Ligand-, copper-, and amine-free one-pot synthesis of 2-substituted indoles via Sonogashira coupling 5-endo-dig cyclization

Article abstract of DOI:10.1016/j.tet.2006.03.035

Results of the optimized conditions for the one-pot synthesis of 2-substituted indoles via palladium acetate catalyzed tandem Sonogashira coupling 5-endo-dig cyclization at room temperature under ultrasonic irradiation and standard stirred conditions are

Full text of DOI:10.1016/j.tet.2006.03.035

Tetrahedron 62 (2006) 5109–5115
Ligand-, copper-, and amine-free one-pot synthesis of
2-substituted indoles via Sonogashira coupling
5-endo-dig cyclization
*
Sanjay S. Palimkar, P. Harish Kumar, Rajgopal J. Lahoti and Kumar V. Srinivasan
Division of Organic Chemistry, Technology, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
Received 5 January 2006; revised 22 February 2006; accepted 9 March 2006
Available online 17 April 2006
Abstract—Results of the optimized conditions for the one-pot synthesis of 2-substituted indoles via palladium acetate catalyzed tandem
Sonogashira coupling 5-endo-dig cyclization at room temperature under ultrasonic irradiation and standard stirred conditions are described.
Electron-donating and electron-withdrawing groups present in both coupling partners were well tolerated under these mild conditions. A
copper-, ligand- and amine-free condition is an important feature of this protocol. Significant enhancement of reaction rates was observed
for the reactions employing ultrasonic irradiation.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
reported methods suffer from some drawbacks such as harsh
reaction conditions, prolonged reaction period, and cumber-
some isolation procedure. Many of these methods employ
moisture sensitive phosphine ligands and phosphine based
palladium catalysts such as PdCl2(PPh3)2 and Pd(PPh3)4
and also make use of copper iodide as co-catalyst. With
the presence of copper(I) co-catalyst the Glaser type oxida-
tive dimerization of alkynes15 is encountered thus lowering
chemoselectivity. In addition, the starting amines have
a characteristic foul smell and industrial wastes containing
them would require treatment for environmental purposes.
Indole derivatives occur widely in natural products and
possess unique biological activity.1 Various 2-substituted in-
doles exhibit interesting pharmacological properties such as
antithrombatic,2 anti-cancer,3 histamine H3 receptor antago-
nism,4 etc. Many synthetic methods for the construction of
indole ring have been reported.5 Among these palladium cat-
alyzed annulation of o-halo anilines and alkynes has been
employed widely due to the versatile nature of these proto-
cols, increased functional group tolerance, and improved
yields.6
As a part of our continuing interest in palladium catalyzed
carbon–carbon cross coupling reactions,16 we recently re-
ported the ultrasound promoted ligand- and copper-free So-
nogashira reaction at ambient temperature.16c Our interest in
exploring the potential of this reaction prompted us to extend
studies to the palladium catalyzed one-pot synthesis of
2-substituted indoles via Sonogashira coupling 5-endo-dig
cyclization. To the best of our knowledge, a copper-, ligand-,
and amine-free one-pot synthesis of indole derivatives via
Sonogashira coupling 5-endo-dig cyclization has not been
reported. Herein, we wish to report an efficient one-pot
synthesis of 2-substituted indoles via Sonogashira coupling
5-endo-dig cyclization under ligand-, copper-, and amine-
free conditions at room temperature using ultrasound irradi-
ation and standard stirred conditions, respectively. The
methodology developed makes use of 2 mol % of Pd(OAc)2
in the presence of Bu4NOAc as a base. Considerable rate
enhancement and in most cases marginally improved yields
were observed for the sonochemical reactions.
The synthesis of indoles via Sonogashira reaction is gener-
ally carried out in two steps viz. the palladium–copper cata-
lyzed Sonogashira cross coupling between 2-aminoaryl
halide and alkyne followed by cyclization of the resulting
2-alkynylanilines. The various catalysts and promoters
reported for the cyclization of 2-alkynylanilines include
copper(I),7 metal alkoxide,8 fluorides,9 Lewis acids,10
gold(III),11 and iodine.12 Very recently Sakamoto et al.
reported cyclization of 2-ethynylaniline derivatives to in-
doles catalyzed by copper(II) salts in aqueous medium.13a
Konakahara et al. reported cyclization of 2-alkynylanilines
catalyzed by Indium bromide.13b Also, several methods are
reported for one-pot synthesis of indole via tandem Sonoga-
shira coupling 5-endo-dig cyclization.14 Most of these
Keywords: Indole; Synthesis; 5-endo-dig Cyclization; Ultrasound.
* Corresponding author. Tel.: +91 20 25889089; fax: +91 20 25893614;
e-mail: kv.srinivasan@ncl.res.in
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.035

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S. S. Palimkar et al. / Tetrahedron 62 (2006) 5109–5115
Table 2. Effect of solvent on Sonogashira coupling 5-endo-dig-cyclization
reaction
2. Results and discussion
I
2 mol% Pd(OAc)2
Palladium catalyzed reactions are strongly dependent on
a number of factors such as base, solvent, stabilizing ligand,
temperature, and the combined effect of these. Based on our
ongoing work on copper- and ligand-free palladium cata-
lyzed C–C coupling reactions,16c our initial aim was to opti-
mize the reactions conditions for this protocol under both
ultrasound irradiation and standard stirred conditions at
room temperature. For this purpose, we systematically eval-
uated the role of base and solvent for this synthetic protocol
by subjecting 2-iodo-4-methyl-N-tosylbenzenamine to the
tandem coupling–cyclization process. The results are sum-
marized in Tables 1 and 2, respectively.
Ph
+
Ph
solvent, Bu4NOAc 2.5 eq, 30°C
)))), 6 h (or) standard
condition, 48 h
N
NHTs
Ts
Entry
Solvent
Yield (%)a
Ultrasonic
irradiation
Standard stirred
conditions
1
2
3
4
5
6
7
DMF
NMP
DMA
THF
CH3CN
CH3CN
Acetone
50
0
5
44
74
74b
50
32
0
14
26
71
71c
49
Bu4NOAc was found to be the most effective base (entry 14,
Table 1). Other bases (entries 1–7, Table 1) were substan-
tially less effective. Potassium-tert-butoxide failed to pro-
mote the reaction. Tetrabutylammonium salts are known to
facilitate the reduction of Pd(OAc)2 to catalytically active
Pd(0) species.17 Recently Verkade and Urgaonkar reported
the Bu4NOAc promoted Sonogashira reaction.18 We investi-
gated the effect of counter anions (entries 10–14, Table 1) of
the tetrabutylammonium salts. It was found that acetate and
fluoride (entry 13 and 14, Table 1) promote this coupling–
cyclization reaction whereas, bromide and hydroxide (entry
10 and 11, Table 1) did not promote the reaction. Even
though Bu4NF (in THF 1 M solution) gave an appreciable
yield nearly comparable to that with Bu4NOAc under stan-
dard stirred conditions, surprisingly, the yield was low under
ultrasound irradiation.
a
Isolated yields.
Yield after 5 h.
Yield after 30 h.
b
c
for synthesizing 2-substituted indoles required 2 mol % of
Pd(OAc)2, 2.5 equiv of Bu4NOAc and acetonitrile as the
solvent.
The reaction time was optimized for the benchmark reaction
under both ultrasonic irradiation and standard stirred condi-
tions. The isolated yields at various time intervals are given
in Table 3. It can be observed for the reaction employing
ultrasonic irradiation, the yield was found to increase up to
5 h after which there was no further conversion. Similarly,
for the standard stirred conditions the isolated yield was
optimized at 30 h.
Next, the above benchmark reaction using Bu4NOAc as the
base was examined in various solvents. As is evident, from
Table 2 acetonitrile was found to be the most suitable sol-
vent. These tests showed that the optimal reaction conditions
Table 3. Optimization of reaction time for the benchmark reaction
Standard stirred
conditions
Time (h)
5
39
12
48
18
58
24
64
30
71
36
71
Yield (%)a
Ultrasonic
irradiation
Time (h)
3
58
4
65
5
74
6
74
Table 1. Effect of base on Sonogashira coupling 5-endo-dig-cyclization
reaction
Yield (%)a
a
I
Isolated yields.
2 mol% Pd(OAc)2
Ph
+
Ph
CH3CN, Base 2.5 eq, 30°C
)))), 6 h (or) standard
condition, 48 h
N
NHTs
Ts
For the identical time (5 h) yield for the reaction employing
ultrasonic irradiation was 74% in comparison to that for the
standard stirred condition, which gave only 39% yield. This
clearly shows significant enhancement in the reaction rate
for the reaction employing ultrasonic irradiation.
Entry
Base
Yield (%)a
Ultrasonic
irradiation
Standard stirred
conditions
1
2
3
4
5
6
7
8
Diisopropyl amine
DABCO
Et3N
NaOAc
Cs2CO3
7
44
23
4
10
13
11
0
6
25
26
5
9
12
9
0
0
0
0
To survey the generality of this protocol the optimized reac-
tion conditions were applied to the synthesis of various 2-
substituted indole derivatives. The results are summarized
in Table 4. In all the cases, the reaction time was optimized
as for the benchmark reaction. The time of reaction indicated
in Table 4 is the optimized time after which no further
conversion and improvement in the isolated yield were
observed. We studied the effect of different substituents on
o-iodoanilides and 1-alkynes. Both the unsubstituted
o-iodoanilides and the substituted o-iodoanilides having an
electron-donating group on the aromatic ring moiety gave
indoles in good yields. It is noteworthy that even if R1 (Table
4) is an electron-withdrawing group (–COMe, –CO2Me,
entries 11–18, Table 4) the reaction proceeded smoothly to
afford the 2-substituted indoles in moderate yields. Another
K2CO3
K3PO4
Piperidine
9
10
11
KOtBu
Bu4NBr
0
0
0
Bu4NOH (in methanol
0.1 N)
Bu4NF (in water 75%
solution)
Bu4NF (in THF 1 M
solution)
Bu4NOAc
12
13
23
39
74
15
68
71
14
a
Isolated yields.

S. S. Palimkar et al. / Tetrahedron 62 (2006) 5109–5115
Table 4. Synthesis of indole derivatives under silent conditions and ultrasound irradiationa
5111
2 mol% Pd(OAc)2,
2.5 eq Bu4NOAc
R1
I
R1
R3
+
R3
CH3CN, 30°C, )))) (or)
standard condition
N
NHR2
R2
R1 = H, CH3, CO2Me, COMe
R2 = Ts, Ms
R3 = Ph, p-tolyl, 4-methoxy phenyl, 3-fluoro phenyl, naphthyl,
1-hydroxy ethyl
Entry
o-Iodoanilide 1
1-Alkyne 2
Product 3
Ultrasonic irradiation
Yield (%)b
Standard stirred conditions
Yield (%)b
Time (h)
Time (h)
I
Ph
N
Ts
1
2
4
82
24
80
NHTs
2a
3a
1a
1a
1a
5
6
71
72
30
30
69
76
N
Ts
3b
2b
OMe
OMe
3
4
N
2c
Ts
3c
1a
6
6
63
44
24
24
67
41
N
Ts
2d
3d
OH
OH
Ph
5
1a
N
Ts
3e
2e
I
N
6
7
8
9
2a
2b
2c
2d
5
5
5
6
74
90
90
42
30
36
36
30
71
87
74
46
NHTs
Ts
3f
1b
1b
1b
1b
N
Ts
3g
OMe
N
Ts
3h
N
Ts
3i
F
F
10
11
1b
6
6
65
51
36
12
56
43
N
Ts
3j
2f
O
O
I
NHMs
MeO
MeO
2a
Ph
N
Ms
1c
3k
(continued)

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S. S. Palimkar et al. / Tetrahedron 62 (2006) 5109–5115
Table 4. (continued)
Entry
o-Iodoanilide 1
1-Alkyne 2
Product 3
Ultrasonic irradiation
Time (h)
Yield (%)b
Standard stirred conditions
Time (h)
Yield (%)b
O
MeO
O
12
1c
1c
2b
6
6
54
12
12
58
N
Ms
3l
OMe
13
2c
60
54
N
Ms
3m
O
MeO
N
14
15
1c
1c
2d
2e
6
6
61
58
12
12
60
56
Ms
3n
O
OH
MeO
N
Ms
3o
O
O
I
Ph
16
17
2a
2b
6
6
52
65
12
12
45
71
N
NHMs
Ms
1d
3p
O
1d
1d
N
Ms
3q
O
OMe
18
2c
6
66
12
67
N
Ms
3r
a
Reaction conditions: 1.0 mmol 2-iodoanilide, 1.1 mmol alkyne, 0.02 mmol Pd(OAc)2, and 2.5 mmol Bu4NOAc with 5 mL of acetonitrile.
Isolated yields.
b
remarkable feature of this protocol is that the base sensitive
uncyclized product. However, the formation of the homo-
coupled product arising out of the terminal acetylene was
observed to an extent of 2–8%. It should also be noted that
we did not observe any reaction when 2-bromo-N-tosyl-
benzenamine and phenyl acetylene was subjected to this
coupling–cyclization protocol under the optimized reaction
conditions. Moreover, the reaction of o-iodoaniline with
the free amino group and phenyl acetylene using the stan-
dard reaction conditions yielded only Sonogashira coupled
product in 92 and 82% yield by employing the ultrasonic ir-
radiation and standard stirred conditions, respectively. It is
worth noting that the p-toluene sulfonyl/methane sulfonyl
groups were found to be stable under the mild reaction
conditions of this protocol. The corresponding N-p-toluene
sulfonyl/methane sulfonyl indoles 3a–r were isolated in
ester group was not affected by our mild reaction conditions.
Moreover, various substituted terminal alkynes reacted
smoothly giving moderate to good yields.
Ultrasound as a non-thermal energy transfer source is well
known to enhance reaction rates/yields/selectivity in organic
synthesis and has found widespread application in synthetic
organic chemistry.19 Significant enhancement in rate of reac-
tion (5–10 folds) and improved yields for the sonochemical
reactions relative to the standard stirred reactions were
observed (Table 4).
During the course of the reaction under standard conditions
as well as ultrasound conditions we did not observe any

S. S. Palimkar et al. / Tetrahedron 62 (2006) 5109–5115
5113
1
moderate to good yields. These N-protected indole deriva-
tives allow us the flexibility to further functionalize the
indole nucleus.
1215, 669; H NMR (200 MHz, CDCl3) d 2.20 (s, 3H),
6.47 (s, 1H), 6.96 (d, J¼8.13 Hz, 2H), 7.15–7.29 (m, 4H),
7.32–7.46 (m, 6H), 8.24 (d, J¼7.58 Hz, 1H); 13C NMR
(50 MHz, CDCl3) d 21.4, 113.2, 116.6, 120.5, 124.2,
124.5, 126.7, 129.1, 130.1, 130.6, 134.5, 138.1, 138.5,
142.2, 144.4. Anal. Calcd for C21H17NO2S: C, 72.60; H,
4.93; N, 4.03. Found: C, 72.79; H, 5.15; N, 4.27.
3. Conclusion
In conclusion, we have developed a mild, efficient, and
general one-pot synthesis of 2-substituted indoles at room
temperature under ultrasound irradiation and standard
stirred conditions in the absence of any ligand, copper, and
amine by using Pd(OAc)2 as the catalyst, Bu4NOAc as the
base, in acetonitrile. Both electron-donating and electron-
withdrawing substituents on the aryl ring of o-iodoanilides
were tolerated.
4.2.2. 2-p-Tolyl-1-tosyl-1H-indole 3b. Light brown solid;
mp 108–110 ꢁC; IR (film, cmꢃ1) 3027, 2922, 1597, 1504,
1449, 1188, 812, 752, 571; H NMR (200 MHz, CDCl3)
d 2.20 (s, 3H), 2.36 (s, 3H), 6.43 (s, 1H), 6.96 (d,
J¼8.08 Hz, 2H), 7.14–7.37 (m, 9H), 8.22 (d, J¼8.58 Hz,
1H); 13C NMR (50 MHz, CDCl3) d 21.4, 113.2, 116.6,
120.5, 124.2, 124.5, 126.7, 129.1, 130.1, 130.6, 131.3,
134.6, 138.1, 138.5, 142.2, 144.4. Anal. Calcd for
C22H19NO2S: C, 73.10; H, 5.30; N, 3.88. Found: C, 72.96;
H, 5.28; N, 4.26.
1
4. Experimental
4.1. General
4.2.3. 2-(4-Methoxyphenyl)-1-tosyl-1H-indole 3c. Light
brown solid; mp 126–128 ꢁC; IR (film, cmꢃ1) 3019, 2400,
1505, 1215, 668, 572; H NMR (200 MHz, CDCl3) d 2.28
1
Melting points were recorded in open capillary using Buchi
melting point B540 apparatus. Column chromatography was
performed using silica gel (60–120 mesh size), and TLC was
carried out using aluminum sheets precoated with silica gel
60F254. All solvents and chemicals used were reagent grade
procured commercially and used without further purifica-
(s, 3H), 3.88 (s, 3H), 6.48 (s, 1H), 6.93–7.05 (m, 4H),
7.24–7.34 (m, 4H), 7.40–7.44 (m, 3H), 8.30 (d,
J¼8.28 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 21.4, 55.2,
112.7, 112.9, 116.5, 120.4, 122.3, 124.1, 126.6, 127.4,
129.1, 129.5, 131.6, 134.9, 135.9, 137.5, 139.1, 144.1,
144.4, 160.0. Anal. Calcd for C22H19NO3S: C, 70.00; H,
5.07; N, 3.71. Found: C, 69.54; H, 4.72; N, 3.81.
1
tion. H NMR and 13C NMR spectra were recorded on
a Bruker Avance DPX 200 spectrometer. Infra red spectra
were recorded with ATI MATT-SON RS-1 FTIR spectrom-
eter. Elemental analysis was performed on Flash EA 1112
Thermo Finnigan instrument. The reactions were carried
out in a thermostated (30ꢀ1 ꢁC) ultrasonic cleaning bath
at 50 kHz. The ultrasonic cleaner had an output power of
120 W and a power supply of 450 W. The tank dimensions
were 290ꢂ240ꢂ150 mm with a liquid holding capacity of
9.5 L. The reactions were carried out in a RB flask of
10 mL capacity suspended at the center of the cleaning
bath, 5 cm below the surface of the liquid. o-Iodoanilines
were prepared according to the procedure described in the
literature.20
4.2.4. 2-(Naphthalen-1-yl)-1-tosyl-1H-indole 3d. Light
brown solid; mp 132–134 ꢁC; IR (film, cmꢃ1) 3019, 2400,
1598, 1449, 1373, 667, 569; H NMR (200 MHz, CDCl3)
1
d 2.24 (s, 3H), 6.65 (s, 1H), 6.94 (d, J¼8.06 Hz,
2H), 7.24–7.34 (m, 5H), 7.39–7.54 (m, 4H), 7.64 (d,
J¼8.79 Hz, 1H), 7.91 (dd, J¼13.19, 8.06 Hz, 2H), 8.39 (d,
J¼8.79 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 21.4,
113.6, 115.7, 120.7, 123.9, 124.4, 124.7, 125.7, 126.0,
126.2, 126.8, 127.9, 129.1, 129.4, 129.9, 132.9, 133.3,
135.2, 137.5, 138.7, 144.5. Anal. Calcd for C25H19NO2S:
C, 75.54; H, 4.82; N, 3.52. Found: C, 75.64; H, 4.52; N,
3.20.
4.2. General procedure for preparation of 2-substituted
indoles
4.2.5. 1-(1-Tosyl-1H-indol-2-yl) ethanol 3e. Light brown
solid; mp 136–137 ꢁC; IR (film, cmꢃ1) 3551, 3018, 2985,
2401, 1597, 1451, 1215, 668; H NMR (200 MHz, CDCl3)
1
To the mixture of o-iodoanilide 1 (1 mmol), Pd(OAc)2
(2 mmol %), and Bu4NOAc (2.5 mmol) in dry acetonitrile
under argon atmosphere was added phenyl acetylene 2
(1.1 mmol). The reaction mixture was then stirred at room
temperature or sonicated for the time as shown in Table 3.
The progress of the reaction was monitored by TLC. After
completion of the reaction, acetonitrile was evaporated
under reduced pressure, diluted with water, and extracted
with ethyl acetate. The organic layer was dried over sodium
sulfate, filtered, and concentrated under vacuum. The resi-
due thus obtained was purified by column chromatography
using ethyl acetate/petroleum benzine as eluent to afford
the desired product 3. To the best of our knowledge, N-tosyl
derivative of indoles 3 have not been previously reported and
hence the complete characterization data is given as follows.
d 1.67 (d, J¼6.57 Hz, 3H), 2.33 (s, 3H), 3.48 (br s, 1H),
5.35 (q, J¼6.57 Hz, 1H), 6.68 (s, 1H), 7.16–7.33 (m, 4H),
7.45–7.50 (m, 1H), 7.66 (td, J¼8.33, 1.76 Hz, 2H), 8.09
(d, J¼8.08 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 21.4,
21.5, 62.6, 108.8, 114.7, 121.1, 123.8, 124.9, 126.3, 127.4,
129.1, 129.9, 135.6, 137.2, 144.8, 145.0. Anal. Calcd for
C17H17NO3S: C, 64.74; H, 5.43; N, 4.44. Found: C, 64.62;
H, 5.32; N, 4.34.
4.2.6. 5-Methyl-2-phenyl-1-tosyl-1H-indole 3f. Light
brown solid; mp 113–114 ꢁC; IR (film, cmꢃ1) 3019, 2400,
1598, 1372, 1215, 668, 588; H NMR (200 MHz, CDCl3)
1
d 2.19 (s, 3H), 2.33 (s, 3H), 6.39 (s, 1H), 6.94 (d,
J¼8.31 Hz, 2H), 7.06–7.21 (m, 4H), 7.32–7.45 (m, 5H),
8.09 (d, J¼8.52 Hz, 1H); 13C NMR (50 MHz, CDCl3)
d 21.2, 21.5, 113.5, 116.4, 120.6, 126.1, 126.7, 127.4,
129.1, 130.2, 131.4, 133.9, 134.6, 136.5, 142.2, 144.4.
4.2.1. 2-Phenyl-1-tosyl-1H-indole 3a. Light brown solid;
mp 145–147 ꢁC; IR (film, cmꢃ1) 3019, 2400, 1450, 1374,

5114
S. S. Palimkar et al. / Tetrahedron 62 (2006) 5109–5115
Anal. Calcd for C22H19NO2S: C, 73.10; H, 5.30; N, 3.88.
Found: C, 72.97; H, 5.21; N, 4.27.
1H NMR (200 MHz, CDCl3) d 2.48 (s, 3H), 2.86 (s, 3H),
4.01 (s, 3H), 6.77 (s, 1H), 7.30 (d, J¼7.92 Hz, 2H), 7.50
(d, J¼8.08 Hz, 2H), 8.10 (dd, J¼7.27, 1.61 Hz, 1H), 8.22
(d, J¼8.88 Hz, 1H), 8.36 (d, J¼1.29 Hz, 1H); 13C NMR
(50 MHz, CDCl3) d 21.4, 40.4, 52.1, 112.4, 115.3, 122.9,
125.9, 128.5, 130.2, 139.3, 143.1, 167.1. Anal. Calcd for
C18H17NO4S: C, 62.96; H, 4.99; N, 4.08. Found: C, 62.64;
H, 4.88; N, 4.36.
4.2.7. 5-Methyl-2-p-tolyl-1-tosyl-1H-indole 3g. Light
brown solid; mp 145–147 ꢁC; IR (film, cmꢃ1) 3025, 2921,
1597, 1371, 1174, 811, 573; H NMR (200 MHz, CDCl3)
1
d 2.20 (s, 3H), 2.33 (s, 3H), 2.36 (s, 3H), 6.36 (s, 1H), 6.96
(d, J¼8.00 Hz, 1H), 7.05–7.23 (m, 7H), 7.33 (td, J¼8.21,
1.91 Hz, 2H), 8.08 (d, J¼8.45 Hz, 1H); 13C NMR
(50 MHz, CDCl3) d 21.2, 21.4, 21.5, 113.2, 116.4, 120.5,
125.9, 126.8, 128.2, 129.1, 129.6, 130.1, 130.9, 133.8,
134.6, 138.5, 144.3. Anal. Calcd for C23H21NO2S: C,
73.57; H, 5.64; N, 3.73. Found: C, 73.85; H, 5.75; N, 3.92.
4.2.13. 1-Methanesulfonyl-2-(4-methoxyphenyl)-1H-
indole-5-carboxylic acid methyl ester 3m. Colorless solid;
mp 144–146 ꢁC; IR (film, cmꢃ1) 3019, 2400, 1716, 1290,
1
669; H NMR (200 MHz, CDCl3) d 2.74 (s, 3H), 3.81 (s,
3H), 3.90 (s, 3H), 6.64 (s, 1H), 6.91 (d, J¼8.73 Hz, 2H),
7.43 (d, J¼8.83 Hz, 2H), 7.98 (dd, J¼7.19, 1.64 Hz, 1H),
8.11 (d, J¼8.73 Hz, 1H), 8.24 (d, J¼1.19 Hz, 1H); 13C
NMR (50 MHz, CDCl3) d 40.4, 52.1, 55.3, 112.1, 113.3,
115.3, 118.9, 122.8, 123.4, 125.8, 129.8, 131.6, 140.2,
142.8, 160.3, 167.1. Anal. Calcd for C18H17NO5S: C,
60.15; H, 4.77; N, 3.90. Found: C, 59.70; H, 4.59; N, 4.30.
4.2.8. 2-(4-Methoxyphenyl)-5-methyl-1-tosyl-1H-indꢃol1e
3h. Light brown solid; mp 138–139 ꢁC; IR (film, cm
)
3028, 2924, 1611, 1506, 1371, 1175, 575; 1H NMR
(200 MHz, CDCl3) d 2.28 (s, 3H), 2.40 (s, 3H), 3.88 (s,
3H), 6.41 (s, 1H), 6.92–7.05 (m, 4H), 7.12–7.27 (m, 4H),
7.42 (td, J¼8.83, 2.14 Hz, 2H), 8.16 (d, J¼8.44 Hz, 1H);
13C NMR (50 MHz, CDCl3) d 21.2, 21.4, 55.2, 112.7,
112.9, 116.3, 120.4, 122.8, 124.8, 125.8, 126.7, 129.1,
131.5, 133.8, 134.6, 136.3, 139.2, 142.1, 144.3, 159.9.
Anal. Calcd for C23H21NO3S: C, 70.56; H, 5.41; N, 3.58.
Found: C, 70.26; H, 5.35; N, 3.81.
4.2.14. 1-Methanesulfonyl-2-(naphthalen-1-yl)-1H-
indole-5-carboxylic acid methyl ester 3n. Colorless solid;
mp 144–146 ꢁC; IR (film, cmꢃ1) 3020, 2400, 1715, 1375,
1
1215, 668; H NMR (200 MHz, CDCl3) d 2.91 (s, 3H),
3.98 (s, 3H), 6.86 (s, 1H), 7.45–7.61 (m, 4H), 7.71 (d,
J¼8.97 Hz, 1H), 7.90–7.99 (m, 2H), 8.09–8.22 (m, 2H),
8.39 (d, J¼1.65 Hz, 1H); 13C NMR (50 MHz, CDCl3)
d 41.1, 52.2, 112.9, 114.5, 123.2, 124.7, 125.5, 126.1,
126.2, 126.7, 128.4, 128.8, 129.2, 129.5, 129.9, 133.1,
133.3, 139.5, 139.9, 167.1. Anal. Calcd for C21H17NO4S:
C, 66.48; H, 4.52; N, 3.69. Found: C, 66.87; H, 4.71; N, 3.94.
4.2.9. 5-Methyl-2-(naphthalen-1-yl)-1-tosyl-1H-indole 3i.
Light brown solid; mp 159–161 ꢁC; IR (film, cmꢃ1) 3020,
2924, 1597, 1365, 1172, 592; H NMR (200 MHz, CDCl3)
1
d 2.25 (s, 3H), 2.46 (s, 3H), 6.58 (s, 1H), 6.95 (d,
J¼7.95 Hz, 2H), 7.21–7.36 (m, 5H), 7.41–7.55 (m, 3H),
7.66 (d, J¼8.34 Hz, 1H), 7.85–7.96 (m, 2H), 8.26 (d,
J¼8.46 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 21.2, 21.3,
113.6, 115.5, 120.6, 124.4, 125.6, 126.1, 126.8, 127.4,
127.9, 129.1, 129.2, 129.4, 129.5, 129.9, 130.2, 130.3,
133.0, 133.3, 133.5, 135.2, 135.7, 138.8, 144.4. Anal. Calcd
for C26H21NO2S: C, 75.89; H, 5.14; N, 3.40. Found: C,
75.59; H, 5.03; N, 3.39.
4.2.15. 1-Methanesulfonyl-2-(1-hydroxyethyl)-1H-indole-
5-carboxylic acid methyl ester 3o. Colorless solid; mp 132–
133 ꢁC; IR (film, cmꢃ1) 3326, 3019, 2930, 2400, 1716, 1215,
1
668; H NMR (200 MHz, CDCl3) d 1.72 (d, J¼6.57, 3H),
3.24 (s, 3H), 3.95 (s, 3H), 5.39 (q, J¼6.44 Hz, 1H), 6.78 (s,
1H), 8.03–8.05 (m, 2H), 8.28 (d, J¼1.39 Hz, 1H); 13C
NMR (50 MHz, CDCl3) d 21.6, 41.3, 52.1, 62.1, 108.1,
113.7, 123.4, 126.2, 128.5, 131.1, 139.5, 145.4, 167.0.
Anal. Calcd for C13H15NO5S: C, 52.52; H, 5.09; N, 4.71.
Found: C, 52.56; H, 4.64; N, 4.44.
4.2.10. 2-(3-Fluorophenyl)-5-methyl-1-tosyl-1H-indole
3j. Yellow Oil; IR (film, cmꢃ1) 2925, 2856, 1615, 1373,
757, 588; 1H NMR (200 MHz, CDCl3) d 2.21 (s, 3H), 2.33
(s, 3H), 6.42 (s, 1H), 6.95–7.33 (m, 10H), 8.09 (d,
J¼8.33 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 21.2, 21.4,
114.2, 116.3, 116.7, 120.8, 126.1, 126.5, 126.7, 129.1,
130.6, 134.1, 136.6, 140.7, 144.6, 159.4, 164.3. Anal. Calcd
for C22H18FNO2S: C, 69.64; H, 4.78; F, 5.01; N, 3.69.
Found: C, 69.54; H, 4.72; F, 4.98; N, 3.81.
4.2.16. 1-(1-Methanesulfonyl-2-phenyl-1H-indol-5-yl)-
ethanone 3p. Colorless solid; mp 170–171 ꢁC; IR (film,
1
cmꢃ1) 3019, 2919, 2400, 1681, 1374, 1215, 668; H NMR
(200 MHz, CDCl3) d 2.69 (s, 3H), 2.83 (s, 3H), 6.77 (s,
1H), 7.44–7.47 (m, 3H), 7.56 (dd, J¼7.57, 2.24 Hz, 2H),
8.00 (dd, J¼7.41, 1.40 Hz, 1H), 8.19 (d, J¼8.87 Hz, 1H),
8.23 (s, 1H); 13C NMR (50 MHz, CDCl3) d 26.7, 40.6,
112.7, 115.4, 121.8, 125.1, 127.8, 129.2, 130.3, 133.8,
140.3, 143.1, 197.5. Anal. Calcd for C17H15NO3S: C,
65.16; H, 4.82; N, 4.47. Found: C, 65.15; H, 4.42; N, 4.52.
4.2.11. 1-Methanesulfonyl-2-phenyl-1H-indole-5-car-
boxylic acid methyl ester 3k. Colorless solid; mp 131–
132 ꢁC; IR (film, cmꢃ1) 3019, 2400, 1717, 1375, 1216,
1
669; H NMR (200 MHz, CDCl3) d 2.82 (s, 3H), 3.96 (s,
3H), 6.76 (s, 1H), 7.43–7.46 (m, 2H), 7.54–7.59 (m, 2H),
8.03–8.20 (m, 2H), 8.32 (d, J¼1.75 Hz, 1H); 13C NMR
(50 MHz, CDCl3) d 40.4, 52.2, 112.6, 115.3, 123.1, 126.1,
127.8, 130.3, 131.4, 140.3, 142.9, 167.1. Anal. Calcd for
C17H15NO4S: C, 61.99; H, 4.59; N, 4.25. Found: C, 62.31;
H, 4.65; N, 4.47.
4.2.17. 1-(1-Methanesulfonyl-2-p-tolyl-1H-indol-5-yl)-
ethanone 3q. Colorless solid; mp 138–139 ꢁC; IR (film,
cmꢃ1) 3019, 2400, 1678, 1375, 1216, 668; 1H NMR
(200 MHz, CDCl3) d 2.35 (s, 3H), 2.61 (s, 3H), 2.75 (s,
3H), 6.67 (s, 1H), 7.18 (d, J¼7.75 Hz, 2H), 7.38 (d,
J¼8.17 Hz, 2H), 7.91 (dd, J¼7.02, 1.70 Hz, 1H), 8.12 (d,
J¼9.56 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 21.3, 26.6,
40.4, 112.4, 115.3, 121.7, 124.8, 128.2, 128.4, 130.1,
4.2.12. 1-Methanesulfonyl-2-p-tolyl-1H-indole-5-car-
boxylic acid methyl ester 3l. Colorless solid; mp 146–
147 ꢁC; IR (film, cmꢃ1) 3011, 2400, 1716, 1215, 669;

S. S. Palimkar et al. / Tetrahedron 62 (2006) 5109–5115
5115
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Kondo, Y.; Sakamoto, T. J. Chem. Soc., Perkin Trans. 1 1999,
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C18H17NO3S: C, 66.03; H, 5.23; N, 4.28. Found: C, 65.89;
H, 4.93; N, 4.52.
4.2.18. 1-(1-Methanesulfonyl-2-(4-methoxyphenyl)-1H-
indol-5-yl)-ethanone 3r. Colorless solid; mp 187–189 ꢁC;
IR (film, cmꢃ1) 3019, 2400, 1677, 1216, 758, 669; 1H
NMR (200 MHz, CDCl3) d 2.69 (s, 3H), 2.81 (s, 3H), 3.87
(s, 3H), 6.72 (s, 1H), 6.97 (td, J¼8.87, 2.19 Hz, 2H), 7.49
(d, J¼8.87, 2.19 Hz, 2H), 7.98 (dd, J¼6.97, 1.74 Hz, 1H),
8.18 (d, J¼8.71 Hz, 2H); 13C NMR (50 MHz, CDCl3)
d 26.7, 40.4, 55.2, 112.2, 113.3, 115.5, 121.6, 123.4,
124.8, 129.9, 131.6, 140.3, 143.1, 160.4, 197.6. Anal. Calcd
for C18H17NO4S: C, 62.96; H, 4.99; N, 4.08. Found: C,
62.91; H, 4.91; N, 4.48.
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Acknowledgments
S.S.P. thanks CSIR, New Delhi for providing the Research
Fellowship.
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