Heterogeneous gold(III)-catalysed double hydroamination of 2-alkynylanilines with terminal alkynes leading to N-vinylindoles

Article abstract of DOI:10.3184/174751918X15403975136742

Heterogeneous double hydroamination of 2-alkynylanilines with terminal alkynes was achieved by using a magnetic nanoparticles-supported gold(III)-2,2′-bipyridine complex and silver trifluoromethanesulfonate as catalysts to afford the corresponding N-vinyl

Full text of DOI:10.3184/174751918X15403975136742

558 RESEARCH PAPER
VOL. 42 NOVEMBER, 558–563
JOURNAL OF CHEMICAL RESEARCH 2018
Heterogeneous gold(III)-catalysed double hydroamination of 2-alkynylanilines
with terminal alkynes leading to N-vinylindoles
Weisen Yanga,b, Li Weib, Feiyan Yib and Mingzhong Caib*
aFujian Key Laboratory of Eco-Industrial Green Technology, College of Ecology and Resources Engineering, Wuyi University, Wuyishan 354300, P.R. China
bCollege of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang 330022, P.R. China
Heterogeneous double hydroamination of 2-alkynylanilines with terminal alkynes was achieved by using a magnetic nanoparticles-
supported gold(III)-2,2′-bipyridine complex and silver trifluoromethanesulfonate as catalysts to afford the corresponding N-vinylindoles
in moderate to good yields under mild and solvent-free conditions. The heterogeneous gold catalyst can easily be separated from the
reaction mixture by simply applying an external magnet and can be recycled up to seven times without significant loss of activity.
Keywords: hydroamination, N-vinylindole, magnetic nanoparticles, gold(III)-2,2′-bipyridine complex, heterogeneous catalysis
Indoles play an important role in organic synthesis and exhibit
a wide range of biological and pharmacological activities.1–5
Among the various indole derivatives, N-vinylindoles are
important chemicals because they represent key structural
motifs in numerous natural products and biologically active
compounds.6–8 In addition, N-vinylindole compounds are
of increasing importance in materials science as monomers
for preparation of poly(N-vinylindoles), which can be used
as semiconductors and photosensitive materials.9–12 Of the
various synthetic routes to N-vinylindoles, the transition
metal-catalysed cross-coupling reaction of indoles with
prefunctionalised alkenes, such as vinyl halides13–15 and vinyl
trifluoromethanesulfonates,16 is one of the most efficient
approaches. Palladium-catalysed oxidative cross-coupling of
N-tosylhydrazones with indoles has proven to be an alternative
method for the synthesis of N-vinylindoles.17 Recently, the
Verma18–20 and Wacharasindhu21 groups have reported base-
mediated or copper-catalysed intermolecular hydroaminations
of alkynes with indoles leading to N-vinylindoles. Also, acid-
promoted condensation of alkyl or aryl α-branched aldehydes
with indole derivatives can produce N-vinylindoles.22 Despite
significant progress made in the preparation of N-vinylindoles,
the narrow scope of substrates, high cost and harsh reaction
conditions make these protocols of limited synthetic utility.
Considering the importance of N-vinylindoles and the
drawbacks of the existing methods, the development of a more
efficient and practical approach to construct N-vinylindoles is
highly desirable.
Homogeneous catalysis of organic reactions by gold
complexes has become a highly efficient and powerful tool
for the synthesis of valuable building blocks.23–27 Recently,
gold-catalysed construction of N-heterocyclic compounds
such as pyrroles,28–30 indoles31–33 and oxazoles34–36 has attracted
great interest due to their high efficiency and mild reaction
conditions, which greatly enriched the synthetic methods for
N-heterocycles. However, applications of these homogeneous
gold complexes in large-scale synthesis or multistep syntheses
remain a challenge because they are expensive, not recyclable
and difficult to separate from the product mixture. Recycling
of homogeneous precious metal catalysts is a task of great
economic and environmental importance in the chemical and
pharmaceutical industries. The heterogenisation of the existing
homogeneous catalysts appears to be a logical solution to this
problem.37 Moreover, heterogeneous catalysis can reduce waste
derived from reaction workup, contributing to the development
of green and sustainable chemical processes.38 However, to
the best of our knowledge, no examples of heterogeneous gold
complex-catalysed construction of indoles have been described
until now, despite the practical benefits of heterogeneous
catalysis.
To solve the problems of catalyst recovery and recycling,
magnetic nanoparticles-supported catalysts are a good choice
because their magnetic separation is an alternative to filtration
or centrifugation and it prevents loss of catalyst and improves
the reusability.39–41 Recently, we reported the synthesis of
a magnetic nanoparticles-supported gold(III)-bipy (bipy =
2,2′-bipyridine) complex (Fe3O4@SiO2-bipy-AuCl3) and its
successful application to the oxidative α-cyanation of tertiary
amines.42 To expand applications of this heterogeneous gold(III)
catalyst, we report here a double hydroamination reaction of
o-alkynylanilines with terminal alkynes catalysed by Fe3O4@
SiO2-bipy-AuCl3 leading to N-vinylindoles in moderate to
good yields. The heterogeneous gold(III) catalyst can be easily
separated from the reaction mixture by simply applying an
external magnet and its catalytic efficiency remains unaltered
even after recycling seven times.
Results and discussion
The magnetic nanoparticles-supported gold(III)-bipy complex
(Fe3O4@SiO2-bipy-AuCl3) was prepared by a simple two-step
procedureasshowninScheme1.42 Firstly, thesilica-coatedFe3O4
(Fe3O4@SiO2)43 was reacted with 4,4′-bis[3-(triethoxysilyl)-
propylaminomethyl]-2,2′-bipyridine (BTESBPY)44 in toluene
under reflux for 24 h to generate the bipyridine-functionalised
magnetic nanoparticles (Fe3O4@SiO2-bipy). The latter were
treated with AuCl3 in methanol at 65 ºC for 24 h to give the
magnetic nanoparticles-supported gold(III)-bipy complex
(Fe3O4@SiO2-bipy-AuCl3) as brown nanoparticles. The gold
content was determined to be 0.62 mmol g–1 by inductively
coupled plasma atomic emission spectroscopy (ICP-AES).
The magnetic nanoparticles-supported gold(III)-bipy
complex (Fe3O4@SiO2-bipy-AuCl3) was then used as the catalyst
for the double hydroamination reaction of o-alkynylanilines
with terminal alkynes. In our initial screening, the double
hydroamination of 2-(phenylethynyl)aniline (1a) with
phenylacetylene (2a) under neat conditions was selected as
the model reaction to optimise the reaction conditions and
the results are summarised in Table 1. When AuCl3 was used
as the catalyst, the reaction at 60 ºC gave the desired product
3a in 69% yield (Table 1, entry 1). Various silver salts such as
AgOTf (silver trifluoromethanesulfonate), AgSbF6 and AgBF4
could also catalyse this transformation, but the yield of 3a
was moderate (Table 1, entries 2–4). However, a combination
of AuCl3 (5 mol%) and AgOTf (15 mol%) proved to be more
efficient and afforded an 83% yield at room temperature
(Table 1, entry 5). We next examined the catalytic efficiency
* Correspondent. E-mail: caimzhong@163.com

JOURNAL OF CHEMICAL RESEARCH 2018 559
(EtO)3Si(CH2)3NH
Et
O
O
O
N
N
i
S
N
H
N
N
e
Fe O
F
3 O
4
3
4
e
Fe O
F
3 O
4
3
4
(EtO)3Si(CH2)3NH
O
O
H
N
i
S O2
i
S O2
i
S
Toluene, reflux, 24 h
Et
O
Fe3O4@SiO2
Fe3O4@SiO2-bipy
Et
O
O
O
l
C
i
S
N
N
N
AuCl3
l
C
H
e
e
O
3 O
3
F
F
Au
4
4
,
Methanol 65 oC
O
O
l
C
H
i
S O2
i
S
N
Et
O
Fe3O4 SiO -bipy-AuCl
@
2
3
Scheme 1
Table 1 Optimisation of reaction conditionsa
Entry
1
2
3
4
Catalyst (%)
AuCl3 (5)
AgOTf (5)
AgSbF6 (5)
AgBF4 (5)
AuCl3 (5)/AgOTf (15)
T (°C)
60
60
60
60
r.t.
Time (h)
Yield (%)b
69
58
51
55
2
2
2
2
2
5
83
6
7
8
9
10
11
Fe3O4@SiO2-bipy-AuCl3 (5)
Fe3O4@SiO2-bipy-AuCl3 (5)/AgOTf (15)
Fe3O4@SiO2-bipy-AuCl3 (5)/AgSbF6 (15)
Fe3O4@SiO2-bipy-AuCl3 (5)/AgBF4 (15)
Fe3O4@SiO2-bipy-AuCl3 (5)/AgOTf (15)
Fe3O4@SiO2-bipy-AuCl3(2.5)/AgOTf (7.5)
60
r.t.
r.t.
r.t.
60
r.t.
2
4
4
4
2
10
65
81
71
75
78
76
aAll reactions were performed using 1a (0.2 mmol), 2a (0.4 mmol) under Ar.
bIsolated yield.
of Fe3O4@SiO2-bipy-AuCl3 in this reaction. The use of Fe3O4@
SiO2-bipy-AuCl3 alone at 60 ºC gave the desired 3a in only 65%
yield (Table 1, entry 6). To our delight, use of various silver
salts as co-catalysts allowed the reaction to proceed smoothly at
room temperature to give 3a in 71–81% yields (Table 1, entries
7–9). AgOTf was found to be most efficient. When Fe3O4@
SiO2-bipy-AuCl3 (5 mol%) and AgOTf (15 mol%) were used
as catalysts, the reaction at 60 ºC afforded a slightly lower
yield (Table 1, entry 10). Reducing the amount of the catalysts
resulted in a lower yield and a longer reaction time was required
(Table 1, entry 11). Therefore, the optimised reaction conditions
for this transformation are Fe3O4@SiO2-bipy-AuCl3 (5 mol%)
and AgOTf (15 mol%) at room temperature under Ar for 4 h
(Table 1, entry 7).
double hydroamination reactions of both electron-rich and
electron-deficient arylacetylenes 2b–f with 2-(phenylethynyl)
aniline (1a) proceeded smoothly under the optimised conditions
to afford the corresponding N-vinylindoles 3b–f in good yields
(Table 2, entries 2–6). Aliphatic alkynes appeared less reactive.
For instance, the reaction of cyclopropylacetylene (2g) with
1a gave the desired product 3g in only 43% yield (Table 2,
entry 7). On the other hand, the reactivity of alkyl-substituted
acetylenic anilines was lower than that of phenyl-substituted
acetylenic anilines. Reactions of alkyl-substituted acetylenic
anilines 1b–d with arylacetylenes provided the desired
N-vinylindoles 3h–k in moderate yields (Table 2, entries 8–11).
2-(4-Chlorophenylethynyl)aniline (1e) was also a suitable
substrate and the reactions with arylacetylenes produced the
expected products 3l and 3m in good yields (Table 2, entries
12 and 13). In addition, halo-substituted 2-(phenylethynyl)
anilines 1f–h also proved to be good substrates and showed
a similar reactivity to 2-(phenylethynyl)aniline (1a). For
Subsequently, we investigated the scope of this heterogeneous
gold(III)-catalysed double hydroamination reaction by using
various 2-alkynylanilines and a range of terminal alkynes as
the substrates and the results are summarised in Table 2. The

560 JOURNAL OF CHEMICAL RESEARCH 2018
Table 2 Heterogeneous Au(III)-catalysed double hydroamination of 2-alkynylanilines with terminal alkynesa
R1
R2
R1
R2
Fe3O4@SiO2-bipy-AuCl3 (5 mol%)
AgOTf (15 mol%)
+
N
R3
neat, Ar, rt, 4 h
NH2
R3
3
1
2
Entry
1
2
3
4
5
6
7
8
R1
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Br
Br
Br
Br
F
R2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
R3
Ph
Product
Yield (%)b
81
78
70
75
3a
3b
3c
3d
3e
3f
3g
3h
3i
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-FC6H4
2-ClC6H4
Cyclopropyl
Ph
Ph
Ph
4-ClC6H4
Ph
4-ClC6H4
Ph
4-MeC6H4
4-MeOC6H4
Ph
4-ClC6H4
4-MeC6H4
1-Naphthyl
Ph
69
66
43
51
42
44
41
68
66
75
74
71
73
70
72
65
67
n-Bu
9
Cyclohexyl
Cyclopropyl
Cyclopropyl
4-ClC6H4
4-ClC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
3u
3v
3w
Me
Me
Ph
4-MeC6H4
65
63
aReaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), Fe3O4@SiO2-bipy-AuCl3 (5 mol%), AgOTf (15 mol%), room temperature under Ar for 4 h.
bIsolated yield.
example, 4-chloro-2-(phenylethynyl)aniline (1f), 4-bromo-2-
(phenylethynyl)aniline (1g) and 4-fluoro-2-(phenylethynyl)
aniline (1h) could undergo the double hydroamination with
various arylacetylenes effectively to furnish the corresponding
5-halo-substituted N-vinylindoles 3n–s and 3u in 67–75%
yields (Table 2, entries 14–19 and 21). Interestingly, the
reaction of 4-bromo-2-(phenylethynyl)aniline (1g) with bulky
1-ethynylnaphthalene (2h) also gave the desired product 3t in
65% yield (Table 2, entry 20). It is noteworthy that 4-methyl-
2-(4-chlorophenylethynyl)aniline (1i) was also a suitable
substrate and afforded the expected products 3v and 3w in good
yields (Table 2, entries 22 and 23).
A possible mechanism for this heterogeneous gold(III)-catalysed
double hydroamination reaction of 2-alkynylanilines 1 with
terminal alkynes 2 is outlined in Scheme 2.31 Firstly, coordination
of the Fe3O4@SiO2-bipy-Au(OTf)3 complex generated in situ from
Fe3O4@SiO2-bipy-AuCl3 and AgOTf to the carbon–carbon triple
bond in terminal alkyne 2 affords a magnetic nanoparticles-bound
bipy-Au(III) alkyne complex A. Intermediate A further reacts with
2-alkynylaniline 1 to give the first hydroamination product, which
is followed by coordination of Fe3O4@SiO2-bipy-Au(OTf)3 to the
alkyne moiety in the product again to generate intermediate B.
Intermediate B undergoes an intramolecular nucleophilic addition
of the imine nitrogen to the carbon–carbon triple bond to form
intermediate C. Finally, the C-3 position of indole in intermediate
C is protonated to afford the desired product 3 and regenerate the
Fe3O4@SiO2-bipy-Au(OTf)3 complex.
For the practical application of a heterogeneous precious
metal catalyst, its stability and reusability are important
factors. We next investigated the recycling of the Fe3O4@SiO2-
bipy-AuCl3 complex by using the double hydroamination of
2-(phenylethynyl)aniline (1a) with phenylacetylene (2a) as a
model reaction. After the reaction was completed, the reaction
mixture was diluted with EtOAc and more than 99% of the
gold catalyst could be recovered by simply fixing a magnet
near to the reaction vessel. The recovered catalyst was washed
with MeOH, air-dried and used directly in the next run without
further purification. The recovered gold catalyst was used for
seven further consecutive cycles using fresh substrates under
identical conditions and the results are presented in Fig. 1.
As shown in Fig. 1, the yield of the desired product 3a in all
cases was found to be closely similar, which confirmed that
the developed heterogeneous gold(III) catalyst can be recycled
efficiently for at least seven times without significant loss of
activity. It is noteworthy that the reaction catalysed by the
recovered catalyst did not need the addition of AgOTf because
Fe3O4@SiO2-bipy-AuCl3 had been changed to Fe3O4@SiO2-
bipy-Au(OTf)3 after the first cycle. The excellent reusability of
the catalyst may result from the chelating action of the bidentate
bipyridine ligand on gold and the magnetic separation. The
result is important from industrial and environmental points of
view.
In conclusion, we have developed a novel, efficient and
practical method for the synthesis of N-vinylindoles through

JOURNAL OF CHEMICAL RESEARCH 2018 561
Fe3O4 SiO -bipy-AuCl
@
2
3
AgOTf
R
N
R1
Fe3O4@SiO2
( )
3
R1
bipy
( )
2
[Au]3+
H+
Fe3O4@SiO2
Fe3O4@SiO2
bipy
[Au]2+
bipy
[Au]3+
( )
A
R1
R
N
C
( )
Fe3O4@SiO2
R1
bipy
[Au]3+
R
R
H+
H
N
( )
B
N
( )
1
H
R1
Scheme 2
Experimental
All reagents were used as received without further purification.
2-Alkynylanilines 1a–i were prepared by palladium/copper-catalysed
Sonogashira coupling reactions of 2-iodoanilines with terminal
alkynes according to a literature method.31 The Fe3O4@SiO2-bipy-
AuCl3 complex was prepared according to our previous procedure.42
The gold content was determined to be 0.62 mmol g–1. All reactions
were carried out under Ar in oven-dried glassware with magnetic
1
stirring. H NMR spectra were recorded on a Bruker Avance 400 (at
400 MHz) spectrometer with TMS as an internal standard using CDCl3
as the solvent. 13C NMR spectra were recorded on a Bruker Avance 400
(at 100 MHz) spectrometer using CDCl3 as the solvent. HRMS spectra
were recorded on a quadrupole-time of flight Bruker MicroTOF-Q
II mass spectrometer equipped with an ESI and APCI source. Gold
content was determined using ICP-AES on an Atomscan16 instrument
(TJA Corporation).
Synthesis of 2-phenyl-1-(1-phenylvinyl)-1H-indole (3a); general
procedure
Fig. 1 Recycling of the Fe3O4@SiO2-bipy-AuCl3 catalyst.
Fe3O4@SiO2-bipy-AuCl3 (16 mg, 0.01 mmol) and AgOTf (8 mg,
0.03 mmol) were added to a mixture of 2-(phenylethynyl)aniline
(0.2 mmol) and phenylacetylene (0.4 mmol) under Ar at room
temperature. The reaction mixture was stirred at room temperature.
During this procedure the reaction mixture became a deep black
liquid very quickly. After 4 h the resulting mixture was diluted with
ethyl acetate and the supported catalyst was magnetically separated.
The reaction solution was evaporated and the residue was purified
by column chromatography on silica gel (eluting with hexane/ethyl
acetate = 25:1) to give the desired product 3a. The recovered catalyst
was washed with MeOH (2 × 2 mL) and air-dried. When appropriate it
could be used directly for the next run.
the double hydroamination reaction of 2-alkynylanilines with
terminal alkynes by using a magnetic nanoparticles-supported
gold(III)-bipy complex (Fe3O4@SiO2-bipy-AuCl3) and AgOTf
as catalysts. The reactions generated a variety of N-vinylindole
derivatives in moderate to good yields under mild and solvent-
free conditions. Importantly, this heterogeneous gold catalyst
can be recovered by simply applying an external magnet and
recycled up to seven times without significant loss of activity.
The Fe3O4@SiO2-bipy-AuCl3 catalyst not only solves the basic
problems of catalyst separation and recovery but also avoids the
use of AgOTf in the recycling process. This makes our protocol
facile, economical and environmentally benign.
2-Phenyl-1-(1-phenylvinyl)-1H-indole (3a):31 Oil; 1H NMR (400
MHz, CDCl3): δ 7.67 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 7.2 Hz, 2H),
7.28–7.20 (m, 6H), 7.19–7.11 (m, 5H), 6.77 (s, 1H), 5.89 (s, 1H), 5.25 (s,

562 JOURNAL OF CHEMICAL RESEARCH 2018
1H); 13C NMR (100 MHz, CDCl3): δ 143.6, 141.3, 139.1, 137.3, 132.8,
128.8, 128.6, 128.4, 128.3, 128.1, 127.5, 125.9, 122.3, 120.7, 120.5,
113.8, 111.5, 103.7.
13C NMR (100 MHz, CDCl3): δ 143.8, 142.2, 138.0, 135.9, 134.8, 128.8,
128.1, 127.2, 121.3, 120.1, 119.8, 114.1, 110.3, 98.1, 8.2, 7.8; HRMS
calcd for C19H1635ClN+: [M+]: 293.0971; found: 293.0976.
2-Phenyl-1-(1-p-tolylvinyl)-1H-indole (3b):31 Oil; 1H NMR
(400 MHz, CDCl3): δ 7.68–7.62 (m, 1H), 7.51–7.46 (m, 2H), 7.28–7.18
(m, 3H), 7.18–7.06 (m, 5H), 7.04 (d, J = 8.2 Hz, 2H), 6.77 (s, 1H),
5.84 (s, 1H), 5.16 (s, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 143.5, 141.3, 139.1, 138.8, 134.4, 132.8, 129.3, 128.9, 128.4, 128.1,
127.4, 125.8, 122.2, 120.5, 120.4, 113.0, 111.6, 103.6, 21.2.
2-(4-Chlorophenyl)-1-(1-phenylvinyl)-1H-indole (3l): Green solid;
1
m.p. 77–79 °C (lit.45 123–124 °C); H NMR (400 MHz, CDCl3): δ
7.66 (d, J = 7.6 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.24–7.20 (m, 4H),
7.19–7.09 (m, 6H), 6.76 (s, 1H), 5.92 (s, 1H), 5.28 (s, 1H); 13C NMR
(100 MHz, CDCl3): δ 143.5, 139.9, 139.2, 137.1, 133.4, 131.3, 129.5,
129.0, 128.6, 128.4, 128.2, 125.8, 122.6, 120.8, 120.6, 113.9, 111.5,
104.0.
1-[1-(4-Methoxyphenyl)vinyl]-2-phenyl-1H-indole
(3c):31
Oil;
1H NMR (400 MHz, CDCl3): δ 7.66 (d, J = 7.0 Hz, 1H), 7.51–7.46 (m,
2H), 7.28–7.21 (m, 3H), 7.16–7.10 (m, 5H), 6.76 (d, J = 8.4 Hz, 2H),
6.74 (s, 1H), 5.78 (s, 1H), 5.13 (s, 1H), 3.75 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 160.1, 143.1, 141.3, 139.1, 132.8, 130.9, 128.9, 128.3,
128.1, 127.4, 127.3, 122.2, 120.5, 120.4, 114.0, 111.9, 111.5, 103.5, 55.2.
1-[1-(4-Chlorophenyl)vinyl]-2-phenyl-1H-indole (3d):Oil; 1H NMR
(400 MHz, CDCl3): δ 7.67 (d, J = 6.8 Hz, 1H), 7.45 (d, J = 6.8 Hz,
2H), 7.27–7.23 (m, 3H), 7.19–7.12 (m, 5H), 7.06 (d, J = 8.4 Hz, 2H),
6.77 (s, 1H), 5.89 (s, 1H), 5.31 (s, 1H); 13C NMR (100 MHz, CDCl3):
δ 142.7, 141.2, 139.0, 135.8, 134.7, 132.6, 128.8, 128.4, 128.3, 128.2,
127.6, 127.2, 122.4, 120.8, 120.6, 114.2, 111.3, 103.9; HRMS calcd for
C22H1635ClN+: [M+]: 329.0971; found: 329.0980.
1-[1-(4-Fluorophenyl)vinyl]-2-phenyl-1H-indole (3e):31 Oil; 1H NMR
(400 MHz, CDCl3): δ 7.67 (d, J = 7.4 Hz, 1H), 7.46 (d, J = 7.8 Hz,
2H), 7.28–7.24 (m, 3H), 7.19–7.15 (m, 3H), 7.12–7.06 (m, 2H), 6.88 (t,
J = 8.0 Hz, 2H), 6.76 (s, 1H), 5.84 (s, 1H), 5.29 (s, 1H); 13C NMR (100
MHz, CDCl3): δ 163.0 (d, 1JC–F = 247.4 Hz), 142.8, 141.2, 139.0, 133.5 (d,
4JC–F = 2.9 Hz), 132.7, 130.9, 128.3, 128.1, 127.7 (d, 3JC–F = 8.3 Hz), 127.5,
122.3, 120.8, 120.6, 115.5 (d, 2JC–F = 21.7 Hz), 113.4, 111.3, 103.8.
1-[1-(2-Chlorophenyl)vinyl]-2-phenyl-1H-indole (3f): Oil; 1H NMR
(400 MHz, CDCl3): δ 7.66–7.64 (m, 1H), 7.44–7.40 (m, 3H), 7.25–7.17
(m, 6H), 7.05–7.00 (m, 1H), 6.96–6.92 (m, 1H), 6.75–6.72 (m, 1H),
6.67 (s, 1H), 5.91 (s, 1H), 5.74 (s, 1H); 13C NMR (100 MHz, CDCl3):
δ 140.7, 140.4, 139.0, 136.1, 133.0, 132.2, 130.3, 129.2, 128.6, 128.5,
128.0, 127.4, 126.5, 122.4, 120.8, 120.6, 117.1, 111.2, 104.2; HRMS
calcd for C22H1635ClN+: [M+]: 329.0971; found: 329.0965.
1-(1-Cyclopropylvinyl)-2-phenyl-1H-indole (3g): Oil; 1H NMR
(400 MHz, CDCl3): δ 7.66 (d, J = 7.8 Hz, 2H), 7.61 (d, J = 7.4 Hz, 1H),
7.43–7.38 (m, 3H), 7.34 (d, J = 7.2 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.13
(t, J = 7.4 Hz, 1H), 6.69 (s, 1H), 5.33 (s, 1H), 5.24 (s, 1H), 1.34–1.28
(m, 1H), 0.54–0.52 (m, 2H), 0.41–0.38 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 147.0, 140.1, 138.8, 133.5, 132.2, 128.5, 128.3, 128.2, 127.6,
122.1, 120.3, 111.0, 110.9, 103.1, 16.4, 7.8; HRMS calcd for C19H17N+:
[M+]: 259.1361; found: 259.1357.
2-Butyl-1-(1-phenylvinyl)-1H-indole (3h):31 Oil; 1H NMR
(400 MHz, CDCl3): δ 7.57 (d, J = 7.6 Hz, 1H), 7.31–7.27 (m, 3H),
7.16–7.10 (m, 3H), 7.07 (t, J = 7.4 Hz, 2H), 6.39 (s, 1H), 6.06 (s, 1H),
5.42 (s, 1H), 2.51 (t, J = 7.4 Hz, 2H), 1.63–1.58 (m, 2H), 1.34–1.28 (m,
2H), 0.84 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 143.0,
141.9, 138.0, 137.1, 128.9, 128.7, 128.2, 125.7, 121.0, 119.9, 119.6, 113.7,
110.5, 100.4, 30.71, 26.7, 22.3, 13.8.
2-Cyclohexyl-1-(1-phenylvinyl)-1H-indole (3i): Oil; 1H NMR
(400 MHz, CDCl3): δ 7.56 (d, J = 7.4 Hz, 1H), 7.34 (d, J = 7.4 Hz, 1H),
7.29–7.23 (m, 3H), 7.12 (d, J = 6.8 Hz, 2H), 7.06 (t, J = 7.4 Hz, 2H),
6.42 (s, 1H), 6.09 (s, 1H), 5.45 (s, 1H), 2.97–2.77 (m, 1H), 1.98–1.41 (m,
10H); 13C NMR (100 MHz, CDCl3): δ 146.6, 143.2, 138.0, 137.1, 128.9,
128.7, 128.5, 125.6, 121.1, 119.9, 119.7, 114.1, 110.4, 98.1, 37.5, 33.6,
29.7, 25.3; HRMS calcd for C22H23N+: [M+]: 301.1830; found: 301.1819.
2-Cyclopropyl-1-(1-phenylvinyl)-1H-indole (3j):45 Oil; 1H NMR
(400 MHz, CDCl3): δ 7.54–7.52 (m, 1H), 7.31–7.27 (m, 3H), 7.19–7.16
(m, 2H), 7.15–7.12 (m, 1H), 7.09–7.03 (m, 2H), 6.19 (s, 1H), 6.05 (s,
1H), 5.49 (s, 1H), 1.67–1.60 (m, 1H), 0.79–0.71 (m, 2H), 0.70–0.63 (m,
2H); 13C NMR (100 MHz, CDCl3): δ 144.0, 143.2, 138.1, 137.4, 128.8,
128.6, 128.0, 125.9, 121.1, 120.0, 119.7, 113.6, 110.4, 97.7, 8.2, 7.8.
1-[1-(4-Chlorophenyl)vinyl]-2-cyclopropyl-1H-indole (3k): Oil;
1H NMR (400 MHz, CDCl3): δ 7.54–7.52 (m, 1H), 7.26 (d, J = 8.0 Hz,
2H), 7.12–7.09 (m, 2H), 7.08–7.05 (m, 3H), 6.19 (s, 1H), 6.04 (s, 1H),
5.50 (s, 1H), 1.64–1.60 (m, 1H), 0.79–0.74 (m, 2H), 0.70–0.62 (m, 2H);
2-(4-Chlorophenyl)-1-[1-(4-chlorophenyl)vinyl]-1H-indole (3m):
Oil; H NMR (400 MHz, CDCl3): δ 7.70–7.64 (m, 1H), 7.41–7.36
1
(m, 2H), 7.25–7.22 (m, 2H), 7.21–7.19 (m, 1H), 7.18–7.15 (m, 4H),
7.06–7.02 (m, 2H), 6.76 (s, 1H), 5.92 (s, 1H), 5.33 (s, 1H); 13C NMR
(100 MHz, CDCl3): δ 142.5, 139.8, 139.0, 135.5, 134.9, 133.6, 131.1,
129.4, 128.9, 128.5, 128.2, 127.1, 122.7, 121.0, 120.7, 114.4, 111.3,
104.2; HRMS calcd for C22H1535Cl2NNa+: [M + Na]+: 386.0479; found:
386.0468.
1
5-Chloro-2-phenyl-1-(1-phenylvinyl)-1H-indole (3n): Oil; H NMR
(400 MHz, CDCl3): δ 7.62 (s, 1H), 7.47–7.44 (m, 2H), 7.28–7.19
(m, 6H), 7.13–7.11 (m, 2H), 7.07–7.03 (m, 2H), 6.69 (s, 1H), 5.90 (s,
1H), 5.25 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 143.4, 142.6, 137.4,
136.9, 132.3, 129.3, 129.0, 128.7, 128.4, 128.2, 127.8, 126.3, 125.8,
122.5, 119.8, 114.1, 112.5, 103.1.; HRMS calcd for C22H1635ClN+: [M+]:
329.0971; found: 329.0962.
1
5-Chloro-2-phenyl-1-(1-p-tolylvinyl)-1H-indole (3o): Oil; H NMR
(400 MHz, CDCl3): δ 7.61 (s, 1H), 7.47 (d, J = 6.4 Hz, 2H), 7.28–7.21
(m, 3H), 7.04–7.02 (m, 6H), 6.69 (s, 1H), 5.84 (s, 1H), 5.15 (s, 1H),
2.29 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 143.2, 142.6, 139.1, 137.4,
134.0, 132.3, 129.4, 129.3, 128.4, 128.2, 127.8, 126.2, 125.7, 122.4,
119.8, 113.3, 112.6, 103.0, 21.2; HRMS calcd for C23H1835ClN+: [M+]:
343.1128; found: 343.1140.
5-Chloro-1-[1-(4-methoxyphenyl)vinyl]-2-phenyl-1H-indole (3p):
1
Oil; H NMR (400 MHz, CDCl3): δ 7.61 (s, 1H), 7.47 (d, J = 6.6 Hz,
2H), 7.29–7.22 (m, 3H), 7.11–7.00 (m, 4H), 6.75 (d, J = 8.8 Hz, 2H),
6.69 (s, 1H), 5.78 (s, 1H), 5.12 (s, 1H), 3.75 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 160.3, 143.0, 142.6, 137.5, 132.4, 129.5, 129.3, 128.4,
128.1, 127.7, 127.2, 126.2, 122.4, 119.8, 114.1, 112.5, 112.1, 102.9,
55.2; HRMS calcd for C23H1835ClNNaO+: [M + Na]+: 382.0975; found:
382.0973.
1
5-Bromo-2-phenyl-1-(1-phenylvinyl)-1H-indole (3q): Oil; H NMR
(400 MHz, CDCl3): δ 7.78 (s, 1H), 7.47–7.43 (m, 2H), 7.29–7.17
(m, 6H), 7.14–6.97 (m, 4H), 6.69 (s, 1H), 5.89 (s, 1H), 5.25 (s, 1H);
13C NMR (100 MHz, CDCl3): δ 143.3, 142.4, 137.7, 136.8, 132.2, 130.0,
129.0, 128.7, 128.5, 128.2, 127.8, 125.8, 125.1, 122.9, 114.1, 113.8,
112.9, 103.0; HRMS calcd for C22H1679BrNNa+: [M + Na]+: 396.0364;
found: 396.0371.
5-Bromo-1-[1-(4-chlorophenyl)vinyl]-2-phenyl-1H-indole (3r): Oil;
1H NMR (400 MHz, CDCl3): δ 7.78 (s, 1H), 7.43–7.41 (m, 2H), 7.28–7.16
(m, 6H), 7.03–7.00 (m, 3H), 6.69 (s, 1H), 5.89 (s, 1H), 5.31 (s, 1H);
13C NMR (100 MHz, CDCl3): δ 141.3, 141.2, 136.5, 134.3, 133.8, 131.0,
128.9, 127.8, 127.3, 127.2, 126.9, 126.0, 124.1, 122.0, 113.5, 112.9, 111.6,
102.1; HRMS calcd for C22H1579Br35ClNNa+: [M + Na]+: 429.9974; found:
429.9971.
1
5-Bromo-2-phenyl-1-(1-p-tolylvinyl)-1H-indole (3s): Oil; H NMR
(400 MHz, CDCl3): δ 7.78 (s, 1H), 7.48–7.46 (m, 2H), 7.27–7.24 (m,
3H), 7.18–7.14 (m, 1H), 7.08–7.02 (m, 4H), 6.97 (d, J = 8.6 Hz, 1H),
6.70 (s, 1H), 5.85 (s, 1H), 5.16 (s, 1H), 2.30 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 143.2, 142.4, 139.1, 137.7, 134.0, 132.2, 129.9, 129.4,
128.4, 128.2, 127.8, 125.7, 125.0, 122.9, 113.8, 113.3, 113.0, 102.8,
21.2; HRMS calcd for C23H1879BrNNa+: [M + Na]+: 410.0520; found:
410.0515.
5-Bromo-1-[1-(naphthalen-1-yl)vinyl]-2-phenyl-1H-indole
(3t):
Beige solid; m.p. 159–161 °C; 1H NMR (400 MHz, CDCl3): δ 7.86 (d,
J = 8.6 Hz, 1H), 7.77 (d, J = 1.6 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.64
(d, J = 8.2 Hz, 1H), 7.40–7.37 (m, 1H), 7.35–7.30 (m, 1H), 7.29–7.24
(m, 3H), 7.24–7.20 (m, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.12–7.04 (m, 3H),
7.02–6.97 (m, 1H), 6.57 (s, 1H), 5.78 (s, 1H), 5.68 (s, 1H); 13C NMR

JOURNAL OF CHEMICAL RESEARCH 2018 563
6
M. Ogata, H. Matsumoto, S. Shimizu, S. Kida, M. Shiro and K. Tawara, J.
Med. Chem., 1987, 30, 1348.
A.G. Schultz, W.P. Malachowski and Y. Pan, J. Org. Chem., 1997, 62, 1223.
H. Li, N. Boonnak and A. Padwa, J. Org. Chem., 2011, 76, 9488.
F. Brustolin, V. Castelvetro, F. Ciardelli, G. Ruggeri and A. Colligiani, J.
Polym. Sci., A: Polym. Chem., 2001, 39, 253.
(100 MHz, CDCl3): δ 142.4, 141.7, 137.4, 135.1, 133.8, 132.5, 130.7,
130.3, 129.3, 128.6, 128.5, 127.9, 127.7, 126.8, 126.6, 125.7, 125.3,
124.9, 124.5, 123.1, 116.4, 114.0, 112.9, 103.8; HRMS calcd for
C26H1879BrNNa+: [M + Na]+: 446.0520; found: 446.0527.
5-Fluoro-2-phenyl-1-(1-phenylvinyl)-1H-indole (3u): Brown solid;
m.p. 82–84 °C; 1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 6.6 Hz, 2H),
7.29–7.27 (m, 1H), 7.26–7.22 (m, 6H), 7.16–7.13 (m, 2H), 7.06–7.01
(m, 1H), 6.87–6.82 (m, 1H), 6.72 (s, 1H), 5.89 (s, 1H), 5.25 (s, 1H);
13C NMR (100 MHz, CDCl3): δ 158.4 (d,1JC–F = 233.9 Hz), 143.5, 142.9,
137.0, 135.6, 132.5, 128.9, 128.7, 128.6 (d,3JC–F = 9.4 Hz), 128.4, 128.2,
127.7, 125.9, 114.0, 112.2 (d, 3JC–F = 9.5 Hz), 110.5 (d, 2JC–F = 25.9 Hz),
105.2 (d, 2JC–F = 23.4 Hz), 103.5 (d, 4JC–F = 4.3 Hz); HRMS calcd for
C22H16FN+: [M+]: 313.1267; found 313.1276.
7
8
9
10 A. Priola, G. Gatti and S. Cesca, Makromol. Chem., 1979, 180, 1.
11 E. Gipstein and W.A. Hewett, Macromolecules, 1969, 2, 82.
12 Y. Maki, H. Mori and T. Endo, Macromolecules, 2007, 40, 6119.
13 Y. Artyom, V.V.I. Lebedev, N. Denis, I.P. Beletskaya and A.Z.
Voskoboynikov, Org. Lett., 2002, 4, 623.
14 Q. Liao, Y. Wang, L. Zhang and C. Xi, J. Org. Chem., 2009, 74, 6371.
15 H. Li, N. Boonnak and A. Padwa, Tetrahedron Lett., 2011, 52, 2062.
16 M.M.A.E. Ondrus, J. Org. Chem., 2005, 70, 8638.
17 X. Zeng, G. Cheng, J. Shen and X. Cui, Org. Lett., 2013, 15, 3022.
18 A.K. Verma, M. Joshi and V.P. Singh, Org. Lett., 2011, 13, 1630.
19 M. Joshi, R. Tiwari and A.K. Verma, Org. Lett., 2012, 14, 1106.
20 M. Joshi, M. Patel, R. Tiwari and A.K. Verma, J. Org. Chem., 2012, 77,
5633.
21 E. Rattanangkool, T. Vilaivan, M. Sukwattanasinitt and S. Wacharasindhu,
Eur. J. Org. Chem., 2016, 4347.
22 G. Fridkin, N.D. Boutard and W. Lubell, J. Org. Chem., 2009, 74, 5603.
23 A.S.K. Hashmi and F.D. Toste (eds), Modern gold catalyzed synthesis.
Wiley-VCH, Weinheim, 2012.
24 A. Corma, A. Leyva-Perez and M.J. Sabater, Chem. Rev., 2011, 111, 1657.
25 R. Dorel and A.M. Echavarren, Chem. Rev., 2015, 115, 9028.
26 D.B. Huple, S. Ghorpade and R.-S. Liu, Adv. Synth. Catal., 2016, 358, 1348.
27 D. Pflästerer and A.S.K. Hashmi, Chem. Soc. Rev., 2016, 45, 1331.
28 P.W. Davies and N. Martin, Org Lett., 2009, 11, 2293.
29 H. Ueda, M. Yamaguchi, H. Kameya, K. Sugimoto and H. Tokuyama, Org
Lett., 2014, 16, 4948.
30 X. Li, M. Chen, X. Xie, N. Sun, S. Li and Y. Liu, Org Lett., 2015, 17, 2984.
31 Y. Zhang, J.P. Donahue and C.-J. Li, Org. Lett., 2007, 9, 627.
32 Y. Matuda, S. Naoe, S. Oishi, N. Fujii and H. Ohno, Chem. Eur. J., 2015,
21, 1463.
2-(4-Chlorophenyl)-5-methyl-1-(1-phenylvinyl)-1H-indole
(3v):
Brown solid; m.p. 136–138 °C; 1H NMR (400 MHz, CDCl3): δ 7.44 (s,
1H), 7.39 (d, J = 8.4 Hz, 2H), 7.25–7.18 (m, 5H), 7.15–7.11 (m, 2H),
7.04 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 6.68 (s, 1H), 5.89 (s,
1H), 5.24 (s, 1H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 143.7,
140.0, 137.7, 137.2, 133.3, 132.5, 131.5, 130.1, 129.5, 128.9, 128.6,
128.3, 125.9, 124.1, 120.2, 113.6, 111.1, 103.6, 21.3; HRMS calcd for
C23H1835ClN+: [M+]: 343.1128; found 343.1133.
2-(4-Chlorophenyl)-5-methyl-1-(1-p-tolylvinyl)-1H-indole
(3w):
1
Beige solid; m.p. 145–147 °C; H NMR (400 MHz, CDCl3): δ 7.44
(s, 1H), 7.43–7.38 (m, 2H), 7.23–7.19 (m, 2H), 7.08–7.00 (m, 5H),
6.96–6.93 (m, 1H), 6.68 (s, 1H), 5.84 (s, 1H), 5.15 (s, 1H), 2.44 (s, 3H),
2.30 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 143.4, 140.0, 139.0, 137.7,
134.2, 133.2, 131.4, 130.1, 129.4, 128.5, 128.4, 125.8, 124.1, 120.2,
112.9, 111.3, 103.5, 21.5, 21.3; HRMS calcd for C24H2035ClNNa+: [M +
Na]+: 380.1182; found: 380.1173.
33 H. Jin, L. Huang, J. Xie, M. Rudolph, F. Rominger and A.S.K. Hashmi,
Angew. Chem., Int. Ed., 2016, 55, 794.
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 21462021) and the Natural Science Foundation of Jiangxi
Province of China (No. 20161BAB203086) for financial
support.
34 W. He, C. Li and L. Zhang, J. Am. Chem. Soc., 2011, 133, 8482.
35 P. Querard, S.A. Girard, N. Uhlig and C.-J. Li, Chem. Sci., 2015, 6, 7332.
36 M. Chen, N. Sun, H. Chen and Y. Liu, Chem. Commun., 2016, 52, 6324.
37 N.T.S. Phan, M.V.D. Sluys and C.W. Jones, Adv. Synth. Catal., 2006, 348,
609.
38 M. Poliakoff, J.M. Fitzpatrick, T.R. Farren and P.T. Anastas, Science, 2002,
297, 807.
39 V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara and J.-M. Basset,
Chem. Rev., 2011, 111, 3036.
40 R.B.N. Baig and R.S. Varma, Chem. Commun., 2013, 49, 752.
41 D. Wang and D. Astruc, Chem. Rev., 2014, 114, 6949.
42 W. Yang, L. Wei, F. Yi and M. Cai, Tetrahedron, 2016, 72, 4059.
43 P. Li, L. Wang, L. Zhang and G.-W. Wang, Adv. Synth. Catal., 2012, 354,
1307.
44 F.-Y. Tsai, B.-N. Lin, M.-J. Chen, C.-Y. Mou and S.-T. Liu, Tetrahedron,
2007, 63, 4304.
45 Z.-Q. Wang, X. Zhang, L.-T. Yu, W.-T. Mao, C.-Z. Chen and K. Xu, Org.
Biomol. Chem., 2015, 13, 6931.
Received 1 July 2018; accepted 19 September 2018
Paper 1805499
https://doi.org/10.3184/174751918X15403975136742
Published online: 6 November 2018
References
1
2
3
4
5
R.J. Sundberg, Indoles. Academic Press, London, 1996.
G.W. Gribble, J. Chem. Soc., Perkin Trans. 1, 2000, 1045.
D.J. Faulkner, Nat. Prod. Rep., 1999, 16, 155.
G.R. Humphrey and J.T. Kuethe, Chem. Rev., 2006, 106, 2875.
M. Shiri, Chem. Rev., 2012, 112, 3508.