Bronsted guanidine acid-base ionic liquids: Novel reaction media for the palladium-catalyzed heck reaction

Article abstract of DOI:10.1021/ol052543p

Bronsted acid-base ionic liquids (GILs) based on guanidine and acetic acid are efficient reaction media for palladium-catalyzed Heck reactions. They offer the advantages of high activity and reusability. GIL2 plays multiple roles in the reaction: it could act as solvent, as a strong base to facilitate β-hydride elimination, and as a ligand to stabilize activated Pd species.

Full text of DOI:10.1021/ol052543p

ORGANIC
LETTERS
2006
Vol. 8, No. 3
391-394
Brønsted Guanidine Acid−Base Ionic
Liquids: Novel Reaction Media for the
Palladium-Catalyzed Heck Reaction
Shenghai Li,† Yingjie Lin,† Haibo Xie,‡ Suobo Zhang,*,‡ and Jianing Xu†
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of
Applied Chemistry, Graduate School of the Chinese Academy of Sciences,
Changchun 130022, China, and College of Chemistry, Jilin UniVersity,
Changchun 130023, China
sbzhang@ciac.jl.cn
Received October 20, 2005
ABSTRACT
Brønsted acid
They offer the advantages of high activity and reusability. GIL2 plays multiple roles in the reaction: it could act as solvent, as a strong base
to facilitate -hydride elimination, and as a ligand to stabilize activated Pd species.
−base ionic liquids (GILs) based on guanidine and acetic acid are efficient reaction media for palladium-catalyzed Heck reactions.
â
The palladium-catalyzed couplings of olefins with aryl or
vinyl halides, known as the Heck reaction,1 have attracted
increasing attention due to their synthetic versatility. The
recent development of many efficient procedures involving
Pd catalyst precursors, such as those associated with car-
benes,2 N-, S-, P-, and Se-containing palladacycles,3 and even
ligand-free approaches,4 are quite impressive. However, most
of them are homogeneous systems and share common
drawbacks; that is, catalyst/product separation and catalyst
reuse are difficult. This problem has been solved by the
immobilization of Pd catalysts5 and by using heterogeneous
catalysts.6 However, these systems do not reach the high
activities of homogeneous catalysts and often suffer from
(4) For recent ligand-free approaches, see: (a) Reetz, M. T.; de Vries,
J. G. Chem. Commun. 2004, 1559. (b) Yao, Q.-W.; Kinney, E. P.; Yang,
Z. J. Org. Chem. 2003, 68, 7528. (c) Jeffery, T. Tetrahedron 1996, 52,
10113. (d) de Vries, A. H. M.; Mulders, J. M. C. A.; Mommers, J. H. M.;
Henelerickx, H. J. W.; de Vries, J. G. Org. Lett. 2003, 5, 3285. (e)
Chandrasekhar, S.; Narsihmulu, C.; Sultana, S. S.; Reddy, N. R. Org. Lett.
2002, 4, 4399. (f) Gozzi, C.; Lavenot, L.; Ilg, K.; Penalva, V.; Lemaire, M.
Tetrahedron Lett. 1997, 38, 8867.
† Jilin University.
‡ Changchun Institute of Applied Chemistry.
(1) (a) Heck, R. F. Acc. Chem. Res. 1979, 12, 146. (b) Beletskaya, I. P.;
Cheprakov, A. V. Chem. ReV. 2000, 100, 3009.
(2) (a) Bohm, V. P. W.; Herrmann, W. A. Chem.-Eur. J. 2000, 6, 1017.
(b) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(3) For recent representative papers on phosphine-free catalysts, see: (a)
Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem. 2001, 1917. (b)
Benford, R. B. Chem. Commun. 2003, 1787. (c) Gruber, A. S.; Zim, D.;
Ebeling, G.; Monteiro, A. L.; Dupont, J. Org. Lett. 2000, 2, 1287. (d)
Bergbreiter, D. E.; Osburn, P. L.; Wilson, A.; Sink, E. M. J. Am. Chem.
Soc. 2000, 122, 9058. (e) Gai, X.; Grigg, R.; Ramzan, M. I.; Sridharan, V.;
Collard, S.; Muir, J. E. Chem. Commun. 2000, 2053. (f) Alonso, D. A.;
Najera, C.; Pacheco, M. C. Org. Lett. 2000, 2, 1823. (g) Consorti, C. S.;
Zanini, M. L.; Leal, S.; Ebeling, G.; Dupont, J. Org. Lett. 2003, 5, 983.
(5) For recent immobilization of palladium catalysts, see: (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) Schwarz, J.; Bo¨hm, V. P. W.;
Gardiner, M. G.; Grosche, M.; Gerrmann, W. A.; Hieringer, W.; Raudaschl-
Sieber, G. Chem.-Eur. J. 2000, 6, 1773. (c) Biffis, A.; Zecca, M.; Basato,
M. Eur. J. Inorg. Chem. 2001, 1131. (d) Biffis, A. J. Mol. Catal. A: Chem.
2001, 165, 303. (e) Yamada, Y. M. A.; Takeda, K.; Takahashi, H.; Ikegami,
S. Tetrahedron Lett. 2003, 44, 2379. (f) Dahan, A.; Portnoy, M. Org. Lett.
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103, 3401.
10.1021/ol052543p CCC: $33.50
© 2006 American Chemical Society
Published on Web 01/10/2006

substantial Pd leaching.7 Therefore, finding more simple,
efficient, and reusable catalytic systems for the Heck reaction
is of importance practically and is still in demand.
GIL3 are white solids, and GIL2 is a colorless liquid at room
temperature.
Ionic liquids (ILs), known for their nonvolatile, nonflam-
mable, and thermally stable properties, have recently been
used in the Heck reaction under the catalysis of palladium
with or without a phosphine ligand.8 As an alternative to a
volatile, toxic, organic solvent, ILs can serve as an excellent
medium and as a mobile support for Pd catalysts. To avoid
catalyst leaching in IL systems, some efforts have been made
by introducing functional groups into the ionic liquid which
can complex with metal centers.9 Another way is the
introduction of imidazolium tags into a metal complex to
enhance the solubility of the catalyst in ionic liquids.10
However, the syntheses of functionalized ionic liquids or
ionic metal complexes are rather complicated and multistep
procedures have to be used.
Figure 1. Structures of GILs1-3.
The coupling reactions of bromobenzene (5 mmol) with
styrene (6 mmol) in different GILs (6 mmol) at 140 °C in a
sealed flask were investigated, in which Pd(OAc)2 or PdCl2
was used as the catalyst. As can be seen from the data in
Table 1, the catalyst system based on GIL2 displayed
The essential requirement for the Heck reaction includes
a base, a ligand-stabilized active Pd species, and a reaction
medium. Guanidine is a strong organic base and is able to
form a complex with a Pd(II) salt. It is also known that ionic
liquids based on guanidinium salts are excellent reaction
media for organic reactions.11 Herein, we wish to report that
Brønsted guanidine acid-base ionic liquids (GILs) are
efficient media for the Heck reaction. To the best of our
knowledge, the guanidine acid-base ionic liquid is one of
the simplest catalyst systems, which could be used not only
as a solvent but also as a ligand and a base and offers the
advantage of high activity and reusability without the need
of a phosphine ligand.
Table 1. Palladium-Catalyzed Heck Reaction of
Bromobenzene and Styrenea
entry
GIL
catalyst
t (h)
20
yield (%)b
TON
620
620
620
1
GIL1
GIL2
GIL2
GIL3
GIL2
GIL2
PdCl2
99
99
99
0
2
3
4
5c
6d
Pd(OAc)2
PdCl2
Pd(OAc)2
PdCl2
2
0.25
4
20
48
0
GILs1-3 (Figure 1) were prepared by neutralizing guani-
dine with acetic acid or HPF6, respectively. The GIL1 and
98
34
9800
340000
PdCl2
a Unless otherwise indicated, the reaction conditions were as follows:
bromobenzene (5 mmol), styrene (6 mmol), GIL (6 mmol), PdCl2 (0.16
mol %) or Pd(OAc)2 (0.16 mol %), 140 °C. b Average of isolated yields of
two runs. c Catalyst (0.01 mol %). d Catalyst (0.0001 mol %).
(6) For recent palladium-catalyzed heterogeneous catalysts, see: (a)
Ramchandani, R. K.; Uphade, B. S.; Vinod, M. P.; Wakharkar, R. D.;
Choudhary, V. R.; Sudalai, A. Chem. Commun. 1997, 2071. (b) Mehnert,
C. P.; Weaver, D. W.; Ying, J. K. J. Am. Chem. Soc. 1998, 120, 12289. (c)
Anson, M. S.; Mirza, A. R.; Tonks, L.; Williams, J. M. J. Tetrahedron
Lett. 1999, 40, 7147. (d) Zhao, F.-Y.; Bhanage, B. M.; Shirai, M.; Arai, M.
Chem.-Eur. J. 2000, 6, 843. (e) Djakovitch, L.; Koehler, K. J. Am. Chem.
Soc. 2001, 123, 5990. (f) Mori, K.; Yamaguchi, K.; Hara, T.; Mizugaki,
T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2002, 124, 11572. (g) Biffis,
A.; Zecca, M.; Basato, M. J. Mol. Catal. A: Chem. 2001, 173, 249. (h)
Blaser, H. U.; Indolese, A.; Schnyder, A.; Steiner, H.; Studer, M. J. Mol.
Catal. A: Chem. 2001, 173, 3. (i) Choudary, B. M.; Madhi, S.; Chowdari,
N. S.; Kantam, M. L.; Sreedhar, B. J. Am. Chem. Soc. 2002, 124, 14127.
(j) Molnar, A.; Papp, A.; Miklos, K.; Forgo, P. Chem. Commun. 2003, 2626.
(k) Pro¨ckl, S. S.; Kleist, W.; Gruber, M. A.; Ko¨hler, K. Angew. Chem., Int.
Ed. 2004, 43, 1881.
excellent activity. Quantitative conversion was achieved
within 0.25 h when 0.16 mol % of PdCl2 was applied, and
the selectivity for trans-stilbene was 98% (X/Y/Z ) 98:1.7:
0.3); the same conversion in GIL1 could only be gained by
prolonging the reaction time to 20 h (Table 1, entry 1).
Decreasing the catalyst loading to 0.01% still resulted in
quantitative conversion and high selectivity, even though the
reaction times were prolonged to 20 h (Table 1, entry 5).
Attempts to decrease the catalyst loading even further, to
0.0001 mol % Pd, resulted in the incomplete conversion of
bromobenzene, but a moderate yield could still be obtained
after prolonged heating (entry 6, TON ) 340 000). PdCl2
was more efficient than Pd(OAc)2 in this reaction. There was
no detectable conversion when the reaction was performed
in GIL3 (Table 1, entry 4). In GIL1 and GIL2, a homoge-
neous yellow solution was formed during the reaction.
However, in GIL3, palladium black slowly precipitated,
(7) (a) Djakovitch, L.; Koehler, K. J. Mol. Catal. A: Chem. 1999, 142,
275. (b) Ko¨hler, K.; Heidenreich, R. G.; Krauter, J. G. E.; Pietsch, J. Chem.-
Eur. J. 2002, 8, 622.
(8) For recent Heck reactions in ionic liquids, see: (a) Carmicheal, A.
J.; Earle, M. J.; Holbrey, J. D.; McCormac, P. B.; Seddon, K. R. Org. Lett.
1999, 1, 997. (b) Xu, L.-J.; Chen, W.-P.; Xiao, J.-L. Organometallics 2000,
19, 1123. (c) Bo¨hm, V. P.; Herrmann, W. A. Chem.-Eur. J. 2000, 6, 1017.
(d) Xu, L.-J.; Chen, W.-P.; Ross, J.; Xiao, J.-L. Org. Lett. 2001, 3, 295. (e)
Selvakumar, K.; Zapf, A.; Beller, M. Org. Lett. 2002, 4, 3031. (f) Vallin,
K. S. A.; Emilsson, P.; Larhed, M.; Hallberg, A. J. Org. Chem. 2002, 67,
6243. (g) Hamashima, Y.; Takano, H.; Hotta, D.; Sodeoka, M. Org. Lett.
2003, 5, 3225. (h) Hagiwara, H.; Sugawara, Y.; Isobe, K.; Hoshi, T.; Suzuki,
T. Org. Lett. 2004, 6, 2325. (i) Calo, V.; Nacci, A.; Monopoli, A.; Fornaro,
A.; Sabbatini, L.; Cioffi, N.; Ditaranto, N. Organometallics 2004, 23, 5154.
(j) Calo, V.; Nacci, A.; Monopoli, A.; Ieva, E.; Cioffi, N. Org. Lett. 2005,
7, 671.
(11) (a) Xie, H.-B.; Zhang, S.-B.; Duan, H.-F. Tetrahedron Lett. 2004,
45, 2013. (b) Zhu, A.-L.; Jiang, T.; Wang, D.; Han, B.-X.; Liu, L.; Huang,
J.; Zhang, J.-C.; Sun, D.-H. Green Chem. 2005, 7, 514.
(9) Xiao, J.-C.; Twamley, B.; Shreeve, J. M. Org. Lett. 2004, 6, 3845.
(10) Park, S. B.; Alper, H. Org. Lett. 2003, 5, 3209.
392
Org. Lett., Vol. 8, No. 3, 2006

which indicated the decomposition of active palladium
species.
reaction under these reaction conditions. The difference
between the catalytic activities of GIL1 and GIL2 should
come from that of Pd(II) complexes based on tetrameth-
ylguanidine and 2-butyl-1,1,3,3-tetramethylguanidine. To
Dupont et al. reported that ionic liquids based on dialkyl-
imidazolium were capable of stabilizing the catalytically
active Pd nanoparticles12 in the Heck reaction. However, the
Heck reaction of bromobenzene and olefins performed in
imidazolium-based ionic liquids proceeded very slowly with
a low yield. This is in contrast to the present work performed
in a guanidinium ionic liquid catalyst solution where the
reaction was completed within 0.25 h in a high yield. The
result clearly indicates the significant enhanced effect of the
guanidinium salts on the rate. In a previous paper, we
reported that tetramethylguanidine was an efficient ligand
for palladium-catalyzed Heck reactions.13 In the present
study, GILs1-2 consisted of a strong organic guanidine base
and an organic weak acid. At an elevated reaction temper-
ature (140 °C), GILs may dissociate into guanidine and acetic
acid (Scheme 1), so the generated guanidine acts as a base
15
prove this assumption, the complex (1) L2PdCl2 (L )
2-butyl-1,1,3,3-tetramethylguanidine) was prepared by a
similar procedure for the preparation of tetramethylguanidine
Pd(II) complex 2.13 Its molecular structure is shown in Figure
3. It is known that four molecules of tetramethylguanidine
Scheme 1. Equilibrium Reaction of GIL2 in the Sealed Flask
and a ligand for active Pd species. The efficiency of this
catalyst system would contribute to the stabilization of the
Pd by the guanidine or GILs14 and to the very fast PdH
neutralization by the strong guanidine base. TGA analysis
showed (Figure 2) that the GILs1-2 indeed decomposed into
Figure 3. Molecular Structure of L2PdCl2; L ) 2-n-butyl-1,1,3,3-
tetramethylguanidine.
can coordinate simultaneously to a Pd(II) center in complex
2.13 As shown in Figure 3, however, only two 2-butyl-1,1,3,3-
tetramethylguanidine molecules and two chloride ions co-
ordinated to the Pd(II) center. The active catalyst involved
in the arylation is generally believed to be the 14 e species
L2Pd(0).1 We used 0.1 mol % of complex 1 to catalyze the
reaction between bromobenzene and styrene in DMA. We
observed the complete conversion to stilbene after 2 h at
140 °C. This activity was higher than that of complex 2.13
To examine the versatility of this method, several repre-
sentative aryl halides with electron-withdrawing or electron-
donating substituents were tested in GIL2. The results in
Table 2 show that the regioselectivities and yields were
satisfactory within a short reaction time. The results indicate
that the GIL2/PdCl2 system is efficient for the Heck reaction.
The described GIL2 protocol is of further advantage
because the catalyst and the GILs could be recycled. The
Figure 2. TGA curves of GILs1-3.
(13) Li, S.-H.; Xie, H.-B.; Zhang, S.-B.; Lin, Y.-J.; Xu, J.-N.; Cao, J.-
G. Synlett 2005, 12, 1855.
guanidine and acetic acid, and the GIL3 is stable below 200
°C. This could explain why GIL3 was not active for the Heck
(14) Huang, J.; Jiang, T.; Gao, H.-X.; Han, B.-X.; Liu, Z.-M.; Wu, W.-
Z.; Chang, Y.-H.; Zhao, G.-Y. Angew. Chem., Int. Ed. 2004, 43, 1397.
(15) Crystal data: C18H42Cl2N6Pd (L2PdCl2), M ) 519.88, triclinic space
group P1h, a ) 8.528(2) Å, b ) 8.709(2) Å, c ) 9.053(2) Å, R ) 76.742-
(4)°, â ) 85.015(5)°, γ ) 88.705(4)°, V ) 651.9(3) Å3, T ) 293(2) K,
final R indices [I > 2σ(I)], R1 ) 0.0604, wR2 ) 0.1499.
(12) (a) Cassol, C. C.; Umpierre, A. P.; Machado, G.; Wolke, S. I.;
Dupont, J. J. Am. Chem. Soc. 2005, 127, 3298. (b) Deshmukh, R. R.;
Rajagopal, R.; Srinivasan, K. V. Chem. Commun. 2001, 1544.
Org. Lett., Vol. 8, No. 3, 2006
393

Table 2. PdCl2/GIL2-Catalyzed Heck Reaction of Aryl Halides
and Olefinsa
entry
aryl halide
C6H5I
C6H5I
p-MeC6H4I
R
t (h)
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Ph
CO2Bu
Ph
CO2Bu
Ph
CO2Bu
Ph
CO2Bu
Ph
CO2Bu
Ph
CO2Bu
Ph
CO2Bu
Ph
0.25
0.25
0.5
0.5
1
1
2
2
0.25
0.25
0.25
0.25
0.5
0.5
1.0
1.0
1.0
1.0
5.0
5.0
99
100
96
98
96
98
92
93
99
100
99
100
98
99
95
96
94
97
10
p-MeC6H4I
p-MeC6H4Br
p-MeC6H4Br
p-MeOC6H4Br
p-MeOC6H4Br
p-(CHO)C6H4Br
p-(CHO)C6H4Br
p-NO2C6H4Br
p-NO2C6H4Br
3-Br-Pyridine
3-Br-Pyridine
p-NO2C6H4Cl
p-NO2C6H4Cl
p-(CHO)C6H4Cl
p-(CHO)C6H4Cl
C6H5Cl
Figure 4. Biphasic mixture of PdCl2 in GIL2 (bottom layer) and
toluene/hexane (top layer).
the loss of activity. The amount of palladium that remained
in GIL2 was determined by means of ICP-AES. The
concentration of palladium in GIL2 was 0.45 mg/g, which
was slightly decreased in comparison with the original
loading (0.49 mg/g).
CO2Bu
Ph
CO2Bu
Ph
In summary, the basic guanidine-based room-temperature
ionic liquid (GIL2) was successfully used in the palladium
catalytic Heck reaction. GIL2 played multiple roles in this
system. First, it offered ligands to stabilize the activated Pd-
(0) during the reaction. Second, it offered a strong base to
favor the competitive â-hydride elimination, and finally, it
offered a high polar solvent to increase the reaction rate.
The catalyst and the GIL2 could be recycled at least five
times without the loss of catalytic activity.
C6H5Cl
CO2Bu
12
a Unless otherwise indicated, the reaction conditions were as follows:
aryl halide (5 mmol), olefin (6 mmol), GIL2 (6 mmol), PdCl2 (0.16 mol
%), 140 °C. b Average of isolated yields of two runs.
Heck reaction of bromobenzene (2 mmol) with styrene (2.2
mmol) was carried out in GIL2 (10 mmol). Upon the
completion of the reaction, the products were separated via
simple extraction with toluene/hexane (1:1). A clear dem-
onstration of this phase behavior is given in Figure 4, where
the preferential solubility of the yellow palladium catalyst
in the lower ionic phase is clearly apparent. After the
extraction of the product of the first-time reaction, bro-
mobenzene and styrene were added again in the same ionic
liquid. At this stage, the ionic liquid solution contained GIL2
and guanidinium bromide. This ionic liquid mixture was still
active until all acetate converted to bromide. The catalytic
system was reused five times, and it proceeded well without
Acknowledgment. This research was financially sup-
ported by the national basic research program of China
(2003CB615704).
Supporting Information Available: Analytical data and
spectra (1H NMR) for all the products; typical procedure for
the preparation of the GIL, as well as X-ray crystallographic
data for complex 1 (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
OL052543P
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Org. Lett., Vol. 8, No. 3, 2006