Efficient synthesis of 2-ethoxycarbonyl indoles

Article abstract of DOI:10.1080/00397910802656059

An efficient one-pot procedure for the synthesis of 2-ethoxycarbonyl indoles from commercially available materials has been developed. The one-step procedure involves in situ formation of the hydrazones from phenylhydrazine hydrochloride and ethyl pyruvate in the presence of bismuth nitrate followed by Fischer cyclization in polyphosphoric acid and ethanol. This method is efficient and simple.

Full text of DOI:10.1080/00397910802656059

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Efficient Synthesis of 2-
Ethoxycarbonyl Indoles
A. Sudhakara a , H. Jayadevappa b , K. M.
Mahadevan a & Vijaykumar Hulikal c
a Department of Postgraduate Studies and Research
Chemistry, School of Chemical Sciences, Kuvempu
University, Shankaraghatta, Karnataka, India
b Department of Chemistry, Sahyadri Science
College, Shimoga, Karnataka, India
c Bioorganics and Applied Materials Pvt. Ltd.,
Bangalore, India
Available online: 16 Jun 2009
To cite this article: A. Sudhakara, H. Jayadevappa, K. M. Mahadevan & Vijaykumar
Hulikal (2009): Efficient Synthesis of 2-Ethoxycarbonyl Indoles, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:14, 2506-2515
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Synthetic Communications1, 39: 2506–2515, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802656059
Efficient Synthesis of 2-Ethoxycarbonyl Indoles
A. Sudhakara,1 H. Jayadevappa,2 K. M. Mahadevan,1
and Vijaykumar Hulikal3
1Department of Postgraduate Studies and Research Chemistry,
School of Chemical Sciences, Kuvempu University,
Shankaraghatta, Karnataka, India
2Department of Chemistry, Sahyadri Science College,
Shimoga, Karnataka, India
3Bioorganics and Applied Materials Pvt. Ltd., Bangalore, India
Abstract: An efficient one-pot procedure for the synthesis of 2-ethoxycarbonyl
indoles from commercially available materials has been developed. The one-step
procedure involves in situ formation of the hydrazones from phenylhydrazine
hydrochloride and ethyl pyruvate in the presence of bismuth nitrate followed
by Fischer cyclization in polyphosphoric acid and ethanol. This method is
efficient and simple.
Keywords: Bismuth nitrate, ethyl pyruvate, Fisher indole synthesis, one pot,
phenylhydrazine hydrochloride
In many natural products and biologically active compounds, the indole
scaffold is a privileged substructure.[1] Esters of indole-2-carboxylic acids
may serve as glycine site antagonists and hence aid in the treatment of
human brain injuries.[2] Meanwhile, 2-ethoxycarbonyl indole and its deri-
vatives, which are considered attractive substrates, have been reported to
possess anti-inflammatory activity.[3] In spite of several methods already
available for the synthesis of indoles,[4] there is continuous interest in the
development of new syntheses of the indole ring. As a result, a large
Received September 24, 2008.
Address correspondence to K. M. Mahadevan, Department of Postgraduate
Studies and Research Chemistry, School of Chemical Sciences, Kuvempu Univer-
sity, Shankaraghatta, Karnataka, 577 451, India. E-mail: mady_kmm@yahoo.co.uk
2506

Synthesis of 2-Ethoxycarbonyl Indoles
2507
number of new syntheses or modifications and applications of known
methods countinue to be reported.[5] The most famous synthesis is the
Fischer indole synthesis.[6] Several 2-ethoxycarbonyl indoles have been
prepared by Fischer indole synthesis using polyphosphoric acid (PPA)[7]
from corresponding hydrazones. Usually PPA is required in large
amounts, 8- to 9-fold excess by weight, and PPA-catalyzed cyclization
reactions often result in poor yield. In spite of these drawbacks, PPA is
still used in industry and academia to prepare various indole derivatives.
One-pot approaches to the indole scaffold are attracting considerable
attention because of their significance from both economical and ecolo-
gical points of view.[8] These methods usually start directly from a single,
commercially available precursor, which obviates the preparation or iso-
lation of the unstable arylhydrazones (Scheme 1). Hence, here we report a
simple, convenient, one-pot synthesis of 2-ethoxycarbonyl indoles (3)
from commercially available starting materials.
In our initial study, the reaction of 4-nitrophenylhydrazine hydro-
chloride and ethyl pyruvate was carried out in the presence of bismuth
nitrate in methanol to afford the corresponding hydrazone. This has been
isolated in good yield in the presence of bismuth nitrate rather than with-
out catalyst. The hydrozones were normally cyclized in hot polyphospho-
ric acid into 2-ethoxycarbonyl indoles in poor yields.[9] The product is
isolated by addition to water followed by filtration of the product, and dis-
posal of the phosphoric acid residue can have a considerable environment
impact. Hence, to circumvent these difficulties in isolation, poor yield, and
use of 7- to 9-fold excess of PPA, we used ethanol as cosolvent in this
Scheme 1. Synthesis of 2-ethoxycarbonyl indoles catalyzed by bismuth nitrate/
PPA in EtOH.

2508
A. Sudhakara et al.
Table 1. Effect of solvent and amount of catalyst in the synthesis of
2-ethoxycarbonyl indoles
Entry
Solvent
BiNO3 (mol%)
PPA (%)
Time (h)
Yield (%)
1
2
3
4
5
6
7
EtOH
EtOH
EtOH
MeOH
EtOH
EtOH
CH3CN
—
10
10
20
30
20
20
—
—
3
3
4
>5
>5
2.5
0.50
0.40
1.2
4
00
00
75
90–95
90–95
90–95
70
3
3
one-pot process. Surprisingly, addition of ethanol in the reaction
along with PPA during cyclization of hydrozones at reflux temperature
(70–80 ꢀC) greatly increased the yield (>90%) of the products and
significantly reduced the reaction time (Table 1). Since the development
of one-pot approaches to the indole scaffold is attracting considerable
attention because of their significance from both economical and ecologi-
cal points of view, now we thought to carry out the reaction in one pot by
mixing molar equivalent of 4-nitrophenylhydrazine hydrochloride, ethyl
pyruvate, and catalytic amounts of bismuth nitrate and PPA in MeOH.
This method avoids the preparation or isolation of the arylhydrazones.
This one-pot procedure gave satisfactory results in terms of easy isolation,
improved yield, and reduced reaction time. Thus, it was obvious that the
bismuth nitrate catalyzed initial hydrazone formation and subsequent
cyclization of hydrazones by PPA in MeOH, afforded various indoles.
Hence, the experiments were carried out to establish the optimal
amounts of bismuth nitrate and PPA in a one-pot synthesis. The reaction
with 10 mol% of bismuth nitrate in PPA gave 75% yield after 2.5 h
(Table 1) in one pot. However, the best result (95%) was achieved when
20 mol% of catalyst was used (Table 2), and the reaction time was also
reduced. Increasing the amount of the catalyst and PPA did not change
the isolated yield, but reaction time was reduced in ethanol media
(Table 2). The reaction of phenyl hydrazine hydrochloride, ethyl pyru-
vate, and catalytic amounts of bismuth nitrate and PPA was separately
performed without using MeOH as cosolvent. This failed to complete
the reaction and resulted in poor yield even with longer reaction times.
Further, the effect of solvent on this reaction was also studied, and
EtOH and MeOH gave the best results. Apart from good yields and
shorter reaction times, the other advantage in the use of ethanol
and methanol was their solubility in water, which makes the isolation
of the product from the reaction mixture easy and reduces the amount

Synthesis of 2-Ethoxycarbonyl Indoles
2509
Table 2. Synthesis of 2-ethoxycarbonyl indolesa
Entry
1
Product
Time (h)
0.4
Yield (%)b
90
Mp (ꢀC)
102–105
2
3
3
80
80
171–172
142–144
2.5
4
5
6
2
85
80
80
169–171
145–147
92–94
2.5
2.5
7
8
2.5
2.5
85
85
178–180
167–169
9
2
2
85
80
158–160
168–170
10
aReaction was carried out at reflux temperature in alcohol þ PPA in presence of
20 mol% of BiNO3.
bIsolated yields.

2510
A. Sudhakara et al.
Scheme 2. Mechanism for the synthesis of 2-ethoxycarbonyl indoles.
of PPA used (8- to 9-fold excess to 3-fold) in this reaction, with possible
assistance by ethanol as cosolvent. Similarly, by adopting optimized
reaction conditions, the various 2-ethoxycarbonyl indoles were prepared
with various phenylhydrazine hydrochlorides and ethyl pyruvate in the
presence of 20 mol% of bismuth nitrate and PPA (3-fold) in MeOH
(Scheme 1).
The synthesis requires only a single step: the synthesis of the ethyl-
2-[(4-nitrophenyl) hydrazono] propanoate. Subsequent cyclization occurred
in one pot with two steps as shown in Scheme 2. The characterization data of
all the prepared compounds are given in the experimental section.
In conclusion, the reported protocol is a mild and facile approach to
the synthesis of 2-ethoxy carbonyl indoles by [3,3]-sigmatropic rearrange-
ment by in situ generated hydrazones. The scope appears to be presently
restricted to hydrazones of ethyl pyruvate, and further investigation on
other ketonic hydrazones is under way. Most products can be easily and
directly purified by column chromatography. The procedure is amicable
for scale-up.
EXPERIMENTAL
General
Products were identified by their physical and spectroscopic data, all the
melting points were recorded in open capillaries. The purity of the

Synthesis of 2-Ethoxycarbonyl Indoles
2511
compounds was checked by thin-layer chromatography (TLC) on silica
1
gel. H NMR spectra were recorded on a Bruker 400-Hz spectrometer
using dimethyl sulfoxide (DMSO)-d6 and CDCl3 as an internal standard.
Infrared (IR) spectra were obtained using a FTS-135 spectrometer
instrument. Mass spectra (MS) were recorded on a Jeol SX102 ¼
DA-6000 (10 kV) fast atom bombardment (FAB) mass spectrometer.
Solvents, chemicals, and reagents were purchased from Merck Chemical
Company in high-grade quality.
General Procedure for the Synthesis of Ethyl-2-[(4-nitrophenyl)
hydrazono] Propanoate
The 4-nitrophenylhydrazine hydrochloride (1 g, 0.0069 mol) and ethyl
pyruvate (0.80 g, 0.0068 mol) were dissolved in 20 ml MeOH and 20 mol%
of bismuth nitrate (0.67 g). The reaction mixture was refluxed on a water
bath for the appropriate time. After completion, the reaction mixture was
poured into water (100 ml), and the crude hydrazone was extracted with
ethyl acetate (2 ꢁ 50 ml). The combined ethyl acetate extracts were
washed with brine followed by water, dried over anhydrous Na2SO4,
and evaporated under reduced pressure to provide a crude solid
hydrazone. The solid thus obtained was further purified by column
chromatography using silica gel (60–120 mesh) and eluted with petrol-
eum ether–ethyl acetate to afford ethyl-2-[(4-nitrophenyl)hydrazono]
propanoate.
General Procedure for the Synthesis of 2-Ethoxycarbonyl Indole
The 4-nitro phenylhydrazine hydrochloride (1 g, 0.0069 mol) and ethyl
pyruvate (0.80 g, 0.0068 mol) were dissolved in 20 ml MeOH, then
20 mol% of bismuth nitrate (0.67 g) and 3 g of PPA were added. The
reaction mixture was refluxed on a water bath for the appropriate time.
The completion of the reaction was monitored by TLC (petroleum ether
and ethyle acetate). The reaction mixture was poured into water (100 ml),
and the crude product was extracted with ethyl acetate (2 ꢁ 50 ml). The
combined ethyl acetate extracts were washed with brine followed by
water, dried over anhydrous Na2SO4, and evaporated under reduced
pressure to provide a crude solid. The solid thus obtained was further
purified by column chromatography using silica gel (60–120 mesh) and
eluted with petroleum ether–ethyle acetate to afford 2-ethoxycarbonyl
indoles.

2512
A. Sudhakara et al.
Data
Ethyl (2Z)-2-[(4-nitrophenyl) hydrazono] propanoate (C11H13N3O4)
1
Mp: 94–96ꢀC. IR (KBr): 3399 (NH). H NMR (400 MHz, CDCl3): d
7.10.98 (br, s, NH), 8.2 (1H, d, J ¼ 3.2 Hz), 8.19 (1H, t, J ¼ 9.2), 7.6
(1H, t, 7.2 Hz), 7.01 (1H, d, J ¼ 1.2), 4.41 (2H, q, J ¼ 7.2), 2.25 (3H, t,
J ¼ 2.8), 1.57 (3H, s). 13C NMR: d 11, 13.3, 59, 116, 116, 124, 138, 152,
154, 161. MS (EI, eV 70): m=z (%): (Mþ) 251. Anal. calcd. (%): C,
52.59; H, 5.22; N, 16.72. Found (%): C, 54.58; H, 5.92; N, 17.72.
Ethyl 1H-indole-2-carboxylate 1: C10H11NO2
1
IR (KBr): 3381 (NH). H NMR (400 MHz, CDCl3): d 7.68 (br, s, NH),
7.46 (1H, d, J ¼ 8.05 Hz), 7.24 (1H, d, J ¼ 4 Hz), 7.11 (2H, m, J ¼ 8 Hz),
4.5 (q, 2H, J ¼ 7.2), 1.47 (3H, t, J ¼ 7.15). 13C NMR: d 15, 65, 111, 115,
121, 128, 134, 135, 140, 154, 161. MS (EI eV 70): m=z (%): (Mþ) 177.
Anal. calcd. (%): C, 67.68; H, 6.26; N, 7.09. Found (%): C, 66.18; H,
6.06; N, 6.86.
Ethyl 5-nitro-7-fluoro-1H-indole-2-carboxylate 2: C11H9FN2O4
IR (KBr): 3391 (NH). 1H NMR (300 MHz, CDCl3): d 9.7 (br, s, NH), 8.2
(1H, d, J ¼ 4.05 Hz), 7.9 (1H, d, J ¼ 3.6 Hz), 7.2 (1H, t, J ¼ 9.8 Hz), 4.5 (q,
2H, J ¼ 7.2), 1.47 (3H, t, J ¼ 7.15). 13C NMR: d 14, 61, 108, 111, 121, 128,
134, 135, 140, 154, 161. MS (EI eV 70): m=z (%): (Mþ) 253. Anal. calcd.
(%): C, 55.39; H, 3.60; N, 11.11. Found (%): C, 54.96; H, 3.12; N, 11.01.
Ethyl 5-nitro-1H-indole-2-carboxylate 3: C11H10N2O4
IR (KBr): 3389 (NH). 1H NMR (300 MHz, CDCl3): d 9.3 (br, s, NH), 8.68
(1H, d, J ¼ 2.04), 8.3 (dd, 1H, J ¼ 9.16 Hz), 7.5 (1H, s), 4.47 (q, 2H,
J ¼ 10.7), 1.4 (2H, t, J ¼ 7.12). 13C NMR: d 14, 61, 87, 108, 115, 122,
131, 132, 140, 145, 161. MS (EI eV 70): m=z (%): (Mþ) 235. Anal. calcd.
(%): C, 56.41; H, 4.30; N, 11.96. Found (%) C, 55.81; H, 4.12; N, 11.01.
Ethyl 6-chloro-1H-indole-2-carboxylate 4: C11H10ClNO2
1
IR (KBr): 3387 (NH). H NMR (300 MHz, CDCl3): d 9.13 (br, s, NH),
7.6 (1H, d, J ¼ 8.56 Hz), 7.42 (s, 1H), 7.2 (1H, S), 7.1 (1H, d, J ¼ 6.8 Hz),

Synthesis of 2-Ethoxycarbonyl Indoles
2513
4.6 (q, 2H, J ¼ 7.12 Hz), 1.4 (3H, t, J ¼ 6.04 Hz) Hz. 13C NMR: d 14, 63,
97, 106, 108, 111, 117, 134, 143, 153, 161. MS (EI, eV 70): m=z (%): (Mþ)
224. Anal. calcd. (%): C, 59.07; H, 4.51; N, 6.26. Found (%): C, 59.01; H,
4.11; N, 5.97.
Ethyl 6-nitro-1H-indole-2-carboxylate 5: C11H10N2O4
1
IR (KBr): 3381 (NH). H NMR (300 MHz, CDCl3): d 9.27 (br, s, NH),
8.68 (1H, d, J ¼ 2.04 Hz), 8.24 (1H, dd, J ¼ 3.76 Hz), 7.5 (1H, d,
J ¼ 9.1 Hz), 4.47 (q, 2H, J ¼ 7.16 Hz), 1.4 (3H, t, J ¼ 7.14 Hz). 13C
NMR: d 13.8, 61, 87, 106, 116, 124, 132, 133, 141, 147, 161. MS (EI, eV
70): m=z (%): (Mþ) 235. Anal. calcd (%): C, 56.41; H, 4.30; N, 11.96.
Found (%): C, 55.23; H, 4.21; N, 11.57.
Ethyl 7-nitro-1H-indole-2-carboxylate 6: C11H10N2O4
IR (KBr): 3385 (NH). 1H NMR (300 MHz, CDCl3): d 9.4 (br, s, NH), 8.2
(1H, d, J ¼ 7.89), 7.9 (s, 1H), 7.8 (1H, d, J ¼ 8.25 Hz), 7.4 (1H, t,
J ¼ 8.04 Hz), 4.5 (q, 2H, J ¼ 10.68 Hz) 1.4 (3H, t, J ¼ 7.12 Hz). 13C
NMR: d 14, 59, 88, 108, 115, 124, 130, 133, 141, 145, 161. MS (EI, eV
70): m=z (%): (Mþ) 235. Anal. calcd (%): C, 56.41; H, 4.30; N, 11.96.
Found (%): C, 55.43; H, 4.11; N, 11.87.
Ethyl 6-bromo-1H-indole-2-carboxylate 7: C11H10BrNO2
1
IR (KBr): 3378 (NH). H NMR (300 MHz, CDCl3): d 9.27 (br, s, NH),
8.68 (1H, d, J ¼ 2.04 Hz), 8.24 (1H, dd, J ¼ 3.76 Hz), 7.5 (1H, d,
J ¼ 9.1 Hz), 4.47 (q, 2H, J ¼ 7.16 Hz), 1.4 (3H, t, J ¼ 7.14 Hz). 13C
NMR: d 13.8, 61, 87, 106, 116, 124, 132, 133, 141, 147, 161. MS (EI, eV
70): m=z (%): (Mþ) 268. Anal. calcd (%): C, 49.28; H, 3.76; N, 5.22. Found
(%): C, 49.43; H, 4.01; N, 5.37.
Ethyl 5-bromo-1H-indole-2-carboxylate 8: C11H10BrNO2
1
IR (KBr): 3392 (NH). H NMR (300 MHz, CDCl3): d 9.27 (br, s, NH),
8.68 (1H, d, J ¼ 2.04 Hz), 8.24 (1H, dd, J ¼ 3.76 Hz), 7.5 (1H, d,
J ¼ 9.1 Hz), 4.47 (q, 2H, J ¼ 7.16 Hz), 1.4 (3H, t, J ¼ 7.14 Hz). 13C
NMR: d 13.8, 61, 87, 106, 116, 124, 132, 133, 141, 147, 161. MS (EI, eV
70): m=z (%): (Mþ) 268. Anal. calcd. (%): C, 49.28; H, 3.76; N, 5.22.
Found (%): C, 49.43; H, 4.01; N, 5.37.

2514
A. Sudhakara et al.
Ethyl 5-fluoro-1H-indole-2-carboxylate 9: C11H10FNO2
IR (KBr): 3378 (NH). 1H NMR (300 MHz, CDCl3): d 8.9 (br, s, NH), 7.3
(2H, t, J ¼ 5.91 Hz), 7.1 (1H, d, J ¼ 1.26 Hz), 7.07 (1H, t, J ¼ 2.49 Hz), 4.4
(q, 2H, J ¼ 10.69 Hz), 1.4 (3H, t, J ¼ 10.69 Hz). 13C NMR: d 14, 60, 98, 105,
106, 109, 113, 134, 142, 151, 160. MS (EI, eV 70): m=z (%): (Mþ) 208. Anal.
calcd. (%): C, 63.76; H, 4.86; N, 6.76. Found (%): C, 64.43; H, 4.31; N, 5.87.
Ethyl 4-chloro-1H-indole-2-carboxylate 10: C11H10ClNO2
IR (KBr): 3391 (NH). 1H NMR (300 MHz, CDCl3): d 9.1 (br, s, NH), 7.6
(1H, d, J ¼ 8.58 Hz), 7.4 (s, 1H), 7.2 (1H, d, J ¼ 6.97 Hz), 7.1 (1H, d,
J ¼ 8.58), 4.4 (q, 2H, J ¼ 10.70 Hz), 1.45 (t, 3H, J ¼ 7.91 Hz). 13C NMR:
d 14, 61, 89, 90, 108, 15, 121, 135, 136, 143, 161. MS (EI, eV 70): m=z
(%): (Mþ) 224. Anal. calcd. (%) C, 59.07; H, 4.30; N, 6.26. Found (%):
C, 58.43; H, 4.41; N, 6.17.
ACKNOWLEDGMENTS
The authors are grateful to the Department of Postgraduate Studies
and Research in Chemistry, School of Chemical Sciences, Kuvempu
University, for providing laboratory facilities, to the Indian Institute of
Science Bangalore for spectral data, and finally to Vinay K. M., lecturer
Department of English, for proofreading.
REFERENCES
1. Katritzky, A. R.; Pozharskii, A. F. Handbook of Heterocyclic Chemistry;
Pergamon: Oxford, 2000.
2. For literature on functionalizations of indole nucleus, see references cited
in (a) Hartung, C. G.; Fecher, A.; Chapell, B.; Snieckus, V. Directed
ortho-metalation approach to C-7-substituted indoles: Suzuki–miyaura cross
coupling and the synthesis of pyrrolophenanthridone alkaloids. Org. Lett.
2003, 5, 1899–1902; (b) Ezquerra, J.; Pedregal, C.; Lamas, C.; Barluenga, J.;
Perez, M.; Garcia Martin, M. A.; Gonzales, J. M. Efficient reagents for the
synthesis of 5-, 7-, and 5,7-substituted indoles starting from aromatic amines:
Scope and limitations. J. Org. Chem. 1996, 61, 5804–5812.
3. Gribble, G. W. Recent developments in indole ring synthesis—methodology
and applications. J. Chem. Soc., Perkin Trans. 1 2000, 1045.
4. (a) Humphrey, G. R.; Kuethe, J. T. Practical methodologies for the synthesis
of indoles. Chem. Rev. 2006, 106, 2875–2911; (b) Dalpozzo, R.; Bartoli, G.
Bartoli indole synthesis. Curr. Org. Chem. 2005, 9, 163–178.

Synthesis of 2-Ethoxycarbonyl Indoles
2515
5. For recent reviews on the de novo construction of the indole nucleus, see (a)
Gribble, G. W. Recent developments in indole ring synthesis—Methodology
and applications. J. Chem. Soc., Perkin Trans. 1 2000, 1045–1075; (b)
Gilchrist, T. L. Synthesis of aromatic heterocycles. J. Chem. Soc., Perkin
Trans. 1 1999, 2849–2866; (c) Moody, C. J. Synthesis of carbazole alkaloids.
Synlett 1994, 681–688; (d) Gribble, G. W. Indole derivatives and their use as
thyroid receptor ligands. Contemp. Org. Synth. 1994, 145–172; (e) Sundberg,
R. J. Indoles; Academic Press: San Diego, 1996; (f) Baccolini, G. Topics in
Heterocyclic systems—Synthesis, Reactions, and Properties; Soc. Chim. It.
Ed.: Rome, 1996; vol. 1, pp. 103–118; (g) Robinson, B. The Fisher–Indole
Synthesis; Wiley Interscience: New York, 1982.
6. (a) Sundberg, R. J. The Chemistry of Indoles; Academic Press: New York,
1970: p. 142; (b) Jones, A. R. In Comprehensive Heterocyclic Chemistry;
A. R. Katrizky, C. W. Rees (Eds.); Pergamon Press: Oxford, 1984; vol. 4,
p. 334; (c) Nakazaki, M.; Yamamoto, K. Direct synthesis of indole by the
Fischer indole synthesis. J. Org. Chem. 1976, 41, 1877.
7. Tietze, L. F.; Haunert, F.; Feuerstein, T.; Herzing, T. A concise and efficient
synthesis of seco-duocarmycin SA. Eur. J. Org. Chem. 2003, 562.
8. Simoneau, C. A.; Strohl, A. M.; Ganem, B. One-pot synthesis of polysubsti-
tuted indoles from aliphatic nitro compounds under mild conditions.
Tetrahedron Lett. 2007, 48, 1809.
9. Murakami, Y.; Watanabe, T.; Takahashi, H.; Yokoo, H.; Nakazawa, Y.;
Koshimizu, M.; Adachi, N.; Kurita, M.; Yoshino, T.; Inagaki, T.; Ohishi,
M.; Watanabe, M.; Tani, M.; Yokoyama, Y. Fischer indolization of
2-sulfonyloxyphenylhydrazones: A new and practical approach for preparing
7-oxygenated indoles and application to the first synthesis of eudistomidin-A.
Tetrahedron 1998, 54, 45.