Efficient and convenient C-3 functionalization of indoles through Ce(OAc)3/TBHP-mediated oxidative C-H bond activation in the presence of β-cyclodextrin

Article abstract of DOI:10.1039/c1gc15639j

A simple, green and efficient protocol for the selective C-3 functionalization of indoles with ketones and olefins via Ce(OAc) ₃-TBHP mediated oxidative C-H activation in the presence of β-cyclodextrin in water has been developed. This atom-eco

Full text of DOI:10.1039/c1gc15639j

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COMMUNICATION
Efficient and convenient C-3 functionalization of indoles through
Ce(OAc)3/TBHP-mediated oxidative C–H bond activation in the presence
of b-cyclodextrin
Yu Lin Hu,* Hui Jiang and Ming Lu*
Received 1st June 2011, Accepted 12th August 2011
DOI: 10.1039/c1gc15639j
A simple, green and efficient protocol for the selective C-
3 functionalization of indoles with ketones and olefins via
Ce(OAc)3-TBHP mediated oxidative C–H activation in the
presence of b-cyclodextrin in water has been developed. This
atom-economical protocol affords the target products in
good to excellent yields. The products can be separated by
a simple extraction with organic solvent, and the catalytic
system can be recycled and reused without loss of catalytic
activity.
concept).11 Therefore, the transition metal-catalyzed arylation of
indoles through direct C–H bond activation have been developed
with some innovative progress in recent years,12 and various
oxidative intermolecular cross-dehydrogenative coupling (CDC)
reactions by using two different C–H bonds have also been
developed (e.g., sp3 C–H with sp3 C–H, sp2 C–H with sp2 C–
H, sp3 C–H with sp2 C–H, sp3 C–H with sp C–H),13 whilst most
of the reactions still have some shortcomings, like high reaction
temperatures, long reaction times, the use of expensive, toxic
and moisture sensitive reagents and difficulties in recycling the
catalyst. Consequently, the development of a more general and
practical method under mild conditions, and preferably using
environmentally friendly and inexpensive reagents, is highly
desirable.
Water is a safe, economical and environmentally-benign
solvent.14 However, the fundamental problem with perform-
ing reactions in water is that many organic substrates are
hydrophobic and insoluble in water. Cyclodextrins (CDs),
obtained from the enzymatic degradation of starch, are cyclic
oligosaccharides possessing hydrophobic cavities, which have
attracted much attention as aqueous-based hosts for inclusion
complex phenomena with a wide variety of guests. Inclusion
complex formation occurs as a result of an interaction between
the hydrophobic cavity of the CD with the hydrophobic portion
of the guest. They can bind substrates selectively, and catalyze
a wide range of chemical and photochemical reactions by
supramolecular catalysis, involving the reversible formation
of host–guest complexes with the substrates by non-covalent
bonding, such as seen in enzymes.15 These attractive features
of CDs prompted us to investigate reactions, under biomimetic
conditions. We herein report an efficient and environmentally
friendly protocol for the direct regioselective C-3 alkylation of
indoles with ketones and olefins to synthesize 3-alkylindoles via
Ce(OAc)3/TBHP-mediated oxidative C–H bond activation in
the presence of b-cyclodextrin (b-CD) in water (Scheme 1).
The investigation was initiated by using the direct alkylation
of 1H-indole with pentan-2-one as a model reaction (Table 1).
Initial reaction screening led to disappointing results in the
absence of a catalyst; the reaction proceeded very slowly, and
the yield was only 27% after 24 h (Table 1, entry 1). The results
mean that the oxidant TBHP alone does not work effectively in
Indoles are key structural units in many natural products
and important pharmaceuticals, and have wide applications in
medicinal chemistry.1,2 In particular, 3-alkylated indoles are im-
portant building blocks for the synthesis of various biologically-
active molecules.2 Therefore, there has been tremendous interest
in developing efficient methods for the synthesis of these
molecules, and a well known method constitutes the Friedel–
Crafts alkylation of indoles. Traditionally, the most common
way for such conversions have been Lewis and Brønsted acid-
promoted reactions.3 However, these protocols, are generally
associated with one or more disadvantages, such as long reaction
times, high reaction temperatures, low yields, complex handling
procedures, problematic side reactions, environmental concerns
associated with the use of poorly manageable catalysts and
the release of large amounts of environmentally hazardous
wastes. To overcome these limitations, the use of transition metal
complexes,4 ionic liquids,5 phase transfer catalysis,6 micellar
catalysis,7 microwaves,8 ultrasonic irradiation9 and others10 have
been applied to accomplish this transformation with different
degrees of success. More recently, selectively-direct C–H bond
activation has been extensively studied. This synthetic strategy
is intriguing for the chemical and pharmaceutical industries
because it may not only significantly simplify and shorten
the synthetic route for various types of organic compounds
but also allow the utilization of readily available, cheap and
environmentally-benign starting materials (the atom economy
College of Chemical Engineering, Nanjing University of Science and
Technology, Nanjing, 210094, P. R. China.
E-mail: huyulin1982@163.com, luming1963@163.com; Fax: +86
025-84315030; Tel: +86 025-84315030
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Scheme 1 Direct C-3 alkylation of indoles with ketones and olefins.
Table 1 Optimization of the conditions for C-3 acylation of 1H-indole with pentan-2-onea
Entry
Catalyst
Oxidant
Time/h
Yield (%)b
1
2
3
4
5
6
7
8
—
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
—
24
12
18
12
12
12
16
16
16
12
12
24
12
14
12
12
12
12
27
75
54
72
84
67
78
69
75c
84d
83e
25
58
46
65
77
75
78
Cu(OAc)2
Zn(OAc)2
Fe(OAc)2
Ce(OAc)3
Pd(OAc)2
CeCl3
CuCl2
9
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
Ce(OAc)3
10
11
12
13
14
15
16
17
18
FeCl3
K2S2O8
AgNO3
DDQ
Ag2O
H2O2
a Reactions were carried out using 1H-indole (1 mmol), pentan-2-one (1.5 mmol), catalyst (0.15 mmol), oxidant (2 mmol) and b-CD (0.1 mmol) in
H2O (2 mL) at 100 ◦C. b Isolated yield. c No b-CD was added. d The first run. e The second run.
the reaction. The effects of different catalysts, such as Cu(OAc)2,
Zn(OAc)2, Fe(OAc)2, Ce(OAc)3, Pd(OAc)2, CeCl3 and CuCl2,
were then screened in this alkylation (Table 1, entries 2–8), and it
was observed that Ce(OAc)3 demonstrated the best performance.
For a blank test (Table 1, entry 9), a lower yield of the product
was obtained when the same reaction condition were used in
the absence of b-CD. This result indicates that b-CD must play
an important role in accelerating the rate of the reaction. In
addition, the oxidant is crucial for this reaction, and its lack
leads to a much lower yield (Table 1, entry 12). Besides TBHP,
we also tried to use other types of oxidants in this model
reaction (Table 1, entries 13–18), and the results showed that
TBHP demonstrated the best performance in terms of yield
and reaction rate. Furthermore, the catalytic system could be
typically recovered and reused with no appreciable decrease in
yield and reaction rate (Table 1, entries 10 and 11). Therefore,
the combination of Ce(OAc)3, TBHP and b-CD was chosen as
the optimal materials for further exploration.
The direct C-3 alkylation of a variety of indoles with
ketones was successful and gave the desired corresponding 3-
alkylindoles in good to excellent yields, as summarized in Table
2. Various types of indoles can be successfully converted to their
corresponding products with pentan-2-one (Table 2, entries 1,
6–9), whereas the electron-deficient indoles were less reactive
(Table 2, entries 8 and 9) than the electron-rich examples (Table
2, entries 6 and 7); longer reaction times were required to achieve
good yields. In addition, in order to examine a greater range
of ketones to better illustrate the scope and limitations of this
protocol, we investigated the reactions with other ketones, such
as octan-2-one, 3-oxobutanenitrile, 1-p-tolylpropan-2-one and
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Table 2 C-3 alkylation of indoles with ketonesa
Entry
1
Indole
Ketone
Product
Time/h
12
Yield (%)b
84
2
3
4
5
6
12
10
10
12
12
78
93
90
85
85
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Table 2 (Contd.)
Entry
7
Indole
Ketone
Product
Time/h
12
Yield (%)b
88
8
16
74
9
16
77
a Reactions were carried out using indole (1 mmol), ketone (1.5 mmol), Ce(OAc)3 (0.15 mmol), TBHP (2 mmol), and b-CD (0.1 mmol) in H2O (2 mL)
at 100 ◦C. b Isolated yield.
cyclohexanone, using 1H-indole as a representative substrate
(Table 2, entries 2–5). Good yields of the expected products
were obtained. It was also observed that the electronic nature of
the substituents on the ketones had some impact on the reaction
rate. Electron-deficient ketones (Table 2, entries 3 and 4) were
more reactive than the electron-rich examples (Table 2, entries
1, 2, and 5), providing excellent yields.
The other portion of this work involved the application of
our catalytic protocol to prepare 3-allylic indoles by the direct
C-3 alkylation of indoles with olefins. The optimal reaction
conditions were found to be the similar to those in the case of
the alkylation of indoles with ketones, and the desired products
were obtained in good to excellent yield (Table 3). The results
reveal that our protocol can facilitate efficiently the direct C-3
alkylation of indoles with olefins. Various indoles were efficiently
converted to their corresponding 3-allylic indoles with olefins
using the catalytic protocol (Table 3, entries 1–8). Olefins such
as but-3-enenitrile and allylbenzene (Table 3, entries 1 and 2)
reacted more quickly than hex-1-ene and cyclohexene (Table 3,
entries 3 and 4), giving products in higher yields, which might
be attributed to the electron deficiency effect. Moreover, the
substituents on the benzene ring of the indole greatly influenced
the reaction; electron-rich indoles (Table 3, entries 5 and 6) were
more reactive than electron-deficient examples (Table 3, entries
7 and 8) and shorter reaction times were needed to reach good
yields. Obviously, our protocol was found to be more effective
for the alkylation of indoles with ketones than for the alkylation
of indoles with olefins, which might be attributed to the different
reactive abilities of the active hydrogen of ketones and olefins.
According to the literature16 and the observations in our
reactions, taking the C-3 acylation of 1H-indole with pentan-2-
one as an example, a possible mechanism is proposed (Scheme
2). In the reaction, the catalyst Ce(OAc)3 provides a source of
Ce(III), which reacts with the oxidant TBHP to form Ce(IV)
O
(2). Then, 2 reacts with the substrate to form transition state
3. 3 then very rapidly affords Ce(III) and water to yield the
desired product. The trivalent cerium ion is then re-oxidized to
Ce(IV) O by TBHP to complete the catalytic cycle. It appears
that the formation of 3 from 2 and the substrate is the rate-
determining step.
In conclusion, we have developed an efficient and convenient
Ce(OAc)3/TBHP-mediated oxidative C–H bond activation be-
tween a carbonylic or allylic sp3 C–H and the C-3 position
of indoles in a b-CD/water system. This novel methodology
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Table 3 C-3 alkylation of indoles with olefinsa
Entry
1
Indole
Olefin
Product
Time/h
12
Yield (%)b
87
2
12
85
3
4
14
14
78
81
5
6
7
14
14
18
82
84
68
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Table 3 (Contd.)
Entry
8
Indole
Olefin
Product
Time/h
18
Yield (%)b
73
a Reactions were carried out using indole (1 mmol), olefin (1.5 mmol), Ce(OAc)3 (0.15 mmol), TBHP (2 mmol) and b-CD (0.1 mmol) in H2O (2 mL)
at 110 ◦C. b Isolated yield.
Vario EL III instrument (Elementar Analysensysteme GmbH,
Germany).
Typical procedure for the reaction (Table 2, entry 1)
To a stirred solution of 1H-indole (1 mmol), Ce(OAc)3
(0.15 mmol), TBHP (2 mmol) and b-CD (0.1 mmol) in H2O
(2 mL) was added pentan-2-one (1.5 mmol), and stirring was
then continued at 100 ◦C for 12 h, the reaction progress
being monitored by HPLC. Upon completion, the reaction was
cooled to room temperature, and the mixture was extracted
with dichloromethane (3 ¥ 10 mL), washed with water (2 ¥
10 mL) and then dried using anhydrous sodium sulfate. Then,
the crude mixture was purified by column chromatography on
silica gel to afford a yellow solid of 3-(1H-indol-3-yl)pentan-2-
one (168.5 mg, 84% yield). The bottom aqueous layer (catalytic
Scheme 2 Possible mechanism for the C-3 acylation of 1H-indole with
pentan-2-one.
system) was concentrated under vacuum and fresh substrates
(1H-indole, TBHP) and H2O were then recharged into the
residual b-CD/Ce(OAc)3; the next run was performed under
identical reaction conditions.
provides an efficient and regioselective approach to directly use
carbonylic or allylic sp3 C–H bonds for the purpose of C–C
bond formation. Advantages of our procedure include simplicity
of operation, good yields, low cost and excellent recyclability of
the catalytic system. The scope, definition of the mechanism and
synthetic application of this reaction are currently under study
in our laboratory.
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.34 (t, 3H, CH3),
2.28 (m, 2H, CH2), 2.67 (s, 3H, CH3), 3.89 (t, 1H, CH), 7.08–
7.17 (m, 2H), 7.24 (s, 1H), 7.38–7.52 (m, 2H), 8.06 (br, 1H,
NH); 13C-NMR (500 MHz, CDCl3): d (ppm) = 18.3, 28.7, 31.2,
60.4, 111.5, 112.8, 118.4, 119.7, 122.1, 123.2, 127.5, 138.2, 209.1;
Elemental analysis % calc. (% found): C 77.51 (77.58), H 7.53
(7.51), N 6.99 (6.96), O 7.92 (7.95).
Experimental
3-(1H-Indol-3-yl)octan-2-one (Table 2, entry 2)
All the chemicals were acquired from commercial sources and
used without any pre-treatment. All reagents were of analytical
grade. NMR spectra were recorded on a Bruker 500-MHz
spectrometer using CDCl3 as the solvent and tetramethylsilane
(TMS) as the internal standard. High performance liquid
chromatography (HPLC) experiments were performed on a
liquid chromatograph (Dionex Softron GmbH, America), con-
sisting of a pump (P680) and ultraviolet-visible light detector
(UVD) system (170U). Elemental analyses were performed on a
1H-NMR (500 MHz, CDCl3): d (ppm) = 0.97 (t, 3H, CH3),
1.24–1.36 (m, 6H, CH2CH2CH2), 1.84 (m, 2H, CH2), 2.47 (s,
3H, CH3), 3.78 (t, 1H, CH), 7.09–7.15 (m, 2H), 7.22 (s, 1H),
7.35–7.54 (m, 2H), 8.09 (br, 1H, NH); 13C-NMR (500 MHz,
CDCl3): d (ppm) = 13.9, 22.8, 25.4, 28.2, 31.3, 32.1, 60.2, 111.3,
112.5, 118.6, 119.4, 121.9, 123.5, 127.2, 137.7, 208.9; Elemental
analysis % calc. (% found): C 78.95 (78.97), H 8.67 (8.70), N
5.77 (5.76), O 6.58 (6.57).
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2-(1H-Indol-3-yl)-3-oxobutanenitrile (Table 2, entry 3)
3-(5-Bromo-1H-indol-3-yl)pentan-2-one (Table 2, entry 9)
1H-NMR (500 MHz, CDCl3): d (ppm) = 2.56 (s, 3H, CH3), 4.82
(s, 1H, CH), 7.12–7.16 (m, 2H), 7.26 (s, 1H), 7.41–7.59 (m, 2H),
8.07 (br, 1H, NH); 13C-NMR (500 MHz, CDCl3): d (ppm) = 27.8,
48.3, 111.0, 111.9, 117.5, 119.2, 120.1, 121.7, 122.6, 127.7, 136.8,
207.6; Elemental analysis % calc. (% found): C 72.67 (72.71), H
5.07 (5.08), N 14.10 (14.13), O 8.09 (8.07).
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.31 (t, 3H, CH3), 2.27
(m, 2H, CH2), 2.65 (s, 3H, CH3), 3.83 (t, 1H, CH), 7.21–7.26 (m,
2H), 7.32–7.43 (m, 2H), 8.10 (br, 1H, NH); 13C-NMR (500 MHz,
CDCl3): d (ppm) = 18.7, 28.4, 30.9, 61.2, 111.4, 113.7, 117.1,
120.6, 123.0, 124.3, 128.7, 137.2, 209.4; Elemental analysis %
calc. (% found): C 63.72 (55.73), H 5.05 (5.04), Br 28.54 (28.52),
N 4.97 (5.00), O 5.69 (5.71).
1-(1H-Indol-3-yl)-1-p-tolylpropan-2-one (Table 2, entry 4)
2-(1H-Indol-3-yl)but-3-enenitrile (Table 3, entry 1)
1H-NMR (500 MHz, CDCl3): d (ppm) = 2.62 (s, 3H, CH3), 2.39
(s, 3H, CH3), 4.75 (s, 1H, CH), 7.02–7.19 (m, 7H), 7.24 (s, 1H),
7.49 (m, 1H), 7.78 (m, 1H), 8.36 (br, 1H, NH); 13C-NMR (500
MHz, CDCl3): d (ppm) = 21.7, 28.2, 74.6, 111.3, 118.6, 119.7,
120.5, 121.2, 121.9, 122.5, 126.4, 127.8, 129.6, 136.5, 137.2,
209.4. Elemental analysis % calc. (% found): C 82.09 (82.10),
H 6.53 (6.51), N 5.36 (5.32), O 6.07 (6.08).
1H-NMR (500 MHz, CDCl3): d (ppm) = 4.27 (d, 1H), 5.17 (m,
2H), 5.86 (m, 1H), 7.07–7.21 (m, 3H), 7.42 (d, 1H), 7.75 (d, 1H),
8.25 (br, 1H, NH); 13C-NMR (500 MHz, CDCl3): d (ppm) =
38.5, 110.7, 111.6, 118.5, 119.7, 120.5, 122.4, 123.2, 128.5, 133.6,
138.7; Elemental analysis % calc. (% found): C 79.11 (79.10), H
5.50 (5.53), N 15.38 (15.37).
3-(1-Phenylallyl)-1H-indole (Table 3, entry 2)
1H-NMR (500 MHz, CDCl3): d (ppm) = 4.74–4.89 (m, 3H),
6.27 (m, 1H), 6.97–7.34 (m, 8H), 7.64 (m, 1H), 7.83 (m, 1H),
8.49 (br, 1H, NH); 13C-NMR (500 MHz, CDCl3): d (ppm) =
59.4, 111.6, 119.4, 120.2, 120.9, 121.8, 122.3, 124.9, 128.2, 129.1,
130.5, 132.7, 137.6, 140.8, 144.2; Elemental analysis % calc. (%
found): C 87.50 (87.52), H 6.51 (6.48), N 5.97 (6.00).
2-(1H-Indol-3-yl)cyclohexanone (Table 2, entry 5)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.75–1.87 (m, 6H,
CH2CH2CH2), 2.36 (t, 2H, CH2), 3.62 (t, 1H, CH), 7.09–7.14
(m, 2H), 7.22 (s, 1H), 7.41–7.62 (m, 2H), 8.12 (br, 1H, NH);
13C-NMR (500 MHz, CDCl3): d (ppm) = 26.2, 27.8, 36.5, 44.3,
59.1, 111.6, 112.3, 119.0, 120.4, 121.4, 123.1, 126.5, 136.9, 209.8.
Elemental analysis % calc. (% found): C 78.83 (78.84), H 7.06
(7.09), N 6.58 (6.57), O 7.47 (7.50).
3-(Hex-1-en-3-yl)-1H-indole (Table 3, entry 3)
1H-NMR (500 MHz, CDCl3): d (ppm) = 0.95 (t, 3H, CH3), 1.28
(m, 2H, CH2), 1.64 (m, 2H, CH2), 3.78 (m, 1H, CH), 5.07–5.18
(m, 3H), 7.05–7.21 (m, 3H), 7.37 (d, 1H), 7.68 (m, 1H), 8.27
(br, 1H, NH); 13C-NMR (500 MHz, CDCl3): d (ppm) = 15.7,
20.9, 41.3, 52.5, 110.7, 111.9, 116.4, 118.2, 120.5, 122.0, 124.2,
127.5, 138.7, 142.4; Elemental analysis % calc. (% found): C
84.36 (84.37), H 8.57 (8.60), N 7.01 (7.03).
3-(5-Methyl-1H-indol-3-yl)pentan-2-one (Table 2, entry 6)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.32 (t, 3H, CH3), 2.28
(m, 2H, CH2), 2.65 (s, 3H, CH3), 2.72 (s, 3H, CH3), 3.85 (t,
1H, CH), 7.10–7.28 (m, 3H), 7.54 (s, 1H), 8.08 (br, 1H, NH);
13C-NMR (500 MHz, CDCl3): d (ppm) = 18.5, 23.2, 28.8, 31.0,
60.7, 111.3, 112.1, 118.7, 120.5, 123.4, 127.6, 129.4, 135.7, 209.3;
Elemental analysis % calc. (% found): C 78.07 (78.10), H 7.92
(7.96), N 6.53 (6.51), O 7.42 (7.43).
3-(Cyclohex-2-enyl)-1H-indole (Table 3, entry 4)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.72–2.07 (m, 6H,
CH2CH2CH2), 3.56 (m, 1H, CH), 5.46–5.51 (m, 2H), 7.07–7.24
(m, 3H), 7.45 (m, 1H), 7.72 (m, 1H), 8.59 (br, 1H, NH); 13C-
NMR (500 MHz, CDCl3): d (ppm) = 23.1, 25.4, 33.7, 44.8,
111.3, 112.4, 119.2, 120.5, 122.2, 123.5, 127.6, 128.5, 131.4,
137.7; Elemental analysis % calc. (% found): C 85.20 (85.24),
H 7.67 (7.66), N 7.08 (7.10).
3-(5-Methoxy-1H-indol-3-yl)pentan-2-one (Table 2, entry 7)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.35 (t, 3H, CH3), 2.26
(m, 2H, CH2), 2.64 (s, 3H, CH3), 3.87 (t, 1H, CH), 3.92 (s, 3H,
CH3), 7.01–7.12 (m, 2H), 7.23–7.29 (m, 2H), 8.11 (br, 1H, NH);
13C-NMR (500 MHz, CDCl3): d (ppm) = 18.7, 28.4, 31.0, 53.9,
60.5, 102.6, 111.9, 112.3, 112.7, 123.5, 128.2, 129.4, 151.5, 208.7;
Elemental analysis % calc. (% found): C 72.69 (72.70), H 7.42
(7.41), N 6.04 (6.06), O 13.82 (13.83).
3-(Cyclohex-2-enyl)-5-methyl-1H-indole (Table 3, entry 5)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.68–2.35 (m, 9H),
3.69 (m, 1H, CH), 5.43–5.52 (m, 2H), 7.21–7.35 (m, 3H), 7.75
(m, 1H), 8.67 (br, 1H, NH); 13C-NMR (500 MHz, CDCl3): d
(ppm) = 21.3, 23.8, 25.7, 33.6, 45.4, 111.5, 111.9, 120.1, 121.5,
123.9, 127.8, 129.2, 130.7, 132.5, 136.8; Elemental analysis %
calc. (% found): C 85.21 (85.26), H 8.13 (8.11), N 6.67 (6.63).
3-(5-Nitro-1H-indol-3-yl)pentan-2-one (Table 2, entry 8)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.27 (t, 3H, CH3), 2.25
(m, 2H, CH2), 2.63 (s, 3H, CH3), 3.81 (t, 1H, CH), 7.21 (s, 1H),
7.46 (d, 1H), 7.87–7.95 (m, 2H), 8.13 (br, 1H, NH); 13C-NMR
(500 MHz, CDCl3): d (ppm) = 19.3, 27.9, 30.6, 60.8, 111.2,
112.4, 114.7, 122.8, 127.3, 129.2, 131.5, 142.4, 209.7; Elemental
analysis % calc. (% found): C 63.41 (63.40), H 5.71 (5.73), N
11.39 (11.38), O 19.47 (19.49).
3-(Cyclohex-2-enyl)-5-methoxy-1H-indole (Table 3, entry 6)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.65–2.12 (m, 6H,
CH2CH2CH2), 3.47 (m, 1H, CH), 3.78 (s, 3H, CH3), 5.51–5.62
(m, 2H), 6.92–7.13 (m, 2H), 7.21–7.28 (m, 2H), 8.53 (br, 1H,
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NH); 13C-NMR (500 MHz, CDCl3): d (ppm) = 21.7, 24.5, 33.5,
44.7, 58.7, 103.4, 111.5, 112.3, 114.7, 123.5, 127.4, 128.7, 132.6,
134.5, 152.7; Elemental analysis % calc. (% found): C 79.24
(79.26), H 7.51 (7.54), N 6.17 (6.16), O 7.02 (7.04).
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3-(Cyclohex-2-enyl)-5-nitro-1H-indole (Table 3, entry 7)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.62–2.04 (m, 6H,
CH2CH2CH2), 3.42 (m, 1H, CH), 5.53–5.65 (m, 2H), 7.19 (s,
1H), 7.52 (d, 1H), 7.91–8.05 (m, 2H), 8.37 (br, 1H, NH); 13C-
NMR (500 MHz, CDCl3): d (ppm) = 22.4, 24.8, 34.1, 43.6,
110.7, 113.5, 115.6, 124.0, 125.8, 128.2, 129.3, 132.4, 134.1,
149.2; Elemental analysis % calc. (% found): C 69.37 (69.41),
H 5.83 (5.82), N 11.55 (11.56), O 13.20 (13.21).
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5-Bromo-3-(cyclohex-2-enyl)-1H-indole (Table 3, entry 8)
1H-NMR (500 MHz, CDCl3): d (ppm) = 1.67–1.98 (m, 6H,
CH2CH2CH2), 3.46 (m, 1H, CH), 5.48–5.64 (m, 2H), 7.15–7.27
(m, 2H), 7.37–7.46 (m, 2H), 8.33 (br, 1H, NH); 13C-NMR (500
MHz, CDCl3): d (ppm) = 21.8, 25.2, 34.5, 44.1, 111.5, 114.4,
117.3, 122.7, 123.9, 125.3, 127.5, 130.8, 133.2, 139.5; Elemental
analysis % calc. (% found): C 60.87 (60.89), H 5.09 (5.11), Br
28.92 (28.93), N 5.10 (5.07).
Acknowledgements
We thank the National Basic Research Program (973) of China
(no. 613740101) and the NSFC-NSAF Program (no. 11076017)
for their support of this research.
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