Phosphine-free thiopseudourea-Pd(II) complex catalyzed Larock heteroannulation of 2-haloamines with internal alkynes

Article abstract of DOI:10.1016/j.jorganchem.2013.05.049

We examined the Pd-catalyzed heteroannulation of 2-haloamines with internal alkynes under phosphinefree conditions. The thiopseudourea palladium(II) complex (5) found to be an efficient catalyst for the Pd induced heteroannulation. Achieved high turnover number for the heteroannulation reactions of internal alkynes with 2-iodoaniline. A variety of 2-bromoanilines and N-tosyl substituted 2-bromoanilines effectively reacted with different substituted internal alkynes to give the corresponding indoles in good to high yields (1:1 ratio of regioisomers).

Full text of DOI:10.1016/j.jorganchem.2013.05.049

Journal of Organometallic Chemistry 741-742 (2013) 162e167
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Phosphine-free thiopseudourea-Pd(II) complex catalyzed Larock
heteroannulation of 2-haloamines with internal alkynes
Keesara Srinivas, Parvathaneni Saiprathima, Kodicherla Balaswamy,
*
Mandapati Mohan Rao
I & PC Division, Indian Institute of Chemical Technology, Hyderabad 500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We examined the Pd-catalyzed heteroannulation of 2-haloamines with internal alkynes under phosphine-
free conditions. The thiopseudourea palladium(II) complex (5) found to be an efficient catalyst for the Pd
induced heteroannulation. Achieved high turnover number for the heteroannulation reactions of internal
alkynes with 2-iodoaniline. A variety of 2-bromoanilines and N-tosyl substituted 2-bromoanilines effec-
tively reacted with different substituted internal alkynes to give the corresponding indoles in good to high
yields (1:1 ratio of regioisomers).
Received 10 April 2013
Received in revised form
29 May 2013
Accepted 30 May 2013
Keywords:
Ó 2013 Elsevier B.V. All rights reserved.
Thiopseudourea
Larock indolization
Phosphine free
Palladium
1. Introduction
application for SuzukieMiyaura, Sonogashira, Heck and Hiyama
cross coupling reaction [26].
The phosphine-free palladium catalyzed heteroannulation of
internal alkynes with 2-haloamines is an important synthetic
method for 2,3-disubstituted indole formation [1e3]. The indole
nucleus is an important compound, found in numerous natural
products and biological active materials [4,5]. Widespread use of
indole nucleus in pharmaceutical studies [6,7], aimed to develop
efficient synthetic methods. Compared to many reported methods
for the indole synthesis [8e14], the palladium-catalyzed indoliza-
tion is emerged as a powerful synthetic method (Larock indole
synthesis) (Scheme 1) [1]. This reaction is normally performed with
5 mol% of Pd(OAc)2 for 2-iodoanilines and the same is not possible
for 2-bromo or 2-chloroanilines. A number of heterogeneous [15e
20] and homogeneous [21e25] Pd catalysts were reported for
Larock indolization. Among them N-phenylurea [21] and 1,10-
bis(di-tert-butylphosphino)ferrocene [22] ligands based high
loading Pd catalysts have shown better results. Few reports are
available for the synthesis of 2,3-diphenyl-1-tosyl indole from N-
tosyl-2-haloanilines with diphenylacetylene [1,19].
2. Results and discussion
Initially, we studied the catalytic activity of thiopseudourea
Pd(II) complex (5) for the heteroannulation reaction between 2-
iodoaniline and diphenylacetylene using 0.01 mol% of catalyst
with various bases in DMF (N,N-dimethylformamide) at 130 ꢀC
(Table 1). Among the studied bases, LiOH$H2O found to be the best
(entry 4). Furthermore, the reaction efficiently proceeded with
4.0 equiv of LiOH$H2O (with respect to 2-iodoaniline) to afford 2,3-
diphenylindole in an excellent yield (entry 4). With the optimized
base (4.0 equiv of LiOH$H2O), apart from DMF, the role of various
solvents was studied (entries 8e10). The best results achieved with
DMF solvent. Under the similar experimental conditions with
0.01 mol% Pd(OAc)2 very low yield was observed (entry 11). In order
to study the effect of temperature, we have conducted the experi-
ment at 100 ꢀC for 48 h and observed very low yield (entry 12).
Further, the activity of different phosphine-free ligands 1aec
(Fig. 2) with Pd(OAc)2 was studied under the same reaction con-
ditions that resulted in moderate to good yields (entries 13e15). We
confirm that thiopseudourea-Pd(II) complex is an efficient catalyst
for heteroannulation of 2-haloamine with diphenylacetylene.
From the above optimized reaction conditions (0.01 mol% of 5,
DMF 2 mL, LiOH$H2O 4 equiv at 130 ꢀC), reactions of 2-iodoaniline
Herein, we report heteroannulation of 2-haloamines with in-
ternal alkynes using an efficient thiopseudourea Pd(II) complex (5)
(Fig. 1). Recently, we have reported the synthesis (1) and its
* Corresponding author. Tel.: þ91 40 27193181; fax: þ91 40 27160921.
E-mail addresses: mandapati@iict.res.in, mandapatirao@yahoo.co.in (M.M. Rao).
0022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.05.049

K. Srinivas et al. / Journal of Organometallic Chemistry 741-742 (2013) 162e167
163
Table 1
Thiopseudourea Pd(II) complex (5) catalyzed heteroannulation of 2-iodoaniline with
diphenylacetylene.a
S
Ph
Ph
I
N
N
Pd
OAc
Catalyst 5, Base
+
Ph
N
DMF, 130 ºC, 20 h
O
N
NH2
H
Ph
2a
Fig. 1. Thiopseudourea Pd(II) complex (5).
Entry
Base (equiv)
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
NaOAc (4)
Na2CO3 (4)
K3PO4 (4)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMA
NMP
DMF
DMF
DMF
DMF
DMF
5
23
20
97
96
56
37
12
64
34
20
33
64
82
80
(1.0 mmol) with various alkynes (1.5 mmol) were investigated
(Table 2). Substituent on the diphenylacetylene has modest
effect on the reaction time and yield. Unsymmetrical meta and
para-substituted diphenylacetylenes also resulted in high yields
without any regioselectivity and the isolated indole products
contain both regioisomers in 1:1 ratio (entries 4e6). The complete
deprotection of the acetyl group was observed, when N-acetyl
substituted 2-iodoaniline was used as the substrate, leading to the
formation of corresponding non-N-substituted indole (entry 7). We
tried the indolization of 2-iodoaniline with 1-phenylacetylene and
but-2-yne-1,4-diol without any success.
Further, decrease in catalyst loading to 0.001 mol%, the reaction
also proceeds well with high conversion (entry 2). However, higher
turnover number (TON) (6.3 ꢁ 105) was obtained while using
comparatively lower catalyst concentration (0.0001 mol%) with
prolonged reaction time (entry 3).
Encouraged by these results, we investigated the indolization
of various 2-bromoanilines which are expected less reactive
compared to 2-iodoaniline (Table 3). In our case, reactions of all
the 2-bromoanilines with diphenylacetylene afforded the desired
products (entries 1e5). Higher yields (80e90%) were obtained
with 0.1 mol% of catalyst loading compared to 0.01 mol% (74%
yield, entry 2). When unsymmetrical alkynes reacted with 2-
bromoaniline, the corresponding 2,3-diphenylindole regioisomers
in 1:1 ratio were formed and the same in case of 2-iodoaniline
(entries 6e8).
Further, we have studied the scope of our catalyst system
to N-tosyl substituted 2-bromoaniline with diphenylacetylenes
(Table 4). In all the studied N-tosyl substituted 2-bromoanilines,
the products are corresponding N-tosyl substituted 2,3-
diphenylindoles (entries 1e5) with high yields. Our catalyst sys-
tem could not work well in case of 2-chloroaniline and N-tosyl
substituted 2-chloroaniline with diphenylacetylene (Table 3, entry
9 and Table 4, entry 6).
LiOH$H2O (4)
LiOH$H2O (3)
LiOH$H2O (2)
LiOH$H2O (1)
LiOH$H2O (3)
LiOH$H2O (3)
LiOH$H2O (3)
LiOH$H2O (3)
LiOH$H2O (3)
LiOH$H2O (3)
LiOH$H2O (3)
LiOH$H2O (3)
9
10
11c
12d
13e
14e
15e
a
Reaction conditions: 2-iodoaniline 1 mmol, diphenylacetylene 1.5 mmol, base
4.0 mmol, catalyst 0.01 mol%, solvent 2 mL, reaction temperature 130 ꢀC.
b
Isolated yield.
c
0.1 mol% of the Pd(OAc)2.
Reaction temperature 100 ꢀC and reaction time 48 h.
0.05 mol% of Pd(OAc)2/0.01 mol% of ligand (1a or 1b or 1c).
d
e
3. Conclusions
In conclusion, we proved that the phosphine-free thio-
pseudourea Pd(II) complex is an efficient catalyst for hetero-
annulation of internal alkynes with 2-haloamines and N-
tosyl substituted 2-bromoanilines. The heteroannulation of 2-
bromoanilines and N-tosyl substituted 2-bromoanilines pro-
ceeded well to afford the corresponding products in good to high
yields under a low catalyst loading of 0.1 mol%. Work is in progress
in our laboratory to develop a new catalyst with high regiose-
lectivity for Larock indole synthesis.
4. Experimental section
4.1. General procedure for the synthesis of picolyl sulphonamide
ligand (1a)
We propose the mechanism (Scheme 2) of Pd(II) complex (5)
catalyzed indolization based on previous reports. The means of this
transformation proceed through the following steps: (a) at high
temperatures, the palladium(II) complex (5) converts to Pd(0),
(b) oxidative addition of 2-haloamine (CeX bond) to Pd(0) pro-
ducing a Pd(II)earyl complex [27,28]; (c) insertion of the alkyne
into the PdeC bond of aryl-Pd(II) complex [29,30], (d) CeN
coupling to give the indole and regeneration of Pd(0) catalyst [30].
The alternative Pd(II)/Pd(IV) catalytic cycle seems to be very un-
likely at higher temperatures [31,32].
Picolyl amine (5 mmol) was added drop wise to solution of tosyl
chloride (15 mmol) in dry dichloromethane (30 mL) at 0 ꢀC and
allows stirring for 3 h. After that the mixture was warmed to room
temperature and stirred for another 12 h. After filtration, the sol-
vent was removed under reduced pressure. The residue was puri-
fied by column chromatography on silica gel (hexane/ethyl acetate)
to afford the compound as a white solid (80e85% yield).
R3
R3
O
O
S
O
I
Pd catalyst
R
R2
N
H
R
N
H
+
base, additive
phosphine
N
NHR1
N
N
R1
N
N
1c
R2
DMF, 100-130 °C
1a
1b
Scheme 1. Larock indole synthesis.
Fig. 2. Nitrogen ligands 1aec.

164
K. Srinivas et al. / Journal of Organometallic Chemistry 741-742 (2013) 162e167
Table 2
Thiopseudourea Pd(II) complex (5) catalyzed heteroannulation of 2-iodoanilines with alkynes.a
R2
R2
Ph
I
Catalyst 5
+
R2
Ph +
LiOH.H2O, DMF
130 ºC
N
N
H
NHR1
H
Ph
2b-5b
2a-5a
Entry
R1
R2
Catalyst (mol%)
Product
Ratio
Time/h
Yield (%)b
1
2
3
4
5
6
7
H
H
H
H
H
H
Ac
H
H
H
4-Me
F
0.01
2a
2a
2a
3a/3b
4a/4b
5a/5b
2a
na
na
na
1/1
1/1
1/1
na
20
24
30
20
24
20
20
98
92
63
92
87
86
90
0.001
0.0001
0.01
0.01
0.01
3-Me
H
0.01
a
Reaction conditions: 2-iodoaniline 1 mmol, alkyne 1.5 mmol, LiOH$H2O 4.0 mmol, catalyst 5, DMF 2 mL, reaction temperature 130 ꢀC.
Isolated yield.
b
4.1.1. (Pyridin-2-yl)-N-tosylmethanamine (1a)
1H NMR (500 MHz, CDCl3, TMS):
and allows stirring for 30 min. After that triethylamine (15 mmol)
was added drop wise over 15 min. After the addition, mixture was
warmed to room temperature and stirred for another 12 h. After
filtration, the solvent was removed under reduced pressure. The
residue was purified by column chromatography on silica gel
(eluent: hexane/ethyl acetate) to afford the compound as a white
solid (90% yield).
d
8.44 (d, J ¼ 4.34 Hz, 2H), 7.72
(d, J ¼ 8.12 Hz, 2H), 7.62 (t, J ¼ 8.49 Hz, 1H), 7.34 (d, J ¼ 7.74 Hz, 1H),
7.27 (d, J ¼ 7.93 Hz, 2H), 7.16 (t, J ¼ 6.98 Hz, 1H), 4.16 (d, J ¼ 6.04 Hz,
2H), 3.0 (s,1H), 2.40 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 154.9,148.8,
143.2, 136.7, 136.5, 129.5, 127.0, 122.5, 121.9, 47.4, 21.3; ESI-MS (m/z)
(M
þ
H)þ
¼
263; HRMS: calcd for C13H15O2N2S
(M þ H)þ ¼ 263.08463, found: 263.08487.
4.2.1. N-((Pyridin-2-yl)methyl)benzamide (1b)
4.2. General procedure for the synthesis of N-((pyridin-2-yl)methyl)
benzamide (1b)
1H NMR (500 MHz, CDCl3, TMS):
d
8.56 (d, J ¼ 3.99 Hz, 1H), 7.88
(d, J ¼ 7.99 Hz, 2H), 7.67e7.70 (m, 2H), 7.50 (t, J ¼ 7.99 Hz, 2H), 7.44
(t, J ¼ 7.99 Hz, 2H), 7.21 (t, J ¼ 7.99 Hz, 1H), 4.76 (d, J ¼ 4.99 Hz, 2H);
Picolyl amine (5 mmol) was added drop wise to solution of
benzoyl chloride (7.5 mmol) in dry dichloromethane (30 mL) at 0 ꢀC
13C NMR (75 MHz, CDCl3)
d 167.3, 156.1, 148.8, 136.8, 134.2, 131.4,
128.4, 127.0, 122.4, 122.3, 44.6; ESI-MS (m/z) (M þ H)þ ¼ 213;
Table 3
Thiopseudourea Pd(II) complex (5) catalyzed heteroannulation of 2-bromoanilines with alkynes.a
R2
R2
Ph
Br
Catalyst 5
R1
+
R1
R
1
R2
Ph +
LiOH.H2O, DMF
130 ºC
N
N
H
NH2
H
Ph
2b-4b & 6b-9b
2a-4a & 6a-9a
Entry
R1
R2
Catalyst (mol%)
Product
Ratio
Time/h
Yield (%)b
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
0.1
0.01
0.1
0.1
0.1
0.1
0.1
0.1
1.0
2a
2a
6a
7a
na
na
na
na
20
30
20
20
20
20
20
20
30
90
74
90
94
80
86
80
82
19c
4-F
4-Me
4,6-Me
H
H
H
H
8a
na
4-Me
4-F
4-Cl
H
3a/3b
4a/4b
9a/9b
2a
1/1
1/1
1/1
na
H
a
Reaction conditions: 2-bromoaniline 1 mmol, alkyne 1.5 mmol, LiOH$H2O 4.0 mmol, catalyst 5, DMF 2 mL, reaction temperature 130 ꢀC.
Isolated yield.
Reaction for 2-chlooroaniline.
b
c

K. Srinivas et al. / Journal of Organometallic Chemistry 741-742 (2013) 162e167
165
Table 4
Thiopseudourea Pd(II) complex catalyzed heteroannulation of N-tosyl-2-bromoanilines with alkynes.a
R2
R2
Ph
Br
Catalyst 5
R1
+
R1
R
1
R2
Ph +
LiOH.H2O, DMF
130 ºC
N
N
NHTs
Ts
Ts
Ph
10b-14b
10a-14a
Entry
R1
R2
Catalyst (mol%)
Product
Ratio
Time/h
Yield (%)b
1
2
3
4
5
6
H
H
H
H
4-F
3-Me
H
0.1
0.1
0.1
0.1
0.1
1.0
10a
11a
12a
13a/13b
14a/14b
10a
na
na
na
1/1
1/1
na
24
24
24
24
24
30
90
92
83
92
87
15c
4-Me
4-F
H
H
H
a
Reaction conditions: N-tosyl-2-bromoaniline 1 mmol, alkyne 1.5 mmol, LiOH$H2O 4.0 mmol, catalyst 5, DMF 2 mL, reaction temperature 130 ꢀC.
Isolated yield.
Reaction for N-tosyl-2-chloroaniline.
b
c
HRMS: calcd for C13H13ON2 (M þ H)þ ¼ 213.10204, found:
dried over anhydrous Na2SO4. After removal of the solvent, the
residue was subjected to column chromatography on silica gel
using ethyl acetate and hexane to afford the indole product in high
purity. In case of 2-bromoanilines, 0.1 mol% of catalyst 5 was
applied.
213.10224.
4.3. General procedure for the Larock indolization of 2-iodoaniline
and 2-bromoanilines
4.3.1. 2,3-Diphenyl-1H-indole (2a)
The 25 mL RB-flask was charged with 2-haloamines (1 mmol),
diphenylacetylene (1.5 mmol), LiOH$H2O (4 mmol) and catalyst
(0.001 mol% of 5 in 2 mL N,N-dimethylformamide). The reaction
mixture was stirred at 130 ꢀC for 20 h. The reaction mixture was
cooled to room temperature, diluted with ethyl acetate (20 mL)
and washed with brine water. The combined organic phase was
1H NMR (300 MHz, CDCl3, TMS):
d 8.11 (s, 1H), 7.62 (d,
J ¼ 8.30 Hz, 1H), 7.14e7.41 (m, 12H), 7.08 (t, J ¼ 7.55 Hz, 1H); 13C
NMR (75 MHz, CDCl3) d 135.8, 135.0, 134.0, 132.6, 130.1, 128.6, 128.4,
128.1, 127.6, 126.1, 122.6, 120.3, 119.6, 115.0, 110.8; ESI-MS (m/z)
(M þ H)þ ¼ 270.
Pd(II) complex 5
R1N
R2
R1HN
X
Pd(0)
R3
R1HN
R1N
(II)Pd
X
Pd
(II)
R3
R2
HB X
R2
R3
R1HN
(II)Pd
X
R3
R2
B
Scheme 2. Possible catalytic cycle of Pd(II) complex (5) catalyzed indolization of 2-haloamine with an internal alkyne.

166
K. Srinivas et al. / Journal of Organometallic Chemistry 741-742 (2013) 162e167
4.3.2. 2-p-Tolyl-3-phenyl-1H-indole (3a) and 3-p-tolyl-2-phenyl-
1H-indole (3b)
and washed with brine water. The combined organic phase was
dried over anhydrous Na2SO4. After removal of the solvent, the
residue was subjected to column chromatography on silica gel
using ethyl acetate and hexane to afford the indole product in high
purity.
1H NMR (300 MHz, CDCl3, TMS):
d 8.07 (s, 2H), 7.60 (d,
J ¼ 7.55 Hz, 2H), 7.04e7.40 (m, 24H), 2.38 (s, 3H), 2.33 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 137.5,135.8,135.7 (d),135.2 (d),134.2,133.8,
132.8, 131.9, 130.1, 129.9, 129.7, 129.3, 129.2, 128.8 (d), 128.6, 128.4,
128.0, 127.9, 127.5, 126.1, 122.6, 122.4, 120.3 (d), 119.7, 119.5, 110.8,
110.7, 21.2; ESI-MS (m/z) (M þ H)þ ¼ 284.
4.4.1. 2,3-Diphenyl-1-tosyl-indole (10a)
1H NMR (300 MHz, CDCl3, TMS):
d
8.38 (d, J ¼ 8.30 Hz, 1H), 7.45
(d, J ¼ 7.55 Hz, 1H), 7.37 (t, J ¼ 8.30 Hz, 1H), 7.14e7.30 (m, 11H), 7.05
4.3.3. 2-(4-Fluorophenyl)-3-phenyl-1H-indole (4a) and 3-(4-
fluorophenyl)-2-phenyl-1H-indole (4b)
(d, J ¼ 8.30 Hz, 4H), 2.32 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 144.5,
137.1,136.7,135.2,132.5,132.0,130.8,130.3,129.7,129.2,128.4,128.1,
127.2, 126.8, 125.1, 124.7, 124.1, 119.9, 116.1, 21.5; ESI-MS (m/z)
(M þ H)þ ¼ 424; HRMS: calcd for C27H22NO2S (M þ H)þ ¼ 424.1373,
found: 424.1371.
1H NMR (300 MHz, CDCl3, TMS):
d 8.13 (s, 1H), 8.07 (s, 1H), 7.61
(d, J ¼ 7.55 Hz, 1H), 7.57 (d, J ¼ 7.55 Hz, 1H), 7.23e7.38 (m, 16H), 7.18
(t, J ¼ 8.30 Hz, 2H), 6.96e7.11 (m, 6H); 13C NMR (75 MHz, CDCl3)
d
163.9, 163.2, 135.8, 135.7, 134.8, 134.1, 133.1, 132.4, 131.6, 131.5,
130.0, 129.9, 129.8, 128.7, 128.5, 128.0, 127.7, 126.2, 122.7, 120.4,
4.4.2. 5-Methyl-2,3-diphenyl-1-tosyl-indole (11a)
119.6, 119.3, 115.8, 115.6, 115.3, 110.9, 110.8; EI-MS (m/z) (M)þ ¼ 287.
1H NMR (300 MHz, CDCl3, TMS):
d
8.27 (d, J ¼ 8.49 Hz,1H), 7.20e
7.45 (m, 13H), 7.05e7.07 (m, 3H), 2.39 (s, 3H), 2.30 (s, 3H); 13C NMR
(75 MHz, CDCl3) 144.3,136.9,135.4,135.2,133.8,132.7,132.0,131.5,
4.3.4. 2-m-Tolyl-3-phenyl-1H-indole (5a) and 3-m-tolyl-2-phenyl-
1H-indole (5b)
d
130.9, 130.7, 130.1, 129.8, 129.2, 128.5, 128.3, 128.1, 127.5, 127.2,
1H NMR (300 MHz, CDCl3, TMS):
d
8.08 (s, 2H), 7.63 (d,
126.8, 126.5, 119.7, 115.9, 110.5, 21.5, 21.3; ESI-MS (m/z) (M)þ ¼ 437.
J ¼ 7.36 Hz, 2H), 7.04e7.41 (m, 24H), 2.32 (s, 3H), 2.27 (s, 3H); 13C
NMR (75 MHz, CDCl3)
d
138.1, 137.8, 135.7, 135.0, 134.8, 134.1, 133.8,
4.4.3. 5-Fluoro-2,3-diphenyl-1-tosyl-indole (12a)
132.5, 132.4, 130.6, 130.0, 128.4, 128.3, 128.0, 127.4, 127.1, 126.9,
126.0, 125.4, 122.4, 120.2, 119.6, 119.5, 110.8, 21.4, 21.3; ESI-MS (m/z)
(M þ H)þ ¼ 284; HRMS: calcd for C21H18N (M þ H)þ ¼ 284.1450,
found: 284.1439.
1H NMR (300 MHz, CDCl3, TMS):
d
8.35 (dd, J ¼ 4.53 Hz, 1H),
7.20e7.40 (m, 12H), 7.09e7.15 (m, 2H), 7.02e7.06 (m, 2H), 2.31
(s, 3H); 13C NMR (75 MHz, CDCl3)
161.8, 144.7, 138.5, 134.9, 133.4,
d
132.1, 131.9, 131.6, 130.5, 129.8, 129.5, 129.3, 128.6, 128.5, 128.2,
128.1, 127.8, 127.2, 127.1, 126.8, 117.5, 113.0, 112.7, 21.5; ESI-MS
4.3.5. 5-Fluoro-2,3-diphenyl-1H-indole (6a)
(m/z) (M
þ
H)þ
¼
442; HRMS: calcd for C27H21NO2FS
1H NMR (500 MHz, CDCl3, TMS):
d
8.09 (s, 1H), 6.89e7.36 (m,
(M þ H)þ ¼ 442.1258, found: 442.1277.
13H); 13C NMR (75 MHz, CDCl3)
d 156.8, 135.8, 134.5, 132.3, 130.4,
130.2, 129.8, 129.1, 128.7, 128.6, 128.0, 127.9, 126.4, 111.6, 111.4, 111.1,
4.4.4. 2-(4-Fluorophenyl)-3-phenyl-1-tosyl-indole (13a) and 3-(4-
fluorophenyl)-2-phenyl-1-tosyl-indole (13b)
110.7; EI-MS (m/z) (M)þ ¼ 287.
1H NMR (500 MHz, CDCl3, TMS):
d
8.37 (d, J ¼ 8.90 Hz, 2H), 7.16e
7.45 (m, 21H), 6.87e7.07 (m, 11H), 2.31 (s, 6H); 13C NMR (125 MHz,
CDCl3) 163.3, 144.6, 144.5, 137.2, 137.1, 136.8, 135.6, 135.3, 133.9,
4.3.6. 5-Methyl-2,3-diphenyl-1H-indole (7a)
1H NMR (300 MHz, CDCl3, TMS):
d
8.12 (s, 1H), 7.22e7.44 (m,
d
12H), 7.05 (t, J ¼ 7.93 Hz, 1H), 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3)
133.7, 132.4, 132.0, 131.4, 131.3, 130.7, 130.2 (d), 129.7, 129.3 (d),
128.5, 128.2, 127.3, 127.0, 126.9, 126.8, 125.2 (d), 125.0, 124.2, 124.1,
123.6, 122.7, 120.4, 119.9, 119.6, 116.1, 115.3, 115.0, 114.5, 114.3, 21.5;
ESI-MS (m/z) (M þ H)þ ¼ 442; HRMS: calcd for HRMS: calcd for
C27H20NO2FNaS (M þ Na)þ ¼ 464.1096, found: 464.1107.
d
135.2, 134.1, 132.7, 130.1, 129.6, 128.9, 128.5, 128.4, 128.0, 127.5,
126.1, 124.2, 119.1, 114.6, 110.5, 21.5; ESI-MS (m/z) (M þ H)þ ¼ 284.
4.3.7. 5,7-Dimethyl-2,3-diphenyl-1H-indole (8a)
1H NMR (500 MHz, CDCl3, TMS):
d 7.87 (s, 1H), 7.36e7.39 (m,
4H), 7.32 (t, J ¼ 8.54 Hz, 2H), 7.27 (t, J ¼ 7.32 Hz, 2H), 7.21e7.23 (m,
4.4.5. 2-m-Tolyl-3-phenyl-1-tosyl-indole (14a) and 3-m-tolyl-2-
phenyl-1-tosyl-indole (14b)
3H), 6.81 (s, 1H), 2.49 (s, 3H), 2.38 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
135.3, 133.9, 133.7, 132.9, 130.1, 129.9, 128.5, 128.4, 128.1, 127.4,
1H NMR (300 MHz, CDCl3, TMS):
d
8.38 (d, J ¼ 8.30 Hz, 2H), 7.46
126.1, 124.9, 119.6, 116.8, 21.4, 16.5; ESI-MS (m/z) (M þ H)þ ¼ 298;
(d, J ¼ 7.74 Hz, 2H), 7.18e7.40 (m, 17H), 6.90e7.11 (m, 12H), 6.82 (d,
HRMS: calcd for C22H20N (M þ H)þ ¼ 298.1600, found: 298.1595.
J ¼ 7.55 Hz, 1H), 2.31 (s, 6H), 2.28 (s, 3H), 2.22 (s, 3H); 13C NMR
(75 MHz, CDCl3) d 144.4, 144.1, 137.6, 137.2, 136.9, 136.6, 135.8, 135.7,
4.3.8. 2-(4-Chlorophenyl)-3-phenyl-1H-indole (9a) and 3-(4-
chlorophenyl)-2-phenyl-1H-indole (9b)
135.5, 135.3, 132.7, 132.0, 130.9, 130.6, 130.4, 130.1, 129.7, 129.6,
129.2, 129.0, 128.7, 128.5, 128.3, 128.0, 127.9, 127.6, 127.1, 127.0, 126.9
(d), 125.4, 125.2, 125.0 (d), 124.0, 120.6, 120.4, 120.0, 119.9, 110.8,
110.3, 21.5, 21.3; ESI-MS (m/z) (M)þ ¼ 437.
1H NMR (300 MHz, CDCl3, TMS):
d 8.16 (s, 1H), 8.11 (s, 1H), 7.62
(d, J ¼ 7.55 Hz, 1H), 7.57 (d, J ¼ 5.28 Hz, 1H), 7.04e7.37 (m, 24H); 13C
NMR (75 MHz, CDCl3) d 135.9, 135.8, 134.6, 134.3, 133.5, 133.4, 132.7,
132.6, 132.3, 131.9, 131.3, 131.1, 130.0, 129.3, 128.8, 128.7 (d), 128.6,
128.1, 127.8, 126.4, 126.1, 122.9, 122.8, 120.5, 119.7, 119.3, 110.9 (d);
EI-MS (m/z) (M)þ ¼ 303.
Acknowledgments
K.S., P. S. P. and K. B. thank CSIR, India for their fellowships.
Appendix A. Supplementary material
4.4. General procedure for the Larock indolization of N-tosyl
substituted 2-bromoanilines
Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.jorganchem.2013.05.049.
The 25 mL RB-flask was charged with N-tosyl substituted 2-
bromoanilines (1 mmol), diphenylacetylene (2 mmol), LiOH$H2O
(4 mmol) and 0.1 mol% of catalyst 5 in 2 mL DMF. The reaction
mixture was stirred at 130 ꢀC for 24 h. Then, the reaction mixture
was cooled to room temperature, diluted with ethyl acetate (20 mL)
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