An efficient and reusable palladium catalyst supported on a rasta resin for Suzuki-Miyaura cross-couplings

Article abstract of DOI:10.1002/ejoc.201101075

A short and efficient synthesis of a heterogeneous palladium catalyst supported on a rasta resin bearing diphenylphosphanyl ligands is reported. This catalyst was used successfully for Suzuki-Miyaura reactions of aryl bromides in the presence of only 0.25 milli-equiv. of supported palladium. The catalyst was reused several times with no loss of efficiency, and the amount of palladium leached in the reaction medium is extremely low (< 1 % of the initial amount). An efficient heterogeneous palladium catalyst supported on a rasta resin bearing diphenylphosphanyl groups is reported. The catalyst was successfully used for Suzuki-Miyaura reactions of aryl bromides in the presence of only 0.25 milli-equiv. of supported palladium, it can be used at least five times, and the palladium leaching is very low (< 1 % of the initial amount). Copyright

Full text of DOI:10.1002/ejoc.201101075

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201101075
An Efficient and Reusable Palladium Catalyst Supported on a Rasta Resin for
Suzuki–Miyaura Cross-Couplings
Carine Diebold,[a] Jean-Michel Becht,*[a] Jinni Lu,[b] Patrick H. Toy,[b] and
Claude Le Drian*[a]
Keywords: C-C coupling / Palladium / Heterogeneous catalysis / Polymers / Green chemistry
A short and efficient synthesis of a heterogeneous palladium
catalyst supported on a rasta resin bearing diphenylphos-
phanyl ligands is reported. This catalyst was used success-
fully for Suzuki–Miyaura reactions of aryl bromides in the
presence of only 0.25 milli-equiv. of supported palladium.
The catalyst was reused several times with no loss of effi-
ciency, and the amount of palladium leached in the reaction
medium is extremely low (Ͻ 1% of the initial amount).
Recently, rasta resins have emerged as another class of
polymers possessing an original macromolecular architec-
ture composed of functionalized, flexible, straight, long
polymeric chains attached to a JandaJel core (cross-linked
polystyrene).[19] The use of rasta resins in organic synthesis
has only been very sparsely studied. For example, we have
described their use in chromatography-free Wittig reac-
tions,[20] carbonyl cyanosilylation reactions[21] and, most re-
cently, the addition of carbon dioxide to epoxides.[22] To the
best of our knowledge the use of these resins as support for
transition metal catalysts has not yet been studied. We pres-
ent here a reusable palladium catalyst supported on a rasta
resin for Suzuki–Miyaura cross-couplings.
Introduction
The formation of an aryl–aryl bond often represents a
crucial step in the preparation of elaborated molecules that
find important applications in the fields of pharmaceutical
chemistry,[1] molecular recognition,[2] organic materials for
OLEDs[3] or metal ligands for catalysis.[4] The Suzuki–
Miyaura cross-coupling between an aryl halide and an aryl-
boronic acid is one of the most powerful route to biaryls.[5]
It tolerates the presence of numerous functional groups and
can be carried out on an industrial scale.[6] This coupling is
generally performed under mild and non-anhydrous reac-
tion conditions in the presence of a homogeneous (soluble)
palladium catalyst.[7,8] However, some drawbacks are the
impossibility to recover the expensive catalyst for direct re-
use and the difficulties to avoid the presence of residual
amounts of precious metal in the reaction products.[9]
Therefore, considerable attention is focused on the develop-
ment of heterogeneous reusable palladium catalysts, which
should be at least as efficient as their soluble analogues. For
this purpose, the transition metal is generally grafted on
inorganic,[10,11] or organic[12] supports and especially on
polymers.[13–15] The Merrifield copolymer of styrene and 2-
and 4-(chloromethyl)styrene cross-linked with 1,4-divin-
ylbenzene, is widely used in particular as a support for
transition metal catalysts.[12d,16] For example, we have re-
cently developed various highly reactive polystyrene-sup-
ported palladium catalysts for C–C bond forming reactions
such as Suzuki–Miyaura reactions from aryl bromides or
even chlorides.[17,18]
Results and Discussion
The preparation of the palladium catalyst was performed
in two steps: nucleophilic substitution of the chlorine atoms
of the starting rasta resin 1[23] with (diphenylphosphanyl)-
lithium followed by the introduction of the precious metal
by exchange with a soluble palladium complex (Scheme 1,
see also Supporting Information).
[a] Université de Haute Alsace, Institut de Science des Matériaux
de Mulhouse, LRC-CNRS 7228
Scheme 1. Preparation of the palladium catalyst.
15 rue Jean Starcky, 68057 Mulhouse cedex, France
Fax: +33-3-89608799
The reaction conditions of the Suzuki–Miyaura cross-
coupling were optimized by using 4-bromoacetophenone
and phenylboronic acid as model substrates (Table 1). The
reaction was initially carried out with Na2CO3 in a 5:1:1
E-mail: jean-michel.becht@uha.fr
[b] The University of Hong Kong, Department of Chemistry,
Pokfulam Road, Hong Kong, P. R. of China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101075.
Eur. J. Org. Chem. 2012, 893–896
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. Diebold, J.-M. Becht, J. Lu, P. H. Toy, C. Le Drian
SHORT COMMUNICATION
Table 1. Optimization of the reaction conditions.
Entry[a]
Pd catalyst
Base
Solvent
Yield [%][e]
1[b]
2[b]
3[b]
4[b]
5[c]
6[d]
7[d]
2
Na2CO3
Cs2CO3
CsF
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
toluene/EtOH/H2O (5:1:1)
90
89
41
2
toluene
toluene
toluene
toluene
toluene
toluene
2
2
90 (72)[f]
90
2
Pd EnCat TPP30
Pd EnCat NP30
80
70
[a] Reaction conditions: 4-bromoacetophenone (1.0 equiv., 0.5 mmol), phenylboronic acid (1.1 equiv.) and base (1.2 equiv.). [b] Reaction
performed in the presence of 1 milli-equiv. of supported palladium. [c] Reaction performed in the presence of 0.25 milli-equiv. of supported
palladium. Reaction time reduced to 90 min. [d] Reaction performed in the presence of 1.5 milli-equiv. of supported palladium. [e] Isolated
yields after flash chromatography of the crude reaction mixture on silica gel. [f] Yield obtained after heating at 50 °C only.
mixture of toluene/EtOH/H2O and afforded the desired bi- showed the presence of some Pd aggregates of rather small
aryl 3a in 90% yield in the presence of 1 milli-equiv. of sup- size (1–4 nm) and also that no significant structural modifi-
ported palladium (Entry 1). Excellent results were also ob- cation occurred after use (for further details see Supporting
tained in toluene containing a trace of H2O by using Information). However, as we had noticed earlier, the pres-
Cs2CO3 as base, whereas CsF gave 3a in a much lower yield ence of these aggregates is not necessary for the activity of
(Entries 2 and 3). Remarkably, by performing the cross-cou-
pling in the presence of K3PO4·H2O and 0.25 milli-equiv.
of supported palladium, 3a was obtained in 90% yield after
only 90 min of reaction time (Entry 5). The commercially
available heterogeneous palladium EnCat TPP30 and NP30
catalysts[24] afforded 3a in lower yields of 80% and 70%,
respectively, in the presence of 1.5 milli-equiv. of supported
palladium even after 12 h of reaction time (Entries 6 and
7). Replacement of 4-bromoacetophenone by 4-chloroace-
tophenone gave only traces of 3a (according to conditions
of Table 1, Entry 5), and further attempts by changing the
nature of the base (Na2CO3, Cs2CO3, CsF), of the solvent
[toluene/EtOH/H2O (5:1:1), DMF or 1,4-dioxane] or by in-
creasing the amount of supported palladium were also un-
successful.
Table 2. Recycling test of catalyst 2.
Run[a]
1
2
3
4
5
Yield [%][b]
90
91
86
85
84
[a] Reaction performed under conditions related to those of
Table 1, Entry 5. [b] Isolated yields.
Table 3. Syntheses of biaryls.
The reusability of catalyst 2 was then determined. When
Na2CO3 was used as base (conditions of Table 1, Entry 1)
the second use of 2 afforded 3a in a Ͻ 50% yield. But when
the base was K3PO4·H2O, the catalyst 2 has been used 5
times with no significant decrease in the yield (Table 2). A
hot filtration test was then performed. For this purpose,
after 2 min of reaction time (according to Table 1, Entry 5),
2 was filtered (yield at that point: 6%), another portion of
K3PO4·H2O was added and the filtrate was heated at 100 °C
for another 90 min after which a 22% yield was obtained
showing that soluble palladium entities played somehow a
role in this coupling. The amount of palladium present in
the filtrate, either after 2 min of reaction time or at the end
of the reaction, after its complete mineralization was from
0.8 to 1% of the initial amount (for further details see Sup-
porting Information). To obtain information on the struc-
ture of this catalyst formed of flexible polymeric chains,
Entry[a]
R1
R2
R3
R4
Product Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
4-Ac
4-Ac
4-Ac
4-Ac
4-NO2
H
4-Me
3-Me
2-Me
4-OMe
2-Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3-NO2
2-OMe
4-OMe
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
90
67
70
82
71
82
87
77
76
94
98
70
52
3g
3h
3i
3j
3k
3l
2-Me 4-Me 6-Me
2-iPr 4-iPr 6-iPr
H
H
3m
[a] Reactions performed in the presence of the aryl bromide
(1 equiv., 0.5 mmol), arylboronic acid (1.1 equiv.), K3PO4·H2O
(1.2 equiv.) and the palladium catalyst (0.25 milli-equiv. of sup-
ported palladium) in toluene containing 1% H2O. [b] Isolated
yields after flash chromatography of the crude reaction mixture on
TEM seems to be the method of choice. These images silica gel.
894
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Eur. J. Org. Chem. 2012, 893–896

Palladium Catalyst Supported on a Rasta Resin
[2]
a) L. Pu, Chem. Rev. 1998, 98, 2405 and references cited
therein; b) J. L. Schulte, S. Laschat, V. Vill, E. Nishikawa, H.
Finkelmann, M. Nimtz, Eur. J. Org. Chem. 1998, 2499.
L. F. Tietze, G. Kettschau, U. Heuschert, G. Nordmann, Chem.
Eur. J. 2001, 7, 368.
the catalyst since some batches of catalyst were almost de-
void of these aggregates. The nature of the support pre-
cluded the use of other, more powerful, methods of struc-
tural elucidation such as those that we had used on graphite
surfaces.[25]
[3]
[4]
[5]
A. C. Spivey, T. Fekner, S. E. Spey, Eur. J. Org. Chem. 2000,
65, 3154.
Various biaryls were then prepared under the best reac-
tion conditions (Table 3). The couplings of 4-bromoace-
tophenone with arylboronic acids bearing an electron-do-
nating or an electron-withdrawing group proceeded in good
yields (Entries 1–4). Similar results were obtained in the re-
action of phenylboronic acid with electron-rich or electron-
deficient aryl bromides (Entries 5–13). Remarkably, the
coupling of phenylboronic acid with the sterically hindered
2-bromobiphenyl, 1-bromo-2,4,6-trimethylbenzene or 1-
bromo-2,4,6-triisopropylbenzene afforded the correspond-
ing biaryls (Entries 11–13). However, the reaction of 4-bro-
moacetophenone with (2,6-dimethoxyphenyl)boronic acid
or the reaction of 1-bromo-2,4,6-trimethylbenzene with (2-
methoxyphenyl)boronic acid gave the corresponding biaryl
in Ͻ 20% yields.
a) F. Diederich, P. J. Stang in Metal-Catalyzed Cross-Coupling
Reactions, Wiley-VCH, Weinheim, 1998; b) J. Tsuji in Palla-
dium Reagents and Catalysts: New Perspectives for the 21st Cen-
tury, John Wiley and Sons Ltd, New York, 2004.
J.-P. Corbet, G. Mignani, Chem. Rev. 2006, 106, 2651.
a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457; b) J.
Hassan, M. Sévignon, C. Gozzi, E. Schulz, M. Lemaire, Chem.
Rev. 2002, 102, 1359.
Other powerful transition metal catalyzed synthetic methods
for the preparation of biaryls are available: a) for Cu-catalyzed
cross-coupling reactions, see: P. E. Fanta, Synthesis 1974, 9; b)
for Ni-catalyzed cross-coupling reactions, see: C.-C. Lee, W.-C.
Ke, K. T. Chan, C.-L. Lai, C.-H. Hu, H. M. Lee, Chem. Eur. J.
2007, 13, 582 and references cited therein; c) for C–H activation
reactions, see: D. Alberico, M. E. Scott, M. Lautens, Chem.
Rev. 2007, 107, 174; d) for decarboxylative Pd-catalyzed reac-
tions, see: J.-M. Becht, C. Catala, C. Le Drian, A. Wagner, Org.
Lett. 2007, 9, 1781; e) J.-M. Becht, C. Le Drian, Org. Lett.
2008, 10, 3161.
[6]
[7]
[8]
[9]
a) C. E. Garrett, K. Prasad, Adv. Synth. Catal. 2004, 346, 889;
b) C. J. Welch, J. Albaneze-Walker, W. R. Leonard, M. Biba, J.
DaSilva, D. Henderson, B. Laing, D. J. Mathre, S. Spencer, X.
Bu, T. Wang, Org. Process Res. Dev. 2005, 9, 198.
Conclusions
An efficient palladium catalyst supported on a rasta resin
and its versatile application for the preparation of biaryls
has been described. The catalyst 2 is more efficient than the
commercially available palladium EnCat TPP30 and NP30.
It was reused successfully up to five times, and the palla-
dium leaching was very low satisfying therefore the preser-
vation of scarce and expensive precious metals.
[10]
a) D. E. De Vos, M. Dams, B. F. Sels, P. A. Jacobs, Chem. Rev.
2002, 102, 3615; b) B. M. Choudary, S. Madhi, N. S. Chowdari,
M. L. Kantam, B. Sreedhar, J. Am. Chem. Soc. 2002, 124,
14127; c) K. Mori, T. Yamaguchi, T. Hara, T. Mizukagi, K.
Ebitani, K. Kaneda, J. Am. Chem. Soc. 2002, 124, 11572; d)
H. Bulut, L. Artok, S. Yilmaz, Tetrahedron Lett. 2003, 44, 289;
e) K. I. Shimizu, T. Kan-no, T. Kodama, H. Hagiwara, Y. Ki-
tayama, Tetrahedron Lett. 2002, 43, 5653; f) C. Baleizao, A.
Corma, H. Garcia, A. Leyva, Chem. Commun. 2003, 606; g)
R. Sayah, K. Glegola, E. Framery, V. Dufaud, Adv. Synth. Ca-
tal. 2007, 349, 373; h) M. Trilla, R. Pleixats, M.
Wong Chi Man, C. Bied, J. J. E. Moreau, Adv. Synth. Catal.
2008, 350, 577.
Magnetically recoverable reusable palladium catalysts sup-
ported on inorganic nanoparticles have been developed re-
cently: V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M.
Bouhrara, J.-M. Basset, Chem. Rev. 2011, 111, 3036 and refer-
ences cited therein.
a) N. E. Leadbeater, M. Marco, Chem. Rev. 2002, 102, 3217;
b) C. McNamara, M. J. Dixon, M. Bradley, Chem. Rev. 2002,
102, 3275; c) T. J. Dickerson, N. N. Reed, K. D. Janda, Chem.
Rev. 2002, 102, 3325; d) D. E. Bergbreiter, Chem. Rev. 2002,
102, 3345; e) J. Lu, P. H. Toy, Chem. Rev. 2009, 109, 815; f)
M. Lamblin, L. Nassar-Hardy, J.-C. Hierso, E. Fouquet, F.-X.
Felpin, Adv. Synth. Catal. 2010, 352, 33.
The palladium catalyst can be bound to polymer-supported
carbenes: a) J.-H. Kim, J.-W. Kim, M. Shokouhimehr, Y.-S.
Lee, J. Org. Chem. 2005, 70, 6714; b) J.-W. Byun, Y.-S. Lee,
Tetrahedron Lett. 2004, 45, 1837; c) M. Shokouhimehr, J.-H.
Kim, Y.-S. Lee, Synlett 2006, 4, 618; d) W. J. Sommer, M.
Weck, Adv. Synth. Catal. 2006, 348, 2101.
The palladium catalyst can be bound to polymer-supported
phosphanes: a) C.-M. Andersson, K. Karabelas, A. Hallberg,
J. Org. Chem. 1985, 50, 3891; b) N. Riegel, C. Darcel, O.
Stéphan, S. Jugé, J. Organomet. Chem. 1998, 567, 219; c) Y.
Uozomi, H. Danjo, T. Hayashi, J. Org. Chem. 1999, 64, 3384;
d) A. Dahan, M. Portnoy, Org. Lett. 2003, 5, 1197; e) Y. Uo-
zomi, T. Kimura, Synlett 2002, 2045; f) Y. M. Yamada, K.
Takeda, H. Takahashi, S. Ikegami, J. Org. Chem. 2003, 68,
7733; g) T. Kang, Q. Feng, M. Luo, Synlett 2005, 15, 2305; h)
Experimental Section
Catalyst 2 (4.4 mg, 0.25 milli-equiv. of supported Pd) was added to
a solution of aryl bromide (0.50 mmol, 1.0 equiv.), arylboronic acid
(0.55 mmol, 1.1 equiv.), K3PO4·H2O (138 mg, 0.60 mmol,
1.2 equiv.) in a mixture of toluene (2 mL) and H2O (20 μL). The
reaction mixture was heated at 100 °C for 90 min. After cooling to
room temp., 2 was filtered under vacuum on a 0.2 μm membrane.
The catalyst was washed with AcOEt (3ϫ10 mL). The combined
organic phases were washed with H2O (20 mL), dried with MgSO4,
filtered and concentrated under vacuum. The residue was purified
by flash chromatography on silica gel to afford pure biaryls after
drying under vacuum.
[11]
[12]
Supporting Information (see footnote on the first page of this arti-
1
cle): H NMR spectroscopic data of compounds 3a–m and copies
1
of the H NMR spectra.
[13]
[14]
Acknowledgments
We are grateful to the Centre National de la Recherche Scientifique
(CNRS) and the Research Grants Council of the Hong Kong S. A.
R., P. R. of China (Project No. 704108P) for financial support, to
Dr. Didier Le Nouën (EA 4566) for H NMR spectra, to Dr. Loïc
Vidal (LRC-CNRS 7228) for TEM images and to Amélie Kowal-
czyk for helpful technical assistance.
1
[1] P. Lloyd-Williams, E. Giralt, Chem. Soc. Rev. 2001, 30, 145 and
references cited therein.
Eur. J. Org. Chem. 2012, 893–896
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. Diebold, J.-M. Becht, J. Lu, P. H. Toy, C. Le Drian
SHORT COMMUNICATION
M. Guinó, K. K. Hii, Chem. Soc. Rev. 2007, 36, 608; i) M.
Lombardo, M. Chiarucci, C. Trombini, Green Chem. 2009, 11,
574.
nan, S. Ault-Justus, J. Comb. Chem. 2000, 2, 80; d) J. M. Pawlu-
czyk, R. T. McClain, C. Denicola, J. J. Mulhearn Jr., D. J.
Rudd, C. W. Lindsley, Tetrahedron Lett. 2007, 48, 1497; e)
C. W. Lindsley, J. C. Hodges, G. F. Filzen, B. M. Watson, A. G.
Geyer, J. Comb. Chem. 2000, 2, 550; f) D. Fournier, S. Pascual,
V. Montembault, L. Fontaine, J. Polym. Sci., Part A 2006, 44,
5316; g) D. Fournier, S. Pascual, V. Montembault, D. M.
Haddleton, L. Fontaine, J. Comb. Chem. 2006, 8, 522.
a) P. S.-W. Leung, Y. Teng, P. H. Toy, Synlett 2010, 1997; b)
P. S.-W. Leung, Y. Teng, P. H. Toy, Org. Lett. 2010, 12, 4996.
Y. Teng, P. H. Toy, Synlett 2011, 551.
[15] For recent developments in green nanocatalysis, see: a) V. Pol-
shettiwar, R. S. Varma, Green Chem. 2010, 12, 743; b) M. Cao,
J. Lin, H. Yang, R. Cao, Chem. Commun. 2010, 46, 5088; c) N.
Mejias, R. Pleixats, A. Shafir, M. Medio-Simon, G. Asensio,
Eur. J. Org. Chem. 2010, 5090; d) G. Liu, M. Hou, J. Song, T.
Jiang, H. Fan, Z. Zhang, B. Han, Green Chem. 2010, 12, 65.
[16] a) J. C. Hershberger, L. Zhang, G. Lu, H. C. Malinakova, J.
Org. Chem. 2006, 71, 231; b) C. A. Parrish, S. L. Buchwald, J.
Org. Chem. 2001, 66, 3820; c) L. Bai, J.-X. Wang, Adv. Synth.
Catal. 2008, 350, 315.
[17] a) I. Fenger, C. Le Drian, Tetrahedron Lett. 1998, 39, 4287; b)
S. Schweizer, J.-M. Becht, C. Le Drian, Adv. Synth. Catal.
2007, 349, 1150; c) S. Schweizer, J.-M. Becht, C. Le Drian, Org.
Lett. 2007, 9, 3777; d) S. Schweizer, J.-M. Becht, C. Le Drian,
Tetrahedron 2010, 66, 765.
[18] Our group has recently reported Mizoroki–Heck reactions
using palladium catalysts supported on polystyrene resins: C.
Diebold, S. Schweizer, J.-M. Becht, C. Le Drian, Org. Biomol.
Chem. 2010, 8, 4834.
[19] a) S. R. McAlpine, C. W. Lindsley, J. C. Hodges, D. M. Leo-
nard, G. F. Filzen, J. Comb. Chem. 2001, 3, 1; b) D. D. Wisno-
ski, W. H. Leister, K. A. Strauss, Z. Zhao, C. W. Lindsley, Tet-
rahedron Lett. 2003, 44, 4321; c) J. C. Hodges, L. S. Harikrish-
[20]
[21]
[22]
J. Lu, P. H. Toy, Synlett 2011, 659.
[23] The starting rasta resin 1 was prepared according to the general
procedure described in ref.[20b] by using 4-vinylbenzyl chloride
as the functionalized monomer.
[24] a) C. Ramarao, S. V. Ley, S. C. Smith, I. M. Shirley, N. DeAl-
meida, Chem. Commun. 2002, 1132; b) S. V. Ley, C. Ramarao,
R. S. Gordon, A. B. Holmes, A. J. Morrison, I. F. McConvey,
I. M. Shirley, S. C. Smith, M. D. Smith, Chem. Commun. 2002,
1134.
[25] Z. Yuan, R. Stephan, M.-C. Hanf, J.-M. Becht, C. Le Drian,
M. Hugentobler, W. Harbich, P. Wetzel, Eur. Phys. J. D 2011,
63, 401.
Received: July 22, 2011
Published Online: January 4, 2012
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Eur. J. Org. Chem. 2012, 893–896