Thermodynamically- and kinetically-controlled Friedel-Crafts alkenylation of arenes with alkynes using an acidic fluoroantimonate(v) ionic liquid as catalyst

Article abstract of DOI:10.1039/b705719a

By employing superacidic fluoroantimonate ionic liquid (IL), [bmim][Sb ₂F₁₁], as catalyst, not only thermodynamically-controlled but also kinetically-controlled Friedel-Crafts alkenylations of arenes with alkynes have been realized for the first time. The Royal Society of Chemistry.

Full text of DOI:10.1039/b705719a

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Thermodynamically- and kinetically-controlled Friedel–Crafts
alkenylation of arenes with alkynes using an acidic fluoroantimonate(V)
ionic liquid as catalyst{
Doo Seong Choi, Jin Hong Kim, Ueon Sang Shin, Ravindra R. Deshmukh and Choong Eui Song*
Received (in Cambridge, UK) 16th April 2007, Accepted 11th July 2007
First published as an Advance Article on the web 31st July 2007
DOI: 10.1039/b705719a
Herein we report that superacidic fluoroantimonate(V) ionic
liquid (IL), [bmim][Sb2F11] 1 (bmim = 1-butyl-3-methylimidazo-
lium), exhibited the unprecedented high catalytic activity for the
Friedel–Crafts alkenylation of a broad scope of arenes with
terminal and internal alkynes. Moreover, by employing the super-
acidic IL 1 as catalyst, not only thermodynamically-controlled but
also kinetically-controlled Friedel–Crafts alkenylation of arenes
with alkynes has been realized for the first time.
By employing superacidic fluoroantimonate ionic liquid (IL),
[bmim][Sb2F11], as catalyst, not only thermodynamically-con-
trolled but also kinetically-controlled Friedel–Crafts alkenyla-
tions of arenes with alkynes have been realized for the first time.
The hydroarylation of alkynes (also known as alkenylation of
arenes) catalyzed by transition metal complexes, thereby affording
styrene derivatives, has recently received much research attention
because this approach is, in principle, simpler than those based on
Heck reactions, cross coupling reactions, and olefin cross-
metathesis reactions.1 Depending on the type of interaction
between the metal catalyst and the arene or the triple bond, the
hydroarylation of alkynes proceeds either via s-aryl–metal species
or via alkenyl cation intermediates. Using Pd(II), Pt(II) and Au(III)
catalysts, s-aryl–metal species were proposed as intermediates.2,3
On the other hand, the Friedel–Crafts-type reaction, which
proceeds via an alkenyl cation intermediate followed by its
electrophilic attack on an arene, can be promoted by Lewis acid
catalysts.4,5
It has been well known that acidic chloroaluminate(III) ILs, e.g.,
[bmim][Al2Cl7], exhibit strong catalytic activities in many organic
reactions due to the super Lewis acidity of their anions.6 Therefore,
we envisioned that the anions of the fluoroantimonate ILs, e.g.,
[bmim][Sb2F11], would be more powerful Lewis acid sources than
chloroaluminate anions. Thus, we prepared a pale-yellow colored
superacidic ionic liquid 17 simply by mixing [bmim][SbF6] with one
equivalent of SbF5 under an argon atmosphere at 0 uC (Scheme 1,
for experimental procedure and characterization data, see ESI{)
and investigated its catalytic activity for the alkenylation of arenes.
We first examined the reactions of p-xylene with the challenging,
electron-deficient alkynes such as p-Cl– and p-CF3–phenylacety-
lene using 5 mol% of 1 at 90 uC. The results are summarized in
Table 1, together with the reported data obtained with other
catalyst systems. As shown in Table 1, the fluoroantimonate IL 1
showed surprisingly high catalytic activity and, thus, the reactions
(entries 5 and 9) proceeded within 30 min, which is significantly
faster than those using the other catalyst systems. Other reported
Despite the recent intensive research on this reaction, all catalyst
systems reported so far (e.g., Pd(II),2 Pt(II),2 Au(III),3 Sc(III),4 etc.)
display narrow substrate scope and low catalytic activity, giving
mainly thermodynamically favored isomers. For example, using
Pd, Pt or Au catalysts, acceptable yields were obtained usually
with highly electron-rich arenes with more than two electron-
donating substituents.2,3 Moreover, internal alkynes showed
almost no reactivity with Au catalysts.3a The catalytic activity of
metal triflates such as Sc(OTf)3 was also very low and thus the
reaction of benzene and phenylacetylene in the presence of
10 mol% of Sc(OTf)3 at 85 uC required 186 h.4 Moreover,
Sc(OTf)3 was totally inactive towards electron-deficient alkynes
such as p-CF3–phenylacetylene and p-Cl–phenylacetylene.
Although the substrate scope of metal triflate-catalyzed alkenyla-
tion was broadened by employing an ionic liquid (IL),5 the activity
of this catalyst system is not still high enough to conduct the
reaction at low temperature, which is desirable to obtain
kinetically-controlled products. Therefore, the development of a
new and strongly active catalyst system for hydroarylation of
alkynes that works even under kinetic conditions (i.e., at low
temperatures) is highly desirable.
4
catalyst systems such as AuCl3–AgSbF63a (entry 1) and Sc(OTf)3
(entries 2 and 6) were shown to be nearly inactive. Notably, the
superacidic chloroaluminate(III) IL, [bmim][Al2Cl7] also showed
no catalytic activity with the electron-deficient alkynes (entries 4
and 8). Although the same reactions using Sc(OTf)3–[bmim][SbF6]
afforded the desired adducts in satisfactory yields, much longer
reaction times were required (12 and 22 h, entries 3 and 7,
respectively).5a
Department of Chemistry, Institute of Basic Science, Sungkyunkwan
University, Suwon 440-746, Korea. E-mail: s1673@skku.edu;
Fax: (+82) 31-290-7075; Tel: (+82) 31-290-5964
{ Electronic supplementary information (ESI) available: Experimental
procedure and characterization data for all compounds. See DOI: 10.1039/
b705719a
Scheme 1 Preparation of fluoroantimonate IL 1.
3482 | Chem. Commun., 2007, 3482–3484
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30 min, affording the corresponding alkenylated products in good
to excellent yields with perfect regioselectivity in favor of the
Markovnikov-type 1,1-product (entries 1–4 and 7–9). The perfect
regiochemistry can be attributed to the conjugative stabilizing
effect of the a-aryl group on the vinyl cation intermediate. The
reactions of arenes with a terminal alkyne conjugated to an
electron-withdrawing group (–COMe), 3-butyn-2-one, also pro-
ceeded very fast in regio- and stereoselective manner, giving
thermodynamically favored b-aryl-substituted trans-alkene, (E)-4-
aryl 3-buten-2-ones, nearly as sole products (entries 10 and 13).
Moreover, all reactions of internal alkynes with arenes also
proceeded smoothly with high regio- and stereoselectivity, even
with electron-poor arenes (e.g., p-chlorotoluene, chlorobenzene),
affording the corresponding adducts with very high (Z)-selectivity8
(Z : E-ratio = up to 99 : 1) (entries 5–6, 11–12 and 14–15).
Previously, our group5 and Tsuchimoto’s group4 observed that the
composition of stereoisomers at the initial stage of the reaction
gradually changed over time via Lewis acid-catalyzed isomeriza-
tion, yielding thermodynamically-favored isomer as the major
product at the end of the reaction. In fact, most reactions in Table 2
were completed within 10 min to afford the products, albeit with
lower (Z)/(E)-ratios. Thus, the reaction times were prolonged to
obtain higher (Z)/(E)-ratios. For example, the reaction of
mesitylene with 1-phenyl-1-propyne at 90 uC was completed in
5 min to give a mixture of (Z)- and (E)-1-mesityl-1-phenyl-1-
propene in 70 : 30 ratio. The (Z) : (E) ratio of 99 : 1 was obtained
from the same reaction mixture when the reaction time was
prolonged to 30 min (entry 11).
Table 1 Activities of various catalytic systems for Friedel–Crafts
alkenylation of p-xylene with electron-deficient terminal alkynes
Yield (%)a
(TOF/h)
Entry
R
Catalyst
Time
1b
2c
3d
4e
5f
6c
7d
8e
9f
a
p-ClPh
p-ClPh
p-ClPh
p-ClPh
p-ClPh
AuCl3–AgSbF6
Sc(OTf)3
Sc(OTf)3–[bmim][SbF6] 12 h
4 h
15 h
28 (4.6)
NR (0)
63 (0.5)
NR (0)
[bmim][Al2Cl7]
1
1 h
10 min 71 (85.2)
p-CF3Ph Sc(OTf)3
p-CF3Ph Sc(OTf)3–[bmim][SbF6] 22 h
p-CF3Ph [bmim][Al2Cl7] 1 h
p-CF3Ph
15 h
NR (0)
73 (0.3)
NR (0)
1
30 min 90 (36)
b
Isolated yields based on alkyne. From ref. 3a (using 1.5 mol%
c
catalyst): GC yield (not isolated). From ref. 4 (using 10 mol%
d
e
catalyst). From ref. 5a (using 10 mol% catalyst). The reaction
was carried out at 90 uC using alkyne (1 mmol) and arene (6 mL) in
the presence of [bmim][Al2Cl7] (5 mol%). The reaction was carried
f
out at 90 uC using alkyne (1 mmol) and arene (6 mL) in the
presence of 1 (5 mol%), NR = no reaction.
Following these encouraging results, we carried out a series of
alkenylations of various electron-rich and electron-poor arenes
(benzene, p-xylene, mesitylene, pentamethylbenzene, p-chloroto-
luene and chlorobenzene) with various terminal and internal
alkynes using 5 mol% of 1 at 90 uC to survey the scope of our
protocol. As shown from the results in Table 2, all reactions with
aryl-substituted terminal alkynes were completed within a few to
Having an extremely active catalyst 1 in hand, finally we
investigated the possibility of obtaining the kinetically-controlled
stereoisomer. For this goal, the reactions were carried out using
Table 2 Friedel–Crafts alkenylation of arenes with various alkynes catalyzed by the superacidic fluoroantimonate IL 1a
Entry
Ar–H
R1
R2
Time
Yield (%)b
E : Z-ratioc
1
2
3
4
5
6
7
8
9
10
11
12
13d
14e
Benzene
Benzene
Benzene
p-Xylene
p-Xylene
p-Xylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Pentamethylbenzene
p-Chlorotoluene
Ph
H
H
H
H
Me
Ph
H
H
H
COMe
Me
Ph
COMe
Me
5 min
20 min
30 min
5 min
30 min
30 min
5 min
5 min
5 min
30 min
30 min
2 h
57
68
53
74
89
89
79
84
90
88
81
87
—
—
—
—
7 : 93
9 : 91
—
—
—
98 : 2
1 : 99
2 : 98
94 : 6
7 : 93
10 : 90
17 : 83
1 : 19
p-ClPh
p-CF3Ph
Ph
Ph
Ph
Ph
p-ClPh
p-CF3Ph
H
Ph
Ph
H
Ph
30 min
30 min
65
28 (o)
30 (m)
35 (o)
31 (p)
15f
Chlorobenzene
Ph
Me
30 min
a
Unless otherwise indicated all reactions were carried out using alkyne (1 mmol), and arene (6 mL) in the presence of 1 (5 mol%) as catalyst
b
c
at 90 uC. Isolated yield based on the alkyne. E : Z ratios were determined by GC/MS and NMR spectroscopy, and E/Z configurations of
products were established on the basis of differential NOE experiments (see ESI). 1 Equivalent of solid arene based on alkyne (1 mmol) and
d
e
4 mL of 1,2-dichloroethane as a co-solvent were used. The reaction gave the mixture of ortho- and meta-regioisomers to the methyl group of
f
p-chlorotoluene, including the corresponding (E)/(Z) isomers. The reaction gave the mixture of ortho- and para-regioisomers, including the
corresponding (E)/(Z) isomers.
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Table 3 Kinetically-controlled Friedel–Crafts alkenylation of arenes with internal alkynes catalyzed by the superacidic fluoroantimonate IL 1a
Entry
Ar–H
R1
R2
Temperature/uC
Time/min
Yield (%)b
E : Z- ratioc
1
2
3
4
5
a
p-Xylene
Mesitylene
Mesitylene
Pentamethylbenzene
Pentamethylbenzene
Ph
Ph
Ph
Ph
Ph
Ph
Me
Ph
Me
Ph
225
278
225
278
225
10
15
15
5
4711
72
93 : 7
86 : 14
94 : 6
95 : 5
91 : 9
76
4811
87
5
b
c
For detailed experimental conditions, see ESI. Isolated yield based on the alkyne. E : Z ratios were determined by GC/MS and NMR
spectroscopy, and the E/Z configurations of products were established on the basis of differential NOE experiments (see ESI).
20 mol%10 of catalyst at low temperatures. Quite surprisingly, the
2 (a) C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura and Y. Fujiwara,
Science, 2000, 287, 1992–1995; (b) C. Jia, W. Lu, J. Oyamada,
reactions proceeded very fast even at 278 uC, affording the desired
T. Kitamura, K. Matsuda, M. Irie and Y. Fujiwara, J. Am. Chem. Soc.,
kinetically favored product as a major isomer in good yields
(Table 3). For example, the reaction of mesitylene with 1,2-
diphenylacetylene at 225 uC afforded the adduct with an E : Z
ratio of 94 : 6 (entry 3), whereas the E : Z ratio of product at 90 uC
was 2 : 98 (entry 12 in Table 2). Although a substoichiometric
amount (20 mol%)10 of 1 is still needed, to our knowledge, this is
the first example for not only thermodynamically-controlled but
also kinetically-controlled Friedel–Crafts alkenylation of arenes
with alkynes.
2000, 122, 7252–7263; (c) C. Jia, T. Kitamura and Y. Fujiwara, Acc.
Chem. Res., 2001, 34, 633–639. However, it has recently been suggested
by Tunge and Foresee that the Fujiwara hydroarylation occurs rather
via typical Friedel–Crafts alkenylation pathway: J. A. Tunge and
L. N. Foresee, Organometallics, 2005, 24, 6440–6444.
3 (a) M. T. Reetz and K. Sommer, Eur. J. Org. Chem., 2003, 3485–3496;
(b) Z. Shi and C. He, J. Org. Chem., 2004, 69, 3669–3671.
4 T. Tsuchimoto, T. Maeda, E. Shirakawa and Y. Kawakami, Chem.
Commun., 2000, 1573–1574.
5 (a) C. E. Song, D. Jung, S. Y. Chung, E. J. Roh and S.-g. Lee, Angew.
Chem., Int. Ed., 2004, 43, 6183–6185; (b) M. Y. Yoon, J. H. Kim,
D. S. Choi, U. S. Shin, J. Y. Lee and C. E. Song, Adv. Synth. Catal.,
2007, 349, 1725–1737.
In conclusion, by employing superacidic fluoroantimonate(V) IL
1 as catalyst, not only thermodynamically-controlled but also
kinetically-controlled Friedel–Crafts alkenylation of arenes with
alkynes has been realized for the first time. The fluoroantimonate
IL 1 showed unprecedented high catalytic activity, and thus, by
using 5 mol% of 1 most reactions were completed within 30 min at
90 uC, affording the thermodynamically-controlled isomers as the
main products. More surprisingly, the catalytic activity of acidic
fluoroantimonate IL was shown to be strong enough to conduct
the reactions even at 278 uC, and thus, by using 20 mol% of
catalyst, the desired kinetic isomers could be obtained as the
main products. Studies on the applications of superacidic
fluoroantimonate(V) IL 1 to other catalytic organic reactions are
currently underway in our laboratory.
6 For reviews, see: (a) P. Wasserscheid and W. Keim, Angew. Chem., Int.
Ed., 2000, 39, 3772–3789; (b) T. Welton, Chem. Rev., 1999, 99,
2071–2083.
7 In the case of chloroaluminate IL, 27Al NMR spectral studies showed
2
the predominance of Al2Cl7 anion in the mixure of [bmim]Cl
and AlCl3 in 1 : 2 molar ratio (i.e., 1 : 1 mixture of [bmim][AlCl4]
and AlCl3), see: S. J. Nara, J. R. Harjani and M. M. Salunkhe, J. Org.
Chem., 2001, 66, 8616–8620. Similar to this, FAB-MS analysis of 1
2
clearly showed the existence of Sb2F11 anion as the main acidic
component (see ESI{).
8 In their previous study,2 Fujiwara et al. assigned the (Z)-isomers of
trisubstituted alkenes obtained in their work as the kinetic products.
However, our MP2/6-31G* calculation results5b of both stereoisomers
clearly indicate that the (Z)-isomers obtained in this study are
thermodynamically favored products. In addition, Tsuchimoto et al.’s4
and our experimental data5 signify that the (Z)-isomers are thermo-
dynamically-controlled products rather than kinetically-controlled ones.
9 The non-stereoselectivity of para-isomers may be due to the similar
energy levels of E/Z-isomers.
This work was supported by grants KRF-2005-005-J11901
(MOEHRD), R01-2006-000-10426-0 (KOSEF), and R11-2005-
008-00000-0 (SRC program of MOST/KOSEF).
10 Using 5 mol% of 1 at low temperature, the prolonged reaction times
were needed to complete the reaction, which resulted in lower (E)/(Z)-
ratios, due to Lewis acid-catalyzed isomerization.
11 Yields could be improved with prolonged reaction time. However,
lower (E)/(Z)-ratios were observed due to Lewis acid-catalyzed
isomerization.
Notes and references
1 For a review, see: C. Nevado and A. M. Echavarren, Synthesis, 2005,
167–182 and references therein.
3484 | Chem. Commun., 2007, 3482–3484
This journal is ß The Royal Society of Chemistry 2007