Supported ionic liquid catalyst (Pd-SILC) for highly efficient and recyclable Suzuki-Miyaura reaction

Article abstract of DOI:10.1039/b704098a

Highly efficient Suzuki-Miyaura coupling of aryl halides with arylboronic acid was realized in 50% aqueous ethanol at room temperature employing Pd(OAc)₂ immobilized in diethylaminopropylated (NDEAP) alumina pores with the aid of [bmim]PF₆, which enabled recycle use up to five times in 95% average yield and turnover number of two million. The Royal Society of Chemistry.

Full text of DOI:10.1039/b704098a

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Supported ionic liquid catalyst (Pd-SILC) for highly efficient and
recyclable Suzuki–Miyaura reaction
a
Hisahiro Hagiwara,* Keon Hyeok Ko, Takashi Hoshi and Toshio Suzuki
a
b
b
Received (in Cambridge, UK) 19th March 2007, Accepted 18th April 2007
First published as an Advance Article on the web 1st May 2007
DOI: 10.1039/b704098a
Highly efficient Suzuki–Miyaura coupling of aryl halides with
arylboronic acid was realized in 50% aqueous ethanol at room
Immobilization of Pd(OAc)
on amorphous silica or alumina
2
with the aid of an ionic liquid was carried out in the same manner
5
d
temperature employing Pd(OAc) immobilized in diethylami-
as described previously. Since the choice of solvent was very
important, we focused initially on the effect of solvent in the
coupling reaction of p-bromoacetophenone with phenylboronic
acid, and the results of investigations are shown in Table 1. In
entries 1–5 and 8–10, a large amount of p-bromoacetophenone
was recovered. However, we happened to find that the reaction
2
nopropylated (NDEAP) alumina pores with the aid of
6
[bmim]PF , which enabled recycle use up to five times in 95%
average yield and turnover number of two million.
The Suzuki–Miyaura reaction is one of the most powerful cross
coupling reactions not only for various biaryls but also for
1
arylolefinic compounds. Owing to wide applicability towards a
6
occurred essentially instantaneously in 50% aqueous ethanol as
shown in entries 11 and 12, in which the ethanol : water ratio was
critical for rapid reaction. A larger amount of ethanol slowed
down the reaction (entries 7, 13 and 14). On the other hand, a
higher water content caused separation of the ionic liquid layer
from the alumina (entry 15).
variety of substrates, the reaction has been applied to process
2
chemistry, in which more mild, and efficient protocols are desired.
In designing such protocols, room-temperature ionic liquids have
3
played important roles as a liquid support, which gives stability
4
and recyclability to the catalyst. In order to improve the cost and
Since the reaction of p-bromoacetophenone with phenylboronic
acid was so promising in 50% aqueous ethanol, the reaction of
p-bromoanisole was employed as a probe to tune further reaction
conditions.
handling of the catalyst in recycle use, the catalyst supported by an
ionic liquid was further supported on a porous solid such as silica
5
or molecular sieves. The present paper describes highly efficient
Suzuki–Miyaura reaction in 50% ethanol catalysed by immobilized
2
An optimum support for Pd(OAc) was investigated in 50%
Pd(OAc) on reversed phase alumina with the aid of an ionic liquid
2
aqueous ethanol and the results are shown in Table 2. Silica
(Pd-SILC) (Scheme 1).
grafted octyltrimethoxysilane did not immobilize Pd(OAc) even
2
5e,7
with ionic liquid.
Thus, surfaces of silica and alumina were
grafted with amino groups, and their capability as reversed phase
Table 1 Solvent effect in the reaction of p-bromoacetophenone with
phenylboronic acid
a
b
Yield (%)
Entry
Solvent
Time/min
c,f
1
Et
CH
DMF
AcOEt
Acetone
PEG
EtOH
THF–H
PEG–H
2
O
3
CN
100
90
90
90
90
180
90
180
180
180
,1
,1
180
180
10
0
43
55
61
c
2
c
3
c
4
c
5
67
c,f
6
100
100
38
43
55
100
100
77
c,f
7
d
8
2
O (1 : 1)
O (1 : 1)
d
9
2
d,g
1
1
1
1
1
1
a
0
1
2
3
4
5
t-BuOH–H
2
O (1 : 1)
c
EtOH–H
EtOH–H
EtOH–H
EtOH–H
EtOH–H
2
2
2
2
2
O (1 : 1)
O (1 : 1)
O (3 : 1)
O (22 : 1)
O (1 : 3)
c
e
e
53
—
e,h
Reaction was carried out at room temperature with two
Scheme 1 Suzuki–Miyaura reaction catalyzed by immobilized Pd
equivalents of potassium carbonate employing 0.05 equivalents of
Pd(OAc) immobilized on solid support with the aid of [bmim]PF6.
Yield is for isolated pure product and based on
catalyst on reversed phase alumina.
2
b
c
p-bromoacetophenone. 0.25–0.3 mmol of Pd/g of SiO
2
was used as
was used as catalyst.
2 3
0.25–0.3 mmol of Pd/g of Al O was used as catalyst. Pd was
g
reduced before the reaction by refluxing in n-hexane. Reaction was
a
Graduate School of Science and Technology, Niigata University, 8050,
2-Nocho, Ikarashi, Niigata, 950-2181, Japan.
E-mail: hagiwara@gs.niigata-u.ac.jp
d
catalyst. 0.02–0.025 mmol of Pd/g of Al
O
2 3
e
f
b
Faculty of Engineering, Niigata University, 8050, 2-Nocho, Ikarashi,
Niigata, 950-2181, Japan
h
carried out at 50 uC. Leaching of ionic liquid layer occurred.
2
838 | Chem. Commun., 2007, 2838–2840
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Table 2 Examination of optimum support for Pd(OAc)
reaction of p-bromoanisole and phenylboronic acid
2
in the
Table 4 Coupling of a variety of aryl halides with phenylboronic
acids
a
b
Yield (%)
a
b
Aryl halide and arylboronic acid Time/min Yield (%)
Entry
Support
Entry
1
2
3
4
5
6
7
a
Polyimino-SiO
2
3
24
64
83
83
83
75
1
2
3
4
5
6
7
8
9
10
R = p-Ac, X = Br, R9 = H
R = p-NO , X = Br, R9 = H
1
60
180
100
15
10
40
15
30
100
92
83
61
98
96
97
78
93
100
84
92
Ethylenediamino-SiO
2
2
c
NDEAP-SiO
NDEAP-Al
2
R = p-MeO, X = Br, R9 = H
R = p-Me, X = Br, R9 = H
R = p-Ac, X = Br, R9 = p-MeO
R = p-Ac, X = Br, R9 = p-Ac
R = p-Ac, X = I, R9 = H
2
O
3
[bmim]PF
[bmim]PF
[bmim]NTf
6
-NDEAP-SiO
-NDEAP-Al
-NDEAP-Al
2
6
2
O
3
2
2
O
3
R = p-MeO, X = I, R9 = H
R = p-Cl, X = Br, R9 = H
R = p-EtO C, X = Br, R9 = H
Reaction was carried out at room temperature for 3 h in EtOH–
O (1 : 1); Pd loading was 0.29 mmol g
2
1
b
H
2
.
Yield is for isolated
c
2
240
180
30
pure product and based on p-bromoanisole.
N,N-diethylaminopropylated
NDEAP
=
1
1
a
1
2
R = p-HO C, X = Br, R9 = H
c
2
3-Bromopyridine, R9 = H
Reaction was carried out under the optimized reaction conditions
as described in ref. 9 employing low loading Pd catalyst (0.020–
solid supports was examined. In entries 1 and 2, Pd(OAc) was
2
21
.025 mmol g ). Yield is for isolated pure product and based on
b
0
aryl halide. Purity of the product was determined by NMR
not reduced to Pd(0) and thus a large amount of p-bromoanisole
c
spectroscopy. Reaction was carried out under microwave heating at
was recovered. While Pd(OAc)
2
immobilized on N,N-diethyl-
7
5 uC.
aminopropylated alumina or silica with or without [bmim]PF
6
gave the best results (entries 4–6), immobilization with the aid of
an ionic liquid was desirable especially to inhibit leaching of
satisfactory yields (entries 1–4). The electronic nature of the
arylboronic acid also did not affect the efficiency of the reaction
5b
Pd(OAc) in recycle use. Among solid supports, alumina was
2
preferable due to its stability towards aqueous basic reaction
(entries 5 and 6).
conditions (entries 5 and 6). [Bmim]PF
bmim]NTf (entries 6 and 7).
de Vries and Reetz reported that low Pd loading (0.01–0.1
6
was superior to
The catalyst was re-used up to five times in 95% average yield,
though catalytic activity gradually was lost during recycle use
[
2
(Table 5).
mol%) was more effective for homogeneous catalytic reaction,
since aggregation of Pd nanoparticles into less reactive clusters
8
could be prevented. Actually, Pd(OAc)
Table 5 Recycle of the catalyst in the reaction of p-bromoacetophe-
none and phenylboronic acid
2
at low concentration in
silica pores exhibited higher reactivity in our previous Mizoroki–
a
Yield (%)
Entry
Time/min
5e
Heck reaction in water. To this end, an immobilized catalyst of
2
1
low concentration (0.020–0.025 mmol g of alumina) was used
1
2
3
4
5
a
,1
2
15
45
60
100
90
92
96
97
for further reactions. Actually, leaching of Pd(OAc) was observed
2
2
1
in the reaction of higher loading catalyst (0.25–0.3 mmol g ) in
aqueous ethanol.
The other parameter is the choice of a base. After screening
several different bases, it was found that the reaction was
dependent on base, among which two equivalents of potassium
carbonate was optimum as shown in Table 3, entry 6. The
efficiency of potassium carbonate is yet to be discussed.
Yield is for isolated pure product and based on
p-bromoacetophenone.
High efficiency of the present catalytic system was exemplified
by a remarkably high turnover number of 2 million and high
10
9
Based on the optimized reaction conditions (Table 3, entry 6),
turnover frequency of 30 thousand (Table 6, entry 5). For each
the Suzuki–Miyaura coupling of a variety of aryl halides with
arylboronic acid was investigated and the results are shown in
Table 4. Aryl halides having both electron withdrawing
and donating substituents provided the coupling products in
reaction, a new flask was employed to avoid the possibility of
11
Suzuki–Miyaura reaction catalyzed by Pd contamination.
Table 6 Performance of the catalyst in the reaction of p-bromoace-
tophenone and phenylboronic acid
a
Table 3 Effect of base in the reaction of p-bromoanisole and
phenylboronic acid
2
1
Entry Catalyst (eq.) Time
Yield (%) TON
TOF/h
a
b
Yield (%)
Entry
Base
Amount (equiv.)
23
3
1
2
3
4
5
a
4 6 10
5 6 10
5 6 10
5 6 10
5 6 10
5 min
30 min 100
30 min 100
11 h
70 h
100
250
3 6 10
4 6 10
4 6 10
2 6 10
3 6 10
2
4
3
4
5
6
3
4
4
4
2 6 10
2 6 10
2 6 10
2 6 10
1
2
3
Na
PO
CO
DBU
2
CO
3
2
2
2
1
1
2
3
39
46
58
77
37
83
40
25
26
27
K
3
4
100
98
Cs
2
3
c
4
A new reaction vessel was employed for each run.
5
6
7
a
K
2
K
2
K
2
CO
3
CO
CO
3
3
In summary, we have developed highly efficient Suzuki–
Miyaura coupling of aryl halides with arylboronic acids in 50%
aqueous ethanol employing Pd(OAc) immobilized in NDEAP-
Reaction was carried out at room temperature for 3 h in EtOH–
O (1 : 1). Pd loading on [bmim]PF –NDEAP–Al was 0.020–
Yield is for isolated pure product and based on
H
2
6
2 3
O
2
1 b
.
c
0
.025 mmol g
2
p-bromoanisole. Leaching of ionic liquid layer occurred.
alumina pores with the aid of an ionic liquid, [bmim]PF . The
6
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reaction proceeded without a phosphine ligand at room tempera-
ture in a short period of time. The immobilized catalyst was re-
used up to five times in 95% average yield. The highest turnover
number of two million exemplified high efficiency of the protocol.
This work was partially supported by Grant-in-Aid for
Scientific Research on Priority Areas (17073007 for H. H. and
T. H.) from The Ministry of Education, Culture, Sports, Science
and Technology (MEXT).
8
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Typical experimental procedure: To a stirred solution of p-bromoaceto-
phenone (98 mg, 0.49 mmol), phenylboronic acid (101 mg, 0.83 mmol),
9
and K CO
2
added [bmim]PF
3
(139 mg, 1 mmol) in ethanol (1 mL) and water (1 mL) was
–NDEAP–alumina (896 mg, Pd: 0.024 mmol). After
6
stirring for 1 min, the product was triturated with ethyl acetate several
times. The combined organic layers were evaporated to dryness and the
2
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840 | Chem. Commun., 2007, 2838–2840
This journal is ß The Royal Society of Chemistry 2007