Intramolecular Friedel-Crafts reaction of indoles with carbonyl groups: A simple synthesis of 3- and 4-substituted β-carbolin-1-ones

Article abstract of DOI:10.1055/s-2008-1072613

The intramolecular Friedel-Crafts reaction of indole-2-carboxylic acid β-oxoamides catalyzed by trifluoroacetic acid or InCl₃, is a convenient method for the synthesis of 3-aryl-, 4-aryl-, and 4-alkyl-β-carbolin-1-ones. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1072613

LETTER
1309
Intramolecular Friedel–Crafts Reaction of Indoles with Carbonyl Groups:
A Simple Synthesis of 3- and 4-Substituted b-Carbolin-1-ones
S
ynthesis of 3- an
a
d
4-Substi
f
tuted
b
-C
f
arbolin-
a
1-one
s
ella Cincinelli, Sabrina Dallavalle,* Lucio Merlini
Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133, Milano, Italy
Fax +39(02)50316801; E-mail: sabrina.dallavalle@unimi.it
Received 28 January 2008
R
R4
Abstract: The intramolecular Friedel–Crafts reaction of indole-2-
carboxylic acid b-oxoamides catalyzed by trifluoroacetic acid or
InCl3, is a convenient method for the synthesis of 3-aryl-, 4-aryl-,
EDC, HOBt
THF, r.t., N2
COOH
+
NH2
R2
N
R3
HO
1
2
and 4-alkyl-b-carbolin-1-ones.
R1
R2
R3
R4
Key words: heterocycles, indoles, ring closure, Friedel–Crafts re-
action, b-carbolinones
1a OMe OMe Me
1b OMe Me
1c OMe OMe Bz
2a Ph
H
2b 4-OH-Ph
2c 3-OH-Ph
2d Me
The b-carbolin-1-one nucleus occurs in natural products,1
and some derivatives show significant biological activi-
ty.2 As part of a research program aimed at preparing
some 3-aryl- and 4-aryl-b-carbolin-1-ones we became in-
terested in developing an efficient synthetic strategy for
these compounds.
HO
R4
R1
IBX, EtOAc, 80 °C (3a,e,g)
NH
PCC, CH2Cl2, 40–50 °C (3b–d)
R2
N
R3
O
3
Recently, some 3-aryl-b-carbolin-1-ones displaying anti-
tumor activity have been synthesized3 from non-indole
starting materials. As for 4-aryl-b-carbolin-1-ones, only
one example of synthesis of this class of compounds,
based on an intramolecular cycloaddition–elimination re-
action of 2(1H)-pyrazinones, has been reported, to the
best of our knowledge, in literature.4
O
R4
R4
R1
NH
O
R1
R2
NH
O
TFA
MeCN, 80 °C
R2
N
R3
N
R3
To design a more straightforward route to these com-
pounds, an obvious approach appeared to be the intramo-
lecular Friedel–Crafts (FC) reaction of the appropriate
indole-2-carboxylic acid b-oxoamides. The intermolecu-
lar FC condensation of indoles with aldehydes and ke-
tones for the preparation of bis(1H-indol-3-yl)alkanes is
well documented,5 with a plethora of examples,6 whereas
only a few cases of intermolecular monoalkylation with
ketones have been mentioned.7
5
4
(for R1–R4 of 3–5, see Table 1;
3f was converted into 3g with (Boc)2, K2CO3 in DMF)
Scheme 1
Herein we report a short and efficient synthesis of a series
of 3-aryl-, 4-aryl-, and 4-alkyl-b-carbolin-1-ones, that
was achieved using this neglected, yet simple reaction.
Even less exploited appeared the intramolecular FC reac-
tion. An accurate perusal of the literature showed that this
method has been almost completely neglected. In the re-
cent years several approaches to intramolecular annula-
tion of indoles, such as Michael addition to enones8,9 or
Pd-catalyzed allylic alkylation,8,10 have been devised. On
the contrary, only two old examples of the simple in-
tramolecular FC reaction with carbonyl compounds exist
in the literature,11,12 so that it has not even been mentioned
in the most recent review.8
For the synthesis of 4-aryl-b-carbolin-1-ones 5, the appro-
priate 2-indolecarboxylic acids 1a–c were activated with
EDC and N-hydroxybenzotriazole (HOBt) and were cou-
pled, in high yield, with easily available 2-amino alcohols
2a–d (Scheme 1, Table 1).
The intermediate hydroxyamides 3a and 3e were oxidized
to the corresponding ketoamides 4a and 4e with excellent
yields, using 2-iodoxybenzoic acid (IBX).13 Only when a
phenol ring (that we required) was linked to the amino al-
cohol (compounds 3b–d), low yields were obtained, most
probably due the sensitivity of the phenol ring to this oxi-
dant. The use of PCC improved the yield of the desired ke-
tones, but the best yields were restored when the phenolic
OH was selectively protected with Boc with respect to the
alcohol (see 4g).
SYNLETT 2008, No. 9, pp 1309–1312
x
x.
x
x.
2
0
0
8
Advanced online publication: 07.05.2008
DOI: 10.1055/s-2008-1072613; Art ID: G04108ST
© Georg Thieme Verlag Stuttgart · New York

1310
R. Cincinelli et al.
LETTER
R1
R2
Table 1 Yields for the Synthesis of Compounds 3–5
Entry R1 R2 R3 R4
NHR4
EDC, HOBt
THF, r.t., N2
COOH
+
HO
Yield (%)
N
R3
R5
1
6
3
4
5
a
b
c
d
e
f
OMe OMe Me Ph
63
88
81
96
88
30
25
10
63a
88
47
14
66
44
R1
R2
R3
R4
R5
OMe OMe Me 4-HOC6H4
OMe OMe Me 3-HOC6H4
1a
1d
1e
OMe
OMe
H
OMe
OMe
H
Me
H
NAa
6a
H
Ph
H
6b Bn
OMe
H
Me 4-HOC6H4
R4
OH
R1
R2
80b 98
87
IBX, DMSO, r.t., N2
OMe OMe Me Me
N
R5
OMe OMe Bn 4-HOC6H4
OMe OMe Bn 4-BocOC6H4
N
R3
O
7
g
86
99
CHO
R5
h
OMe OMe
H
4-HOC6H4
52
R1
R2
HN
O
a The yield increased to 69% using InCl3 as a catalyst.
b Yield for the coupling reaction with 5,6-dimethoxy-2-indolecarbox-
ylic acid; methylation of the NH with MeI and K2CO3 was performed
on the amide.
N
H
8
R5
TFA, MeCN, reflux
(for 8c)
R1
R2
N
R4
The crucial cyclization step was obtained with TFA in ac-
etonitrile at 80 °C. In some cases a high yield was ob-
tained. Here the increased nucleophilicity of the indole
ring due to activation by the methoxy substituents might
have played an important role.14 This observation is con-
sistent with the increase of yield from 3d to 3b. Based on
recent work8 on the use of indium salts as mild Lewis ac-
ids in the promotion of Friedel–Crafts-like reactions on
indoles, we repeated the cyclization of 3a using indium
trichloride instead of TFA. Cyclization to 4a was obtained
with a slightly improved yield (69% vs. 63%).
O
N
R3
9
(for R1–R5 of 7–9, see Table 2; NA = 2-naphthylmethyl)
Scheme 2
Table 2 Yields for the Synthesis of Compounds 7 and 9
Entry
R1
R2
R3
R4 R5 Yield (%) Yield (%)
7
9
All the reactions were performed on N-alkyl indoles. To
ascertain that the reaction could be used for preparing N-
unsubstituted indoles, a suitable acid-resistant protecting
group was found in the benzyl group. This group was re-
moved after the cyclization using AlCl3, a reagent that did
not interfere with the double bond in the b-carbolinone
ring (see 5h).
a
b
c
OMe OMe Me
OMe OMe Me
H
Ph 90a
65
7
Bn
H
H
92a
OMe OMe
H
Ph 90
Ph 88
41b
28
d
H
H
NAc
H
a Yield for the coupling reaction with the corresponding 5,6-
dimethoxy-2-indolecarboxylic acid; methylation of the NH with MeI
and K2CO3 was performed on the amide.
A similar scheme was followed for the synthesis of 3-aryl-
b-carbolin-1-ones 9a,c,d and for the unsubstituted 9b
(Scheme 2, Table 2).
b Yield for the reaction from 8c to 9c.
c 2-Naphthylmethyl.
Interestingly, the aldehydes that formed, except for the N-
unsubstituted indole 8c, spontaneously cyclized. It hap-
pened most likely because of their sensitivity to the acidi-
ty of IBX or its reduction products. The possibility that the
acidity of the hypervalent iodine oxidants could induce
further reactions has been recently highlighted.15 This be-
havior allowed us to obtain a good yield of 3-aryl-b-car-
bolin-1-ones in just two steps from readily available
starting materials.
In conclusion, we have developed a short and efficient
synthesis of b-carbolin-1-ones based on the intramolecu-
lar Friedel–Crafts reaction of indoles with carbonyl
groups.17 This procedure allows for the introduction of
various aryl and alkyl substituents in the 3- and 4-posi-
tions of the b-carbolin-1-one ring. It has the advantage of
using simple reactants and favorable reaction conditions
and it does not require air-sensitive organometallic re-
agents and strictly anhydrous solvents. Extension to other
substrates to further investigate the scope and limitations
of this annulation process, as well as application of this
method to the synthesis of natural products or analogues,
are in progress.
These results indicate that this method is competitive with
the existing syntheses of b-carbolinones16 and is likely the
method of choice in the case of 3- or 4-substituted com-
pounds, and of products with activated indole nuclei.
Synlett 2008, No. 9, 1309–1312 © Thieme Stuttgart · New York

LETTER
Synthesis of 3- and 4-Substituted b-Carbolin-1-ones
1311
(16) Harris, J. M.; Padwa, A. Org. Lett. 2003, 5, 4195; and
Acknowledgment
references quoted therein.
This work was supported by the University of Milano (FIRST
funds).
(17) General Procedure for the Synthesis of Hydroxyamides
3 and 7: The appropriate amino alcohol 2 (3 mmol) was
dissolved in anhyd THF (12 mL) and then EDC (3 mmol),
HOBt (3 mmol) and the corresponding indole-2-carboxylic
acid (2 mmol) were added sequentially at 25 °C. After
stirring overnight at r.t., evaporating the solvent, pouring the
product into sat. aq NaHCO3, extracting with EtOAc,
washing with 1 N HCl, sat. aq NaHCO3, brine, drying over
Na2SO4 and concentrating the combined extract gave the
amide.
References and Notes
(1) (a) Jimènez, C.; Quiñoà, E.; Adamczeski, M.; Hunter, L. M.;
Crews, P. J. Org. Chem. 1991, 56, 3403. (b) Larsen, L. K.;
Moore, R. E.; Patterson, G. M. L. J. Nat. Prod. 1994, 57,
419.
(2) (a) Veale, C. A.; Damewood, J. R.; Steelman, G. B.; Bryant,
C.; Gomes, B.; Williams, J. J. Med. Chem. 1995, 38, 86.
(b) Doyle, T. W.; Balitz, D. M.; Grulich, R. E.; Nettleton, D.
E.; Gould, S. J.; Tann, C.; Moews, A. E. Tetrahedron Lett.
1981, 22, 4594. (c) Wu, J.-P.; Wang, J.; Abeywardane, A.;
Andersen, D.; Emmanuel, M.; Gautschi, E.; Goldberg, D. R.;
Kashem, M. A.; Lukas, S.; Mao, W.; Martin, L.; Morwick,
T.; Moss, N.; Pargellis, C.; Patel, U. R.; Patnaude, L.; Peet,
G. W.; Skow, D.; Snow, R. J.; Ward, Y.; Werneburg, B.;
White, A. Bioorg. Med. Chem. Lett. 2007, 17, 4664.
(3) Wang, S.; Dong, Y.; Wang, X.; Hu, X.; Liu, J. O.; Hu, Y.
Org. Biomol. Chem. 2005, 3, 911.
General Procedure for the Synthesis of Ketoamides
4a,e,g, and 8c: A suspension of the appropriate amide 3 or
7c (0.45 mmol) in EtOAc (6 mL) was added with IBX (1.35
mmol), then immersed in an oil bath set to 80 °C and stirred
vigorously open to the atmosphere. After 2.5 h (TLC
monitoring) the reaction was cooled to r.t. and filtered
through a medium glass frit. The filter cake was washed with
EtOAc–CH2Cl2 (50:50, 2 × 6 mL) and the combined filtrates
were concentrated to yield the product.
General Procedure for the Synthesis of Ketoamides 4b–
d: To a well-stirred suspension of the appropriate amide 3 (2
mmol) in anhyd CH2Cl2 (10 mL) was added PCC (4 mmol)
and the mixture was stirred at 40–50 °C, under nitrogen, for
8 h. Silica gel was added, the solvent evaporated and the
residue was purified by flash chromatography (CH2Cl2–
acetone, 90:10).
General Procedure for the Synthesis of b-Carbolin-1-
ones 5 and 9c: Trifluoroacetic acid (0.6 mmol) was added to
a suspension of the appropriate ketoamide 4 or 8c (0.4
mmol) in MeCN (6 mL) and the mixture was refluxed for 16
h. Evaporating the solvent, extracting with EtOAc, washing
with sat. aq NaHCO3, drying over Na2SO4 and concentrating
the extract gave a crude product that was purified by
crystallization or by flash chromatography.
General Procedure for the Synthesis of b-Carbolin-1-
ones 9a,b,d: To a solution of IBX (1 mmol) in DMSO (1.5
mL) the appropriate hydroxyamide 7 (0.521 mmol) was
added and the solution was stirred overnight at r.t. under N2.
The solution was diluted with H2O and extracted with
EtOAc. The combined organic layers were washed with sat.
aq NaHCO3, H2O, dried over Na2SO4 and evaporated. The
crude product was crystallized from EtOAc (9a,d) or
chromatographed on flash silica gel (CH2Cl2–MeOH, 99:1;
9b).
(4) Tahri, A.; Buysens, K. J.; Van der Eycken, E. V.;
Vandenberghe, D. M.; Hoornaert, G. J. Tetrahedron 1998,
54, 13211.
(5) (a) Katritzky, A. R.; Rees, C. W. Comprehensive
Heterocyclic Chemistry; Pergamon Press: Oxford, 1984.
(b) Sundberg, R. J. Indoles; Academic Press: London, 1996.
(6) Among the most recent papers: (a) Karthik, M.;
Palanichamy, M.; Murugesan, V. Stud. Surf. Sci. Catal.
2005, 156, 873. (b) Kantam, M. L.; Aziz, K.; Likhar, P. R.
Catal. Lett. 2004, 98, 117. (c) Bartoli, G.; Bosco, M.;
Foglia, G.; Giuliani, A.; Marcantoni, E.; Sambri, L.
Synthesis 2004, 895. (d) Mi, X. L.; Luo, S. Z.; He, J. Q.;
Chen, J. P. Tetrahedron Lett. 2004, 45, 4567. (e) Ji, S. J.;
Wang, S. Y.; Zhang, Y.; Loh, T. P. Tetrahedron 2004, 60,
2051. (f) Ji, S. J.; Zhou, M. F.; Gu, D. G.; Jiang, D. Q.; Loh,
T. P. Eur. J. Org. Chem. 2004, 1584. (g) Bandgar, B. P.;
Bettigeri, S. V.; Joshi, N. S. Monatsh. Chem. 2004, 135,
1265. (h) Xu-Feng, L.; Sun-Liang, C.; Yan-Guang, W.
Synth. Commun. 2006, 36, 3153.
(7) (a) Freter, K. J. Org. Chem. 1975, 40, 2525. (b) Freter, K.;
Fuchs, V. J. Heterocycl. Chem. 1982, 19, 377. (c) Taylor,
E. T.; Nikam, S. S.; Lambert, G.; Martin, A. R.; Nelson, D.
L. Mol. Pharmacol. 1988, 34, 42. (d) Bailey, D. M.;
DeGrazia, G. D.; Alexander, E. J.; Powles, R. G.; Johnson,
R. E.; Patrick, R. A.; Heerdt, B. G.; Fairbain, M. E.; Pruben,
D. J. J. Med. Chem. 1985, 28, 160. (e) Chakrabarty, M.;
Kundu, T.; Harigaya, Y. J. Chem. Res. 2004, 778.
(8) Bandini, M.; Melloni, A.; Tommasi, S.; Umani-Ronchi, A.
Synlett 2005, 1199; and references quoted therein.
(9) Angeli, M.; Bandini, M.; Garelli, A.; Piccinelli, F.;
Tommasi, S.; Umani-Ronchi, A. Org. Biomol. Chem. 2006,
3291.
(10) (a) Beccalli, E.; Broggini, G. Tetrahedron Lett. 2003, 44,
1919. (b) Abbiati, G.; Beccalli, E.; Broggini, G.; Zoni, C.
J. Org. Chem. 2003, 68, 7625.
(11) Johnson, J. R.; Larsen, A. A.; Holley, A. D.; Gerzon, K.
J. Am. Chem. Soc. 1947, 69, 2364.
(12) Stetter, H.; Lappe, P. Chem. Ber. 1980, 113, 1890.
(13) More, J. D.; Finney, N. S. Org. Lett. 2002, 4, 3001.
(14) Lakhdar, S.; Westermaier, M.; Terrier, F.; Goumont, R.;
Boubaker, T.; Ofial, A. R.; Mayr, H. J. Org. Chem. 2006, 71,
9088.
(15) Gallen, M. J.; Goumont, R.; Clark, T.; Terrier, F.; Williams,
C. M. Angew. Chem. Int. Ed. 2006, 45, 2929.
Deprotection of 5f: To an ice-cooled suspension of 5f (170
mg, 0.399 mmol) in anisole (16 mL), AlCl3 (319 mg, 2.39
mmol) was added and the mixture was stirred for 30 min at
110 °C. Addition of H2O, extraction with EtOAc, washing
with NaHCO3, H2O and brine, then drying, filtering and
evaporating of solvent, followed by flash chromatography
with CH2Cl2–MeOH (94:6) as an eluent, gave 5h (59 mg,
52%); mp 280 °C (MeOH). 1H NMR (300 MHz, DMSO-d6):
d = 11.86 (s, 1 H), 11.31 (s, 1 H), 9.55 (s, 1 H), 7.34 (d, J =
8.6 Hz, 2 H), 6.72–6.94 (m, 5 H), 3.81 (s, 3 H), 3.53 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 157.3, 155.1, 150.3, 144.5,
135.1, 130.7, 127.8, 127.2, 123.2, 122.5, 116.8, 115.6,
114.2, 104.2, 94.9, 55.8.
Spectral data for relevant compounds [unless otherwise
noted: 1H NMR (300 MHz, DMSO-d6) and 13C NMR (75
MHz, DMSO-d6)]
5a: mp 260 °C (dec.). 1H NMR: d = 11.4 (d, J = 4.5 Hz, 1 H),
7.57–7.40 (m, 5 H), 7.15 (s, 1 H), 6.85 (d, J = 4.5 Hz, 1 H),
6.65 (s, 1 H), 4.27 (s, 3 H), 3.88 (s, 3 H), 3.45 (s, 3 H). 13
C
NMR: d = 155.9, 150.5, 144.9, 137.2, 136.3, 129.8 (2 × C),
128.8 (2 × C), 127.9, 125.8, 123.4, 122.7, 116.6, 112.8,
Synlett 2008, No. 9, 1309–1312 © Thieme Stuttgart · New York

1312
R. Cincinelli et al.
LETTER
103.8, 93.6, 56.2, 56.05, 31.6.
(s, 1 H), 7.13–7.38 (m, 7 H), 6.90 (d, J = 7.4 Hz, 2 H), 6.82
(d, J = 4.5 Hz, 1 H), 6.74 (s, 1 H), 6.10 (s, 1 H), 3.79 (s, 3 H),
3.49 (s, 3 H). 13C NMR: d = 157.4, 155.7, 150.6, 144.8,
139.2, 135.8, 130.9, 129.9, 128.8, 127.5, 125.3, 124.3,
116.8, 115.3, 114.7, 113.7, 94.0, 56.3.
5b: mp 258 °C. 1H NMR: d = 11.30 (d, J = 4.8 Hz, 1 H), 9.57
(s, 1 H), 7.30 (d, J = 8.2 Hz, 2 H), 7.12 (s, 1 H), 6.90 (d, J =
8.2 Hz, 2 H), 6.77 (d, J = 4.8 Hz, 1 H), 6.75 (s, 1 H), 4.27 (s,
3 H), 3.87 (s, 3 H), 3.50 (s, 3 H). 13C NMR: d = 157.2, 155.6,
150.7, 144.7, 136.6, 130.9 (2 × C), 128.3, 125.9, 123.9,
122.6, 116.7, 115.5 (2 × C), 113.0, 104.3, 93.8, 56.2, 55.8,
31.6.
9a: mp 156 °C. 1H NMR: d = 7.65–8.12 (m, 5 H), 7.15 (br s,
1 H), 7.05 (s, 1 H), 7.02 (s, 1 H), 7.00 (s, 1 H), 3.95 (s, 3 H),
3.83 (s, 3 H), 3.75 (s, 3 H). 13C NMR: d = 168.5, 164.3,
148.9, 145.8, 135.1 (2 × C), 134.1, 131.6 (2 × C), 130.9,
129.9, 126.7, 120.8, 118.4, 105.6, 102.9, 93.6, 56.1 (2 × C),
32.0.
5c: mp 271 °C. 1H NMR: d = 11.35 (d, J = 5.2 Hz, 1 H), 9.55
(br s, 1 H), 7.30 (t, J = 8.2 Hz, 1 H), 7.16 (s, 1 H), 6.95 (d,
J = 5.2 Hz, 1 H), 6.93 (d, J = 1.5 Hz, 1 H), 6.80–6.86 (m, 3
H), 4.45 (s, 3 H), 3.90 (s, 3 H), 3.50 (s, 3 H). 13C NMR: d =
157.8, 155.9, 150.6, 144.7, 138.3, 136.5, 129.9, 125.8,
123.1, 120.0, 116.8, 116.5, 116.4, 114.8, 112.9, 104.1, 93.5,
56.2, 55.7, 31.7.
9b: mp 201 °C. 1H NMR: d = 7.55 (s, 1 H), 7.44 (d, J = 7.1
Hz, 1 H), 7.22–7.38 (m, 5 H), 7.15 (s, 1 H), 6.97 (d, J = 7.1
Hz, 1 H), 5.22 (s, 2 H), 4.21 (s, 3 H), 3.91 (s, 3 H), 3.83 (s, 3
H). 13C NMR: d = 155.6, 151.0, 145.6, 138.7, 136.4, 129.2,
128.9 (2 × C), 128.0 (2 × C), 127.7, 125.7, 124.5, 113.3,
102.9, 100.4, 93.6, 56.3 (2 × C), 50.8, 31.7.
5d: mp 252 °C. 1H NMR (300 MHz, acetone-d6): d = 7.51 (d,
J = 8.9 Hz, 1 H), 7.38 (d, J = 8.6 Hz, 2 H), 7.11 (dd, J = 2.6,
8.9 Hz, 1 H), 7.02 (d, J = 8.6 Hz, 2 H), 6.91 (s, 1 H), 6.86 (d,
J = 2.6 Hz, 1 H), 4.35 (s, 3 H), 3.67 (s, 3 H).
9c: mp 255 °C. 1H NMR (300 MHz, acetone-d6): d = 11.0 (br
s, 1 H), 10.63 (br s, 1 H), 7.85 (d, J = 8.5 Hz, 2 H), 7.60 (s, 1
H), 7.31–7.54 (m, 3 H), 7.28 (s, 1 H), 7.15 (s, 1 H), 3.88 (s,
6 H).
5e: mp >300 °C. 1H NMR: d = 11.04 (d, J = 5.2 Hz, 1 H),
7.46 (s, 1 H), 7.17 (s, 1 H), 6.75 (d, J = 5.2 Hz, 1 H), 4.21 (s,
3 H), 4.18 (s, 3 H), 3.84 (s, 3 H), 2.50 (s, 3 H). 13C NMR:
d = 155.9, 150.7, 145.3, 136.3, 125.5, 125.1, 122.1, 113.9,
110.6, 104.3, 93.5, 56.4, 56.2, 31.5, 16.6.
9d: mp 199 °C, 1H NMR: d = 8.08 (br s, 1 H), 7.71–7.90 (m,
4 H), 7.64 (d, J = 8.6 Hz, 2 H), 7.37–7.56 (m, 6 H), 7.04–7.29
(m, 4 H), 6.07 (s, 2 H).
5f: mp 153 °C. 1H NMR: d = 11.39 (d, J = 4.5 Hz, 1 H), 9.57
Synlett 2008, No. 9, 1309–1312 © Thieme Stuttgart · New York

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