Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin metathesis

Article abstract of DOI:10.1016/j.tet.2017.09.039

Simple synthetic approaches to pyridocarbazole and azepinocarbazole derivatives have been reported via Fischer indolization, Grignard reaction and olefin metathesis as key steps. In addition, a combination Sonogashira coupling and Pauson-Khand reaction has been used to assemble extended pyridocarbazole derivative.

Full text of DOI:10.1016/j.tet.2017.09.039

Tetrahedron xxx (2017) 1e7
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Tetrahedron
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Synthesis of tricyclic units of indole alkaloids: Application of Fischer
indolization and olefin metathesis
Sambasivarao Kotha*, Vikas R. Aswar, Gaurav Singhal
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Simple synthetic approaches to pyridocarbazole and azepinocarbazole derivatives have been reported
via Fischer indolization, Grignard reaction and olefin metathesis as key steps. In addition, a combination
Sonogashira coupling and Pauson-Khand reaction has been used to assemble extended pyridocarbazole
derivative.
Received 5 July 2017
Received in revised form
20 September 2017
Accepted 21 September 2017
Available online xxx
© 2017 Elsevier Ltd. All rights reserved.
Keywords:
Indole alkaloids
Fischer indolization
Grignard reaction
Olefin metathesis
Sonogashira coupling
Pauson-Khand reaction
1. Introduction
metal complexes as catalyst and usage of expensive precursors,
there is a need to develop simple synthetic strategies to assemble
Indole alkaloids with diverse biological activity has attracted the
attention of the organic and medicinal chemists due to their ap-
plications in the pharmaceutical area.1 Indole unit is an attractive
building block to design new drugs based on alkaloids which are
useful in the treatment of cancer. Among indole based heterocycles,
pyridoindole moiety is found in many natural products (1e4) such
as homofascaplysin C, canthine-6-one, (ꢀ)-goniomitine, and vinc-
amine etc. (Fig. 1).2 Biological activity of these natural products
motivated researcher to design new routes to pyridoindole motifs.
Approaches based on transition-metal-catalyzed annulations,3
domino reactions4 have widely been used and several methods
are reported to assemble pyridoindoles.5
Azepinoindole skeleton, a key structural element present in
many natural alkaloids (5e8) such as arborescidine B, akagerine,
and appogeissoschizine etc. is worthy of synthetic investigation
(Fig. 1).6 They have been tested for different biological activities and
construction of these molecules inspired organic chemists to search
for efficient methods.7 More precisely, the azepinoindole exhibiting
pharmacological activities such as modulators for CNS neuro-
transmitter receptors (Fig. 1).7b,8 Due to high loading of transition-
these core structures.
So, in this context, we have developed a new synthetic approach
to pyridocarbazole and azepinocarbazole systems using Fischer
indolization,9 Grignard reaction10 and ring-closing metathesis
(RCM)11 as key steps. Also, extended pyridocarbazole system has
been constructed by a combination of Sonogashira coupling12 and
Pauson-Khand reaction.13a,11f,13b-e
2. Results and discussion
The synthesis of pyridocarbazole and azepinocarbazole de-
rivatives begin with the preparation of tetrahydrocarbazole deriv-
ative 11 via Fischer indolization of commercially available
cyclohexanone with phenylhydrazine hydrochloride 9. Later,
regioselective oxidation of 11 using periodic acid produce the keto
carbazole derivative 12 (Scheme 1).9a,14
Further, the carbazole derivative 12 was allylated at room
temperature under basic conditions to afford N-allyl derivative 14
because unprotected carbazole derivative 12 failed to give the
Grignard addition product 13. So, N-allyl carbazole 14 was prepared
and then it was subjected to Grignard addition reaction using vinyl
magnesium bromide to afford allyl-vinyl carbazole derivative 15.
Subsequently, RCM with the aid of Grubbs' first generation (G-I)
* Corresponding author.
E-mail address: srk@chem.iitb.ac.in (S. Kotha).
https://doi.org/10.1016/j.tet.2017.09.039
0040-4020/© 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kotha S, et al., Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin
metathesis, Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.09.039

2
S. Kotha et al. / Tetrahedron xxx (2017) 1e7
Fig. 1. Biologically active alkaloids with pyrido and azepino indole core unit.
Scheme 1. Prepration of regioselective keto carbazoles.
catalyst (5 mol %) under ethylene atmosphere in dry CH2Cl2
delivered the pyridocarbazole derivative 16 in good yield (Scheme
2). Along similar lines, pyridocarbazole derivatives 16a-d were also
synthesized.
Next, the azepinocarbazole derivative 18 was synthesized via
Grignard reaction followed by RCM. Allyl magnesium bromide
addition to 14 gave diallyl carbazole 17 which was then subjected to
RCM with Grubbs' second generation (G-II) catalyst to give the
azepinocarbazole skeleton 18. The G-I catalyst (5 mol %) failed to
give the desired azepinocarbazole derivative 18 (Scheme 3).
In addition, another pyridocarbazole derivative 24 was synthe-
sized by a combination of Sonogashira coupling and Pauson-Khand
reaction. In this context, the synthesis of enyne building block 21
was started with bromo carbazole 11d which on Songashira
coupling sequence gave the acetylenic carbazole 19. Further,
deprotection of TMS derivative 19 was carried out with tetra-n-
butylammonium fluoride (TBAF)/THF conditions to deliver acety-
lenic derivative 20, which on N-allylation under basic condition
produced the enyne building block 21. Alternatively, bromo
carbazole 11d was treated with allyl bromide to afford the N-allyl
carbazole 22. Next, Sonogashira coupling reaction was carried out
to afford the enyne 23. Finally, removal of the TMS group using
TBAF furnished the enyne building block 21 (Scheme 4).
It is interesting to note that, allyl installation followed by
Scheme 2. Synthesis of pyridocarbazoles via Grignard and RCM sequence.
Please cite this article in press as: Kotha S, et al., Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin
metathesis, Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.09.039

S. Kotha et al. / Tetrahedron xxx (2017) 1e7
3
Scheme 3. Synthesis of azepinocarbazoles via Grignard and RCM reaction.
Scheme 4. Synthesis of enyne building block via Sonogashira coupling reaction.
medicinal importance of these alkaloids our results may be interest
to researchers who are keen in designing “drug like” molecules.
4. Experimental section
4.1. General information
Scheme 5. Pauson-Khand reaction of enyne building block 21.
Commercially available reagents were used without purification
and reactions involving air sensitive reagents or catalysts were
performed in degassed solvents. Moisture sensitive material like
Grignard reagents were transferred by using standard syringe-
septum techniques and the reactions were maintained under
inert atmosphere. Reactions were monitored by thin-layer chro-
matography (TLC) carried out on 0.25 mm Merck silica gel plates
(60F-254) using UV light as a visualizing agent and KMnO4 stain.
The coupling constants (J) are given in hertz (Hz) and chemical
shifts are reported in parts per million (ppm). The abbreviations s,
d, t, dd and m refer to singlet, doublet, triplet, doublet of doublet
and multiplet respectively. Infrared (IR) spectra were recorded on
Nicolet 6700 spectrophotometer. Proton nuclear magnetic reso-
nance (1H NMR, 400 MHz and 500 MHz) spectra and carbon nu-
clear magnetic resonance (13C NMR,100 MHz and 125 MHz) spectra
were recorded on a Bruker spectrometer. The high-resolution mass
measurements were carried out by using electrospray ionization
(ESI) spectrometer. Column chromatography was carried by using
Acme's silica gel (100e200 mesh) with an appropriate mixture of
ethyl acetate and petroleum ether. Melting points were recorded on
veego VMP-CM melting point apparatus.
Sonogashira coupling reaction gave better yield (75% overall yield)
of enyne building block 21 as compared to Sonogashira coupling
followed by allyl introduction sequence (38% overall yield).
Another type pyridocarbazole derivative was attempted by
enyne metathesis as well as Pauson-Khand reaction. Unfortunately,
enyne metathesis of 21 failed to give pyridocarbazole derivative.
However, when the enyne building block 21 was treated with
Co2(CO)8 in 1,2-dichloroethane under the microwave irradiation
conditions delivered the pyridocarbazole derivative 24 in 79% yield
(see Scheme 5).
3. Conclusion
In summary, we have developed a new synthetic strategy to
pyridocarbazole (16a-d) as well as azepinocarbazole (18a-d) de-
rivatives via Fischer indolization, Grignard reaction, and RCM as key
steps. Moreover, various building blocks prepared here are useful
for the synthesis of alkaloids containing pyridoindole. Also, syn-
thesis of pyridocarbazole derivatives 24 has been accomplished via
Sonogashira and Pauson-Khand reaction as key steps. In view of
Please cite this article in press as: Kotha S, et al., Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin
metathesis, Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.09.039

4
S. Kotha et al. / Tetrahedron xxx (2017) 1e7
4.1.1. General procedure (I) for allylation
and concentrated. The crude product obtained was purified by
silica gel column chromatography (10% EtOAc/Pet. ether) to give
compound 15a as light brown liquid. Yield 72% (81 mg). Rf ¼ 0.45
4.1.1.1. 9-Allyl\-2,3,4,9-tetrahydro-1H-carbazol-1-one (14a). To the
solution of 12a (1 g, 5.4 mmol) in acetone (25 mL), was added NaH
(259 mg, 10.8 mmol) under a nitrogen atmosphere at room tem-
perature. Later, allyl bromide (0.93 mL, 10.8 mmol) was added to
the reaction mixture slowly, and stirring was continued at room
temperature for 2 h. After completion of the reaction (TLC moni-
toring), the reaction mixture was diluted with EtOAc (10 mL) and
quenched with sat. NH4Cl followed by extraction with EtOAc
(3 ꢁ 10 mL). The combined organic layer washed with water and
brine, dried over Na2SO4, and concentrated. The crude product
obtained was purified by silica gel column chromatography (2%
EtOAc/petroleum ether) to give compound 14a as a colorless liq-
uid.9a Yield 63% (0.77 g). Rf ¼ 0.53 (100% petroleum ether). Spectral
data is matching with reported compound.9a
(20% EtOAc/Petroleum ether). 1H NMR (500 MHz, CDCl3)
d
¼ 7.55
(d, J ¼ 8.0 Hz, 1H), 7.28e7.20 (m, 2H), 7.14e7.11 (m, 1H), 6.12 (dd,
J ¼ 17.0,10.5 Hz,1H), 5.96e5.93 (m,1H), 5.25e5.19 (m, 2H), 5.13 (dd,
J ¼ 10.5,1.5 Hz,1H), 4.96 (dd, J ¼ 17.0,1.5 Hz,1H), 4.89e4.88 (m, 2H),
2.81e2.76 (m, 2H), 2.07e2.05 (m, 2H), 1.98e1.93 (m, 3H) ppm. 13C
NMR (125 MHz, CDCl3)
d
¼ 142.9, 137.4, 135.4, 134.9, 126.5, 122.2,
119.2, 119.1, 119.0, 116.1, 114.3, 112.9, 110.1, 47.0, 41.7, 21.7, 20.7 ppm.
IR (neat) ¼ 3361, 2976, 1688, 1513, 1171, 1042 cmꢀ1. HRMS (ESI)
calculated for C17H19KNO [MþK] 292.1098 found 292.1094.
4.1.2.2. 9-Allyl-6-chloro-1-vinyl-2,3,4,9-tetrahydro-1H-carbazol-1-ol
(15b). According to general procedure II, to the stirred solution of
compound 14b (100 mg, 0.38 mmol) in dry THF (15 mL) was added
vinyl magnesium bromide (0.5 mL, 0.50 mmol, 1.0 M solution in
THF) under N2 atmosphere to afford compound 15b as a colorless
liquid which was purified by silica gel column chromatography.
Yield 75% (83 mg). Rf ¼ 0.45 (20% EtOAc/Petroleum ether). 1H NMR
4.1.1.2. 9-Allyl-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-one (14b).
According to general procedure I, to the solution of compound 12b
(500 mg, 2.28 mmol) in acetone (25 mL), NaH (109 mg, 4.56 mmol)
was added under N2 atmosphere followed by addition of allyl
bromide (0.39 mL, 4.56 mmol) to afford compound 14b as a
colorless liquid which was purified by silica gel column chroma-
tography. Yield 65% (364 mg). Rf ¼ 0.52, (100% petroleum ether). 1H
(400 MHz, CDCl3)
d
¼ 7.48 (s, 1H), 7.16e7.11 (m, 2H), 6.08 (dd,
J ¼ 17.2, 10.8 Hz, 1H), 5.95e5.86 (m, 1H), 5.24e5.11 (m, 3H),
4.93e4.83 (m, 3H), 2.77e2.65 (m, 2H), 2.07e2.02 (m, 2H),1.95e1.86
NMR (500 MHz, CDCl3)
d
¼ 7.62 (d, J ¼ 1.5 Hz, 1H), 7.31 (dd, J ¼ 9.0,
(m, 3H) ppm. 13C NMR (100 MHz, CDCl3)
d
¼ 142.5, 136.8, 135.7,
1.5 Hz, 1H),7.25 (J ¼ 1.5 Hz, 1H), 5.95 (m, 1H), 5.19e5.18 (m, 2H),
5.10e5.08 (m, 1H), 4.91 (dd, J ¼ 17.0, 1.3 Hz, 1H), 2.97 (t, J ¼ 6.0 Hz,
2H), 2.64 (t, J ¼ 6.0 Hz, 2H), 2.22 (m, 2H) ppm. 13C NMR (125 MHz,
134.5, 127.6, 124.9, 122.4, 118.5, 116.3, 114.6, 112.5. 111.1, 72.4, 47.2,
41.6, 21.5, 20.5 ppm. IR (neat) ¼ 3432, 2933, 1465, 1183, 924 cmꢀ1
.
HRMS (ESI) calculated for C17H18ClNaNO [MþNa] 310.0967 found
CDCl3)
d
¼ 191.9, 137.3, 133.6, 130.6, 128.6, 127.0, 125.9, 125.8, 120.5,
310.0967.
116.2, 111.9, 46.9, 39.9, 24.6, 21.7 ppm. IR (neat) 2913, 1724, 1420,
1115, 915 cmꢀ1. HRMS (ESI) calculated for C15H14ClNaNO [MþNa]
282.0656 found 282.0656.
4.1.2.3. 9-Allyl-6-bromo-1-vinyl-2,3,4,9-tetrahydro-1H-carbazol-1-
ol (15c). According to general procedure II, to the stirred solution of
compound 14c (100 mg, 0.33 mmol) in dry THF (15 mL) was added
vinyl magnesium bromide (0.4 mL, 0.42 mmol, 1.0 M solution in
THF) under N2 atmosphere to afford compound 15c as a colorless
liquid which was purified by silica gel column chromatography.
Yield 77% (84 mg). Rf ¼ 0.44 (20% EtOAc/Petroleum ether). 1H NMR
4.1.1.3. 9-Allyl-6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one (14c).
According to general procedure I, to the solution of compound 12c
(1 g, 3.38 mmol) in acetone (25 mL), NaH (183 mg, 7.63 mmol) was
added under N2 atmosphere followed by addition of allyl bromide
(0.85 mL, 7.63 mmol) to afford colorless liquid 14c which was pu-
rified by silica gel column chromatography. Yield 63% (0.73 g).
Rf ¼ 0.50 (100% petroleum ether). Spectral data is matching with
reported compound.9a
(500 MHz, CDCl3)
d
¼ 7.63 (d, J ¼ 1.6 Hz,1H), 7.24 (dd, J ¼ 6.0, 2.0 Hz,
1H), 7.10 (d, J ¼ 8.4 Hz,1H), 6.08 (dd, J ¼ 17.2,10.8 Hz,1H), 5.93e5.86
(m, 1H), 5.22e5.09 (m, 3H), 4.91e4.82 (m, 3H), 2.72e2.67 (m, 2H),
2.04e1.90 (m, 5H) ppm. 13C NMR (100 MHz, CDCl3)
d
¼ 142.5, 136.7,
136.0, 136.4, 128.3, 125.0, 121.6, 116.3, 114.6, 112.5, 112.4, 111.6, 72.5,
4.1.1.4. 9-Allyl-8-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one
(14d). According to general procedure I, to the solution of com-
pound 12d (1 g, 3.38 mmol) in acetone (25 mL), NaH (183 mg,
7.63 mmol) was added under N2 atmosphere followed by addition
of allyl bromide (0.85 mL, 7.63 mmol) to afford compound 14d as a
colorless liquid which was purified by silica gel column chroma-
tography. Yield 70% (0.81 g). Rf ¼ 0.5, 100% petroleum ether. 1H
47.1, 41.6, 21.5, 20.6 ppm. IR (neat) ¼ 3261, 2942, 1458, 1058 cmꢀ1
.
HRMS (ESI) calculated for C17H18BrKNO [MþK] 370.0203 found
370.0203.
4.1.2.4. 9-Allyl-8-bromo-1-vinyl-2,3,4,9-tetrahydro-1H-carbazol-1-
ol (15d). According to general procedure II, to the stirred solution of
compound 14d (100 mg, 0.33 mmol) in dry THF (15 mL) was added
vinyl magnesium bromide (0.4 mL, 0.42 mmol, 1.0 M solution in
THF) under N2 atmosphere to afford 15d as a colorless liquid which
was purified by silica gel column chromatography. Yield 78%
(85 mg). Rf ¼ 0.45 (20% EtOAc/Petroleum ether). 1H NMR (500 MHz,
NMR (400 MHz, CDCl3)
d
¼ 7.60 (d, J ¼ 8.0 Hz, 1H), 7.58 (d, J ¼ 8.0,
1H), 6.97 (t, J ¼ 8.0 Hz, 1H), 6.06e5.98 (m, 1H), 5.75e5.73 (m, 2H),
5.04 (dd, J ¼ 10.4, 1.6 Hz, 1H), 4.75 (dd, J ¼ 15.6, 1.6 Hz, 1H), 2.99 (t,
J ¼ 6.0 Hz, 2H), 2.65 (t, J ¼ 6.0 Hz, 2H), 2.24e2.17 (m, 2H) ppm. 13C
NMR (125 MHz, CDCl3)
d
¼ 191.7, 135.9, 135.4, 132.4, 131.1, 130.1,
CDCl3)
d
¼ 7.45 (dd, J ¼ 8.0, 1.0 Hz, 1H), 7.35 (dd, J ¼ 7.5, 1.0 Hz, 1H),
128.3, 121.2, 120.7, 115.3, 104.6, 47.2, 40.5, 24.5, 21.9 ppm. IR (neat)
2933, 1719, 1421, 1135, 928 cmꢀ1. HRMS (ESI) calcd for C15H15BrNO
[M þ H] 304.0333 found 304.0334.
6.93 (t, J ¼ 8.0 Hz, 1H), 6.12 (dd, J ¼ 17.0, 11.0 Hz, 1H), 6.05e5.98 (m,
1H), 5.54e5.50 (m, 1H), 5.24e5.20 (m, 2H), 5.15e5.10 (m, 1H), 5.05
(dd, J ¼ 10.5, 1.5 Hz, 1H), 4.55 (dd, J ¼ 17.0, 1.5 Hz,1H), 2.76e2.70 (m,
2H), 2.09 (s, 1H), 2.02e1.92 (m, 4H) ppm. 13C NMR (100 MHz,
4.1.2. General procedure (II) for vinyl Grignard reaction
4.1.2.1. 9-Allyl-1-vinyl-2,3,4,9-tetrahydro-1H-carbazol-1-ol
CDCl3)
d
¼ 143.1, 137.9, 137.7, 134.0, 130.4, 128.6, 120.8, 118.7, 115.1,
(15a).
114.8, 114.4, 104.3, 72.7, 47.8, 42.4, 22.0, 20.7 ppm. IR (neat) ¼ 3672,
2996, 1413, 1161, 929 cmꢀ1. HRMS (ESI) calculated for C17H18BrKNO
[MþK] 370.0203 found 370.0202.
To the solution of 14a (100 mg, 0.44 mmol) in dry THF (10 mL) was
added vinyl magnesium bromide (0.6 mL, 0.58 mmol,1.0 M solution
in THF), then resulting mixture was stirred for 2 h at 0 ꢂC. After the
completion of reaction (TLC monitoring), the reaction mixture was
quenched with water and extracted with EtOAc (10 ꢁ 3 mL). The
combined organic layer was washed with brine, dried over Na2SO4,
4.1.3. General procedure (III) of RCM
4.1.3.1. 2,3-Dihydro-1H-pyrido[3,2,1-jk] carbazole (16a). To the
stirred solution of 16a (50 mg, 0.19 mmol) in dry CH2Cl2 (10 mL)
Please cite this article in press as: Kotha S, et al., Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin
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S. Kotha et al. / Tetrahedron xxx (2017) 1e7
5
was added G-I catalyst (8 mg, 5 mol %) under ethylene atmosphere.
The resulting mixture was stirred for 2 h at room temperature. After
the completion of reaction (TLC monitoring), the solvent was
removed from reaction mixture. The crude product obtained was
purified by silica gel column chromatography to afford 16a as green
fluorescent liquid. Yield 85% (35 mg). Rf ¼ 0.75 (100% petroleum
mixture was quenched with water and extracted with EtOAc
(10 ꢁ 3 mL). The combined organic layer was washed with brine,
dried over Na2SO4, and concentrated. The crude product obtained
was purified by silica gel column chromatography (10% EtOAc/Pet.
ether) to give compound 17a as light brown liquid. Yield 72%
(85 mg). Rf ¼ 0.45 (20% EtOAc/petroleum ether). 1H NMR (500 MHz,
ether). 1H NMR (400 MHz, CDCl3)
d
¼ 8.05 (dd, J ¼ 7.2, 0.8 Hz, 1H),
CDCl3)
d
¼ 7.51 (d, J ¼ 7.5 Hz, 1H), 7.25e7.19 (m, 2H), 7.11 (t,
7.87 (dd, J ¼ 8.0, 0.8 Hz, 1H), 7.79e7.77 (m, 1H), 7.42e7.38 (m, 1H),
7.30e7.27 (m, 1H), 6.48 (d, J ¼ 6.0 Hz, 1H), 6.38e6.35 (m, 1H), 3.09
(t, J ¼ 6.0 Hz, 2H), 2.93 (t, J ¼ 6.4 Hz, 2H), 2.17e2.11 (m, 2H) ppm. 13C
J ¼ 7.5 Hz, 1H), 6.03e6.02 (m, 1H), 5.84e5.81 (m, 1H), 5.28e5.27 (m,
1H), 5.25e5.24 (m, 3H), 5.17e5.15 (m, 2H), 2.83e2.65 (m, 4H),
2.24e2.20 (m, 1H), 1.92e1.81 (m, 4H) ppm. 13C NMR (100 MHz,
NMR (100 MHz, CDCl3)
d
¼ 134.3, 130.8, 129.3, 127.1, 122.0, 121.4,
CDCl3)
d
¼ 137.7, 137.2, 134.6, 133.7, 126.6, 122.2, 119.2, 118.9, 118.9,
119.1, 118.8, 114.8, 110.7, 108.3, 101.8, 28.4, 23.3, 21.7 ppm. IR
116.1, 112.4, 110.1, 71.6, 47.4, 44.5, 38.9, 21.7, 21.2 ppm. IR
(neat) ¼ 3449, 2926, 1612, 1369, 1202, 1047 cmꢀ1. HRMS (ESI)
calculated for C18H21NKO [MþK] 306.1251 found 306.1253.
(neat) ¼ 3292, 1399, 1236, 1048 cmꢀ1. HRMS (ESI) calculated for
C
15H14N [MþH] 208.1121 found 208.1127.
4.1.3.2. 10-Chloro-2,3-dihydro-1H-pyrido[3,2,1-jk] carbazole (16b).
According to general procedure III, compound 15b (50 mg,
0.17 mmol) was stirred in dry CH2Cl2 (15 mL) followed by addition
of G-I (7 mg, 5 mol %) under ethylene atmosphere. Further, purified
by silica gel column chromatography to afford 16b as green fluo-
rescent liquid. Yield 84% (35 mg). Rf ¼ 0.76 (100% petroleum ether).
4.1.4.2. 1,9-Diallyl-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-ol
(17b). According to general procedure IV, to the stirred solution of
compound 14b (100 mg, 0.38 mmol) in dry THF (15 mL) was added
allyl magnesium bromide (0.5 mL, 0.50 mmol, 1.0 M solution in
diethyl ether) under N2 atmosphere to afford colorless liquid 17b
which was purified by silica gel column chromatography. Yield 75%
(84 mg). Rf ¼ 0.45 (20% EtOAc/petroleum ether). 1H NMR (500 MHz,
1H NMR (400 MHz, CDCl3)
d
¼ 8.00 (d, J ¼ 7.2 Hz, 1H), 7.72 (t,
J ¼ 8.4 Hz,1H), 7.68 (s, 1H), 7.17 (d, J ¼ 8.4 Hz,1H), 6.49 (d, J ¼ 6.4 Hz,
CDCl3)
d
¼ 7.45 (d, J ¼ 0.5 Hz, 1H), 7.13e7.12 (m, 2H), 6.01e5.95 (m,
1H), 6.38 (t, J ¼ 6.4 Hz,1H), 3.00 (t, J ¼ 6.8 Hz, 2H), 2.89 (t, J ¼ 6.8 Hz,
1H), 5.84e79 (m, 1H), 5.25e5.14 (m, 4H), 4.92e4.85 (m, 2H), 3.79
(dd, J ¼ 14.0, 7.5 Hz, 1H), 2.69e2.61 (m, 3H), 2.23e2.21 (m, 1H),
2H), 2.12e2.06 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3)
d
¼ 135.4,
2.20e1.78 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3)
134.2, 133.2, 127.7, 124.9, 122.3, 119.3, 118.4, 116.3, 111.9, 111.1, 71.5,
d
¼ 138.7, 136.0,
130.8, 128.0, 127.8, 127.7, 121.4, 119.3, 118.1, 115.6, 111.7, 108.9, 101.7,
28.3, 23.1, 21.4 ppm. IR (neat) ¼ 2943, 1452, 1200, 976 cmꢀ1. HRMS
(ESI) calculated for C15H13ClN [MþH] 242.0737 found 242.0731.
47.5, 44.4, 38.8, 21.5, 21.1 ppm. IR (neat) ¼ 3293, 2935, 1603, 1401,
1046 cmꢀ1
340.0865 found 340.0864.
.
HRMS (ESI) calculated for C18H20ClKNO [MþK]
4.1.3.3. 10-Bromo-2,3-dihydro-1H-pyrido[3,2,1-jk] carbazole (16c).
According to general procedure III, compound 15c (50 mg,
0.15 mmol) was stirred in dry CH2Cl2 (15 mL) followed by addition
of G-I catalyst (6 mg, 5 mol %) under ethylene atmosphere. Further,
purified by silica gel column chromatography to afford 16c as a
fluorescent yellow liquid. Yield 86% (37 mg). Rf ¼ 0.75 (100% pe-
4.1.4.3. 1,9-Diallyl-6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ol
(17c). According to general procedure IV, to the stirred solution of
compound 14c (100 mg, 0.33 mmol) in dry THF was added allyl
magnesium bromide (0.4 mL, 0.42 mmol, 1.0 M solution in diethyl
ether) under N2 atmosphere to afford light yellow liquid 17c which
was purified by silica gel column chromatography. Yield 72%
(82 mg). Rf ¼ 0.45 (20% EtOAc/petroleum ether). 1H NMR (500 MHz,
troleum ether). 1H NMR (500 MHz, CDCl3)
d
¼ 7.98 (d, J ¼ 7.2,
0.8 Hz, 1H), 7.67 (d, J ¼ 8.8 Hz, 1H), 7.58e7.53 (m, 1H), 7.29 (dd,
J ¼ 8.4, 2.0 Hz, 1H), 6.49 (d, J ¼ 6.0 Hz, 1H), 6.38 (t, J ¼ 6.4 Hz, 1H),
2.99 (t, J ¼ 6.0 Hz, 2H), 2.88 (t, J ¼ 6.0 Hz, 2H), 2.12e2.05 (m, 2H)
ppm. 13C NMR (100 MHz, CDCl3)
d
¼ 135.2,130.8, 128.5, 127.9, 121.8,
CDCl3)
d
¼ 7.60 (d, J ¼ 1.6 Hz, 1H), 7.24 (d, J ¼ 1.6 Hz, 1H), 7.09 (d,
J ¼ 8.8 Hz, 1H), 6.01e5.77 (m, 2H), 5.24e5.13 (m, 4H), 4.91e4.85 (m,
121.4, 121.3, 115.7, 115.6, 112.9, 108.5, 101.5, 28.2, 23.1, 21.4 ppm. IR
(neat) ¼ 3293, 1404, 1196, 1051, 883 cmꢀ1. HRMS (ESI) calculated
for C15H13BrN [MþH] 286.0226 found 286.0221.
2H), 2.76e2.63 (m, 4H), 2.23e2.18 (m, 1H), 1.91e1.78 (m, 4H) ppm.
13C NMR (100 MHz, CDCl3)
d
¼ 138.6, 136.3, 134.2, 133.3, 128.4,
124.9,121.5,119.3,116.3,112.5,111.9,111.6, 71.6, 47.5, 44.4, 38.8, 21.5,
21.1 ppm. IR (neat) ¼ 3426, 2928, 1602, 1349, 1223, 1047 cmꢀ1
.
4.1.3.4. 8-Bromo-2,3-dihydro-1H-pyrido[3,2,1-jk] carbazole (16d).
According to general procedure III, compound 15d (50 mg,
0.15 mmol) was stirred in dry CH2Cl2 (15 mL) followed by addition
of G-I catalyst (6 mg, 5 mol %) under ethylene atmosphere. Further,
purified by silica gel column chromatography to afford 16d as
fluorescent yellow liquid. Yield 84% (36 mg). Rf ¼ 0.75 (100% pe-
HRMS (ESI) calculated for C18H20BrNKO [MþK] 384.0360 found
384.0360.
4.1.4.4. 1,9-Diallyl-8-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ol
(17d). According to general procedure IV, to the stirred solution of
compound 14d (100 mg, 0.33 mmol) in dry THF (15 mL) was added
allyl magnesium bromide (0.4 mL, 0.42 mmol, 1.0 M solution in
diethyl ether) under N2 atmosphere to afford light yellow liquid
compound 17d which was purified by silica gel column chroma-
tography. Yield 75% (85 mg). Rf ¼ 0.45 (20% EtOAc/petroleum
troleum ether). 1H NMR (500 MHz, CDCl3)
d
¼ 9.26 (d, J ¼ 7.5 Hz,
1H), 7.67 (d, J ¼ 8.0 Hz, 1H), 7.39 (d, J ¼ 7.5 Hz, 1H), 7.16 (t, J ¼ 7.5 Hz,
1H), 6.50 (d, J ¼ 6.5 Hz,1H), 6.37 (t, J ¼ 6.5 Hz,1H), 3.03 (t, J ¼ 6.0 Hz,
2H), 2.90 (t, J ¼ 6.0 Hz, 2H), 2.09 (m, 2H) ppm. 13C NMR (100 MHz,
CDCl3)
d
¼ 135.4, 130.4, 130.0, 126.0, 124.0, 123.8, 122.5, 117.7, 115.7,
108.2, 106.2, 102.9, 28.6, 22.9, 21.5 ppm. IR (neat) ¼ 3426, 2928,
1602, 1349, 1223, 1047 cmꢀ1. HRMS (ESI) calculated for C15H13BrN
[MþH] 286.0226 found 286.0224.
ether). 1H NMR (500 MHz, CDCl3)
d
¼ 7.43 (dd, J ¼ 8.0, 1.0 Hz, 1H),
7.41 (d, J ¼ 8.0,1.0 Hz,1H), 6.92 (t, J ¼ 8.0 Hz,1H), 6.07e6.04 (m, 1H),
5.87e5.81 (m, 1H), 5.62e5.61 (m, 1H), 5.46e5.43 (m, 1H), 5.18e5.14
(m, 2H), 5.07 (dd, J ¼ 10.5,1.0 Hz,1H), 4.58 (dd, J ¼ 17.0,1.5,1H), 2.84
(dd, J ¼ 7.0, 1.0 Hz, 1H), 2.70 (m, 2H), 2.64 (dd, J ¼ 7.0, 1.0 Hz, 1H),
2.22e2.05 (m, 1H), 1.96e1.78 (m, 4H) ppm. 13C NMR (100 MHz,
4.1.4. General procedure (IV) allyl Grignard reaction
4.1.4.1. 1,9-Diallyl-2,3,4,9-tetrahydro-1H-carbazol-1-ol
(17a).
To the solution of 14a (100 mg, 0.44 mmol) in dry THF (10 mL) was
added allyl magnesium bromide (0.6 mL, 0.57 mmol, 1.0 M solution
in diethyl ether), then resulting mixture was stirred for 2 h at 0 ꢂC.
After the completion of reaction (TLC monitoring), the reaction
CDCl3)
d
¼ 139.2, 137.1, 133.8, 133.5, 130.2, 128.1, 120.4, 119.0, 118.2,
114.7, 113.2, 103.2, 71.8, 47.8, 44.1, 39.2, 21.6, 20.9 ppm. IR
(neat) ¼ 3466, 2928, 1652, 1322, 1234, 1011 cmꢀ1. HRMS (ESI)
calculated for C18H20BrNKO [MþK] 384.0360 found 384.0360.
Please cite this article in press as: Kotha S, et al., Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin
metathesis, Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.09.039

6
S. Kotha et al. / Tetrahedron xxx (2017) 1e7
4.1.5. General procedure (V) of RCM
(100 mg, 0.4 mmol) in Et3N (10 mL) was degasified with N2 at room
temperature and Pd(PPh3)2Cl2 (14 mg, 0.02 mmol), CuI (4 mg,
0.02 mmol) and TMS acetylene (0.1 mL, 0.60 mmol) were added
sequentially. The resulting reaction mixture was stirred for 12 h at
50 ꢂC. After completion of reaction (TLC monitoring) the solvent
was removed in rotary evaporator. The crude residue was purified
by silica gel column chromatography (2% EtOAc- petroleum ether)
to afford 19 as a light yellow solid. Yield 84% (90 mg). M.p.
68e70 ꢂC. Rf ¼ 0.60 (100% petroleum ether). 1H NMR (500 MHz,
4.1.5.1. 2,3,4,7-Tetrahydroazepino[3,2,1-jk]carbazol-3a(1H)-ol (18a).
To the stirred solution of 17a (50 mg, 0.19 mmol) in dry CH2Cl2
(10 mL) was added G-II catalyst (8 mg, 5 mol %) under ethylene
atmosphere. The resulting mixture was stirred for 2 h at room
temperature. After the completion of reaction (TLC monitoring), the
solvent was removed from reaction mixture. The crude product
obtained was purified by silica gel column chromatography (100%
Pet. ether) to give compound 18a as green fluorescent liquid. Yield
70% (31 mg). Rf ¼ 0.42 (20% EtOAc/petroleum ether). 1H NMR
CDCl3)
d
¼ 7.96 (s,1H), 7.45 (d, J ¼ 7.5 Hz,1H), 7.27 (d, J ¼ 8.0 Hz,1H),
(500 MHz, CDCl3)
d
¼ 7.52 (d, J ¼ 7.5 Hz,1H), 7.29e7.20 (m, 2H), 7.09
7.04e7.00 (m, 1H), 2.78 (t, J ¼ 6.0 Hz, 2H), 2.71 (t, J ¼ 6.0 Hz, 2H),
(t, J ¼ 7.0 Hz, 1H), 5.93e5.91 (m, 1H), 5.75 (t, J ¼ 3.0 Hz, 1H),
1.95e1.88 (m, 4H), 0.33 (s, 9H) ppm. 13C NMR (125 MHz, CDCl3)
4.82e4.76 (m, 2H), 2.81e2.76 (m, 1H), 2.69e2.64 (m, 3H), 2.12 (s,
d
¼ 136.8, 134.5, 127.6, 124.9, 119.1, 118.9, 111.0, 105.2, 102.0, 97.9,
1H), 2.05e1.89 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3)
d
¼ 138.2,
23.4, 23.4, 23.3, 21.1, 0.42 ppm. IR (neat) ¼ 3471, 2938, 2145, 1693,
1461, 1249, 843 cmꢀ1. HRMS (ESI) calculated for C17H21NNaSi
[MþNa] 290.1335 found 290.1335.
137.1, 127.6, 126.3, 124.4, 122.0, 119.1, 119.0, 111.8, 109.0, 70.0, 43.9,
41.8, 41.4, 21.7, 21.6 ppm. IR (neat) ¼ 3576, 3294, 1463, 1400,
1048 cmꢀ1
262.1202 found 262.1207.
.
HRMS (ESI) calculated for C16H17NNaO [MþNa]
4.1.7. General procedure (VII) for deprotection of TMS
4.1.7.1. 8-Ethynyl-2,3,4,9-tetrahydro-1H-carbazole (20). To the so-
lution of compound 19 (80 mg, 0.29 mmol) in dry THF (10 mL) was
added TBAF (0.4 mL, 0.36 mmol, 1.0 M solution in THF) at room
temperature. The resulting reaction mixture was stirred for 2 h at
room temperature. After completion of reaction (TLC monitoring),
the reaction mixture was quenched with sat. NH4Cl solution and
extracted by EtOAc (3 ꢁ 10 mL), washed with brine, dried over
Na2SO4. The crude product was purified by silica gel column
chromatghraphy (2% EtOAc- petroleum ether) to afford 20 as a
yellow solid. Yield 96% (57 mg). M.p. 64e66 ꢂC. Rf ¼ 0.58 (silica gel,
4.1.5.2. (S)-11-Chloro-2,3,4,7-tetrahydroazepino[3,2,1-jk]carbazol-
3a(1H)-ol (18b). According to general procedure V, compound 17b
(50 mg, 0.17 mmol) was stirred in dry CH2Cl2 (10 mL) followed by
addition of G-II catalyst (7 mg, 5 mol %) under ethylene atmosphere
to afford 18b which was purified by silica gel column chromatog-
raphy. Yield 80% (36 mg). Rf ¼ 0. 43 (20% EtOAc/petroleum ether).
1H NMR (500 MHz, CDCl3)
d
¼ 7.46 (d, J ¼ 2.0 Hz, 1H), 7.18e7.12 (m,
2H), 5.91e5.89 (m, 1H), 5.75e5.73 (m, 1H), 4.74 (d, J ¼ 1.5 Hz, 2H),
2.71e2.58 (m, 4H), 2.11e1.86 (m, 5H) ppm. 13C NMR (100 MHz,
CDCl3)
d
¼ 139.4, 135.7, 128.0, 127.7, 124.7, 124.1, 121.7, 112.2, 111.4,
100% petroleum ether). 1H NMR (400 MHz, CDCl3)
d
¼ 8.03 (s, 1H),
110.5, 69.9, 44.0, 41.8, 41.3, 21.6, 21.5 ppm. IR (neat) ¼ 3407, 2931,
1654, 1460, 1068 cmꢀ1. HRMS (ESI) calculated for C16H16ClKNO
[MþK] 312.0552 found 312.0550.
7.47 (d, J ¼ 8.0 Hz, 1H), 7.29 (d, J ¼ 0.8 Hz,1H), 7.03 (t, J ¼ 8.0 Hz, 1H),
3.35, (s, 1H), 2.77e2.69 (m, 4H), 1.96e1.88 (m, 4H) ppm. 13C NMR
(125 MHz, CDCl3)
d
¼ 137.1, 134.7, 127.6, 124.9, 119.2, 119.1, 111.1,
104.1, 80.9, 80.8, 23.4, 23.3, 21.1 ppm. IR (neat) ¼ 3436, 2928, 2338,
1464, 1320, 1150 cmꢀ1. HRMS (ESI) calculated for C14H14N [MþH]
196.1121 found 196.1122.
4.1.5.3. (S)-11-Bromo-2,3,4,7-tetrahydroazepino[3,2,1-jk]carbazol-
3a(1H)-ol (18c). According to general procedure V, compound 17c
(50 mg, 0.14 mmol) was stirred in dry CH2Cl2 (10 mL) followed by
addition of G-II catalyst (6 mg, 5 mol %) under ethylene atmosphere
to afford 18c as a brown liquid which was purified by silica gel
column chromatography. Yield 85% (39 mg). Rf ¼ 0.43 (20% EtOAc/
4.1.7.2. 9-Allyl-8-ethynyl-2,3,4,9-tetrahydro-1H-carbazole
(21).
According to general procedure I, to the solution of compound 19
(50 mg, 0.25 mmol) in acetone (10 mL), NaH (9 mg, 0.38 mmol) was
added under N2 atmosphere followed by addition of allyl bromide
(0.05 mL, 0.38 mmol) and stirred for 4 h. The crude product was
purified by silica gel column chromatography to afford 22 as a
yellow liquid. Yield 48% (28 mg). Rf ¼ 0.72 (100% petroleum ether).
Compound 21 was synthesized from 23. According to general
procedure VII, to the solution of compound 23 (100 mg, 0.33 mmol)
in dry a THF (10 mL), TBAF (0.5 mL, 0.48 mmol, 1.0 M solution in
THF) was added and stirred for 1 h. The crude product was purified
by silica gel column chromatography to afford 22 as a yellow liquid.
Yield 94% (72 mg). Rf ¼ 0.72 (100% petroleum ether). 1H NMR
petroleum ether). 1H NMR (500 MHz, CDCl3)
d
¼ 7.61 (d, J ¼ 1.5 Hz,
1H), 7.27e7.25 (m, 1H), 7.13 (d, J ¼ 9.0 Hz, 1H), 5.93e5.89 (m, 1H),
5.75e5.72 (m, 1H), 4.75 (s, 2H), 2.80e2.58 (m, 4H), 2.10e1.86 (m,
5H) ppm. 13C NMR (100 MHz, CDCl3)
d
¼ 139.4, 135.7, 128.0, 127.7,
124.7, 124.1, 121.7, 112.2, 111.4, 110.5, 69.9, 44.0, 41.8, 41.3, 21.6,
21.5 ppm. IR (neat) ¼ 3449, 1606, 1398, 1046 cmꢀ1. HRMS (ESI)
calculated for C16H16BrNKO [MþK] 356.0044 found 356.0047.
4.1.5.4. (S)-9-Bromo-2,3,4,7-tetrahydroazepino[3,2,1-jk]carbazol-
3a(1H)-ol (18d). According to general procedure V, compound 17d
(50 mg, 0.14 mmol) was stirred in dry CH2Cl2 (10 mL) followed by
addition of G-II catalyst (6 mg, 5 mol %) under ethylene atmosphere
to afford 18d as a light brown liquid, which was purified by silica gel
column chromatography. Yield 82% (37 mg). Rf ¼ 0.44 (20% EtOAc/
(500 MHz, CDCl3)
d
¼ 7.50 (d, J ¼ 8.0 Hz, 1H), 7.34 (d, J ¼ 7.5 Hz, 1H),
7.02 (t, J ¼ 7.5 Hz, 1H), 6.07e6.00 (m, 1H), 5.16 (d, J ¼ 1.8 Hz, 2H),
5.10 (dd, J ¼ 10.0, 1.0 Hz, 1H), 4.80 (dd, J ¼ 18.5, 1.5 Hz, 1H), 3.30 (s,
1H), 2.73 (t, J ¼ 6.0 Hz, 2H), 2.68 (t, J ¼ 6.5 Hz, 2H), 1.93 (dd, J ¼ 10.5,
4.5 Hz, 2H), 1.88 (dd, J ¼ 10.5, 4.5 Hz, 2H) ppm. 13C NMR (125 MHz,
petroleum ether). 1H NMR (500 MHz, CDCl3)
1H), 7.35e7.34 (m, 1H), 6.91e6.88 (m, 1H), 6.20e6.16 (m, 1H),
6.06e5.98 (m, 1H), 5.75e5.73 (m, 1H), 4.78 (d, J ¼ 17.0 Hz, 1H),
2.74e2.58 (m, 4H), 2.12 (s, 1H), 2.05e1.87 (m, 4H) ppm. 13C NMR
d
¼ 7.42 (d, J ¼ 8.0 Hz,
CDCl3)
d
¼ 136.9, 135.5, 135.0, 128.5, 127.9, 119.3, 118.5, 115.5, 110.2,
103.8, 82.7, 80.3, 45.7, 23.4, 23.2, 22.1, 21.0 ppm. IR (neat) ¼ 2928,
2338, 1542, 1446, 1158, 997 cmꢀ1. HRMS (ESI) calculated for
(100 MHz, CDCl3)
d
¼ 139.9, 133.1, 129.8, 128.5, 128.1, 125.0, 120.2,
C
17H18N [MþH] 236.1434 found 236.1434.
118.4, 112.5, 103.8, 70.1, 43.2, 42.0, 41.8, 21.5, 21.5 ppm. IR
(neat) ¼ 3748, 2944, 1606, 1410, 1047, 822 cmꢀ1. HRMS (ESI)
calculated for C16H16BrNKO [MþK] 356.0046 found 356.0047.
4.1.7.3. 9-Allyl-8-bromo-2,3,4,9-tetrahydro-1H-carbazole
(22).
According to general procedure I, to the solution of compound 11d
(500 mg, 2.00 mmol) in dry acetone (10 mL) NaH (72 mg,
3.01 mmol) was added under N2 atmosphere followed by addition
of allyl bromide (0.3 mL, 3.01 mmol) and stirred for 4 h. The crude
product was purified by silica gel column chromatography to afford
4.1.6. General procedure (VI) for Sonogashira coupling reaction
4.1.6.1. 8-((Trimethylsilyl)ethynyl)-2,3,4,9-tetrahydro-1H-carbazole
(19). To the solution the solution of bromo carbazole derivative 11d
Please cite this article in press as: Kotha S, et al., Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin
metathesis, Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.09.039

S. Kotha et al. / Tetrahedron xxx (2017) 1e7
7
22 as a yellow liquid. M.p. 100e102 ꢂC. Yield 92% (533 mg).
References
Rf ¼ 0.65 (100% petroleum ether). 1H NMR (400 MHz, CDCl3)
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d
¼ 7.42 (d, J ¼ 1.2 Hz,1H), 7.40 (d, J ¼ 1.2 Hz,1H), 6.93e6.89 (m,1H),
6.06e5.95 (m, 1H), 5.11e5.08 (m, 3H), 4.72 (s, 1H), 4.68 (d,
J ¼ 0.8 Hz, 1H), 2.72e2.65 (m, 4H), 1.97e1.92 (m, 2H), 1.90e1.87 (m,
2H) ppm. 13C NMR (100 MHz, CDCl3)
d
¼ 137.8, 135.5, 132.7, 130.9,
126.3, 120.0, 117.3, 115.5, 110.5, 103.3, 45.9, 23.4, 23.3, 22.3,
21.1 ppm. IR (neat) ¼ 2932, 1440, 1154, 997, 865 cmꢀ1. HRMS (ESI)
calculated for C15H17BrN [MþH] 290.0539 found 290.0537.
4.1.7.4. 9-Allyl-8-((trimethylsilyl)ethynyl)-2,3,4,9-tetrahydro-1H-
carbazole (23). According to general procedure of VI, compound 22
(220 mg, 0.76 mmol) in Et3N (10 mL) was added Pd(PPh3)2Cl2
(26 mg, 0.038 mmol), CuI (7 mg, 0.038 mmol) and TMS acetylene
(0.2 mL, 1.14 mmol) were added and stirred for 12 h. The crude
product was purified by column chromatography (2% EtOAc- pe-
troleum ether) to afford 19 as a yellow liquid. Yield 87% (203 mg).
Rf ¼ 0.70 (100% petroleum ether). 1H NMR (400 MHz, CDCl3)
d
¼ 7.45 (dd, J ¼ 6.8, 0.8 Hz, 1H), 7.28 (dd, J ¼ 7.2, 2.4 Hz, 1H), 6.98 (t,
J ¼ 7.6 Hz, 1H), 6.05e5.98 (m, 1H), 5.19e5.07 (m, 2H), 5.17 (dt,
J ¼ 7.2, 0.8 Hz, 1H), 5.09 (dt, J ¼ 7.2, 0.8 Hz, 1H), 2.27e2.65 (m, 4H),
1.94e1.90 (m, 2H), 1.88e1.84 (m, 2H), 0.28 (s, 9H) ppm. 13C NMR
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(c) Bennasar ML, Jimenez J-M, Vidal B, Sufi BA, Bosch J. J Org Chem. 1999;64:
(100 MHz, CDCl3)
d
¼ 136.9, 135.6, 134.9, 128.5, 127.5, 119.1, 118.5,
115.5, 110.2, 105.0, 104.2, 97.3, 45.8, 23.4, 23.3, 22.1, 21.1, 0.10 ppm.
IR (neat) ¼ 3288, 2935, 2101, 1678, 1463, 1149, 1049 cmꢀ1. HRMS
(ESI) calculated for C20H26NSi [MþH] 308.1825 found 308.1829.
ꢀ
9605.
4.1.8. 6a,7,9,10,11,12-hexahydrocyclopenta[4,5]pyrido[3,2,1-jk]
carbazol-5(6H)-one(24)
7. (a) Shenje R, Martin MC, France S. Angew Chem Int Ed. 2014;53:13907;
(b) Cera G, Piscitelli S, Chiarucci M, et al. Angew Chem Int Ed. 2012;51:9891.
8. Ennis MD, Hoffman RL, Ghazal NB, et al. Bioorg Med Chem Lett. 2003;13:2369.
9. (a) Kotha S, Saifuddin M, Aswar VR. Org Biomol Chem. 2016;14:9868;
(b) Kotha S, Chinnam AK, Shirbhate ME. J Org Chem. 2015;80:9141;
To the solution of Co2(CO)8 (160 mg, 0.21 mmol) in dry 1,2-
dichloroethane was added enyne 21 (50 mg, 0.21 mmol) and
resulting reaction mixture was stirred for 10 min at rt. The resulting
reaction mixture stirred for 25 min at 90 ꢂC. After completion of
reaction (TLC monitoring), the reaction mixture was concentrated
in vaccum. The crude product was purified by silica gel column
chromatography (10% EtOAc in petroleum ether) to afford com-
pound 25 as yellow solid. Yield 79% (44 mg). M.p. 172e174 ꢂC.
Rf ¼ 0.25 (10% EtOAc in petroleum ether). 1H NMR (500 MHz,
€
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_
11. (a) Jana A, Misztal K, Zak A, Grela K. J Org Chem. 2017;82:4226;
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thesis. second ed. Weinheim: Germany: Wiely-VCH; 2015;
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Weinheim: Wiley -VCH; 2010;
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(l) Kotha S, Shah VR. Eur J Org Chem. 2008:1054;
(m) Kotha S, Shah VR, Mandal K. Adv Synth Catal. 2007;349:1159;
(n) Grela K. Angew Chem Int Ed. 2008;47:5504;
CDCl3)
d
¼ 7.54 (d, J ¼ 8.0 Hz, 1H), 7.36 (d, J ¼ 7.5 Hz, 1H), 7.09 (t,
J ¼ 8.0 Hz, 1H), 6.46 (s, 1H), 4.41 (dd, J ¼ 10.5, 5.5 Hz, 1H), 3.52e3.42
(m, 2H), 2.83 (dd, J ¼ 18.0, 6.5 Hz, 1H), 2.79e2.64 (m, 4H), 2.21 (dd,
J ¼ 18.0, 6.5 Hz, 1H), 1.96e1.93 (m, 4H) ppm. 13C NMR (100 MHz,
CDCl3)
d
¼ 206.5, 168.9, 136.4, 134.9, 126.7, 123.2, 121.7, 119.7, 117.7,
114.6, 110.6, 45.9, 39.8, 37.8, 23.2, 23.0, 21.8, 21.3 ppm. IR
(neat) ¼ 2930, 1698, 1613, 1186, 1043 cmꢀ1. HRMS (ESI) calculated
for C18H17NNaO [MþNa] 286.1202 found 286.1202.
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Acknowledgment
(p) Kotha S, Dipak MK. Chem Eur J. 2006;12:4446;
ꢀ
(q) Zeng Y, Reddy DS, Hirt E, Aube J. Org Lett. 2004;6:4993;
We are grateful to Department of Science and Technology (DST),
New Delhi for the financial support. VRA thanks CSIR-New Delhi for
financial support and award of SRF. GS thanks to IIT Bombay. S. K.
thanks the DST for the award of a J. C. Bose fellowship (SR/S2/JCB-
33/2010) and Praj industries for Chair Professorship (Green
chemistry).
(r) Kotha S, Mandal K. Tetrahedron Lett. 2004;45:1391;
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1618.
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Appendix A. Supplementary data
ꢀ
ꢀ
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2017.09.039.
Please cite this article in press as: Kotha S, et al., Synthesis of tricyclic units of indole alkaloids: Application of Fischer indolization and olefin
metathesis, Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.09.039