Dramatic enhancement of catalytic activity in an ionic liquid: Highly practical Friedel-Crafts alkenylation of arenes with alkynes catalyzed by metal triflates

Article abstract of DOI:10.1002/anie.200460292

A simple and highly efficient method for the Friedel-Crafts alkenylation of aromatic compounds has been developed by using a metal triflate (OTf) catalyst in an ionic liquid (see scheme, bmim = 1-butyl-3-methylimidazolium). Not only is the catalytic activity significantly enhanced in the ionic liquid and by-product formation decreased, but some reactions that were not possible in conventional organic solvents were shown to proceed smoothly.

Full text of DOI:10.1002/anie.200460292

Angewandte
Chemie
Synthetic Methods
deficient alkynes, such as p-trifluoromethylphenylacetylene
and p-chlorophenylacetylene. Therefore, a more efficient and
practical catalytic system for Friedel–Crafts alkenylation is
still highly desirable. Herein, we report that the use of ionic
liquids in Friedel–Crafts alkenylations of aromatic com-
pounds by alkynes catalyzed by metal triflates not only
enhanced catalytic activity markedly but also decreased by-
product formation, which resulted in higher yields of the
monoalkenylated arenes. Moreover, in some cases, reactions
that do not usually occur in conventional organic solvents
were found to proceed smoothly in ionic liquids.
Dramatic Enhancement of Catalytic Activity in an
Ionic Liquid: Highly Practical Friedel–Crafts
Alkenylation of Arenes with Alkynes Catalyzed
by Metal Triflates**
Choong Eui Song,* Da-un Jung, Su Yhen Choung,
Eun Joo Roh, and Sang-gi Lee*
The Friedel–Crafts alkylation of aromatic compounds with
alkenes is one of the fundamental methods for incorporating
carbon skeletons into aromatic systems and, thus, has been
extensively studied and is well established.[1] In contrast, the
corresponding alkenylation process with alkynes still remains
to be solved. One major drawback from the direct Friedel–
Crafts alkenylation of arenes is alkyne polymerization, which
results in the formation of a variety of undesirable side
products.[2] Well-known Lewis acidic metal chlorides, such as
ZrCl4 and AlCl3, produce the desired alkenylated products
but in extremely low yields (for example, 1 and 6% yields of
1-phenyl-1-(p-xylyl)ethene for the reaction of p-xylene with
phenylacetylene at 858C, respectively).[3] Recently, a number
of catalysts, such as the solid acid zeolite HSZ-360,[4]
phenoxymagnesium bromide,[5] and SnCl4/NBu3,[6] were
found to be active for the ortho selective alkenylation of
phenols with a limited range of alkynes (only aryl-substituted
terminal alkynes underwent this reaction). It has been also
found that GaCl3 can promote the alkenylation of arenes with
silylethyne, but excessive amounts of this Lewis acid (3 equiv)
are required.[7] Recently, Tsuchimoto et al. made a break-
through on this important reaction by finding that some metal
triflates [M(OTf)n; M = Sc, Zr, In]catalyze the alkenylation
of arenes with internal alkynes as well as terminal alkynes
through an alkenyl cation intermediate.[3] However, the
catalytic activity of these metal triflates is far too low for
preparative use. For example, the reaction of benzene and
phenylacetylene in the presence of 10 mol% of Sc(OTf)3 at
858C requires 186 hours to give 1,1-diphenylethene in 73%
yield.[3] Moreover, Sc(OTf)3 was totally inactive for electron-
Room-temperature ionic liquids (RTILs) are now
regarded as eco-friendly alternatives to volatile organic
solvents in chemical processes.[8] During the course of our
extensive efforts on the utilization of RTILs in various
catalytic reactions, we found that switching from an organic
solvent to an ionic liquid often resulted in significant
improvements in catalytic performance (for example,
increased reaction rates, improved selectivities, etc.) as well
as catalyst recycling.[9] Recently, we found that the Sc(OTf)3-
catalyzed Friedel–Crafts alkylation of aromatic compounds
with alkenes is dramatically accelerated in the presence of
hydrophobic ionic liquids, such as [bmim][PF6]or [bmim]
[SbF6](bmim = 1-butyl-3-methylimidazolium).[9a] This result
encouraged us to investigate the metal triflate catalyzed
Friedel–Crafts alkenylation of aromatics with alkynes in ionic
liquids.
To investigate the effect of ionic liquids on the catalytic
activity of metal triflates in Friedel–Crafts alkenylation we
first examined the reaction between benzene and 1-phenyl-1-
propyne under various conditions (Table 1).
As observed by Tsuchimoto et al.,[3] the alkenylation of
benzene with 1-phenyl-1-propyne in the presence of 10 mol%
of Sc(OTf)3 without an ionic liquid proceeded very slowly
with a yield of only 27% after 96 hours (entry 1). Moreover,
this long reaction time resulted in increased the formation of
undesired side products. On the other hand, when the
reaction was carried out in hydrophobic ionic liquids, such
as [bmim][PF6]or [bmim[]SbF 6], the catalytic activity of
Sc(OTf)3 was dramatically enhanced: the reaction was
completed within 4 hours to afford the desired product (1,1-
diphenyl-1-propene) in excellent yields (91 or 90%, respec-
tively; entries 2 and 3).[10,11] Among the various metal triflates
investigated for catalytic activity, indium triflate, hafnium
triflate, and yttrium triflate in particular were found to exhibit
higher activity than scandium triflate, with the reaction
completed within 2.5, 1, and 2 hours, respectively (entries 4,
7, and 10). The reactions proceeded smoothly with excellent
yields even in the presence of smaller amounts of these metal
triflates (5 and 2.5 mol%; entries 5, 6, 8, and 9). Ytterbium
triflate and lutetium triflate also exhibited similar catalytic
acivities to that of scandium triflate (entries 11 and 12). This
[*] Prof. C. E. Song, S. Y. Choung
Institute of Basic Science
Department of Chemistry, Sungkyunkwan University
300 Chunchun, Jangan, Suwon, Kyunggi, 440-746 (Korea)
Fax: (+82)31-290-7075
E-mail: s1673@skku.edu
D.-u. Jung, Dr. E. J. Roh, Dr. S.-g. Lee
Life Sciences Division
Korea Institute of Science and Technology
PO Box 131, Cheongryang, Seoul 130-650 (Korea)
Fax: (+82)2-958-5189
E-mail: sanggi@kist.re.kr
[**] This work was supported by the BK21 project of the Ministry of
Education in Sungkyunkwan University (SKKU) and the National
Research Laboratory Program in Korea Institute of Science and
Technology (KIST).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2004, 43, 6183 –6185
DOI: 10.1002/anie.200460292
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6183

Communications
Table 1: Friedel–Crafts alkenylation of benzene by 1-phenyl-1-propyne.[a]
Table 2: Friedel–Crafts alkenylation of various arenes with various
alkynes.[a]
Entry R1
R2
Arene
Catalyst t [h] Yield [%][b]
Entry
Catalyst (equiv)
Ionic liquid
t [h]
Yield [%][b]
1
Ph
Me
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
p-xylene
benzene
p-xylene
p-xylene
p-xylene
benzene
benzene
benzene
benzene
p-xylene
toluene
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
In(OTf)3
Hf(OTf)4
Sc(OTf)3
Sc(OTf)3
In(OTf)3
Hf(OTf)4
Sc(OTf)3
Sc(OTf)3
4
4
4
3
3
2
4
2
1
4
2
6
2
96[c]
68
60
80
85
59
62
72
92
1
2
3
4
5
6
7
8
9
Sc(OTf)3 (0.1)
Sc(OTf)3 (0.1)
Sc(OTf)3 (0.1)
In(OTf)3 (0.1)
In(OTf)3 (0.05)
In(OTf)3 (0.025)
Hf(OTf)4 (0.1)
Hf(OTf)4 (0.05)
Hf(OTf)4 (0.025)
Y(OTf)3 (0.1)
none
96
4
4
2.5
6
24
1
5
9
2
4
27
91
90
81
94
91
90
91
85
80
81
94
2
Ph
[bmim][SbF6]
[bmim][PF6]
[bmim][SbF6]
[bmim][SbF6]
[bmim][SbF6]
[bmim][SbF6]
[bmim][SbF6]
[bmim][SbF6]
[bmim][SbF6]
[bmim][SbF6]
[bmim][SbF6]
3
Ph
4
Ph
5
Ph
6
Ph
Ph
Ph
7[d]
8
9
Ph
10
Ph
80[c]
83[e]
44[e]
73[e]
73
10
11
12
11
12
13
14
15
16
17
18
19
20
Ph
Ph
Ph
p-CF3Ph
p-CF3Ph
p-CF3Ph
p-ClPh
p-ClPh
Ph
Yb(OTf)3 (0.1)
Lu(OTf)3 (0.1)
chlorobenzene Sc(OTf)3
4
anisole
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
Sc(OTf)3
Sc(OTf)3 22
[a] All reactions were carried out at 858C using 1-phenyl-1-propyne
(1 mmol),benzene (6 mL), and the ionic liquid (1 mL) in the presence of
the metal triflate as a catalyst. [b] Yield of isolated product based on 1-
phenyl-1-propyne.
H
H
H
H
In(OTf)3
Hf(OTf)4
5
5
78
58
Sc(OTf)3 12
Hf(OTf)4
63
70
4
CO2Et benzene
CO2Et p-xylene
Hf(OTf)4 22
Hf(OTf)4 10
89
Ph
70[c]
[a] All reactions were carried out with an alkyne (1 mmol), an arene
(6 mL), and [bmim][SbF6] (1 mL) in the presence of the metal triflate
catalyst (10 mol%) at 858C. [b] Yield of isolated product based on the
significant rate acceleration may be ascribed to the stabiliza-
tion of the unstable vinyl cationic intermediate in a highly
polar ionic liquid, in which the polar vinyl cation may gain a
longer lifetime. The catalytic activities of other metal triflates
were also investigated, for example (yields are given in
parentheses), Ag(OTf) (4%), Cu(OTf)2 (27%), Mg(OTf)2
(21%), Zn(OTf)2 (2%), Sn(OTf)2 (69%), La(OTf)3 (62%),
Pr(OTf)3 (19%), Nd(OTf)3 (37%), Sm(OTf)3 (15%),
Eu(OTf)3 (16%), Gd(OTf)3 (23%), Tb(OTf)3 (34%),
Dy(OTf)3 (28%), Ho(OTf)3 (30%), Er(OTf)3 (40%), and
Tm(OTf)3 (22%). However, their catalytic activities were
much lower than those of Sc(OTf)3, In(OTf)3, Hf(OTf)4,
Y(OTf)3, Yb(OTf)3, and Lu(OTf)3.
To study the scope of this reaction a series of Friedel–
Crafts alkenylations of arenes with various types of alkynes
were carried out in [bmim][SbF6](Table 2). In all cases, the
reactions proceeded successfully within a few hours to afford
the corresponding alkenylated products in good to excellent
yields. In particular, Sc(OTf)3, In(OTf)3, and Hf(OTf)4
effectively catalyzed the alkenylation of the electron-defi-
cient alkynes, such as p-tifluoromethylphenylacetylene and p-
chlorophenylacetylene, which were totally inactive without
the presence of an ionic liquid (entries 14–18).[3] Similarly, the
reaction of arenes with ethyl phenylpropiolate in the presence
of Hf(OTf)4 proceeded smoothly in [bmim][SbF6](entries 19
and 20), whereas without [bmim][SbF6]a conversion of only
< 5% was observed. It should also be noted that the ionic
liquid phase containing the metal triflate could be readily
recovered by simple decantation of the organic layer (the
upper phase) after reaction. The recovered ionic liquid phase
containing the metal triflate was reused without further
addition of metal triflate. However, a decrease in catalytic
activity over successive reactions was observed and, thus, the
reaction time became longer upon reuse (compare entries 6
and 7 in Table 2).
1
alkyne. [c] cis/trans ratios were determined by H NMR spectroscopy as
follow: 96/4 (entry 1), 88/12 (entry 10), and 87/13 (entry 20). [d] Reac-
tion was carried out with the recovered ionic liquid phase from entry 6
without further addition of Sc(OTf)3. [e] The reaction gave an inseparable
mixture of four isomers of ortho and para regioisomers, including the
corresponding cis/trans isomers. The isomer ratios determined by GC-
MS analysis are as follows; 2/33/32/32 (entry 11); 2/35/31/32
(entry 12); 8/18/34/40 (entry 13).
Finally, our protocol has been further extended to intra-
molecular Friedel–Crafts alkenylations. The intramolecular
reaction of aryl phenyl propiolates catalyzed by Hf(OTf)4
(10 mol%) in a mixture of [bmim][SbF6]and methylcyclo-
hexane at 858C for 9–10 hours resulted in the formation of the
4-phenylcoumarins in moderate yields (Scheme 1). Surpris-
ingly, the reaction of aryl-2-butynoates also was successfully
performed to afford the corresponding coumarin in an
excellent yield (89%; Scheme 1). The smaller stabilizing
influence of the alkyl group on the vinyl cation intermediate
Scheme 1. Synthesis of 4-phenylcoumarins by intramolecular Friedel–
Crafts alkenylations.
6184
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Chemie
chromatography on silica gel (hexane/diethyl ether) to give 113 mg
(51%) of pure 4-phenylcoumarin as a pale yellow solid.
resulted in the alkyl-substituted alkynes usually undergoing
self-oligomerization rather than the desired alkenylation
reaction. Intramolecular alkenylation allowed us to synthe-
size 2(1H)-quinolinones from the corresponding aryl amides
of phenylpropiolic acid in good yields (Scheme 2).
Received: April 12, 2004
À
Keywords: alkenylation · C C bond formation ·
homogeneous catalysis · ionic liquids · Lewis acids
.
[1]For reviews of Friedel–Crafts alkylation reactions, see: a) Frie-
del–Crafts and Related Reactions, Vol.II , part 1 (Ed.: G. A.
Olah), Wiley-Interscience, New York, 1964; b) Friedel–Crafts
Alkylation Chemistry.A Centry of Discovery (Eds.: R. M
Roberts, A. A. Khalaf), Marcel Dekker, New York, 1984;
c) G. A. Olah, R. Krishnamurit, G. K. S. Prakash, in Friedel–
Crafts Alkylations in Comprehensive Organic Synthesis (Eds.:
B. M. Trost, I. Fleming), Pergamon, Oxford, 1991.
[2]O. W. Cook, V. J. Chaber, J.Am.Chem.Soc. 1921, 43, 334; J. S.
Reichert, J. A. Nieuwland, J.Am.Chem.Soc.
1923, 45, 3090;
J. A. Reilly, J. A. Nieuwland, J.Am.Chem.Soc. 1928, 50, 2564.
[3]T. Tsuchimoto, T. Maeda, E. Shirakawa, Y. Kawakami, Chem.
Commun. 2000, 1573.
[4]G. Sartori, F. Bigi, A. Pastorio, C. Porta, A. Arienti, R. Maggi, N.
Moretti, G. Gnappi, Tetrahedron Lett. 1995, 36, 9177.
[5]G. Casiraghi, G. Casnati, G. Puglia, G. Sartori, G. Terenghi,
Synthesis 1977, 122.
Scheme 2. Synthesis of 2(1H)-quinolinones by intramolecular Friedel–
Crafts alkenylations.
[6]M. Yamaguchi, Y. Kido, A. Hayashi, M. Hirama, Angew.Chem.
In conclusion, we have found that the employment of
hydrophobic ionic liquids dramatically enhanced the catalytic
activities of metal triflates in Friedel–Crafts alkenylations,
and thus allowed the development of a simple and highly
efficient method for coupling aromatic compounds with
various alkyl- and aryl-substituted alkynes. In some cases,
reactions that were not possible in conventional organic
solvents also proceeded smoothly in the presence of ionic
liquids. To our knowledge, the described protocol could be the
most efficient preparative Friedel–Crafts alkenylation
method published to date for the synthesis of a range of
alkenylated arenes,[12] such as styrenes, cis-aryl-a,b-unsatu-
rated carbonyl compounds, coumarines, and 2(1H)-quinoli-
nones. Studies into the origin of the effects of ionic liquids on
catalytic activity are in progress.
1997, 109, 1370; Angew.Chem.Int.Ed.Engl.
Kido, S. Yoshimura, M. Yamaguchi, T. Uchimaru, Bull.Chem.
Soc.Jpn. 1999, 72, 1445.
1997, 36, 1313; Y.
[7]M. Yamaguch, A. Hayashi, M. Hirama, J.Am.Chem.Soc. 1995,
117, 1151.
[8]For recent reviews on ionic liquids, see: a) C. E. Song, Chem.
Commun. 2004, 1033; b) R. Sheldon, Chem.Commun. 2001,
2399; c) P. Wasserscheid, W. Kein, Angew.Chem. 2000, 112,
3926; Angew.Chem.Int.Ed. 2000, 39, 3772; d) T. Welton, Chem.
Rev. 1999, 99, 2071.
[9]Our recent examples: a) C. E. Song, W. H. Shim, E. J. Roh, J. H.
Choi, Chem.Commun. 2000, 1695; b) C. E. Song, E. J. Roh,
Chem.Commun. 2000, 837; c) C. E. Song, W. H. Shim, E. J. Roh,
S.-g. Lee, J. H. Choi, Chem.Commun. 2001, 1122; d) S.-g. Lee,
J. W. Park, J. Kang, J. K. Lee, Chem.Commun. 2001, 1698;
e) D. W. Kim, C. E. Song, D. Y. Chi, J.Am.Chem.Soc. 2002, 124,
10278; f) S.-g. Lee, J. W. Park, Bull.Korean Chem.Soc. 2002, 23,
1367; g) D. W. Kim, C. E. Song, D. Y. Chi, J.Org.Chem. 2003, 68,
4281; h) E. J. Kim, S. Y. Ko, C. E. Song, Helv.Chim.Acta 2003,
86, 894; i) S.-g. Lee, Y. J. Zhang, P. Z. Yu, H. Yoon, C. E. Song,
J. H. Choi, J. Hong, Chem.Commun. 2003, 2624; j) S.-g. Lee,
J. W. Park, J.Mol.Catal.A 2003, 194, 49.
Experimental Section
Typical procedure for intermolecular Friedel–Crafts alkenylations in
an ionic liquid: 1-Phenyl-1-propyne (178.2 mg, 1 mmol) was added to
a mixture of Sc(OTf)3 (49.2 mg, 0.1 mmol), benzene (6 mL), and
[bmim][SbF6](1 mL) under a nitrogen atmosphere. Two phases
formed and the mixture was heated to reflux for 4 h. After completion
of the reaction, the reaction mixture was cooled to room temperature.
The organic layer (upper phase) was separated by extraction with
benzene to leave the ionic liquid phase containing the catalyst, which
could be reused. All the volatile organic compounds were then
removed under reduced pressure and the residue was purified by flash
column chromatography on silica gel (hexane) to give 177 mg (91%)
of pure 1,1-diphenyl-1-propene as a pale yellow solid.
[10]In sharp contrast to these results, only very small amounts of the
alkenylated product was obtained (< 2% yield) in the hydro-
philic ionic liquids, [bmim][BF4]or [bmim][OTf].
[11]Recently, Rogers and co-workers reported the instability of the
ionic liquidsꢀ counterion PF6 towards moisture, which resulted in
hydrolysis and the formation of HF (R. P. Swatloski, J. D.
Holbrey, R. D. Rogers, Green Chem. 2003, 5, 361). Therefore, to
examine the possible catalytic effect of HF on this reaction, we
also carried out the reaction only in [bmim][SbF6]or in a mixture
of [bmim][SbF6]and water (1:1, v/v) without any metal triflate
catalyst. However, the reaction did not occur at all.
[12]A new synthetic route to alkenylated arenes involving Pd- and
Pt-catalyzed addition of arenes to alkynes in the presence of
trifluoroacetic acid was recently reported: a) C. Jia, D. Piao, J.
Oyamada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287,
1992; b) C. Jia, W. Lu, J. Oyamada, T. Kitamura, K. Matsuda, M.
Irie, Y. Fujiwara, J.Am.Chem.Soc. 2000, 122, 7252.
Typical procedure for intramolecular Friedel–Crafts alkenyla-
tions in an ionic liquid: A mixture of Hf(OTf)4 (77.4 mg, 0.1 mmol),
phenyl 3-phenylpropiolate (222.1 mg, 1 mmol), methylcyclohexane
(6 mL), and [bmim][SbF6](1 mL) was heated to reflux for 9 h under a
nitrogen atmosphere. The reaction mixture was then cooled to room
temperature. All the volatile organic compounds were then removed
under reduced pressure and the residue was purified by flash column
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