A novel system for the Suzuki cross-coupling reaction catalysed with light fluorous palladium-NHC complex

Article abstract of DOI:10.1016/j.jfluchem.2012.08.005

A novel Pd-NHC catalyst containing fluorous tags was synthesized and characterized. The catalytic activity and stability of the catalyst has been evaluated for the Suzuki cross-coupling reaction of aryl halides and aryl boronic acids in the mixture solvent of C₆F₆ and EtOH to afford the corresponding products in excellent yields. In addition, the catalyst can be reused three times without obvious loss of catalytic activity. The structure of the catalyst was characterized by elemental analyses, FT-IR, ¹H NMR, ¹³C NMR and ¹⁹F NMR.

Full text of DOI:10.1016/j.jfluchem.2012.08.005

Journal of Fluorine Chemistry 144 (2012) 143–146
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Short Communication
A novel system for the Suzuki cross-coupling reaction catalysed with light
fluorous palladium–NHC complex
Hong Yu, Li Wan, Chun Cai *
Chemical Engineering College, Nanjing University of Science and Technology, 200 Xiaolingwei, Nanjing 210094, PR China
A R T I C L E I N F O
A B S T R A C T
Article history:
A novel Pd–NHC catalyst containing fluorous tags was synthesized and characterized. The catalytic
activity and stability of the catalyst has been evaluated for the Suzuki cross-coupling reaction of aryl
Received 24 June 2012
Received in revised form 10 August 2012
Accepted 25 August 2012
Available online 30 August 2012
6 6
halides and aryl boronic acids in the mixture solvent of C F and EtOH to afford the corresponding
products in excellent yields. In addition, the catalyst can be reused three times without obvious loss of
1
catalytic activity. The structure of the catalyst was characterized by elemental analyses, FT-IR, H NMR,
13
19
C NMR and F NMR.
Keywords:
ß 2012 Elsevier B.V. All rights reserved.
Pd–NHC
Suzuki cross-coupling reaction
Fluorous tag
1
. Introduction
The palladium-catalyzed Suzuki cross-coupling reaction, in-
catalyze reactions and can be recovered from the reaction mixture
by means of fluorous liquid–liquid separation [23,24]. But most of
the fluorous catalysts are insoluble in most organic solvents, which
limited their application in organic synthesis.
volving cross-coupling of aryl halides with aryl boronic acids, has
been shown as an powerful, attractive and convenient synthetic
method for the construction of carbon–carbon bonds [1–4] and has
been widely used for the synthesis of fine chemicals, pharmaceu-
ticals and dyes [5,6].
In recent years, various efficient Pd catalyst precursors have
been investigated [7–11]. In general, these reactions were carried
out in the presence of a variety of phosphine based ligands [12–14].
Recently, some palladium–NHC catalysts containing a fluorous
tag have been reported with low catalytic activity in cross-
coupling reactions [25,26]. Suzuki cross-coupling reactions have
typically been performed under heterogeneous palladium cata-
lysts where the palladium is fixed to a solid support in order to be
recycled conveniently [27,28]. However, heterogeneous palladium
catalysts have lower catalytic activity and selectivity compared to
homogeneous catalysts. But homogeneous processes suffer from
the problems concerning separation of products from reaction
mixture, recycling of potentially expensive complexes and
potential residual metals contamination in the product.
Lately, N-heterocyclic carbenes (NHCs), as
phosphorus-containing ligands [15,16], have been introduced as
potentially effective ligands for Suzuki cross-coupling reactions.
a substitute of
Due to their strong
s-donating and low p-accepting abilities, the
metal complexes of these carbenes showed high thermal stability
and hydrolytic durability. Additional advantages of these ligands
over the classic phosphines include easy preparation, variable
structures and low toxicity. Therefore, these complexes have
emerged as effective catalysts for a wide range of catalytic
reactions. However, most of metal–NHC complexes were difficult
to recycle when they worked as catalysts [17–19].
In the past decade, fluorous chemistry has attracted a great deal
of attention for facilitating catalyst recovery [20–22]. Metal
complexes with ligands containing fluorous tags exhibit special
features, such as it can be used in fluorous biphase solvents to
Based on an overall consideration of various factors, we sought
for an adequate solution to the problem. In the last few years, we
oriented our research on the study of heavy fluorous metal–NHC
complex [29]. In continuation of our studies in developing new
fluorous catalysts, we reported a novel system of the Suzuki cross-
coupling reaction catalysed with light fluorous palladium–NHC
complex. Compared with heavy fluorous catalysts, light fluorous
catalysts can be recovered easily by using simple fluorous liquid–
liquid separation, and also with better solubility in organic
solvents. Herein, we prepared a new functionalized palladium–
NHC complex containing a fluorous tag and its application in the
Suzuki cross-coupling reaction in homogeneous system consisted
6 6
of EtOH and C F . In this case, the catalyst can be readily recovered
and reused for several times only with slightly decrease in its
activity.
*
Corresponding author. Tel.: +86 25 84315514; fax: +86 25 84315030.
E-mail address: c.cai@mail.njust.edu.cn (C. Cai).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.08.005

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44
H. Yu et al. / Journal of Fluorine Chemistry 144 (2012) 143–146
Scheme 1. Preparation of the fluorous palladium–NHC catalyst.
6 6
better dispersion. Then, we chose EtOH/C F (1:1 v/v) as the
solvent for the Suzuki reaction.
Under same catalytic conditions, different bases were investi-
gated in the experiments (Table 2). As can be seen in Table 2,
potassium hydroxide gave the highest yield. Other inorganic bases
such as K
2
CO
3
, K
3
PO
4
Á3H
2 2 3
O, NaOH and Cs CO , proved to be less
effective for the cross-coupling of 4-bromoanisole with phenyl-
boronic acid (Table 2, entries 1–4). Also, the organic base t-BuONa
and Et
3
N were studied but no satisfactory yields were obtained
(
Table 2, entries 6 and 7). KOH was found to be the most effective
Fig. 1. IR spectra of 1,3-bis(polyfluoroalkyl)imidazolium salts (A) and fluoruos
base for the reaction (Table 2, entry 5). Because KOH has properly
alkaline in this system, and the size of cation K also has benefit to
palladium–NHC catalyst (B).
+
promote the synthesis of ylide(Pd) efficiently to give high yields
[30–32]. Then, different catalyst loadings were tested for the
reaction. As the results shown in Table 2, 0.1 mol% of catalyst was
sufficient to catalyze the reaction successfully. Thus, we select KOH
2
. Results and discussion
The palladium–NHC catalyst was prepared according to Scheme
. In order to ascertain fluorous NHC chelated with palladium, IR
1
6 6
as base, EtOH/C F (1:1 v/v) as solvent, and 0.1 mol% of catalyst as
spectra were recorded separately at the different stage of
the best conditions for the Suzuki reaction.
preparation. As shown in Fig. 1, the C–H peaks between 2800
After optimising the reaction conditions, we performed the
Suzuki cross-coupling reaction of various aryl halides with aryl
boronic acid, good yields of cross-coupling products were obtained
and the results were summarized in Table 3. Both electron
deficient and electron rich arylbromides afforded the correspond-
ing biphenyls in good to excellent yields (Table 3, entries 1–8). The
catalyst can tolerate a wide range of functional groups, such as –
À1
and 3200 cm
PdCl (PPh )]
almost disappeared after introduction of
. Moreover, the peak at about 1140–1250 cm
À1
[
2
3
2
was weakened, which attributed to the vibration of C–N. The
catalyst was dissolved in C , but not in H O and EtOH.
6
F
6
2
To evaluate the catalytic performance of palladium–NHC
complex, a series of experiments have been performed with 4-
bromoanisole and phenylboronic acid as model reaction to
optimize the reaction conditions. As illustrated in Table 1, initial
studies were performed by using different solvents in the presence
of palladium–NHC catalyst. It was found that the single solvent
2 3
OMe, –Me, –NO , –CF , and –COMe. Also, the coupling reaction
could be efficiently executed with aryl boronic acids containing
electron-donating and electron-withdrawing groups (Table 3,
entries 1, 9 and 10). And the coupling of aryl iodides with phenyl
boronic acid gave excellent yields (Table 3, entries 11–14). We also
performed the reaction with aryl chlorides in our system. However,
only moderate yield was obtained in the coupling reaction (Table 3,
entries 15–17).
such as H
entries 1–3), and the fluorous biphase solvents also give the low
yields (Table 1, entry 4). However, in EtOH/C (1:1 v/v), we
2
O, EtOH and THF gave low to moderate yields (Table 1,
6 6
F
obtained the desired product in 50% yield (Table 1, entry 7), as we
found the reaction can goes in homogeneous way, in this case, the
catalyst have higher catalytic activity and selectivity owing to its
Recycling experiments have been investigated using 4-bro-
moanisole and phenylboronic acid as model substrates with
Table 1
a
Effect of solvents for the Suzuki cross-coupling reaction.
K CO , cat
2
3
MeO
Br
B(OH)2
MeO
solvent, 80 °C
b
Entry
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
H
2
O
Trace
32
EtOH
THF
39
H
2
O/C
Toluene/C
MeOH/C
DMF/C
6
F
6
(1:1 v/v)
(1:1 v/v)
(1:1 v/v)
(1:1 v/v)
18
6
F
6
49
6
F
6
44
6
F
6
Trace
50
EtOH/C
EtOH/C
EtOH/C
6
F
6
F
6
F
6
(1:1 v/v)
6
6
(1:0.5 v/v)
(0.5:1 v/v)
39
1
1
45
EtOH/H
2
6
O/C F
6
(0.5:0.5:1 v/v/v)
30
a
Reaction conditions: 4-bromoanisole (1.0 mmol), phenylboronic acid (1.5 mmol), K
Isolated yield.
2
3
CO (2.0 mmol), catalyst (0.1 mol%) in 2 ml solvent at 80 8C for 3 h.
b

H. Yu et al. / Journal of Fluorine Chemistry 144 (2012) 143–146
145
Table 2
a
Effect of base and catalyst loadings for Suzuki cross-coupling reaction.
base, cat
MeO
Br
B(OH)2
MeO
EtOH/C F , 80 °C
6
6
b
Entry
Catalyst loading (mol%)
Base
Yield (%)
1
2
3
4
5
6
7
8
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
K
K
2
CO
PO
3
50
67
61
51
85
52
39
63
3
4
Á3H
2
O
NaOH
Cs CO
KOH
t-BuONa
Et
KOH
2
3
3
N
a
Reaction conditions: 4-bromoanisole (1.0 mmol), phenylboronic acid (1.5 mmol), base (2.0 mmol), 2 ml EtOH/C
6 6
F (1:1 v/v) at 80 8C for 3 h.
b
Isolated yield.
Table 3
a
Suzuki cross-coupling reaction of aryl halides with aryl boronic acids.
KOH,cat
X
B(OH)
2
EtOH/C F , 80°C
R2
R1
R2
6
6
R1
b
Entry
X
R
1
R
2
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
H
H
83
85
90
98
91
95
86
93
91
88
99
98
99
98
21
56
16
4-CH
4-CH
3
O
H
3
H
4-NO
2-NO
2
H
2
H
4-CHO
4-CF
H
3
H
4-CH
H
3
CO
H
4-Cl
4-CH
H
1
1
1
1
1
1
1
1
H
3
4-CH
4-CH
3
O
I
3
H
I
4-NO
H
2
H
I
H
Cl
Cl
Cl
4-CH
3
H
4-NO
H
2
H
H
a
Reaction conditions: aryl halide (1.0 mmol), aryl boronic acid (1.5 mmol), KOH (2.0 mmol), catalyst (0.1 mol%) in 2 ml EtOH/C
6 6
F (1:1 v/v) at 80 8C for 3 h.
b
Isolated yield.
0
.1 mol% catalyst loading at 80 8C. After the reaction completed,
catalyst and was dried under vacuum for the next cycle. And the
solvent collected, which include perfluorobenzene and EtOH, could
be reused without further purification. Fig. 2 shows the results
obtained after three reuse cycles, and the yields are 85, 84, 82 and
the reaction mixture was cooled to room temperature, then
concentrated to get the mixture of products and catalyst, which
2
was washed with H O and EtOH, the residue was the recycled
71% and the purity of the recycled catalyst are 94, 93, 91 and 90%
respectively to run 1, run 2, run 3 and run 4; as it can be seen, there
was no significant loss of catalytic activity after three cycles. The
slight decrease of the yield may be due to the small amount of
catalyst lost during manipulation.
3. Conclusions
In conclusion, we have successfully prepared a new light
fluorous palladium–NHC catalyst which was performed as an
efficient catalyst for the Suzuki cross-coupling reaction. Short
reaction times, high yields, easy purification and recyclability are
main characteristic of the process which can be used to generate a
diverse range of biphenyls in excellent yields. Further studies on
the reaction mechanism with this catalytic system and further
applications are currently under investigation.
Fig. 2. Recycling experiments.

1
46
H. Yu et al. / Journal of Fluorine Chemistry 144 (2012) 143–146
4
. Experimental
The mixture was reacted at 80 8C for a certain time (monitored by
GC). After the reaction completed, the reaction mixture was cooled
to room temperature, then concentrated to get the mixture of
4.1. General remarks
products and catalyst, which was washed with H
and EtOH (2 Â 10 ml), the residue is the catalyst recycled. And the
EtOH washings were dried over anhydrous Na SO , and evaporated
to obtain the crude products. After that the crude products were
purified by flash chromatography with n-hexane/EtOAc as eluent
affording the corresponding products. All products were known
compounds and were identified by comparison of their physical
and spectra data with those of authentic samples.
2
O (2 ml  10 ml)
All chemicals were reagent grade and used as purchased. IR
spectra were recorded in KBr disks with a Bomem MB154S FT-IR
spectrometer. GC analyses were performed on an Agilent 7890A
instrument. Elemental analyses were performed on a Vario EL III
2
4
1
13
recorder. H NMR and C NMR spectra were recorded on Bruker
1
9
DRX 500 and tetramethylsilane (TMS) was used as a reference.
F
NMR spectra was recorded on Bruker DRX 500 using CCl F as the
3
internal standard. All the products are known compounds and
were identified by comparing of their physical and spectra data
with those reported in the literature.
4.5. Recycling of catalyst
A round-bottomed flask was charged with 4-bromoanisole
(1.0 mmol), phenylboronic acid (1.5 mmol), KOH (2.0 mmol),
4.2. Preparation of 1,3-bis(polyfluoroalkyl)imidazolium salts
6 6
EtOH/C F (1:1 v/v, 2 ml) and catalyst (0.1 mol%). The mixture
The preparation of polyfluoroalkylated imidazolium salts was
based on the reaction of imidazole with polyfluoroalkyl halide.
Imidazole (0.34 g, 5 mmol) and 1H,1H,2H,2H-perfluorooctyl iodide
was reacted at 80 8C for 3 h. After the reaction completed, the
reaction mixture was cooled to room temperature, then concen-
trated to get the mixture of products and catalyst, which was
(
5.22 g, 11 mmol) were dissolved in 5 ml toluene. The mixture was
washed with H
2
O (2 ml  10 ml) and EtOH (2  10 ml), the residue
stirred at 110 8C for 24 h. After being cooled to room temperature,
organic phase was washed with water (2 ml  20 ml). Combined
organic phases were dried with anhydrous magnesium sulfate,
solvents were removed by rotary vacuum evaporator. Then the
crude product was dissolved in EtOAc (20 ml) and precipitated
with 10-fold excess of hexane (200 ml).The precipitate was
separated and dried in vacuum. And the product was obtained
was the recycled catalyst and was dried under vacuum for the next
cycle. And the solvent collected, which include C
could be reused without further purification.
6 6
F and EtOH,
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1
6
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N:3.18%.
.3. Preparation of the fluorous palladium–NHC catalyst
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(
(
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cooling to room temperature, the volatiles were removed. The
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CH
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2 2 2
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1
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d
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19
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Anal. Calc. for C37 PPd: C: 37.02, H: 2.08, N: 2.33; Found
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3
),
d
: À80.7 (bs, 6F), À113.6 (bs, 4F),
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Under air atmosphere, round-bottomed flask was charged with
aryl halide (1.0 mmol), phenylboronic acid (1.5 mmol), KOH
2.0 mmol), EtOH/C (1:1 v/v, 2 ml) and catalyst (0.1 mol%).
(
6 6
F