New palladium carbene catalysts for the Heck reaction of aryl chlorides in ionic liquids.

Article abstract of DOI:10.1021/ol020103h

[reaction: see text] The Heck reaction of aryl chlorides was investigated in the presence of defined monocarbenepalladium(0) complexes. Activated and nonactivated aryl chlorides provide the corresponding cinnamic esters and stilbenes in (n)Bu(4)NBr as a ionic liquid in good to excellent yields.

Full text of DOI:10.1021/ol020103h

ORGANIC
LETTERS
2002
Vol. 4, No. 18
3031-3033
New Palladium Carbene Catalysts for
the Heck Reaction of Aryl Chlorides in
Ionic Liquids
Kumaravel Selvakumar, Alexander Zapf, and Matthias Beller*
Institut fu¨r Organische Katalyseforschung an der UniVersita¨t Rostock e. V. (IfOK),
Buchbinderstrasse 5-6, D-18055 Rostock, Germany
matthias.beller@ifok.uni-rostock.de
Received May 21, 2002
ABSTRACT
The Heck reaction of aryl chlorides was investigated in the presence of defined monocarbenepalladium(0) complexes. Activated and nonactivated
aryl chlorides provide the corresponding cinnamic esters and stilbenes in nBu4NBr as a ionic liquid in good to excellent yields.
Palladium-catalyzed coupling reactions of aryl chlorides are
of general interest for the synthesis of organic building blocks
and pharmaceutical and agrochemical derivatives. In addition
to small-scale applications (from <1 to 100 g), there is an
increasing awareness of this type of reaction for industrial
fine chemical synthesis (from 1 to >100 t/a).1 Regarding
the availability and the economic viability, aryl chlorides are
the most attractive starting materials among the different aryl
halides. To develop palladium-catalyzed coupling reactions
of aryl chlorides to a practical level, we started, some time
ago, a research program on this topic. The palladacycles
introduced by Herrmann and co-workers and us are stable
and robust palladium catalysts for Heck and Suzuki coupling
reactions of activated aryl chlorides with high turnover
numbers.2 However, the catalyst activity is not sufficient to
allow an efficient activation of neutral and electron-rich aryl
chlorides. Hence, we and other research groups3 developed
more active palladium catalysts based on sterically hindered
basic phosphine ligands for aryl chloride activation. In this
respect, we were the first to introduce diadamantylalkylphos-
phines as ligands for various coupling reactions with aryl
chlorides.4 In addition, we also demonstrated that basic
chelating phosphines based on the ferrocene core allow
carbonylation reactions of nonactivated chloroarenes.5
(3) (a) Hillier, A. C.; Nolan, S. N. Platinum Metals ReV. 2002, 46, 50
and references therein. (b) Shaughnessy, K. H.; Kim, P.; Hartwig, J. F. J.
Am. Chem. Soc. 1999, 121, 2123. (c) Hartwig, J. F.; Kawatsura, M.; Hauck,
S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64,
5575. (d) Lee, S.; Hartwig, J. F. J. Org. Chem. 2001, 66, 3402. (e) Stambuli,
J. P.; Stauffer, S. R.; Shaughnessy, K. H.; Hartwig, J. F. J. Am. Chem. Soc.
2001, 123, 2677. (f) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719.
(g) Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem.
Soc. 2001, 123, 7727. (h) Parrish, C. A.; Buchwald, S. L. J. Org. Chem.
2001, 66, 3820. (i) Grasa, G. A.; Viciu, M. S.; Huang, J.; Nolan, S. P. J.
Org. Chem. 2001, 66, 7729. (j) Gsto¨ttmayr, C. W. K.; Bo¨hm, V. P. W.;
Herdtweck, E.; Grosche, M.; Herrmann, W. A. Angew. Chem. 2002, 114,
1421; Angew. Chem., Int. Ed. 2002, 41, 1363. (k) Yin, J.; Rainka, M. P.;
Zhang, X.-X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162. (l)
Beare, N. A.; Hartwig, J. F. J. Org. Chem. 2002, 67, 541.
(1) (a) Beller, M.; Zapf, A.; Ma¨gerlein, W. Chem. Eng. Techn. 2001, 4,
575. (b) Beller, M.; Zapf, A. Top. Catal. 2002, 19, 101. (c) de Vries, J. G.
Can. J. Chem. 2001, 79, 1086.
(2) (a) Herrmann, W. A.; Brossmer, C.; O¨ fele, K.; Priermeier, T.; Beller,
M.; Fischer, H. Angew. Chem. 1995, 107, 1989; Angew. Chem., Int. Ed.
Engl. 1995, 34, 1844. (b) Beller, M.; Fischer, H.; Herrmann, W. A.;
Brossmer, C. Angew. Chem. 1995, 107, 1992; Angew. Chem., Int. Ed. Engl.
1995, 34, 1848. (c) Beller, M.; Riermeier, T. H.; Haber, S.; Kleiner, H.-J.;
Herrmann, W. A. Chem. Ber. 1996, 129, 1259. (d) Herrmann, W. A.;
Brossmer, C.; Reisinger, C.-P.; O¨ fele, K.; Beller, M.; Riermeier, T. H. Chem.
Eur. J. 1997, 3, 1357. (e) Beller, M.; Riermeier, T. H. Eur. J. Inorg. Chem.
1998, 29. (f) Beller, M.; Riermeier, T. H.; Ma¨gerlein, W.; Mu¨ller, T. E.;
Scherer, W. Polyhedron 1998, 17, 1165. (g) Zapf, A.; Beller, M. Chem.
Eur. J. 2001, 7, 2908.
(4) (a) Go´mez Andreu, M.; Zapf, A.; Beller, M. Chem. Commun. 2000,
2475. (b) Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem. 2000, 112,
4315; Angew. Chem., Int. Ed. 2000, 39, 4153. (c) Ehrentraut, A.; Zapf, A.;
Beller, M. Synlett 2000, 1589. (d) Ehrentraut, A.; Zapf, A.; Beller, M. J.
Mol. Cat. 2002, 182-183, 515. (e) Ehrentraut, A.; Zapf, A.; Beller, M.
AdV. Synth. Cat. 2002, 344, 209.
(5) (a) Ma¨gerlein, W.; Indolese, A.; Beller, M. Angew. Chem. 2001, 113,
2940; Angew. Chem., Int. Ed. 2001, 40, 2856. (b) Beller, M.; Ma¨gerlein,
W.; Indolese, A. F.; Fischer, C. Synthesis 2001, 1098. (c) Beller, M.;
Indolese, A. F. Chimia 2001, 55, 684. (d) Ma¨gerlein, W.; Indolese, A. F.;
Beller, M. J. Organomet. Chem. 2002, 641, 30.
10.1021/ol020103h CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/16/2002

by reacting 1 equiv of 1,3-dimesitylimidazol-2-ylidene with
(naphthoquinone)Pd(cod)11 in tetrahydrofuran medium at
-78 °C. In addition, (1,3-dimesitylimidazol-2-ylidene)-
(benzoquinone)palladium(0) 3 was synthesized in a similar
fashion.8
Scheme 1. Pd-Catalyzed Heck Reaction of Aryl Chlorides
with Styrene
Table 1. Pd-Catalyzed Heck Reaction of Aryl Chlorides
Pd
temp
(°C)
conversion
(%)
yield
(%)
entry
R1
R2
catalyst
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
H
H
H
H
H
H
H
H
H
H
H
CN
CN
H
H
H
H
H
H
1
2
3
2
3
2
3
2
3
2
3
2
3
3
3
140
140
140
160
160
140
140
140
140
140
140
140
140
140
160
23
69
71
80
83
100
100
100
100
88
14
62
62
72
67
92
88
96
97
86
84
94
99
39
62
Having prepared the monocarbenepalladium(0) complexes
1-3, we tested the catalytic activity of these complexes for
the Heck reaction12 of aryl chlorides with styrene (Scheme
1, Table 1) and an acrylic ester, respectively (Scheme 2,
Table 2).13 Some preliminary experiments using 3 in common
NO2
NO2
COCH3
COCH3
CF3
CF3
H
H
Me
Me
Scheme 2. Pd-Catalyzed Heck Reaction of Aryl Chlorides
with 2-Ethylhexyl Acrylate
93
100
100
40
H
65
Recently, we became interested in the use of carbene
ligands for palladium-catalyzed reactions. In the past few
years, palladium carbene complexes were increasingly used
as catalysts for Heck, Suzuki, and Sonogashira reactions,
copolymerizations, and aminations of aryl halides.6 In
general, mixtures of imidazolium salts and palladium salts
have been used as precatalysts for these reactions. We believe
that it is advantageous to use defined palladium(0) carbene
complexes, which directly lead to the active palladium(0)
complexes without side reactions. In principle, this will allow
a more efficient use of the actual catalyst. Despite the
increasing use of palladium carbene complexes, there are
only a few examples of well-defined palladium(0) car-
bene complexes known.7 Of special interest to palladium
catalysis would be monocarbenepalladium(0) complexes,
which can generate a highly reactive 12e-palladium species.
So far, there are only two monocarbenepalladium(0) com-
plexes, 1 and 2, without additional strongly coordinating
phosphine ligands structurally characterized. We thought that
complexes 1 and 2 constitute interesting catalysts for
coupling reactions of aryl chlorides. Hence, we prepared
1,3-dimesitylimidazol-2-ylidene-palladium(0)-(η2,η2)-1,1,3,3-
tetramethyl-1,3-divinyl disiloxane 18 by reacting palladium(0)-
diallyl ether complex (Pd2(dae)3)9 with 1,3-dimesitylimidazol-
2-ylidene in the presence of an excess of 1,1,3,3-tetramethyl-
1,3-divinyl-disiloxane.10 The synthesis of (1,3-dimesityl-
imidazol-2-ylidene)(naphthoquinone)palladium(0) 2 is achieved
n
Table 2. Heck Arylation of 2-Ethylhexyl Acrylate in Bu4NBr
catalyst temp time conversion yield
entry R1
R2
(mol %) (°C)
(h)
(%)
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
CN
CN
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
NO2
NO2
COCH3 2 (0.5)
COCH3 3 (0.5)
CF3
COCH3 2 (0.5)
COCH3 2 (0.2)
COCH3 2 (0.1)
COCH3 2 (0.1)
COCH3 2 (0.1)
2 (0.5)
3 (0.5)
2 (0.5)
3 (0.5)
140
140
140
140
140
140
140
140
140
140
140
160
24
24
24
24
24
24
24
4
24
24
48
24
24
48
48
100
100
100
100
100
100
98
99
100
61
99
97
98
96
99
99
90
98
99
51
74
47
9
2 (0.5)
84
80
22
82
COCH3 2 (0.05) 140
H
CH3
2 (1)
2 (1)
140
140
40
32
48
dipolar aprotic solvents such as DMAc in the presence of
different bases (Cs2CO3, K3PO4, NaOAc) have shown that
3032
Org. Lett., Vol. 4, No. 18, 2002

only moderate conversions and selectivities could be obtained
with activated chloroarenes. A screening of various reaction
conditions revealed that simple ionic liquids such as nBu4NBr
give significantly improved results for this reaction. Ionic
liquids are considered “green solvents” due to their high
boiling point, low vapor pressure at elevated temperature,
and their possible use for extended runs.14 Tetraalkylammo-
nium salts are the most advantageous ionic liquids due to
their low price and availability. Hence, all further reactions
the catalytic reactions. Activated aryl chlorides such as
4-chloronitrobenzene, 2-chlorobenzonitrile, and 4-chloro-
acetophenone furnished the corresponding stilbenes in excel-
lent yields (88-99%) in the presence of catalyst 2 or 3.
4-Chlorobenzotrifluoride gives the desired product in 84-
86% yield. Interestingly, the reaction of nonactivated aryl
chlorides, e.g., chlorobenzene and 4-chlorotoluene, proceeds
with moderate to good yield (67-72%). These reactions
constitute one of the successful examples of Heck reactions
of nonactivated chloroarenes with styrene in the presence
of palladium carbene complexes. The Heck reaction of aryl
chlorides was extended to 2-ethylhexyl acrylate in the
presence of 2 and 3 as catalysts. Again, activated aryl
chlorides (4-chloronitrobenzene, 2-chlorobenzonitrile, 4-
chloroacetophenone) provide the corresponding cinnamic
esters in excellent yields (97-99%), while 4-chlorobenzo-
trifluoride yields 90% of the desired product. Chlorobenzene
and 4-chlorotoluene gave lower yields, 40 and 32%, respec-
tively, even in the presence of 1 mol % catalyst. Catalyst
loading was reduced below 0.5 mol % for activated aryl
chlorides. 4-Chloroacetophenone gave 99% yield in the
presence of 0.2 mol % catalyst and 74% yield in the presence
of 0.1 mol % catalyst. Poor yields were obtained by reducing
the catalyst amount below 0.1 mol %.
n
were conducted in Bu4NBr, which becomes a liquid at
reaction temperature.
The three defined monocarbene complexes 1-3 were
compared in the Heck reaction of both activated and
nonactivated chlorobenzenes with styrene in nBu4NBr at 140
°C. Complex 1 was found to be thermally unstable and
decomposed to palladium black during the catalysis. No
decomposition was noticed with complexes 2 and 3 during
(6) (a) Hillier, A. C.; Nolan, S. N. Platinum Metals ReV. 2002, 46, 50
and references therein. (b) Herrmann, W. A.; Bo¨hm, V. P. W.; Gsto¨ttmayr,
C. W. K.; Grosche, M.; Reisinger, C.-P.; Weskamp, T. J. Organomet. Chem.
2001, 617-618, 616 and references therein. (c) Done, M. C.; Ruther, T.;
Cavell, K. J.; Kilner, M.; Peacock, E. J.; Braussaud, N.; Skelton, B. W.;
White, A. J. Organomet. Chem. 2000, 607, 78. (d) Fu¨rstner, A.; Leitner,
A. Synlett 2001, 2, 290. (e) McGuinness, D. S.; Saendig, N.; Yates, B. F.;
Cavell, K. J. J. Am. Chem. Soc. 2001, 123, 4029. (f) Mathews, C. J.; Smith,
P. J.; Welton, T.; White, A. J. P.; Williams, D. J. Organometallics 2001,
20, 3848. (g) Peris, E.; Loch, J. A.; Mata, J.; Crabtree, R. H. Chem. Commun.
2001, 201.
(7) (a) McGuiness, D. S.; Cavell, K. J.; Skelton, B. W.; White, A. H.
Organometallics 1999, 18, 1596. (b) Bo¨hm, V. P. W.; Gsto¨ttmayr, C. W.
K.; Weskamp, T.; Herrmann, W. A. J. Organomet. Chem. 2000, 595, 186.
(8) (a) Jackstell, R.; Go´mez Andreu, M.; Frisch, A.; Selvakumar, K.;
Zapf, A.; Klein, H.; Spannenberg, A.; Ro¨ttger, D.; Briel, O.; Karch, R.;
Beller, M. Angew. Chem. 2002, 114, 1028; Angew. Chem., Int. Ed. 2002,
41, 986. (b) Selvakumar, K.; Zapf, A.; Spannenberg, A.; Beller, M. Chem.
Eur. J. 2002, in press.
In summary, we have shown for the first time that defined
monocarbenepalladium(0) complexes are suitable catalysts
for the palladium-catalyzed Heck reaction of activated and
nonactivated aryl chlorides. It is shown that tetraalkyl-
ammonium halides constitute superior high-temperature
solvents for this type of Heck reaction. This makes this type
of catalyst of general interest to industrial fine chemical
synthesis.
(9) Krause, J.; Cestanic, G.; Haack, K.-J.; Seevogel, K.; Storm, W.;
Po¨rschke, K.-R. J. Am. Chem. Soc. 1999, 121, 9807.
(10) Arduengo, A. J.; Dias, H. V. R.; Harlow, R. L.; Kline, M. J. Am.
Chem. Soc. 1992, 114, 5530.
(11) (a) Hiramatsu, M.; Fujinami, T.; Sakai, S. J. Organomet. Chem.
1981, 218, 409. (b) Hiramatsu, M.; Shiozaki, K.; Fujinami, T.; Sakai, S. J.
Organomet. Chem. 1983, 246, 203.
(12) (a) de Meijere, A.; Meyer, F. E. Angew. Chem. 1994, 106, 2473;
Angew. Chem., Int. Ed. Engl. 1994, 33, 2379. (b) Beletskaya, I. P.;
Cheprakov, A. V. Chem. ReV. 2000, 100, 3009.
(13) Standard reaction conditions: 1 mmol of aryl chloride, 1.5 mmol
of olefin, 1.2 mmol of sodium acetate, catalyst (0.5 mol %), and 2 g of
tetrabutylammonium bromide were stirred under argon at 140 °C for 24 h
in a Schlenk tube. After the mixture was cooled, the internal standard
(diethyleneglycol di-n-butyl ether) was added, and the mixture was diluted
with 5 mL of water and extracted with 3 × 5 mL of ether. The combined
organic layers were dried over sodium sulfate. The conversion and the yield
were determined by gas chromatography.
Acknowledgment. This work has been supported by the
state Mecklenburg-Western Pommerania, the Fonds der
Chemischen Industrie, and the Bundesministerium fu¨r Bil-
dung und Forschung (BMBF). The authors thank Dr. R.
Karch (OMG) and Dr. O. Briel (OMG) for general discus-
sions regarding the new palladium complexes. K.S. thanks
the Alexander von Humboldt Foundation for a fellowship.
Supporting Information Available: Experimental pro-
cedures and characterization data for selected Heck products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(14) (a) Welton, T. Chem. ReV. 1999, 99, 2071. (b) Wasserscheid, P.;
Keim, W. Angew. Chem. 2000, 112, 3926; Angew. Chem., Int. Ed. 2000,
39, 3772.
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