N-Heterocyclic carbene adducts of cyclopalladated ferrocenylpyridine: Synthesis, structural characterization and reusable catalytic system for Suzuki and amination of aryl chlorides in poly(ethylene glycol-400)

Article abstract of DOI:10.1016/j.ica.2012.01.063

Two air-stable carbene adducts of cyclopalladated ferrocenylpyridine 1-2 have been synthesized and characterized by elemental analysis, IR, ESI-MS, ¹H and ¹³C NMR. Additionally, their detailed structures have been determined by singl

Full text of DOI:10.1016/j.ica.2012.01.063

Inorganica Chimica Acta 386 (2012) 22–26
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Note
N-Heterocyclic carbene adducts of cyclopalladated ferrocenylpyridine: Synthesis,
structural characterization and reusable catalytic system for Suzuki and
amination of aryl chlorides in poly(ethylene glycol-400)
Chen Xu a, , Hong-Mei Li b, Hu Liu b, Zhi-Qiang Zhang b, Zhi-Qiang Wang a, Wei-Jun Fu a, Yu-Qing Zhang b,
⇑
⇑
a College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang, Henan 471022, China
b Henan University of Science and Technology, School of Chemical Engineering and Pharmaceutics, Luoyang, Henan 471003, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Two air-stable carbene adducts of cyclopalladated ferrocenylpyridine 1–2 have been synthesized and
characterized by elemental analysis, IR, ESI-MS, 1H and 13C NMR. Additionally, their detailed structures
have been determined by single-crystal X-ray analysis. The use of these complexes as catalysts for the
Suzuki and Buchwald–Hartwig amination of aryl chlorides was examined. Compound 2 was found to
be very efficient for these reactions. Typically, using 0.5–1 mol% of catalyst in the presence of 3 equiva-
lents of KtOBu as base in PEG-400 [poly(ethylene glycol-400)] at 120 °C provided coupling products in
excellent yields. Moreover, the 2/PEG-400 system could be recycled and reused three times.
Crown Copyright Ó 2012 Published by Elsevier B.V. All rights reserved.
Received 22 November 2011
Received in revised form 27 January 2012
Accepted 31 January 2012
Available online 8 February 2012
Keywords:
N-Heterocyclic carbene adduct
Palladacycle
Crystal structure
Suzuki coupling
Amination
1. Introduction
induced by the presence of a palladacycle framework with the high
activity commonly associated with phosphine ligands, and were far
Palladium-catalyzed coupling reactions such as the Suzuki cou-
pling and the Buchwald–Hartwig amination have become an extre-
mely powerful method in organic synthesis for the formation of
carbon–carbon or carbon–heteroatom bonds [1]. Employing aryl
chlorides for this reaction has been a focus because aryl chlorides
are cheaper and more available than their bromides and iodide
counterparts [2]. In recent years, N-heterocyclic carbenes (NHCs)
more active than the corresponding dimeric palladacycle. More-
over, the palladacycles containing halide acted as substrates and
efficient catalysts in the coupling reactions [18]. In view of these
findings and our continuous interest in the synthesis and applica-
tion of cyclopalladated complexes [17–20], we prepared two
carbene adducts of palladacycle 1–2 (Scheme 1) and examined their
catalytic activity in Suzuki and Buchwald–Hartwig amination. Here,
we report that 2, in combination with PEG-400 as the solvent, is an
extremely effective and reusable system for the coupling reactions
of aryl chlorides.
have become a paradigmatically new generation of strong
r-donor
ligands and widely used in palladium-catalyzed coupling reactions
[3–5]. Among them, a combination of a palladacycle framework
with highly donating and sterically demanding NHCs has been re-
ported [6–11]. However, in most cases the catalysts employed
need to be used in relatively high loadings (1–2 mol%) [6–9], and
poor recovery, which negated the advantages associated with the
use of aryl chlorides. PEGs have clear advantages as a solvent in or-
ganic synthesis because they are cheap, steady, readily available,
and nontoxic [12,13]. Recently, liquid PEGs have been adopted as
a new approach for catalyst recycling, in a broad range of catalytic
organic reactions [14–16].
2. Experimental
2.1. General procedures
Solvents were dried and freshly distilled prior to use. All other
chemicals were commercially available expect for the chloride-
bridged palladacyclic dimer A which was prepared according to
the published procedure [18]. Elemental analyses were determined
with a Carlo Erba 1160 Elemental Analyzer. IR spectra were
collected on a Bruker VECTOR22 spectrophotometer in KBr pellets.
NMR spectra were recorded on a Bruker DPX-400 spectrometer in
CDCl3 with TMS as an internal standard. Mass spectra were
measured on a LC-MSD-Trap-XCT instrument. Crystallographic data
were collected on a Bruker SMART APEX-II CCD diffractometer.
We have also found biaryl phosphine adducts of cyclopalladated
ferrocenylpyrimidine are very efficient for the amination of aryl
chlorides in PEG-400 [17]. The above adducts combine the stability
⇑
Corresponding authors.
E-mail addresses: xubohan@163.com (C. Xu), zhangyq8@126.com (Y.-Q. Zhang).
0020-1693/$ - see front matter Crown Copyright Ó 2012 Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2012.01.063

C. Xu et al. / Inorganica Chimica Acta 386 (2012) 22–26
23
Ar
N
Br
Br
OCH3
1 Ar =
2 Ar =
N
Cl
N
Cl
2
Cl
KtOBu
THF
Fe
Fe
Pd
Pd
N
Ar
Ar
Ar
N
N
A
1-2
Scheme 1. Synthesis of 1–2.
2.2. General procedure for the synthesis of carbene adducts of
cyclopalladated ferrocenylpyridine 1–2
(3 mL) was evacuated and charged with nitrogen. The reaction
mixture was then placed in an oil bath and heated at 120 °C for
16–24 h. After being cooled, the mixture was extracted with dry
diethyl ether and evaporated, the residue was isolated by flash
chromatography on silica gel to afford the desired coupled prod-
ucts. After extracting with diethyl ether, the mixture of catalyst,
and PEG-400 was solidified (cooled and then evaporated under va-
cuo) and subjected to a second run of the amination by charging
with the same substrates.
A Schlenk tube was charged with the palladacyclic dimer A
(0.1 mmol), 1,3-di-4-methoxyphenylimidazolium chloride or 1,
3-bis(2,6-diisopropylphenyl) imidazolium chloride (IPrHCl) (0.25
mmol) and KtOBu (0.3 mmol) under nitrogen. Dry THF was added
by a cannula and stirred at room temperature for 3 h. The product
was separated by passing through a short silica gel column with
CH2Cl2 as eluent, the second band was collected and afforded the
corresponding carbene adduct of cyclopalladated ferrocenylpyri-
dine complex 1–2.
3. Results and discussion
3.1. Synthesis and characterization of complexes 1–2
2.2.1. [PdCl{[(g g
5-C5H5)]Fe[( 5-C5H3)–NC5H3–Br]}(C3N2H2)(C6H4–
OCH3)2] (1)
Two new carbene adducts of palladacycle 1–2 have been easily
prepared in situ from the reaction of the chloride-bridged pallada-
cyclic dimer and the corresponding imidazolium salt in THF at
room temperature under N2 (Scheme 1). The one-pot synthesis
avoids multi-step reactions employing free carbenes [21]. These
new complexes were fully characterized by elemental analysis,
IR, ESI-MS, NMR. The 1H NMR spectra of these complexes were
consistent with the proposed structures and showed only one set
of signals in a symmetrical surrounding indicating the exclusive
formation of one isomer.
Red solid, yield 93%. 1H NMR (400 MHz, CDCl3): d 9.15 (s, 1H, py),
8.35 (d, J = 8.8 Hz, 2H, Ar), 7.80 (d, J = 8.8 Hz, 2H, Ar), 7.58 (d,
J = 8.4 Hz, 1H, py), 7.40 (s, 1H, NCHCHN), 7.33 (s, 1H, NCHCHN),
7.12 (d, J = 8.8 Hz, 2H, Ar), 6.89 (d, J = 8.4 Hz, 1H, py), 6.82 (d,
J = 8.8 Hz, 2H, Ar), 4.35 (s, 1H, C5H3), 4.11 (s, 1H, C5H3), 3.79 (s, 3H,
OCH3), 3.70 (s, 3H, OCH3), 3.44 (s, 5H, C5H5), 3.32 (s, 1H, C5H3). 13
C
NMR (100 MHz, CDCl3): 170.2, 164.9, 150.9, 146.5, 140.4, 137.8,
136.7, 135.2, 134.5, 133.7, 132.1, 127.2, 126.5, 123.3, 122.8, 118.1,
116.3, 114.8, 114.4, 114.2, 94.4, 87.2, 73.3, 70.1, 68.7, 63.0, 55.8,
55.6. MS-ESI+: m/z 726.0 [M+–Cl]. IR (KBr, cmÀ1): 2934, 1598,
1510, 1492, 1451, 1410, 1371, 1305, 1249, 1175, 1106, 941, 838,
814, 737, 692, 662. Anal. Calc. for C32H27BrClFeN3O2Pd: C, 50.36;
H, 3.57; N, 5.51. Found: C, 50.57; H, 3.38; N 5.75%.
The crystals were obtained by recrystallization from CH2Cl2–
petroleum ether solution at room temperature. The molecules
are shown in Fig. 1 and 2. The Pd atom in each complex is in a
2.2.2. [PdCl{[(g g
5-C5H5)]Fe[( 5-C5H3)–NC5H3–Br]}(C3N2H2)(C6H3–
2C3H7)2] (2)
Red solid, yield 90%. 1H NMR (400 MHz, CDCl3): d 9.19 (s, 1H,
py), 7.56 (d, J = 8.4 Hz, 1H, py), 7.45–7.49 (m, 3H, NCHCHN + Ar),
7.29–7.38 (m, 2H, Ar), 7.17–7.21 (m, 2H, Ar), 7.06 (d, J = 7.6 Hz,
1H, Ar), 6.91 (d, J = 8.4 Hz, 1H, py), 4.63–4.66 (m, 1H, CH), 4.44
(s, 1H, C5H3), 4.22 (s, 1H, C5H3), 3.81 (s, 1H, C5H3), 3.35 (s, 5H,
C5H5), 3.16–3.19 (m, 1H, CH), 2.87–2.96 (m, 2H, CH), 1.58–1.62
(m, 6H, CH3), 1.55 (d, J = 6.4 Hz, 3H, CH3), 1.42 (d, J = 6.0 Hz, 3H,
CH3), 1.19 (d, J = 6.4 Hz, 3H, CH3), 0.98 (d, J = 6.4 Hz, 3H, CH3),
0.85 (d, J = 6.4 Hz, 3H, CH3), 0.58 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3): 174.2, 164.7, 151.2, 148.1, 147.1, 145.5, 144.6, 140.1,
136.7, 136.4, 130.3, 130.0, 125.4, 125.0, 124.9, 124.6, 124.4,
123.4, 117.4, 113.8, 95.7, 86.9, 72.3, 70.5, 68.8, 62.9, 29.1, 29.0,
28.6, 28.5, 27.9, 27.3, 25.5, 25.1, 23.8, 23.5, 23.4, 21.7. MS-ESI+:
m/z 834.1 [M+–Cl]. IR (KBr, cmÀ1): 2960, 1593, 1492, 1459, 1443,
1406, 1331, 1306, 1277, 1265, 1105, 1027, 931, 909, 828, 816,
796, 762, 752, 739, 704. Anal. Calc. for C42H47BrClFeN3Pd: C,
57.89; H, 5.44; N, 4.82. Found: C, 58.05; H, 5.31; N 4.97%.
2.3. General procedure for the Suzuki and amination of aryl chlorides
Fig. 1. Molecular structure of complex 1ÁCH2Cl2. CH2Cl2 and H atoms are omitted
for clarity. Selected bond lengths (Å) and angles (°): Pd(1)–C(1) 1.973(3), Pd(1)–
C(16) 1.977(3), Pd(1)–N(1) 2.108(3), Pd(1)–Cl(1) 2.4391(9), and C(1)–Pd(1)–Cl(1)
173.48(9), C(16)–Pd(1)–N(1) 168.58(11), C(16)–Pd(1)–C(1) 90.34(13), C(1)–Pd(1)–
N(1) 80.90(12).
In a Schlenk tube, a mixture of the prescribed amount of cata-
lyst, aryl chloride (1.0 mmol), phenyl boronic acid (1.5 mmol) or
amine (1.5 mmol) and the selected base (3.0 mmol) in PEG-400

24
C. Xu et al. / Inorganica Chimica Acta 386 (2012) 22–26
Table 1
Influence of base and catalyst on the Suzuki coupling of phenyl chloride with phenyl
boronic acid.a
Entry
Catalyst (mol%)
Base
Yield(%)b
1
2
3
4
5
6
7
8
9
2(0.5)
2(0.5)
2(0.5)
2(0.5)
2(0.5)
2(0.5)
1(0.5)
A/IPrHCl (0.25/1)
Entry 6 cycle 1, 2, 3
Cs2CO3
K2CO3
Na2CO3
KOH
43
48
31
39
72
98
trace
40
98, 96, 93
NatOBu
KtOBu
KtOBu
KtOBu
KtOBu
a
Reaction conditions: PhCl (1.0 mmol), PhB(OH)2 (1.5 mmol), base (3.0 mmol),
PEG-400 (3 mL), 120 °C, 16 h.
b
Isolated yields (average of two experiments).
experiments, the Suzuki coupling of a variety of electronically
and structurally diverse aryl chlorides with phenylboronic acid
was investigated under the same reaction conditions (Table 2).
Similar to the result of chlorobenzene, excellent yields (95–96%)
were also obtained in the case of other electron-rich aryl chlorides
(entries 1–2). Ortho-substituents were tolerated and even the very
sterically hindered 2-chloro-m-xylene provided the product in 88%
isolated yield (entries 3–5). For electron-deficient aryl chlorides,
they could be coupled very efficiently with a catalytic loading as
low as 0.1 mol% (entries 6–7). Finally, heteroaryl chlorides such
as 2-chloropyridine and 3-chloropyridine were found to be
efficient coupling partners in this system (entries 8–9).
Fig. 2. Molecular structure of complex 2. H atoms are omitted for clarity. Selected
bond lengths (Å) and angles (°): Pd(1)–C(2) 1.973(3), Pd(1)–C(16) 1.995(3), Pd(1)–
N(1) 2.122(2), Pd(1)–Cl(1) 2.3888(10), and C(2)–Pd(1)–Cl(1) 173.06(8), C(16)–
Pd(1)–N(1) 170.61(11), C(16)–Pd(1)–C(2) 95.77(11), C(2)–Pd(1)–N(1) 80.87(11).
slightly distorted square-planar environment bonded to the C atom
of NHC, the chlorine atom, the nitrogen atom and the C atom of the
ferrocenyl moiety. The Pd–Ccarb [1.995(3) Å] bond length of
complex 2 is similar to those of related carbene adducts [1.992–
1.998 Å] [10,22], while it is longer than those of related complexes
1ÁCH2Cl2 [1.977(3) Å] possibly due to the steric bulk of the IPr
ligand. The imidazole ring plane of NHC is almost perpendicular
to the square plane formed by the Pd(II) center (dihedral angles
of 95.3°, 74.4° for complexes 1ÁCH2Cl2, 2, respectively). In this type
of arrangement the N-substituents of NHC reduce the steric inter-
action with palladacyclic ligand.
Table 2
Suzuki coupling of aryl chlorides with phenyl boronic acid catalyzed by 2.a
Entry Aryl halide
1
Product
Yield(%)b
96
Cl
2
95
93
Cl
H3CO
H3CO
3.2. The Suzuki coupling
3
4
In 2005, Li. et al. developed a highly efficient and reusable
Pd(OAc)2/DABCO (triethylene-diamine)/PEG system for the Suzuki
coupling [23]. However, the catalytic system could not be reused
for the reaction of aryl chlorides. To the best of our knowledge,
there was no report concerning the reusable catalytic system for
the Suzuki coupling of aryl chlorides in PEGs. Our initial explora-
tion of reaction conditions focused on the coupling of chloroben-
zene with phenylboronic acid using 0.5 mol% of 2 in PEG-400 at
120 °C for 16 h. After screening a variety of bases (Table 1, entries
1–6), KtOBu was found to give the best result. Other conditions
(0.1 mol% of 2 or 80 °C) afforded low coupled product yields (33%
and 47%, respectively. data not shown). However, 1 was almost
inactive under the same reaction conditions (entry 7) and the yield
was improved by the addition of IPrHCl (40%, entry 8) suggesting
that carbene ligand IPr participated in the catalytic cycles. It was
shown that the cyclopalladated ligand was released from the metal
center during activation of the Pd(II) precatalyst. We proposed that
the coupling reaction catalyzed by palladacycle proceeded through
a Pd(0)/Pd(II) cycle [18,24,25].
To check the reusability of the solvent PEG-400 as well as the
catalyst, the same reaction was first examined in the presence of
0.5 mol% of 2. After initial experimentation, the reaction mixture
was extracted with dry diethyl ether, and the PEG and catalyst
were solidified and subjected to a second run of the Suzuki cou-
pling by charging with the same substrates. The results of this
experiment and two subsequent experiments were consistent in
yields (98%, 96% and 93%, respectively, entry 9). In the following
Cl
92
88
OCH3
Cl
OCH3
5
Cl
6c
97
O
C
O
C
Cl
Cl
7c
8
98
96
O2N
O2N
N
Cl
Cl
N
9
90
N
N
a
Reaction conditions: catalyst 2 (0.5 mol%), aryl chloride (1.0 mmol), PhB(OH)2
(1.5 mmol), KtOBu (3.0 mmol), PEG-400 (3 mL), 120 °C, 16 h.
b
Isolated yields (average of two experiments).
Catalyst 2 (0.1 mol%).
c

C. Xu et al. / Inorganica Chimica Acta 386 (2012) 22–26
25
Table 3
Aminations of various amines with hindered aryl chlorides catalyzed by 2.a.
Entry
1
Aryl Chloride
Amine
Product
Yield(%)b
92
NH
H2N
Cl
2
3
Entry 1 cycle 1, 2, 3
91, 88, 83
95
NH
N
H2N
HN
Cl
4
5
90
89
O
Cl
Cl
O
H
N
NH2
6
93
OCH3
Cl
OCH3
H2N
H2N
NH
7
8
87
84
H
N
Cl
Cl
H
N
NH2
a
Reaction conditions: aryl chloride (1 mmol), amine (1.5 mmol), KtOBu (3.0 mmol), 2 (1 mol%), PEG-400 (3 mL), 120 °C, 24 h.
Isolated yields (average of two experiments).
b
3.3. The Buchwald–Hartwig amination
in other palladium-catalyzed reactions are underway in our
laboratory.
The high activity of 2 in the Suzuki coupling of aryl chlorides
encouraged us to examine its activity toward the Buchwald–Har-
twig amination. Based on our previous experiments [17], the reac-
tion of 2-chlorotoluene with 2,5-dimethylaniline was performed
under nitrogen atmosphere in PEG-400 in the presence of 1 mol%
of 2 as catalyst and KtOBu as base at 120 °C for 24 h, affording
the coupled product in 92% yield (Table 3, entry 1). We also
observed that the above catalytic system could be recycled and
reused three times without loss of activity for the same reaction
(entry 2). Furthermore, a variety of electronically and structurally
diverse aryl chlorides could be coupled efficiently with various
amines under the same conditions. Similar to the result of the
2,5-dimethylaniline, the reactions of aniline, morpholine and 2,
6-dimethylbenzenamine with 2-chlorotoluene provided high iso-
lated yields (89–95%, entries 3–5). For the very sterically hindered
2-chloro-m-xylene also gave the desired products in high yields
(entries 7–8).
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (No. 20902043) and the Natural Science Foundation of He-
nan Province and Henan Education Department, China (Nos.
102300410220 and 2009B150019) for financial support of this
work.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.ica.2012.01.063.
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