Iron-Promoted Construction of Indoles via Intramolecular Oxidative C-N Coupling of 2-Alkenylanilines Using Persulfate

Article abstract of DOI:10.1055/s-0037-1611521

Indole scaffold synthesis relies primarily on oxidative C-H amination of N-protected alkenylanilines for C-N intramolecular cyclization reactions. Herein, for the first time, without N-protection, various readily prepared 2-alkenylanilines were transformed into the desired indole products in good yields by using K ₂ S ₂ O ₈ as oxidant in the presence of catalytic amounts of FeF ₂. The K ₂ S ₂ O ₈ /FeF ₂ system offers a direct and benign synthetic route to 3-arylindoles and it is applicable to a wide range of substituted indoles including drug intermediates.

Full text of DOI:10.1055/s-0037-1611521

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–F
paper
A
en
M. Wang et al.
Paper
Synthesis
Iron-Promoted Construction of Indoles via Intramolecular Oxidative
C–N Coupling of 2-Alkenylanilines Using Persulfate
Menglan Wanga,b
Yudong Lib
Qing-An Wu*a
Shuping Luoa
Yuehui Li*b
R1
R1
K2S2O8 (3.0 equiv)
FeF2 (10 mol%)
R2
R2
R'
R'
Et3N (0.5 equiv)
THF, 70 °C, 16 h
N
NH2
H
Good group tolerance
16 examples
R = Alkyl or Aryl
One-pot reaction
Cheap reagents
No N-protection
Mild conditions
a State Key Laboratory Breeding Base of Green Chemistry-Synthesis
Technology, Zhejiang University of Technology, Hangzhou 310014,
P. R. of China
Appreciable yields up to 80%
qawu@zjut.edu.cn
b State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Suzhou Research Institute of LICP, Lanzhou Institute of Chemical
Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000,
P. R. of China
yhli@licp.cas.cn
Received: 15.02.2019
Accepted after revision: 01.04.2019
Published online: 30.04.2019
bonds have been reported by groups of Cacchi,8a de Lera,8b
and Liu,8c using palladium-catalyzed reactions. The groups
of Saá,9a Xi,9b Maiti,9c and Li9d have also reported the synthe-
sis of 2-substituted indoles from anilines and olefins by us-
ing Rh(III) or Pd(II) catalyst. While Youn and co-workers
used palladium as catalyst for an aza-Wacker type indole
synthesis from tosylated 2-alkenylanilines, Cheng’s group
also reported copper-mediated intramolecular aza-Wacker-
type cyclization of 2-alkenylanilines toward 3-aryl in-
doles.11
DOI: 10.1055/s-0037-1611521; Art ID: ss-2019-h0099-op
Abstract Indole scaffold synthesis relies primarily on oxidative C–H
amination of N-protected alkenylanilines for C–N intramolecular cy-
clization reactions. Herein, for the first time, without N-protection, var-
ious readily prepared 2-alkenylanilines were transformed into the de-
sired indole products in good yields by using K2S2O8 as oxidant in the
presence of catalytic amounts of FeF2. The K2S2O8/FeF2 system offers a
direct and benign synthetic route to 3-arylindoles and it is applicable to
a wide range of substituted indoles including drug intermediates.
CO2H
Key words indoles, C–N coupling, 2-alkenylanilines, oxidative amina-
tion, iron catalysis, 3-arylindoles, unprotected anilines
O
MeO
Me
N
The indole skeleton is a widely encountered structural
motif in naturally occurring and synthetic bioactive com-
pounds.1 The indole scaffold is present in many potent
drugs and is regarded as a privileged motif for the design
and development of therapeutic agents. 3-Aryl indole de-
rivatives constitute an important structural core of many
pharmaceuticals such as Murrapanine, Binedaline, and Se-
rotonin 5-HT2 antagonist, which are known to possess bio-
logical activity as anticancer, antidepressant and antipsy-
chotic medications (Figure 1).2 Moreover, the indole struc-
tural motif has also found many applications beyond
biology in chemicals and materials sciences.3 Since the orig-
inal Fisher synthesis of indole from phenylhydrazine and
ketones followed by Nenitzescu synthesis of hydroxyindole
derivatives, a great number of procedures have been devel-
oped.4
O
OMe
O
N
Cl
H
Indomethacin
Murrapanine
(anticancer)
F
N
N
NMe2
N
R
Binedaline
(antidepressant)
Serotonin 5-HT2 antagonist
(antipsychotic drug)
Figure 1 Bioactive drugs based on 3-arylindole derivatives
Moreover, various approaches have been developed for
the direct oxidative amination coupling of alkenes in indole
synthesis using solely oxidants and excluding transition
metals (Scheme 1). For example, the use of ArI(OAc)2 (3,5-
Me2-C6H3I(OAc)2) and 2,3-dichloro-5,6-dicyano-1,4-benzo-
quinone (DDQ) were used to affect this transformation with
N-tosylated 2-alkenylanilines.5,6 Deng’s work prominently
The widespread applications of the indolic moiety
prompted the development of more efficient procedures for
its construction, especially using oxidant and/or transition-
metal catalytic methods, which remain an area of intensive
research.5–7 In this regard, transition-metal-catalyzed cy-
clization of 2-alkynyanilines for constructing new C–N/C–C
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–F

B
M. Wang et al.
Paper
Synthesis
uses molecular oxygen to transform N-tosylated 2-alke-
nylanilines and prepare N-Ts-indoles.7 Although this reac-
tion has been researched extensively, alkenylanilines that
were not N-alkylated were not studied in most of these
transformations, because of possible oxidative side reac-
tions.12 Thus, we wanted to explore the potential of direct
heterocyclic indole formation from free ‘NH’ unprotected
alkenylanilines using common oxidants.
Herein, we report an efficient synthesis of substituted
indoles with potassium persulfate for intramolecular C–H
amidation of 2-alkenylanilines promoted by Fe(II) salts in
the presence of triethylamine. 2-Alkenylanilines substrates,
not limited to monosubstituted terminal alkenes, could
easily be transformed into 3-substituted and 2,3-disubsti-
tuted indoles. This is a complementary approach to the
above mentioned protocols of intramolecular cyclization of
-substituted 2-alkenylanilines. The reactions proceeded
smoothly and the corresponding indoles were obtained in
typically good yields as single products. This protocol uses
primarily unprotected alkenylanilines, mild oxidant with
iron salts as catalysts and is distinct from previously report-
ed protocols for amine and alkene coupling reactions
(Scheme 1).
screened but only K2S2O8 afforded product 2a in 13% yield
(Table 1). We then screened the effect of several metal salts
in the presence of K2S2O8. We found iron salts FeF2 and FeF3
were more effective in combination with K2S2O8. To our de-
light, when FeF2 was used as catalyst in the presence of
K2S2O8 as oxidant, the desired product 2a was obtained in
28% isolated yield (entry 10). To further enhance the reac-
tion, we explored the effects of base as additives. We found
that addition of Et3N improved the reaction by increasing
the yield to 35% (entries 11–13).
Furthermore, we found that lowering the reaction tem-
perature to 70 °C was remarkably beneficial and afforded
the target product in 73% yield. During our investigation of
the optimal reaction conditions, we found that K2S2O8 re-
quires iron catalyst FeF2 and base Et3N promotion for effi-
cient conversion of 2-vinylanilines into the corresponding
indole products. Interestingly, reaction of 2-vinylanilines
Table 1 Optimization of Reaction Conditionsa
K2S2O8 (3.0 equiv)
FeF2 (10 mol%)
Et3N (0.5 equiv)
THF, 16 h
NH2
a) Deng's work: (ref. 7)
N
R1
H
O2
1
2
R1
R'
R'
DMSO/dioxane = 1/1
120 °C, 24 h
N
NHTs
Entry
Oxidant
Lewis acid
Base (0.5 equiv) Yield (%)
Ts
b) Mo's work: (ref.5)
R1
R1
1
2
BQ
–
–
trace
0
R2
ArI(OAc)2
TBPB
–
–
R'
R2
R'
CH3CN, 100 °C
NH
R
N
3
H2O2
–
–
0
R
R1
R = Ts, Ac, Bn
4
DDQ
–
–
trace
13
trace
trace
0
c) Youn's work: (ref. 6)
R1
R3 = H
5
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
–
–
R2
R'
R'
R2
6
AgOTf
CoCl2
NiCl2
FeF3
FeF2
FeF2
FeF2
FeF2
–
–
N
DDQ
R'
Ts
R2
R3
7
–
CH3CCl3,
120 °C
NH
Ts
8
–
R
1 = H
R2 = Aryl
R3 = H
R3
9
–
23
28
35
0
N
d) Others' work: (ref. 9–11)
R1
Ts
10
11
12
13
14b
15b
16b
17b
18c
19d
–
R1
Et3N
DBU
Na2CO3
–
R2
[Pd] / [Rh] / [Cu]
Oxidant
R2
R'
R'
N
NH
0
R
R
40
51
73
63
68
5
R = Ts, Aryl
R1
Our work:
–
Et3N
Et3N
–
R1
K2S2O8 (3.0 equiv)
FeF2 (10 mol%)
R2
FeF2
FeF2
FeF2
FeF2
R2
R'
R'
Et3N (0.5 equiv)
THF, 70 °C, 16 h
N
NH2
H
Et3N
Et3N
Scheme 1 Metal and/or metal-free indole synthesis from 2-alkenylani-
lines
a Reaction conditions: 1 (0.3 mmol), Lewis acid (0.1 equiv), K2S2O8 (3.0
equiv), 120 °C, 16 h, isolated yield; BQ = benzoquinone; TBPB = tert-butyl
peroxybenzoate.
Initially, we employed 2-vinylaniline 1a as model sub-
strate, which was easily synthesized through Wittig reac-
tion. Various commonly used molecular oxidants were
b 70 °C.
c 60 °C.
d 40 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–F

C
M. Wang et al.
Paper
Synthesis
with K2S2O8 alone provided the target product in 40% yield,
while the addition of triethylamine improved the reaction
to 51% yield upon lowering reaction temperature to 70 °C in
the absence of FeF2 (Table 1, entries, 14–16).
while electron-donating groups afforded better yield (2k,
67%). However, substrates bearing an electron-withdrawing
cyano group on the vinyl moiety (R1 = cyano, R2, R′ = H) or
nitro group on the aromatic ring (R′ = nitro, R1 = phenyl, R2 =
H) resulted in no desired reaction. The double substitution
at the alkene moiety of vinylanilines where R1 is an aryl and
R2 is either methyl or an ethyl group gave the corresponding
indoles in lower yields (2m–p, 31–51%). The observed lower
yields are presumably due to steric hindrance (Scheme 2).
The efficiency and ease of this protocol is a result of
concerted action of iron catalyst mediated by persulfate and
assisted by triethylamine. We next focused on the mecha-
nism of this reaction starting with control experiments.
Firstly, the formation of indole product 2 was unsuccessful
upon adding 4 equivalents of 2,2,6,6-tetramethylpiperi-
dine-1-oxyl (TEMPO) to the model reaction, suggesting that
the reaction may involve a radical process (Scheme 3, eq. 1).
Secondly, FeF2 can be oxidized under the reaction condi-
tions and therefore we deliberately added FeF3 to rule out
Fe(III) catalysis (Scheme 3, eq. 2).
With the optimal reaction conditions established, we
examined the substrate scope with respect to various sub-
stitutions on 2-vinylaniline. Reactions of anilines having
electron-withdrawing or electron-donating groups pro-
ceeded efficiently with moderate to good yield (Scheme 2).
1H-Indole was obtained from vinylanilines, where R1, R2,
R′ = H, in moderate yield (2a, 45%). Substitution with methyl
or phenyl at the indole 3-position where R2, R′ = H, R1 = Me
or Ph afforded indole derivatives in good yield (2b, 2c; 54%,
73%). Tolyl substitution at the 3-position gave indoles 2d–f
in 71%, 78%, and 53% yields. Vinylanilines with R1 substitu-
tion with haloaryls gave products in slightly lower yields
(2g–i, 38–52%). Indolic products where R′ is electron-with-
drawing were also obtained in lower yield (2j, 2l; 42%, 39%),
R1
R1
K2S2O8 (3.0 equiv)
Ph
FeF2 (10 mol%)
R2
Ph
R2
standard conditions
R'
R'
(1)
Et3N (0.5 equiv)
THF, 70 oC, 16 h
N
TEMPO (4.0 equiv)
H
NH2
N
H
NH2
1
2
no reaction
Ph
Ph
FeF3 (3.0 equiv)
(2)
Et3N (0.5 equiv)
THF, 70 °C
N
H
NH2
no reaction
N
N
N
H
N
H
H
H
Scheme 3 Control experiments
2a, 45%
2b, 54%
2c, 73%
2d, 71%
F
On the basis of our experimental results and on litera-
ture reports,12–14 we propose a tentative reaction pathway
for this catalytic system (Scheme 4). Initially, oxidation of 2-
alkynyaniline (a) by K2S2O8 in the presence of Fe salts gen-
erates amino radical cation (b), wherein [Fe] functions to
pull the nitrogen atom and the C=C bond together to form
intermediate (c). This is followed by deprotonation to form
(d) and subsequent oxidation generates intermediate (e).
Finally, deprotonation gives the target product (f).
In summary, we have developed an iron-catalyzed di-
rect coupling of alkene and amine to form indoles. The in-
tramolecular C–N coupling was promoted efficiently by
FeF2 and potassium persulfate as oxidant. The amines of vi-
nylaniline substrates were unprotected and the transforma-
tion was carried out under relatively mild conditions. This
protocol offers an efficient method to access 3-substituted
indoles conveniently with relatively good group tolerance of
functionalized alkenes.
Br
N
H
N
H
N
H
N
H
2e, 78%
2f, 53%
2g, 52%
2h, 38%
Cl
F
Cl
Cl
N
N
N
H
N
H
H
H
2i, 46%
2j, 42%
2k, 67%
2l, 39%
F
Cl
N
N
H
N
H
N
H
H
2m, 40%
2n, 50%
2o, 51%
2p, 31%
Scheme 2 Substrate scope examination. Reaction conditions: 1
(0.3 mmol), FeF2 (0.1 equiv), K2S2O8 (3.0 equiv), Et3N (0.5 equiv) at
70 °C for 16 h. Yields refer to isolated compounds.
Unless stated otherwise, reactions were conducted in flame-dried
glassware under air using anhydrous solvents (freshly distilled). Com-
mercially available reagents were used as received. Substituted 2-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–F

D
M. Wang et al.
Paper
Synthesis
Ph
N
Ph
N
Ph
O
O
O
[Fe]
K2S2O8
[Fe]
– [Fe]
O
S
S
O
O
O
O
O
NH2
H
O
H
H
O
O
H
S
S
O
O
(c)
O
O
(a)
(b)
Ph
– H+
Ph
Ph
K2S2O8
base
– H+
N
N
N
H
H
H
(d)
(e)
(f)
Scheme 4 Proposed reaction pathway
aminobenzophenone and alkyltriphenylphosphonium bromide and
all metal salts were purchased from Alfa Aesar, TCI and Aladdin. Sub-
stituted 2-vinylanilines were prepared according to the literature. Re-
action temperatures were controlled with an IKAmag temperature
modulator. Reactions were monitored using thin-layer chromatogra-
phy (TLC) on commercial silica gel plates (HSGF254). Visualization of
the developed plates was performed under UV light (254 nm). 300–
400 mesh silica gel (Qingdao, China) was used for flash column chro-
matography. 1H NMR spectra were recorded with Bruker spectrome-
ters (400 MHz) and are reported relative to tetramethylsilane (TMS)
as internal standard. Data for 1H NMR spectra are reported as follows:
chemical shift (, ppm), multiplicity, coupling constant (Hz) and inte-
gration. 13C NMR spectra were recorded with Bruker Spectrometers
(100 MHz). 13C NMR spectra were calibrated with CDCl3 ( = 77.0
ppm). The following abbreviations are used: s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet. All measurements were carried
out at r.t. unless otherwise stated.
3-Phenylindole (2c)17
Yield: 42.5 mg (73%); white solid; mp 78–80 °C; Rf = 0.68 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 8.23 (s, 1 H), 7.87 (d, J = 7.6 Hz, 1 H),
7.61 (s, 2 H), 7.43 (d, J = 7.2 Hz, 1 H), 7.31–7.12 (m, 6 H).
13C NMR (100 MHz, CDCl3):  = 136.6, 129.0, 128.9, 125.7, 123.3,
122.5, 121.6, 120.4, 119.5, 115.7, 115.5, 111.4.
3-(m-Tolyl)-1H-indole (2d)18
Yield: 44.1 mg (71%); pale-yellow solid; mp 74–76 °C; Rf = 0.67 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 8.14 (s, 1 H), 7.89 (d, J = 8.0 Hz, 1 H),
7.43–7.35 (m, 3 H), 7.30–7.28 (m, 2 H), 7.20–7.11 (m, 2 H), 7.06–7.04
(d, J = 8.0 Hz, 1 H), 2.37 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 135.5, 128.6, 128.2, 126.8, 124.6,
122.4, 121.7, 120.2, 119.9, 111.3, 21.6.
Indoles 2; General Procedure
3-(p-Tolyl)-1H-indole (2e)18
To a solution of the 2-vinylaniline (0.3 mmol) and catalyst FeF2 (0.03
mmol, 2.8 mg) in THF (3 mL) was added K2S2O8 (0.9 mmol, 0.2433 g)
and Et3N (0.15 mmol, 21 μL), open to the air. The mixture was stirred
at 70 °C for 16 h, then diluted with water (10 mL) and extracted with
CH2Cl2 (3 × 10 mL). The combined organic extracts were washed with
brine and dried with Na2SO4, filtered and concentrated under vacuum
(eluted with EtOAc/hexane 1:20 to 1:5) to give the corresponding
product.
Yield: 48.5 mg (78%); white solid; mp 88–90 °C; Rf = 0.68 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 8.20 (s, 1 H), 7.92 (d, J = 8.0 Hz, 1 H),
7.56 (d, J = 8.0 Hz, 2 H), 7.42 (d, J = 8.0 Hz, 2 H), 7.34 (s, 1 H), 7.27–7.17
(m, 4 H), 2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 136.7, 135.6, 132.6, 129.5, 127.4,
122.3, 121.5, 120.2, 119.9, 111.4, 21.2.
Indole (2a)15
3-(o-Tolyl)-1H-indole (2f)19
Yield: 15.9 mg (45%); white solid; mp 51–54 °C; Rf = 0.72 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.81 (s, 1 H), 7.64 (d, J = 7.8 Hz, 1 H),
7.27–7.18 (m, 1 H), 7.16–7.04 (m, 3 H), 6.52 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 135.5, 127.6, 124.2, 121.8, 120.6,
119.7, 111.0, 102.3.
Yield: 31.5 mg (52%); pale-yellow oil; Rf = 0.67 (hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 8.08 (s, 1 H), 7.48 (d, J = 8.8 Hz, 1 H),
7.36 (d, J = 5.6 Hz, 2 H), 7.28–7.10 (m, 6 H), 2.28 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 136.9, 135.9, 134.5, 130.9, 130.4,
127.2, 126.8, 125.7, 122.8, 122.2, 120.2, 120.0, 117.5, 111.2, 20.8.
3-(4-Fluorophenyl)-1H-indole (2g)16
3-Methylindole (2b)16
Yield: 32.3 mg (52%); brown solid; mp 96–98 °C; Rf = 0.65 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 8.05 (s, 1 H), 7.78 (d, J = 8.0 Hz, 1 H),
7.50 (t, J = 8.0 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 1 H), 7.17–7.08 (m, 3 H),
7.06–7.01 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 161.5, 136.5, 131.5, 131.5, 128.9,
128.8, 125.7, 122.5, 121.6, 120.4, 119.5, 117.3, 115.7, 115.5, 111.4.
Yield: 21.3 mg (54%); yellow solid; mp 94–96 °C; Rf = 0.68 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.83 (s, 1 H), 7.72 (d, J = 7.2 Hz, 1 H),
7.42 (d, J = 8.1 Hz, 1 H), 7.34–7.24 (m, 2 H), 7.03 (s, 1 H), 2.46 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 136.3, 128.3, 121.9, 121.7, 119.2,
118.9, 111.7, 111.1, 9.8.
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M. Wang et al.
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Synthesis
3-(3-Bromophenyl)-1H-indole (2h)20
13C NMR (100 MHz, CDCl3):  = 135.3, 135.2, 132.4, 131.2, 129.3,
129.2, 127.9, 121.4, 119.8, 118.8, 114.3, 110.2, 21.2, 12.4.
Yield: 30.5 mg (38%); white solid; mp 71–73 °C; Rf = 0.61 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 8.27 (s, 1 H), 7.91 (d, J = 7.6 Hz, 1 H),
7.80 (s, 1 H), 7.59 (d, J = 7.6 Hz, 1 H), 7.42–7.19 (m, 6 H).
2-Ethyl-3-(4-fluorophenyl)-1H-indole (2o)24
Yield: 36.6 mg (51%); yellow oil; Rf = 0.63 (hexane/EtOAc, 10:1).
1H NMR (100 MHz, CDCl3):  = 7.98 (s, 1 H), 7.64 (d, J = 7.6 Hz, 1 H),
7.50–7.43 (m, 3 H), 7.34–7.28 (m, 2 H), 7.19–7.09 (m, 2 H), 2.91–2.85
(m, 2 H), 1.31 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 137.9, 137.7, 136.6, 130.2, 128.8,
125.9, 125.5, 122.8, 122.7, 122.1, 120.6, 119.5, 111.5.
3-(4-Chlorophenyl)-1H-indole (2i)16
13C NMR (100 MHz, CDCl3):  = 139.8, 139.2, 137.2, 135.5, 135.2,
129.6, 128.5, 125.9, 121.6, 120.0, 119.0, 113.9, 110.4, 19.7, 14.3.
Yield: 31.8 mg (46%); brown solid; mp 134–135 °C; Rf = 0.63 (hex-
ane/EtOAc, 10:1).
1H NMR (100 MHz, CDCl3):  = 8.23 (s, 1 H), 7.88 (d, J = 7.6 Hz, 1 H),
7.59 (d, J = 6.8 Hz, 2 H), 7.43–7.33 (m, 4 H), 7.26–7.20 (m, 2 H).
5-Chloro-2-methyl-3-phenyl-1H-indole (2p)25
Yield: 22.5 mg (31%); yellow oil; Rf = 0.30 (hexane/EtOAc, 10:1).
1H NMR (100 MHz, CDCl3):  = 7.96 (s, 1 H), 7.60 (s, 1 H), 7.46 (d, J =
4.4 Hz, 4 H), 7.32–7.30 (m, 1 H), 7.24–7.20 (m, 1 H), 7.11–7.09 (m,
1 H), 2.48 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 136.7, 134.1, 131.6, 128.9, 128.6,
125.6, 122.6, 121.8, 120.5, 119.6, 111.5.
5-Chloro-3-phenyl-1H-indole (2j)18
13C NMR (100 MHz, CDCl3):  = 134.7, 133.6, 132.9, 129.3, 129.1,
128.6, 126.1, 125.8, 121.7, 118.3, 111.2, 12.5.
Yield: 28.7 mg (42%); white solid; mp 88–90 °C; Rf = 0.41 (hex-
ane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 8.16 (s, 1 H), 7.81 (s, 1 H), 7.54 (d, J =
8.0 Hz, 2 H), 7.37 (t, J = 4.0 Hz, 2 H), 7.28–7.21 (m, 3 H), 7.16–7.11 (m,
1 H).
13C NMR (100 MHz, CDCl3):  = 135.0, 134.8, 128.9, 127.5, 126.3,
126.2, 123.0, 122.8, 119.3, 118.3, 112.4.
Funding Information
The authors acknowledge financial support of this work by the Na-
tional Natural Science Foundation of China (21633013, 21101109,
21602228) and Natural Science Foundation of Jiangsu Province
(BK20160394).
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Yield: 41.7 mg (67%); yellow solid; mp 95–98 °C; Rf = 0.65 (hex-
ane/EtOAc, 10:1).
Supporting Information
1H NMR (400 MHz, CDCl3):  = 8.23 (s, 1 H), 7.53 (d, J = 7.6 Hz, 1 H),
7.46–7.44 (m, 2 H), 7.35–7.33 (m, 1 H), 7.28–7.23 (m, 3 H), 7.20 (d, J =
2.4 Hz, 1 H), 7.17–7.13 (m, 1 H), 2.34 (s, 3 H).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611521.
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13C NMR (100 MHz, CDCl3):  = 138.3, 136.7, 135.4, 128.7, 128.3,
126.8, 124.6, 122.4, 121.7, 120.2, 119.9, 118.5, 111.4, 21.6.
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