Immobilization of Pd(OAc)2 in ionic liquid on silica: Application to sustainable Mizoroki-Heck reaction

Article abstract of DOI:10.1021/ol049343i

(Equation Presented) Palladium acetate was supported on amorphous silica with the aid of an ionic liquid, [bmim]PF₆. The immobilized catalyst was highly efficient in promoting the Mizoroki-Heck reaction without a ligand in n-dodecane for at least six reuses, in 89-98% yields. The TON and TOF reached 68 400 and 8000, respectively.

Full text of DOI:10.1021/ol049343i

ORGANIC
LETTERS
2004
Vol. 6, No. 14
2325-2328
Immobilization of Pd(OAc)2 in Ionic
Liquid on Silica: Application to
Sustainable Mizoroki−Heck Reaction
,†
Hisahiro Hagiwara,* Yoshitaka Sugawara,† Kohei Isobe,† Takashi Hoshi,‡ and
Toshio Suzuki‡
Graduate School of Science and Technology, Niigata UniVersity, 8050,
2-Nocho, Ikarashi, Niigata 950-2181, Japan, and Faculty of Engineering,
Niigata UniVersity, 8050, 2-Nocho, Ikarashi, Niigata 950-2181, Japan
hagiwara@gs.niigata-u.ac.jp
Received April 9, 2004
ABSTRACT
Palladium acetate was supported on amorphous silica with the aid of an ionic liquid, [bmim]PF6. The immobilized catalyst was highly efficient
in promoting the Mizoroki−Heck reaction without a ligand in n-dodecane for at least six reuses, in 89∼98% yields. The TON and TOF reached
68 400 and 8000, respectively.
The Mizoroki-Heck reaction1 has been one of the most
fundamental Pd-catalyzed carbon-carbon bond-forming
reactions. Since its invention, numerous efforts have been
devoted to further development of the reaction because of
its usefulness and especially the wide applicability to various
substrates. Recent developments in this area enabled the
introduction of various new ligands,2 new bases,3 new
techniques such as microwave4 or ultrasonic irradiation,5 and
so on.3 Another current interest is the development of
environmentally as well as economically benign reaction
conditions due to the high price of Pd. Since a homogeneous
Pd catalyst easily loses catalytic activity, forming Pd clusters,
a heterogeneous catalyst is desirable6 especially for recycling,
though it is not always as reactive compared to homogeneous
catalysts.
To satisfy both recyclability and reactivity, immobilization
of a reactive homogeneous catalyst was devised to bind the
Pd catalyst on a polymer.7 A more facile method is to
immobilize the catalyst in a liquid phase by dissolving it
into a nonvolatile and nonmixing liquid such as PEG.8 From
such a standpoint, a room-temperature ionic liquid9 is
expected to be a candidate as a support of the catalyst10 due
† Graduate School of Science and Technology.
‡ Faculty of Engineering.
(1) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc., Jpn. 1971, 44,
581. Heck, R. F. Org. React. 1982, 27, 345. Tsuji, J. Palladium Reagents
and Catalysts; InnoVations in Organic Synthesis; Wiley: Chichester, UK,
1996.
(2) For example: Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123,
6989.
(3) Yao, Q.; Kinney, E. P.; Yang, Z. J. Org. Chem. 2003, 68, 7528 and
earlier references therein.
(6) Some recent examples of heterogeneous Pd catalysts fixed on
inorganic support for aryl coupling reactions: (a) Ramchandani, R. K.;
Uphade, B. S.; Vinod, M. P.; Wakharkar, R. D.; Choudhary, V. R.; Sudalai,
A. Chem. Commun. 1997, 2071. (b) Anson, M. S.; Mirza, A. R.; Tonks,
L.; Williams, J. M. J. Tetrahedron Lett. 1999, 40, 7147. (c) Mori, K.;
Yamaguchi, K.; Hara, T.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am.
Chem. Soc. 2002, 124, 11572. (d) Molnar, A.; Papp, A.; Miklos, K.; Forgo,
P. Chem. Commun. 2003, 2626. (e) Daku, K. M. L.; Newton, R. F.; Pearce,
S. P.; Vile, J.; Williams, J. M. J. Tetrahedron Lett. 2003, 44, 5095. See
also earlier references cited in these references.
(4) Vallin, K. S. A.; Emilsson, P.; Larhed, M.; Hallberg, A. J. Org. Chem.
2002, 67, 6243.
(5) Deshmukh, R. R.; Rajagopal, R.; Srinivasan, K. V. Chem. Commun.
2001, 1544.
(7) (a) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach,
A. G.; Longbottom, D, A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S.
J. J. Chem. Soc., Perkin Trans. 1 2000, 3815. (b) Yamada, Y. M. A.; Takeda,
K.; Takahashi, H.; Ikegami, S. Tetrahedron Lett. 2003, 44, 2379.
10.1021/ol049343i CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/16/2004

Table 1. Optimization of Reaction Conditions Employing Supported Pd Catalyst
entry
R′
Pd source
base
solvent
temp (°C)
time (h)
yield (%)e
1
2
3
4a
5
Me
Me
Me
Me
cyclohexyl
Me
Meb
Me
Me
cyclohexyl
cyclohexyl
cyclohexyl
Pd Black
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Et3N
Et3N
Et3N
Et3N
K2CO3
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
n-Bu3N
n-dodecane
n-dodecane
n-dodecane
toluene
n-dodecane
methylcyclohexane
n-octane
120
120
120
120
120
100
120
120
120
120
150
150
7
7
7
17
11.5
5
7
5
5
31
59
59
64
21
22
68
51
51
75
99
96
6
7
8c
9c
10
11d
12
n-octane
n-dodecane
n-dodecane
n-dodecane
n-dodecane
16.5
15.5
15
a Pd(OAc)2 dissolved from silica surface in toluene layer. b Performed with 2 equiv of acrylate. c Sodium m-diphenylphosphinobenzene-sulfonate was
added. d Reaction was carried out in a sealed tube at 150 °C. e Yield is for isolated pure product and is based on iodobenzene 1a.
to its nonlipophilic and nonhydrophobic nature. However,
there are two major drawbacks, i.e., the higher cost of ionic
liquids for larger scale use and the higher viscosity in
handling as a liquid support.
Another option is to immobilize the catalyst on a solid-
phase such as silica, which is chemically and mechanically
stable. Williams et al.6b,e reported immobilization of
Pd(PPh3)4 on reversed-phase silica beads, which exhibited
high efficiency in Pd-catalyzed reactions in aqueous media,
while Mehnert et al.11 demonstrated immobilization of a
rhodium catalyst in [bmim]PF6 on a silica surface. Our recent
sustainable Mizoroki-Heck reactions with high efficiency
and recyclability. Immobilization of the Pd catalyst on silica
with the aid of an ionic liquid should provide the following
features: (1) stabilization of the Pd catalyst, (2) inexpensive
immobilization without using expensive coupling reagents
or a large amount of ionic liquid, and (3) accumulation of
Pd on silica to facilitate catalytic reaction.
The procedure of immobilization is quite simple.13
A
suspension of spherical amorphous silica in a solution of
Pd(OAc)2 in [bmim]PF6 and THF was evaporated to dryness
to afford a powdery and free-flowing immobilized catalyst.
Among the ionic liquids tested, [bmim]PF6 was better to at
holding Pd(OAc)2 than [bmim]Br, [bmim](CF3SO2)2N, or
[hmim]PF6.
According to scanning electron microscopy (SEM), the
shape of the immobilized catalyst was round (×1700). In
contrast to the original unsupported silica, primary particles
were observed clearly in a magnified picture (×70 000). This
result indicates that ionic charges exist on the round surface
or in pores of the primary silica particles. Electron X-ray
microanalyses (EPMA) showed that phosphorus, fluorine,
and Pd distributed on the surface of silica uniformly. By
atomic force microscopy (AFM), a smooth surface of the
supported silica was observed compared to that of unsup-
ported silica (see Supporting Information). These results
along with the dry character of the catalyst suggest that
solution of Pd(OAc)2 in an ionic liquid exists in the pores
of silica. In a similar manner, Pd(PPh3)4 and Pd black were
immobilized according to the procedure, though Pd/C and
Figure 1.
interest in the development of sustainable organic reactions
in an ionic liquid by homogeneous as well as heterogeneous
catalysts10c,12 led us to investigate a facile immobilization
of the Pd catalyst in an ionic liquid in silica pores for use in
(8) Heldebrant, D. J.; Jessop, P. G. J. Am. Chem. Soc. 2003, 125, 5600.
Chandrasekhar, S.; Narsihmlu, C.; Sultana, S. S.; Reddy, N. R. Chem.
Commun. 2003, 1716.
(12) Hagiwara, H.; Tsuji, S.; Okabe, T.; Hoshi, T.; Suzuki, T.; Suzuki,
H.; Shimizu, K.; Kitayama, Y. Green Chem. 2002, 4, 461. Hamaya, J.;
Suzuki, T.; Hoshi, T.; Shimizu, K.; Kitayama, Y.; Hagiwara, H. Synlett.
2003, 873. Hagiwara, H.; Okabe, T.; Hoshi, T.; Suzuki, T. J. Mol. Catal.
A, Chem. 2004, 214, 167.
(13) Representative Procedure for Catalyst Preparation. To a stirred
solution of Pd(OAc)2 (690 mg) in [bmim]PF6 (1 g) and THF (10 mL) was
added silica powder (10 g, spherical for flash column chromatography,
diameter ) 40-50 µm, pore size ) 5-7 nm, pore volume ) 0.80-1.00
mL/g, surface area ) 600-700 m2/g). After being stirred for 90 min, THF
was evaporated to dryness in vacuo to give a light brown dry powder that
was rinsed with diethyl ether until the diethyl ether layer became colorless
and then dried in vacuo. The amount of Pd(OAc)2 supported was 560 mg
(0.25 mmol/g) based on weight gain.
(9) Welton, T. Chem. ReV. 1999, 99, 2071. Wassersheid, P.; Keim, W.
Angew. Chem., Int. Ed. 2000, 39, 3773. Sheldon, R. Chem. Commun. 2001,
2399. Gordon, C. M. Appl. Catal. 2001, 222, 101. Ionic Liquids in Synthesis,
Wasserscheid, P., Welton, T., Eds.; Wiley-VCH: Weinheim, 2003.
(10) (a) Carmichael, A. J.; Earle, M. J.; Holbrey, J. D.; McCormac, P.
B.; Seddon, K. R. Org. Lett. 1999, 1, 997. (b) Xu, L.; Chen, W.; Xiao, J.
Organomet. 2000, 19, 1123. (c) Hagiwara, H.; Shimizu, Y.; Hoshi, T.;
Suzuki, T.; Ando, M.; Ohkubo, K.; Yokoyama, C. Tetrahedron Lett. 2001,
42, 4349.
(11) Mehnert, C. P.; Mozeleski, E. J.; Cook, R. A. Chem. Commun. 2002,
3010.
2326
Org. Lett., Vol. 6, No. 14, 2004

PdCl2(PPh3)2 could not be immobilized due to negligible
solubility of the catalysts in [bmim]PF6 and THF.
Table 3. Mizoroki-Heck Reaction with Various Aryl Halides
1 with Cyclohexyl Acrylate 2
By employing a reaction of iodobenzene 1a and acrylate
2 as a probe, the reaction conditions were optimized. To
prevent removal of the ionic liquid layer from the silica, the
reaction was carried out in a hydrocarbon solvent. The results
are compiled in Table 1.
entrya
1
time (h)
3 yield (%)b
1
2
3
4
5
6
7
8
9d
1b
1c
1d
1e
1f
1g
1h
1i
1.3
5.0
1.3
2.0
2.5
2.0
2.0
2.5
6.0
82
68
81
86
96
85
59c
88
60
Among Pd sources, Pd(OAc)2 was chosen for further
reactions due to the lack of phosphine ligand, stability, and
economy since Pd(OAc)2 and Pd(PPh3) showed similar
activities (entries 2 and 3). Triethylamine was a superior base
to potassium carbonate (entries 3 and 5). Reuse of the catalyst
was difficult in hot toluene due to solubility of the ionic
liquid (entry 4). Addition of sodium m-diphenylphos-
phinobenzenesulfonate did not show significant improvement
(entries 8 and 9). With cyclohexyl acrylate 2 (R′ ) C6H11),
the yield was improved to a certain degree (entry 10). When
the reaction temperature was raised to 150 °C in a sealed
tube, the reaction proceeded almost quantitatively (entry 11).
Finally, the optimized reaction condition was obtained using
tri-n-butylamine as a base (entry 12) in an open vessel.
The catalyst was easily reused up to three times as shown
in Table 2 without taking any precautions after taking up
1a
a Reaction was carried out under the optimized reaction condition as
described in Table 1, entry 12. b Yield is for isolated pure product and is
based on aryl halide 1. c Product 3 was accompanied with vanillin in 17%
yield. d Styrene was used instead of acrylate 2.
listed in Table 3. Not only aryl halides 1b-e having electron-
withdrawing substituents (entries 1-4) but also 1f-h having
electron-donating substituents (entries 5-7) provided cou-
pling products 3 in satisfactory yields. In entry 7, a certain
amount of reduction occurred. In the reaction of iodobenzene
Scheme 1
Table 2. Recycling of the Immobilized Catalyst
entrya
cycle
yield (%)
1
2
3
4
5
6b
1
2
3
4
5
6
96
98
96
90
89
93
a Reaction was carried out under the optimized reaction conditions as
described in Table 1, entry 12. b Catalyst was washed with dilute aqueous
NaOH.
the supernatant n-dodecane layer. A decrease of the catalytic
activity was observed after three cycles, in which the free-
flowing nature of the catalyst was lost. This result might
arise from covering the silica surface with the resulting
tributylammonium iodide, which could not be removed due
to its insolubility in n-dodecane. This shortcoming was solved
by washing the catalyst with dilute aqueous sodium hydrox-
ide to retrieve the catalytic activity14 as shown in entry 6,
Table 2.
1a and cyclohexyl acrylate 2, the turnover number (TON)
and turnover frequency (TOF) reached 68 400 and 8000
(h-1), respectively (Table 4, entry 4), which are quite high
Table 4. Performance of the Immobilized Catalyst
entry catalyst (equiv) time (h) yield (%) TON TOF (h-1
)
1
2
3
4
0.0103
0.0053
0.0024
0.0013
5.5
6.0
8.0
8.5
91
96
91
94
8800
18 000
38 000
68 400
1600
3000
4800
8000
According to the optimized reaction conditions in entry
12, Table 1,15 the Mizoroki-Heck reaction with several aryl
halides 1 was examined, and some representative results are
(14) Handy, S. T.; Okello, M.; Dickenson, G. Org. Lett. 2003, 5, 2513.
(15) Representative Procedure for Mizoroki-Heck Reaction. To a
suspension of the immobilized catalyst (400 mg, 0.1 mmol as Pd(OAc)2)
in n-dodecane (2 mL) were added iodobenzene 1 (112 mg, 1 mmol),
cyclohexyl acrylate 2 (189 mL, 1.2 mmol), and tri(n-butyl)amine (279 mL,
2 mmol) under a nitrogen atmosphere. The suspension was heated at 150
°C until disappearance of iodobenzene 1 by GLC monitoring. After being
cooled to room temperature, the n-dodecane layer was passed through a
silica column with the aid of n-hexane to remove n-dodecane. Subsequently,
the product was eluted with n-hexane-ethyl acetate. The n-hexane-ethyl
values among other heterogeneous Pd catalysts,6c except for
recently developed polymer-bound catalysts.7b By recycling
acetate eluent was evaporated to dryness to give a residue that was purified
by medium-pressure LC (eluent ) ethyl acetate/n-hexane 1:20) to afford
cyclohexyl cinnamate 3 (234 mg, 98%). The catalyst was reused intact for
the next reaction without any pretreatment.
Org. Lett., Vol. 6, No. 14, 2004
2327

the catalyst, the TON could be multiplied. The higher
concentration (3.4 M) of Pd(OAc)2 in the pores distributed
on the wide surface area might provide the remarkably high
efficiency.
immobilized in this way was air-stable and thermally stable
to allow easy use and storage without any precautions, which
would enable wide application in various Pd-catalyzed
reactions.
The supernatant n-dodecane layer was filtered through a
membrane filter (pore diameter: 7 µm) after the reaction
was complete, and the mixture was analyzed by ICP, in
which 0.24 ppm of Pd was found in the layer when 10 mol
% Pd(OAc)2 was used in the reaction; that is, less than 0.24%
Pd was dissolved from the silica support. The level of
leaching is quite reasonable compared to other heterogeneous
catalysts6b,d supported on solid.
In summary, we have demonstrated an environmentally
benign, economically friendly, and sustainable ligandless
Mizoroki-Heck reaction of aryl halides 1 employing Pd-
(OAc)2 supported in an ionic liquid layer in silica pores. The
immobilization was simple without requiring any multistep
operations or expensive coupling reagents. The catalyst
Acknowledgment. We thank Dr. Ken-ichi Shimizu,
Graduate School of Science and Technology, Niigata Uni-
versity, for helpful discussions.
Supporting Information Available: Copies of EPMA,
SEM, and AFM pictures of Pd-supported and unsupported
silica before use, SEM and EPMA pictures of the catalyst
after six cycles, 1H NMR spectra of the products 1a -i, and
a representative experimental procedure of the catalyst
preparation and Mizoroki-Heck reaction. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL049343I
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Org. Lett., Vol. 6, No. 14, 2004