An efficient and recyclable fluorous palladium catalyst for the room-temperature suzuki reaction

Article abstract of DOI:10.1007/s10562-011-0609-z

A new fluorous nano-palladium catalyst was prepared and characterized. The catalytic activity of the catalyst has been evaluated for the Suzuki reaction of aryl halides and aryl boronic acids to afford the corresponding products in high yields. The reaction proceeded smoothly in the presence of 0.1 mol% catalyst in EtOH/H₂O at room temperature. In addition, the catalyst could be recovered by fluorous liquid-liquid separation and reused for three times without significant loss of activity. Graphical Abstract: The Suzuki reaction catalyzed by a new fluorous nano-palladium catalyst to afford the products in high yields at room temperature has been described. The catalyst can be recovered by fluorous liquid-liquid separation and reused for several times without significant loss of activity. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-011-0609-z

Catal Lett (2011) 141:839–843
DOI 10.1007/s10562-011-0609-z
An Efficient and Recyclable Fluorous Palladium Catalyst
for the Room-Temperature Suzuki Reaction
Li Wan Chun Cai
•
Received: 13 March 2011 / Accepted: 13 April 2011 / Published online: 26 April 2011
Ó Springer Science+Business Media, LLC 2011
Abstract A new fluorous nano-palladium catalyst was
prepared and characterized. The catalytic activity of the
catalyst has been evaluated for the Suzuki reaction of aryl
halides and aryl boronic acids to afford the corresponding
products in high yields. The reaction proceeded smoothly
methods for the Suzuki reaction has attracted much
interest.
A wide range of metal complexes have been used as
catalysts in Suzuki coupling reactions, attention particu-
larly being focused on palladium. Palladium catalysts with
phosphines ligand [10], carbenes ligand [11], palladacycle
[12] and other coordinates [13] have shown high activity
and have improved the stability of the reactions with water
or under air. However, problems such as expensive poi-
sonous phosphine ligands and unrecyclability of the cata-
lyst, which impacts cost and palladium contamination in
the product, extremely limited their industrial applications.
Thus, the development of efficient and recyclable catalysts
that utilize cheap and phosphine-free ligands is a topic of
enormous importance.
in the presence of 0.1 mol% catalyst in EtOH/H O at room
2
temperature. In addition, the catalyst could be recovered by
fluorous liquid–liquid separation and reused for three times
without significant loss of activity.
Keywords Nano-palladium Á Suzuki reaction Á
Co-solvent Á Fluorous palladium catalyst
1
Introduction
Recently, some phosphine-free ligands have been shown
to have interesting applications, such as thioureas [14–16],
imines [17], bispyridines [18], oxazolines [19], tetrazoles
[20], and bisimidazoles [21]. These ligands are potentially
advantageous for being chemically stable and economi-
cally inexpensive. Guo [22] reported amino acids can serve
as excellent ligands for copper-catalyzed amidation of aryl
iodides. Wang and co-workers [23] described a palladium
anchored on proline-functionalized silica gel as catalyst to
catalyze the Heck reaction. Therefore, simple amino acids
and their derivatives as ligands for metal-catalyzed reac-
tions attracted our attention.
The Suzuki reaction is one of the most versatile and uti-
lized reactions for the formation of biaryl compounds [1–
3
]. In the past decade, the biaryl motif has received
increased attention as a privileged structure by the agro-
chemical and pharmaceutical industries [4, 5]. The core of
many types of natural products [6], advanced materials [7],
polymers [8] and sensors [9] contain the biaryl moiety.
Consequently, the development of new and efficient
L. Wan Á C. Cai
In the last few years, fluorous chemistry has emerged as a
powerful strategy for facilitating catalyst recovery [24–28].
Introducing a fluorous tag into the catalyst can make it easily
recoverable by using simple fluorous liquid–liquid separa-
tion [29, 30]. Herein, we report a facile process to synthesize
nano-palladium catalyst with a fluorous tag derived from
proline. And the catalyst has been applied for the Suzuki
reaction of aryl halides and aryl boronic acid at room
Chemical Engineering College, Nanjing University of Science &
Technology, 200 Xiaolingwei, Nanjing 210094, People’s
Republic of China
C. Cai (&)
Key Laboratory of Organofluorine Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Lu, Shanghai 200032, People’s Republic of China
e-mail: c.cai@mail.njust.edu.cn
123

8
40
L. Wan, C. Cai
temperature. Recyclability experiments of the fluorous nano-
palladium catalyst were performed up to three runs without
significant loss of activity under moist conditions.
2.2.2 Preparation of the Fluorous Nano-palladium
Catalyst
In a round-bottom flask, fluorous pyrrolidine imide
(120 mg, 0.2 mmol) was mixed with Pd(OAc) (45 mg,
2
2
Experimental
0.2 mmol) in anhydrous EtOH (2 mL). The mixture was
stirred for 12 h under N at room temperature. The mixture
2
2
.1 General Remarks
was filtered and the solid was washed with acetone and
MeOH. The solid was dried under reduced pressure at
room temperature for 6 h. The catalyst was obtained as a
black solid (136 mg). The amount of palladium in the
catalyst was found to be 12.6% based on ICP analysis.
All of the reagents and solvents are commercially available
and were used without further purification. IR spectra were
recorded in KBr disks with a Bomem MB154S FT-IR
spectrometer. Mass spectra were taken on an Agilent
LC–MS 1100 series instrument in the electrospray ioniza-
tion (positive ESI) mode. GC analyses were performed on
2.2.3 Typical Procedure for Suzuki Reactions
1
13
an Agilent 7890A instrument. H NMR and C NMR were
recorded on Bruker DRX 500 and tetramethylsilane (TMS)
was used as a reference. Palladium content of the catalyst
was measured by inductively coupled plasma (ICP) on
PE5300DV analyzer. Transmission electron microscope
Under air atmosphere, round-bottomed flask was charged
with aryl halide (1.0 mmol), phenylboronic acid
(1.5 mmol), K CO (2.0 mmol), EtOH/H O (v/v = 1:1,
2 3 2
2 mL) and catalyst (0.1 mol% Pd). The mixture was
reacted at room temperature for a certain time (monitored
by GC). After the reaction completed, water (3 mL) and
EtOAc (5 mL) was added to the mixture. The organic
(
TEM) images were collected on a JEOL-2100 transmis-
sion electron microscopy at 200 kV and the images were
recorded digitally with a Gatan 794 charge-coupled device
phase was separated, dried over anhydrous Na SO , and
2 4
(
CCD) camera.
evaporated. 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
.2 Preparation of the Catalyst
2
.2.1 Preparation of Fluorous Pyrrolidine Imide
Under a dry N atmosphere, to a stirred solution of Boc-
2
2.2.4 Recycling of Catalyst
proline (0.43 g, 2 mmol) and perflurooctane sulfluramide
(
0.99 g, 2 mmol) in 25 mL EtOAc, DMAP (4-dimethyl-
A vial was charge with 4-bromoanisole (1.0 mmol),
aminopyridine, 0.58 g, 0.48 mmol) and EDCI (1-ethyl-
phenylboronic acid (1.5 mmol), K
2
CO (2.0 mmol), EtOH/
3
3
0
-(3-dimethylaminopropyl)carbodiimidehydrochloride,
.57 g, 3 mmol) were added respectively. The reaction
H
2
O (v/v = 1:1, 2 mL) and catalyst (0.1 mol% Pd). The
reaction was run at room temperature for 1 h. After the
reaction completed, water (3 mL), EtOAc (5 mL) and
mixture was stirred at room temperature for 96 h. Then the
mixture was washed with 30 mL 1 M aqueous HCl and
perfluorodecalin (C10F18, cis and trans-mixture, 5 mL)
5
0 mL half-saturated brine. The organic layer was dried
were added. Then the mixture heated to 100 °C for 10 min.
After the mixture was cooled to room temperature, the
fluorous phase was separated and concentrated to afford the
catalyst for the next cycle. And perfluorodecalin was col-
lected for the next use without further purification. The
yields of the reaction were determined by GC analysis.
over Na SO and concentrated in vacuo to give a colorless
2
4
oil product. And the oil product was directly used in the
next step without further purification. Deprotection Boc-
group was performed by using 15 mL TFA (trifluoroacetic
acid) for 2 h at 0 °C. After concentration, TFA salts were
removed by triturating the residue with 30 mL MeOH
saturated with ammonia (15 mL) to obtain the product.
And the product was obtained as a white solid (0.62 g,
3 Results and Discussion
1
4
9
3
1
1
1%). mp 217–219 °C. H NMR (500 MHz, DMSO-d ) d:
6
.04 (s, 1H), 8.34 (s, 1H), 4.04–4.02 (t, 1H, J = 6.0 Hz),
The nano-palladium catalyst was prepared according to
Scheme 1. In order to ascertain fluorous pyrrolidine imide
chelated with palladium, IR spectra were recorded sepa-
rately at the different stage of preparation. As shown in
.20(s, 1H), 3.13–3.09 (m, 1H), 2.20–2.16 (m, 1H),
1
3
.90–1.82 (m, 3H); C NMR (125 MHz, DMSO-d ) d:
6
72.82, 108-121 (m, CF , CF ), 62.72, 45.84, 29.24, 23.53;
3
2
?
-1
MS (ESI) calcd for C H F N O S (M ? Na) 619.25,
13 9 17 2 3
Fig. 1, the N–H peaks between 3000 and 3200 cm
found 619.22.
almost disappeared after introduction of Pd(OAc) .
2
1
23

An Efficient and Recyclable Fluorous Palladium Catalyst
841
Scheme 1 Preparation of fluorous nano-
palladium catalyst
O
O
O
O
O
S
C8F17SO NH2
CF COOH
2
3
OH
N
N
S C
O
8
F
17
N
C F
8 17
DMAP, EDCI
EtOAc
N
H
N
H
O
H
Boc
Boc
O
O
Pd(OAc) , EtOH
2
N
S
C8F17
N
H
H
O
Pd
AcO
OAc
EtOAc, CH Cl , MeOH, EtOH and H O gave low to
2
2
2
A
B
moderate yields ranging from 11 to 82% (Table 1, entries
–7). However, when we adopted the organic/water
1
co-solvent, satisfactory results were obtained (Table 1,
entries 9–10). 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 EtOH/H O as a solvent at room temperature. And
2
yields of 89–98% were obtained in 1 h. Evidently, the best
volume ratio of EtOH/H O is 1:1. Compared to the fluorous
2
nano-palladium catalyst, lower yield was obtained when
4000
3500
3000
2500
2000
1500
1000
500
Pd(OAc) used as catalyst (Table 1, entry 11).
2
-
1
Next, we examined the effect of bases for the room
Wavenumbers/cm
temperature Suzuki reaction in EtOH/H O. Some bases
2
Fig. 1 IR spectra of fluorous pyrrolidine imide (A) and fluoruos
nano-palladium catalyst (B)
including K PO , K CO , Na CO , NaOAc, NaHCO ,
3
4
2
3
2
3
3
Et N, NaOH and KOH were all investigated (Table 2,
3
entries 1–8). K CO was found to be the most effective
2
3
-
1
Moreover, the peak at about 1400–1420 cm was weak-
ened, which attributed to the vibration of C–N. The TEM
analysis of catalyst (Fig. 2) showed the formation of palla-
dium nanoparticles with a diameter in the range 30–40 nm.
With these good results at hand, we optimized the
Suzuki reaction conditions. Initially, the reaction between
base for the reaction. Slightly lower yields were obtained
when K PO and Na CO were used as base (Table 2,
3
4
2
3
entries 1, 3). Also, the organic base Et N was studied but
3
not satisfactory yield was obtained (Table 2, entry 6).
Then, different catalyst loadings were tested for the reac-
tion. As the results shown in Table 2, 0.1 mol% of catalyst
was sufficient to catalyze the reaction successfully (entries
2, 9, 10). Thus, we select K CO as base, EtOH/H O (v/
4
-bromoanisole and phenylboronic acid was chosen as a
model reaction. Various parameters including solvent, base
and catalyst loading were screened to optimize the reaction
2
3
2
v = 1:1) as solvent, and 0.1 mol% of catalyst which are
conditions. The single solvent such as DMF, CH CN,
3
the best conditions for the Suzuki reaction.
Fig. 2 TEM micrographs of
palladium nanoparticles
123

8
42
L. Wan, C. Cai
Table 1 Effect of solvent and catalyst on the room-temperature
a
Suzuki reaction
Table 3 Suzuki cross-coupling reaction of aryl halides with arylbo-
a
ronic acids
K
2
CO
3
, Cat.
K CO , Cat.
2
3
CH
3
O
Br
+
(HO)
2
B
CH
3
O
2
X + (HO) B
solvent, rt
EtOH/H O, rt
R1
R2
2
R1
R2
c
Yield (%)
Entry
Solvent
DMF
Time (h)
b
Yield (%)
Entry
X
R
1
R
2
Time (h)
1
2
3
4
5
6
7
8
9
3
3
11
21
36
33
68
82
23
89
98
94
76
1
2
3
4
5
6
7
8
9
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
H
H
1
1
3
5
5
2
2
1
1
2
2
2
2
1
1
3
3
3
3
99
98
87
92
85
99
98
96
99
99
96
94
95
99
98
88
16
43
23
CH
EtOAc
CH Cl
3
CN
4-CH
2-CH
3
O
O
H
3
3
H
2
2
3
4-NO
2-NO
2
H
MeOH
EtOH
3
2
H
3
4-CF
2-CF
4-CH
3
H
2
H O
12
1
3
H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
2
2
2
2
O (v/v = 1:0.5)
O (v/v = 1:1)
O (v/v = 0.5:1)
O (v/v = 1:1)
3
CO
H
1
4-CHO
H
1
1
a
0
1
1
10
11
12
13
14
15
16
17
18
19
a
H
H
H
H
H
4-Cl
4-CF
b
1
3
Reaction conditions: 4-bromoanisole (1.0 mmol), phenylboronic
acid (1.5 mmol), K CO (2.0 mmol), catalyst (0.1 mol% Pd) in 2 mL
solvent at room temperature
4-CH
4-CH
H
3
O
2
3
3
b
Pd(OAc)
2
used as catalyst
I
4-NO
2
H
c
Isolated yield
I
4-CH
H
3
H
Cl
Cl
Cl
H
Table 2 Effect of base and catalyst loading on the room-temperature
a
Suzuki reaction
4-NO
4-CH
2
H
3
H
base, Cat.
CH3O
Br
+
(HO)2B
CH3O
Reaction conditions: aryl halide (1.0 mmol), arylboronic acid
1.5 mmol), K CO (2 mmol), catalyst (0.1 mol% Pd) in 2 mL EtOH/
O (v/v = 1:1) at room temperature
EtOH/H2O, rt
(
2
3
H
b
2
b
Yield (%)
Entry
Catalyst loading
mol %)
Base
Time (h)
Isolated yield
(
1
2
3
4
5
6
7
8
9
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
1
K
3
PO
4
1
1
1
1
1
1
1
1
1
1
95
98
92
23
45
41
56
77
99
83
K
2
CO
3
100
Na
CO
2 3
8
6
0
0
NaOAc
NaHCO
99
93
88
3
Et
3
N
40
NaOH
KOH
2
0
0
K
2
CO
CO
3
3
1
2
3
1
0
0.05
K
2
Run
a
Reaction conditions: 4-bromoanisole (1.0 mmol), phenylboronic
acid (1.5 mmol), base (2.0 mmol), catalyst in 2 mL EtOH/H
v/v = 1:1) at room temperature
Fig. 3 Recycling experiments
2
O
(
b
Isolated yield
products in good to excellent yields. Also, the coupling
reaction could be efficiently executed of aryl boronic acids
with electron-donating and electron-withdrawing groups
(Table 3, entries 10–13). Then, we examined aryl iodides
for the Suzuki reaction. And excellent yields of the cor-
responding products were obtained under the optimized
condition. We also investigated the reactivity of aryl
chlorides with phenylboronic acid in our system. However,
To survey the generality of the catalytic protocol, we
investigated the reaction using a variety of aryl halides
coupled with aryl boronic acids under the optimized con-
dition. As shown in Table 3, aryl bromides bearing either
electron-donating or electron-withdrawing substituents in
the ortho and para positions afforded the corresponding
1
23

An Efficient and Recyclable Fluorous Palladium Catalyst
843
only moderate yield was obtained in the coupling reaction
3. Miyaura N, Suzuki A (1995) Chem Rev 95:2457
4
5
6
. Bellina F, Carpita A, Rossi R (2004) Synthesis 2419
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(
Table 3, entry 18). Recycling experiments were investi-
gated with 0.1 mol% catalyst loading at room temperature.
The catalyst can be recovered by fluorous liquid–liquid
separation and reused for three times without significant
loss of activity (Fig. 3). The slight decrease of the yield
may be due to the small amount of catalyst lost by
manipulation. The coupling products were obtained by
purification on silica column chromatography, only very
low palladium amount (\2.0 ppm) was detected.
7. Lightowler S, Hird M (2005) Chem Mater 17:5538
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9
0. Barder TE, Walker SD, Martinelli JR, Buchwald SL (2005) J Am
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4
Conclusions
1
1
In summary, we have successfully prepared a new fluorous
nano-palladium catalyst which was performed as an effi-
cient catalyst for the Suzuki reaction at room temperature.
The catalyst has showed highly catalytic activity for the
reaction affording a diverse range of biphenyls in excellent
1
1
4
5:7689
yields. And EtOH/H O as solvent is more eco-friendly than
2
20. Gupta AK, Song CH, Oh CH (2004) Tetrahedron Lett 45:4113
21. Park SB, Alper H (2003) Org Lett 5:3209
DMF, which was mostly used as solvent in Suzuki reac-
tions. Furthermore, the catalyst could be easily recovered
by fluorous liquid–liquid separation and reused for three
times without significant loss of activity. The simple pro-
cedure for catalyst preparation, easy recovery and reus-
ability of the catalyst are expected to contribute its
utilization for the development of benign chemical process
and products. To increase the recyclability of the catalyst is
continuous in our further work.
2
2. Deng W, Wang YF, Zou Y, Liu L, Guo QX (2004) Tetrahedron
Lett 45:2311
3. Liu HQ, Wang L, Ph Li (2008) Synthesis 15:2405
2
24. Croxtall B, Hope EG, Stuart AM (2003) Chem Commun
2003:2430
2
2
2
5. Matsugi M, Curran DP (2005) J Org Chem 70:1636
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6. Moln a´ r A (2011) Chem Rev 111:2251
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