Heterogeneous Suzuki reactions catalyzed by Pd(0)-Y zeolite

Article abstract of DOI:10.1016/j.tetlet.2004.03.126

The Pd(0)-Y zeolite showed high activity in the Suzuki cross-coupling reactions of aryl bromides without added ligands. The type of base and organic solvent were found to be critical for the efficiency of the reaction. The presence of water was essential within the reaction medium. The coupling reactions occurred on the external surface of the zeolite. The catalyst is reusable.

Full text of DOI:10.1016/j.tetlet.2004.03.126

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3881–3884
Heterogeneous Suzuki reactions catalyzed by Pd(0)–Y zeolite
Levent Artok* and Hatice Bulut
Department of Chemistry, Faculty of Science, Izmir Institute of Technology, Urla 35430 Izmir, Turkey
Received 18 December 2003; revised 16 March2004; accepted 22 March2004
Abstract—The Pd(0)–Y zeolite showed high activity in the Suzuki cross-coupling reactions of aryl bromides without added ligands.
The type of base and organic solvent were found to be critical for the efficiency of the reaction. The presence of water was essential
within the reaction medium. The coupling reactions occurred on the external surface of the zeolite. The catalyst is reusable.
Ó 2004 Elsevier Ltd. All rights reserved.
The Pd-catalyzed cross-coupling of aryl halides with aryl
boronic acids, that is the Suzuki reaction, is recognized
as being one of the most powerful and popular methods
for the construction of unsymmetrical biaryls, which are
widely used for the synthesis of valuable organic com-
deactivated bromoarenes. Pd/C was determined to be
active in Suzuki reactions for iodoarenes in ethanol/
water mixtures3 and iodophenols in water,4 yet led to low
yields for bromoarenes. In a study by Heidenreichet al.,
a relatively high reaction temperature (120 °C) was
required for effective coupling of bromo- and iodoarenes
over Pd/C, the activity being markedly reduced by more
than 50% when reused.5 It was shown that Pd/C cata-
lyzes the Suzuki cross-coupling reaction of activated
chloroarenes with various arylboronic acids upon fine
adjustment of the N,N-dimethylacetamide (DMA)/water
ratio.6 However, long reaction times were required (24 h)
and reusability was not tested for the catalyst. Also, it
was shown in a recent study, that Pd/C can be used as a
recyclable catalyst in the Suzuki reactions of aryl halides
in water and in the presence of surfactants.7 In a study by
Kabalka et al., while a Pd-doped alumina support was
found to be activating for iodoarenes in Suzuki reac-
tions, it had low activity for bromoarenes.8
1
pounds suchas pahrmaceuticals and agrochemicals.
The particular merits of this reaction are that the reac-
tion can be performed under mild conditions in aqueous
solutions and that it tolerates a broad range of func-
tional groups.
R
R'
X
B(OH)2
R
R'
Pd, base
+
Many Pd complexes have been investigated in homo-
geneous systems in the Suzuki reaction of aryl halides.
However, palladium reagents tend to be expensive and
sometimes difficult to manipulate, recover, and reuse.
One method to construct a recoverable and reusable
catalyst is to immobilize the active palladium species on
a solid material. Several types of solid materials have
been used to support palladium species.
One method of immobilization of Pd complexes is
covalent anchoring of the complex onto a solid carrier.
Researchers have found that a Pd–phosphine loaded
MCM-41 zeolite and alumina catalyze the cross cou-
9
pling of 4-iodoanisole withpehnylboronic acid.
Tzschucke et al. used a silica surface to immobilize a
perfluoro-tagged Pd complex for Suzuki reactions.10
However, the catalyst showed poor activity for electron-
richbromoarenes. An oxime-carbapalladacycle complex
covalently anchored onto silica was recently reported to
be highly active for the Suzuki reaction of 4-chloroace-
tophenone and phenylboronic acid in water and to be
reusable without decreased activity.11 A silica supported
A few groups have used polymer-supported palladium
compounds.2 However, in some cases recovery, reuse or
activity of the catalyst have not been satisfactory for
Keywords: Suzuki reaction; Coupling; Palladium; Zeolite; Hetero-
geneous catalysts; Aryl halides.
palladacyle complex12 and
a Pd–dihydroimidazole
complex13 were shown to be active and reusable for
Suzuki coupling reactions.
* Corresponding author. Tel.: +90-232-750-7529; fax: +90-232-750-
7509; e-mail: leventartok@iyte.edu.tr
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.126

3882
L. Artok, H. Bulut / Tetrahedron Letters 45 (2004) 3881–3884
In initial studies, we tested the Pd(II) exchanged NaY
zeolite in Suzuki reactions of activated and unactivated
bromobenzenes, and an activated chlorobenzene.14 We
found that the catalyst displayed high activity for
bromobenzenes in an N,N-dimethylformamide (DMF)/
water (1:1) mixture, almost quantitative coupling yields
being obtained at room temperature (rt), and was
moderately active for 4-chlorobenzotrifluoride at rela-
tively higher temperatures. In a study by another group,
PdCl2 adsorbed zeolites were tested in Suzuki reac-
tions.15 Substantial palladium leaching was observed
when a polar solvent system (alcohol/water mixture) was
used, however, the use of toluene as a solvent eliminated
the Pd leaching, but the reaction rate was remarkably
slow even at higher reaction temperatures.
(entries 3–5). It is noteworthy that the reactions pro-
ceeded under very mild conditions.
Various bases were examined for their effect on reaction
efficiency. It is apparent that the efficiency does not
follow basicity and that carbonate bases worked best. It
seems that carbonate bases are more effective in acti-
vating the palladium catalyst (Table 1). The catalyst
showed either no or very poor activity when no car-
bonate bases were used (entries 13–19). It was reported
previously that sodium acetate and trialkylamine bases
activate the coupling reactions over Pd-loaded zeolites
when reactions were performed at higher temperatures
(100–140 °C),18–20 yet no detectable coupling products
were observed in the presence of these bases in our
study. This apparent difference may result mainly from
the different mechanistic details of the reactions. When
using a base/substrate molar ratio of 2, yields of 95%
and 100% were obtained for Na2CO3 and Cs2CO3,
respectively. A lower coupling product yield (88%) was
obtained witha Na 2CO3/substrate ratio of 1. Increasing
the ratio to 3 afforded the coupled product quantita-
tively. Nevertheless, for economy, Na2CO3 was the best
choice of base and a base/substrate ratio of 2 was used in
all experiments.
In this study we first showed that the Pd(0)–NaY zeolite,
which is prepared by reduction of Pd(II) exchanged
NaY,16 is also highly active in Suzuki reactions of aryl
bromides witharylboronic acids as had previously been
known for the cross coupling of alkenyl halides with
arylboronic acids,17 Heck,18 a-arylation of malonate,19
and amination20 reactions, and our results are reported
herein. 4-Bromoanisole was used as a probe to investi-
gate the scope of the Suzuki reaction using the cata-
lyst.21
A proposed mechanism for the Suzuki reaction suggests
that the base is involved in the coordination sphere of
the palladium and the formation of Ar–PdL2–B from
reversible oxidative addition, for example, Ar–PdL2–X,
is known to accelerate the subsequent transmetallation
step.1 It seems that carbonate accomplishes activation of
the palladium better than other bases.
The presence of water appears to be essential in order to
perform the reactions under mild conditions (Table 1).
The conversion of 4-bromoanisole was negligible when
DMF was the only solvent, even at 80 °C (entry 1). In
neat water, no coupling took place at rt. The optimum
ratio of the solvent mixture was determined to be 1:1 in
the presence of Na2CO3 as the base at rt and for 1 h
The fact that no homo-coupling products were detected
is an important advantage. The reactions were routinely
performed under an Ar atmosphere, however, it was an
adventitious finding that the process was tolerant to the
atmosphere (entry 8).
Table 1. The effect of base and DMF/water ratio on the Pd(0)–NaY
a
catalyzed Suzuki reaction of 4-bromoanisole withphenylboronic acid
Entry
Base (mol equiv)
DMF/H2O
Yield(%)b
The type of organic co-solvent was evaluated for those
water miscible agents within the solvent mixture, using
an organic solvent/water ratio of 1:1 (Table 2). Polar
aprotic amides and their cyclic counterpart a lactam,
N-methylpyrrolidone (NMP), were most efficacious for
1c
2
Na2CO3 (2)
Na2CO3 (2)
Na2CO3 (2)
Na2CO3 (2)
Na2CO3 (2)
Na2CO3 (1)
Na2CO3 (3)
Na2CO3 (2)
Li2CO3 (2)
K2CO3 (2)
Rb2CO3 (2)
Cs2CO3 (2)
NaF (2)
1/0
0/1
1/1
2/1
1/2
1/1
1/1
1/1
1/1
1/1
1/1
1/1
1/1
1/1
1/1
1/1
1/1
1/1
2
0
3
95
23
64
88
100
98
60
87
74
100
33
26
0
4
5
6
7
8d
9
Table 2. The effect of organic solvent in the organic solvent/water
mixture (1:1) on the Pd(0)–NaY catalyzed Suzuki reaction of
10
11
12
13
14
15
16
17
19
a
4-bromoanisole withphenylboronic acid
Entry
Solvent
Yield(%)b
NaHCO3 (2)
NaOAc (2)
K3PO4 (2)
N(C2H5)3 (2)
NaOH (2)
20
21
22
23
24
25
26
27
28
DMA
NMP
96
76
0
3
THF
DMSO
0
0
7
Acetonitrile
Dioxane
Ethanol
Isopropyl alcohol
Acetone
0
13
7
a Reaction conditions: 1.0 mmol of 4-bromoanisole, 1.2 mmol of
phenylboronic acid, 0.025 mmol Pd, 10 mL of DMF/H2O mixture, 1 h
at room temperature under Ar.
14
30
b GC yield based on 4-bromoanisole.
c At 80 °C.
a Reaction conditions are the same as those of entry 3 in Table 1.
b GC yield based on 4-bromoanisole.
d Open to the atmosphere.

L. Artok, H. Bulut / Tetrahedron Letters 45 (2004) 3881–3884
3883
Table 3. Pd(0)–NaY catalyzed Suzuki cross-coupling reaction of aryl
halides and arylboronic acidsa
It is a matter of debate whether the reactions are
homogeneously or heterogeneously catalyzed in the
presence of supported catalysts. Some conclusions can
be drawn from the palladium level passed into the sol-
vent during the course of reaction, because dissolved Pd
may be the main active species that catalyzes the reac-
tion.5;18a;22 After the catalyst was filtered off through a
membrane filter with0.2 lm porosity and washed with
DCM and water, at the end of the reactions we observed
a Pd concentration of only <0.4 ppm (<0.3% loss based
on the initial Pd quantity) in the filtrates, this being
about one fifth of the amount that leached from Pd(II)
loaded zeolite.14 This observation coincides with previ-
ous findings that higher Pd leaching was observed from
Pd(II) loaded zeolites than from Pd(0)–zeolites in Heck
reactions.18a After 5 min, for a reaction performed under
the conditions of entry 3, (at which stage the coupling
product formation was found to be 44%) the product
mixture was filtered and an AAS analysis of the filtrate
revealed no detectable amount of Pd. Moreover, the
reaction ceased when the solid catalyst was removed at
this stage. These results may indicate that the reaction is
truly heterogeneous.
Entry
Aryl halide
Arylboronic acid
Yield(%)b
29
30
31
32
33
34
35
36
3-MeOC6H4Br
2-MeOC6H4Br
C6H5Br
C6H5B(OH)2
C6H5B(OH)2
97
85
4-MeC6H4B(OH)2
4-MeOC6H4B(OH)2
C6H5B(OH)2
98
92
C6H5Br
4-CNC6H4Br
4-NO2C6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Cl
100
51
C6H5B(OH)2
C6H5B(OH)2
C6H5B(OH)2
71
26c
a Reaction conditions are the same as those of entry 3 in Table 1.
b GC yield based on aryl halide.
c At 100 °C, 25% acetophenone was also formed.
the reaction, implying that amides probably acted as
ligands to beneficially activate the palladium species.
DMA was comparable to DMF in reaction efficiency
(entry 20). The use of NMP with water resulted in a
lower coupled product yield (76%). This may be asso-
ciated withthe less polar nature of NMP. Product for-
mation was nil in tetrahydrofuran (THF),
dimethylsulfoxide (DMSO), and acetonitrile, and very
low in dioxane, isopropyl alcohol, ethanol and acetone
(entries 25–28).
We also performed probe reactions to verify whether the
coupling process took place within the zeolite cages or
not. As a probe reaction, the Suzuki reaction was car-
ried out with 1-bromonaphthalene and phenylboronic
acid. The product, 1-phenylnaphthalene, would not be
detectable in the reaction solvent unless the zeolite
matrix collapses, because the large size of 1-phenyl-
naphthalene would not allow it to pass through the
The effect of varying the aryl halide and arylboronic
acids was also tested (Table 3). 3-Bromoanisole under-
went excellent coupling (97% yield). Sterically hindered
2-bromoanisole was well tolerated by the catalytic sys-
tem and provided the corresponding coupled product
in high yield (85%) under the established condi-
tions. Nonactivated bromobenzene also revealed excel-
lent reactivity towards the coupling reactions with
4-methyl- and 4-methoxyphenylboronic acids (entries 31,
32). Coupling product formation was quantitative with
4-bromobenzonitrile. Though it is an activated aryl
bromide, 4-bromonitrobenzene afforded only a moder-
ate yield of the corresponding coupled product (51%).
ꢀ
zeolite apertures (ꢀ7 A). Nevertheless, we found that 1-
phenylnaphthalene formation was 95% after one hour of
reaction at rt and the Pd concentration was 0.19 ppm in
the solvent at the end of the reaction. This result verifies
that this coupling reaction did not occur within the
zeolite.
In another experiment we performed the Suzuki reaction
of 4-bromoanisole with phenylboronic acid in the pres-
ence of PPh3. Phosphines are commonly used as ligand
additives in activating homogeneous Pd-catalyzed
coupling reactions. If the coupling reactions were intra-
zeolite reactions, the presence of PPh3 would not influ-
ence the course of the reaction at all, either in a positive
or a negative manner, because PPh3 in its most stable
conformation has cross sections larger than the aper-
tures of faujasite-type zeolites.23 Nevertheless it was
striking that the addition of PPh3 in twofold molar
equivalent with respect to Pd brought the coupling
reaction to a halt. The presence of phosphine should
have destroyed the activity of any exposed Pd species,
but not those in the interior of the zeolite. Thus, these
results presented us with precise evidence that the cou-
pling reactions did not take place within the zeolite.
4-Chloroacetophenone was used as an electron-deficient
probe for chloroarenes for the Suzuki coupling reaction.
The conversion was complete, however, the yield was
only 26% and was accompanied by the dechlorination
product, acetophenone, in 25% yield at a reaction tem-
perature of 100 °C. We also attempted a reaction with
the activated chloroarene under the conditions of entry
36, but in the absence of boronic acid. The yield of 88%
for the dechlorinated product verifies the oxidative
activity of the catalyst for activated chloroarenes.
The catalyst was recovered by filtration and washed with
bothDCM and water, and subsequently reused under
the conditions of entry 3. It was determined that the
catalyst activity was reduced to 31% at rt, but the cou-
pling product formation was quantitative at 50 °C dur-
ing second use. However, regeneration of the catalyst by
consecutive treatments withO 2 and H2 was necessary to
obtain high yields after the second use. The product
yields were 93% and 94% after the third and fourth uses,
respectively, at 50 °C and 1 hand reduced to 69% and
54% after the fifth and sixth uses, respectively.
In summary, we have found that aryl bromides, in
general, can be coupled witharylboronic acids in
excellent yields using a Pd(0)-loaded NaY zeolite under
mild conditions. However, the reactions occurred on the
external surface of the catalyst. The catalyst can be
reused subsequent to regeneration.

3884
L. Artok, H. Bulut / Tetrahedron Letters 45 (2004) 3881–3884
15. Corma, A.; Garcia, H.; Leyva, A. Appl. Catal., A 2002,
236, 179–185.
Acknowledgements
16. Catalyst preparation: The preparation of Pd(II)–NaY
zeolite has been described elsewhere.14 Pd(0)–NaY was
obtained by reduction under a flow of hydrogen (70 mL/
min) and at a temperature of 200 °C for 30 min. The AAS
analysis gave a Pd content of 1.0 Æ 0.1 wt %. When the
catalyst reduction was carried out at higher temperature
(350 °C) as was applied in the preparation of the catalyst
for the Heck reactions in previous studies (Refs. 18b–
d,19,20) the Suzuki coupling yield was much lower. It was
reported that higher reduction temperatures, typically
>300 °C, reduces the Pd dispersion on NaY zeolite (see
articles: Primet, M.; Taarit, Y. B. J. Catal. 1977, 81, 1317–
1324; Sachtler, W. M. H.; Cavalcanti, F. A. P.; Zhang, Z.
Catal. Lett. 1991, 9, 261–272).
This work was financially supported by the Research
Funding Office of IZTECH. The authors would like to
ꢁ
thank Dr. A. Eroglu, Mr. S. Yılmaz and Ms. A. Erdem
for AAS analysis.
References and notes
1. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–
2483; (b) Suzuki, A. J. Organomet. Chem. 1999, 57, 147–
168; (c) Kotha, S.; Lahiri, K.; Kashninath, D. Tetrahedron
Lett. 2002, 9633–9695.
17. Sun, Y.; LeBlond, Y.; Sowa, J. R. Jr. U.S. Patent
6,603,013, August 2003.
18. (a) Dams, M.; Drijkoningen, L.; Pauwels, B.; Tandeloo,
G. V.; Vos, D. E. D.; Jacobs, P. A. J. Catal. 2002, 209,
2. (a) Uozumi, Y.; Danjo, H.; Terasawa, M.; Imanaka, T.;
Teranishi, S. J. Org. Chem. 1999, 64, 3384–3388; (b) Jang,
S.-B. Tetrahedron Lett. 1997, 38, 1793–1796; (c) Fenger, I.;
Drian, C. L. Tetrahedron Lett. 1998, 39, 4287–4290; (d)
Zhang, T. Y.; Allen, M. J. Tetrahedron Lett. 1999, 40,
5813–5816; (e) Bergbreiter, D. E.; Osburn, P. L.; Liu, Y. S.
J. Am. Chem. Soc. 2000, 122, 9058–9064; (f) Akiyama, R.;
Kobayashi, S. Angew. Chem., Int. Ed. 2001, 40,
3469–3471.
3. Marck, G.; Villiger, A.; Buchecker, R. Tetrahedron Lett.
1994, 35, 3277–3280.
4. Sakurai, H.; Tsukuda, T.; Hirao, T. J. Org. Chem. 2002,
67, 2721–2722.
€
225–236; (b) Djakovitch, L.; Heise, H.; Kohler, K. J.
Organomet. Chem. 1999, 584, 16–26; (c) Djakovitch, L.;
€
Kohler, K. J. Mol. Catal. A: Chem. 1999, 142, 275–284;
(d) Djakovitch, L.; Kohler, K. J. Am. Chem. Soc. 2001,
€
123, 5990–5999.
19. Djakovitch, L. M.; Kohler, K. J. Organomet. Chem. 2000,
€
606, 101–107.
20. Djakovitch, L.; Wagner, M.; Kohler, K. J. Organomet.
Chem. 1999, 592, 225–234.
€
21. Typical reaction procedure: In a 50 mL flask equipped with
a magnetic stirring bar were charged aryl halide (1 mmol),
Na2CO3 (2 mmol), arylboronic acid (1.2 mmol) and Pd(0)–
NaY (0.025 mmol Pd) in succession. The flask was
attached to an argon line and the reaction was initiated
by the addition of 10 mL DMF/water mixture (1:1). The
mixture was vigorously stirred for 1 hat room tempera-
ture. The catalyst was filtered off and washed with
dichloromethane and 0.6 mmol of hexadecane was added
to the solution as an internal standard. The organic phase
was separated from the aqueous phase and dried over
Na2SO4. Products were analyzed by GC and GC/MS and
isolated by column chromatography on silica gel using
hexane and hexane/ethyl acetate mixture (9:1 v/v) as
eluents, successively.
€
5. Heidenreich, R. G.; Kohler, K.; Krauter, J. G. E.; Pietsch,
J. Synlett 2002, 1118–1122.
6. LeBlond, C. R.; Andrews, A. T.; Sun, Y.; Sowa, R. S., Jr.
Org. Lett. 2001, 13, 1555–1557.
7. Arcadi, A. A.; Cerichelli, G.; Chiarini, M.; Correa, M.;
Zorzan, D. Eur. J. Org. Chem. 2003, 4080–4086.
8. Kabalka, G. W.; Pagni, R. M.; Wang, L.; Namboodiri, V.;
Hair, C. M. Green Chem. 2000, 2, 120–122.
€
9. (a) Kosslick, H.; Monnich, I.; Paetzold, E.; Fuhrmann, H.;
Fricke, R.; Muller, D. Microporous Mesoporous Mater.
€
2001, 44–45, 537–545; (b) Paetzold, E.; Oehme, G.;
Fuhrmann, H.; Richter, M.; Eckelt, R.; Pohl, M.-M.;
Kosslick, H. Microporous Mesoporous Mater. 2001, 44–45,
517–522.
10. Tzschucke, C. C.; Markert, C.; Glatz, H.; Bannwarth, W.
Angew. Chem., Int. Ed. 2002, 41, 4500–4503.
11. Baleizao, C.; Corma, A.; Garcia, H.; Leyva, A. Chem.
Commun. 2003, 606–607.
22. (a) Zhao, F.; Shirai, M.; Ikushima, Y.; Arai, M. J. Mol.
€
Catal. A: Chem. 2002, 180, 211–219; (b) Kohler, K.;
Heidenreich, R. G.; Krauter, J. G. E. Chem. Eur. J. 2002,
8, 622–631; (c) Heidenreich, R. G.; Krauter, J. G. E.;
ꢂ
12. Paul, S.; Clark, J. H. Green Chem. 2003, 5, 635–638.
€
_
€
Pietsch, J.; Kohler, K. J. Mol. Catal. A: Chem. 2002, 182–
183, 499–509.
13. Gurbuz, N.; Ozdemir, I.; Cßetinkaya, B.; Seßckin, T. Appl.
Organomet. Chem. 2003, 17, 776–780.
14. Bulut, H.; Artok, L.; Yilmaz, S. Tetrahedron Lett. 2003,
44, 289–291.
23. Hanson, B. E. H.; Davis, M. E.; Taylor, D.; Rode, E.
Inorg. Chem. 1984, 23, 52–56.