Sheldrick GM (2008) Acta Crystallogr A64:112
30. Liu QX, Zhao LX, Zhao XJ, Zhao ZX, Wang ZQ, Chen AH,
Wang XG (2013) J Organomet Chem 731:35
31. Ma MT, Lu JM (2012) Appl Organometal Chem 26:175
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