Iron(III)-catalyzed hydroarylation of propiolic acid with activated arenes

Article abstract of DOI:10.1016/j.tetlet.2009.11.130

FeCl₃/AgOTf-catalyzed hydroarylation of propiolic acid with electron-rich arenes such as mesitylene, tetramethylbenzene, and pentamethylbenzene in trifluoroacetic acid proceeded to give 3-arylpropenoic acids in moderate to high yields. The same reactions with anisole and 1,4-dimethoxybenzene afforded double hydroarylation products, 3,3-diarylpropionic acids.

Full text of DOI:10.1016/j.tetlet.2009.11.130

Tetrahedron Letters 51 (2010) 761–763
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Tetrahedron Letters
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Iron(III)-catalyzed hydroarylation of propiolic acid with activated arenes
*
Takuya Hashimoto, Takayuki Izumi, Md. Shahajahan Kutubi, Tsugio Kitamura
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi, Saga 840-0502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
FeCl3/AgOTf-catalyzed hydroarylation of propiolic acid with electron-rich arenes such as mesitylene,
tetramethylbenzene, and pentamethylbenzene in trifluoroacetic acid proceeded to give 3-arylpropenoic
acids in moderate to high yields. The same reactions with anisole and 1,4-dimethoxybenzene afforded
double hydroarylation products, 3,3-diarylpropionic acids.
Received 6 October 2009
Revised 25 November 2009
Accepted 30 November 2009
Available online 2 December 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Iron(III) chloride
Silver triflate
Hydroarylation
Propiolic acid
Trifluoroacetic acid
Recently much attention has been paid to direct C–H bond func-
tionalization in organic chemistry because the direct functionaliza-
tion has several advantages compared with conventional synthetic
methods requiring prefunctionalization of C–H bonds.1 As one of
aromatic C–H bond functionalizations, hydroarylation of alkynes
is an atom-economic and valuable reaction for preparing aromatic
alkenes directly from arenes and alkynes.2 Noble and rare metals
such as palladium and platinum have been used as catalysts for
the hydroarylation reaction.3–5 For example, we have reported that
the hydroarylation reaction of propiolic acids proceeds effectively
in the presence of palladium and platinum catalysts to give cin-
namic acid derivatives. However, such noble metals are rare,
expensive, and not economical. If the noble catalysts could be
replaced by abundant and economical metals, the hydroarylation
reactions would be a more valuable method for synthesis of aro-
matic alkenes.
Iron is one of the most abundant metals on earth, an inexpen-
sive and environmentally benign metal, and has been applied to
organic synthesis as catalysts.6 However, there are only two exam-
ples of the hydroarylation reaction of alkynes with the most versa-
tile iron catalyst.7 The reported procedures include iron(III)
chlorides (FeCl3 and FeCl3Á6H2O) as catalysts and electron-rich aro-
matic alkynes as substrates.7 In the hydroarylation of an electron-
deficient propiolic acid, it is necessary to use a more reactive iron
catalyst in order to cause the hydroarylation reaction effectively.
Thus, we decided to use iron(III) chlorides activated with silver
triflate (AgOTf). Here we report a convenient, simple, and more
reactive catalytic system consisting of FeCl3 and AgOTf for the
hydroarylation of propiolic acid.
Since we have found that trifluoroacetic acid (TFA) is a good sol-
vent for hydroarylation reactions,4c–f the iron-catalyzed hydroary-
lation of propiolic acid was carried out in a mixed solvent of TFA
and 1,2-dichloroethane (DCE). First, we optimized the conditions
of hydroarylation of propiolic acid (2) with mesitylene (1a) giving
3-(2,4,6-trimethylphenyl)propenoic acid (3a) (Scheme 1). For the
iron catalyst, FeCl3, FeCl3Á6H2O, FeCl3/AgOTf, and FeCl3Á6H2O/AgOTf
were examined. The results are given in Table 1.
Even in the case of FeCl3 only, the hydroarylation reaction pro-
ceeded to afford 3a in 62% yield (entry 1). The addition of 3 equiv of
AgOTf significantly improved the hydroarylation reaction, which
proceeded almost quantitatively to give 3a in 99% yield (entry
2).8 However, a lower loading of the catalyst or AgOTf resulted in
poor yields of 3a (entries 3 and 4). Interestingly, selective forma-
tion of the trans isomer of 3a was observed in the hydroarylation
reaction with FeCl3/AgOTf catalyst. This behavior is different from
that of the hydroarylation reaction with Pd and Pt catalysts.5 We
also examined the reaction with FeCl3Á6H2O catalyst. However, it
was found that FeCl3Á6H2O catalyst was not effective under the
present conditions even in the presence of AgOTf (entries 5–8).
Fe catalyst
CO2H
+
CO2H
TFA, DCE
60 oC, 15 h
1a
2
3a
* Corresponding author. Tel.: +81 952 28 8550; fax: +81 952 28 8548.
E-mail address: kitamura@cc.saga-u.ac.jp (T. Kitamura).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.11.130

762
T. Hashimoto et al. / Tetrahedron Letters 51 (2010) 761–763
Table 1
Ar
FeCl3/AgOTf
Hydroarylation of propiolic acid (2) with mesitylene (1a) in the presence of iron
+
CO2H
Ar
H
catalystsa
CO2H
TFA, DCE
60 oC, 15 h
3
Entry
Catalyst
(mol %)
Yieldb (%)
E/Zc
1
2
1
2
3
4
5
6
7
8
FeCl3
FeCl3/AgOTf
FeCl3/AgOTf
FeCl3/AgOTf
(20)
62
99
38
46
15
12
22
32
3
71/29
66/34
66/34
72/28
10/90
16/84
11/89
14/86
12/88
58/42
—
Scheme 2.
(20/60)
(10/30)
(20/20)
(20)
(10/30)
(20/20)
(20/60)
(20/60)
(20/60)
(20/60)
FeCl3Á6H2O
The addition of MS 4A retarded the reaction (entry 9). Since the
reactions with AgOTf only and without any catalysts do not
proceed efficiently,4e FeCl3 is considered to be an actual catalyst
for hydroarylation. Replacement of DCE by nitromethane as the
co-solvent decreased the product yield to 88% (entry 10). When
the reaction was conducted in nitromethane only, no hydroaryla-
tion products were formed (entry 11). This result differs from the
result reported by Lu and co-workers.7b
On the basis of the optimization of the reaction conditions, the
scope of this hydroarylation with various arenes was explored
(Schemes 2 and 3).8 The results are given in Table 2. For elec-
tron-rich arenes such as pentamethylbenzene (1b) and 2,4,6-tri-
FeCl3Á6H2O/AgOTf
FeCl3Á6H2O/AgOTf
FeCl3Á6H2O/AgOTf
FeCl3Á6H2O/AgOTf
FeCl3/AgOTf
9d
10e
11f
88
0
FeCl3/AgOTf
a
Reaction conditions: catalyst, 1a (4 mmol), 2 (2 mmol), TFA (0.5 mL), and DCE
(0.5 mL) at 60 °C for 15 h.
b
Isolated yield.
Determined by 1H NMR.
c
d
Molecular sieves 4A (0.126 g) were added.
TFA (0.5 mL) and nitromethane (0.5 mL) were used as solvents.
Nitromethane (1 mL) was only used as a solvent.
e
f
Table 2
FeCl3/AgOTf-catalyzed hydroarylation of propiolic acid (2) with various arenesa
Entry
1
Arene 1
TFA (mL)
DCE (mL)
Product 3
Yieldb (%)
92
E/Zc
H
H
CO2H
CO2H
1
2
70/30
3b
3b
1b
1c
2
3
0.5
0.5
0.5
0.5
28
7
69/31
68/32
H
CO2H
3d
3e
1d
4d
5
1d
1
1
1
3d
11
9
69/31
63/37
H
CO2H
0.5
1e
H
CO2H
3f
6
0.5
0.5
48
70/30
1f
OH
OH
H
CO2H
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
17
22
76
72/28
—
3g
1g
Br
Br
MeO
H
MeO
1h
3h
2
CO2H
H
MeO
1i
OMe
MeO
Me
—
3i
2
CO2H
OMe
H
Me
1j
OMe
10
0.5
0.5
58
—
3j
2
CO2H
OMe
a
b
c
Reaction conditions: FeCl3 (0.4 mmol), AgOTf (1.2 mmol), 1 (4 mmol), 2 (2 mmol), TFA, and DCE at 60 °C for 15 h.
Isolated yield.
Determined by 1H NMR.
At refluxing temperature.
d

T. Hashimoto et al. / Tetrahedron Letters 51 (2010) 761–763
763
FeCl3/AgOTf
lyst system. Especially, in the case of electron-rich arenes, the iron-
catalyzed hydroarylation proceeded well and gave cinnamic acids
in moderate to high yields. Even FeCl3 only is capable of catalyzing
the hydroarylation reaction, but the addition of AgOTf enhances
the reactivity. Further investigation of the iron-catalyzed hydro-
arylation of alkynes is now in progress.
Ar
+
CO2H
Ar
H
2
CO2H
TFA, DCE
60 oC, 15 h
1
2
4
Scheme 3.
References and notes
FeCl3 + 3AgOTf
3AgCl
Fe(OTf)3
CO2H
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Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698–1712; (c) Kakiuchi, F.; Chatani,
N. Adv. Synth. Catal. 2003, 345, 1077–1101; (d) Kakiuchi, F.; Murai, S. In
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Berlin, 1999; pp 47–79; (e) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97,
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Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047–1055; (j) Kakiuchi, F.; Kochi, T.
Synthesis 2008, 3013–3039.
Ar
CO2H
H
(TfO)3Fe
(TfO)3Fe
(TfO)3Fe
Fe(OTf)3
CO2H
H
O
O
C
OH
O
or
C
C C
HC
C
HC C C
Ar
OH
OH
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A. M. Synthesis 2005, 167–182.
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Chem. Soc. 2003, 125, 12102–12103; (e) Jia, C.; Piao, D.; Kitamura, T.; Fujiwara,
Y. J. Org. Chem. 2000, 65, 7516–7522; (f) Lu, W.; Jia, C.; Kitamura, T.; Fujiwara, Y.
Org. Lett. 2000, 2, 2927–2930; (g) Oyamada, J.; Jia, C.; Fujiwara, Y.; Kitamura, T.
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C.; Fujiwara, Y. Bull. Chem. Soc. Jpn. 2003, 76, 1889–1895; (i) Kotani, M.;
Yamamoto, K.; Oyamada, J.; Fujiwara, Y.; Kitamura, T. Synthesis 2004, 1466–
1470.
4. Pt: (a) Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett. 2003, 5, 1055–1058; (b)
Pastine, S. J.; Youn, S. W.; Sames, D. Tetrahedron 2003, 59, 8859–8868; (c)
Oyamada, J.; Kitamura, T. Tetrahedron Lett. 2005, 46, 3823–3827; (d) Oyamada,
J.; Kitamura, T. Chem. Lett. 2005, 34, 1430–1431; (e) Oyamada, J.; Kitamura, T.
Tetrahedron 2007, 63, 12754–12762; (f) Oyamada, J.; Hashimoto, T.; Kitamura J.
Organomet. Chem. 2009, 694, 3626–3632.
5. Pd and Pt: (a) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y.
Science 2000, 287, 1992–1995; (b) Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.;
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Jia, C.; Kitamura, T.; Fujiwara, Y. J. Synth. Org. Chem. Jpn. 2001, 59, 1052–1061.
6. Bolm, C.; Legros, J.; Paih, J. L.; Zani, L. Chem. Rev. 2004, 104, 6217–6254.
7. (a) Zotto, C. D.; Wehbe, J.; Virienx, D.; Campagne, J.-M. Synlett 2008, 2033–
2035; (b) Li, R.; Wang, S. R.; Lu, W. Org. Lett. 2007, 9, 2219–2222.
8. General procedure for FeCl3/AgOTf-catalyzed hydroarylation of propiolic acid: After
a mixture of FeCl3 (0.4 mmol) and AgOTf (1.2 mmol) in TFA and DCE was stirred
at room temperature for 10 min, arene (4 mmol) and propiolic acid (2 mmol)
were added and then the mixture was stirred at 60 °C for 15 h. The reaction
mixture was poured into water, neutralized with NaHCO3, and washed with
ether. The ethereal layer was extracted with 2 M NaOH. The aqueous layer was
washed with ether, acidified with HCl (ca. 36%), and extracted with CH2Cl2. The
organic layer was dried over anhydrous Na2SO4 and concentrated under
reduced pressure to give cinnamic acids as solids. The products were identified
by spectral data (1H and 13C NMR) and the data were compared with those in
the literature. Representative spectral data are as follows: Compound 3a (a
mixture of E and Z isomers):4f 1H NMR (300 MHz, CDCl3) d 2.16 (s, CH3), 2.26 (s,
CH3), 2.27 (s, CH3), 2.31 (s, CH3), 6.03 (d, J = 16 Hz, @CH), 6.10 (d, J = 12 Hz,
@CH), 6.82 (s, ArH), 6.88 (s, ArH), 7.08 (d, J = 12 Hz, @CH), 7.91 (d, J = 16 Hz,
@CH), 10.80 (br s, CO2H); 13C NMR (75 MHz, CDCl3) d 20.00, 20.89, 122.07,
127.89, 131.99, 134.44, 136.92, 146.28, 171.10. Compound 3h:10 1H NMR
(300 MHz, CDCl3) d 3.01 (d, J = 7.5 Hz, 2H, CH2), 3.75 (s, 6H, OCH3), 4.42 (t,
J = 7.5 Hz, 1H, CH), 6.80 (d, J = 9 Hz, 2H, ArH), 7.11 (d, J = 9 Hz, 2H, ArH), 8.71 (br
s, 1H, CO2H); 13C NMR (75 MHz, CDCl3) d 40.72, 45.10, 55.20, 113.99, 128.47,
135.78, 158.17, 177.94.
Ar
H
H
Scheme 4.
methylphenol (1f) the hydroarylation proceeded well (entries 1
and 6), but for moderately activated or unactivated arenes the
reaction gave low yields of the hydroarylation products 3 (entries
2–5). On the other hand, anisole (1g), 1,4-dimethoxybenzene
(1h), and 4-methoxytoluene (1i) underwent double hydroarylation
to give 3,3-diarylpropionic acids 4 (entries 7–9).
In the FeCl3/AgOTf-catalyzed hydroarylation reaction of propi-
olic acid, there exist the following characteristic results to consider
the reaction mechanism. (1) The hydroarylation reaction catalyzed
by FeCl3/AgOTf in TFA provided trans-cinnamic acids as the major
products. This strongly contrasts with the reaction catalyzed by
platinum compounds where the cis-cinnamic acids are formed
selectively.5 (2) In the present reaction, isomerization of cis to
trans-cinnamic acids is not important because the hydroarylation
with FeCl3Á6H2O under similar conditions gives cis-cinnamic acid
3a as the major isomer. (3) Activated, electron-rich arenes show
high reactivity.
A proposed mechanism is shown in Scheme 4. First, FeCl3 reacts
with AgOTf to generate a highly cationic, reactive Fe(OTf)3, which
interacts with propiolic acid to form a vinyl cation. Since a primary
open vinyl cation is very unstable and the formation is not possi-
ble,9 Fe(OTf)3 should coordinate with the oxygen atom acid and
activate the propiolic acid. Formation of a bridged vinyl cation is
possible but it may be ruled out by judging from the major forma-
tion of the trans isomer of cinnamic acids. The resulting vinyl cat-
ion undergoes electrophilic aromatic substitution with an electron-
rich arene and finally generates a product by protonation. At the
same time, regeneration of Fe(OTf)3 is concomitant and completes
the catalytic cycle.
9. (a) Rappoport, Z.; Stang, P. J. Dicoordinated Carbocations; John Wiley & Sons:
Chichester, 1997; (b) Stang, P. J.; Rappoport, Z.; Hanack, M.; Subramanian, L. R.
Vinyl Cations; Academic Press: New York, 1979.
10. Bergmann, F.; Weizmann, M.; Dimant, E.; Patai, J.; Szmuskowics, J. J. Am. Chem.
Soc. 1948, 70, 1612–1617.
In conclusion, we have demonstrated that iron-catalyzed
hydroarylation of propiolic acid with various arenes in TFA. The
reaction proceeded efficiently in the presence of FeCl3/AgOTf cata-