Ferrocene-tagged N-heterocyclic carbene-Pd complex for Suzuki-Miyaura coupling

Article abstract of DOI:10.1007/s00706-013-0970-2

We demonstrate that the ferrocene-tagged N-heterocyclic carbene (NHC)-Pd(II) complex can act as an efficient heterogeneous catalyst for Suzuki-Miyaura cross-coupling in dimethylformamide (DMF)-water. This complex was found to be an active and efficient ca

Full text of DOI:10.1007/s00706-013-0970-2

Monatsh Chem (2013) 144:1355–1361
DOI 10.1007/s00706-013-0970-2
ORIGINAL PAPER
Ferrocene-tagged N-heterocyclic carbene-Pd complex
for Suzuki–Miyaura coupling
•
Dattaprasad M. Pore Dipak S. Gaikwad
•
Jayavant D. Patil
Received: 6 February 2013 / Accepted: 12 March 2013 / Published online: 8 May 2013
Ó Springer-Verlag Wien 2013
Abstract We demonstrate that the ferrocene-tagged N-
heterocyclic carbene (NHC)-Pd(II) complex can act as an
efficient heterogeneous catalyst for Suzuki–Miyaura cross-
coupling in dimethylformamide (DMF)-water. This com-
plex was found to be an active and efficient catalyst for
coupling of aryl iodides, bromides, and even less reactive
chlorides with boronic acids and pinacol ester of boronic
acid.
termination of the catalytic cycle [17–19]. The difficulties
involved in removal of these byproducts and the high price
of phosphine ligands are other drawbacks that have spurned
enormous interest in the discovery of new NHCs as supe-
rior alternatives to phosphine ligands.
Ferrocene-containing compounds have wide applica-
tions in the fields of catalysis, material science, and
coordination chemistry [20–23]. Atkinson et al. have stated
that ‘‘the ferrocene moiety has played a significant role as a
backbone or a substituent in ancillary ligands in coordi-
nation chemistry, due to (1) the specific and unique
geometries that the ferrocene provides and (2) its electronic
(redox) properties, whereby the possibility of switching the
redox state of the ferrocene backbone gives access to
potential control of reactivity at a metal center’’ [23].
Hence, synthetic chemists have focused their attention on
ferrocene-tagged NHC metal complexes of W(0), Pd(II),
and Hg(II) containing a monodentate imidazolylidene
ligand [24]. These ferrocene-tagged NHCs have been pre-
pared in situ by deprotonation of the imidazolium
precursor, viz. 1-(ferrocenylmethyl)-3-methylimidazolium
iodide [24, 25]. There are also reports on synthesis of cy-
clopalladated ferrocenylimine palladium catalyst and its
activity in cross-coupling reactions [26–30]. The first
example of a ferrocene-based ligand containing two NHCs
was reported by Coleman et al. [31], and later on NHCs
possessing one or two 3,4-dimethylphosphaferrocenyl
substituents were prepared by Ganter’s group [32].
Impressed by these and in continuation of our interest in
coupling reactions [33, 34], we wish to explore ferrocene-
tagged NHC-Pd complex as an efficient heterogeneous
catalyst for Suzuki–Miyaura coupling (Scheme 1), the
most celebrated tool for constructing C–C bond [35, 36]
which was recognized with the 2010 Nobel Prize in
Chemistry.
Keywords Suzuki reaction Á Boronic acid pinacol ester Á
N-heterocyclic carbene Á Aerobic condition
Introduction
Transition-metal complexes of N-heterocyclic carbenes
(NHCs) in cross-coupling reactions have made revolu-
tionary changes in synthetic chemistry [1–14]. As
compared with phosphine ligands, NHCs bind through
stronger bonds with most of the metals, avoiding the
necessity of excess ligand in catalytic reaction [15, 16].
Hence, they play a dual role of catalyst as well as ligand
and overcome limitations raised due to use of phosphine
ligands in catalytic reactions, viz. oxidation of phosphines
to phosphine oxides, formation of stable phosphido-
bridged catalytically inactive dimers, and also cleavage of
P–C bond causing degradation of the ligand and thus
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-0970-2) contains supplementary
material, which is available to authorized users.
D. M. Pore (&) Á D. S. Gaikwad Á J. D. Patil
Department of Chemistry, Shivaji University,
Kolhapur 416 004, India
e-mail: p_dattaprasad@rediffmail.com
123

1356
D. M. Pore et al.
X
Scheme 1
R
R'O
R'O
Cat. 3 + Na2CO3
B
R
+
DMF:H2O 3:1
Y
Y
1
2
4
X = I, Br, Cl
Y = COCH3, OCH3, CN, CHO,
NO2, CH3, NH2
Fe
I
N
N
N
N
Pd
I
Fe
3
Fig. 1 Solid-state 13C NMR of ferrocene-tagged NHC-Pd complex
Results and discussion
Initially, ferrocene-tagged NHC-Pd complex 3 (Fig. 1) was
synthesized by using reported procedure from ferrocene
and benzimidazole [25]. The Fourier-transform infrared
(FT-IR) result for the synthesized complex 3 is in accor-
dance with the literature [25]. Due to insufficient solubility
of Pd complex in dimethyl sulfoxide (DMSO), we further
characterized the complex by solid-state nuclear magnetic
resonance (NMR) (Fig. 1), as a confirmation and support-
ing tool. The solid-state NMR of 3 exhibits signals at
d = 33.2 and 49.0 ppm for N-methyl and methylene car-
bon, respectively. Cyclopentadiene (Cp) ring carbons were
centered at 68.6 ppm, while the ipso-carbon of the substi-
tuted Cp ring appeared at 79.7 ppm. Aromatic carbons of
benzimidazole moiety were observed in the region
of 108.9–138.4 ppm, and –CH2 of NHC appeared at
176.9 ppm.
Fig. 2 SEM image of ferrocene-tagged NHC-Pd complex
analysis (TGA) carried out in nitrogen atmosphere over the
temperature range of 20–1,000 °C with heating rate of
10 °C/min showed that the catalyst is stable up to 200 °C,
after which slow decomposition starts and continues until
The crystalline morphology with fibrous crystal growth
was confirmed from scanning electron microscopy (SEM)
micrograph, displayed in Fig. 2. Thermal gravimetric
123

Ferrocene-tagged N-heterocyclic carbene-Pd complex
1357
Table 1 Effect of solvent, base, and amount of catalyst on Suzuki–
Miyaura cross-couplinga
HO
O H
B
F
HO
O H
B
Time/h Yield/%b
O
O
Entry Catalyst/mol% Solvent
Base
B
1
2
Toluene
Toluene
Toluene
Na2CO3
K3PO4
K2CO3
7
7
7
8
9
9
6
6
6
8
7
8
63
60
56
54
52
50
65
65
61
68
60
58
50
45
40
75
71
65
88
78
75
89
72
58
2
2
N N
3
2
4
2
Acetonitrile Na2CO3
Acetonitrile K3PO4
Acetonitrile K2CO3
5
6
7
5
2
6
2
Fig. 3 Diversity of boronic acids
7
2
Dioxane
Dioxane
Dioxane
THF
Na2CO3
K3PO4
K2CO3
Na2CO3
K3PO4
K2CO3
8
2
water with 3 mmol Na2CO3 is the best option, resulting in
88 % yield of the product.
9
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
a
2
Various solvents, viz. toluene, acetonitrile, dioxane,
tetrahydrofuran (THF), DMF, and water, were screened for
Suzuki reaction, with observed yield of the desired product
of 40–68 % (Table 1, entries 1–16). However, when DMF
was employed, the yield was increased to 75 % (Table 1,
entry 16). Water plays an important role in improving the
reactivity of Suzuki reaction [37]. Hence, we tried the
DMF:water system and observed that the yield of the
desired product was boosted to 88 % (Table 1, entry 19).
After further examination of the catalyst loading, a good
result was obtained by using 2 mol % of the catalyst
(Table 1, entries 19, 22–24), and we found the best con-
dition for Suzuki reaction as mentioned in entry 19
(Table 1).
2
THF
2
THF
2
Water
Water
Water
DMF
Na2CO3 10
K3PO4 10
K2CO3 10
2
2
2
Na2CO3
K3PO4
K2CO3
3
2
DMF
3
2
DMF
3
2
DMF:water Na2CO3
DMF:water K3PO4
2
2
2.5
2
DMF:water K2CO3 2.5
2.5
1
DMF:water Na2CO3
DMF:water Na2CO3
2
3
After optimization of the reaction conditions, to delin-
eate this approach, particularly in regard to library
construction, this methodology was evaluated by using aryl
halides and different boronic acids (Fig. 3). A wide range
of aryl halides, possessing electron-rich or electron-defi-
cient substituents, worked well with arylboronic acids. In
Suzuki coupling, activation of aryl chloride substrates has
been limited as compared with activation of aryl bromides
and iodides [38]. Recently, special emphasis on Suzuki
coupling of aryl chlorides with boronic acid has been
reported by Sau et al. [38] and Terashima et al. [39]. It is
noteworthy that iodo-, bromo-, as well as less reactive
chloro-substituted aromatic halides undergo smooth cou-
pling with boronic acid under optimized reaction
conditions. Coupling of heteroarylboronic acid pinacol
ester (Table 2, entries g, o) with aryl halides was also
performed smoothly under the optimized reaction condi-
tions. We next examined the performance of the catalyst in
the coupling of dihalide, viz. 1-bromo-4-iodobenzene with
phenylboronic acid (Table 2, entry s) and found that the
Suzuki–Miyaura coupling worked equally well to produce
terphenyl.
0.5
DMF:water Na2CO3 4.5
Reaction conditions: bromobenzene (1 mmol), phenylboronic acid
(1.2 mmol), base (3 mmol), 80 °C; for entries 19–24, DMF:water:
3:1 (v/v) is used
b
Isolated yield
THF, tetrahydrofuran
850 °C. Finally, the residue of 22.71 % remaining at
1,000 °C is due to the elemental forms of Fe and Pd, since
the possibility of alloy formation is ruled out due to the
very high melting points of both Fe and Pd. This helped us
to quantify the amount of Fe and Pd in 3, which was cal-
culated to be 11.63 and 11.08 %, respectively. CHNS
elemental analysis of the catalyst showed 43.01 % C,
3.5 % H, and 4.8 % N. Thus, from these calculations, the
content of iodine emerges as 25.98 %. All these elemental
compositions agree with the molecular formula of the
catalyst, i.e., C38H36Fe2I2N4Pd.
We next shifted our attention towards screening for the
best condition for Suzuki reaction of bromobenzene and
phenylboronic acid by varying (1) solvent composition, (2)
nature of the base, and (3) catalyst loading. The results of
optimization are summarized in Table 1. The examination
of solvent/base combination revealed that use of DMF/
To evaluate the role of the catalyst, viz. homogeneous/
heterogeneous, hot filtration test was carried out by using
optimized reaction conditions for coupling of bromobenzene
123

1358
D. M. Pore et al.
Table 2 Ferrocene-tagged NHC-Pd complex-catalyzed Suzuki–Miyaura cross-couplinga
Entry
a
Product 4
Boronic acid
Time/h
2
Yield/%b
88
5
b
5
2.5
93
O
CH3
c
5
2.5
84
O
CH3
d
e
5
5
2
93
82
NC
2.5
O
H
f
5
3.5
78
CHO
g
h
6
7
3
78
79
N
N
CH3
NC
2.5
F
O
CH3
123

Ferrocene-tagged N-heterocyclic carbene-Pd complex
Table 2 continued
1359
Entry
i
Product 4
Boronic acid
Time/h
3
Yield/%b
85
5
O2N
j
5
2
81
O
CH3
k
5
5
2.5
76
78
l
2
H3C
m
5
5
2
83
75
n
2.5
H2N
o
6
2.5
79
N
N
CH3
O
CH3
p
5
4
69
O
CH3
123

1360
D. M. Pore et al.
Table 2 continued
Entry
Product 4
Boronic acid
Time/h
4
Yield/%b
66
q
5
O
H
r
5
5
4
71
78
s
3.5
a
Reaction conditions: aryl halide (1 mmol), boronic acid (1.2 mmol), Na2CO3 (3 mmol), Pd-NHC complex (2 mol%), DMF:water 3:1 (v/v),
80 °C; for entries a–h, i–o, p–r corresponding aryl bromides, iodide, and chloride used, respectively
b
Isolated yield
with phenylboronic acid. After 50 % of the cross-coupling
reaction was completed [30 min, gas chromatography
(GC)], the catalyst was filtered off and the reaction was
continued further. However, no further progress in the
reaction was observed even after a prolonged reaction time
(3 h, GC). These results revealed that Pd is not being leached
out from 3 during the course of reaction, thus 3 acts as a
heterogeneous catalyst in the present transformation.
obtained by using an STA 1500 instrument in the presence of
static air at linear heating rate of 10 °C/min from 20 to
1,000 °C. C, H, N analysis of the complexes was obtained
using a Carlo ERBA (Italy) model EA 1108 analyzer.
Typical Procedure
To a 25-cm3 round-bottom flask, a mixture of aryl halide
(1 mmol), arylboronic acid (1.2 mmol), Pd-NHC (2 mol %),
and Na2CO3 (3 mmol) was added in DMF:water (3:1 cm3).
The reaction was stirred at 80 °C and monitored by thin-layer
chromatography (TLC). After completion of reaction, the
mixture was cooled and content of the flask was diluted with
water and extracted with ethyl acetate (3 9 10 cm3). The
organic layer obtained was dried over anhydrous Na2SO4,
filtered, and concentrated to furnish the desired biaryl com-
pound, which was then purified by column chromatography
(5 % ethyl acetate). All synthesized products were confirmed
from physical constant [40–43], IR, and 1H and 13C NMR.
Conclusions
We explored a ferrocene-tagged NHC-Pd complex as an
efficient heterogeneous catalyst for Suzuki–Miyaura cross-
coupling in DMF/water medium at 80 °C. All reactions
were carried out in air atmosphere, illustrating the property
of catalyst 3 as air and moisture stable. In the presence of
NHC-Pd catalyst aryl bromides, iodides, and even less
reactive aryl chlorides could be coupled with a variety of
arylboronic acids to form biaryls in moderate to excellent
yields. The protocol is also applicable to pinacol ester of
boronic acid.
Acknowledgments Author D.S.G. thanks UGC-SAP BSR New
Delhi for a research fellowship.
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