The PdCl2-catalyzed sequential heterocyclization/Michael addition cascade in the synthesis of 2,3-disubstituted indoles

Article abstract of DOI:10.1016/j.tet.2013.01.081

A cascade reaction of 2-N-unprotected-2-alkynylanilines and various electron-deficient alkenes in the presence of PdCl₂ provided 2,3-disubstituted indole derivatives, whereas, in the presence of Pd(OAc) ₂, the same reaction resulted in the production of N-alkylated-2-alkynylaniline derivatives.

Full text of DOI:10.1016/j.tet.2013.01.081

Tetrahedron 69 (2013) 3323e3330
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Tetrahedron
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The PdCl2-catalyzed sequential heterocyclization/Michael addition
cascade in the synthesis of 2,3-disubstituted indoles
Donala Janreddy, Veerababurao Kavala, Chun-Wei Kuo, Ting-Shen Kuo, Chiu-Hui He,
*
Ching-Fa Yao
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 July 2012
Received in revised form 11 January 2013
Accepted 28 January 2013
Available online 14 February 2013
A cascade reaction of 2-N-unprotected-2-alkynylanilines and various electron-deficient alkenes in the
presence of PdCl2 provided 2,3-disubstituted indole derivatives, whereas, in the presence of Pd(OAc)2,
the same reaction resulted in the production of N-alkylated-2-alkynylaniline derivatives.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Cascade reaction
PdCl2
2,3-Disubstituted indoles
2-Alkynylanilines
a,b-Unsaturated ketones
1. Introduction
Indole and its derivatives play a leading role in medicinal and
synthetic chemistry due to the presence of this structure in a number
of natural products and pharmaceutical agents.1 A survey of the lit-
erature indicates that a wide variety of synthetic protocols exist for
the construction of an indole moiety.2 Among them, the transition
metal-catalyzed intramolecular cyclization of 2-alkynylaniline is the
most widely employed method for generating an indole moiety. The
advantages of this method include a wide tolerance for functional
groups, its simplicity and the fact that the yields of indole derivatives
are acceptable.3 A wide range of transition metal catalysts, including
Cu, Au, In, Fe, Pd, Rh, Ag, Hg etc., can be used to generate indole de-
rivatives via the annulation of 2-haloanilines with alkynes.4
Scheme 1. Previous reports on the differential reactivity of 2-alkynyl-anilines with
various electron-deficient alkenes.
From all these reports, it is quite clear that both the reaction con-
ditions and the additives used have an important impact on the
reaction. The differential reactivity of 2-alkynylaniline with
electron-deficient alkenes prompted us to further investigate this
reaction. In fact, in recent years, we reported on some protocols for
the synthesis of functionalized indole and quinoline derivatives.9 In
a continuation of these studies, we report herein on the reaction of
2-N-unprotected-2-alkynylanilines with electron-deficient alkenes
in the presence of various metal catalysts.
On the other hand, the reaction of 2-alkynylanilines and
electron-deficient alkenes in the presence of various transition
metal catalyst results in the production of two different types of
indole derivatives, namely, 3-substituted-2-alkenylindoles and 3-
substituted-2-alkylindoles, depending on the conditions employed
(Scheme 1). The formation of 3-substituted-2-alkenylindole de-
rivatives involves a b
-hydride elimination (the Heck reaction),5,6
whereas the formation 3-substituted-2-alkyl substituted indole
derivatives is the result of the protonolysis of metalecarbon bond
and is achieved bycontrolling the extent of b
-hydride elimination.7,8
2. Results and discussion
To study this reaction, we chose 2-(phenylethynyl) aniline and
methyl vinyl ketone as model substrates. Lu and his co-worker
* Corresponding author. E-mail addresses: cheyaocf@ntnu.edu.tw, cheyaocf@
yahoo.com.tw (C.-F. Yao).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.01.081

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D. Janreddy et al. / Tetrahedron 69 (2013) 3323e3330
Table 3
reported on the reaction of N-(2-(phenylethynyl) phenyl)meth-
anesulfonamide derivatives and acrolein7 in the presence of
Pd(OAc)2 and LiBr in which 3-(N-Mesyl-20-phenylindol-30-yl)
propanal was produced as the major product. However, they did
not investigate the use of 2-(phenylethynyl)aniline and methyl vi-
nyl ketone substrates in their reaction. To determine whether these
substrates could be employed in this process, we examined the
reaction of 2-(phenylethynyl)aniline and methyl vinyl ketone in the
presence of Pd(OAc)2 and LiBr in THF or CH3CN solvent at room
temperature (Table 1, entry 2). Under these conditions, the final
product of the reaction produced was the Michael adduct 4-((2-
(phenylethynyl) phenyl)amino)butan-2-one. Even when the re-
action was run at 60 ꢀC, the outcome was the same, but a shorter
reaction time was required (Table 1, entry 3). To further verify this
result, we examined the reactions of a variety of 2-alkynylanilines
Investigation of reactivity of 2-(phenylethynyl) aniline with methyl vinyl ketone in
the presence of various metal catalysts
Entrya
Catalyst
Temp (ꢀC)
Time (h)
Yield (%)b
,d
lc
PdCl2/LiCl
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
24
24
24
24
6
24
4
4
45
40
42
33
65
50
65
90
Trace
10
9
Trace
Trace
Trace
35
25
27
6
62
2c,d
3c,d
4d
5d
6d
7d
8
Pd(PPh3)2Cl2/LiCl
Pd(CH3CN)2Cl2/LiCl
PdCl2 (5 mol %)
PdCl2 (10 mol %)
Pd(PPh3)2Cl2(10 mol %)
Pd(CH3CN)2Cl2 (10 mol %)
PdCl2 (20 mol %)
ZnCl2 (20 mol %)
CuCl2 (20 mol %)
CuBr2 (20 mol %)
CuI (20 mol %)
CuBr (20 mol %)
CuCl (20 mol %)
VCl3 (20 mol %)
InCl3 (10 mol %)
FeCl3 (20 mol %)
FeCl2 (20 mol %)
In(OTf)3 (10 mol %)
BF3.Et2O (30 mol %)
TiCl4 (20 mol %)
with various a,b-unsaturated ketones. All of the substrates tested
in this reaction, produced the corresponding Michael adduct in
moderate to good yield (Table 2, entries 1e5). However, the desired
product, the 2,3-disubstituted indole was not obtained under these
reaction conditions (Table 1).
9
4
10
11
12
13
14
15
16
17
18
19
20
21
24
24
12
12
12
24
24
4
4
9
8.5
2
Table 1
The reactivity of 2-(phenylethynyl)aniline with methyl vinyl ketone catalyzed by
Pd(OAc)2
57
54
Bold values indicate optimum reaction conditions for this reaction.
a
Unless otherwise noted, all the reactions were carried out at 0.25 mmol scale in
acetonitrile solvent.
Entrya Catalyst (5 mol %) Additive (2 equiv) Temp (ꢀC) Time (h) Yield (%)b
b
NMR yields (CH2Br2 as internal standard).
5 mol % of catalyst and 2 equiv of LiCl were used.
c
1
2
3
Pd(OAc)2
Pd(Oac)2
Pd(Oac)2
LiCl
LiBr
LiCl
rt
rt
60
24
24
24
60
60
80
d
Unreacted starting material 1a was recovered.
produced, along with some unreacted starting material (Table 3,
entry 2). Moreover, another palladium catalyst Pd(CH3CN)2Cl2/LiCl
gave the 2,3-disubstituted indole derivative but the reaction failed
to reach completion, even after 24 h (Table 3, entry 3). On the other
hand, when the same reaction was conducted with palladium
chloride in the absence of lithium chloride, the yield of the desired
product was similar (Table 3, entry 4). Based on these observations,
we envisioned that PdCl2 represents an ideal catalyst for this
transformation. To evaluate this further, we carried out the reaction
using increasing amounts of catalyst to 10 mo% at 60 ꢀC. Under
these conditions, the reaction afforded 65% of the desired product
(Table 3, entry 5). However, an excellent yield was obtained when
the reaction was performed using 20 mol % palladium chloride as
catalyst (Table 3, entry 8). Further increases in catalyst loading
failed to improve the product yield or the rate of the reaction. To
compare the efficacy of the catalyst, we tested the reaction with
various other transition metal catalysts such as, CuBr, CuBr2, CuCl,
CuI, ZnCl2, FeCl3, FeCl2, InCl3, VCl3, ZnBr2, In(OTf)3, BF3$OEt2, and
TiCl4 in acetonitrile at 60 ꢀC (Table 3, entries 9e21). In(OTf)3,
BF3.OEt2, and TiCl4 resulted in the production of the desired
product in moderate yields, but the remaining catalysts were in-
effective for this transformation (Table 3, entries 19e21).
Bold values indicate optimum reaction conditions for this reaction.
a
Unless otherwise noted, all reactions were carried out on a 0.25 mmol scale in
THF solvent.
b
NMR yields (CH2Br2 as internal standard).
Table 2
Reactions of 2-alkynylanilines with various Michael acceptors in the presence
Pd(OAc)2/LiCl
Entrya
R0
R00
X
Product
Time (h)
Yield (%)b
1
2
3
4
5
Ph
Me
Me
Me
Et
H
5a
5b
5c
5d
5e
24
30
48
24
24
65
68
72
78
62
Cyclopentyl
n-Butyl
Ph
4-Me
4-Cl
H
Ph
Ph
H
a
Unless otherwise noted, the reactions were carried out under the following
conditions, 2-alkynylaniline (1.0 mmol), methyl vinyl ketone (1.5 mmol), Pd(OAc)2
(5 mol %), LiCl (2 equiv) in THF solvent at 60 ꢀC.
b
Isolated yields.
We next investigated the effect of solvent; by carrying out the
reaction in solvents such as DMF, DMSO, MeOH, THF and CH2Cl2. The
use of polar solvents such as DMF, DMSO, and MeOH resulted in poor
yields. The yield of product was comparable in case of CH2Cl2 but
a longer time was needed for the reaction to reach completion. The
best result was obtained when the reaction was performed in the
presence of 20 mol % of PdCl2 with acetonitrile as the solvent at 60 ꢀC.
The product, 4-(2-phenyl-1H-indol-3-yl)butan-2-one was well
characterized by 1H NMR,13C NMR, LRMS, and HRMS. In addition, the
structure was confirmed by the single crystal X-RD analysis (Fig. 1).
In an attempt to examine the reaction using other palladium(II)
catalysts, we performed the reaction using 5 mol % palladium
chloride in the presence of lithium chloride in acetonitrile as the
solvent at 60 ꢀC. In this case, the reaction produced 4-(2-phenyl-
1H-indol-3-yl)butan-2-one as the sole product and no trace of the
N-alkylated product was observed (Table 3, entry 1) however, the
starting material was not completely consumed. On the other hand,
when Pd(PPh3)2Cl2 was used as catalyst, two products, the 2,3-
disubstituted indole derivative and the N-alkylated product were

D. Janreddy et al. / Tetrahedron 69 (2013) 3323e3330
3325
products than substrates with electron withdrawing groups (Table
4, entries 1e5). In order to check the effect of a lower catalyst
loading, we conducted all these reactions using 10 mol % of PdCl2.
As shown in Table 3, in the presence of 10 mol % PdCl2 catalyst, the
reactions required a longer time to produce the corresponding
product and the yields of the product were comparatively less.
Consequently, we examined the reaction with different
substituted 2-cycloalkyl(alkylethynyl)anilines and 2-(alkylethynyl)
anilines (Table 5). Reactions involving 2-cycloalkyl(alkylethynyl)an-
ilines and 2-(alkylethynyl)anilines were much faster, compared to
reactions using 2-(phenylethynyl)anilines (Tables 4 and 5). On the
other hand, sensitive groups like ester, alcohol, and cyclopropyl
functionalities tolerated the present reaction conditions. The yield of
products was moderate to good in the case of cycloalkyl and long
Table 5
Synthesis of various 2,3-disubstituted indole derivatives
Fig. 1. ORTEP diagram of the single crystal X-ray diffraction structure of 3a.12
With optimized reaction conditions determined, we in-
vestigated the scope and limitations of the reaction using various
substituted 2-(aryl/alkylethynyl)aniline and methyl vinyl ketone
derivatives. In this regard, we first examined the reaction of various
2-(phenylethynyl)anilines with different substitutions on the phe-
nyl ring (Table 4). The reaction of 2-(phenylethynyl)anilines con-
taining electron releasing groups produced slightly higher yields of
Entrya
Substrate
Product
Time (h) Yield (%)b
6
0.25
0.5
0.3
2
75
70
70
60
67
Table 4
Synthesis of various 2,3-disubstituted indole derivatives
7
8
Entrya
1
Substrate
Product
Time (h)
4 (6)
Yield (%)b
70 (60)
9
2
3
5 (8)
69 (60)
70 (58)
10
1
1.5 (4)
11
12
1
1
40
65
4
2 (5)
65 (55)
50 (45)
5
6 (10)
13
1
97
a
Unless otherwise noted, all reactions were carried out under the following
conditions, 2-alkynylaniline (1.0 mmol), methyl vinyl ketone (1.5 mmol), PdCl2
(20 mol %) in acetonitrile at 60 ꢀC.
Isolated yields. The yields and reaction times given in parentheses corresponds
to the reactions using 10 mol % of PdCl2.
a
Unless otherwise noted, all reactions were carried out under the following
conditions, 2-alkynylaniline (1.0 mmol), methyl vinyl ketone (1.5 mmol), PdCl2
(20 mol %) in acetonitrile at 60 ꢀC.
b
b
Isolated yields.

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D. Janreddy et al. / Tetrahedron 69 (2013) 3323e3330
chain alkyl substituted 2-(alknylethynyl)anilines (Table 5, entries
6e12). However, the reaction of 2,4-dimethyl-6-(3-methylbut-1-
ynyl)aniline gave the desired product in excellent yield (Table 5,
entry 13).
To explore the generality and scope of this protocol, further, we
examined the reaction when various Michael acceptors were used
(Table 6). The reaction of ethyl vinyl ketone with 1d gave the
desired product in excellent yield (Table 6, entry 1). Moreover, the
reaction of phenyl vinyl ketone with 1a and 1j furnished the cor-
responding 2,3-disubstituted indole derivatives in good yields
(Table 6, entries 2 and 3). However, the reactions required a long
time compared to the ethyl vinyl ketone (Table 6, entries 1e3). The
reactions of substituted vinyl ketones like trans-2-butenone, trans-
1-phenyl-2-butenone and trans-chalcone took a longer time to
produce the corresponding product in good yields (Table 6, entries
4e6). At the same time, sterically hindered and a less reactive
enone10 like cyclopentenone gave the desired product (51%) along
with some 2-substituted indole (20%) (Table 6, entry 7). However,
the reaction in the presence of weak Michael acceptors such as
methyl acrylate and acrylonitrile resulted in the formation of 2-
phenylindole as the final product. No trace of 2,3-disubstituted
indole was obtained in both cases (Table 6, entries 8 and 9).
Finally, we tested the reaction of N-protected 2-alkynylaniline
derivatives with methyl vinyl ketone under the present reaction
conditions. Here, only the N-protected 2-phenylindole was ob-
tained as a final product (Scheme 2, 4C). We also examined the
reaction of 2-ethynylaniline and 2-trimethylsillylethynylaniline. In
this case, the expected product was not produced under the present
reaction conditions (Scheme 2).
Table 6
Reactions of 2-alkynylanlines with various Michael acceptors
Entrya Substrate
Enone
Product
Time (h) Yield (%)b
1
1d
1.5
96
2
3
4
5
6
1a
1j
8
6
75
82
70
70
75
51
1d
1a
1a
1b
48
Scheme 2. Limitations of the protocol.
48
48
24
In order to extend the scope of the methodology, we carried out
the reaction on a large scale using 5 mmol of 2-(phenylethynyl)
aniline and 7.5 mmol of methyl vinyl ketone in presence of 10 mol %
PdCl2 in acetonitrile at 60 ꢀC. The reaction proceeded without any
difficulty and a good yield of the desired product was obtained
(Scheme 3).
7c
8d
1a
1a
24
24
54
77
Scheme 3. 5 mmol scale reaction of 2-(phenylethynyl)aniline with methyl vinyl
ketone.
9d
We speculate that the mechanism for this reaction is very
similar to that proposed by Alfonsi et al.,8 which involves the co-
ordination of palladium chloride with the triple bond of a 2-
akynylaniline and followed by aminopalladation to furnish an in-
dole palladium intermediate (I) (Scheme 4), which then undergoes
protonolysis in the presence of the strong acid HCl that was
a
Unless otherwise noted, all the reactions were carried out under the following
conditions, 2-alkynylaniline (1.0 mmol), methyl vinyl ketone (1.5 mmol), PdCl2
(20 mol %) in acetonitrile solvent at 60 ꢀC.
b
Isolated yields.
c
20% of 6-methyl-2-phenylindole (4a) was formed as side product.
Only 2-phenylindole was formed.
d

D. Janreddy et al. / Tetrahedron 69 (2013) 3323e3330
3327
observations from the literature. This procedure offers a mild and
easy method to access a variety of 2,3-disubstituted indole de-
rivatives in moderate to good yields. A variety of functional groups
readily tolerated under the reaction conditions employed.
4. Experimental section
4.1. General information
All reactions were performed at 60 ꢀC. Analytical thin-layer
chromatography was performed with E. Merck silica gel 60F glass
plates and flash chromatography by using E. Merck silica gel 60
(230e400 mesh). MS or HRMS were measured by JEOL JMS-D300
or JEOL JMS-HX110 spectrometer. 1H and 13C NMR spectra were
recorded with a Bruker Avance EX 400.
4.2. General experimental procedure for the synthesis of
2,3-disubstituted indoles
Scheme 4. Plausible mechanistic pathways.
The substituted 2-alkynylaniline (1.0 mmol) was dissolved in
acetonitrile (5.0 mL) and stirred until the solution became homo-
geneous. To this solution, methyl vinyl ketone (1.5 mmol) followed
by 20 mol % of PdCl2 (59e60%, 35 mg) was added under a nitrogen
atmosphere, then heated to 60 ꢀC and monitored by TLC. After
completion of the reaction, the mixture was cooled to room tem-
perature and the acetonitrile was removed by vacuum evaporation.
The resulting crude product was purified by column chromatog-
raphy to afford the desired 2,3-disubstituted indoles.
produced during the aminopalladation to afford the 2-substituted
indole derivative (II). The resulting 2-substituted indole then re-
acts with the
a,b-unsaturated ketone in the presence palladium
chloride to give the corresponding 2,3-disubstituted indole de-
rivative.8 Alternatively the indole palladium intermediate (I) could
react with the
a,b-unsaturated ketone to produce intermediate
(III), which then undergoes protonolysis to produce the desired
product (Scheme 4).7,11 The experimental results such as the for-
mation of 2-phenylindole derivatives in the case of the reactions
with methyl acrylate and acrylonitrile (Table 6, entries 8 and 9) as
well as the reaction of N-(2-(phenylethynyl)phenyl)benzamide
with methyl vinyl ketone (Scheme 2, 4C) supports the pathway 1
4.3. Spectral data
4.3.1. 4-(2-Phenyl-1H-indol-3-yl)butan-2-one (3a). Yield: (184 mg,
70%); White solid; mp: 114e116 ꢀC. FT-IR (KBr) ( /cmꢁ1): 3343,
n
mechanism. As in both cases, after the formation of
a 2-
1708. 1H NMR (400 MHz, CDCl3) dH (ppm): 8.12 (br s, 1H), 7.61 (d,
J¼7.92 Hz, 1H), 7.55e7.52 (m, 2H), 7.49e7.45 (m, 2H), 7.40e7.63 (m,
2H), 7.25e7.21 (m, 1H), 7.18e7.14 (m, 1H), 3.22e3.18 (m, 2H),
2.84e2.80 (m, 2H), 2.11 (s, 3H). 13C NMR (100 MHz, CDCl3) dC (ppm):
208.8, 136.0, 134.6, 133.2, 129.1, 128.9, 128.1, 127.9, 122.5, 119.8,
119.0, 111.9, 111.1, 44.6, 30.1, 18.9. LRMS (EI) (m/z) (relative in-
tensity): 263 (Mþ, 50), 221.4 (100), 205.5 (90), 179.1 (25); HRMS
calcd for C18H17O1N1 (Mþ): 263.1310, found 263.1314.
phenylindole derivative from the indole palladium intermediate
(I), a Michael addition did not take place. In the former case both
acrylonitrile and methyl acrylate are weak Michael acceptors
whereas in the later case the presence of a benzoyl substituent on
the indole moiety decreases the nucleophilicity.
Moreover when 2-phenylindole and methyl vinyl ketone was
reacted in the presence of palladium chloride, the reaction pro-
duced 4-(2-phenyl-1H-indol-3-yl)butan-2-one in quantitative
yield (Scheme 5). This reaction also supports the Pathway 1
mechanism for the formation of 2,3-disubstituted indole derivative
4.3.2. 4-(6-Methyl-2-phenyl-1H-indol-3-yl)butan-2-one (3b). Yield:
(191 mg, 69%); White solid; mp: 170e172 ꢀC. FT-IR (KBr) ( /cmꢁ1):
n
from the reaction of 2-alkynylanilines with various
ketones.
a,b-unsaturated
3358, 1713. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.97 (br s, 1H),
7.53e7.44 (m, 5H), 7.38e7.34 (m, 1H), 7.16 (s, 1H), 6.99 (dd, J¼8.0,
0.9 Hz, 1H), 3.20e3.16 (m, 2H), 2.83e2.79 (m, 2H), 2.48 (s, 3H), 2.11
(s, 3H). 13C NMR (100 MHz, CDCl3) dC (ppm): 208.9, 136.5, 133.9,
133.4, 132.4.9, 129.1, 128.0, 127.7, 126.8, 121.6, 118.7, 111.8, 111.1, 44.7,
30.4, 21.9, 19.0. LRMS (EI) (m/z) (relative intensity): 277 (Mþ, 55),
220 (100), 234 (65), 236 (58); HRMS calcd for C19H19O1N1 (Mþ):
277.1467, found 277.1460.
4.3.3. 4-(5,7-Dimethyl-2-phenyl-1H-indol-3-yl)butan-2-one
Scheme 5. Reaction of 2-phenylindole with methyl vinyl ketone.
(3c). Yield: (204 mg, 70%); White solid. Mp: 154e155 ꢀC. FT-IR
(KBr) (n
/cmꢁ1): 3358, 1715. 1H NMR (400 MHz, CDCl3) dH (ppm):
3. Conclusion
7.94 (br s, 1H), 7.59e7.56 (m, 2H), 7.51e7.47 (m, 2H), 7.42e7.37 (m,
1H), 7.25 (s, 1H), 6.90 (s, 1H), 3.20e3.16 (m, 2H), 2.85e2.81 (m, 2H),
2.50 (s, 3H), 2.49 (s, 3H), 2.14 (s, 3H). 13C NMR (100 MHz, CDCl3) dC
(ppm): 209.0, 134.6, 133.9, 133.5, 129.4, 129.0, 128.7, 128.1, 127.8,
124.9, 120.0, 116.3, 112.0, 44.8, 30.1, 21.7, 19.1, 16.7. LRMS (EI) (m/z)
(relative intensity): 291 (Mþ, 2), 249.0 (80), 105 (100); HRMS calcd
for C20H21O1N1 (Mþ): 291.1623, found 291.1627.
In conclusion, we report on cascade reaction of 2-N-unprotected-
2-alkynylanilines and various electron-deficient alkenes using pal-
ladium chloride and Pd(OAc)2/LiCl catalytic systems. The presence of
PdCl2 resulted in the formation of 2,3-disubstituted indole de-
rivatives whereas the Pd(OAc)2/LiCl catalytic system produced N-
alkylated-2-alkynylaniline derivatives. A mechanism was proposed
for the formation of 2,3-disubstituted indole derivatives based
on experimental outcome, which is consistent with related
4.3.4. 4-(5-Chloro-2-phenyl-1H-indol-3-yl)butan-2-one (3d). Yield:
(193 mg, 65%); White solid; mp: 170e171 ꢀC. FT-IR (KBr) ( /cmꢁ1):
n

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D. Janreddy et al. / Tetrahedron 69 (2013) 3323e3330
3345,1702.1HNMR(400MHz, CDCl3)dH (ppm):8.13(brs,1H), 6.95(s,
1H), 7.54e7.45 (m, 5H), 7.41e7.36 (m,1H), 7.28e7.26 (m,1H), 7.15 (dd,
J¼8.5,1.96 Hz,1H), 3.14e3.10 (m, 2H), 2.79e2.75 (m, 2H), 2.11 (s, 3H).
13C NMR (100 MHz, CDCl3) dC (ppm): 208.5, 136.1, 134.4, 132.7, 130.1,
129.2,128.3,128.1,125.5,122.7,118.5,112.1,111.6, 44.5, 30.1,18.7. LRMS
(EI) (m/z) (relative intensity): 297 (Mþ, 42), 240 (100), 204 (40);
HRMS calcd for C18H16Cl1 O1N1 (Mþ): 297.0920, found 297.0912.
(d, J¼1.9 Hz, 1H), 7.16 (d, J¼8.5 Hz, 1H), 7.05 (dd, J¼8.5, 1.9 Hz, 1H),
2.94e2.90 (m, 2H), 2.76e2.70 (m, 4H), 2.12 (s, 3H), 1.66e1.59 (m,
2H), 1.36e1.27 (m, 8H), 0.88 (t, J¼6.9 Hz, 3H). 13C NMR (100 MHz,
CDCl3) dC (ppm): 208.8, 137.6, 133.8, 129.6, 125.0, 121.3, 117.6, 111.5,
110.2, 44.51, 31.9, 30.3, 29.9, 29.5, 29.3, 26.2, 22.8, 18.3, 14.2. LRMS
(EI) (m/z) (relative intensity): 319 (Mþ, 81), 262 (100), 177 (79);
HRMS calcd for C19H26Cl1O1N1 (Mþ): 319.1703, found 319.1709.
4.3.5. 4-(5-Nitro-2-phenyl-1H-indol-3-yl)butan-2-one (3e). Yield:
4.3.11. Dimethyl 2-((5-nitro-3-(3-oxobutyl)-1H-indol-2-yl)methyl)
(154 mg, 50%); Yellow solid. Mp: 172e173 ꢀC. FT-IR (KBr) (
n
/cmꢁ1):
malonate (3k). Yield: (150 mg, 40%); Yellow crystalline solid. Mp:
3338, 1702. 1H NMR (400 MHz, CDCl3) dH (ppm): 8.7 (br s, 1H), 8.54
(d, J¼2.0 Hz, 1H), 8.09 (dd, J¼8.9, 2.1 Hz, 1H), 7.55e7.53 (m, 2H),
7.50e7.47 (m, 2H), 7.44e7.38 (m, 2H) 3.21e3.17 (m, 2H), 2.80e2.79
(m, 2H), 2.12 (s, 3H). 13C NMR (100 MHz, CDCl3) dC (ppm): 208.1,
141.8, 139.0, 137.9, 131.9, 129.3, 128.8, 128.4, 128.1, 118.1, 116.3, 114.0,
110.0, 44.3, 30.1, 18.5. LRMS (EI) (m/z) (relative intensity): 308 (Mþ,
55), 251 (100), 204 (40); HRMS calcd for C18H16O3N2 (Mþ):
308.1161, found 308.1159.
120e122 ꢀC. FT-IR (KBr) ( /cmꢁ1): 3449, 1735. 1H NMR (400 MHz,
n
CDCl3) dH (ppm): 8.44 (br s, 1H), 8.06 (m, 1H), 7.33e7.26 (m, 1H),
6.40 (s, 1H), 4.45 (t, J¼7.1 Hz, 2H), 3.96e3.9 (m, 1H), 3.76 (s, 6H),
3.41e3.39 (m, 2H), 3.00e2.92 (m, 2H), 2.15 (s, 3H). 13C NMR
(100 MHz, CDCl3) dC (ppm): 205.7, 168.8, 142.0, 140.2, 139.5, 127.3,
117.4, 117.3, 109.2, 102.3, 53.2, 50.7, 43.0, 38.1, 30.4, 26.0. LRMS (EI)
(m/z) (relative intensity): 376 (Mþ, 100), 285 (100); HRMS calcd for
C18H20O7N2 (Mþ): 376.1271, found 376.1279.
4.3.6. 4-(2-Cyclopropyl-6-methyl-1H-indol-3-yl)butan-2-one
4.3.12. (2-(4-Hydroxybutyl)-5-nitro-1H-indol-3-yl)butan-2-one
(3f). Yield: (181 mg, 75%); Yellow Liquid. FT-IR (KBr) (
n
/cmꢁ1):
(3l). Yield: (197 mg, 65%); Yellow crystalline solid; mp:
3342, 1710. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.58 (br s, 1H), 7.35
(d, J¼8.0 Hz, 1H), 7.04 (s, 1H) 6.92 (dd, J¼8.0, 0.8 Hz, 1H), 3.07 (t,
J¼7.7 Hz, 2H), 2.82e2.78 (m, 2H), 2.44 (s, 3H), 2.25 (s, 3H),
2.07e2.00 (m, 1H), 1.00e0.95 (m, 2H), 0.74e0.700 (m, 2H). 13C NMR
(100 MHz, CDCl3) dC (ppm): 209.5, 135.4, 135.3, 131.0, 126.4, 121.0,
117.6, 111.6, 110.7, 44.6, 30.3, 21.8, 18.7, 7.4, 6.4. LRMS (EI) (m/z)
(relative intensity): 241.15 (Mþ, 100); HRMS calcd for C16H19O1N1
(Mþ): 241.1469, found 241.1467.
160e161 ꢀC. FT-IR (KBr) ( /cmꢁ1): 3423, 1638. 1H NMR (400 MHz,
n
CDCl3) dH (ppm): 10.36 (br s, 1H), 8.25 (d, J¼2.0 Hz, 1H), 7.81 (dd,
J¼8.8, 2.16 Hz, 1H), 7.14 (d, J¼8.8 Hz, 1H), 3.50 (q, J¼5.8 Hz, 2H), 3.40
(t, J¼5.0 Hz, 1H), 2.83 (t, J¼7.4 Hz, 2H), 2.60e2.60 (m, 4H), 1.97 (s,
3H), 1.66e1.59 (m, 2H), 1.50e1.43 (m, 2H). 13C NMR (100 MHz,
CDCl3) dC (ppm): 208.1, 140.6, 139.9, 138.8, 127.3, 116.1, 114.7, 111.9,
110.2, 60.4, 44.2, 31.8, 30.0, 25.7, 25.3, 17.8. LRMS (EI) (m/z) (relative
intensity): 304 (Mþ, 100), 247 (80); HRMS calcd for C16H20O4N2
(Mþ): 304.3142, found 304.1427.
4.3.7. 4-(2-Cyclopentyl-6-methyl-1H-indol-3-yl)butan-2-one
(3g). Yield: (188 mg, 70%); Thick red gummy liquid. FT-IR (KBr) (
n
/
4.3.13. 4-(2-Isopropyl-5,7-dimethyl-1H-indol-3-yl)butan-2-one
cmꢁ1): 3350, 1715. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.65 (br s,
1H), 7.35 (d, J¼8.0 Hz, 1H), 7.08 (s, 1H), 6.91 (d, J¼7.9 Hz, 1H),
3.33e3.28 (m, 1H) 3.0e2.96 (m, 2H), 2.75 (t, J¼7.66 Hz, 2H), 2.44 (s,
3H), 2.11 (s, 3H), 2.08e2.06 (m, 2H),1.85e1.82 (m, 2H),1.76e1.73 (m,
2H), 1.62e1.60 (m, 2H). 13C NMR (100 MHz, CDCl3) dC (ppm): 209.7,
138.1, 135.9, 131.0, 126.3, 121.0, 117.7, 110.7, 109.9, 45.0, 37.0, 33.6,
30.5, 25.9, 21.8, 18.8; LRMS (EI) (m/z) (relative intensity): 269.1 (Mþ,
100); HRMS calcd for C18H23O1N1 (Mþ): 269.1780, found 269.1779.
(3m). Yield: (250 mg, 97%); Yellow solid. Mp: 109e110 ꢀC. FT-IR
(KBr) (n
/cmꢁ1): 3346, 1713. 1H NMR (400 MHz, CDCl3) dH (ppm):
7.59 (br s, 1H), 7.13 (s, 1H), 6.79 (s, 1H), 3.34e3.27 (m, 1H),
2.99e2.95 (m, 2H), 2.79e2.76 (m, 2H), 2.45 (s, 3H), 2.43 (s, 3H), 2.15
(s, 3H), 1.34 (s, 3H), 1.32 (s, 3H). 13C NMR (100 MHz, CDCl3) dC
(ppm): 209.2, 140.8, 133.0, 128.8, 128.1, 123.6, 119.5, 115.5, 108.9,
44.9, 30.3, 25.7, 23.0, 21.6, 18.6, 16.7. LRMS (EI) (m/z) (relative in-
tensity): 257 (Mþ, 50), 200 (100); HRMS calcd for C17H23O1N1 (Mþ):
257.1780, found 257.1789.
4.3.8. 4-(2-Cyclohexyl-6-methyl-1H-indol-3-yl)butan-2-one
(3h). Yield: (198 mg, 70%); Pale brown liquid. FT-IR (KBr) (
n
/cmꢁ1):
4.3.14. 1-(5-Chloro-2-phenyl-1H-indol-3-yl)pentan-3-one (3n). Yield:
3356, 1725. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.74 (br s, 1H), 7.37
(d, J¼8.0 Hz, 1H), 7.10 (s, 1H), 6.92 (dd, J¼7.9, 0.9 Hz, 1H), 3.0e2.96
(m, 2H), 2.90e2.84 (m, 1H), 2.79e2.75 (m, 2H), 2.47 (s, 3H), 2.15 (s,
3H), 1.89e1.78 (m, 6H), 1.51e1.40 (m, 4H). 13C NMR (100 MHz,
CDCl3) dC (ppm): 209.3, 139.8, 135.8, 130.9, 126.1, 120.9, 117.8110.7,
108.7, 45.0, 35.8, 33.6, 30.4, 26.8, 26.3, 21.8, 18.6. LRMS (EI) (m/z)
(relative intensity): 283 (Mþ, 100), 284 (22); HRMS calcd for
C19H25O1N1 (Mþ): 283.1936, found 283.1938.
(300 mg, 96%); Colorless solid. Mp: 138e140 ꢀC. FT-IR (KBr) (
n/
cmꢁ1): 3370, 1711. 1H NMR (400 MHz, CDCl3) dH (ppm): 8.10 (br s,
1H), 7.55e7.53 (m, 3H), 7.47 (t, J¼7.5 Hz, 2H), 7.40e7.36 (m, 1H), 7.27
(d, J¼8.56 Hz, 1H), 7.15 (dd, J¼8.5, 1.9 Hz, 1H), 3.15e3.11 (m, 2H),
2.77e2.73 (m, 2H), 2.39 (q, J¼7.3 Hz, 2H), 1.03 (t, J¼7.3 Hz, 3H). 13C
NMR (100 MHz, CDCl3) dC (ppm): 211.1, 136.1, 134.4, 132.7, 130.1,
129.2, 128.3, 128.1, 125.5, 122.7, 118.6, 112.1, 111.9, 43.1, 36.2, 18.9, 7.9.
LRMS (EI) (m/z) (relative intensity): 311 (Mþ, 50), 328 (100); HRMS
calcd for C19H18Cl1O1N1 (Mþ): 311.1077, found 311.1086.
4.3.9. 4-(2-Butyl-5-chloro-1H-indol-3-yl)butan-2-one (3i). Yield:
(166 mg, 60%); Yellow Liquid. FT-IR (KBr) (
n
/cmꢁ1): 3372, 1704. 1H
4.3.15. 1-Phenyl-3-(2-phenyl-1H-indol-3-yl)propan-1-one (3o). Yield:
NMR (400 MHz, CDCl3) dH (ppm): 7.87 (br s, 1H), 7.42 (d, J¼1.9 Hz,
1H), 7.16 (d, J¼8.5 Hz,1H), 7.05 (dd, J¼8.5, 1.9 Hz,1H), 2.94e2.90 (m,
2H), 2.75e2.70 (m, 4H), 2.1 (s, 3H) 1.65e1.57 (m, 2H), 1.42e1.33 (m,
2H), 0.92 (t, J¼3.7 Hz, 3H). 13C NMR (100 MHz, CDCl3) dC (ppm):
208.8, 137.6, 133.8, 129.6, 125.0, 121.3, 117.6, 111.5, 110.2, 44.5, 32.0,
30.0, 25.9, 22.7, 18.3, 14.0. LRMS (EI) (m/z) (relative intensity): 277
(Mþ, 75), 220 (100), 177 (37); HRMS calcd for C16H20Cl1O1N1 (Mþ):
277.1233, found 277.1228.
(243 mg, 75%); Yellow Liquid. FT-IR (KBr) (n
/cmꢁ1): 3340, 1716. 1H
NMR (400 MHz, CDCl3) dH (ppm): 8.1 (br s, 1H), 7.92 (d, J¼7.4 Hz,
1H), 7.64 (d, J¼7.84 Hz, 1H), 7.58e7.52 (m, 3H), 7.49e7.36 (m, 6H)
7.23 (d, J¼7.32 Hz, 1H), 7.17 (t, J¼7.46 Hz, 1H), 3.37 (s, 4H). 13C NMR
(100 MHz, CDCl3) dC (ppm): 200.0, 137.0, 136.1, 134.7, 133.2,
133.1, 129.1, 129.0, 128.7, 128.2, 128.1, 128.0, 122.6, 119.9, 119.1, 112.3,
111.1, 39.9, 19.4. LRMS (EI) (m/z) (relative intensity): 325 (Mþ, 40),
206 (100); HRMS calcd for C23H19O1N1 (Mþ): 325.1467, found
325.1469.
4.3.10. 4-(5-Chloro-2-heptyl-1H-indol-3-yl)butan-2-one (3j). Yield:
(214 mg, 67%); Colorless solid. Mp 88e89 ꢀC. FT-IR (KBr) (
n
/cmꢁ1):
4.3.16. 3-(2-Butyl-6-chloro-1H-indol-3-yl)-1-phenylpropan-1-one
3364, 1707. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.89 (br s, 1H), 7.43
(3p). Yield: (277 mg, 82%); Yellowgummy solid. FT-IR (KBr) (n
/cmꢁ1):

D. Janreddy et al. / Tetrahedron 69 (2013) 3323e3330
3329
3358, 1710. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.94 (d, J¼7.48 Hz,
178 (5); HRMS calcd for
207.1050.
C
15H13N1 (Mþ): 207.1048, found
2H), 7.82 (br s, 1H), 7.55 (t, J¼7.34 Hz, 1H), 7.48e7.42 (m, 3H), 7.19 (d,
J¼8.48 Hz,1H), 7.07 (dd, J¼8.56,1.8Hz,1H), 3.28(t, J¼7.62 Hz, 2H), 3.11
(t, J¼7.58 Hz, 2H), 2.76 (t, J¼7.68 Hz, 2H),1.66e1.59 (m, 2H),1.44e1.34
(m, 2H), 0.94 (t, J¼7.32 Hz, 3H). 13C NMR (100 MHz, CDCl3) dC (ppm):
200.0, 137.6, 137.7133.8, 133.8, 133.2, 129.7, 128.7, 128.2, 125.1, 121.4,
117.7, 111.5, 110.5, 39.7, 32.1, 26.0, 22.7, 18.8, 14.1. LRMS (EI) (m/z)
(relative intensity): 339 (Mþ, 100), 220 (86); HRMS calcd for
C21H22Cl1O1N1 (Mþ): 339.1390, found 339.1390.
4.3.22. 2-Phenyl-1H-indole (4b). White solid. Mp: 190e192 ꢀC. FT-
IR (KBr) (
/cmꢁ1): 3430, 1457. 1H NMR (400 MHz, CDCl3) dH
n
(ppm): 8.31 (br s, 1H), 7.68e7.64 (m, 3H), 7.47e7.40 (m, 3H),
7.35e7.32 (m, 1H), 7.23e7.19 (m, 1H), 7.16e7.12 (m, 1H), 6.85 (d,
J¼1.9 Hz, 1H). 13C NMR (100 MHz CDCl3) dC (ppm): 138.1, 137.0,
132.6, 129.4, 129.2, 127.9, 125.3, 122.5, 120.8, 120.5, 111.1, 100.2.
LRMS (EI) (m/z) (relative intensity): 193 (Mþ, 100), 165 (19); HRMS
calcd for C14H11N1 (Mþ): 193.0891, found 193.0895.
4.3.17. 4-(5-Chloro-2-phenyl-1H-indol-3-yl)pentan-2-one (3q). Yield:
(218 mg, 70%); Colorless solid. Mp: 170e171 ꢀC. FT-IR (KBr) ( /cmꢁ1):
n
3423, 1638. 1H NMR (400 MHz, CDCl3) dH (ppm): 8.08 (br s, 1H), 7.70
(d, J¼1.9 Hz, 1H), 7.52e7.44 (m, 4H), 7.42e7.37 (m, 1H), 7.27e7.24 (m,
1H), 7.15e7.12 (m, 1H), 3.79e3.70 (m, 2H), 3.01e2.88 (m, 2H), 1.98 (s,
3H),1.44 (d, J¼7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) dC (ppm): 208.3,
135.9, 134.7, 132.8, 129.0, 128.9, 128.4, 128.3, 125.1, 122.3, 119.7, 116.3,
112.3, 50.5, 30.6, 27.0, 21.5. LRMS (EI) (m/z) (relative intensity): 311
(Mþ, 38), 254 (100); HRMS calcd for C19H18Cl1O1N1 (Mþ): 311.1077,
found 311.1080.
4.3.23. Phenyl(2-phenyl-1H-indol-1-yl)methanone
(4c). Yield:
/cmꢁ1):
(279 mg, 94%); White solid. Mp: 123e125 ꢀC. FT-IR (KBr) (
n
3059, 1686. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.71e7.69 (m, 1H),
7.67e7.61 (m, 3H), 7.41e7.37 (m, 1H), 7.32e7.24 (m, 6H), 7.20e7.16
(m, 2H), 7.15e7.11 (m,1H), 6.78 (s,1H). 13C NMR (100 MHz, CDCl3) dC
(ppm): 170.2, 141.4, 138.4, 135.3, 133.2, 132.9, 130.4, 129.4, 128.5,
128.4, 128.3, 127.7, 124.4, 123.3, 120.9, 114.2, 109.6. LRMS (EI) (m/z)
(relative intensity): 297 (Mþ, 77), 105 (100), 250 (12); HRMS calcd
for C21H15O1N1 (Mþ): 297.1154, found 297.1155.
4.3.18. 4-Phenyl-4-(2-phenyl-1H-indol-3-yl)butan-2-one
(3r). Colorless solid; Yield: (237 mg, 75%); mp: 123e125 ꢀC; FT-IR
4.3.24. 4-((2-(Phenylethynyl)phenyl)amino)butan-2-one (5a). Yield:
(KBr):
n
/cmꢁ1 3401, 1680; 1H NMR (400 MHz, CDCl3) dH (ppm):
(170 mg, 65%); Yellow Liquid. FT-IR (KBr) (n
/cmꢁ1): 3348, 1710. 1H
8.14 (br s, 1H), 7.61 (d, J¼8 Hz, 1H), 7.54e7.52 (m, 2H), 7.47e7.33 (m,
6H), 7.29e7.26 (m, 2H), 7.21e7.17 (m, 2H), 7.12e7.09 (m, 1H), 5.08 (t,
J¼7.3 Hz, 1H), 3.49e3.34 (m, 2H),1.97 (s, 3H). 13C NMR (100 MHz,
CDCl3) dC (ppm): 207.7, 144.6, 136.4, 135.9, 133.1, 129.0, 128.9, 128.6,
128.3, 127.8, 127.6, 126.2, 122.2, 120.8, 119.9, 114.1, 111.4, 49.5, 37.2,
30.5. LRMS (EI) (m/z) (relative intensity): 339 (Mþ, 50), 282 (100),
204 (85), 78 (80); HRMS calcd for C24H21O1N1 (Mþ): 339.1614,
found 339.1623.
NMR (400 MHz, CDCl3) dH (ppm): 7.54 (dd, J¼7.78 Hz, 2H),
7.38e7.31 (m, 4H), 7.23e7.19 (m, 1H), 6.68e6.62 (m, 2H), 5.0 (br
s, 1H), 3.52 (t, J¼6.32 Hz, 2H), 2.79 (t, J¼6.30 Hz, 2H), 2.18 (s, 3H).
13C NMR (100 MHz, CDCl3) dC (ppm): 207.7, 148.5, 132.4, 131.6,
130.1, 128.5, 128.3, 123.5, 116.8, 109.6, 108.2, 95.4, 85.9, 42.9, 38.2,
30.5. LRMS (EI) (m/z) (relative intensity): 263 (Mþ, 58), 206.2
(100), 193 (25); HRMS calcd for C20H21O1N1 (Mþ): 263.1310,
found 263.1316.
4.3.19. 1,3-Diphenyl-3-(2-phenyl-1H-indol-3-yl)propan-1-one
4.3.25. 4-((2-(Cyclopentylethynyl)-5-methylphenyl)amino)butan-2-
one (5b). Yield: (182 mg, 68%); Light Yellow Liquid. FT-IR (KBr) (n/
(3s). Colorless solid; Yield: (307 mg, 70%); mp 98e100 ꢀC; FT-IR
(KBr):
n
/cmꢁ1 3387, 1675; 1H NMR (400 MHz, CDCl3) dH (ppm):
cmꢁ1): 3357, 1712. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.11 (d,
J¼7.63 Hz, 1H), 6.41 (t, J¼7.74 Hz, 2H), 4.72 (br s, 1H), 3.46 (t,
J¼7.96 Hz, 2H), 2.89e2.85 (m, 1H), 2.75 (t, J¼6.32 Hz 2H), 2.27 (s,
2H), 2.17 (s, 3H), 2.16 (s, 3H), 2.02e1.97 (m, 2H), 1.82e1.77 (m, 2H),
1.75e1.71 (m, 2H), 1.70e1.62 (m, 2H). 13C NMR (100 MHz, CDCl3) dC
(ppm): 207.6, 148.2, 139.2, 131.9, 117.6, 110.2, 106.4, 100.0, 43.1, 38.2,
34.4, 31.2, 31.1, 30.5, 25.2, 22.1. LRMS (EI) (m/z) (relative intensity):
269.2 (Mþ, 100), 199.2 (80), 170 (60); HRMS calcd for C20H21O1N1
(Mþ): 269.1780, found 269.1786.
8.05 (br s, 1H), 7.83e7.81 (m, 2H), 7.61 (d, J¼7.96 Hz, 1H) 7.52e7.50
(m, 3H), 7.48e7.41 (m, 2H), 7.40e7.33 (m, 6H), 7.27e7.24 (m, 2H),
7.21e7.15 (m, 2H), 7.11e7.07 (m, 1H), 5.32 (t, J¼6.94 Hz, 1H),
4.01e3.87 (m, 2H). 13C NMR (100 MHz, CDCl3) dC (ppm): 198.8,
144.7, 137.2, 136.4, 135.7, 133.2, 133.0, 129.0, 128.9, 128.6, 128.5,
128.3, 128.2, 128.0, 127.8, 126.1, 122.2, 120.8, 119.9, 114.9, 111.3, 44.6,
37.0, LRMS (EI) (m/z) (relative intensity): 401 (Mþ, 35), 282 (100),
105 (100), 77 (87); HRMS calcd for C29H23O1N1 (Mþ): 401.1788,
found 401.1780.
4.3.26. 4-((4-Chloro-2-(hex-1-yn-1-yl)phenyl)amino)butan-2-one
4.3.20. 3-(6-Methyl-2-phenyl-1H-indol-3-yl)cyclopentanone
(5c). Yield: (199 mg, 72%); Yellow gummy solid; FT-IR (KBr) (n/
(3t). Yield: (147 mg, 51%); Colorless solid. Mp: 208e209 ꢀC. FT-IR
cmꢁ1): 3335, 1702. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.19 (d,
J¼2.32 Hz, 2H), 7.07 (dd, J¼8.74, 2.42 Hz 1H), 6.48 (d, J¼8.8 Hz, 1H),
4.81 (br s, 1H), 3.44 (t, J¼6.3 Hz, 2H), 2.74 (d, J¼6.28 Hz, 2H), 2.46 (t,
J¼7.02 Hz, 2H), 2.16 (s, 3H), 1.62e1.56 (m, 2H), 1.50e1.45 (m, 2H),
0.95 (t, J¼7.28 Hz, 3H). 13C NMR (100 MHz, CDCl3) dC (ppm): 207.4,
147.0,131.6,129.0,121.0,110.6,110.4, 97.6, 75.9, 42.8, 38.3, 31.0, 30.5,
22.2, 19.5, 13.8. LRMS (EI) (m/z) (relative intensity): 277 (Mþ, 100),
279 (50), 220 (42); HRMS calcd for C18H16Cl1 O1N1 (Mþ): 277.1233,
found 277.1236.
(KBr) (n
/cmꢁ1): 3336, 1737. 1H NMR (400 MHz, CDCl3) dH (ppm):
8.00 (br s, 1H), 7.55 (d, J¼8.1 Hz, 1H), 7.52e7.46 (m, 4H), 7.44e7.39
(m, 1H), 7.20 (s, 1H), 6.97 (dd, J¼8.1, 0.9 Hz, 1H), 3.80e3.71 (m, 1H),
2.91e2.83 (m, 1H), 2.61e2.49 (m, 3H), 2.48 (s, 3H). 13C NMR
(100 MHz, CDCl3) dC (ppm): 219.8, 137.0, 134.9, 133.3, 132.3,
129.0, 128.9, 128.2, 124.6, 121.5, 119.7, 113.2, 111.6, 44.8, 39.7,
34.8, 30.1, 21.8. LRMS (EI) (m/z) (relative intensity): 289 (Mþ, 100),
231 (55); HRMS calcd for C20H19O1N1 (Mþ): 289.1467, found
289.1472.
4.3.27. 1-((2-(Phenylethynyl)phenyl)amino)pentan-3-one (5d). Yield:
4.3.21. 6-Methyl-2-phenyl-1H-indole (4a). Yield: (41 mg, 20%);
(216 mg, 78%); Yellow gummy solid. FT-IR (KBr) (n
/cmꢁ1): 3348,
Colorless solid. Mp: 192e193 ꢀC. FT-IR (KBr) (
n
/cmꢁ1): 3430,
1712. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.57 (dd, J¼7.72,
1.48 Hz, 2H), 7.39e7.34 (m, 4H), 7.24e7.20 (m, 1H), 6.69e6.64
(m, 2H), 4.99 (t, J¼5.76 Hz, 1H), 3.54 (q, J¼6.34 Hz, 2H), 2.77 (t,
J¼6.34 Hz, 2H), 2.44 (q, J¼7.34 Hz, 2H), 1.08 (t, J¼7.32 Hz, 3H).
13C NMR (100 MHz, CDCl3) dC (ppm): 210.4, 148.6, 132.4, 131.6,
130.1, 128.5, 128.3, 123.5, 116.7, 109.7, 108.2, 95.4, 85.9, 41.6, 38.3,
36.6, 7.8. LRMS (EI) (m/z) (relative intensity): 277 (Mþ, 45), 206
1453. 1H NMR (400 MHz, CDCl3) dH (ppm): 8.20 (br s, 1H),
7.65e7.63 (m, 2H), 7.53 (d, J¼8.0 Hz, 1H), 7.46e7.42 (m, 2H),
7.34e7.30 (m, 1H), 7.18 (s, 1H), 6.98 (d, J¼8.04 Hz, 1H), 6.80e6.79
(m, 1H) 2.48 (s, 3H). 13C NMR (100 MHz CDCl3) dC (ppm): 137.5,
137.4, 132.7, 132.4, 129.1, 127.6, 127.2, 125.1, 122.2, 120.5, 111.0,
100.0, 22.0. LRMS (EI) (m/z) (relative intensity): 207 (Mþ, 100),

3330
D. Janreddy et al. / Tetrahedron 69 (2013) 3323e3330
(100); HRMS calcd for C19H19O1N1 (Mþ): 277.1467, found
277.1462.
Isono, N.; Lautens, M. Org. Lett. 2009, 11, 1329e1331; (d) Banik, B. K.; Fernandez, M.;
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Rep. 2005, 22, 73e103.
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2009, 351, 2615e2618; (f) Pinhua, L.; Lei, W.; Min, W.; Feng, Y. Eur. J. Org. Chem.
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Kakiuchia, K. Adv. Synth. Catal. 2008, 350, 2498e2502; (i) Ambrogio, I.; Arcadi,
A.; Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett 2007, 1775e1779; (j) Terrasson, V.;
Michaux, J.; Gaucher, A.; Wehbe, J.; Marque, S.; Prim, D.; Campagne, J.-M. Eur. J.
Org. Chem. 2007, 5332e5335; (k) Yan, Y.; Wenying, M.; Zhuo, C.; Gang, Z. J. Org.
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6689e6690.
4.3.28. 1-Phenyl-3-((2-(phenylethynyl)phenyl)amino)propan-1-one
(5e). Yield: (201 mg, 62%); Yellow Liquid. FT-IR (KBr) (n
/cmꢁ1):
3350, 1705. 1H NMR (400 MHz, CDCl3) dH (ppm): 7.98e7.96 (m, 2H),
7.59e7.55 (m, 3H), 7.46 (t, J¼7.6 Hz, 2H) 7.38e7.32 (m, 2H),
7.25e7.21 (m, 1H), 6.72e6.66 (m, 2H), 5.12 (br s, 1H), 3.74 (q,
J¼5.9 Hz, 2H), 3.34 (t, J¼6.36 Hz, 2H). 13C NMR (100 MHz, CDCl3) dC
(ppm): 199.1, 148.6, 136.9, 133.5, 132.4, 131.7130.1, 128.8, 128.5,
128.3, 128.2, 123.5, 116.7, 109.6, 108.2, 95.4, 86.0, 38.6, 38.1. LRMS
(EI) (m/z) (relative intensity): 325 (Mþ, 52), 206 (100); HRMS calcd
for C23H19O1N1 (Mþ): 325.1467, found 325.1468.
Acknowledgements
Financial support for this work by the National Science Council
of the Republic of China (NSC 99-2119-M-003-003-MY2) and Na-
tional Taiwan Normal University (99T3030-2, 99-D, 100-D-06) is
gratefully acknowledged.
5. (a) Yasuhara, A.; Kaneko, M.; Suzuki, N.; Sakamoto, T. Chem. Pharm. Bull. 2002,
50, 235e238; (b) Yasuhara, A.; Kaneko, M.; Sakamoto, T. Heterocycles 1998, 48,
1793e1799.
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M. Chem.dEur. J. 2010, 16, 12746e12753.
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8. Alfonsi, M.; Arcadi, A.; Aschi, M.; Bianchi, G.; Marinelli, F. J. Org. Chem. 2005, 70,
Supplementary data
2265e2273.
Supplementary data related to this article can be found at http://
dx.doi.10.1016/j.tet.2013.01.081.
9. (a) Janreddy, D.; Kavala, V.; Bosco, J. W.; Kuo, C.-W.; Yao, C.-F. Eur. J. Org. Chem.
2011, 2360e2365; (b) Ramesh, C.; Kavala, V.; Kuo, C.-W.; Yao, C.-F. Tetrahedron
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