Synthesis of 1-indanones by intramolecular Friedel-Crafts reaction of 3-arylpropionic acids catalyzed by Tb(OTf)3

Article abstract of DOI:10.1016/j.tetlet.2003.12.085

Intramolecular Friedel-Crafts acylation reaction of 3-arylpropionic acids was efficiently catalyzed by Tb(OTf)₃ at 250°C to give 1-indanones. Even deactivated 3-arylpropionic acids with halogen atoms on the aromatic ring can be cyclized in moderation to good yields.

Full text of DOI:10.1016/j.tetlet.2003.12.085

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1741–1745
Synthesis of 1-indanones by intramolecular Friedel–Crafts
reaction of 3-arylpropionic acids catalyzed by Tb(OTf)3
Dong-Mei Cui, Chen Zhang, Masato Kawamura and Shigeru Shimada*
National Institute of Advanced Industrial Science and Technology (AIST),
Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
Received 7 November 2003; revised 12 December 2003; accepted 15 December 2003
Abstract—Intramolecular Friedel–Crafts acylation reaction of 3-arylpropionic acids was efficiently catalyzed by Tb(OTf)3 at 250 °C
to give 1-indanones. Even deactivated 3-arylpropionic acids with halogen atoms on the aromatic ring can be cyclized in moderation
to good yields.
Ó 2003 Elsevier Ltd. All rights reserved.
1-Indanones are important synthetic intermediates for
pharmaceuticals1, ligands of olefin polymerization cat-
alysts2 and discotic liquid crystals.3 Among various
methods used for preparation of 1-indanones,4 intra-
molecular Friedel–Crafts cyclization reaction of 3-aryl-
propionic acids or 3-arylpropionyl chlorides is one of
the most general and useful methods. The direct
dehydrative cyclization of 3-arylpropionic acids is less
easier than the cyclization via acid chlorides, but pref-
erable from environmental point of view because the
former, one-step reaction produces water as the only
by-product while the latter, two-step reaction produces
large amounts of toxic and corrosive by-products.
However, the direct cyclization has been performed by
using an excess of protic acids (often as solvents) such as
sulfuric acid,5 hydrogen fluoride,5 polyphosphoric acid,6
methanesulfonic acid (MSA)7 and a mixture of MSA
and P2O5,8 or Lewis acids such as AlCl3 and SnCl4,5 and
therefore forms a large amount of acid wastes after the
reaction. Recently it was reported that Y-faujasite-type
zeolite was an effective catalyst for dehydrative cycliza-
tion to form tricyclic ketones containing indanone
structure, although it was not very effective for the
synthesis of simple indanones.9 Here we report some
lanthanoid triflates, in particular Tb(OTf)3 are useful
catalysts for dehydrative cyclization of 3-arylpropionic
acids to form 1-indanones.10
We have recently reported Lewis acid-catalyzed cycli-
zation of 4-arylbutyric acids to form 1-tetralones.11 It is
known that formation of five-membered ring by
Friedel–Crafts cyclization is more difficult than that of
12
six-membered ring.5 Indeed, Bi(NTf2)3 and some lan-
thanoid triflates, which were effective for 1-tetralone
synthesis,11 were proved not to catalyze the cyclization
of 3-phenylpropionic acid (1a) under the conditions
suitable for 1-tetralone synthesis at 180 °C. Similar
results were reported for Nafion-H; it was effective for
the cyclization of 4-phenylbutyric acid and gave 1-tetra-
lone in 88–90% yields, while it did not catalyze the
cyclization of 3-phenylpropionic acid efficiently and
1-indanone was obtained only in 0–5% yields.13
Survey of reaction conditions revealed that the cycliza-
tion of 1a was highly influenced by reaction tempera-
ture, Lewis acid catalysts and concentration of 1a.
Bi(NTf2)3 afforded 1-indanone at 200 °C or higher
(Table 1, entries 1–5). However, considerable side
reactions took place and the yield of 1-indanone did not
exceed 30%. Then, catalytic performance of commer-
cially available Ga(OTf)3, In(OTf)3, lanthanoid triflates
and Hf(OTf)4 was examined at 240–250 °C (representa-
tive results are shown in Table 1). Ga(OTf)3, In(OTf)3,
Hf(OTf)4 and some lanthanoid triflates were not effec-
tive in this reaction, while 10 mol % of Pr(OTf)3,
Nd(OTf)3, Gd(OTf)3 and Tb(OTf)3 produced 1-inda-
none in 58–70% yield (Table 1, entries 10, 11, 14, and
Keywords: Indanone; Lewis acid; Friedel–Crafts reaction; Acylation;
Dehydration; Lanthanoid; Cyclization.
* Corresponding author. Tel.: +81-29-861-4588; fax: +81-29-861-4511;
e-mail: s-shimada@aist.go.jp
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.12.085

1742
D.-M. Cui et al. / Tetrahedron Letters 45 (2004) 1741–1745
Table 1. Cyclization of 3-arylpropionic acid in the presence of Lewis acid catalystsa
Lewis acid
+
CO2H
C6H5Cl
O
1a
O
2a
3a
Entry
Catalyst (mol %)
Temperature (°C)
Time (h)
Yield (%)b
3a
2a
1
Bi(NTf2)3 (5)
Bi(NTf2)3 (5)
Bi(NTf2)3 (5)
Bi(NTf2)3 (10)
Bi(NTf2)3 (1)
Ga(OTf)3 (5)
In(OTf)3 (5)
200
220
240
240
240
240
240
250
250
250
250
250
250
250
250
250
250
250
250
250
250
250
250
250
250
10
8
16
29
29
nd
nd
nd
nd
nd
0
2
3
8
4
6
Trace
24
5
12
2
6
3
12
7
3
nd
nd
4
8
Sc(OTf)3 (10)
Ce(OTf)3 (10)
Pr(OTf)3 (10)
Nd(OTf)3 (10)
Eu(OTf)3 (10)
Eu(NTf2)3 (10)
Gd(OTf)3 (10)
Tb(OTf)3 (10)
Tb(OTf)3 (10)
Tb(OTf)3 (5)
Tb(OTf)3 (1)
Tb(OTf)3 (5)
Tb(OTf)3 (5)
Dy(OTf)3 (10)
Yb(OTf)3 (10)
Lu(OTf)3 (10)
Hf(OTf)4 (5)
TfOH (15)
1
7
21
9
1
10
11
12
13
14
15
16c
17c
18c
19d
20e
21
22
23
24c
25c
3
70
66
14
10
nd
nd
11
8
2
1
44
25
1
1
65
58
1
1
93
95 (83)
28
Trace
Trace
0
1.5
4.5
2
Trace
0
40
0
2
0
1
11
nd
4
1
20
33
1
1.5
1.5
5
13
10
8
a The reaction was performed using 0.25 mmol of 1a in 2 mL of C6H5Cl in a sealed glass tube unless otherwise noted.
b GC yield using dodecane as an internal standard. Isolated yields are shown in parentheses. nd ¼ not determined.
c C6H5Cl (6 mL) was used as a solvent.
d Sulfolane (6 mL) was used as a solvent.
e Bu2O (6 mL) was used as a solvent.
15). Eu(NTf2)3, which was effective for intermolecular
Friedel–Crafts reaction using carboxylic acids as acyl-
ating agents,14 was not suitable for this reaction (Table
1, entry 13). Although some of 1a remained after the
reaction in most cases, considerable side reactions also
took place. One of the by-products was isolated and
identified to be 3a, an aldol condensation product of
2a.15 Therefore, we examined the effect of concentration
of 1a in order to suppress the self-condensation of 2a.
Generally lower concentration of 1a decreased the for-
mation of 3a when Pr(OTf)3, Nd(OTf)3, Gd(OTf)3 or
Tb(OTf)3 was used as a catalyst, while the degree of
improvement in the yield of 2a depended on the cata-
lysts. The highest yield of 2a was obtained when 0.04 M
C6H5Cl solution of 1a was heated at 250 °C in the
presence of 5 mol % of Tb(OTf)3 (Table 1, entry 17).
Lower amount (1 mol %) of catalyst was not enough to
complete the reaction (Table 1, entry 18) and other
solvents such as sulfolane and Bu2O completely stopped
the reaction (Table 1, entries 19 and 20). TfOH did not
effectively catalyze the cyclization of 1a (Table 1, entry
25). Preliminary study on catalyst recycling showed that
after the reaction at 250 °C in PhCl, Tb(OTf)3 was still
active (at least partially) and could be reused.16
Table
2
summarizes the scope and limitation
of Tb(OTf)3-catalyzed cyclization of 3-arylpropionic
acids.17;18 Substitution at a-position of aliphatic chain of
propionic acid retarded the cyclization, and required
longer reaction time and larger amount of catalysts
(Table 2, entries 1 and 3), while substitution at b-posi-
tion has little effect on the cyclization and 1-indanones
were obtained in good yields (Table 2, entries 2, 4 and
6). 3-Arylpropionic acids with electron-donating sub-
stituents on the aromatic ring generally afforded
1-indanones in good yields (Table 2, entries 5–10). In the
case of 1i and 1j, both of possible regio-isomers were
produced (Table 2, entries 8 and 9). It is noteworthy that
deactivated substrates, which have one or two halogen
atoms on the aromatic ring, were successfully cyclized to
give 1-indanones (Table 2, entries 11–13). However,
CF3-substituted 1o could not be cyclized efficiently
(Table 2, entry 14). The cyclization of indole derivative
1p proceeded in moderate yield (Table 2, entry 15).

D.-M. Cui et al. / Tetrahedron Letters 45 (2004) 1741–1745
Table 2. Synthesis of 1-indanones and a related cyclic ketonea
1743
2
2
R
R
Tb(OTf)3
CO H
2
1
R
250 ˚C
– H2O
1
R
H
O
2b - 2p
1b - 1p
Entry
1
Carboxylic acid
Tb(OTf)3 (mol %)
Reaction time (h)
8
Product
Yield (%)b
83 (99)
CO2H
Me
1b
2b
Me
10
O
Me
O
Me
CO2H
1c
1d
2c
2
3
5
4
88
52
CO2H
15
14
Ph
Ph
2d
O
Ph
Ph
O
CO H
1e
2
4
5
5
5
10
71
74
2e
CO2H
2
1f
2f
Me
Me
O
Me Me
Me
Me
Me
O
CO2H
6
5
3
91
1g
2g
Me
CO2H
1h
7
8
10
2
3
58
62
12
2h
MeO
MeO
MeO
O
CO2H
5
2iA
1i
O
OMe
2iB
O
MeO
CO2H
MeO
MeO
9
5
1
65
1j
2jA
2jB
MeO
O
O
OMe
5
MeO
MeO
(continued on next page)

1744
D.-M. Cui et al. / Tetrahedron Letters 45 (2004) 1741–1745
Table 2 (continued)
Entry
Carboxylic acid
Tb(OTf)3 (mol %)
5
Reaction time (h)
0.5
Product
Yield (%)b
72
MeO
MeO
MeO
CO2H
10
2k
1k
MeO
MeO
O
OMe
Cl
Cl
CO H
1l
2
2l
11
12
20
10
24
11
(49)
O
CO2H
CO2H
64 (73)
1m
1n
2m
2n
F
F
O
F
F
F
F
13
14
20
10
8
8
(46)
O
CO2H
1o
Trace
2o
F3C
F3C
O
CO2H
15
1p
5
3
2p
42
O
N
N
H
H
a The reaction was performed using 0.25 mmol of carboxylic acids in 6 mL of C6H5Cl in a sealed glass tube.
b Isolated yields. GC yields using dodecane as an internal standard are shown in parentheses.
3. For example, see: Sato, Y. Jpn. Kokai Tokkyo Koho 1998,
10298126;
Chem. Abstr. 1999, 130, 13852.
In summary, 1-indanones were efficiently synthesized by
the intramolecular Friedel–Crafts acylation reaction of
3-arylpropionic acids using catalytic amounts of
Tb(OTf)3 at 250 °C. Further studies to improve the
reaction efficiency at lower reaction temperature and on
recycling of the catalyst are underway.
4. For example, see: (a) Bhattacharya, A.; Segmuller, B.;
Ybarra, A. Synth. Commun. 1996, 26, 1775–1784; (b) De
Castro, C.; Primo, J.; Corma, A. J. Mol. Catal. A: Chem.
1998, 134, 215–222; (c) Gevorgyan, V.; Quan, L. G.;
Yamamoto, Y. Tetrahedron Lett. 1999, 40, 4089–4092; (d)
Rudler, H.; Denise, B. J. Mol. Catal. A: Chem. 2000, 154,
277–279; (e) Prakash, G. K. S.; Yan, P.; Torok, B.; Olah,
G. A. Catal. Lett. 2003, 87, 109–112; (f) Gagnier, S. V.;
Larock, R. C. J. Am. Chem. Soc. 2003, 125, 4804–4807; (g)
Fillion, E.; Fishlock, D. Org. Lett. 2003, 5, 4653, and
references cited therein.
Acknowledgements
This work was financially supported by New Energy and
Industrial Technology Development Organization
(NEDO). D.C. thanks NEDO for a postdoctoral fel-
lowship.
5. Johnson, W. S. Org. React. 1949, 2, 114–177.
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References and notes
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organic synthesis, see: Kobayashi, S.; Sugiura, M.; Kita-
gawa, H.; Lam, W. W. Chem. Rev. 2002, 102, 2227–2302.
11. Cui, D. M.; Kawamura, M.; Shimada, S.; Hayashi, T.;
Tanaka, M. Tetrahedron Lett. 2003, 44, 4007–4010.

D.-M. Cui et al. / Tetrahedron Letters 45 (2004) 1741–1745
1745
12. Picot, A.; Repicheta, S.; Le Roux, C.; Dubac, J.;
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13. (a) Yamato, T.; Hideshima, C.; Prakash, G. K. S.; Olah,
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filtered and concentrated under vacuum. The residue was
separated by column chromatography on silica gel (hex-
ane/EtOAc ¼ 5/1) to give 2c (32 mg, 88% yield).
18. All cyclic ketones reported in this paper are known
compounds. However, for some compounds NMR data
are not reported in the literature; 2k: 1H NMR
(499.1 MHz, CDCl3) d 2.65–2.71 (m, 2H), 3.02 (quasi t,
J ¼ 5:8 Hz, 2H), 3.85 (s, 3H), 3.94 (s, 3H), 4.04 (s, 3H),
6.68 (s, 1H); 13C NMR (125.4 MHz, CDCl3) d 25.71,
37.20, 56.29, 61.41, 61.94, 103.78, 122.86, 140.63, 151.55,
153.32, 159.72, 203.31. 2m: 1H NMR (499.1 MHz, CDCl3)
d 2.73–2.78 (m, 2H), 3.12 (quasi t, J ¼ 5:7 Hz, 2H), 7.31
(td, J ¼ 8:5, 2.4 Hz, 1H), 7.40 (dd, J ¼ 7:5, 2.4 Hz, 1H),
7.45 (dd, J ¼ 8:5, 4.4 Hz, 1H); 13C NMR (125.4 MHz,
CDCl3) d 25.28, 37.00, 109.54 (d, J ¼ 22 Hz), 122.33 (d,
J ¼ 24 Hz), 128.03 (d, J ¼ 8 Hz), 138.79 (d, J ¼ 7 Hz),
150.47, 162.28 (d, J ¼ 248 Hz), 206.02. 2n: 1H NMR
(499.1 MHz, CDCl3) d 2.73–2.75 (m, 2H), 3.13 (quasi t,
J ¼ 5:3 Hz, 2H), 7.28 (dd, J ¼ 9:5, 6.7 Hz, 1H), 7.52 (quasi
t, J ¼ 8:1 Hz, 1H); 13C NMR (125.4 MHz, CDCl3) d 25.46
(d, J ¼ 2 Hz), 36.51, 111.77 (dd, J ¼ 18, 2 Hz), 114.94 (d,
J ¼ 22 Hz), 133.47 (dd, J ¼ 5, 2 Hz), 150.68 (dd, J ¼ 251,
15 Hz), 151.63 (dd, J ¼ 8, 2 Hz), 156.18 (dd, J ¼ 259,
14. Kawamura, M.; Cui, D. M.; Hayashi, T.; Shimada, S.
Tetrahedron Lett. 2003, 44, 7715–7717.
15. A small amount of Z-isomer of 3a was also produced. The
structure of 3a was unambiguously determined by X-ray
analysis, which showed 3a co-crystallized with a small
amount of its Z-isomer. Crystallographic data (excluding
structure factors) for the structure in this paper, have been
deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC-
223357. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (Fax: +44(0)-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk).
16. After the reaction, the catalyst was recovered by extraction
with water. Evaporation of water afforded crystalline
nonahydrate [Tb(H2O)9](OTf)3, whose structure was
unambiguously determined by single crystal X-ray anal-
ysis.19Further drying under vacuum gave Tb(OTf)3 (may
be partially hydrated) as white powder in ca. 90%
recovery.
17. Typical procedure: A mixture of Tb(OTf)3 (7 mg), 3-phen-
ylbutyric acid 1c (41 mg, 0.25 mmol) and C6H5Cl (6 mL) in
a sealed glass tube was heated in an oil bath at 250 °C for
4 h. Then the mixture was diluted with EtOAc (10 mL) and
washed with a saturated NaHCO3 solution (10 mL). The
organic layer was separated and the aqueous layer was
extracted with EtOAc (10 mLꢀ3). The combined organic
layer was washed with brine (15 mL), dried over MgSO4,
1
15 Hz), 204.57. 2p: H NMR (499.1 MHz, CDCl3) d 3.02–
3.04 (m, 2H), 3.11–3.14 (m, 2H), 7.19 (quasi t, J ¼ 8:5 Hz,
1H), 7.40 (quasi t, J ¼ 8:5 Hz, 1H), 7.49 (d, J ¼ 8:5 Hz,
1H), 7.71 (d, J ¼ 8 Hz, 1H), 9.03 (br s, 1H); 13C
NMR (125.4 MHz, CDCl3) d 20.14, 41.02, 113.50,
120.73, 121.59, 123.59, 127.39, 138.70, 143.81, 147.28,
194.64.
19. (a) Harrowfield, J. M.; Kepert, D. L.; Patrick, J. M.;
White, A. H. Aust. J. Chem. 1983, 36, 483–492; (b)
Chatterjee, A.; Maslen, E. N.; Watson, K. J. Acta
Crystallogr., Sect. B. 1988, 44, 381–386.