A highly efficient and recyclable fluorous palladium catalyst for Heck reactions in water

Article abstract of DOI:10.1007/s11243-011-9528-5

A fluorous nano-palladium catalyst has been synthesized and characterized. The catalyst is highly active for the Heck reaction of aryl halides with substituted styrenes in water under air. The corresponding Heck products were obtained in high yields with good stereoselectivity (E/Z up to 98:2). In addition, the catalyst could be recovered by fluorous liquid-liquid separation and reused four times without significant loss of activity or stereoselectivity. Graphical Abstract: The Heck reaction catalyzed by a new fluorous nano-palladium catalyst in water to afford the products in high yields 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/s11243-011-9528-5

Transition Met Chem (2011) 36:747–750
DOI 10.1007/s11243-011-9528-5
A highly efficient and recyclable fluorous palladium catalyst
for Heck reactions in water
•
Li Wan Chun Cai
Received: 7 June 2011 / Accepted: 8 August 2011 / Published online: 20 August 2011
Ó Springer Science+Business Media B.V. 2011
Abstract A fluorous nano-palladium catalyst has been
synthesized and characterized. The catalyst is highly active
for the Heck reaction of aryl halides with substituted sty-
renes in water under air. The corresponding Heck products
were obtained in high yields with good stereoselectivity (E/Z
up to 98:2). In addition, the catalyst could be recovered by
fluorous liquid–liquid separation and reused four times
without significant loss of activity or stereoselectivity.
products were obtained in good to excellent yields under
phosphine-free conditions, high catalyst loading and
dimethylformamide were required in their experiments,
which would restrict the industrial applications of this
system. Polar aprotic solvents (DMF, NMP, DMA) still
remain the preferred media for carrying out Heck reactions.
However, these solvents are toxic and difficult to remove
from the reaction mixture. Therefore, numerous efforts
have been made to investigate this reaction in non-con-
ventional reaction media [6], such as water [7], ionic
liquids [8], and supercritical CO2 [9].
Introduction
Water, which is cheap, readily available, nontoxic, and
nonflammable, has obvious advantages as a solvent in
chemistry. Recently, Heck coupling reactions of water-
soluble aryl iodides performed in water with palladium
catalysts have been reported [10–13]. However, high cat-
alyst loading (1–3 mol%) and high temperatures were
required in most of these studies. Hence, the challenge
of developing an efficient catalyst for Heck reactions with
low catalyst loadings in water remains.
The Heck reaction is one of the most powerful tools in
organic synthesis for carbon–carbon bond formation, and it
has found widespread applications in the stereoselective
synthesis of various alkenes [1–4]. The reaction is normally
carried out with a palladium phosphine catalyst in homo-
geneous solution. However, phosphine ligands have the
disadvantages of being expensive, toxic, and air and mois-
ture sensitive. Therefore, in recent years, much attention has
been paid to developing phosphine-free ligands for the
Heck reaction. Wang and co-workers [5] described a Heck
reaction catalyst based on palladium anchored on proline-
functionalized silica gel. Although the cross-coupling
In the past decade, amino acids have been found to be
excellent ligands for copper-catalyzed amidation of aryl
iodides [14–16]. Although the amino acid ligand is easily
removed after the reaction because of its high solubility
in water, it is difficult to recycle the analogous palladium
catalysts. Recently, fluorous chemistry has emerged as a
powerful strategy for facilitating catalyst recovery [17–21].
Introducing a fluorous tag into the catalyst can make it
easily recoverable through a simple fluorous liquid–liquid
separation [22, 23]. Herein, we describe a facile process
(Scheme 1) to synthesize a palladium catalyst with a flu-
orous ligand derived from proline [24]. This catalyst was
applied in the Heck reaction of aryl halides with substituted
styrenes with low catalyst loading (0.1 mol% Pd) in water
under air. Recyclability experiments of the fluorous
L. Wan Á C. Cai
Chemical Engineering College, Nanjing University of Science
and 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

748
Transition Met Chem (2011) 36:747–750
palladium catalyst were performed up to four runs without
significant loss of activity.
Results and discussion
In order to evaluate the catalytic activity of the fluorous
palladium complex in Heck coupling reactions, we first
investigated the reaction of iodobenzene and styrene in the
presence of 0.1 mol% catalyst. The results are summarized
in Table 1. Compared to the reaction performed in water, a
good yield was obtained at 100 °C for 6 h in DMF (Table 1,
entries 1 and 2). It has been reported that additives such as
tetrabutylammonium bromide (TBAB) can give remarkable
rate enhancements in the Heck reaction [25]. When the
quantity of TBAB was increased to 50 mol%, the product
was obtained in good yield (Table 1, entry 5). Prolonging
the reaction time to 12 h, the product was obtained in 98%
yield (Table 1, entry 6). The role of TBAB is thought to be
that it facilitates solvation of the organic substrate in water.
Due to the sensitivity of Heck reactions to the base used,
the effects of K2CO3, KOH, NaOH, Cs2CO3, K3PO4, and
Et3N were investigated (Table 1, entries 6–11). The highest
yield was obtained with Et3N; however, the product was
obtained in lower stereoselectivity (Table 1, entry 11).
Therefore, we chose K2CO3 as the base for our continuous
reactions. In a control experiment, the fluorous palladium
catalyst was replaced with the conventional catalytic pre-
cursor Pd(OAc)2. In this case, lower yield and stereose-
lectivity were obtained under the same reaction conditions
(Table 1, entry 12). These results indicate that the fluorous
palladium complex is an efficient catalyst for the Heck
reaction in water in the presence of 50 mol% TBAB.
With these favorable results in hand, we investigated the
efficiency of the fluorous palladium catalyst with different
substrates. As shown in Table 2, a range of aryl iodides and
bromides was found to give the desired products in mod-
erate to high yields with good stereoselectivity (the ratio of
E/Z was up to 98:2). Aryl iodides bearing either electron-
donating or electron-withdrawing substituents in the ortho
and para positions afforded the corresponding products
in good to excellent yields with good stereoselectivity
(Table 2, entries 1–7). The ortho-substituted aryl iodides
gave the products in lower yields because of steric effects.
In addition, the coupling reaction could be efficiently car-
ried out using aryl bromides with electron-withdrawing
groups (Table 2, entries 9–11). However, aryl bromides
Experimental
The catalyst was prepared and characterized as recently
described [24]. All of the reagents and solvents were
commercially available and were used without further puri-
fication. GC analyses were performed on an Agilent 7890A
instrument. Palladium content was measured by inductively
coupled plasma (ICP) on a PE5300DV instrument.
Typical procedure for Heck reactions
Under air, a glass tube was charged with aryl halide (1.0 mmol),
substituted styrene (1.5 mmol), K2CO3 (2.0 mmol), tetra-
n-butylammonium bromide (TBAB, 50 mol%), H2O (2 mL)
and catalyst (0.1 mol% Pd). The tube was sealed and the
mixture was reacted at 100 °C for a certain period of time
(monitored by GC). After the reaction was complete, the
product was extracted with EtOAc. The organic phase was
separated, dried over anhydrous Na2SO4, and evaporated. The
crude products were purified by flash chromatography with
n-hexane/EtOAc as eluent. All the products were known
compounds and were identified by comparison with their
physical and spectroscopic data with those of authentic
samples.
Recycling of catalyst
A glass tube was charged with iodobenzene (1.0 mmol),
styrene (1.5 mmol), TBAB (50 mol%), K2CO3 (2.0 mmol),
H2O (2 mL), and catalyst (0.1 mol% Pd) and then sealed.
The reaction was performed at 100 °C for 12 h. After the
reaction was complete, EtOAc (5 mL) and perfluorodecalin
(C10F18, cis and trans-mixture, 5 mL) were added. The
mixture was heated to 100 °C for 10 min and then cooled
to room temperature. The fluorous phase was separated and
concentrated to recover the catalyst for the next cycle. Per-
fluorodecalin was collected by distillation for reuse without
further purification. The crude products were purified by
flash chromatography with n-hexane/EtOAc as eluent.
Scheme 1 Preparation of the
fluorous palladium catalyst
O
O
O
O
S
O
S
C8F17SO2NH2
CF3COOH
N
C8F17
N
C8F17
OH
DMAP, EDCI
EtOAc
N
H
N
H
N
O
O
H
Boc
Boc
O
O
Pd(OAc)2, EtOH
N S C8F17
N
H
H
O
Pd
AcO
OAc
123

Transition Met Chem (2011) 36:747–750
749
Table 1 Optimization of the Heck reaction conditions
I
base, cat.
solvent
+
Entry
Solvent
TBAB (mol %)
Temperature (°C)
Time (h)
Base
Yielda (%)
E/Zb
1
DMF
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
0
0
100
100
100
100
100
100
100
100
100
100
100
100
6
6
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOH
87
43
52
69
88
98
97
96
91
86
99
79
90:10
93:7
94:6
94:6
93:7
93:7
92:8
92:8
92:8
93:7
91:9
88:12
2
3
5
6
4
20
50
50
50
50
50
50
50
50
6
5
6
6
12
12
12
12
12
12
12
7
8
NaOH
Cs2CO3
K3PO4
Et3N
9
10
11
12c
K2CO3
Reaction conditions Iodobenzene (1.0 mmol), styrene (1.5 mmol), TBAB, base (2.0 mmol), fluorous palladium catalyst (0.1 mol% Pd) in 2 mL
solvent
a
Isolated yield
b
The ratio of E/Z was determined by GC analysis of the crude product
c
Pd(OAc)2 used as catalyst
Table 2 Heck reactions of aryl halides and substituted styrenes
X
R2
K2CO3, cat.
H2O,TBAB R1
R1
R2
+
Entry
X
R1
R2
Time (h)
Yielda (%)
E/Zb
1
I
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
12
12
12
12
12
12
12
24
24
24
24
24
24
24
24
24
12
12
12
12
98
99
91
89
90
83
80
73
89
93
90
69
63
13
45
29
96
90
97
92
93:7
93:7
93:7
94:6
92:8
91:9
91:9
96:4
98:2
98:2
97:3
90:10
96:4
92:8
94:6
93:7
93:7
92:8
94:6
93:7
2
I
4-CH3
3-CH3
2-CH3
4-NO2
3-NO2
2-NO2
H
3
I
4
I
5
I
6
I
7
I
8
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
I
9
4-NO2
4-CF3
3-CF3
4-CH3
4-CH3O
H
10
11
12
13
14
15
16
17
18
19
20
4-NO2
4-CH3
H
4-CH3
2-CH3
4-Cl
I
H
I
H
I
H
2-Cl
Reaction conditions Aryl halide (1.0 mmol), substituted styrene (1.5 mmol), TBAB (50 mol %), K2CO3 (2.0 mmol), catalyst (0.1 mol% Pd) in 2 mL H2O
a
Isolated yield
b
The ratio of E/Z was determined by GC analysis of the crude product
123

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Transition Met Chem (2011) 36:747–750
reaction in water. The catalyst shows high catalytic activity
for the reaction of aryl halides and substituted styrenes with
low catalyst loading, and the corresponding products were
obtained in moderate to excellent yields with good stere-
oselectivity toward trans-stilbenes (with E/Z ratio of up to
98:2). Water as a solvent is more eco-friendly than DMF
that is mostly used in Heck reactions. Moreover, the cat-
alyst could be easily recovered by fluorous liquid–liquid
separation and reused for four times without significant loss
of activity or stereoselectivity. The excellent performance
of the catalyst in water under air and its easy preparation
and reusability make it a useful alternative to other palla-
dium catalysts.
Table 3 Recycling of the fluorous catalyst in the Heck reaction
I
K2CO3, cat.
H2O,TBAB
+
Cycle
Time (h)
Yielda (%)
E/Zb
1
2
3
4
12
12
12
12
98
96
93
90
93:7
93:7
92:8
92:8
Reaction conditions Iodobenzene (1.0 mmol), styrene (1.5 mmol),
TBAB (50 mol %), K2CO3 (2.0 mmol), fluorous palladium catalyst in
2 mL H2O
a
Isolated yield
b
The ratio of E/Z was determined by GC analysis of the crude
product
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In summary, we have prepared a new fluorous nano-
palladium catalyst and successfully applied it for the Heck
123