Perfluoro-tagged nano-palladium catalyst immobilized on fluorous silica gel: Application in the Suzuki-Miyaura reaction

Article abstract of DOI:10.1016/j.catcom.2012.03.032

The Suzuki-Miyaura reaction has been performed using a phosphine-free perfluoro-tagged palladium catalyst that is readily immobilized on fluorous silica gel through fluorous-fluorous interactions (Pd-1/FSG). The reactions are carried out under aerobic and phosphine-free conditions with excellent to quantitative product yields, and very low palladium content (< 0.8 ppm) in the products was detected by ICP-AES. The catalyst can be recovered by simple filtration and reused several times without significant loss of activity.

Full text of DOI:10.1016/j.catcom.2012.03.032

Catalysis Communications 24 (2012) 105–108
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Perfluoro-tagged nano-palladium catalyst immobilized on fluorous silica gel:
Application in the Suzuki–Miyaura reaction
Li Wan a, Chun Cai a,b,
⁎
a
Chemical Engineering College, Nanjing University of Science & Technology, 200 Xiaolingwei, Nanjing 210094, PR China
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, PR China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
The Suzuki–Miyaura reaction has been performed using a phosphine-free perfluoro-tagged palladium
catalyst that is readily immobilized on fluorous silica gel through fluorous–fluorous interactions (Pd-1/FSG).
The reactions are carried out under aerobic and phosphine-free conditions with excellent to quantitative
product yields, and very low palladium content (b0.8 ppm) in the products was detected by ICP-AES. The
catalyst can be recovered by simple filtration and reused several times without significant loss of activity.
© 2012 Elsevier B.V. All rights reserved.
Received 31 January 2012
Received in revised form 14 March 2012
Accepted 23 March 2012
Available online 1 April 2012
Keywords:
Nano-palladium
Suzuki reaction
Co-solvent
FSG
1. Introduction
heterogeneous palladium catalysts, such systems still suffer from high
catalyst loadings and a lower efficiency compared to their analogues in
Palladium catalyzed Suzuki cross-coupling reactions have been
increasingly employed for construction of unsymmetrical biaryl units
which have a wide range of applications such as pharmaceutical,
herbicides and natural products [1–6]. The explosive growth of studies
in this area in the last decade is mainly due to low toxicity and high
stability of organoboranes towards air and moisture. In addition, the
handling and removal of boron-containing byproducts is easier when
compared to other organometallic reagents, especially in a large scale
synthesis [7]. However, palladium catalysts are expensive, and this
may limit their applications in industry. Furthermore, their use might
result in palladium contamination of the desired isolated products, a
significant problem for the pharmaceutical industry, which has to
meet strict specifications to limit the presence of heavy metal
impurities in active substances [8]. To overcome these problems,
immobilized palladium catalysts [9] provide a way to separate,
recover, and reuse catalysts, thus reducing palladium contamination
of the isolated products.
the homogeneous phase. Moreover, phosphines remain the most
employed ligands in these heterogeneous palladium catalysts. How-
ever, phosphine ligands are expensive, toxic and in large-scale
applications the phosphines may be a more serious economical burden
than even the metal itself [21].
Recently, palladium nanoparticles have been shown to be
stabilized by entrapment in perfluoro-tagged, phosphine-free com-
pounds [22–24]. Bannwarth et al. [25,26] have reported a successful
example of immobilizing perfluoro-tagged palladium. Several cata-
lysts were prepared by adsorption of palladium complexes containing
perfluorinated phosphine ligands on fluorous silica gel (FSG) and
showed the advantages of their utilization (separation and recovery
of perfluoro-tagged palladium) in the Suzuki–Miyaura cross-coupling
reaction in comparison with fluorous biphasic catalysis approaches
using expensive and environmentally-persistent perfluorinated sol-
vents. However, phosphines are often air-sensitive and some limits to
their use in large-scale applications still remain. Vallribera et al.
[27–29] have developed some new immobilized phosphine-free
palladium systems in the alkynylation of aryl halides and the Heck
reaction. Although these systems are efficient in catalyzing these two
C\C bond-forming reactions, the palladium catalysts were prepared
in multiple steps, using expensive starting materials and high
palladium contamination in the products still limit their industrial
applications. To address these concerns, the use of simple, low-cost,
phosphine-free, recoverable and recyclable heterogeneous catalyst
would provide obvious advantages in many synthetic applications.
In our previous work, we have reported a facile process to synthesize
a novel fluorous nano-palladium catalyst and its utilization in the
A number of studies have been devoted to immobilizing palladium
on inert support materials, including activated carbon [10], silica gel
[11,12], polymers containing covalently-bound ligands [13], metal
oxides [14–17], ionic liquid [18], porous aluminosilicates and other
inorganic materials, as well as microporous and mesoporous supports
[19,20]. Although significant efforts have been achieved to develop
⁎
Corresponding author at: Chemical Engineering College, Nanjing University of
Science & Technology, 200 Xiaolingwei, Nanjing 210094, PR China. Tel.: +86 25
84315514; fax: +86 25 84315030.
E-mail address: c.cai@mail.njust.edu.cn (C. Cai).
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2012.03.032

106
L. Wan, C. Cai / Catalysis Communications 24 (2012) 105–108
Suzuki–Miyaura reaction at room temperature in ethanol/water
mixture [30]. The catalyst was air and moisture-stable, and could be
reused several times without a significant degradation in catalytic
activity. However, using perfluorinated solvents when recycling the
catalyst has prompted various concerns, the majority of which involve
cost, fluorous solvent leaching, and environmental persistence [31]. In
this context, we describe the synthesis of a novel heterogeneous cross-
2.4. Recycling of catalyst
A sealed tube was charged with 4-bromoanisole (1.0 mmol),
phenylboronic acid (1.5 mmol), K2CO3 (2.0 mmol), MeOH/H2O (v/v=
1:0.5, 2 mL) and catalyst (0.1 mol% Pd), the mixture was stirred at 80 °C
for 6 h under aerobic conditions. Then the reaction mixture was cooled
at room temperature, and filtered to obtain the solid immobilized
palladium catalyst. The residual catalyst was washed with CH2Cl2
(3×5 mL) and H2O (3×5 mL) and then dried under vacuum at 50 °C for
2 h. After this, it could be used for the next run.
coupling catalyst by immobilization of
a functionalized fluorous
palladium complex on fluorous silica gel.
2. Experimental
3. Results and discussion
2.1. General
The amount of palladium in the immobilized catalyst was found to
be 0.25% based on ICP-AES analysis. Transmission electron microsco-
py (TEM) of the catalyst showed well-defined spherical particles
dispersed in the silica matrix (Fig. 1a and 1b). The mean diameter of
the nanoparticles was about 2.9 0.7 nm. The particle size was
diminished compared to the starting particles Pd-1. It was reported
that palladium nanoparticles could be entrapped in heavily fluori-
nated compounds [32]. Poly(tetrafluoroethylene) (PTFE) has been
reported as stabilizing agents of transition-metal nanoparticles as
well as dendrimers fluorinated in the surface. Fluorous silica gel is
similar to PTFE as a heavily fluorinated material, it is probably the
inclusion of nanoparticulated palladium into the interstices of the
nonfluorinated core of the dendrimer that caused the diminution of
the particle size [33,34]. In addition, using perfluorooctane, which is a
heavily fluorinated compound, as solvent in the preparation of the
immobilized catalyst, might disperse the palladium particles well in
the process and lead to diminution of the particle size.
All reagents and solvents were commercially available and used
without any further purification. GC analyses were performed on an
Agilent 7890A instrument. Palladium content was measured by
inductively coupled plasma-atomic emission spectroscopy (ICP-AES)
on a PE5300DV instrument. Transmission electron microscope (TEM)
images were collected on a JEOL-2100 transmission electron mi-
croscope at 200 kV and the images were recorded digitally with a
Gatan 794 charge-coupled device (CCD) camera. The TEM measure-
ments were made by sonication of the nanoparticulate material in
perfluorodecalin for several minutes, then one drop of the finely
divided suspension was placed on a specially produced structureless
carbon support film having a thickness of 4–6 nm and dried before
observation.
2.2. Preparation of Pd-1/FSG
The phosphine-free perfluoro-tagged nano-palladium catalyst
(Pd-1) was prepared according to our previously reported procedure
[30]. 0.02 g of Pd-1 was added to 15 mL perfluorooctane and the
mixture was refluxed for 12 h. Then, 1 g of FSG (C8; 35–70 μm) was
added and the mixture was stirred at the same temperature for 2 h.
After this time, the solvent was evaporated under vacuum to obtain
the immobilized catalyst. Palladium content: 0.25%. The size of
the palladium particles was about 2.9 0.7 nm, as determined by
transmission electron microscopy.
The immobilized catalyst (Pd-1/FSG) was assessed for its activity
in the Suzuki–Miyaura reaction initially by studying the coupling of
4-bromoanisole with phenylboronic acid to form 4-methoxybipheyl
as the sole product. Various parameters including solvent, base and
catalyst loading were screened to optimize the reaction conditions.
Single solvents such as DMF, CH3CN, EtOAc, THF, MeOH, and EtOH
gave low to moderate yields ranging from 11 to 81% (Table 1, entries
1–6). However, when we adopted the organic/aqueous co-solvent,
satisfactory results were obtained (Table 1, entries 7 and 8). The merit
of the co-solvent is attributed to the good solubility of the organic
reactants and the inorganic base. Then, we tested the influence of
different volume ratios of MeOH/H2O as a solvent under identical
conditions. Evidently, the best volume ratio of MeOH/H2O is 1:0.5
(Table 1, entry 9).
Next, an optimization of the base for the Suzuki–Miyaura reaction
was performed using K3PO4, K2CO3, Na2CO3, NaHCO3, NaOH, KOH,
and Et3N. K2CO3 was found to be the most effective base for the
reaction. Slightly lower yields were obtained when using K3PO4 and
Na2CO3 as the base (Table 2, entries 1 and 3). Then, different catalyst
loadings between 0.05 and 1 mol% were investigated for the reaction.
For the higher catalyst loading, the desired product was obtained in
an almost quantitative yield (Table 2, entry 8). On the contrary, the
yield of the reaction was lower with 0.05 mol% catalyst loading.
2.3. Typical procedure for Suzuki–Miyaura reactions using 0.1 mol%
Pd-1/FSG
A sealed tube was charged with aryl halide (1.0 mmol), arylboronic
acid (1.5 mmol), K2CO3 (2.0 mmol), MeOH/H2O (v/v=1:0.5, 2 mL) and
catalyst (0.1 mol% Pd), the mixture was stirred at 80 °C for 6 h under air
atmosphere. After cooling to room temperature, the mixture was
diluted with CH2Cl2 and filtered. The organic phase was separated and
dried over Na2SO4. The solvent was removed under vacuum and the
residual was purified by column chromatography on silica gel with
EtOAc/petroleum ether as eluent. All the products were known
compounds and were identified by comparison of their physical and
spectroscopic data with those of authentic samples.
Fig. 1. TEM images of the immobilized catalyst. (a) and (b) TEM images of Pd-1/FSG. (c) TEM image of Pd-1/FSG after fifth cycle for the Suzuki–Miyaura reaction.

L. Wan, C. Cai / Catalysis Communications 24 (2012) 105–108
107
Table 1
Table 3
Effect of solvents for the Suzuki–Miyaura reaction.a
Suzuki cross-coupling reactions of aryl halides with arylboronic acids.a
Yieldb (%)
Entry
Solvent
Time (h)
Yieldb (%)
Entry
X
R1
R2
Time (h)
1
2
3
4
5
6
7
8
DMF
CH3CN
EtOAc
THF
MeOH
EtOH
EtOH/H2O (v/v=1:1)
MeOH/H2O (v/v=1:1)
MeOH/H2O (v/v=1:0.5)
MeOH/H2O (v/v=0.5:1)
H2O
6
6
6
6
6
6
6
6
6
6
6
43
11
31
26
81
68
83
89
97
74
13
1
2
3
4
5
6
7
8
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
H
H
H
H
H
H
H
H
H
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
99
97
89
96
85
99
98
96
98
98
97
>99
92
98
97
95
21
45
7
4-CH3O
2-CH3O
4-NO2
2-NO2
4-CF3
3-CF3
4-CH3CO
4-CHO
4-CH3O
4-CH3O
4-CH3O
4-CH3O
H
9
10
11
9
H
4-Cl
4-CF3
4-CH3O
10
11
12
13
14
15
16
17
18
19
a
Reaction conditions: 4-bromoanisole (1.0 mmol), phenylboronic acid (1.5 mmol),
K2CO3 (2.0 mmol), catalyst (0.1 mol%) in 2 mL solvent at 80 °C.
4-CH3
H
H
H
H
H
H
b
Isolated yield.
I
I
Cl
Cl
Cl
4-NO2
4-CH3
H
4-NO2
4-CH3
Therefore, it was decided to use K2CO3 as the base, MeOH/H2O in
volume ratio of 1:0.5 as solvent, and 0.1 mol% catalyst as the optimal
conditions in further studies. It should be noted that the absence of
phosphines in the system not only reduces process costs but also
eliminates side reactions that may occur between the phosphines and
phenylboronic acid [35].
a
Reaction conditions: aryl halide (1.0 mmol), arylboronic acid (1.5 mmol), K2CO3
(2 mmol), catalyst (0.1 mol% Pd) in 2 mL MeOH/H2O (v/v=1:0.5) at 80 °C.
b
Isolated yield.
To survey the generality of the catalytic protocol, we investigated
the reaction using various aryl halides coupled with arylboronic acids
under the optimized conditions. As shown in Table 3, aryl bromides
containing both electron-donating and electron-withdrawing groups
in the para position afforded the corresponding products in excellent
yields. The ortho-substituted aryl bromides gave the products lower
yields because of steric effects (Table 3, compare entry 2 with entry 3,
entry 4 with entry 5). Also, the coupling reaction could be efficiently
carried out using arylboronic acids bearing either electron-rich or
electron-poor substituted groups (Table 3, entries 10–13). Next, we
examined aryl iodides for the Suzuki reaction. And excellent yields of
the corresponding products were obtained under the optimized
conditions (Table 3, entries 14–16). In addition, we also investigated
whether aryl chlorides were active for the Suzuki–Miyaura reaction
under the same conditions. In this case, the corresponding products
were obtained in poor yields except for 4-nitrochlorobenzene
afforded the product in a moderate yield (Table 3, entry 18).
Reusability is an important feature that determines the appli-
cability of a heterogeneous catalyst. The coupling reaction of 4-
bromoanisole with phenylboronic acid was chosen as the model
reaction. As shown in Fig. 2, the immobilized fluorous palladium
catalyst can be recovered and reused in further reactions without a
significant loss of activity. Although the catalytic activity gradually
diminished, a yield of over 80% was still achieved in the fifth cycle.
The recovered catalyst was also examined by TEM after the fifth cycle
and it was observed that the size of palladium nanoparticles
increased to about 5 nm and the particle already has aggregation,
which proved a decrease in its activity after several cycles (Fig. 1c).
Moreover, very low palladium content (b0.8 ppm) was detected by
ICP-AES in the obtained products. This result is much better than the
catalyst system reported by Vallribera and co-workers [28]. It should
be pointed out that this low Pd level satisfies specifications required
by the pharmaceutical industry regarding the final purity of the
products (Pdb2.0 ppm).
4. Conclusions
In summary, we have successfully prepared a novel perfluoro-
tagged nano-palladium catalyst immobilized on fluorous silica gel
(Pd-1/FSG). The immobilized catalyst exhibits high activity towards
the Suzuki–Miyaura cross-coupling reaction without any added
phosphine ligands under aerobic conditions. Low palladium contam-
ination in the products was detected by ICP-AES, which meets the
level required by the pharmaceutical industry. And the catalyst can be
recovered by simple filtration and reused after washing without a
significant degradation in activity.
Table 2
Effect of bases and catalyst loadings for the Suzuki–Miyaura reaction.a
100
80
Entry
Catalyst loading
(mol%)
Base
Time (h)
Yieldb (%)
95
93
90
88
84
1
2
3
4
5
6
7
8
9
0.1
0.1
0.1
0.1
0.1
0.1
0.1
1
K3PO4
K2CO3
Na2CO3
NaHCO3
NaOH
KOH
Et3N
K2CO3
K2CO3
6
6
6
6
6
6
6
6
6
95
97
90
46
58
72
43
>99
86
60
40
20
0
1
2
3
4
5
0.05
Cycle
a
Reaction conditions: 4-bromoanisole (1.0 mmol), phenylboronic acid (1.5 mmol),
base (2.0 mmol), catalyst in 2 mL MeOH/H2O (v/v=1:0.5) at 80 °C.
Fig. 2. Reusability of the immobilized fluorous palladium catalyst for the Suzuki
b
Isolated yield.
reaction.

108
L. Wan, C. Cai / Catalysis Communications 24 (2012) 105–108
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