Synthesis of di-, tri-, and tetra-substituted carbazole analogs involving annulation methodology

Article abstract of DOI:10.1016/j.tet.2009.03.009

Synthesis of substituted carbazole analogs was achieved via Michael addition followed by intramolecular cyclization and subsequent aromatization.

Full text of DOI:10.1016/j.tet.2009.03.009

Tetrahedron 65 (2009) 3592–3602
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of di-, tri-, and tetra-substituted carbazole analogs involving
annulation methodology
*
Neelamegam Ramesh, Ganesan Gobi Rajeshwaran, Arasambattu K. Mohanakrishnan
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis of substituted carbazole analogs was achieved via Michael addition followed by intramolecular
cyclization and subsequent aromatization.
Received 19 November 2008
Received in revised form 25 February 2009
Accepted 4 March 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 9 March 2009
Keywords:
Indolylmethylsulfoxide
Michael addition
Intramolecular cyclization
Annulation
Substituted carbazoles
1. Introduction
Several annulation strategies based on the Michael addition
followed by intramolecular cyclization have been reported.6 Over
During the past 50 years the focus on the synthesis of indole
derivatives1 is due to its undisputable importance in nature,
where this particular heterocycle is embedded in countless
number of natural products and medicinally relevant com-
pounds.2 Among the indole alkaloids, the carbazole system 1a–e
is the most explored one. Ever since the first isolation of carbazole
alkaloid, murraynine,3 organic chemists have been interested in
the synthesis of carbazole and its derivatives4 due to their
promising biological activities. Kno¨lker and Reddy have exten-
sively reviewed5 the synthesis and biological activities of carb-
azole alkaloids.
the years, the synthesis of large number of carbazole derivatives has
been achieved through Diels–Alder reaction7 of 2/3-vinylindoles.
Similarly, the synthesis of different types of carbazole derivatives
has also been realized through Pd-mediated reactions.8 Jagtap
and Mali have reported9 an annelation of ethyl-N-methyl-2-ben-
zylindole-3-carboxylate. Mohanakrishnan and Srinivasan have
outlined a simple synthesis of 4-hydroxy carbazoles using 3-carb-
ethoxy-2-indolylmethyl sulfoxide as a bidentate synthon, involving
a Michael addition followed by intramolecular cyclization.10
Recently, Hauser and co-workers have fully exploited sulfide-,
sulfoxide-, and sulfonyl-stabilized carbanions to the synthesis of
polycyclic aromatic systems.11 However, annulation methodologies
for carbazoles using 2,3-disubstituted indoles as bidentate syn-
thons have not been thoroughly explored. In further continuation
of our studies on carbazole alkaloids,12 we report here our results
on the synthesis of various types of substituted carbazoles via
Michael addition promoted annulation strategy.
R4
R3
R1
Me
N
H
R2
1a R1 = H, R2 = Me, R3 & R4 = OMe (carbazomycin A)
1b R1 = H, R2 = Me, R3 = OMe, R4 = OH (carbazomycin B)
1c R1 = OMe, R2 = Me, R3 = OMe, R4 = OH (carbazomycin C)
1d R1 = H, R2 = Ph, R3 = OMe, R4 = H (hyellazole)
2. Results and discussion
1e R1 = H, R2 = (CH2)4Me, R3 = OH, R4 = NHAc (antiostatin A1)
Required bromomethylindoles 2a–e13 were prepared from the
corresponding methylindoles via allylic bromination using NBS in
CCl4 at reflux. The bromomethylindoles 2a–e on treatment with
thiophenol using NaH as base in dry THF led to indolylmethyl
sulfides 3a–e.
* Corresponding author. Tel.: þ91 44 22202813; Fax: þ91 44 22300488.
E-mail address: mohan_67@hotmail.com (A.K. Mohanakrishnan).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.009

N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
3593
R1
R1
R1
HO
R3
R2
R2
t-BuOK/THF
R2
R1
CO2Et
R2
R3
O
NaH/PhSH/THF
0 °C, 3 h
SPh
SPh
Br
N
SO2Ph
0 °C, 2-5 h
36-77%
N
N
N
SO2Ph
SO2Ph
SO2Ph
5a-j
4a R1 = OMe
2a R1 = OMe, R2 = CO2Et
2b R1 = H, R2 = CO2Et
2c R1 = H, R2 = COMe
2d R1 = H, R2 = CN
3a-e
4b R1 = H
Scheme 2.
2e R1 = H, R2 = CH2=CHCO2Et
Table 2
As a representative case, the oxidation of indolylmethyl sulfide 3a
with 1 equiv of m-CPBA led to the formation of sulfoxide 4a (70%)
along with corresponding sulfone 5 (15–20%). A slow addition of m-
CPBA to a solution of sulfide 3a at 0 ꢀC also led to the formation of
sulfone 5 as a minor product. Even with less than 1 equiv of m-
CPBA, sulfone 5 was always observed in minor amount along with
starting material 3a.
Finally, the required sulfoxides 4a–e can be smoothly prepared
(Scheme 1) using a combination of KF/m-CPBA.14 The interaction of
KF/m-CPBA in CH3CN/H2O at 0 ꢀC for 10 min followed by addition of
sulfides 3a–e led to the isolation of respective sulfoxides 4a–e in
good yields. Further oxidation of sulfoxides 4a–e into the corre-
sponding sulfones was not observed under this condition, which
might be due to the non-nucleophilic character of the fluorine
oxide (KOF).14 The different substituents of the sulfides 3a–e as well
as sulfoxides 4a–e along with their yields are presented in Table 1.
Carbazole
R1
R2
R3
Yield (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
OMe
OMe
OMe
OMe
H
H
H
H
H
H
H
H
H
H
H
H
H
CO2Me
COMe
CHO
70
77
68
70
70
69
64
70
45
0
CN
CO2Me
COMe
CHO
CN
NO2
Ph
4-OMePh
Me
5j
5k
H
H
NO2
CO2Me
36
proceed in almost comparable yields to afford the corresponding
carbazoles 5a–h. The annulation of sulfoxide 4b with 2-nitrostyrene
was proceeded only in 45% of yield to furnish 3-nitro-2-phenyl-4-
hydroxycarbazole 5i. All attempts to carry out annulation of 4b with
p-methoxyphenyl-2-nitrostyrene were found to be unsuccessful;
only the starting sulfoxide was recovered unchanged. However
using similar condition, the annulation of 4b with methyl crotonate
yielded the respective tri-substituted carbazole 5k in 36% of yield.
As expected, the annulation of sulfoxide 4c could be smoothly
carried out with methyl acrylate as well as MVK to afford the
expected 4-methylcarbazoles 5l/5m in 53 and 48% yields, re-
spectively (Scheme 3).
MeO
CO2Et
MeO
CO2Et
O
m-CPBA
O
3a
SPh
0 °C
S
N
N
Ph
O
SO2Ph
4a
SO2Ph
4a'
R1
R2
R1
R2
O
KF/m-CPBA
CH3CN:H2O
SPh
SPh
N
O
0 °C, 30 min
N
Me
R1
SO2Ph
Me
SO2Ph
4a-e
O
3a-e
t-BuOK/THF
R1
SPh
N
Scheme 1.
N
SO2Ph
4c
0 °C, 2 h
SO2Ph
5l R1 = COCH3 (48%)
Table 1
5m R1 = CO2CH3 (53%)
Sulfide/sulfoxide
R1
R2
Yield (%)
3a/4a
3b/4b
3c/4c
3d/4d
3e/4e
OMe
H
H
H
H
CO2Et
CO2Et
COCH3
CN
90/92
84/90
86/90
82/91
68/94
Scheme 3.
The annulation of sulfoxide 4d with Michael acceptors such as
methyl acrylate, MVK, and acrylonitrile afforded respective 4-
aminocarbazoles 5n–p in 45–50% of yields (Scheme 4). Surpris-
ingly, the annulation of sulfoxide 4d with acrolein didn’t afford the
expected product 5q, only an insoluble polymeric material was
obtained. Presumably, the formation of polymeric material may be
due to the intermolecular self condensation of an aldehyde and
amino function of 5q.
CH2]CHCO2Et
Having prepared the required sulfoxides 4a–e, next the annu-
lation of these sulfoxides using Michael addition as a key step was
initiated. The generation of required sulfoxide stabilized carbanion
was tried using bases such as K2CO3 and NaH. After adjudicating
different bases and conditions, finally, the reaction of sulfoxides 4a/
4b with various Michael acceptors using t-BuOK as a base led to the
formation of respective 4-hydroxy carbazoles 5a–j in 36–77% of
yields (Scheme 2, Table 2).
The mechanism of this annulation reaction involves the initial
Michael addition of the sulfoxide stabilized carbanion followed by
intramolecular cyclization. The resulting intermediate on elimina-
tion of PhSOH unit furnished the respective carbazoles 5a–j.
The annulation of sulfoxides 4a/4b with Michael acceptors such
as methyl acrylate, MVK, acrolein, and acrylonitrile was found to
H2N
R1
CN
O
SPh
t-BuOK/THF
R1
N
N
SO2Ph
4d
0 °C, 2 h
SO2Ph
5n R1 = CO2CH3 (48%)
5o R1 = COCH3 (50%)
5p R1 = CN (45%)
5q R1 = CHO (0%)
Scheme 4.

3594
N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
Attempted double Michael addition of sulfoxide with methyl
acrylate using t-BuOK/n-BuLi was found to be unsuccessful, only
the sulfoxide was recovered unchanged (Scheme 5).
(Scheme 7). Thus, it may be concluded that the annulation of
sulfoxide stabilized carbanion can be successfully performed only
at the indole-2-position (Schemes 2–4). All attempts to perform the
similar annulation at the indole-3-position were unsuccessful due
to the migration of the carbanion to form the corresponding quino-
dimethane system (Schemes 6 and 7).
EtO2C
CO2Et
CO2Me
t-BuOK/THF, O °C
(or)
O
SPh
X
N
n-BuLi/THF
-78 °C
N
SO2Ph
4e
CHO
SPh
SO2Ph
5r
i) NaBH4
CO2Me
MeOH-THF
KF/m-CPBA
CO2Et
CO2Et
N
H
12
ii) PhSH/p-TSA
benzene, reflux
Scheme 5.
CH3CN:H2O
0 °C, 0.5 h
N
H
13
35%
Having succeeded in synthesizing 4-hydroxy carbazoles and 4-
aminocarbazoles, next the synthesis of 1-hydroxycarbazoles was
planned using isomeric indole-3-methylsulfoxide. Hence, the N-
phenylsufonyl-3-bromomethylindoles 6a/6b were transformed
into the respective sulfides 7a/7b. The usual oxidation of sulfides
7a/7b using KF/m-CPBA afforded the required sulfoxides 8a/8b.
Surprisingly, the annulation of sulfoxides 8a/8b with methyl acry-
late/MVK in the presence of NaH or t-BuOK didn’t give the expected
1-hydroxycarbazoles 9a/9b. It should be mentioned that the
attempted Michael addition of sulfoxides 8a/8b with Michael ac-
ceptors even at ꢁ78 ꢀC using n-BuLi/LDA as base also found to be
unsuccessful. In all these conditions, only an insoluble polymeric
mixture was obtained. The failure to obtain 1-hydroxycarbazoles
9a/9b may be due to the stabilization of the carbanion, which may
lead to the formation of ketene-like intermediate 11 (Scheme 6).
Obviously, the ketene intermediate 11 may lead to the formation of
glassy polymeric material.
O
SPh
n-BuLi/THF
-78 °C
(or)
X
CO2Et
CO2Me
N
H
14
LDA/THF
N
H
0 °C
OH
CO2Me
15
Scheme 7.
In addition to the annulation methodology based on sulfoxide
stabilized carbanion mentioned above, Katritzky and co-workers
reported15 a facile synthesis of carbazole analogs using carbanion
generated from benzotriazolemethylindoles. In these methods,
sulfoxide/benzotriazole group was eliminated during aromatiza-
tion process. Thus, in general most of the annulation reactions were
carried out using carbanion stabilized by leaving groups such as
PhSO, PhSO2, NO2, and benzotriazole with vinylic dienophiles.
Since, tri- and tetra-substituted carbazoles16 are most abundant
among naturally occurring carbazoles, next the synthesis of these
types of carbazoles using carbanion stabilized by electron donating/
withdrawing groups such as OMe, Ph/CN, CO2Me was planned. Of
course, in this case the annulation has to be carried out with triple
bonded dienophiles rather than olefinic dienophiles.
R1
R1
Br
SPh
NaH
KF/m-CPBA
PhSH/THF
CO2Et
N
CH3CN:H2O
0 °C, 30 min
CO2Et
0 °C, 2 h
N
SO2Ph
SO2Ph
6a R1 = H
Accordingly, the indolylmethyl ether 16 was prepared from the
bromo compound 2b by refluxing in MeOH for 3 h. However, the
expected Michael addition of 16 with DMAD in the presence of
bases such as t-BuOK or LHMDS was found to be futile, only the
starting material was recovered (Scheme 8).
7a R1 = H
7b R1= OMe
6b R1= OMe
O
S
R1
t-BuOK/THF
R1
0 °C
Ph
(oXr)
CO2Et
N
CO2Me
n-BuLi/THF
-78 °C
N
SO2Ph
OH
CO2Et
Br
CO2Et
OMe
8a R1 = H
8b R1= OMe
SO2Ph
9a R1 = H
MeOH
9b R1= OMe
reflux
65%
N
N
SO2Ph
2b
SO2Ph
16
O
S
R1
O
R1
S
Ph
Ph
LDA/THF
(or)
LHMDS/THF
X
DMAD, 0 °C
2 h
OEt
HO
CO2Me
C
N
O
N
O
SO2Ph
10
SO2Ph
11
16
CO2Me
OMe
N
Scheme 6.
SO2Ph
17
Finally, an attempt was made to synthesize 1-hydroxycarbazole
involving N-free sulfoxide to circumvent the above-mentioned
ketene-like intermediate formation. Accordingly, the required
sulfoxide 14 was prepared from commercially available ethyl in-
dole-2-carboxylate. Vilsmeier–Haack formylation followed by
NaBH4 reduction and subsequent displacement of the benzylic
alcohol with thiophenol led to sulfide 13.
Oxidation of sulfide 13 using KF/m-CPBA in CH3CN/H2O fur-
nished sulfoxide 14 in 77% of yield. Unfortunately, the Michael
addition of sulfoxide 14 with methyl acrylate also led to the for-
mation of polymeric material. Now, it is obvious that the ketene-
like intermediate formation was facile even with the sulfoxide
stabilized carbanion generated from the N-free sulfoxide 14
Scheme 8.
Next, a smooth phenylation of bromo compound 2b was carried
out using phenylboronic acid in the presence of Pd(PPh3)2Cl2 to
afford 2-benzylindole 18 in 55% of yield. When compound 18 was
reacted with DMAD using LDA as a base in dry THF furnished the
tetra-substituted carbazole 19 in 40% of yield (Scheme 9).
The indolylmethyl acetates 20a/20b were prepared from the
corresponding bromo compounds 2a/2b using Stille carbonyla-
tion.17 The indolylmethyl acetates 20a/20b on reaction with DMAD/
methyl propiolate using t-BuOK in dry THF underwent smooth
Michael addition followed by intramolecular cyclization and

N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
3595
PhB(OH)2
Unfortunately, the interaction of isomeric 3-bromomethylindole
6a with NaCN in DMSO/THF at 0 ꢀC for 30 min led to the isolation of
indolylmalononitrile 23 instead of required 3-cyanomethylindole
24. The mechanism of formation of 23 could be visualized only
through the intermediacy of the elusive 3-cyanomethylindole 24.
Obviously, the cyanide ion behaves as a base to abstract the acidic
indole-3-methylene proton, which on cleavage of phenylsulfonyl
group followed by nucleophilic addition of cyanide ion led to the
formation of 23 (Scheme 12).
CO2Et
Ph
PdCl2(PPh3)2
2b
THF/aq.Na2CO3
60 °C, 12 h
55%
N
SO2Ph
18
HO
CO2Me
CO2Me
i) LDA/THF
18
ii) DMAD
N
-78 °C to 0 °C
Ph
SO2Ph
19 (40%)
2 h
NC
Br
Scheme 9.
NaCN
DMSO-THF
CN
CO2Et
CO2Et
0 °C, 30 min
45%
N
N
H
subsequent aromatization to afford tetra-substituted carbazoles
21a–d in 45–55% yields (Scheme 10, Table 3).
SO2Ph
6a
23
Next, the reaction of bromo compounds 2a, 2b, 2c, and 2e with
NaCN in DMSO/THF at 0 ꢀC for 1 h led to the isolation of respective
2-cyanomethylindoles 22a–d in 42–58% yields (Scheme 11,
Table 4).
CN
CN
CN
CO2Et
SO2Ph
24
CO2Et
N
N
SO2Ph
25
CO2Et
CO2Et
CO2Me
R1
R1
10% Pd(PPh3)2Cl2
CO (1atm)
Br
CN
CN
N
K2CO3
N
23
CO2Et
SO2Ph
N
26
THF/MeOH, rt, 12 h
SO2Ph
2a R1 = OMe
20a R1 = OMe (50%)
20b R1 = H (57%)
2b R1 = H
Scheme 12.
HO
R1
CO2Me
R2
t-BuOK/THF
0 °C
20a/20b
As expected, Michael addition of the 2-cyanomethylindoles 22a/
22b with methyl propiolate/DMAD in the presence of t-BuOK in dry
THF gave the respective 1-cyano carbazoles 27a–d in low yields
(Scheme 13). The use of LHMDS in place of t-BuOK also led to the
isolation of these carbazoles only in moderate yields. As expected,
when the cyano compound 22c was reacted with DMAD using
t-BuOK as a base in dry THF furnished the respective carbazole 27e
of course only in 36% of yield (Table 5).
R2
CO2Me
2-5 h
N
CO2Me
SO2Ph
21a-d
Scheme 10.
Table 3
Compound
R1
R2
H
CO2Me
H
Yield (%)
21a
21b
21c
21d
H
H
OMe
OMe
45
50
52
55
Me
O
CO2Me
CO2Me
t-BuOK/THF
Me
CN
0 °C
CO2Me
MeO2C
CO2Me
N
N
CN
36%
SO2Ph
22c
SO2Ph
27e
R1
R1
R2
R2
Scheme 13.
NaCN
CN
Br
N
DMSO-THF
0 °C, 1 h
N
SO2Ph
SO2Ph
2a R1 = OMe, R2 = CO2Et
2b R1 =H, R2 = CO2Et
2c R1 = H, R2 = COMe
22a-d
Table 5
HO
R1
CO2Me
R2
CO2Et
CN
t-BuOK/THF
2d R1 = H, R2 = CH=CHCO2Et
R1
0 °C
R2
CO2Me
2-5 h
Scheme 11.
N
N
CN
SO2Ph
27a-d
SO2Ph
22a R1 = OMe
22b R1 = H
Table 4
R1
R2
Yield (%)
Compound
R1
R2
Yield (%)
Compound
22a
22b
22c
22d
OMe
H
H
CO2Et
CO2Et
COMe
58
53
55
42
27a
27b
27c
27d
H
H
OMe
OMe
H
45
32
62
40
CO2Me
H
CO2Me
H
CH]CHCO2Et

3596
N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
The attempted double Michael addition of the 2-cyanomethyl-
9.0 Hz, ArH), 7.93 (2H, d, J 8.1 Hz, ArH), 7.57–7.22 (9H, m, ArH), 6.94
(1H, d, J 8.7 Hz, ArH), 5.07 (2H, s, CH2SPh), 4.10 (2H, q, J 7.0 Hz, OCH2),
3.82 (3H, s, OCH3), 1.27 (3H, t, J 7.0 Hz, CH3); dC (75.6 MHz, CDCl3)
164.0,157.1,144.2,134.7,134.6,134.2,133.5,130.5,129.3,128.7,128.2,
127.8, 126.9, 115.4, 114.6, 113.2, 104.4, 60.5, 55.5, 31.1, 14.1.
indole 22d with methyl propiolate in the presence of t-BuOK as
a base didn’t give the expected carbazole 28, only the starting
material was recovered (Scheme 14).
CO2Et
CO2Me
4.2.2. Ethyl-1-phenylsulfonyl-2-phenylthiomethylindole-3-
carboxylate (3b)
CO2Et
t-BuOK/THF
0 °C
X
Yield: 0.9 g (84%); colorless solid; mp 90 ꢀC. [Found: C, 63.5; H,
4.5; N, 3.3; S, 14.4. C24H21NO4S2 requires C, 63.84; H, 4.69; N, 3.10; S,
14.20%.] Rf (15% EtOAc/hexane) 0.81; nmax (KBr) 1170, 1368,
CN
CO2Me
3 h
N
N
CN
SO2Ph
22d
SO2Ph
28
1708 cmꢁ1
; dH (300 MHz, CDCl3) 7.99 (1H, d, J 8.4 Hz, ArH), 7.82 (2H,
d, J 7.5 Hz, ArH), 7.58–7.48 (2H, m, ArH), 7.39 (3H, t, J 7.8 Hz, ArH),
7.27–7.20 (6H, m, ArH), 4.31–4.26 (4H, m, CH2SPh and OCH2), 1.32
(3H, t, J 7.0 Hz, CH3); dC (75.6 MHz, CDCl3) 164.0, 143.8, 138.7, 135.9,
134.5, 134.3, 133.5, 129.3, 128.7, 127.8, 127.0, 125.5, 124.5, 122.2,
114.5, 113.3, 60.6, 31.0, 14.2.
Scheme 14.
3. Conclusions
In summary, a systematic study on the synthesis of carbazole
analogs was carried out using Michael addition promoted annula-
tion methodology as a key step. Thus, using indole-2-methylsulf-
oxides as bidentate synthons, synthesis of 4-hydroxy, 4-methyl,
and 4-aminocarbazole derivatives was successfully achieved in
reasonable yields. However, all attempts to prepare the 1-hydroxy-
carbazoles from the corresponding indole-3-methylsulfoxides
were found to be unsuccessful. Similarly, using indole-2-methyl-
acetates/indole-2-methylcyanides, synthesis of tri- as well as tetra-
substituted carbazoles is achieved in moderate yields.
4.2.3. 1-Phenylsulfonyl-2-phenylthiomethyl-3-acetylindole (3c)
Yield: 0.92 g (86%); colorless solid; mp 116 ꢀC. [Found: C, 65.3;
H, 4.5; N, 3.5; S, 15.5. C23H19NO3S2 requires C, 65.53; H, 4.54; N,
3.32; S, 15.21%.] Rf (15% EtOAc/hexane) 0.5; nmax (KBr) 1170, 1373,
1680 cmꢁ1
; dH (300 MHz, CDCl3) 8.13 (1H, d, J 8.1 Hz, ArH), 7.97 (2H,
t, J 7.5 Hz, ArH), 7.71 (1H, d, J 7.2 Hz, ArH), 7.56 (1H, t, J 7.2 Hz, ArH),
7.44 (2H, t, J 7.8 Hz, ArH), 7.34–7.24 (7H, m, ArH), 5.01 (2H, s,
CH2SPh), 2.29 (3H, s, CH3); dC (75.6 MHz, CDCl3) 195.9, 141.7, 138.7,
136.0, 134.3, 133.6, 129.4, 128.9, 127.9, 127.0, 126.5, 125.4, 124.5,
122.5, 122.4, 120.9, 114.9, 31.5, 30.9.
4. Experimental
4.1. General
4.2.4. 1-Phenylsulfonyl-3-cyano-2-phenylthiomethylindole (3d)
Yield: 0.88 g (82%); colorless solid; mp 140 ꢀC. [Found: C, 65.1; H, 4.1;
N, 6.5; S, 15.5. C22H16N2O2S2 requires C, 65.32; H, 3.99; N, 6.93; S,
15.85%.] Rf (15% EtOAc/hexane) 0.61; nmax (KBr) 1189, 1376, 2221 cmꢁ1
;
All melting points are uncorrected. Solvents were purified using
standard procedure. Reactions were done under atmosphere of dry
nitrogen with magnetic stirring. All chemicals were used as received.
Analytical thin layer chromatography (TLC) was performed on silica
and components were visualized by observation under iodine or
UV-light. Column chromatography was performed using silica gel
(60–120 mesh). IR spectra were recorded on a SHIMADZU FT-IR 8300
instrument. 1H and 13C NMR spectra were recorded in CDCl3 using
TMS as an internal standard on a JEOL 400 and Bruker-300 spec-
trometers. Elemental analyses were performed on either Perkin–
Elmer series II 2400 (IIT Madras) elemental analyzer or Euro EA 3000
(CLRI, Chennai). The mass spectra were recorded on a JEOL DX 303 HF
mass spectrometer. The bromomethylindoles 2a–e were prepared
from the corresponding methyl compounds using published
procedure.12a
dH (300 MHz, CDCl3)8.07(2H, d, J7.2 Hz, ArH), 7.62(1H, d, J6.9 Hz, ArH),
7.51 (3H, t, J 7.8 Hz, ArH), 7.42–7.26 (8H, m, ArH), 4.63 (2H, s, CH2SPh); dC
(CDCl3, 75.5 MHz) 145.6, 138.1, 135.6, 134.8, 134.2, 132.9, 130.5, 129.8,
129.5, 129.3, 127.3, 126.6, 126.5, 124.9, 119.7, 114.9, 112.8, 33.2.
4.2.5. Ethyl-3-[2-(phenylthiomethyl)-1-(phenylsulfonyl)-indol-3-yl]-
acrylate (3e)
Yield: 0.72 g (68%); mp 134 ꢀC. [Found: C, 65.1; H, 4.7; N, 3.1; S,
13.8. C26H23NO4S2 requires C,65.39;H, 4.85;N,2.93;S,13.43%.]Rf (15%
EtOAc/hexane) 0.54; nmax (KBr) 1162, 1360, 1690 cmꢁ1
; dH (300 MHz,
CDCl3) 8.17 (1H, d, J 8.1 Hz, ArH), 7.98–7.83 (5H, m, ArH), 7.79 (2H, d, J
8.1 Hz, ArH), 7.67–7.53 (3H, m, ArH), 7.47–7.14 (4H, m, ArH), 6.26 (1H,
d, J 15.9 Hz, HC]CH), 4.61 (2H, s, CH2SPh), 4.24 (2H, q, J 7.2 Hz, OCH2),
1.29 (3H, t, J 7.2 Hz, CH3); dC (CDCl3, 75.5 MHz) 164.4, 138.2, 137.6,
135.7, 135.1, 134.5, 132.5, 128.4, 127.7, 126.2, 125.6, 123.9, 120.2, 119.5,
119.3, 114.7, 60.1, 21.5, 14.2; m/z (EI) 479 (16, Mþþ2), 477 (42, Mþ).
4.2. A representative procedure for the preparation of sulfide
3a from indolyl bromo compound 2a (procedure A)
4.3. A representative procedure for the preparation
of sulfoxide 4a from indolyl sulfide 3a (procedure B)
4.2.1. Ethyl-1-phenylsulfonyl-5-methoxy-2-phenylthiomethyl-
indole-3-carboxylate (3a)
4.3.1. Ethyl-1-phenysulfonyl-5-methoxy-2-phenylsulfinyl-
To a well stirred suspension of NaH (0.24 g, 10 mmol) in dry THF
(30 mL) at 0 ꢀC, a solution of thiophenol (1.1 mL,11 mmol) in dry THF
(10 mL) was slowly added under N2 atmosphere. After 5 min, a so-
lution of bromo compound 2a (4.50 g, 10 mmol) in THF (20 mL) was
added dropwise with vigorous stirring. Then, the reaction mixture
was stirred for 2 h and then poured over crushed ice containing
concd HCl (5 mL). The precipitated crude sulfide was filtered,
washed with water, and dried (CaCl2), which was crystallized from
MeOH togive the title compound 3a (4.40 g, 90%) as a colorless solid;
mp 93 ꢀC. [Found: C, 61.9; H, 4.7; N, 3.0; S,13.6. C25H23NO5S2 requires
C, 62.35; H, 4.81; N, 2.91; S,13.32%.] Rf (15% EtOAc/hexane) 0.64; nmax
methylindole-3-carboxylate (4a)
To a solution of KF (80 mg, 1.43 mmol) in acetonitrile/water
(10 mL, 2 mL), m-CPBA (0.25 g, 1.43 mmol) was added and the
mixture was stirred at 0 ꢀC for 30 min. To this, sulfide 3a (0.48 g,
1.00 mmol) was added and the stirring was continued for an
additional 30 min. The reaction mixture was then poured into
saturated NaHCO3 solution, extracted with EtOAc (2ꢂ10 mL), and
the combined extract was dried (Na2SO4). Removal of solvent
followed by crystallization from MeOH afforded sulfoxide 4a
(0.46 g, 92%) as a colorless solid; mp 94 ꢀC. [Found: C, 60.5; H,
4.8; N, 3.0; S, 13.1. C25H23NO6S2 requires C, 60.35; H, 4.66; N,
2.81; S, 12.89%.] Rf (20% EtOAc/hexane) 0.18; nmax (KBr) 1079,
(KBr) 1169, 1369, 1710 cmꢁ1
; dH (300 MHz, CDCl3) 8.00 (1H, d, J

N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
3597
1181, 1362, 1702 cmꢁ1
ArH), 7.81 (2H, d, J 7.2 Hz, ArH), 7.61–7.40 (9H, m, ArH), 6.99–
6.95 (1H, dd, J 2.7 and 9.3, ArH), 5.39 (1H, d, J 12.3 Hz, CHaHb-
SOPh), 5.11 (1H, d, J 12.3 Hz, CHaHbSOPh), 4.29 (2H, q, J 7.2 Hz,
;
dH (300 MHz, CDCl3) 7.99 (1H, d, J 9.3 Hz,
9, 3 Hz, ArH) 5.76 (2H, s, CH2SO2Ph), 4.20 (2H, q, J 7.2 Hz, OCH2),
3.76 (3H, s, OCH3), 1.33 (3H, t, J 7.2 Hz, CH3); dC (75.5 MHz, CDCl3)
163.8, 157.3, 138.9, 137.9, 134.4, 133.8, 133.5, 131.0, 129.4, 128.2,
127.0, 126.6, 117.3, 115.8, 115.7, 115.4, 104.3, 61.0, 55.5, 53.4, 14.2.
OCH2), 3.83 (3H, s, OCH3), 1.39 (3H, t,
J 7.2 Hz, CH3); dC
(75.6 MHz, CDCl3) 163.9, 157.3, 143.6, 138.1, 136.3, 134.4, 131.3,
130.8, 129.1, 128.9, 128.3, 126.6, 126.4, 124.3, 115.5, 115.3, 104.5,
60.9, 55.5, 55.4, 14.2.
4.4. A representative procedure for the preparation
of carbazole 5a from the sulfoxide 4a (procedure C)
4.4.1. Methyl-9-phenylsulfonyl-4-hydroxy-6-methoxycarbazole-3-
carboxylate (5a)
4.3.2. Ethyl-1-phenylsulfonyl-2-phenylsulfinylmethylindole-3-
carboxylate (4b)
To a solution of sulfoxide 4a (0.5 g, 1.0 mmol) in dry THF (10 mL)
under N2, t-BuOK (0.11 g, 1 mmol) in THF (5 mL) was added and
stirred at 0 ꢀC for 15 min. To this methyl acrylate (0.10 g, 1.21 mmol)
in THF (2 mL) was slowly added. After stirring for 5 h at 0 ꢀC, the
reaction mixture was quenched with aq NH4Cl (5 mL), extracted
with CHCl3 (2ꢂ20 mL), and dried (Na2SO4). Removal of solvent fol-
lowed by crystallization from MeOH afforded carbazole 5a (0.29 g,
70%) as brown solid; mp 160 ꢀC; Rf (15% EtOAc/hexane) 0.65. [Found:
C, 61.0; H, 4.3; N, 3.1; S, 8.0. C21H17NO6S requires: C, 61.30; H, 4.16; N,
Yield: 0.93 g (90%); colorless solid; mp 110 ꢀC. [Found: C, 61.5; H,
4.4; N, 3.2; S,13.9. C24H21NO5S2 requires C, 61.65; H, 4.53; N, 3.00; S,
13.72%.] Rf (20% EtOAc/hexane) 0.22; nmax (KBr) 1074, 1180, 1368,
1728 cmꢁ1
; dH (300 MHz, CDCl3) 8.07 (2H, d, J 6.8 Hz, ArH), 7.86 (2H,
d, J 8.3 Hz, ArH), 7.62 (2H, d, J 7.8 Hz, ArH), 7.58–7.50 (4H, m, ArH),
7.48–7.38 (2H, m, ArH), 7.36–7.30 (2H, m, ArH), 5.43 (1H, d, J
12.2 Hz, CHaHbSOPh), 5.13 (1H, d, J 12.7 Hz, CHaHbSOPh), 4.30 (2H,
q, J 7.2 Hz, OCH2), 1.40 (3H, t, J 7.3 Hz, CH3); dC (75.5 MHz, CDCl3)
163.9, 143.7, 138.1, 136.2, 134.4, 131.3, 129.5, 128.9, 126.8, 125.9,
124.8, 124.3, 122.5, 122.4, 114.6, 114.5 (2C), 60.9, 55.3, 14.2; m/z (EI)
451 (24, Mþ), 311 (24%).
3.40; S, 7.79%.] nmax (KBr) 1178, 1368, 1705 cmꢁ1
; dH (300 MHz,
CDCl3) 11.61 (1H, s, OH), 8.19 (1H, d, J 9.3 Hz, ArH), 7.92–7.77 (5H, m,
ArH), 7.49–7.44 (1H, m, ArH), 7.32 (2H, t, J 7.8 Hz, ArH), 7.06 (1H, dd,
J 6.3 and 2.7 Hz, ArH), 3.97 (3H, s, OCH3), 3.89 (3H, s, OCH3); dC
(75.5 MHz, CDCl3) 171.4, 158.4, 157.1, 143.7, 137.7, 133.9, 131.9, 129.1,
128.6, 126.4, 126.2, 115.4, 115.2, 114.5, 114.3, 106.4, 106.2, 55.8, 52.3.
4.3.3. 1-Phenylsulfonyl-2-phenylsulfinylmethyl-3-acetylindole (4c)
Yield: 0.93 g (90%); colorless solid; mp 130 ꢀC. [Found: C, 63.3; H,
4.1; N, 3.5; S, 14.5. C23H19NO4S2 requires C, 63.14; H, 4.38; N, 3.20; S,
14.66%.] Rf (20% EtOAc/hexane) 0.16; nmax (KBr) 1080, 1182, 1372,
4.4.2. 6-Methoxy-9-phenylsulfonyl-4-hydroxy-3-acetyl-
carbazole (5b)
1676 cmꢁ1
; dH (300 MHz, CDCl3) 8.12–8.09 (1H, m, ArH), 7.86 (2H, d,
J 7.5 Hz, ArH), 7.81–7.78 (1H, m, ArH), 7.69–7.66 (2H, m, ArH), 7.58–
7.44 (6H, m, ArH), 7.42–7.32 (2H, m, ArH), 5.27 (1H, d, J 12.9 Hz,
CHaHbSOPh), 5.03 (1H, d, J 13.2 Hz, CHaHbSOPh), 2.63 (3H, s, CH3); dC
(75.6 MHz, CDCl3) 196.4, 143.6, 138.1136.3, 134.5, 134.0, 131.4 129.6,
129.2, 127.0, 126.8, 126.7, 125.9, 124.8, 124.3, 121.1, 115.0, 55.2, 32.2.
Yield: 0.18 g (77%); brown solid; mp 190 ꢀC. [Found: C, 63.6; H,
4.5; N, 3.40; S, 8.3. C21H17NO5S requires C, 63.79; H, 4.33; N, 3.54; S,
8.1%.] Rf (15% EtOAc/hexane) 0.66; nmax (KBr) 1170,1360,1650 cmꢁ1
;
dH (300 MHz, CDCl3) 13.33 (1H, s, OH), 8.17 (1H, d, J 8.7 Hz, ArH),
7.80–7.78 (5H, m, ArH), 7.47–7.26 (3H, m, ArH), 7.06 (1H, d, J 8.7 Hz,
ArH), 3.89 (3H, s, OCH3), 2.67 (3H, s, CH3); dC (75.5 MHz, CDCl3)
204.1, 159.7, 157.2, 143.9, 137.7, 134.1, 131.8, 129.6, 129.2, 126.4, 126.3,
115.3 (2C), 115.1, 106.2, 106.1, 55.8, 26.8; m/z (EI) 395 (14, Mþ), 394
(55), 254 (100), 77 (43%).
4.3.4. 1-Phenylsulfonyl-3-cyano-2-phenylsulfinylmethylindole (4d)
Yield: 0.94 g (91%); colorless solid; mp 142 ꢀC. [Found: C, 62.9;
H, 4.0; N, 6.5; S, 15.2. C22H16N2O3S2 requires C, 62.84; H, 3.84; N
6.66, S, 15.25%.] Rf (20% EtOAc/hexane) 0.18; nmax (KBr) 1083, 1181,
1380, 2221 cmꢁ1
;
dH (400 MHz, CDCl3) 8.07 (1H, d, J 8.0 Hz, ArH),
4.4.3. 6-Methoxy-9-phenylsulfonyl-4-hydroxycarbazole-3-
carboxaldehyde (5c)
7.88 (2H, d, J 8.0 Hz, ArH), 7.65 (2H, d, J 8.4 Hz, ArH), 7.54–7.47 (8H,
m, ArH), 7.26 (1H, d, J 7.9 Hz, ArH), 4.71 (2H, s, CHaHbSOPh); dC
(100.5 MHz, CDCl3) 143.1, 137.7, 137.5, 135.8, 135.1, 132.0, 129.9,
129.5, 127.2, 126.9, 125.4, 124.2, 120.0, 114.9, 112.8, 99.4, 57.8; m/z
(EI) 405 (9, Mꢁ16), 231 (35), 154 (39), 141 (28%).
Yield: 0.16 g (68%); brown solid; mp 196 ꢀC. [Found: C, 62.7; H,
3.8; N, 3.8; S, 8.6. C20H15NO5S requires C, 62.98; H, 3.96; N, 3.67; S,
8.41%.] Rf (15% EtOAc/hexane) 0.59; nmax (KBr) 1170, 1370,
1640 cmꢁ1
; dH (500 MHz, CDCl3) 12.04 (1H, s, OH), 9.96 (1H, s,
CHO), 8.21 (1H, d, J 8.3 Hz, ArH), 8.92 (2H, d, J 7.3 Hz, ArH), 7.86–7.68
(2H, m, ArH), 7.45–7.34 (5H, m, ArH), 3.86 (3H, s, OCH3); dC
(125 MHz, CDCl3) 189.8, 158.3, 137.8, 137.7, 134.3, 129.7, 128.6, 127.4,
126.8, 126.4, 125.2, 124.4, 123.4, 123.2, 115.4, 114.3, 107.5, 55.8.
4.3.5. Ethyl-3-[2-phenylsulfinylmethyl-1-(phenylsulfonyl)-indol-3-
yl]acrylate (4e)
Yield: 0.97 g (94%); colorless solid; mp 118 ꢀC. [Found: C, 63.4; H,
4.9; N, 2.7; S,12.7. C26H23NO5S2 requires C, 63.27; H, 4.70; N, 2.84; S,
12.99%.] Rf (20% EtOAc/hexane) 0.16; nmax (KBr) 1040, 1162, 1360,
4.4.4. 6-Methoxy-9-phenylsulfonyl-4-hydroxy-3-cyano-
carbazole (5d)
1690 cmꢁ1
; dH (300 MHz, CDCl3) 7.70 (1H, d, J 7.8 Hz), 7.49–7.46
(3H, m, ArH), 7.41–7.34 (3H, m, ArH), 7.33–7.29 (6H, m, ArH), 7.19–
7.27 (2H, m, ArH), 6.36 (1H, d, J 15.9 Hz, CH]CH), 4.70 (1H, d, J
3.2 Hz, CHaHbSOPh), 4.54 (1H, d, J 13.2 Hz, CHaHbSOPh), 4.19 (2H, q,
J 7.2 Hz, OCH2),1.27 (3H, t, J 7.1 Hz, CH3); dC (75.6 MHz, CDCl3) 166.6,
143.3, 138.2, 136.9, 134.4, 133.7, 131.5, 130.9, 129.5, 129.2, 127.1,
126.5, 126.3, 124.8, 124.2, 122.0, 121.0, 120.7, 115.0, 60.6, 56.6, 14.4;
m/z (EI) 477 (46, Mþꢁ16), 336 (27%).
Yield: 0.7 g (70%); colorless solid; mp 184 ꢀC. [Found: C, 63.6; H,
3.9; N, 7.6; S, 8.6. C20H15NO5S requires C, 63.48; H, 3.73; N, 7.40; S,
8.47%.] Rf (15% EtOAc/hexane) 0.50; nmax (KBr) 1172, 1380,
2221 cmꢁ1
; dH (300 MHz, CDCl3) 12.96 (1H, s, OH), 8.13 (2H, d, J
8.4 Hz, ArH), 7.98 (2H, d, J 7.4 Hz, ArH), 7.67–7.42 (3H, m, ArH), 7.12–
7.36 (3H, m, ArH,) 3.93 (3H, s, OCH3); dC (75.5 MHz, CDCl3) 158.7,
137.7,137.5,134.7,129.7,128.2,127.6,126.8,126.7,125.0,124.8,123.4,
123.1, 115.5, 114.6, 114.4, 107.5, 55.8.
4.3.6. Ethyl-1-phenylsulfonyl-5-methoxy-2-phenylsulfonyl-
me thylindole-3-carboxylate (4a0)
4.4.5. Methyl-9-phenylsulfonyl-4-hydroxycarbazole-3-
carboxylate (5e)
Colorless solid; mp 140–141 ꢀC. [Found: C, 58.6; H, 4.4; N, 2.9; S,
12.2. C25H23NO7S2 requires C, 58.47; H, 4.51; N, 2.73; S, 12.49.] Rf
(20% EtOAc/hexane) 0.40; nmax (KBr) 1700, 1150, 1170, 1200,
Yield: 0.28 g (70%); brown solid; mp 152 ꢀC. [Found: C, 62.8; H,
3.8; N, 3.8; S, 8.5. C20H15NO5S requires C, 62.98; H, 3.96; N, 3.67;
S, 8.41%.] Rf (15% EtOAc/hexane) 0.67; nmax (KBr) 1168, 1374,
1320 cmꢁ1
;
dH (300 MHz, CDCl3) 7.89–7.85 (1H, d, J 9.3 Hz, ArH),
7.78–7.71 (4H, m, ArH), 7.55–7.37 (7H, m, ArH), 6.98–6.94 (1H, dd, J
1705, 3331 cmꢁ1
; dH (400 MHz, CDCl3) 8.30 (2H, d, J 8.1 Hz, ArH),

3598
N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
7.95–7.82 (4H, m, ArH), 7.48–7.33 (5H, m, ArH), 3.98 (3H, s, CH3); dC
(CDCl3, 100.6 MHz) 170.8, 158.4, 143.2, 137.7, 134.1, 129.2, 128.7,
126.9, 126.5, 125.1, 124.5, 123.4, 123.3, 114.7, 114.4, 107.6, 106.2, 52.3;
m/z (EI) 382 (33, Mþþ1), 381 (54, Mþ), 77 (90%).
S, 8.82%.] Rf (15% EtOAc/hexane) 0.72; nmax (KBr) 1178, 1365,
1670 cmꢁ1
dH (300 MHz, CDCl3) 8.35 (1H, d, J 8.4 Hz, ArH), 8.21
;
(1H, d, J 9.0 Hz, ArH), 8.09 (1H, d, J 7.8 Hz, ArH), 7.74 (2H, d, J 7.2 Hz,
ArH), 7.68 (1H, d, J 9.0 Hz, ArH), 7.49–7.29 (5H, m, ArH), 2.83 (3H, s,
CH3), 2.59 (3H, s, CH3); dC (75.5 MHz, CDCl3) 201.2, 158.7, 147.2,
139.7, 134.9, 129.2, 128.3, 127.6, 127.3, 126.9, 126.5, 124.2, 123.4,
114.9, 111.9, 96.1, 30.5, 17.9.
4.4.6. 9-Phenylsulfonyl-4-hydroxy-3-acetylcarbazole (5f)
Yield: 0.27 g (69%); colorless solid; mp 178 ꢀC. [Found: C, 65.6;
H, 4.30; N, 4.0; S, 8.6. C20H15NO4S requires C, 65.74; H, 4.14; N, 3.83;
S, 8.78%.] Rf (15% EtOAc/hexane) 0.63; nmax (KBr) 1178, 1365, 1692,
4.4.12. Methyl-9-phenylsulfonyl-4-methylcarbazole-3-
carboxylate (5m)
3366 cmꢁ1
; dH (400 MHz, CDCl3) 13.31 (1H, s, OH), 8.31 (2H, t, J
8.0 Hz, ArH), 7.89–7.81 (4H, m, ArH), 7.50 (2H, t, J 8.0 Hz, ArH), 7.43–
7.34 (3H, m, ArH), 2.69 (3H, s, CH3); dC (CDCl3, 100.6 MHz) 204.4,
159.9, 138.1, 137.9, 134.5, 129.9, 129.6, 127.3, 126.8, 125.5, 124.9,
123.7, 115.7, 115.3, 114.6, 106.2, 27.2; m/z (EI) 367 (37, Mþþ2), 365
(74, Mþ), 166 (49%).
Yield: 0.23 g (53%); brown solid; mp 154 ꢀC. [Found: C, 66.3; H,
4.4; N, 3.8; S, 8.2. C21H17NO4S requires C, 66.47; H, 4.52; N, 3.69; S,
8.45%.] Rf (15% EtOAc/hexane) 0.71; nmax (KBr) 1172, 1368,
1712 cmꢁ1
; dH (300 MHz, CDCl3) 8.29 (1H, d, J 8.2 Hz, ArH), 7.98 (1H,
d, J 7.8 Hz, ArH), 7.71 (3H, m, ArH), 7.50–7.37 (6H, m, ArH), 3.97 (s,
3H, OCH3), 2.78 (s, 3H, CH3); dC (75.5 MHz, CDCl3) 165.6, 147.2,
139.2, 135.3, 134.3, 131.3, 130.9, 128.9, 127.7, 127.3, 127.1, 125.7, 123.4,
117.6, 114.9, 114.7, 99.3, 53.6, 17.4.
4.4.7. 9-Phenylsulfonyl-4-hydroxycarbazole-3-carboxaldehyde (5g)
Yield: 0.24 g (64%); colorless solid; mp 154–158 ꢀC. [Found: C,
64.8; H, 4.0; N, 3.7; S, 8.9. C19H13NO4S requires C, 64.95; H, 3.73; N,
3.99; S, 9.13%.] Rf (15% EtOAc/hexane) 0.64; nmax (KBr) 3330, 1682,
4.4.13. Methyl-9-phenylsulfonyl-4-aminocarbazole-3-
carboxylate (5n)
1367, 1172, 3425 cmꢁ1
; dH (400 MHz, CDCl3) 12.01 (1H, s, OH), 9.95
(1H, s, CHO), 8.31 (1H, t, J 8.8 Hz, ArH), 8.10 (1H, d, J 8.4 Hz, ArH),
7.87 (2H, d, J 7.2 Hz, ArH), 7.64 (1H, d, J 8.8 Hz, ArH), 7.52 (2H, t, J
8.0 Hz, ArH), 7.41 (4H, quint, J 6.8 Hz, ArH); dC (CDCl3, 100.6 MHz)
181.1, 159.5, 138.1, 136.6, 134.3, 129.9, 129.8, 127.0, 126.8, 125.9,
124.8, 124.7, 115.7, 115.6, 114.6, 106.3; m/z (EI) 353 (81, Mþþ2), 351
(62, Mþ), 173 (28%).
Yield: 0.22 g (48%); brown solid; mp 198 ꢀC. [Found: C, 62.1; H,
4.5; N, 7.5; S, 8.6. C20H16N2S requires C, 63.14; H, 4.24; N, 7.36; S,
8.43%.] Rf (15% EtOAc/hexane) 0.77; nmax (KBr) 1178, 1368, 1698,
3240 cmꢁ1
; dH (300 MHz, CDCl3) 7.98 (1H, d, J 8.4 Hz, ArH), 7.88–
7.57 (5H, m, ArH), 7.49–7.39 (2H, m, ArH), 7.29 (2H, t, J 7.3 Hz, ArH),
7.14 (1H, d, J 6.7 Hz, ArH), 4.67 (2H, br s, NH2), 3.98 (3H, s, CH3); dC
(75.5 MHz, CDCl3) 172.3, 158.4, 157.6, 143.5, 137.8,137.7, 136.6, 134.3,
130.8, 128.8, 127.7, 126.9, 126.6, 115.7, 115.5, 106.4, 106.3, 55.8.
4.4.8. 9-Phenylsulfonyl-4-hydroxy-3-cyanocarbazole (5h)
Yield: 0.26 g (70%); colorless solid; mp 178 ꢀC. [Found: C, 65.4;
H, 3.3; N, 8.2; S, 9.0. C19H12N2O3S requires C, 65.51; H, 3.47; N, 8.04;
S, 9.20%.] Rf (15% EtOAc/hexane) 0.63; nmax (KBr) 1178, 1360, 2221,
4.4.14. 9-Phenylsulfonyl-4-amino-3-acetylcarbazole (5o)
Yield: 0.22 g (50%); brown solid; mp 204 ꢀC. [Found: C, 65.8; H,
4.2; N, 7.4; S, 9.0. C20H16N2O3S requires C, 65.92; H, 4.43; N, 7.69; S,
8.80%.] Rf (15% EtOAc/hexane) 0.79; nmax (KBr) IR (KBr) 1164, 1372,
3325 cmꢁ1
; dH (400 MHz, CDCl3) 10.96 (1H, s, OH), 8.12 (1H, d, J
8.2 Hz, ArH), 7.98 (2H, d, J 7.2 Hz, ArH), 7.63–7.51 (4H, m, ArH), 7.43–
6.98 (4H, m, ArH); dC (100.6 MHz, CDCl3) 159.1, 138.1, 137.9, 134.7,
134.5, 129.9, 129.6, 127.7, 126.8, 125.2, 124.9, 123.4, 123.3, 115.7,
115.3,114.7,106.9; m/z (EI) 349 (76, Mþþ1), 348 (34, Mþ), 207 (35%).
1682, 3248 cmꢁ1
; dH (300 MHz, CDCl3) 8.17 (1H, d, J 8.7 Hz,), 7.79–
7.26 (9H, m, ArH), 7.08 (1H, d, J 8.7 Hz, ArH), 3.39 (2H, br s, NH2),
2.68 (3H, s, CH3); dC (, 75.5 MHz) 203.9, 159.2, 138.1, 137.9, 134.6,
134.5, 129.5, 127.6, 126.4, 125.1, 124.7, 123.7, 121.6, 118.5, 115.7, 112.3,
104.7, 26.9.
4.4.9. 9-Phenylsulfonyl-4-hydroxy-3-nitro-2-phenylcarbazole (5i)
Yield: 0.21 g (40%); colorless solid; mp 204–206 ꢀC. [Found: C,
65.0; H, 3.5; N, 6.1; S, 7.0. requires C24H16N2O5S C, 64.86; H, 3.63; N,
6.30; S, 7.21%.] Rf (15% EtOAc/hexane) 0.60; nmax (KBr) 1178, 1372,
4.4.15. 9-Phenylsulfonyl-4-amino-3-cyanocarbazole (5p)
Yield: 0.18 g (45%); brown solid; mp 232 ꢀC. [Found: C, 65.4; H,
3.6; N, 12.3; S, 9.0. C19H13N3O2S requires C, 65.69; H, 3.77; N, 12.10;
S, 9.23%.] Rf (15% EtOAc/hexane) 0.73; nmax (KBr) 1176, 1380, 2221,
1548, 3325 cmꢁ1
; dH (500 MHz, CDCl3) 10.98 (1H, s, OH), 8.33–8.31
(2H, m, ArH), 7.89 (1H, s, ArH), 7.88–7.86 (2H, m, ArH), 7.58–7.53
(2H, m, ArH), 7.50–7.46 (4H, m, ArH), 7.42 (2H, t, J 7.8 Hz, ArH), 7.37–
7.36 (2H, m, ArH); dC (125 MHz, CDCl3) 151.8, 141.3, 139.5, 139.0,
138.2, 137.6, 134.7, 130.2, 129.6, 128.8, 128.1, 127.9, 127.8, 126.7, 125.1,
124.6, 123.7, 114.7, 114.6, 110.6; m/z (EI) 446 (52, Mþþ2), 444 (25,
Mþ), 398 (17%).
3235 cmꢁ1
; dH (400 MHz, CDCl3) 8.18 (1H, d, J 8.2 Hz, ArH), 7.98–
7.87 (4H, m, ArH), 7.76–7.45 (4H, m, ArH), 7.32–7.17 (2H, m, ArH),
3.79 (2H, s, NH2); dC (75.5 MHz, CDCl3) 158.7, 137.7, 137.5, 134.7,
129.7, 128.2, 127.6, 126.8, 126.7, 125.0, 124.8, 123.4, 123.1, 115.5,
114.6, 114.4, 107.5.
4.4.10. Methyl-9-phenylsulfonyl-4-hydroxy-2-methylcarbazole-3-
carboxylate (5k)
4.4.16. Ethyl-1-phenylsulfonyl-3-phenylthiomethylindole-2-
carboxylate (7a)
Yield: 0.15 g (36%); colorless solid; mp 188–190 ꢀC. [Found: C,
65.0; H, 4.4; N, 3.4; S, 7.9. C21H17NO5S requires C, 63.79; H, 4.33; N,
3.54; S, 8.11%.] Rf (15% EtOAc/hexane) 0.69; nmax (KBr) 1178, 1365,
Yield: 0.92 g (84%); colorless solid; mp 90 ꢀC. [Found: C, 64.0; H,
4.9; N, 3.0; S, 14.0. C24H21NO4S2 requires C, 63.84; H, 4.69; N, 3.10; S,
14.20%.] Rf (15% EtOAc/hexane) 0.83; nmax (KBr) 1182, 1370,
1704, 3324 cmꢁ1
;
dH (400 MHz, CDCl3) 10.98 (1H, s, OH), 8.21 (1H,
1720 cmꢁ1
; dH (300 MHz, CDCl3) 7.94 (1H, d, J 8.2 Hz, ArH), 7.81 (2H,
d, J 8.1 Hz, ArH), 7.86 (2H, d, J 7.1 Hz,), 7.81 (1H, s, ArH), 7.56–7.50
(2H, m, ArH), 7.49 (2H, t, J 7.8 Hz,), 7.39–7.27 (2H, m, ArH), 4.00 (3H,
s, OCH3), 2.78 (3H, s, CH3); dC (100.6 MHz, CDCl3) 168.8, 141.3, 139.4,
137.6, 134.5, 128.7, 128.3, 127.7, 127.3, 126.7, 125.5, 124.6, 123.8,
123.7,117.0,114.8,114.5, 53.2,18.2; m/z (EI) 396 (22, Mþþ1), 395 (37,
Mþ), 254 (17%).
d, J 6.9 Hz, ArH), 7.52 (2H, d, J 7.1 Hz, ArH), 7.48–7.22 (8H, m, ArH),
6.98 (1H, t, J 6.9 Hz, ArH), 4.28 (2H, s, CH2SPh), 4.23 (2H, q, J 7.2 Hz,
OCH2), 1.34 (3H, t, J 7.2 Hz, CH3); dC (75.5 MHz, CDCl3) 161.7, 157.0,
137.2, 137.0, 135.0, 133.7, 132.0, 131.6, 130.1, 129.9, 129.1, 128.9, 127.5,
127.4, 127.2, 127.0, 125.9, 116.6, 116.5, 103.0, 62.4, 29.3, 13.9.
4.4.17. Ethyl-5-methoxy-1-phenylsulfonyl-3-phenylthiomethyl-
indole-2-carboxylate (7b)
Yield: 4.15 g (85%); colorless solid; mp 98 ꢀC. [Found: C, 62.5; H,
5.1; N, 3.1; S, 13.1. C25H23NO5S2 requires C, 62.35; H, 4.81; N, 2.91; S,
4.4.11. 9-Phenylsulfonyl-4-methyl-3-acetylcarbazole (5l)
Yield: 0.19 g (48%); brown solid; mp 162–164 ꢀC. [Found: C, 69.1;
H, 4.5; N, 3.6; S, 8.7. C21H17NO3S requires C, 69.40; H, 4.71; N, 3.85;

N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
3599
13.32%.] Rf (15% EtOAc/hexane) 0.82; nmax (KBr) 1183, 1370,
1720 cmꢁ1
dH (300 MHz, CDCl3) 7.67 (1H, d, J 7.8 Hz, ArH) 7.61 (2H,
t, J 7.2 Hz, ArH), 4.79 (1H, d, J 13.2 Hz, CHaHbSOPh), 4.64 (1H, d, J
12.1 Hz, CHaHbSOPh), 4.32 (2H, q, J 7.1 Hz, OCH2), 1.36 (3H, t, J 7.1 Hz,
CH3); dC (75.5 MHz, CDCl3) 161.6, 143.6, 135.7, 131.0, 128.7, 125.8,
125.4, 124.3, 120.9, 120.5, 112.2, 110.8, 61.2, 54.8, 14.3.
;
d, J 7.1 Hz, ArH), 7.55–7.49 (3H, m, ArH), 7.38–7.02 (7H, m, ArH), 4.10
(2H, s, CH2SPh), 4.18 (2H, q, J 7.2 Hz, OCH2), 3.57 (3H, s, OCH3), 1.26
(3H, t, J 7.1 Hz, CH3); dC (75.5 MHz, CDCl3) 161.6, 156.9, 137.2, 137.0,
134.9, 133.7, 132.0, 131.6, 130.0, 129.9, 129.1, 128.9, 128.8, 127.5,
127.4, 127.2, 127.0, 125.9, 116.6, 116.5, 103.0, 62.2, 55.6, 29.2, 13.9.
4.4.23. Ethyl-2-(methoxymethyl)-1-(phenylsulfonyl)-1H-indole-3-
carboxylate (16)
The bromo compound 2b (0.42 g, 1 mmol) was refluxed in
MeOH (20 mL) for 3 h. The solvent was evaporated and the crude
product was crystallized from MeOH to afford indolyl ether 16
(0.24 g, 65%) as a colorless solid; mp 106 ꢀC. [Found: C, 62.4; H, 5.3;
N, 3.9; S, 8.5. C19H19NO5S requires C, 61.11; H, 5.13; N, 3.75; S,
8.59%.] Rf (20% EtOAc/hexane) 0.72; nmax (KBr) 1182, 1370,
4.4.18. Ethyl-1-phenylsulfonyl-3-phenylsulfinylmethylindole-2-
carboxylate (8a)
Yield: 0.87 g (85%); colorless solid; mp 118 ꢀC. [Found: C, 61.5; H,
4.4; N, 3.2; S,13.5. C24H21NO5S2 requires C, 61.65; H, 4.53; N, 3.00; S,
13.72%.] Rf (15% EtOAc/hexane) 0.23; nmax (KBr) 1082, 1190, 1370,
1720 cmꢁ1
;
dH (300 MHz, CDCl3) 7.94 (1H, d, J 8.3 Hz, ArH), 7.84 (2H,
1702 cmꢁ1
; dH (300 MHz, CDCl3) 8.19–8.00 (4H, m, ArH), 7.56–7.29
d, J 7.5 Hz, ArH), 7.49 (1H, d, J 7.4 Hz, ArH), 7.38 (2H, t, J 7.8 Hz, ArH),
7.32–7.04 (8H, m, ArH), 4.37–4.01 (4H, m, OCH2 & CHaHbSOPh), 1.28
(3H, t, J 7.2 Hz, CH3); dC (75.5 MHz, CDCl3) 161.1, 142.8, 137.9, 136.8,
134.0, 131.4, 130.8, 129.0, 128.9, 127.4, 127.2, 124.4, 124.1, 120.7, 117.9,
115.4, 115.3, 62.4, 53.6, 13.9.
(5H, m, ArH), 5.33 (2H, s, CH2), 4.43 (2H, q, J 6.9 Hz, OCH2), 3.38 (s,
3H, OCH2), 1.45 (3H, t, J 7.2 Hz, CH3); dC (75.5 MHz, CDCl3) 164.2
142.4, 138.9, 135.9, 134.0, 129.4, 129.0, 127.2, 126.7, 125.8, 124.4,
122.5, 114.5, 62.8, 60.9, 57.9, 14.4.
4.4.24. Ethyl-1-phenylsulfonyl-2-benzyl-3-carboxylate (18)
4.4.19. Ethyl-5-methoxy-1-phenylsulfonyl-3-phenylsulfinylmethyl-
indole-2-carboxylate (8b)
A mixture of 2-bromomethylindole 2b (0.3 g, 0.71 mmol), phe-
nylboronic acid (0.1 g, 0.78 mmol), and Pd(PPh3)2Cl2 (0.03 g,
0.035 mmol) in THF (20 mL) was stirred well under N2. To this, aq
Na2CO3 solution (0.18 g in 5 mL water) was added and the reaction
mixture was heated 60 ꢀC for 12 h. The solid was filtered off and the
solvent was completely removed under vacuum. Extraction of the
crude product with EtOAc (2ꢂ10 mL) followed by column chro-
matography purification (5% EtOAc/hexane) afforded product 18
(0.16 g, 55%) as a colorless solid; mp 138 ꢀC. [Found: C, 68.9; H, 5.2;
N, 3.4; S, 7.4. C24H21NO4S requires C, 68.72; H, 5.05; N, 3.34; S,
7.64%.] Rf (20% EtOAc/hexane) 0.81; nmax (KBr) 1187, 1378,
Yield: 0.45 g (90%); colorless solid; mp 146 ꢀC. [Found: C, 60.1;
H, 4.8; N, 3.0; S, 12.6. C25H23NO6S2 requires C, 60.35; H, 4.66; N,
2.81; S, 12.89%.] Rf (15% EtOAc/hexane) 0.18; nmax (KBr) 1078, 1187,
1373, 1720 cmꢁ1
; dH (300 MHz, CDCl3) 7.91–7.83 (3H, m, ArH), 7.56
(1H, d, J 7.5 Hz, ArH), 7.45 (2H, d, J 7.2 Hz, ArH), 7.40–7.24 (5H, m,
ArH), 6.97 (1H, dd, J 2.4, 6.9 Hz, ArH), 6.52 (1H, d, J 2.4 Hz,), 4.42–
4.23 (4H, m, OCH2 and CHaHbSOPh), 3.69 (3H, s, OCH3), 1.37 (3H, t, J
7.1 Hz, CH3); dC (75.5 MHz, CDCl3) 161.1, 157.0, 143.0, 137.5, 133.9,
131.5, 131.4, 131.3, 130.0, 128.9, 127.1, 124.2, 118.2, 116.4, 117.1, 102.1,
62.4, 55.6, 53.7, 13.9.
1705 cmꢁ1
; dH (300 MHz, CDCl3) 8.23–8.18 (2H, m, ArH), 7.43 (3H, d,
J 6.9 Hz, ArH), 7.28–7.19 (7H, m, ArH), 7.40–7.36 (2H, m, ArH), 5.08
(2H, s, CH2Ph), 4.41 (2H, q, J 7.2 Hz, OCH2), 1.39 (3H, t, J 7.2 Hz, CH3);
dC (75.5 MHz, CDCl3) 164.6, 146.3, 138.4, 137.8, 135.9, 133.9, 129.1,
128.6, 127.3, 126.6, 126.2, 125.2, 124.5, 122.1, 114.6, 113.3, 60.6, 31.8,
14.3.
4.4.20. Ethyl 3-formyl-1H-indole-2-carboxylate (12)
Yield: 1 g (87%); colorless solid; mp 182 ꢀC; Rf (15% EtOAc/hex-
ane) 0.38; nmax (KBr) 3235, 1726, 1665 cmꢁ1
; dH (300 MHz, CDCl3)
10.77 (1H, s, CHO), 9.46 (1H, s, NH), 8.49 (1H, d, 8.1 Hz), 7.49–7.33
(3H, m, ArH), 4.54 (2H, J 7.2 Hz, q, OCH2), 1.48 (3H, t, J 7.2 Hz, CH3);
dC (75.5 MHz, CDCl3) 187.9, 160.3, 135.6, 132.3, 125.4, 124.8, 123.0,
122.5, 118.5, 112.6, 61.5, 13.8.
4.4.25. Dimethyl 4-hydroxy-1-phenyl-9-(phenylsulfonyl)-9H-
carbazole-2,3-dicarboxylate (19)
To a stirred solution of compound 16 (0.2 g, 0.47 mmol) in THF
at ꢁ78 ꢀC under N2, 1 M solution of LDA (0.15 g, 1.43 mmol) in dry
THF (10 mL) was added slowly and stirred. After 15 min, DMAD
(0.11 mL, 0.95 mmol) was added and stirring was continued at the
same temperature for 2 h. Then, the reaction mixture was
quenched with cold aq NH4Cl (15 mL) and extracted with EtOAc
(2ꢂ10 mL). Removal of solvent followed by column chromato-
graphic purification afforded carbazole 19 (0.1 g, 40%) as a colorless
solid; mp 222 ꢀC. [Found: C, 65.5; H, 4.32; N, 2.8; S, 6.4.
C28H21NO7S requires C, 65.23; H, 4.11; N, 2.72; S, 6.22%.] Rf (20%
4.4.21. Ethyl 3-((phenylthio)methyl)-1H-indole-2-carboxylate (13)
To a stirred solution of aldehydic ester 12 (1 g, 4.60 mmol) in
THF/MeOH (10:1) at room temperature, NaBH4 (0.18 g, 4.7 mmol)
was added portion wise and stirred for 2 h, then the reaction
mixture was quenched with cold dil HCl (2 mL), extracted with
EtOAc (10 mL). Then, the solvent was evaporated to afford the crude
alcohol (0.9 g), which was used as such for next step. To a solution
of crude alcohol (0.9 g, 4.10 mmol), thiophenol (0.56 g, 2.19 mmol),
p-TSA (0.16 g, 0.36 mmol) was refluxed with toluene (20 mL) for
3 h, then extracted with EtOAc, followed by column chromato-
graphic purification (2% EtOAc/hexane) afforded the required sul-
fide 13 (0.65 g, 70%); mp 130 ꢀC. [Found: C, 69.6; H, 5.7; N, 4.4; S,
10.1. C18H17NO2S requires C, 69.43; H, 5.50; N, 4.50; S, 10.30%.] Rf
EtOAc/hexane) 0.21; nmax (KBr) 1182, 1365, 1715, 3386 cmꢁ1
; dH
(300 MHz, CDCl3) 11.93 (1H, s, OH), 8.28 (1H, d, J 7.2 Hz, ArH), 8.13
(1H, d, J 8.1 Hz, ArH), 7.49–7.35 (4H, m, ArH), 7.32–7.14 (8H, m,
ArH), 3.94 (3H, s, OCH3), 3.51 (3H, s, OCH3); dC (75.5 MHz, CDCl3)
169.6, 167.4, 157.6, 143.4, 140.9, 137.3, 136.9, 135.9, 133.2, 130.7,
128.6, 127.6, 127.4, 127.2, 126.5, 126.0, 125.5, 123.5, 123.2, 117.9,
105.9, 53.1, 52.0.
(15% EtOAc/hexane) 0.71; nmax (KBr) 3241, 1726 cmꢁ1
; dH (300 MHz,
CDCl3) 8.89 (1H, s, NH), 7.68 (1H, d, J 8.1 Hz, ArH), 7.38–7.10 (8H, m,
ArH), 4.68 (2H, s, CH2SPh), 4.33 (2H, q, J 7.1 Hz, OCH2), 1.36 (3H, t, J
7.1 Hz, CH3); dC (75.5 MHz, CDCl3) 161.9, 136.5, 135.8, 131.4, 128.6,
127.4, 126.7, 125.8, 124.1, 120.5, 121.2, 119.2, 111.8, 61.0, 29.5, 14.3.
4.5. A representative procedure for the preparation of
indolylmethyl ester from indolyl bromides (procedure D)
4.4.22. Ethyl-3-((phenylsulfinyl)methyl)-1H-indole-2-
carboxylate (14)
4.5.1. Ethyl 5-methoxy-2-(2-methoxy-2-oxoethyl)-1-phenylsulfonyl-
Yield: 0.11 g (35%); thick liquid. [Found: C, 65.0; H, 5.0; N, 4.2; S,
9.7. C18H17NO3S requires C, 66.03; H, 5.23; N, 4.28; S, 9.79%.] Rf (20%
1H-indole-3-carboxylate (20a)
To
a stirred suspension of bromo compound 2a (0.5 g,
EtOAc/hexane) 0.20; nmax (KBr) 3247, 1729, 1172, 1381 cmꢁ1
;
dH
1.10 mmol), PdCl2(PPh3)2 (0.07 g, 0.11 mmol), and K2CO3 (0.23 g,
1.6 mmol) in dry THF (5 mL) dry CO gas was purged for 5 min. Then,
(300 MHz, CDCl3) 9.85 (1H, s, NH), 7.41–7.23 (8H, m, ArH), 7.03 (1H,

3600
N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
dry MeOH (2 mL) was added into the reaction mixture and allowed
to stir under CO atmosphere at room temperature for 12 h. The
reaction mixture was diluted with water (30 mL) and extracted
with EtOAc (2ꢂ15 mL). The combined organic layer was dried
(Na2SO4) and the removal of solvent followed by column chro-
matographic purification (10% EtOAc/hexane) afforded 20a (0.24 g,
50%) as a colorless solid; mp 118 ꢀC. [Found: C, 58.6; H, 5.0; N, 3.1; S,
7.1. C21H21NO7S requires C, 58.46; H, 4.91; N, 3.25; S, 7.43%.] Rf (20%
4.6.3. Dimethyl 4-hydroxy-6-methoxy-9-(phenylsulfonyl)-9H-
carbazole-1,3-dicarboxylate (21c)
Yield: 0.25 g (52%); colorless solid; mp 168 ꢀC. [Found: C, 58.6;
H, 4.3; N, 2.73; S, 7.0. C23H19NO8S requires C, 58.84; H, 4.08; N, 2.98;
S, 6.83%.] Rf (15% EtOAc/hexane) 0.37; nmax (KBr) 1169, 1370, 1705,
3331 cmꢁ1
; dH (400 MHz, CDCl3) 13.21 (1H, s, OH), 8.16 (2H, d, J
8.1 Hz, ArH), 7.77 (1H, s, ArH), 7.98–7.82 (2H, m, ArH), 7.67–7.36
(4H, m, ArH), 4.04 (3H, s, OCH3), 4.03 (3H, s, OCH3), 3.91(3H, s,
OCH3); dC (100.6 MHz, CDCl3) 164.2, 163.8, 157.6, 148.7, 146.5, 137.4,
136.7, 134.5, 128.8, 127.4, 127.1, 126.8, 125.7, 123.6, 118.2, 116.7, 115.2,
114.5, 55.8, 53.4, 53.2; m/z (EI) 471 (35, Mþþ2), 469 (17, Mþ), 328
(49%).
EtOAc/hexane) 0.68; nmax (KBr) 1175, 1375, 1707, 1740 cmꢁ1
; dH
(400 MHz, CDCl3) 7.93 (1H, d, J 6.9 Hz, ArH), 7.87 (2H, d, J 5.5 Hz,
ArH), 7.55–7.59 (2H, m, ArH), 7.45 (2H, t, J 8.0 Hz,), 6.92–6.95 (1H,
m, ArH), 4.69 (2H, s, CH2CO), 4.39 (2H, q, J 7.2 Hz, OCH2), 3.85 (3H, s,
OCH3), 3.71 (3H, s, OCH3), 1.43 (3H, t, J 7.1 Hz, CH3); dC (100.6 MHz,
CDCl3) 167.4, 165.2, 159.6, 134.2, 129.4, 126.8, 125.8, 124.5, 124.4,
121.7, 119.4, 115.1, 114.5, 104.4, 60.7, 55.6, 52.3, 33.1, 14.3; m/z (EI)
432 (45, Mþþ1), 431 (11%, Mþ).
4.6.4. Trimethyl 4-hydroxy-6-methoxy-9-(phenylsulfonyl)-9H-
carbazole-1,2,3-tricarboxylate (21d)
Yield: 0.28 g (52%); colorless solid; mp 142 ꢀC. [Found: C, 57.2;
H, 3.8; N, 2.4; S, 6.2. C25H21NO10S requires C, 56.92; H, 4.01; N, 2.66;
S, 6.08%.] Rf (15% EtOAc/hexane) 0.33; nmax (KBr) 1180, 1368, 1709,
4.5.2. Ethyl 2-(2-methoxy-2-oxoethyl)-1-(phenylsulfonyl)-1H-
indole-3-carboxylate (20b)
3328 cmꢁ1
; dH (400 MHz, CDCl3) 12.5 (1H, s OH), 8.20 (1H, d, J
Yield: 0.25 g (57%); colorless solid; mp 174 ꢀC. [Found: C, 60.0; H,
4.9; N, 3.7; S, 8.2. C20H19NO6S requires C, 59.84; H, 4.77; N, 3.49; S,
7.99%.] Rf (20% EtOAc/hexane) 0.84; nmax (KBr) 1168, 1370, 1715,
8.2 Hz, ArH), 7.73 (2H, d, J 7.3 Hz, ArH), 7.61 (2H, t, J 7.3 Hz, ArH),
7.43–7.11 (3H, m, ArH), 4.05 (3H, s, OCH3), 4.01 (3H, s, OCH3), 3.98
(3H, s, OCH3), 3.87 (3H, s, OCH3); dC (100.6 MHz, CDCl3) 163.8, 163.6,
163.3,157.2,148.7,145.2,136.7,134.5,128.9,128.8,127.1,126.6,125.7,
125.6, 124.7, 123.5, 117.4, 115.2, 113.9, 55.6, 53.1, 52.8, 52.3; m/z (EI)
529 (11, Mþþ2), 527 (35, Mþ), 356 (18%).
1738 cmꢁ1
; dH (300 MHz, CDCl3) 8.27 (1H, d, J 8.4 Hz, ArH), 7.95 (1H,
d, J 7.5 Hz, ArH), 7.84 (2H, d, J 7.5 Hz, ArH), 7.55 (1H, t, J 7.5 Hz, ArH),
7.44 (2H, t, J 7.5 Hz, ArH), 7.24–7.35 (2H, m, ArH), 4.75 (2H, s,
CH2CO), 4.08 (3H, s, OCH3), 3.58 (2H, q, J 7.1 Hz, OCH2), 1.03 (3H, t, J
7.1 Hz, CH3); dC (75.5 MHz, CDCl3) 169.9, 164.5, 140.4, 138.6, 135.7,
134.3, 129.4, 126.9, 126.8, 125.4, 124.5, 122.2, 114.2, 113.7, 60.8, 52.3,
32.9, 14.3.
4.7. A representative procedure for the preparation of
indolylmethyl cyanide 21a from bromide 2a (procedure E)
4.7.1. Ethyl 2-(cyanomethyl)-5-methoxy-1-(phenylsulfonyl)-1H-
indole-3-carboxylate (22a)
4.6. A representative procedure for the preparation of
carbazole 26a from indolylmethyl acetate 20a (procedure F)
To a stirred suspension of NaCN (60 mg, 1.22 mmol) in DMSO
(5 mL) and THF (15 mL) at 0 ꢀC, bromo compound 2a (0.45 g,
1.0 mmol) was added and stirred at same temperature for 1 h. The
reaction mixture was then diluted with water (20 mL). The crude
product was extracted with EtOAc (2ꢂ15 mL) and washed water
(2ꢂ20 mL) and dried (Na2SO4). Evaporation of solvent, followed by
crystallization from EtOH afforded cyano compound 22a (0.23 g,
58%) as a colorless solid; mp 164 ꢀC. [Found: C, 60.5; H, 4.8; N, 7.2; S,
7.8. C20H18N2O5S requires C, 60.29; H, 4.55; N, 7.03; S, 8.05%.] Rf
4.6.1. Dimethyl 4-hydroxy-9-(phenylsulfonyl)-9H-carbazole-1,3-
dicarboxylate (21a)
To a stirred suspension of t-BuOK (0.13 g, 1.16 mmol) in dry THF
(10 mL) at 0 ꢀC, indolylmethyl acetate 20b (0.40 g, 1.00 mmol) in
THF (5 mL) was slowly added. After 5 min, methyl propiolate
(0.11 g, 1.30 mmol) was added at the same temperature and stirring
was continued for 2 h. Then it was quenched with saturated am-
monium chloride solution (10 mL), extracted with EtOAc
(2ꢂ20 mL), and the extracts were combined and dried (Na2SO4).
Removal of solvent followed by column chromatographic purifi-
cation (5% EtOAc/hexane) afforded 21a (0.2 g, 45%) as a colorless
(20% EtOAc/hexane) 0.44; nmax (KBr) 1176, 1382, 1709, 2222 cmꢁ1
;
dH (300 MHz, CDCl3) 1.49 (3H, t, J 7.2 Hz, CH3), 3.86 (3H, s, OCH3),
4.47 (2H, q, J 7.2 Hz, OCH2), 4.82 (2H, s, CH2CN), 7.02 (1H, dd, J 2.4,
6.6 Hz, ArH), 7.52–7.47 (2H, m, ArH), 7.64–7.59 (2H, m, ArH), 7.97–
7.94 (2H, m, ArH), 8.03 (1H, d, J 9.3 Hz, ArH); dC (75.5 MHz, CDCl3)
163.7, 157.4, 137.7, 134.9, 134.8, 130.3, 129.6, 127.7, 126.9, 115.8, 115.6,
115.4, 114.3, 104.4, 61.3, 55.6, 16.4, 14.3.
solid; mp 130 ꢀC. [Found: C, 60.3; H, 3.7; N, 3.3; S, 7.0. C25H21NO10
requires C, 60.13; H, 3.90; N, 3.19; S, 7.30%.] Rf (15% EtOAc/hexane)
0.48; nmax (KBr) 1178, 1365, 1712, 3391 cmꢁ1
dH (300 MHz, CDCl3)
S
;
12.62 (1H, s, OH), 7.93–7.78 (3H, m, ArH), 7.69 (2H, d, J 7.3 Hz, ArH),
7.72 (1H, s, ArH), 7.62 (2H, d, J 7.2 Hz, ArH), 7.45–7.21 (2H, m, ArH),
4.05 (3H, s, OCH3), 4.03 (3H, s, OCH3); dC (75.5 MHz, CDCl3) 163.8,
163.5, 157.2, 148.7,146.5, 136.7, 134.5, 129.2, 127.1, 126.7, 125.7, 125.5,
124.7, 123.5, 117.4, 115.2, 114.1, 53.4, 53.2; m/z (EI) 441 (7, Mþþ2),
439 (26%, Mþ).
4.7.2. Ethyl 2-(cyanomethyl)-1-(phenylsulfonyl)-1H-indole-3-
carboxylate (22b)
Yield: 0.23 g (53%); brown solid; mp 102 ꢀC. [C, 62.1; H, 4.5; N,
7.5; S, 8.9. C19H16N2O4S requires C, 61.94; N, 7.60; S, 8.70H, 4.38%.] Rf
(20% EtOAc/hexane) 0.47; nmax (KBr) 1176, 1383, 1709, 2222 cmꢁ1
;
dH (300 MHz, CDCl3) 1.47 (3H, t, J 7.1 Hz, CH3), 4.47 (2H, q, J 7.1 Hz,
CH2), 4.86 (2H, s, CH2CN), 7.38 (2H, quint, J 8.4 Hz, ArH), 7.49 (2H, t, J
7.5 Hz, ArH), 7.61 (1H, t, J 7.2 Hz, ArH), 7.98 (2H, d, J 7.8 Hz, ArH), 8.12
(2H, d, J 8.7 Hz, ArH); dC (75.5 MHz, CDCl3) 163.8, 137.6, 134.9, 134.8,
130.5, 129.7, 127.1, 126.3, 125.0, 122.5, 115.8, 115.4, 114.4, 61.3, 16.3,
14.3.
4.6.2. Trimethyl 4-hydroxy-9-(phenylsulfonyl)-9H-carbazole-1,2,3-
tricarboxylate (21b)
Yield: 0.25 g (50%); colorless solid; mp 128 ꢀC. [Found: C, 57.7;
H, 4.0; N, 3.1; S, 6.3. C24H19NO9S requires C, 57.94; H, 3.85; N, 2.82;
S, 6.45%.] Rf (15% EtOAc/hexane) 0.38; nmax (KBr) 1178, 1365, 1704,
3328 cmꢁ1
; dH (400 MHz, CDCl3), 13.2 (1H, s, OH), 8.18 (2H, d, J
8.1 Hz, ArH), 7.68 (2H, t, J 7.2 Hz, ArH), 7.51–7.34 (3H, m, ArH), 7.12
(2H, d, J 7.1 Hz, ArH), 4.05 (3H, s, OCH3), 4.03 (3H, s, OCH3), 4.00 (3H,
s, OCH3); dC (100.6 MHz, CDCl3) 163.8, 163.6, 163.3, 148.9, 148.7,
145.2, 136.7, 134.5, 128.9, 128.7, 126.9, 126.6, 125.5, 125.3, 124.7,
123.5, 117.4, 115.2, 114.6, 52.9, 52.5, 52.3; m/z (EI) 499 (21, Mþþ2),
497 (35, Mþþ1), 326 (54%).
4.7.3. 2-[3-Acetyl-1-(1-phenylsulfonyl)-1H-indol-2yl]aceto-
nitrile (22c)
Yield: 0.24 g (55%); brown solid; mp 150 ꢀC. [Found: C, 64.0; H,
4.3; N, 8.1; S, 9.9. C18H14N2O3S requires C, 63.89; H, 4.17; N, 8.28; S,
9.48%.] Rf (20% EtOAc/hexane) 0.42; nmax (KBr) 1172, 1365, 1696,
2221 cmꢁ1
; dH (300 MHz, CDCl3) 8.19–8.17 (1H, m, ArH), 7.53–7.39

N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
3601
(4H, m, ArH), 7.65–7.58 (1H, m, ArH), 7.87–7.84 (1H, m, ArH), 8.02–
7.97 (2H, m, ArH), 4.75 (2H, s, CH2CN), 2.73 (3H, s, CH3); dC
(75.5 MHz, CDCl3) 195.5, 137.7, 135.9, 134.9, 133.8, 129.7, 127.1, 126.1,
125.9, 125.0, 121.9, 121.1, 115.9, 114.9, 32.3.
3.92; N, 6.06; S, 6.93%.] Rf (15% EtOAc/hexane) 0.43 nmax (KBr)
1172, 1365, 1706, 2221 cmꢁ1
dH (300 MHz, CDCl3) 8.24 (1H, d, J
;
8.4 Hz, ArH), 7.99 (1H, d, J 8.1 Hz, ArH), 7.59–7.56 (3H, m, ArH),
7.51–7.41 (2H, m, ArH), 7.31 (2H, t, J 7.8 Hz, ArH), 4.04 (3H, s,
OCH3), 3.96 (3H, s, OCH3), 2.80 (3H, s, CH3); dC (75.5 MHz, CDCl3)
167.1, 165.8, 141.5, 140.0, 136.9, 136.7, 135.3, 134.3, 131.3, 130.9,
129.0, 128.9, 127.0, 126.3, 125.8, 123.4, 117.8, 114.7, 100.1, 53.5,
53.1, 18.3.
4.7.4. Ethyl 30-[1-(phenylsulfonyl)-2-cyanomethylindol-3-yl]-
acrylate (22d)
Yield: 0.18 g (42%); brown solid; mp 210 ꢀC. [Found: C, 64.1; H,
4.8; N, 6.9; S, 8.3. C21H18N2O4S requires C, 63.94; H, 4.60; N, 7.10; S,
8.13%.] Rf (20% EtOAc/hexane) 0.35; nmax (KBr) 1164, 1381, 1720,
4.7.10. Ethyl-3-(dicyanomethyl)-1H-indole-2-carboxylate (23)
Yield: 0.13 g (45%); brown solid; mp 164 ꢀC. [Found: C, 66.6; H,
4.6; N, 16.3. C14H11N3O2 requires C, 66.40; H, 4.38; N, 16.59%.] Rf
2245 cmꢁ1
; dH (300 MHz, CDCl3) 8.22 (1H, d, J 8.2 Hz, ArH) 7.82–
7.71 (2H, m, ArH), 7.38–7.10 (7H, m, ArH), 6.57 (1H, d, J 15.9 Hz,
CH¼CH), 4.78 (2H, s, CH2CN), 4.18 (2H, q, J 7.1 Hz, OCH2), 1.27 (3H, t,
J 7.1 Hz, CH3); m/z (EI) 394 (5, Mþ), 348 (25), 207 (68%).
(20% EtOAc/hexane) 0.60; nmax (KBr) 1687, 2222, 3234 cmꢁ1
; dH
(300 MHz, CDCl3) 9.13 (1H, s, NH), 7.91 (1H, d, J 9.0 Hz, ArH), 7.44–
7.26 (3H, m, ArH), 6.35 (1H, s, CHCN), 4.44 (2H, q, J 7.2 Hz, OCH2),
1.41 (3H, t, J 7.2 Hz, CH3); dC (75.5 MHz, CDCl3) 159.4, 134.4, 126.0,
123.8, 123.1, 121.6, 118.8, 111.5, 110.5, 105.2, 61.2, 17.7, 13.2.
4.7.5. Methyl 1-cyano-4-hydroxy-9-(phenylsulfonyl)-9H-
carbazole-3-carboxylate (27a)
Yield: 0.18 g (45%); colorless solid; mp 167 ꢀC. [Found: C, 62.3; H,
3.6; N, 6.6; S, 8.1. C21H14N2S requires C, 62.06; H, 3.47; N, 6.89; S,
7.89%.] Rf (15% EtOAc/hexane) 0.50; nmax (KBr) 1178, 1365, 2222,
Acknowledgements
3328 cmꢁ1
; dH (300 MHz, CDCl3) 12.5 (1H, s, OH), 8.35–8.25 (4H, m,
The authors thank CSIR, New Delhi (01/(2071)06/EMR-II) for
financial support. G.G.R. thanks CSIR for a fellowship. Authors thank
DST-FIST for 300 MHz NMR facility.
ArH), 7.79 (1H, d, J 7.8 Hz, ArH), 7.59–7.55 (2H, m, ArH), 7.49–7.42
(3H, m, ArH), 4.06 (3H, s, OCH3); dC (75.5 MHz, CDCl3) 166.2, 159.8,
141.5, 140.0, 136.7, 136.6, 135.4,134.4, 131.3,129.2, 128.7,127.1, 126.5,
125.3, 123.5, 116.7, 115.1, 114.2, 53.2; m/z (EI) 406 (56, Mþ), 408 (21,
Mþþ2), 380 (39%).
References and notes
1. (a) Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875–2911; (b) Cacchi,
S.; Fabrizi, G. Chem. Rev. 2005, 105, 2875–2911.
4.7.6. Dimethyl 1-cyano-4-hydroxy-9-(phenylsulfonyl)-9H-
carbazole-2,3-dicarboxylate (27b)
2. (a) Gribble, G. W. In The Alkaloids; Brossi, A., Ed.; Academic: New York, NY, 1990;
Vol. 39, p 239; (b) Kno¨lker, H. J. In Advances in Nitrogen Heterocycles; Moody,
C. J., Ed.; JAI: Greenwich, 1995; Vol. 1, p 173; (c) Gribble, G. W.; Comprehensive
Heterocyclic Chemistry, 2nd ed.; Pergamon: New York, NY, 1996; Vol. 2, p 203;
(d) Chakraborty, D. P.; Roy, S. In Progress in the Chemistry of Organic Natural
Products; Herz, W., Griesebach, H., Kirby, G. W., Tamm, C., Eds.; Springer: Wien,
1991; Vol. 57, p 71; (e) Chakraborty, D. P. In The Alkaloids; Cordell, G. A., Ed.;
Academic: New York, NY, 1993; Vol. 44, p 257.
3. Chakraborty, D. P.; Barman, B. K.; Bose, P. K. Tetrahedron 1965, 21, 681–685.
4. (a) Bergman, J.; Peloman, B. Pure Appl. Chem. 1990, 62, 1967–1976; (b) Moody,
C. J. Synlett 1994, 681–688; (c) Kno¨lker, H. J. Chem. Soc. Rev. 1999, 28, 151–157;
(d) Freeman, A. W.; Urvoy, M.; Criswell, M. E. J. Org. Chem. 2005, 70, 5014–5019;
(e) Liu, C.-Y.; Knochel, P. Org. Lett. 2005, 7, 2543–2546.
Yield: 0.16 g (32%); colorless solid; mp 222 ꢀC. [Found: C, 60.4;
H, 4.18; N, 5.3; S, 6.28. C25H22N2S requires C, 60.72; H, 4.48; N, 5.66;
S, 6.48%.] Rf (15% EtOAc/hexane) 0.38; nmax (KBr) 1172, 1378, 1712,
2221, 3349 cmꢁ1
; dH (300 MHz, CDCl3) 12.38 (1H, s, OH), 8.33–8.27
(2H, m, ArH), 7.87 (2H, d, J 7.6 Hz, ArH), 7.56 (2H, q, J 7.2 Hz, ArH),
7.44 (3H, quint, J 7.8 Hz, ArH), 4.04 (3H, s, OCH3), 4.01 (3H, s, OCH3);
dC (75.5 MHz, CDCl3) 168.5, 166.6, 160.9, 142.1, 140.9, 139.5, 137.6,
134.5, 129.3, 128.4, 127.1, 125.5, 123.9, 123.7, 117.8, 115.9, 114.8, 106.0,
91.8, 53.7.
5. (a) Kno¨lker, H.-J.; Reddy, K. R. Chem. Rev. 2002,102, 4303–4427; (b) Kno¨lker, H. J.;
Reddy, K. R. In The Alkaloids; Cordell, G. A, Ed.; Elsevier Science, 2008; Vol. 65,
pp 1–430.
4.7.7. Methyl 1-cyano-4-hydroxy-6-methoxy-9-(phenylsulfonyl)-
9H-carbazole-3-carboxylate (27c)
6. (a) Rathwell, K.; Brimble, M. A. Synthesis 2007, 643–662; (b) Hill, B.; Rodrigo, R.
Org. Lett. 2005, 7, 5223–5225; (c) Hauser, F. M.; Liao, H.; Sun, Y. Org. Lett. 2002,
4, 2241–2243; (d) Hauser, F. M.; Yin, H. Org. Lett. 2000, 2, 1045–1047; (e)
Hauser, F. M.; Xu, Y.-J. Org. Lett. 1999, 1, 335–336; (f) Katritzky, A. R.; Zhang, G.;
Xie, L.; Ghiviriga, I. J. Org. Chem. 1996, 61, 7558–7563; (g) Hauser, F. M.; Zhou, M.
J. Org. Chem. 1996, 61, 5722; (h) Uchida, T.; Endo, Y.; Hizatate, S.; Shudo, K. Chem.
Pharm. Bull. 1994, 42, 419–421; (i) Terpstra, J. W.; van Leusen, A. M. J. Org. Chem.
1986, 51, 230–238.
7. (a) Tamura, Y.; Mohri, S.; Maeda, H.; Tsugoshi, T.; Sasho, M.; Kita, Y. Tetrahedron
Lett. 1984, 25, 309–312; (b) Kita, Y.; Mohri, S.; Tsugoshi, T.; Maeda, H.; Tamura, Y.
Chem. Pharm. Bull. 1985, 33, 4723–4731; (c) Jackson, P. M.; Moody, C. J. Synlett
1990, 521–522; (d) Jackson, P. M.; Moody, C. J.; Mortimer, R. J. J. Chem. Soc.,
Perkin Trans. 1 1991, 2941–2944; (e) Elango, S.; Srinivasan, P. C. Tetrahedron Lett.
1993, 34, 1347–1350; (f) Rao, M. V. B.; Satyanarayana, J.; Ila, H.; Junjappa, H.
Tetrahedron Lett. 1995, 36, 3385–3388; (g) Nonaka, Y.; Kawasaki, T.; Sakamoto,
M. Heterocycles 2000, 53, 1681–1684; (h) Joseph, B.; Da Costa, H.; Me´rour, J.-Y.;
Yield: 0.25 g (62%); colorless solid; mp 198 ꢀC. [Found: C, 60.7;
H, 3.9; N, 6.2; S, 7.1. C25H21NO10S requires C, 60.54; H, 3.70; N, 6.42;
S, 7.35%.] Rf (20% EtOAc/hexane) 0.48; nmax (KBr) 1178, 1365, 1712,
2222, 3328 cmꢁ1
; dH (400 MHz, CDCl3) 12.38 (1H, s, OH), 7.82 (1H, s,
ArH), 7.78–7.71 (2H, m, ArH), 7.57 (3H, d, J 7.2 Hz, ArH), 7.48–7.37
(m, 3H, ArH), 4.03 (3H, s, OCH3), 3.89 (3H, s, OCH3); dC (100.6 MHz,
CDCl3) 163.2, 157.2, 148.7, 146.5, 136.9, 136.5, 135.2, 134.7, 132.3,
129.2, 126.8, 126.7, 125.1, 123.7, 122.7, 117.4, 114.9, 114.3, 55.4, 53.2.
4.7.8. Dimethyl 1-cyano-4-hydroxy-6-methoxy-9-(phenylsulfonyl)-
9H-carbazole-2,3-dicarboxylate (27d)
Yield: 0.19 g (40%); colorless solid; mp 198 ꢀC. [Found: C, 58.5; H,
3.4; N, 5.4; S, 6.3. C24H18N2O8S requires C, 58.30; H, 3.67; N, 5.67; S,
6.48%.] Rf (20% EtOAc/hexane) 0.38; nmax (KBr) 1176, 1382, 1709,
´
Leonce, S. Tetrahedron 2000, 56, 3189–3196; (i) Vessels, J. T.; Janicki, S. Z.; Petillo,
P. A. Org. Lett. 2002, 2, 73–76; (j) Witulski, B.; Alayrae, C. Angew. Chem., Int. Ed.
2002, 41, 3281–3284; (k) Back, T. G.; Pandyra, A.; Wulff, J. E. J. Org. Chem. 2003,
2221, 3342 cmꢁ1
; dH (400 MHz, CDCl3) 12.52 (1H, s, OH), 8.17 (1H, d,
´
´
´
´
68, 3299–3302; (l) Martınes-Esperon, M. F.; Rodrıguez, D.; Castedo, L.; Saa, C.
Org. Lett. 2005, 7, 2213–2216; (m) Martı´nes-Espero´n, M. F.; Rodrı´guez, D.;
J 8.8 Hz, ArH), 7.78 (3H, d, J 8.0 Hz, ArH), 7.53 (1H, d, J 7.2 Hz, ArH),
7.41–7.37 (2H, m, ArH), 7.15 (1H, d, J 7.2 Hz, ArH), 4.05 (3H, s, OCH3),
4.00 (3H, s, OCH3), 3.90 (3H, s, OCH3); dC (100.6 MHz, CDCl3) 168.3,
166.6, 160.9, 157.5, 142.2, 140.9, 139.7, 137.9, 134.8, 129.6, 126.9,
125.6, 123.9, 123.7, 117.8, 115.8, 114.7, 105.9, 55.6, 53.7, 53.6.
´
Castedo, L.; Saa, C. Tetrahedron 2008, 64, 3674–3686.
8. (a) Scott, T. L.; Yu, X.; Gorugantula, S. P.; Carrero-Martı´nez, G.; S3oderberg, B. C.
G. Tetrahedron Lett. 2006, 62, 10835–10842; (b) Kong, A.; Han, X.; Lu, X. Org. Lett.
2006, 8, 1339–1342; (c) Rajeswaran, W. G.; Srinivasan, P. C. Synthesis 1994, 270–
272; (d) De Koning, C. B.; Michael, J. P.; Rousseau, A. L. J. Chem. Soc., Perkin Trans.
1 2000, 1705–1713; (e) Cai, X.; Snieckus, V. Org. Lett. 2004, 6, 2293–2295; (f) Liu,
Z.; Larock, R. C. Org. Lett. 2004, 6, 3739–3741; (g) Merlic, C. A.; McInnes, D. M.
Tetrahedron Lett. 1997, 38, 7661–7664.
4.7.9. Dimethyl 1-cyano-4-methyl-9-(phenylsulfonyl)-9H-
carbazole-2,3-dicarboxylate (27e)
Yield: 0.16 g (36%); colorless solid; mp 164 ꢀC. [Found: C,
62.5; H, 4.0; N, 6.2; S, 6.7. C24H18N2O6S requires C, 62.33; H,
9. Mali, R. S.; Jagtap, P. G. Tetrahedron Lett. 1992, 33, 1655–1656.
10. Mohanakrishnan, A. K.; Srinivasan, P. C. Tetrahedron Lett. 1993, 34, 1343–1346.
11. (a) Hauser, F. M.; Dorsch, W. A.; Mal, D. Org. Lett. 2002, 4, 2237–2239; (b)
Hauser, F. M.; Dorsch, W. A. Org. Lett. 2003, 5, 3753–3754.

3602
N. Ramesh et al. / Tetrahedron 65 (2009) 3592–3602
12. (a) Mohanakrishnan, A. K.; Srinivasan, P. C. J. Org. Chem. 1995, 60, 1939–1946;
(b) Mohanakrishnan, A. K.; Balamurugan, R. Tetrahedron Lett. 2005, 46,
4045–4048; (c) Mohanakrishnan, A. K.; Dhayalan, V.; Arul Clement, J.;
Balamurugan, R.; Sureshbabu, R.; Senthil Kumar, N. Tetrahedron Lett. 2008, 49,
5850–5854.
13. (a) Balamurugan, R.; Mohanakrishnan, A. K. Tetrahedron 2007, 63, 11078–11085;
(b) Ramesh, N.; Prakash, C.; Dhayalan, V.; Sureshbabu, R.; Mohanakrishnan, A. K.
Tetrahedron 2008, 64, 2071–2079.
15. (a) Katritzky, A. R.; Xie, L. J. Org. Chem. 1995, 60, 3707–3710; (b) Katritzky, A. R.;
Li, J.; Stevens, C. V. J. Org. Chem. 1995, 60, 3401–3404.
16. (a) Cardellina, J. H., II; Kirkup, M. P.; Moore, R. E.; Mynderse, J. S.; Seff, K.;
Simmons, C. J. Tetrahedron Lett. 1979, 20, 4915–4916; (b) Kato, S.; Kawai, H.;
Kawasaki, T.; Toda, Y.; Urata, T.; Hayakawa, Y. J. Antibiot. 1989, 42, 1879–1881;
(c) Mo, C.-J.; Ya, K. S.; Furihata, K.; Shimazu, A.; Hayakawa, Y.; Seto, H. J. Antibiot.
1990, 43, 1337–1349; (d) Kotoda, N.; Ya, K. S.; Furihata, K.; Hayakawa, Y.; Seto,
H. J. Antibiot. 1997, 50, 770–772.
14. Mohanakrishnan, A. K.; Ramesh, N. Tetrahedron Lett. 2005, 46, 4231–4233.
17. Mohanakrishnan, A. K.; Ramesh, N. Tetrahedron Lett. 2005, 46, 4577–4579.