A Heteroarylamine Library: Indium-Catalyzed Nucleophilic Aromatic Substitution of Alkoxyheteroarenes with Amines

Article abstract of DOI:10.1002/adsc.201701452

Under indium Lewis acid catalysis, electron-rich five-membered heteroaryl electrophiles fused with/without a benzene ring were found to couple with amines to produce heteroarylamines with broad structural diversity. The heteroarylamine formation proceeds through the cleavage of a heteroaryl?OMe bond by the nucleophilic attack of the amine based on the nucleophilic aromatic substitution (S_NAr) reaction. In contrast to the corresponding traditional S_NAr amination, the present S_NAr-based heteroaryl amination can be performed without relying on both heteroaryl electrophiles with electron-withdrawing groups and nucleophilicity-enhanced metal amides. High compatibility towards the functional groups such as NO₂, Br, I, CF₃, CN, CO₂Et, pyridyl, thiazolyl, C=C, and OH groups was observed, thus showing the practicality and reliability of this method. Mechanistic studies indicated that a carbon?indium bond is likely to be formed on the heteroaryl ring during the process. (Figure presented.).

Full text of DOI:10.1002/adsc.201701452

Title: A Heteroarylamine Library: Indium-Catalyzed Nucleophilic
Aromatic Substitution of Alkoxyheteroarenes with Amines
Authors: Kyohei Yonekura, Yasuhiro Yoshimura, Mizuri Akehi, and
Teruhisa Tsuchimoto
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701452
Link to VoR: http://dx.doi.org/10.1002/adsc.201701452

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
A Heteroarylamine Library: Indium-Catalyzed Nucleophilic
Aromatic Substitution of Alkoxyheteroarenes with Amines
Kyohei Yonekura,a Yasuhiro Yoshimura,a Mizuri Akehi,a and Teruhisa Tsuchimotoa*
a
Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku,
Kawasaki 214-8571, Japan
Fax: (+81)-44-934-7228; e-mail: tsuchimo@meiji.ac.jp
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. Under indium Lewis acid catalysis, electron-rich nucleophilicity-enhanced metal amides. High compatibility
five-membered heteroaryl electrophiles fused with/without a towards the functional groups such as NO2, Br, I, CF3, CN,
benzene ring were found to couple with amines to produce CO2Et, pyridyl, thiazolyl, C=C, and OH groups was
heteroarylamines with broad structural diversity. The observed, thus showing the practicality and reliability of
heteroarylamine formation proceeds through the cleavage of this method. Mechanistic studies indicated that a carbon–
a heteroaryl–OMe bond by the nucleophilic attack of the indium bond is likely to be formed on the heteroaryl ring
amine based on the nucleophilic aromatic substitution during the process.
(SNAr). In contrast to the corresponding traditional SNAr
amination, the present SNAr-based heteroaryl amination can
be performed without relying on both heteroaryl
electrophiles with electron-withdrawing groups and
Keywords: Amination; Aromatic substitution;
Heterocycles; Indium; Lewis acids
of nucleophilic aromatic substitution (SNAr) reaction
(Scheme 1, route C).[9] However, performing the
SNAr amination on the heteroaryl ring is not an easy
task because amines and heteroaryls are intrinsically
both electron-rich, and thus behave as nucleophiles in
general. In order to connect each other with the same
electronic requirement, heteroaryls with one or more
electron-withdrawing groups (EWGs) have been used
as electrophiles to accept nucleophilic attack of
amines. This is also the well-known technique to
attain the SNAr process with nucleophiles other than
amines.[10] For the successful SNAr amination, further
enhancing the nucleophilicity of amines by using
metal amides (R1R2N–met) is another approach,
which, however, may be often combined with the use
of the X–heteroaryl–(EWG)n (see also route C).[11]
These requisites seem to have limited the widespread
applicability of the heteroarylamine synthesis via the
SNAr pathway.
On the other hand, we have disclosed the first
example of the SNAr-based catalytic biheteroaryl
synthesis by connecting two electron-rich heteroaryl
molecules.[12] The key strategic idea of the method is
that an indium Lewis acid temporarily behaves as an
EWG by forming an indium–heteroaryl -complex,
thus allowing to use heteroaryl electrophiles without
having the EWGs as well as non-metalated heteroaryl
nucleophiles, in contrast to the conventional SNAr-
based biheteroaryl synthesis. We therefore envisioned
that if the indium–heteroaryl -complex could react
with amines without forming an unfavorable complex
between the indium Lewis acid and the amine Lewis
Introduction
The ubiquity of amines with electron-rich heteroaryl
groups in biologically active compounds and drugs[1]
as well as functional materials[2] and synthetic
intermediates[3] has continued to inspire chemists to
develop new methods for preparing such molecules
more efficiently. In fact, a variety of approaches have
been reported and, among them, the nitrogen–
heteroaryl bond-forming process with easily available
amines as nucleophiles appears to be straightforward
to address heteroarylamines. In this regard, the
coupling of heteroaryl (pseudo)halides and amines
with the aid of transition metals would be
undoubtedly one of the reliable and powerful
strategies, the origin of which dates back to the
Ullmann amination with a stoichiometric amount of
copper metal, first reported over 100 years ago.[4]
This transition metal strategy has now been achieved
as a catalytic process and still been continuing to
evolve (Scheme 1, route A).[5,6] At present, the
palladium-catalyzed Buchwald–Hartwig amination
would be one of the representative of this category.[7]
In addition to the C–X bond amination, lately, a C–H
bond of heteroarenes has been reportedly used in a
direct manner for the same purpose, while requiring
the assistance of a directing group (DG) to guide
transition metals for the site-selective amination
(Scheme 1, route B).[8]
An alternative amine-based nitrogen–heteroaryl
bond-forming transformation should be the utilization
1
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
base,[13] the catalytic heteroarylamine synthesis will
be achieved without depending on both of the EWG-
substituted heteroaryl electrophile and the metal
amide (Scheme 1, route D: this work). During the
course of our investigation on the basis of this
idea,[14] very recently, triflic acid has been reported to
catalyze the amination but only for 3-
methoxythiophene as a heteroaryl electrophile.[15] In
contrast, we herein disclose the new protocol to
synthesize heteroarylamines from a variety of
combinations of methoxyheteroarenes and amines.
As a remaining category, the C–N bond-forming
heteroarylamine synthesis in which amines behave as
electrophiles has been known as well. This group
should be divided further into the transition metal
catalysis (Scheme 2, route E1)[16] and non-transition-
metal catalysis (Scheme 2, route E2),[17] but, herein,
umpolung oxidation of amines to prepare the
electrophilic amine substrate is necessary.[18]
Results and Discussion
Initially, we examined suitable reaction conditions for
the SNAr amination of 2-methoxythiophene (2a) with
morpholine (1a) (Table 1). Thus, treating 1a and 2a
with In(OTf)3 (10 mol%, Tf = SO2CF3) in 1,4-
dioxane at 110 ºC for 24 h gave desired 2-
morpholinothiophene (3aa), albeit only in a small
amount based on the low conversion of 2a (entry 1).
Using other metal triflates based on Sc, Cu, Ag, Zn,
and Bi metals lowered the reaction efficiency, and
thus resulted in no improvements in the yield of 3aa
(entries 2–6). Changing the ligand of In(OTf)3 to
NTf2 increased the reaction rate, while In(ONf)3 (Nf
= SO2C4F9) was less effective (entries 7 and 8). A
survey on the effect of solvents indicated that the
choice of chlorobenzene is suitable, thereby giving
3aa in 66% yield (entries 9–14). Increasing the molar
equivalent of 1a to 2a from 2.5 to 3 had no positive
effect on the yield of 3aa (entries 14 and 15).
Reducing the amount of 1a to 2 molar equivalents
route A
X
Het
cat. transition metal
R1R2N Het
R1R2NH
(X = I, Br, Cl,...)
route B
DG
Table 1. Lewis acid-catalyzed SNAr amination of 2-
methoxythiophene with morpholine.[a]
H
Het
DG
cat. transition metal
O
N
R1R2N Het
R1R2NH
S
Lewis acid
(10 mol%)
3aa
O
NH
O
+
+
solvent
110 ºC
24 h
route C
S
2a
(EWG)n
1a
O
N
(EWG)n
R1R2N Het
R1R2NH
or
X
Het
S
4aaa
S
(X = F, Cl, Br, I,...)
R1R2N–met
Lewis
Entry acid
Conv. [%] Yield [%][d]
Solvent[b] 2a[c]
3aa
4aaa
route D: this work
O
Het
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15[e]
16[f]
17[g]
18
In(OTf)3 Dioxane
Sc(OTf)3 Dioxane
Cu(OTf)2 Dioxane
9
21
12
7
7
6
<1
<1
<1
3
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
1
cat. indium Lewis acid
R1R2N Het
R1R2NH
In
AgOTf
Dioxane
Het
O
R1R2NH
Zn(OTf)2 Dioxane
Bi(OTf)3 Dioxane
In(ONf)3 Dioxane
In(NTf2)3 Dioxane
In(NTf2)3 Bu2O
In(NTf2)3 DEE
In(NTf2)3 MeNO2
In(NTf2)3 PrCN
In(NTf2)3 p-Xylene 78
In(NTf2)3 PhCl
In(NTf2)3 PhCl
In(NTf2)3 PhCl
In(NTf2)3 PhCl
5
12
22
43
84
35
52
13
indium–heteroaryl
p-complex
4
29
59
21
26
5
59
66
61
63
61
<1
Scheme 1. Synthetic methods of heteroarylamines by
using amines as nucleophiles based on the C–N bond
formation. In = an indium salt.
93
89
91
98
3
(DG)
M
Het
(DG)
5
<1
route E1 cat. transition metal
(M = B, Al, Si, H)
R1R2N Het
none
PhCl
[a] Reagents (unless otherwise specified): 1a (0.625 mmol),
2a (0.250 mmol), Lewis acid [25.0 mol (10 mol%)],
solvent (1.0 mL). Solvent abbreviations: Dioxane = 1,4-
R1R2NY
[b]
Y = OCOPh, OSiR3,
OSO2Ar, Cl
metal Het
route E2
[c]
R1R2N Het
dioxane; DEE = 1,2-diethoxyethane. Determined by GC
[d]
(metal = Mg, Cu)
using n-decane as an internal standard.
Determined by
1H NMR using nitromethane as an internal standard.
[e]
[f]
Scheme 2. Synthetic methods of heteroarylamines using
amines as electrophiles based on the C–N bond formation.
Performed with 1a (0.750 mmol).
Performed with 1a
(0.500 mmol). [g] Performed with 1a (0.375 mmol).
2
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
similarly provided 3aa in a comparable yield of 63%
(entry 16), but the further lower loading of 1a (1.5
molar equivalents) slightly brought about the SNAr
biheteroaryl formation between 2a and product 3aa
(entry 17), as in our preceding study.[12] No amination
was observed in the absence of a Lewis acid catalyst
(entry 18).
methoxythiophenes 2a and 2b, the C3 of 3-
methoxythiophene (2c) accepted nucleophilic attack
of 1a and 1e to give 3ac and 3ec, respectively. In the
case of 3,4-dimethoxythiophene (2d), only the single
amination proceeded, whereby mono-aminated
methoxythiophene 3ed was obtained in a high yield
of 86%. In addition to this result, the selective single
and double aminations of 2d are feasible by the
appropriate choice of the reaction conditions, when
using aniline (1i) as a primary amine nucleophile
(Scheme 3). Thus, the reaction carried out with a
slight excess of 1i to 2d (1.1:1) in solvent PhCl at
60 °C led to the selective single amination (3id), and,
on the other hand, the treatment of 2d with a ten-fold
excess of 1i under the solvent-free conditions at
70 °C exclusively provided diaminothiophene 3iid.
Importantly, 1i that has the two N–H bonds
underwent no over-thienylation to give, for instance,
dithienylaniline 3idd, and thus favorably resulted in
the exclusive mono-thienylation. This trend also
holds true for other entries with a variety of primary
amines, as collected in Table 3 (vide infra), and is in
sharp contrast to the palladium-catalyzed amination
of 3-bromothiophene with primary amines to
generate a mixture of mono- and di-thienylated
amines.[20] A further unique aspect of this method is
the MeO-selective SNAr amination to 3-bromo-4-
methoxythiophene (2e) wherein the Br group that can
also behave as a leaving group co-exists (Scheme 4).
Thus, the reaction of 2e with 1i gave 3ie exclusively
without the formation of 3’ie. This unusual functional
With the promising reaction conditions in hand, the
SNAr amination of a series of thiophene electrophiles
2 with some amine nucleophiles 1 was examined
(Table 2). As similar to the nitrogen atom of
morpholine (1a), those of cyclic dialkylamines
including thiomorpholine (1b), N-phenyl- (1c) and N-
acetylpiperazine (1d) reacted as nucleophilic sites
with 2-methoxythiophene (2a), thus providing 2-
aminothiophenes 3ba–3da in moderate to high yields.
The MeO group of 2a was also readily substituted by
simple and functionalized indolines of cyclic
alkylarylamines, in which even 1f with the strongly
electron-withdrawing nitro group worked well as a
nucleophile (3ea–3ga). Of importance to note is that
the NO2 and Br groups on the aryl unit can act as
leaving groups in the general SNAr reaction,[19] but
here remained intact under the reaction conditions.
The indium catalyst also connected some amines with
2-methoxy-5-methylthiophene (2b) to produce the
corresponding aminothiophenes 3ab–3hb. Besides 2-
Table 2. Indium-catalyzed SNAr amination of thiophene
electrophiles with secondary amines.[a]
R4
R4
In(NTf2)3
(1–15 mol%)
1.1–2.5:1
R3
R1R2N
R3
R1R2NH
O
+
PhCl, T ºC, t h
1i:2d = 1.1:1
In(NTf2)3
(10 mol%)
S
S
O
1
2
3
O
N
+
O
S
PhCl
60 ºC, 24 h
HN
3aa (X = O); 63% yield, In = 10, T = 110, t = 24
3ba (X = S); 56% yield, In = 10, T = 110, t = 24
3ca (X = PhN); 66% yield, In = 10, T = 130, t = 24
3da (X = AcN); 80% yield, In = 10, T = 130, t = 48
S
X
N
NH2
1i
S
S
3id; 93% yield
(+3iid; 2% yield)
3idd
+
NO2
O
Br
1i:2d = 10:1
In(NTf2)3
(10 mol%)
O
S
HN
N
N
N
70 ºC, 40 h
2d
S
S
S
HN
S
3ea; 74% yield
In = 1, T = 90, t = 24
3fa; 76% yield
In = 1, T = 90, t = 24
3ga; 67% yield
In = 1, T = 90, t = 24
3iid; 94% yield
Scheme 3. Indium-catalyzed SNAr amination of 3,4-
dimethoxythiophene with aniline.
O
N
N
N
S
S
S
3ab; 67% yield
In = 10, T = 110, t = 96
3eb; 93% yield
In = 1, T = 90, t = 48
3hb; 91% yield
In = 10, T = 110, t = 21
O
NH2
Br
HN
O
N
N
N
1i
+
+
S
S
S
In(NTf2)3 (5 mol%)
HN
3ie; 64% yield
O
3ac;[b] 73% yield
3ec; 85% yield
3ed; 86% yield
S
S
PhCl, 110 ºC, 24 h
Br
In = 15, T = 130, t = 24 In = 3, T = 110, t = 24 In = 10, T = 110, t = 24
3'ie
O
[a]
Reagents (unless otherwise noted): 1 (0.275–0.625
S
mmol), 2 (0.250 mmol), In(NTf2)3 (2.50–37.5 mol), PhCl
(1.0 mL). Yields of isolated 3 based on 2 are shown here.
In: mol% of In(NTf2)3 used. See the Experimental Section
for further details. [b] Performed in PhCl (0.50 mL).
2e
Scheme 4. Indium-catalyzed SNAr amination of 3-bromo-
4-methoxythiophene with aniline.
3
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
group selectivity is in sharp contrast to the transition
metal catalysis[5e,j] and also other reactions.[21] As
already stated, the indium salt catalyzes the SNAr-
based biheteroary synthesis.[12] By utilizing our
original reaction, as shown in Scheme 5, the
remaining nucleophilic -site of the thienyl ring in
3ha derived from the amination of 2a with 1h is
available in situ for the tandem heteroaryl–heteroaryl
bond formation. Thus, different from the standard
reaction conditions with an excess amount of amine 1
to 2, treating a 1:2.5 mixture of 1h and 2a at 130 ºC
for 48 h provided 4haa in 56% yield, without
contamination by 3ha.
NH
S
In(NTf2)3
(10 mol%)
1h
N
+
N
+
PhCl
130 ºC, 48 h
S
S
O
S
4haa; 56% yield
3ha; <1% yield
2a
Scheme 5. Indium-catalyzed tandem SNAr reaction of 2-
methoxythiophene with N-methyl-p-toluidine.
Table 3. Indium-catalyzed SNAr amination of 3- and 2-methoxybenzothiophenes.[a]
1.2–2.5:1
In(NTf2)3 (1–30 mol%)
R1R2NH
R1R2N
+
O
PhCl, T ºC, t h
S
S
1
2f or 2g
3
N
S
O
N
N
N
N
3ef; 94% yield
S
S
S
S
3af; 93% yield
In = 15, T = 130, t = 48
3jf;[b] 75% yield
In = 15, T = 150, t = 72
3kf;[c] 89% yield
In = 30, T = 110, t = 8
3lf;[d] 80% yield
In = 30, T = 110, t = 24
In = 10, T = 110, t = 14
O
I
HO
HN
S
HN
S
HO HN
S
HN
HN
S
S
3if; 99% yield
In = 1, T = 90, t = 24
3mf; 94% yield
In = 1, T = 90, t = 24
3nf; 88% yield
In = 1, T = 90, t = 24
3of; 81% yield
In = 1, T = 90, t = 24
3pf; 89% yield
In = 5, T = 50, t = 9
CF3
NC
EtO2C
Br
F3C
HN
HN
HN
3sf; 84% yield
HN
S
S
S
S
3qf; 90% yield
3rf; 85% yield
3tf; 91% yield
In = 5, T = 50, t = 9
In = 5, T = 50, t = 24
In = 5, T = 50, t = 48
In = 3, T = 90, t = 24
H
N
N
S
N
N
HN
S
HN
S
HN
S
HN
S
3uf; 72% yield
3vf; 92% yield
3wf;[e] 70% yield
3xf;[e] 66% yield
In = 1, T = 90, t = 24
In = 10, T = 110, t = 3
In = 10, T = 130, t = 48
In = 10, T = 110, t = 48
HN
S
HN
S
3yf;[d] 79% yield
In = 30, T = 130, t = 48
HN
HN
HN
3abf;[d] 65% yield
S
S
S
3zf; 93% yield
In = 30, T = 130, t = 96
3aaf; 75% yield
In = 30, T = 130, t = 24
3ig; 98% yield
In = 1, T = 90, t = 24
In = 30, T = 130, t = 48
[a] Reagents (unless otherwise noted): 1 (0.300–0.625 mmol), 2 (0.250 mmol), In(NTf2)3 (2.50–75.0 mol), PhCl (1.0 mL).
Yields of isolated 3 based on 2 are shown here. In: mol% of In(NTf2)3 used. See the Experimental Section for further
[b]
[c]
[d]
details. Performed with o-Cl2C6H4 instead of PhCl as a solvent. Performed in PhCl (0.50 mL). Performed in PhCl
(0.25 mL). [e] Performed with a 1:2 mixture of 1 (0.250 mmol) and 2f.
4
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
We successively investigated the scope of the
NH3•HOCOMe salt, the indium catalyst put NH3
together with 2 molar equivalents of 2f to give 3aeff
as a sole product, without the corresponding mono-
and tri-benzothienylated amines being detected.
In contrast to amines so far examined, an N–H
bond was found to not necessarily lead to the N–C
bond formation. Thus, the C–C bond formation
occurred exclusively in the reaction of 2f with cyclic
diarylamine 1af, thereby giving 3’aff in a good yield
(Scheme 7).[24]
Besides the thienyl and benzothienyl electrophiles,
oxygen- and nitrogen-based heteroaryl rings can be
incorporated as a part of the product to further expand
the library of this heteroarylamine synthesis (Table 4).
Even though the furan ring is the least aromatic of the
5-membered 1-heteroatom-containing heteroaryl
rings[25] and, in general, is not a good substrate for
this type of substitution,[26] the amination of 2-
methoxy-5-phenylfuran (2h) with indoline (1e) or N-
methylaniline (1k) proceeded to give 3eh or 3kh in a
moderate yield, respectively. For the coupling of 2-
methoxybenzofuran (2i) with 1e, 1 mol% of
In(NTf2)3 is enough, leading to the isolation of 3ei in
amination, and found that 3-methoxybenzothiophene
(2f) is a good heteroaryl electrophile to accept a
broad range of amines highly efficiently (Table 3).
Not only the types of amines used for the reaction of
2-methoxythiophene (2a) (3af, 3ef and 3kf), but also
other types, that is, acyclic dialkylamine 1j and
diarylamine 1l constructed the desired N–C bonds
with 2f, giving 3jf and 3lf. Moreover, aniline (1i) and
its derivatives (1m–1u) with high substitutional
diversity can be also installed onto the benzothienyl
ring (3if–3uf). In regard to the amination with the
aniline derivatives, the present method again
demonstrated favorable chemo-selectivity on the
leaving group: the aryl–OMe, –I, –Br and –CN
moieties that possibly undergo nucleophilic
substitution were survived safely (3mf, 3pf, 3qf and
3sf).[19] The OH groups co-existing with the NH2 one
in 1n and 1o did not disturb the amination process by
acting as nucleophilic sites, and 3nf and 3of were
thus obtained in high yields. The generation of 3qf–
3tf clearly indicates that electron-withdrawing groups
do not interfere with the nucleophilic attack of the
aniline substrates. Furthermore, the CO2Et
functionality has been known to react with amines to
form amides in the presence of acid catalysts
including an indium salt, but In(NTf2)3 catalyzed only
the desired amination without the amidation (3tf).[22]
Diheteroaylamines 3vf–3xf consisting of two
different heteroaryl units can be also prepared from
aminoheteroarenes with, for instance, indolyl, pyridyl
and benzothiazolyl structures. This protocol is
applicable as well to primary alkylamines with linear
and branched alkyl chaines as well as benzyl and
alkenyl moieties, whereas these aminations required
higher loadings of In(NTf2)3 and higher reaction
temperatures (3yf–3abf). This may be due to higher
nucleophilicity of the primary alkylamine that
possibly impairs the catalytic activity of the indium
Lewis acid. Notably, in the reaction of 1ab to form
3abf, the C=C bond was tolerated without suffering
Lewis acid-induced hydroamination.[23] Similar to 2f,
2-methoxybenzothiophene (2g) can be activated
under indium catalysis, thereby reacting smoothly
with 1i to give 3ig in 98% yield. Since both of the
aminations of 2f and 2g with 1i equally proceeded in
a quantitative manner under the same reaction
conditions (3if and 3ig), a wide variety of amines
other than 1i should be expected to be applied to the
amination of 2g.
In(NTf2)3
(10 mol%)
Me2NH/THF (2 M)
or
+
3:1
O
Me2N
S
S
PhCl
130 ºC, 72 h
O
2f
•
Me2NH HO
N
with Me2NH/THF: 3acf; trace
with Me2NH•HOCONMe2: 3acf; 47% yield
1ac
In(NTf2)3
(20 mol%)
MeNH •
+
3:1
O
MeHN
HCl
2
S
S
PhCl
130 ºC, 48 h
1ad
2f
3adf; 54% yield
S
O
In(NTf2)3
(10 mol%)
•
NH3 HO
+
2:1
O
HN
3aeff; 60% yield
S
S
PhCl
130 ºC, 48 h
1ae
2f
Scheme 6. Indium-catalyzed SNAr amination of 3-
methoxybenzothiophene with small molecular weight
amines.
S
In order to broaden the scope of this reaction, we
tried the use of small molecular weight amines, which
are originally gaseous and thus are troublesome to
handle (Scheme 6). With the 2 M THF solution of
Me2NH for easy handling, almost no nucleophilic
substitution on 2f was unfortunately observed. In
marked contrast, its salt with N,N-dimethylcarbamic
acid that can be also easily handled successfully
reacted with 2f to afford desired product 3acf.
Introducing the MeHN group is also possible by
using the HCl salt of MeNH2 (1ad), giving 3adf in a
moderate yield of 54%. In a similar manner with the
In(NTf2)3 (30 mol%)
O
NH
+
NH
S
PhCl, 110 ºC, 24 h
3:1
1af
2f
3'aff; 77% yield
Scheme 7. Indium-catalyzed SNAr C–C bond formation of
3-methoxybenzothiophene with cyclic diarylamine 1af.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
97% yield. In spite of the fact that pyrrole and indole
rings are the most electron-rich heteroaryl
molecules,[27] the indium catalyst here again
successfully worked as a tentative EWG to connect
pyrrole 2j and indole 2k with amines, thus providing
3aj, 3ak, and 3ek in good yields. When synthesizing
the aminoindole, commercially available 3-
acetyloxyindole (2k) wherein not the alkoxy group
but the acetyloxy (AcO) one acts as a leaving group
can be used, and only the ipso substitution desirably
occurred. This outcome is in sharp contrast to the
preceding SNAr-based heteroaryl–heteroaryl bond
formation of 2k, which resulted in the non-selective
ipso and cine substitutions.[12]
Not only to the amination, but this system is also
applicable to the alkoxylation and thiolation (Table
5).[28] For example, the MeO group of 2-
methoxythiophene (2a) can be replaced with another
alkoxy group with a longer alkyl chain with the aid of
the indium catalyst. Upon treatment of a 4:1 mixture
of n-decanol (5a) and 2a with 10 mol% of In(NTf2)3
in a manner similar to the amination, 63% yield of 2-
decyloxythiophene (7aa) was thus obtained. The
introduction of the multi-oxygenated alkoxy unit is
also feasible (7ba). As shown separately in Scheme 8,
due probably to the lower nucleophilicity of phenol
(5c), no phenoxylation of 2f leading to 7cf was
attained, but instead, the SNAr-based dimerization
between the two molecules of 2f selectively
proceeded to afford 9 in 87% yield. The absence of
5c, however, substantially reduced the yield of 9. At
present, while it is unclear how phenol affects to the
selective dimerization, a survey to ascertain the
unique behavior of phenol is ongoing. Returning to
the discussion of Table 5, the progress of the
thiolation of 2a and 2d provided us with desired
alkylthiothiophenes 8aa and 8bd in high yields.
As already demonstrated in Schemes 3, 4 and 6
and Table 3, the NH2 moiety of primary amines
undergoes the mono-heteroarylation exclusively, and
we naturally expected that this would be a good
opportunity to evolve the remaining NH group of the
product. Since a biphenyl structure sandwiched by
two diarylamino groups has been attracting
Table 5. Indium-catalyzed SNAr alkoxylation and
thiolation of thiophene electrophiles.[a]
In(NTf2)3 (1–10 mol%)
O
R1Y
n
R1YH
+
4:1
n
PhCl, T ºC, t h
S
S
Table 4. Indium-catalyzed SNAr amination of furan,
5 (Y = O)
6 (Y = S)
2
7 (Y = O)
8 (Y = S)
benzofuran, pyrrole, and indole electrophiles.[a]
O
Z
R3
n-C10H21
O
O
O
O
2h: Z = O, R3 = Ph
S
S
2j: Z = NPh, R3 = H
R1R2N
7aa; 63% yield
In = 10, T = 50, t = 4
7ba; 41% yield
In = 3, T = 80, t = 24
In(NTf2)3 (2 or 10 mol%)
PhCl, T ºC, t [min or h]
Z
R3
3eh, 3kh, 3aj
n-C12H25
S
R1R2NH
n-C10H21
S
n-C12H25
S
R4O
1
S
S
(2.5 equiv.)
Z
8aa;[b] 82% yield
In = 1, T = 50, t = 5
8bd; 86% yield
In = 10, T = 100, t = 24
2i: R4 = Me, Z = O
2k: R4 = Ac, Z = NH
R1R2N
[a] Reagents (unless otherwise noted): 5 or 6 (1.00 mmol), 2
(0.250 mmol), In(NTf2)3 (2.50–25.0 mol), PhCl (1.0 mL).
Yields of isolated 7 and 8 based on 2 are shown here. In:
In(NTf2)3 (1–10 mol%)
PhCl, T ºC, t h
Z
3ei, 3ak, 3ek
mol% of In(NTf2)3 used. See the Experimental Section for
[b]
further details.
Performed with 1.2 molar equiv. of 6a
(0.300 mmol) to 2a (0.250 mmol).
N
N
N
O
O
O
3eh; 50% yield
In = 10, T = 90
t = 10 min
3kh; 65% yield
In = 2, T = 110
t = 2 h
3ei;[b] 97% yield
In = 1, T = 50
t = 24 h
OH
O
O
N
In(NTf2)3
(10 mol%)
5c
N
+
O
+
S
S
PhCl
90 ºC, 24 h
S
O
N
N
NH
NH
7cf; <1% yield
9; 91% (87%) yield
without 5c: 9; 15% yield
3aj; 60% yield
In = 10, T = 90
t = 46 h
3ak;[c] 61% yield
In = 10, T = 110
t = 6 h
3ek;[c] 69% yield
In = 5, T = 100
t = 4 h
O
S
2f
[a]
Reagents (unless otherwise noted): 1 (0.625 mmol), 2
(0.250 mmol), In(NTf2)3 (2.50–25.0 mol), PhCl (1.0 mL).
Yields of isolated 3 based on 2 are shown here. In: mol%
Scheme 8. Indium-catalyzed SNAr reaction of 3-
methoxybenzothiophene in the presence of phenol. Yields
of 7cf and 9 determined by 1H NMR using nitromethane as
an internal standard are shown here. The yield of isolated 9
based on 2f is shown in parentheses.
of In(NTf2)3 used. See the Experimental Section for further
[b]
details.
Performed with 1.2 molar equiv. of 1e (0.300
mmol) to 2i (0.250 mmol). [c] Performed in PhCl (0.50 mL).
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
in situ at the C3- or C5-position of the thienyl ring
was trapped by D+ originating in the N–D part of 1e-
1-d. Besides these results, the kinetic isotope effect
(KIE) experiment was carried out with 1e or 1e-1-d in
the reaction of 2a, and indicated that, due to the kH/kD
value of 1.0, the stage of the N–H bond cleavage is
unlikely to be involved in the rate-determining step.
(Scheme 12).
N
NH
+
I
I
2.2:1
S
3uf
10
On the basis of the above experimental results and
of previous findings reported by us and others,
possible reaction mechanisms exemplified by the
reaction of 2a and R1R2ND (1-d) are proposed in
Scheme 13, where path a and b leading to 3-5-d and
3-3-d, respectively, are depicted. First up is the
coordination of 2a to the indium Lewis acid (In) to
form In–thienyl -complex 12,[12,33] wherein In
withdraws the electron from 2a, which then becomes
highly electrophilic to accept amine nucleophile 1.
The attack of 1-d to 12 occurs from the side opposite
to the coordinated In to afford allylindium type
intermediate 13-d or 13’-d,[34] which subsequently
CuI (10 mol%) t-BuOK (3 equiv.)
1,10-phenanthroline (30 mol%) toluene, 120 ºC, 15 h
N
N
N
N
S
S
11; 43% yield, lmax = 407 nm, FF = 0.19
Scheme 9. Synthetic application: copper-catalyzed
coupling of 3uf with 4,4’-diiodobiphenyl. A fluorescence
spectrum excited at 265 nm was measured in CH2Cl2 (c =
1.5 x 10–6 M). The quantum yield of 11 was determined
with reference to that of p-terphenyl.
NH
1e
In(NTf2)3 (1 mol%)
N
n-C10H21OH
+
+
PhCl, 90 ºC, 24 h
considerable attention as charge transport materials[29]
found in, for instance, organic light-emitting
diodes[30] and photovoltaic cells,[31] a heteroarylamine
in hand was applied to construct such a related
architecture but designed uniquely. Amongst a lot of
candidates, we picked up 3uf, which was then treated
with 4,4’-diiodobiphenyl (10) under the Ullmann–
Goldberg conditions,[32] thereby giving potentially
useful structure 11. It was found that 11 is a blue-
violet light-emitting photoactive molecule with the
emission maximum at 407 nm when excited at 265
nm in CH2Cl2 (Scheme 9).
Some experimental observations are available for
the mechanistic studies of this reaction. We first
confirmed whether the heteroarylamine formation in
fact proceeds via the nucleophilic substitution on the
heteroaryl ring. Thus, after the treatment of 1e and 2-
decyloxythiophene (7aa) with the long alkyl chain
under the conditions shown in Scheme 10, n-decanol
(5a) was secured in 53% yield with 58% conversion
of 7aa and with the generation of 3ea in 54% yield,
showing that the decyloxy group on the aromatic
thienyl ring is replaced by the N-indolinyl unit, and
that this reaction is thus based on the SNAr route. In
addition, the result already demonstrated in entry 18
of Table 1 reveals that the indium catalyst is
indispensable and accordingly a key activator for the
SNAr process. We next carried out the reaction of a
deuterium labelling experiment (Scheme 11). Under
the same reaction conditions as those for the reaction
of 2a with 1e, the replacement of the amine substrate
(1e) with the corresponding deuterium labelled
indoline (1e-1-d; 85%-d) led to the formation of 3ea-
3-d and 3ea-5-d with 50% total deuterium content.
This result implies that a carbon–indium bond formed
S
3ea; 54% yield 5a; 53% yield
n-C10H21
O
S
7aa; 58% conversion
Scheme 10. A confirmation experiment of a released
alcohol.
ND
1e-1-d
(85%-d)
D
In(NTf2)3 (1 mol%)
+
N
+
N
PhCl, 90 ºC, 24 h
S
S
D
O
S
2a
3ea-3-d
(20%-d)
3ea-5-d
(30%-d)
total; 76% yield, 50%-d
Scheme 11. A deuterium labelling study: reaction of 1e-1-
d with 2a.
In(NTf2)3 (1 mol%)
NH
N
+
O
O
PhCl, 90 ºC, 10–60 min
S
S
2a
2.5:1
3ea
1e
(H)D
In(NTf2)3 (1 mol%)
N
ND
+
PhCl, 90 ºC, 10–60 min
S
S
D(H)
2.5:1
1e-1-d
2a
3ea-3-d, 3ea-5-d
kH/kD = 1.0
Scheme 12. Kinetic isotope effect experiments.
7
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
undergoes regioselective deuteration at the  site of
the allylindium unit by the migration of the D+ from
the R1R2N+D moiety, as previously demonstrated.[35]
The elimination of MeOH(D) from 14-5-d or 14’-3-d
for the re-aromatization provides desired product 3-5-
d or 3-3-d, respectively. As observed in Scheme 11,
the decrease of the D content from substrate 1e-1-d
(85%-d) to product 3ea-d (total 50%-d) should be
ascribed to the final step in which MeOD would be
able to be eliminated.
starting substrate is unlikely. A possible route from
3ea to 3ea-3-d is presented in Scheme 15, and thus
starts with the formation of -complex 15, which then
accepts the nucleophilic attack of MeOD to give 16’-
d but not to do possible alternative 16-d, due possibly
to the steric repulsion between the indolinyl and In
moieties. The -selective deuteration of the
allylindium unit in 16’-d leading to 17’-d[35] followed
by the elimination of MeOH(D) results in the
generation of 3ea-3-d. No formation of 2a-3-d by the
elimination of 1e-1-d from 17’-d should be
responsible for the higher leaving ability of the
methoxy group than the indolinyl one.[36] Throughout
the present study, of note is that the successful SNAr
heteroaryl amination would be largely dependent on
no participation of the reverse process on the basis of
the lower leaving ability of the R2N group.
The additional experiment shown in Scheme 14 is
likely to be available for discussing which of path a
or b is in operation. Thus, in the presence of MeOD
instead of MeOH being the by-product in the
amination, the treatment of product 3ea under the
standard reaction conditions gave only 3ea-3-d
deuterated at the C3-position of the thienyl ring in
91% yield with 23% deuterium incorporation. The
results of Scheme 14 as well as Scheme 11 (vide
supra) seem to provide us with important mechanistic
insights. Firstly, since the deuterium content of 3ea-
3-d produced in the two reactions is almost equal, the
C3-deuterium incorporation of 3ea may occur not
during the amination process of 2a but after the
formation of 3ea. Next, since no 3ea-5-d is produced
in the reaction of Scheme 14, the C5-deuterium
incorporation of 3ea is considered to occur only
during the amination process of 2a. From these taken
collectively, path a leading to the formation of 3-5-d
would be more plausible than path b as the route of
the present amination. On the other hand, as shown
also in Scheme 14, 1e-1-d and 2a-3-d that could be
potentially formed by nucleophilic attack of MeOD to
3ea were neither detected. This result and the result
on the formation of 3ea-3-d, both in Scheme 14,
suggest that re-attack of by-product MeOH to product
3 is plausible under the reaction conditions, but the
existence of the reverse process to go back to the
Finally, with regard to the coordination mode of 2a
to In, there could be four possibilities of A–D at least
as shown in Figure 1. Among them, D may be
(23%-d)
D
MeOD
(99%-d)
In(NTf2)3 (1 mol%)
+
N
PhCl, 90 ºC, 24 h
S
3ea-3-d; 91% yield
N
(H)D
S
3ea
O
NH(D)
S
2a-3-d
1e-1-d
not detected
Scheme 14. A deuterium labelling study: reaction of
MeOD with 3ea.
N
+
MeOD
path a
path b
S
3ea
MeO
S
In
In
In
2a
In
In
+
MeO
MeO
In–
S
S
12
In
R1R2ND
12
R1R2ND
R1R2ND
N
N
In–
1-d
N
S
S
15
S
MeOD
MeOD
+
+
In
In
16-d
MeOD
16'-d
In–
unfavored
favored
a
g
b
b
MeO
MeO
In–
g
a
S
S
R1R2ND
R1R2ND
– In
+
+
NH(D)
1e-1-d
13-d
13'-d
(H)D
MeO
(H)D
MeO
R1R2N
D(H)
D(H)
S
S
R1R2N
O
14-5-d
14'-3-d
S
D(H)
2a-3-d
N
MeOH(D)
S
MeO
(H)D
N
(H)D
R1R2N
17'-d
R1R2N
S
3-5-d
S
3-3-d
S
3ea-3-d
MeOH(D)
Scheme 13. Proposed reaction mechanisms. In = an
indium salt.
Scheme 15. A possible route from 3ea to 3ea-3-d in the
presence of MeOD.
8
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
excluded first from the candidate list because 3-
methoxythiophene (2c) of which the oxygen and
sulfur atoms cannot coordinate concurrently to In
works as a substrate (see 3ac and 3ec in Table 2). At
present, it is difficult to eliminate the possibility of B
and C. However, because of the deuterium labelling
studies showing the possibility of the in situ
formation of the C–In bond, coordination mode A
wherein the carbon atoms of the thienyl ring directly
furans and pyrroles fused with/without a benzene
ring; for the functional group: NO2, Br, I, CF3, CN,
CO2Et, pyridyl, thiazolyl, C=C, and OH groups. As if
to reflect these diversity, 34 structures of 49
heteroarylamines synthesized here are new
compounds unreported in the literature. Moreover,
our method provides at least the following three
advantages, compared to the transition metal catalysis
based on the C–halogen bond amination: (1) amines
selectively substitute the MeO group even in the co-
existence of the Br group (see Scheme 4); (2) the
SNAr-based tandem C–N and C–C bond-forming
reactions are achievable in one step (see Scheme 5);
(3) N-unsubstituted indoles can be used directly as
electrophiles without the protection–deprotection
treatment on the nitrogen atom (see Table 4).[37]
Mechanistic studies revealed that the reaction
proceeds through the SNAr pathway including the
elimination of the MeOH, that the C–In bond is
formed in situ, and that the cleavage of the
amine(N)–H bond is unlikely to be involved in the
interact with In appears to be most likely.
In
MeO
MeO
In
MeO
MeO
S
S
S
S
In
In
A (12)
B
C
D
Figure 1. Possible coordination modes of 2-
methoxythiophene to an indium salt.
Conclusion
rate-determining
step.
Application
of
this
We have demonstrated herein that the indium Lewis
acid acts as an effective catalyst for the SNAr-based
amination of electron-rich heteroarenes. The key to
the achievement would be the choice of the indium
catalyst, which behaves as the tentative EWG capable
of bringing the character of the electron-rich
heteroaryl molecule into the electrophile. Therefore,
in sharp contrast to the corresponding conventional
heteroaryl amination, our system is independent of
both of the EWG-substituted heteroaryl electrophile
and the metal amide, and thus is applicable to a broad
range of substrates with high functional group
compatibility (Figure 2): for the amine nucleophile: 8
types except for cyclic diaryl amines; for the
heteroaryl electrophile: all 6 types of thiophenes,
transformation is in progress in our laboratory.
Experimental Section
General Remarks
All manipulations were conducted with a standard Schlenk
technique under an argon atmosphere. Nuclear magnetic
resonance (NMR) spectra were taken on a JEOL JMN-
ECA 400 (1H, 400 MHz; 13C, 100 MHz) or JEOL JMN-
ECA 500 (1H, 500 MHz; 13C, 125 MHz) spectrometer
using tetramethylsilane (1H and 13C) as an internal standard.
Analytical gas chromatography (GC) was performed on a
Shimadzu model GC-2014 instrument equipped with a
capillary
column
of
ID-BPX5
(5%
phenyl
polysilphenylene-siloxane, 30 m x 0.25 mm x 0.25 m) or
InertCap 5 (5% diphenyl- and 95% dimethylpolysiloxane,
30 m x 0.25 mm x 0.25 m) and with a FID detector, using
nitrogen as carrier gas. Gas chromatography-mass
spectrometry (GC-MS) analyses were performed with a
Shimadzu model GCMS-QP2010 instrument equipped
with a capillary column of ID-BPX5 or InertCap 5 by
electron ionization at 70 eV using helium as carrier gas.
Preparative recycling gel permeation chromatography
(GPC) was performed with JAI LC-9105 equipped with
JAIGEL-1H and JAIGEL-2H columns using chloroform as
eluent. High-resolution mass spectra (HRMS) were
obtained with a JEOL JMS-T100GCV spectrometer.
Elemental analyses were performed on a Vario EL III
elemental analysis instrument. UV-vis absorption spectra
were recorded with a JASCO V-550 spectrophotometer at
room temperature. Fluorescence spectra were recorded
with a JASCO FP-6500 spectrofluorometer at room
temperature using an excitation wavelength of 265 nm. A
solution of p-terphenyl in cyclohexane was used as a
quantum yield standard (F = 0.87 at 265 nm excitation).
All melting points were measured with a Yanaco Micro
Melting Point apparatus and are uncorrected. Kugelrohr
bulb-to-bulb distillation was carried out with a Sibata glass
tube oven GTO-250RS apparatus. 1,4-Dioxane (Dioxane)
and dibutyl ether (Bu2O) were distilled under argon from
sodium just prior to use. Toluene, 1,2-diethoxyethane
El
Nu
cat. In(NTf2)3
R1R2NH
O
R1R2N
+
Z
Z
Z = S, O, NR
H
alkyl
N H
alkyl
N H
N H
H
alkyl
alkyl
alkyl
alkyl
alkyl
N H
Nu =
N H
N H
N H
N H
H
aryl
aryl
aryl
aryl
aryl
N H
H
aryl
aryl
C–C bond formation
alkyl OH
alkyl SH
S
O
N
Ph
=
Z
in
(DEE),
nitromethane
(MeNO2),
p-xylene,
o-
dichlorobenzene, substrates 1a, 1e, 1r, 2a–2f, 2i, 2j, 5, 6,
and 7aa were stored over molecular sieves 4Å (MS 4Å)
under argon. Butyronitrile (PrCN) was distilled under
argon from P2O5 just prior to use. Chlorobenzene (PhCl)
was distilled under argon from CaCl2 just prior to use.
Substrates 1b, 1h–1k, 1q and 1y–1ab were stored over
El
S
O
N
H
Figure 2. Outline of the indium-catalyzed SNAr amination
of methoxyheteroarenes.
9
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
KOH pellets under argon. Anhydrous dimethylacetamide
(DMA) and anhydrous N,N-dimethylformamide (DMF)
were commercially available and used without further
purification. MeOH was stored over molecular sieves 3Å
(MS 3Å) under argon. The following indium salts and
substrates were synthesized according to the respective
literature methods: In(ONf)3,[38] In(NTf2)3,[39] 3,4-
Synthesis of 2-Methoxybenzo[b]furan (2i)
Based on the literature procedure,[40] 2i was synthesized
using the following reagents and conditions: 2-
bromobenzo[b]furan (1.46 g, 7.43 mmol), CuBr (212 mg,
1.48 mmol), NaOMe (638 mg, 11.8 mmol), MeOH (1.5
mL), 90 ºC, 3 h, and was isolated by Kugelrohr bulb-to-
bulb distillation (80 ºC/100 Pa) in 80% yield (881 mg) as a
colorless liquid. Compound 2i was fully characterized by
dimethoxythiophene
(2d),[40]
3-bromo-4-
methoxythiophene (2e),[41] 3-methoxybenzo[b]thiophene
(2f),[42]
4-(2,5-dimethyl-1H-pyrrol-1-yl)benzenamine
1H and 13C NMR spectroscopy and HRMS, as follows: H
1
(1u),[33a] 2-bromobenzo[b]furan,[43] indoline-1-d (1e-1-
d).[44] Unless otherwise noted, other substrates and reagents
were commercially available and used as received without
further purification.
NMR (400 MHz, CDCl3)  3.97 (s, 3 H), 5.52 (d, J = 0.9
Hz, 1 H), 7.11 (td, J = 7.7, 1.7 Hz, 1 H), 7.15 (td, J = 7.6,
1.2 Hz, 1 H), 7.31 (ddd, J = 7.9, 1.8, 1.0 Hz, 1 H), 7.34–
7.39 (m, 1 H); 13C NMR (125 MHz, CDCl3)  57.6, 75.7,
110.1, 119.1, 121.6, 122.9, 129.7, 148.9, 164.3. HRMS
(FI) Calcd for C9H8O2: M, 148.0524. Found: m/z 148.0531.
Synthesis of Methoxyheteroarene Substrates
Substrates 2b, 2g, 2h, 2i and 2j were synthesized based on
the reported or modified literature procedures that have
been used for preparing the related compounds, and were
Synthesis of 2-methoxy-1-phenyl-1H-pyrrole (2j)
According to the modified literature procedure, 2j was
synthesized in two steps of the bromination of 1-phenyl-
1H-pyrrole[47] followed by the methoxylation.[40]
1
fully characterized by H and 13C NMR spectroscopy, and
HRMS, unless otherwise noted.
The first step: A flame-dried 100 mL Schlenk tube was
filled with argon and then charged with anhydrous DMF
(40 mL), 1-phenyl-1H-pyrrole (1.43 g, 10.0 mmol) and N-
bromosuccinimide (1.78 g, 10.0 mmol) at –50 ºC. After
stirring at –20 ºC for 1 h, sodium sulfite (2.00 g) was added
to the mixture, and stirred at room temperature for 5 min.
The resulting mixture was diluted with Et2O (100 mL), and
then washed with water (100 mL x 3) and brine (20 mL).
The organic layer was dried over anhydrous Na2SO4.
Filtration and evaporation of the solvent provided a brown
oil (2.08 g). The formation of 2-bromo-1-phenyl-1H-
Synthesis of 2-Methoxy-5-methylthiophene (2b)
Based on the literature procedure,[40] 2b was synthesized
using the following reagents and conditions: 2-bromo-5-
methylthiophene (8.85 g, 50.0 mmol), CuBr (1.43 g, 10.0
mmol), NaOMe (4.32 g, 80.0 mmol), MeOH (10 mL), 90
ºC, 8 h, and was isolated by Kugelrohr bulb-to-bulb
distillation (120 ºC/67.0 hPa) in 72% yield (4.62 g) as a
colorless liquid. Compound 2b was fully characterized by
1H and 13C NMR spectroscopy and HRMS, as follows: H
1
1
pyrrole was confirmed by GC-MS and H NMR analyses,
NMR (400 MHz, CDCl3)  2.34 (d, J = 1.4 Hz, 3 H), 3.84
(s, 3 H), 5.96 (d, J = 3.7 Hz, 1 H), 7.02 (dq, J = 3.7, 1.2 Hz,
1 H); 13C NMR (100 MHz, CDCl3)  15.5, 60.2, 103.2,
121.8, 126.0, 164.0. HRMS (FI) Calcd for C6H8OS: M,
128.0296. Found: m/z 128.0305.
and the resulting crude product was used for the next step
without purification.
The second step: A flame-dried 50 mL Schlenk tube was
filled with argon and then charged with NaOMe (1.62 g,
30.0 mmol) and MeOH (3.0 mL). The mixture was stirred
at room temperature until NaOMe is completely dissolved.
To this were added CuBr (287 mg, 2.00 mmol) and crude
2-bromo-1-phenyl-1H-pyrrole (2.08 g). After stirring at
100 ºC for 3 h, the solution was filtered through a pad of
Celite. The resulting filtrate was diluted with Et2O (100
mL), and then washed with a saturated NaHCO3 aqueous
solution (20 mL x 2), water (20 mL) and brine (10 mL).
The organic layer was dried over anhydrous sodium sulfate
(Na2SO4). Filtration and evaporation of the solvent
followed by column chromatography on silica gel
Synthesis of 2-Methoxybenzo[b]thiophene (2g)
Based on the literature procedure,[40] 2g was synthesized
using the following reagents and conditions: 2-
bromobenzo[b]thiophene (1.07 g, 5.00 mmol), CuBr (143
mg, 1.00 mmol), NaOMe (459 mg, 8.50 mmol), MeOH
(1.0 mL), 90 ºC, 8 h, and was isolated by Kugelrohr bulb-
to-bulb distillation (120 ºC/400 Pa) in 66% yield (542 mg)
as a white solid, mp 41–42 ºC. Compound 2g has already
appeared in the literature,[45] and its spectral and analytical
data are in good agreement with those reported.
(hexane/EtOAc/Et3N
=
100/2/3) gave 2-methoxy-1-
phenyl-1H-pyrrole (2j) in 37% yield (641 mg) for the two
1
Accordingly, 13C NMR data are omitted here. H NMR
steps as a colorless oil. Compound 2j was fully
(500 MHz, CDCl3)  3.98 (s, 3 H), 6.34 (s, 1 H), 7.15–7.20
(m, 1 H), 7.24–7.29 (m, 1 H), 7.50–7.54 (m, 1 H), 7.58–
7.62 (m, 1 H). HRMS (FD) Calcd for C9H8OS: M,
164.0296. Found: m/z 164.0296.
characterized by 1H and 13C NMR spectroscopy and
1
HRMS, as follows: H NMR (400 MHz, CDCl3)  3.81 (s,
3 H), 5.38–5.44 (m, 1 H), 6.08–6.15 (m, 1 H), 6.45–6.51
(m, 1 H), 7.21–7.30 (m, 1 H), 7.36–7.45 (m, 4 H); 13C
NMR (100 MHz, CDCl3)  57.9, 84.6, 106.6, 113.5, 124.1,
126.0, 128.9, 138.5, 147.8. HRMS (FI) Calcd for
C11H11NO: M, 173.0841. Found: m/z 173.0850.
Synthesis of 2-Methoxy-5-phenylfuran (2h)
Based on the literature procedure,[46] 2h was synthesized
using the following reagents and conditions: 2-
methoxyfuran (736 mg, 7.50 mmol), bromobenzene (785
mg, 5.00 mmol), PdCl2 (44.3 mg, 0.250 mmol),
tricyclohexyl phosphine (701 mg, 0.500 mmol, 20 wt% in
toluene), tetrabutylammonium bromide (1.61 g, 5.00
mmol), KOAc (982 mg, 10.0 mmol), anhydrous DMA (15
Indium-Catalyzed SNAr Amination of Thiophene
Electrophiles with Secondary Amines: A General
Procedure for Table 2
In(NTf2)3 [(2.39 mg, 2.50 mol), (7.16 mg, 7.50 mol),
(23.9 mg, 25.0 mol) or (35.8 mg, 37.5 mol)] was placed
in a 20 mL Schlenk tube, which was heated at 150 °C in
vacuo for 2 h. The tube was cooled down to room
temperature and filled with argon. PhCl (0.50 or 1.0 mL)
was added to the tube, and the mixture was then stirred at
room temperature for 3 min. To this were added 1 (0.275,
0.300 or 0.625 mmol) and 2 (0.250 mmol), and the
resulting mixture was stirred at 90, 110 or 130 °C. After
the time specified in Table 2, a saturated NaHCO3 aqueous
solution (0.5 mL) was added to the mixture, and the
aqueous phase was extracted with EtOAc (5 mL x 3). The
combined organic layer was washed with brine (1 mL) and
then dried over anhydrous sodium sulfate (Na2SO4).
mL), 80 ºC,
8 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc/Et3N =
60/1/1) in 66% yield (575 mg) as a yellow solid, mp 44–45
1
ºC. Compound 2h was fully characterized by H and 13C
1
NMR spectroscopy and HRMS, as follows: H NMR (400
MHz, CDCl3)  3.90 (s, 3 H), 5.25 (d, J = 3.4 Hz, 1 H),
6.53 (d, J = 3.2 Hz, 1 H), 7.17 (tt, J = 7.3, 1.4 Hz, 1 H),
7.30–7.36 (m, 2 H), 7.52–7.57 (m, 2 H); 13C NMR (100
MHz, CDCl3)  57.8, 81.7, 106.3, 122.5, 126.3, 128.6,
130.8, 144.1, 161.5. HRMS (FI) Calcd for C11H10O2: M,
174.0681. Found: m/z 174.0693.
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
Filtration and evaporation of the solvent followed by
purification gave product 3. Unless otherwise noted,
products 3 prepared in this section were fully characterized
by 1H and 13C NMR spectroscopy, and HRMS.
reagents and conditions: 1f (103 mg, 0.625 mmol), 2a
(28.5 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
PhCl (1.0 mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 5/1). A red
1
solid, mp 111–112 ºC. H NMR (500 MHz, CDCl3) 
3.23–3.30 (m, 2 H), 4.08 (t, J = 8.6 Hz, 2 H), 6.67 (dd, J =
3.7, 1.4 Hz, 1 H), 6.91 (dd, J = 5.7, 1.1 Hz, 1 H), 6.97 (dd,
J = 5.4, 3.7 Hz, 1 H), 7.22 (dt, J = 8.0, 1.1 Hz, 1 H), 7.68
(dd, J = 8.0, 1.7 Hz, 1 H), 7.79 (d, J = 1.7 Hz, 1 H); 13C
NMR (100 MHz, CDCl3)  28.1, 54.9, 102.3, 113.3, 115.2,
116.2, 124.5, 126.0, 137.9, 146.6, 148.5, 148.7. HRMS
(FD) Calcd for C12H10N2O2S: M, 246.0463. Found: m/z
246.0472.
4-(2-Thienyl)morpholine (3aa): The title compound was
synthesized using the following reagents and conditions:
1a (54.5 mg, 0.625 mmol), 2a (28.5 mg, 0.250 mmol),
In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0 mL), 110 °C, 24
h, and was isolated by column chromatography on silica
gel (hexane/EtOAc = 10/1). Compound 3aa has already
appeared in the literature,[48] and its spectral and analytical
data are in good agreement with those reported.
Accordingly, 13C NMR data are omitted here. A pale
1
yellow oil. H NMR (500 MHz, CDCl3)  3.10–3.16 (m, 4
5-Bromo-2,3-dihydro-1-(2-thienyl)-1H-indole (3ga): The
title compound was synthesized using the following
reagents and conditions: 1g (124 mg, 0.625 mmol), 2a
(28.5 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
PhCl (1.0 mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 80/1). A
pale green solid, mp 48–49 ºC. 1H NMR (400 MHz,
CDCl3)  3.17 (t, J = 8.6 Hz, 2 H), 3.97 (t, J = 8.6 Hz, 2 H),
6.51 (dd, J = 3.7, 1.4 Hz, 1 H), 6.80 (dd, J = 5.5, 1.4 Hz, 1
H), 6.91 (dd, J = 5.5, 3.7 Hz, 1 H), 6.94 (d, J = 8.5 Hz, 1
H), 7.18–7.25 (m, 2 H); 13C NMR (100 MHz, CDCl3) 
27.9, 54.4, 109.6, 110.96, 111.04, 114.4, 125.7, 127.8,
130.1, 132.7, 146.4, 147.8. HRMS (FI) Calcd for
C12H10BrNS: M, 278.9717. Found: m/z 278.9744.
H), 3.82–3.87 (m, 4 H), 6.15 (dd, J = 3.7, 1.4 Hz, 1 H),
6.64 (dd, J = 5.7, 1.1 Hz, 1 H), 6.80 (dd, J = 5.4, 3.7 Hz, 1
H). HRMS (FI) Calcd for C8H11NOS: M, 169.0561. Found:
m/z 169.0561.
4-(2-Thienyl)thiomorpholine (3ba): The title compound
was synthesized using the following reagents and
conditions: 1b (64.5 mg, 0.625 mmol), 2a (28.5 mg, 0.250
mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0 mL),
110 °C, 24 h, and was isolated by column chromatography
1
on silica gel (hexane/EtOAc = 20/1). A pale green oil. H
NMR (500 MHz, CDCl3)  2.74–2.79 (m, 4 H), 3.45–3.50
(m, 4 H), 6.14 (dd, J = 3.7, 1.4 Hz, 1 H), 6.63 (dd, J = 5.4,
1.4 Hz, 1 H), 6.78 (dd, J = 5.4, 3.7 Hz, 1 H); 13C NMR
(100 MHz, CDCl3)  26.6, 54.2, 106.4, 112.9, 126.1, 159.1. 4-(5-Methyl-2-thienyl)morpholine (3ab): The title
HRMS (FI) Calcd for C8H11NS2: M, 185.0333. Found: m/z
185.0340.
compound was synthesized using the following reagents
and conditions: 1a (26.1 mg, 0.300 mmol), 2b (32.0 mg,
0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0
mL), 110 °C, 96 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 10/1). A
1-Phenyl-4-(2-thienyl)piperazine (3ca): The title
compound was synthesized using the following reagents
and conditions: 1c (101 mg, 0.625 mmol), 2a (28.5 mg,
0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0
mL), 130 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 20/1). A
1
white solid, mp 54–56 ºC. H NMR (500 MHz, CDCl3) 
2.37 (d, J = 1.1 Hz, 3 H), 3.01–3.09 (m, 4 H), 3.78–3.86
(m, 4 H), 5.95 (d, J = 4.0 Hz, 1 H), 6.41 (dq, J = 3.4, 1.1
Hz, 1 H); 13C NMR (100 MHz, CDCl3)  15.3, 52.2, 66.5,
105.8, 123.3, 127.6, 157.0. HRMS (FI) Calcd for
C9H13NOS: M, 183.0718. Found: m/z 183.0718.
1
white solid, mp 120–122 ºC. H NMR (500 MHz, CDCl3)
 3.28–3.37 (m, 8 H), 6.20 (dd, J = 3.6, 1.3 Hz, 1 H), 6.66
(dd, J = 5.6, 1.3 Hz, 1 H), 6.81 (dd, J = 5.4, 3.7 Hz, 1 H),
6.90 (tt, J = 7.3, 1.1 Hz, 1 H), 6.95–7.01 (m, 2 H), 7.27–
7.34 (m, 2 H); 13C NMR (100 MHz, CDCl3)  49.1, 51.9,
106.1, 112.9, 116.6, 120.3, 126.1, 129.2, 151.1, 159.1.
HRMS (FI) Calcd for C14H16N2S: M, 244.1034. Found:
m/z 244.1054.
2,3-Dihydro-1-(5-methyl-2-thienyl)-1H-indole
(3eb):
The title compound was synthesized using the following
reagents and conditions: 1e (35.8 mg, 0.300 mmol), 2b
(32.0 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
PhCl (1.0 mL), 90 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 30/1). A
1
white solid, mp 70–72 ºC. H NMR (400 MHz, CDCl3) 
1-Acetyl-4-(2-thienyl)piperazine
(3da):
The title
2.43 (d, J = 0.9 Hz, 3 H), 3.15 (t, J = 8.5 Hz, 2 H), 3.89 (t,
J = 8.5 Hz, 2 H), 6.34 (d, J = 3.7 Hz, 1 H), 6.51–6.57 (m, 1
H), 6.73–6.79 (m, 1 H), 7.00–7.04 (m, 1 H), 7.07–7.16 (m,
2 H); 13C NMR (100 MHz, CDCl3)  15.4, 28.2, 54.5,
108.2, 111.8, 119.1, 123.1, 124.7, 127.4, 129.2, 130.1,
146.1, 147.9. HRMS (FD) Calcd for C13H13NS: M,
215.0769. Found: m/z 215.0769.
compound was synthesized using the following reagents
and conditions: 1d (80.1 mg, 0.625 mmol), 2a (28.5 mg,
0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0
mL), 130 °C, 48 h, and was isolated by column
chromatography on silica gel (EtOAc). A pale yellow solid,
mp 57–59 ºC. 1H NMR (400 MHz, CDCl3)  2.13 (s, 3 H),
3.07–3.18 (m, 4 H), 3.56–3.65 (m, 2 H), 3.71–3.81 (m, 2
H), 6.19 (dd, J = 3.7, 1.4 Hz, 1 H), 6.67 (dd, J = 5.5, 1.4
Hz, 1 H), 6.79 (dd, J = 5.5, 3.7 Hz, 1 H); 13C NMR (100
MHz, CDCl3)  21.3, 40.9, 45.8, 51.8, 52.1, 107.0, 113.6,
N,5-Dimethyl-N-(4-methylphenyl)-2-thiophenamine
(3hb): The title compound was synthesized using the
126.1, 158.6, 169.0. HRMS (FI) Calcd for C10H14N2OS: M, following reagents and conditions: 1h (75.7 mg, 0.625
210.0827. Found: m/z 210.0814.
mmol), 2b (32.0 mg, 0.250 mmol), In(NTf2)3 (23.9 mg,
25.0 mol), PhCl (1.0 mL), 110 °C, 21 h, and was isolated
by column chromatography on silica gel (hexane/EtOAc =
2,3-Dihydro-1-(2-thienyl)-1H-indole (3ea): The title
compound was synthesized using the following reagents
and conditions: 1e (74.5 mg, 0.625 mmol), 2a (28.5 mg,
0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol), PhCl (1.0
mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 20/1). A
1
40/1). A brown oil. H NMR (500 MHz, CDCl3)  2.27 (s,
3 H), 2.41 (d, J = 1.1 Hz, 3 H), 3.25 (s, 3 H), 6.41 (d, J =
3.4 Hz, 1 H), 6.49–6.53 (m, 1 H), 6.82–6.87 (m, 2 H),
7.01–7.07 (m, 2 H); 13C NMR (100 MHz, CDCl3)  15.8,
20.4, 42.0, 116.2, 118.6, 123.1, 129.1, 129.4, 133.7, 147.3,
151.5. HRMS (FI) Calcd for C13H15NS: M, 217.0925.
Found: m/z 217.0932.
1
white solid, mp 72–74 ºC. H NMR (400 MHz, CDCl3) 
3.16–3.23 (m, 2 H), 3.97 (t, J = 8.5 Hz, 2 H), 6.50 (dd, J =
3.7, 1.4 Hz, 1 H), 6.73–6.84 (m, 2 H), 6.92 (dd, J = 5.5, 3.7
Hz, 1 H), 7.12–7.18 (m, 3 H); 13C NMR (100 MHz,
CDCl3)  28.2, 54.1, 108.4, 110.2, 113.6, 119.4, 124.8,
125.7, 127.4, 130.3, 147.1, 148.4. HRMS (FI) Calcd for
C12H11NS: M, 201.0612. Found: m/z 201.0640.
4-(3-Thienyl)morpholine (3ac): The title compound was
synthesized using the following reagents and conditions:
1a (54.5 mg, 0.625 mmol), 2c (28.5 mg, 0.250 mmol),
In(NTf2)3 (35.8 mg, 37.5 mol), PhCl (0.50 mL), 130 °C,
24 h, and was isolated by column chromatography on silica
gel (hexane/EtOAc = 5/1). Compound 3ac has already
appeared in the literature,[49] and its spectral and analytical
2,3-Dihydro-6-nitro-1-(2-thienyl)-1H-indole (3fa): The
title compound was synthesized using the following
11
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
data are in good agreement with those reported.
Accordingly, 13C NMR data are omitted here. A white
column chromatography on silica gel (hexane/CHCl3/Et3N
= 100/50/3) gave 3iid in 94% yield (62.6 mg). A beige
solid, mp 171–173 ºC. 1H NMR (400 MHz, CDCl3)  5.51
(bs, 2 H), 6.82–6.90 (m, 4 H), 6.90–6.98 (m, 4 H), 7.20–
7.27 (m, 4 H); 13C NMR (100 MHz, CDCl3)  107.9, 115.6,
120.1, 129.4, 135.2, 144.5. HRMS (FI) Calcd for
C16H14N2S: M, 266.0878. Found: m/z 266.0906.
1
solid, mp 75–77 ºC. H NMR (400 MHz, CDCl3)  3.02–
3.15 (m, 4 H), 3.78–3.91 (m, 4 H), 6.20 (dd, J = 3.2, 1.4
Hz, 1 H), 6.86 (dd, J = 5.3, 1.6 Hz, 1 H), 7.26 (dd, J = 5.3,
3.0 Hz, 1 H). HRMS (FI) Calcd for C8H11NOS: M,
169.0561. Found: m/z 169.0561.
2,3-Dihydro-1-(3-thienyl)-1H-indole (3ec): The title
compound was synthesized using the following reagents
and conditions: 1e (35.8 mg, 0.300 mmol), 2c (28.5 mg,
0.250 mmol), In(NTf2)3 (7.16 mg, 7.50 mol), PhCl (1.0
mL), 110 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 40/1). A
Indium-Catalyzed SNAr Amination of 3-Bromo-4-
methoxythiophene with Aniline (Scheme 4)
Synthesis of 3ie was carried out in a similar way to the
procedure described in “Indium-Catalyzed SNAr
Amination of Thiophene Electrophiles with Secondary
Amines: A General Procedure for Table 2”. As shown
1
white solid, mp 44–46 ºC. H NMR (500 MHz, CDCl3) 
1
below, product 3ie was fully characterized by H and 13C
3.14 (t, J = 8.3 Hz, 2 H), 3.92 (t, J = 8.6 Hz, 2 H), 6.63 (dd,
J = 3.4, 1.7 Hz, 1 H), 6.74 (td, J = 7.4, 1.1 Hz, 1 H), 6.98–
7.03 (m, 1 H), 7.09 (td, J = 7.7, 1.1 Hz, 1 H), 7.13–7.17 (m,
1 H), 7.18 (dd, J = 5.2, 1.7 Hz, 1 H), 7.32 (dd, J = 5.2, 3.4
Hz, 1 H); 13C NMR (100 MHz, CDCl3)  28.2, 52.8, 103.7,
107.9, 118.6, 120.6, 124.9, 125.0, 127.3, 130.4, 143.4,
147.5. HRMS (FI) Calcd for C12H11NS: M, 201.0612.
Found: m/z 201.0635.
NMR spectroscopy, and HRMS.
4-Bromo-N-phenyl-3-thiophenamine (3ie): The title
compound was synthesized using the following reagents
and conditions: 1i (58.2 mg, 0.625 mmol), 2e (48.3 mg,
0.250 mmol), In(NTf2)3 (11.9 mg, 12.5 mol), PhCl (1.0
mL), 110 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 50/1). A
1
2,3-Dihydro-1-(4-methoxy-3-thienyl)-1H-indole (3ed):
The title compound was synthesized using the following
reagents and conditions: 1e (32.8 mg, 0.275 mmol), 2d
(36.0 mg, 0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 110 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 40/1). A
pale yellow solid, mp 40–41 ºC. H NMR (400 MHz,
CDCl3)  5.86 (bs, 1 H), 6.75 (d, J = 3.4 Hz, 1 H), 6.94 (tt,
J = 7.3, 1.1 Hz, 1 H), 7.08–7.14 (m, 2 H), 7.24–7.33 (m, 3
H); 13C NMR (100 MHz, CDCl3)  102.1, 105.4, 116.9,
121.1, 122.1, 129.4, 138.9, 143.0. HRMS (FD) Calcd for
C10H8BrNS: M, 252.9561. Found: m/z 252.9570.
1
white solid, mp 96–97 ºC. H NMR (400 MHz, CDCl3) 
3.11 (t, J = 8.4 Hz, 2 H), 3.86 (t, J = 8.5 Hz, 2 H), 3.87 (s,
3 H), 6.30 (d, J = 3.4 Hz, 1 H), 6.69 (d, J = 7.8 Hz, 1 H),
6.72 (td, J = 7.4, 1.0 Hz, 1 H), 6.93 (d, J = 3.4 Hz, 1 H),
7.00–7.06 (m, 1 H), 7.11–7.16 (m, 1 H); 13C NMR (100
MHz, CDCl3)  28.6, 53.7, 57.4, 96.8, 109.3, 110.7, 118.7,
124.6, 127.1, 130.1, 134.9, 149.4, 153.4. HRMS (FI) Calcd
for C13H13NOS: M, 231.0718. Found: m/z 231.0706.
Indium-Catalyzed Tandem SNAr Reaction of 2-
Methoxythiophene with N-Methyl-p-toluidine (Scheme
5)
Synthesis of 4haa was carried out in a similar way to the
procedure described in “Indium-Catalyzed SNAr
Amination of Thiophene Electrophiles with Secondary
Amines: A General Procedure for Table 2”. As shown
Indium-Catalyzed
SNAr
Amination
of
3,4-
below, product 4haa was fully characterized by 1H and 13
NMR spectroscopy, and HRMS.
C
Dimethoxythiophene with Aniline (Scheme 3)
Unless otherwise noted, synthesis of 3id and 3iid was
carried out in a similar way to the procedure described in
“Indium-Catalyzed SNAr Amination of Thiophene
Electrophiles with Secondary Amines: A General
Procedure for Table 2”. As shown below, products 3id
N-Methyl-N-(4-methylphenyl)-[2,2’-bithiophen]-5-
amine (4haa): The title compound was synthesized using
the following reagents and conditions: 1h (30.3 mg, 0.250
mmol), 2a (71.4 mg, 0.625 mmol), In(NTf2)3 (23.9 mg,
25.0 mol), PhCl (1.0 mL), 130 °C, 48 h, and was isolated
by column chromatography on silica gel (hexane). A pale
yellow solid, mp 84–85 ºC. 1H NMR (400 MHz, CDCl3) 
2.31 (s, 3 H), 3.32 (s, 3 H), 6.32 (d, J = 3.7 Hz, 1 H), 6.91
(d, J = 4.1 Hz, 1 H), 6.95 (dd, J = 5.0, 3.7 Hz, 1 H), 6.99
(dd, J = 3.4, 1.1 Hz, 1 H), 7.00–7.06 (m, 2 H), 7.07–7.13
(m, 3 H); 13C NMR (100 MHz, CDCl3)  20.7, 42.1, 113.9,
119.4, 122.2, 122.5, 123.1, 127.4, 127.6, 129.7, 131.6,
138.3, 146.5, 154.2. HRMS (FD) Calcd for C16H15NS2: M,
285.0646. Found: m/z 285.0671.
1
and 3iid were fully characterized by H and 13C NMR
spectroscopy, and HRMS.
4-Methoxy-N-phenyl-3-thiophenamine (3id): The title
compound was synthesized using the following reagents
and conditions: 1i (25.6 mg, 0.275 mmol), 2d (36.0 mg,
0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0
mL), 60 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 20/1). A
pale brown solid, mp 57–59 ºC. 1H NMR (400 MHz,
CDCl3)  3.90 (s, 3 H), 5.97 (bs, 1 H), 6.23 (d, J = 3.2 Hz,
1 H), 6.65 (d, J = 2.7 Hz, 1 H), 6.89 (tt, J = 7.3, 1.1 Hz, 1
H), 7.06–7.13 (m, 2 H), 7.24–7.30 (m, 2 H); 13C NMR
(100 MHz, CDCl3)  57.5, 95.5, 100.1, 116.0, 120.2, 129.3,
131.6, 143.2, 149.0. HRMS (FI) Calcd for C11H11NOS: M,
205.0561. Found: m/z 205.0567.
Indium-Catalyzed SNAr Amination of 3- and 2-
Methoxybenzothiophenes (Table 3)
Synthesis of 3af–3ig was carried out in a similar way to the
procedure described in “Indium-Catalyzed SNAr
Amination of Thiophene Electrophiles with Secondary
Amines: A General Procedure for Table 2”. Unless
otherwise noted, products 3 synthesized in this section
were fully characterized by 1H and 13C NMR spectroscopy,
and HRMS.
N3,N4-Diphenyl-3,4-thiophenediamine
(3iid):
A
procedure for the synthesis of the title compound
conducted in the absence of a solvent is as follows:
In(NTf2)3 (23.9 mg, 25.0 mol) was placed in a 20 mL
Schlenk tube, which was heated at 150 °C in vacuo for 2 h.
The tube was cooled down to room temperature and filled
with argon. To this were added 1i (233 mg, 2.50 mmol)
and 2d (36.0 mg, 0.250 mmol), and the resulting mixture
was stirred at 70 °C for 40 h. A saturated NaHCO3 aqueous
solution (0.5 mL) was added to the mixture, and the
aqueous phase was extracted with EtOAc (5 mL x 3). The
combined organic layer was washed with brine (1 mL) and
then dried over anhydrous sodium sulfate (Na2SO4).
Filtration and evaporation of the solvent followed by
4-Benzo[b]thien-3-ylmorpholine
(3af):
The
title
compound was synthesized using the following reagents
and conditions: 1a (54.5 mg, 0.625 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (35.8 mg, 37.5 mol), PhCl (1.0
mL), 130 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 10/1).
Compound 3af has already appeared in the literature,[49]
and its spectral and analytical data are in good agreement
with those reported. Accordingly, 13C NMR data are
12
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
1
omitted here. A white solid, mp 62–63 ºC. H NMR (400
MHz, CDCl3)  3.14 (t, J = 4.6 Hz, 4 H), 3.94 (t, J = 4.6
Hz, 4 H), 6.64 (s, 1 H), 7.31–7.40 (m, 2 H), 7.72–7.78 (m,
1 H), 7.78–7.84 (m, 1 H). HRMS (FD) Calcd for
C12H13NOS: M, 219.0718. Found: m/z 219.0729.
MHz, CDCl3)  5.75 (bs, 1 H), 6.89 (tt, J = 7.3, 1.1 Hz, 1
H), 6.97–7.05 (m, 3 H), 7.22–7.30 (m, 2 H), 7.34–7.42 (m,
2 H), 7.63–7.70 (m, 1 H), 7.80–7.88 (m, 1 H). HRMS (FI)
Calcd for C14H11NS: M, 225.0612. Found: m/z 225.0633.
N-(4-Methoxyphenyl)benzo[b]thiophen-3-amine (3mf):
The title compound was synthesized using the following
reagents and conditions: 1m (36.9 mg, 0.300 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
PhCl (1.0 mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 10/1).
Compound 3mf has already appeared in the literature,[51]
and its spectral and analytical data are in good agreement
with those reported. Accordingly, 13C NMR data are
omitted here. A beige solid, mp 100–102 ºC. 1H NMR (400
MHz, CDCl3)  3.80 (s, 3 H), 5.62 (bs, 1 H), 6.74 (s, 1 H),
6.86 (dt, J = 9.2, 2.7 Hz, 2 H), 7.04 (dt, J = 9.2, 2.7 Hz, 2
H), 7.34–7.40 (m, 2 H), 7.63–7.69 (m, 1 H), 7.79–7.85 (m,
1 H). HRMS (FI) Calcd for C15H13NOS: M, 255.0718.
Found: m/z 255.0689.
N-Hexyl-N-methylbenzo[b]thiophen-3-amine (3jf): The
title compound was synthesized using the following
reagents and conditions: 1j (34.6 mg, 0.300 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (35.8 mg, 37.5 mol), o-
Cl2C6H4 (1.0 mL) as a solvent, 150 °C, 72 h, and was
isolated by column chromatography on silica gel
1
(hexane/EtOAc = 30/1). A pale yellow oil. H NMR (400
MHz, CDCl3)  0.88 (t, J = 6.9 Hz, 3 H), 1.24–1.40 (m, 6
H), 1.59–1.71 (m, 2 H), 2.85 (s, 3 H), 3.05–3.14 (m, 2 H),
6.53 (s, 1 H), 7.29–7.38 (m, 2 H), 7.72–7.85 (m, 2 H); 13C
NMR (100 MHz, CDCl3)  14.1, 22.7, 26.9, 27.3, 31.8,
41.1, 56.3, 106.2, 122.2, 123.2, 123.5, 124.3, 135.1, 139.3,
147.6. HRMS (FI) Calcd for C15H21NS: M, 247.1395.
Found: m/z 247.1424.
1-(Benzo[b]thien-3-yl)-2,3-dihydro-1H-indole (3ef): The
title compound was synthesized using the following
reagents and conditions: 1e (35.8 mg, 0.300 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 110 °C, 14 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 100/1). A
2-(Benzo[b]thien-3-ylamino)phenol (3nf): The title
compound was synthesized using the following reagents
and conditions: 1n (32.7 mg, 0.300 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol), PhCl (1.0
mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 4/1). A
1
1
white solid, mp 86–88 ºC. H NMR (400 MHz, CDCl3) 
beige solid, mp 81–83 ºC. H NMR (400 MHz, CDCl3) 
3.19 (t, J = 8.2 Hz, 2 H), 3.96 (t, J = 8.2 Hz, 2 H), 6.54 (d,
J = 7.8 Hz, 1 H), 6.75 (td, J = 7.4, 0.8 Hz, 1 H), 7.00 (td, J
= 7.6, 0.8 Hz, 1 H), 7.12 (s, 1 H), 7.20 (dd, J = 7.3, 0.7 Hz,
1 H), 7.33–7.41 (m, 2 H), 7.74–7.78 (m, 1 H), 7.84–7.87
(m, 1 H); 13C NMR (100 MHz, CDCl3)  28.9, 55.0, 109.3,
113.4, 118.8, 122.8, 123.1, 123.7, 124.7, 124.8, 127.2,
130.3, 135.4, 139.0, 139.1, 149.9. HRMS (FD) Calcd for
C16H13NS: M, 251.0769. Found: m/z 251.0740.
5.43 (bs, 1 H), 5.80 (bs, 1 H), 6.58 (s, 1 H), 6.86–7.01 (m,
3 H), 7.17 (dd, J = 7.8, 1.4 Hz, 1 H), 7.36–7.44 (m, 2 H),
7.66–7.73 (m, 1 H), 7.79–7.87 (m, 1 H); 13C NMR (100
MHz, CDCl3)  105.2, 115.3, 120.1, 120.4, 121.3, 123.2,
123.4, 123.9, 124.9, 131.2, 133.7, 136.4, 139.1, 147.3.
HRMS (FI) Calcd for C14H11NOS: M, 241.0561. Found:
m/z 241.0550.
4-(Benzo[b]thien-3-ylamino)benzeneethanol (3of): The
title compound was synthesized using the following
reagents and conditions: 1o (41.2 mg, 0.300 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
PhCl (1.0 mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 10/1). A
N-Methyl-N-phenylbenzo[b]thiophen-3-amine
(3kf):
The title compound was synthesized using the following
reagents and conditions: 1k (67.0 mg, 0.625 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (71.6 mg, 75.0 mol),
PhCl (0.50 mL), 110 °C, 8 h, and was isolated by column
chromatography on silica gel (hexane). Compound 3kf has
already appeared in the literature,[50] and its spectral and
analytical data are in good agreement with those reported.
Accordingly, 13C NMR data are omitted here. A colorless
oil. 1H NMR (400 MHz, CDCl3)  3.39 (s, 3 H), 6.75–6.79
(m, 2 H), 6.82 (tt, J = 7.3, 1.1 Hz, 1 H), 7.13 (s, 1 H),
7.16–7.22 (m, 2 H), 7.22–7.27 (m, 1 H), 7.30–7.36 (m, 1
H), 7.40 (ddd, J = 8.0, 1.3, 0.7 Hz, 1 H), 7.83 (ddd, J = 8.0,
1.1, 0.7 Hz, 1 H). HRMS (FI) Calcd for C15H13NS: M,
239.0769. Found: m/z 239.0798.
1
beige solid, mp 65–67 ºC. H NMR (500 MHz, CDCl3) 
1.40 (bs, 1 H), 2.82 (t, J = 6.6 Hz, 2 H), 3.74–3.89 (m, 2 H),
5.74 (bs, 1 H), 6.91–7.06 (m, 3 H), 7.13 (d, J = 8.0 Hz, 2
H), 7.33–7.42 (m, 2 H), 7.63–7.69 (m, 1 H), 7.79–7.87 (m,
1 H); 13C NMR (125 MHz, CDCl3)  38.4, 63.8, 108.3,
116.5, 120.5, 123.2, 123.9, 124.9, 129.9, 130.0, 134.5,
135.2, 138.9, 143.2. HRMS (FD) Calcd for C16H15NOS: M,
269.0874. Found: m/z 269.0871.
N-(4-Iodophenyl)benzo[b]thiophen-3-amine (3pf): The
title compound was synthesized using the following
reagents and conditions: 1p (65.7 mg, 0.300 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (11.9 mg, 12.5 mol),
PhCl (1.0 mL), 50 °C, 9 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 10/1). A
dark red solid, mp 105–107 ºC. 1H NMR (400 MHz,
CDCl3)  5.72 (bs, 1 H), 6.73 (dt, J = 9.6, 2.5 Hz, 2 H),
7.05 (s, 1 H), 7.33–7.43 (m, 2 H), 7.50 (dt, J = 9.3, 2.5 Hz,
2 H), 7.57–7.66 (m, 1 H), 7.81–7.87 (m, 1 H); 13C NMR
(100 MHz, CDCl3)  81.1, 111.4, 117.8, 120.7, 123.3,
124.1, 125.0, 134.2, 134.6, 138.0, 138.9, 144.7. HRMS
(FI) Calcd for C14H10INS: M, 350.9579. Found: m/z
350.9560.
N,N-Bis(4-methylphenyl)benzo[b]thiophen-3-amine
(3lf): The title compound was synthesized using the
following reagents and conditions: 1l (123 mg, 0.625
mmol), 2f (41.1 mg, 0.250 mmol), In(NTf2)3 (71.6 mg,
75.0 mol), PhCl (0.25 mL), 110 °C, 24 h, and was
isolated by column chromatography on silica gel
(hexane/CHCl3 = 100/1). A pale yellow oil. 1H NMR (400
MHz, CDCl3)  2.29 (s, 6 H), 6.90–6.98 (m, 5 H), 6.98–
7.05 (m, 4 H), 7.19 (ddd, J = 8.1, 7.0, 1.0 Hz, 1 H), 7.30
(dt, J = 10.3, 3.8 Hz, 1 H), 7.35 (ddd, J = 8.0, 1.1, 0.7 Hz,
1 H), 7.80 (dt, J = 8.0, 0.8 Hz, 1 H); 13C NMR (100 MHz,
CDCl3)  20.7, 118.6, 122.3, 122.8, 123.1, 123.9, 124.5,
129.7, 131.7, 135.4, 139.1, 140.8, 145.4. HRMS (FI) Calcd
for C22H19NS: M, 329.1238. Found: m/z 329.1259.
N-(3-Bromophenyl)benzo[b]thiophen-3-amine
(3qf):
The title compound was synthesized using the following
reagents and conditions: 1q (51.6 mg, 0.300 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (11.9 mg, 12.5 mol),
PhCl (1.0 mL), 50 °C, 9 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 15/1). A
pale pink solid, mp 73–74 ºC. 1H NMR (400 MHz, CDCl3)
 5.73 (bs, 1 H), 6.85 (d, J = 8.2 Hz, 1 H), 6.98 (d, J = 7.3
Hz, 1 H), 7.04–7.14 (m, 3 H), 7.34–7.43 (m, 2 H), 7.59–
7.66 (m, 1 H), 7.81–7.89 (m, 1 H); 13C NMR (100 MHz,
CDCl3)  112.1, 114.1, 118.2, 120.7, 122.7, 123.2, 123.3,
124.1, 125.0, 130.7, 133.9, 134.6, 138.9, 146.4. HRMS
N-Phenylbenzo[b]thiophen-3-amine (3if): The title
compound was synthesized using the following reagents
and conditions: 1i (27.9 mg, 0.300 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol), PhCl (1.0
mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 30/1).
Compound 3if has already appeared in the literature,[49]
and its spectral and analytical data are in good agreement
with those reported. Accordingly, 13C NMR data are
1
omitted here. A beige solid, mp 81–83 ºC. H NMR (400
13
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
(FD) Calcd for C14H10BrNS: M, 302.9717. Found: m/z
302.9711.
114.7, 120.1, 123.2, 123.6, 124.7, 129.8, 132.3, 133.9,
136.0, 136.8, 138.3, 139.1. HRMS (FD) Calcd for
C17H14N2S: M, 278.0878. Found: m/z 278.0875.
N-[3,5-Bis(trifluoromethyl)phenyl]benzo[b]thiophen-3-
amine (3rf): The title compound was synthesized using
the following reagents and conditions: 1r (68.7 mg, 0.300
mmol), 2f (41.1 mg, 0.250 mmol), In(NTf2)3 (11.9 mg,
12.5 mol), PhCl (1.0 mL), 50 °C, 24 h, and was isolated
by column chromatography on silica gel (hexane/EtOAc =
N-(Pyridin-3-yl)benzo[b]thiophen-3-amine (3wf): The
title compound was synthesized using the following
reagents and conditions: 1w (18.8 mg, 0.250 mmol), 2f
(82.1 mg, 0.500 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 130 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 1/1).
Compound 3wf has already appeared in the literature,[52]
and its spectral and analytical data are in good agreement
with those reported. Accordingly, 13C NMR data are
1
30/1). A beige solid, mp 68–69 ºC. H NMR (400 MHz,
CDCl3)  5.99 (bs, 1 H), 7.22–7.23 (m, 1 H), 7.24–7.26 (m,
2 H), 7.29–7.32 (m, 1 H), 7.37–7.46 (m, 2 H), 7.57–7.63
(m, 1 H), 7.86–7.91 (m, 1 H); 13C NMR (100 MHz,
CDCl3)  112.6 (sept, J = 4.1 Hz), 114.2 (q, J = 3.5 Hz),
115.4, 120.6, 123.4 (q, J = 272.7 Hz), 123.5, 124.5, 125.4,
132.4, 132.7 (q, J = 32.9 Hz), 134.4, 139.0, 146.5. HRMS
(FI) Calcd for C16H9F6NS: M, 361.0360. Found: m/z
361.0376.
1
omitted here. A pale brown solid, mp 116–117 ºC. H
NMR (500 MHz, CDCl3)  5.91 (bs, 1 H), 7.06 (s, 1 H),
7.14 (dd, J = 8.2, 4.7 Hz, 1 H), 7.20–7.28 (m, 1 H), 7.34–
7.44 (m, 2 H), 7.60–7.67 (m, 1 H), 7.82–7.88 (m, 1 H),
8.10–8.16 (m, 1 H), 8.36 (d, J = 2.9 Hz, 1 H). HRMS (FD)
Calcd for C13H10N2S: M, 226.0565. Found: m/z 226.0556.
4-(Benzo[b]thien-3-ylamino)benzonitrile (3sf): The title
compound was synthesized using the following reagents
and conditions: 1s (35.4 mg, 0.300 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (11.9 mg, 12.5 mol), PhCl (1.0
mL), 50 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 5/1). A
N-Benzo[b]thien-3-yl-2-benzothiazolamine (3xf): The
title compound was synthesized using the following
reagents and conditions: 1x (37.5 mg, 0.250 mmol), 2f
(82.1 mg, 0.500 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 110 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 10/1). A
brown solid, mp 202–204 ºC. 1H NMR (400 MHz, CDCl3)
 7.12–7.19 (m, 1 H), 7.28–7.36 (m, 1 H), 7.38–7.47 (m, 2
H), 7.56 (ddd, J = 8.1, 1.0, 0.5 Hz, 1 H), 7.62 (ddd, J = 7.8,
1.3, 0.6 Hz, 1 H), 7.72–7.81 (m, 2 H), 7.84–7.92 (m, 1 H),
8.23 (bs, 1 H); 13C NMR (100 MHz, CDCl3)  113.7, 119.6,
119.9, 121.0, 122.6, 123.3, 124.4, 125.3, 126.2, 130.5,
131.6, 133.4, 138.6, 151.6, 164.8. HRMS (FI) Calcd for
C15H10N2S2: M, 282.0285. Found: m/z 282.0297.
1
pale beige solid, mp 158–160 ºC. H NMR (400 MHz,
CDCl3)  6.03 (bs, 1 H), 6.85 (dt, J = 9.2, 2.2 Hz, 2 H),
7.24 (s, 1 H), 7.35–7.44 (m, 2 H), 7.47 (dt, J = 9.2, 2.2 Hz,
2 H), 7.54–7.65 (m, 1 H), 7.82–7.93 (m, 1 H); 13C NMR
(100 MHz, CDCl3)  101.2, 114.3, 116.4, 120.0, 120.9,
123.3, 124.4, 125.2, 132.2, 133.8, 134.7, 138.9, 149.2.
HRMS (FI) Calcd for C15H10N2S: M, 250.0565. Found:
m/z 250.0579.
Ethyl 4-(benzo[b]thien-3-ylamino)benzoate (3tf): The
title compound was synthesized using the following
reagents and conditions: 1t (49.6 mg, 0.300 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (7.16 mg, 7.50 mol),
PhCl (1.0 mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 6/1). A
brown solid, mp 127–129 ºC. 1H NMR (400 MHz, CDCl3)
 1.37 (t, J = 7.1 Hz, 3 H), 4.33 (q, J = 7.2 Hz, 2 H), 6.01
(bs, 1 H), 6.88 (dt, J = 9.3, 2.3 Hz, 2 H), 7.20 (s, 1 H),
7.34–7.44 (m, 2 H), 7.58–7.67 (m, 1 H), 7.83–7.89 (m, 1
H), 7.92 (dt, J = 9.2, 2.2 Hz, 2 H); 13C NMR (100 MHz,
CDCl3)  14.4, 60.4, 113.9, 114.2, 120.9, 121.1, 123.3,
124.2, 125.1, 131.5, 133.1, 134.7, 138.8, 149.2, 166.6.
HRMS (FI) Calcd for C17H15NO2S: M, 297.0823. Found:
m/z 297.0813.
N-Hexylbenzo[b]thiophen-3-amine (3yf): The title
compound was synthesized using the following reagents
and conditions: 1y (63.2 mg, 0.625 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (71.6 mg, 75.0 mol), PhCl (0.25
mL), 130 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 100/1).
Compound 3yf has already appeared in the literature,[53]
and its spectral and analytical data are in good agreement
with those reported. Accordingly, 13C NMR data are
omitted here. A pale yellow oil. 1H NMR (400 MHz,
CDCl3)  0.91 (t, J = 7.0 Hz, 3 H), 1.29–1.53 (m, 6 H),
1.74 (quint, J = 7.3 Hz, 2 H), 3.23 (t, J = 7.1 Hz, 2 H), 3.82
(bs, 1 H), 6.03 (s, 1 H), 7.30–7.38 (m, 2 H), 7.54–7.59 (m,
1 H), 7.75–7.81 (m, 1 H). HRMS (FI) Calcd for C14H19NS:
M, 233.1238. Found: m/z 233.1261.
N-[4-(2,5-dimethyl-1H-pyrrol-1-
yl)phenyl]benzo[b]thiophen-3-amine (3uf): The title
compound was synthesized using the following reagents
and conditions: 1u (55.9 mg, 0.300 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol), PhCl (1.0
mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 10/1). A
pink solid, mp 176–178 ºC. 1H NMR (400 MHz, CDCl3) 
2.05 (s, 6 H), 5.85 (bs, 1 H), 5.88 (s, 2 H), 7.02 (dt, J = 9.0,
2.5 Hz, 2 H), 7.08 (dt, J = 9.0, 2.5 Hz, 2 H), 7.13 (s, 1 H),
7.41 (dt, J = 9.8, 3.5 Hz, 2 H), 7.65–7.73 (m, 1 H), 7.82–
7.91 (m, 1 H); 13C NMR (100 MHz, CDCl3)  13.0, 105.2,
110.8, 115.7, 120.6, 123.3, 124.1, 125.0, 129.08, 129.12,
130.9, 134.4, 134.6, 138.9, 144.3. HRMS (FD) Calcd for
C20H18N2S: M, 318.1191. Found: m/z 318.1186.
N-Cyclopentylbenzo[b]thiophen-3-amine (3zf): The title
compound was synthesized using the following reagents
and conditions: 1z (53.2 mg, 0.625 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (71.6 mg, 75.0 mol), PhCl (1.0
mL), 130 °C, 96 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 200/1). A
1
brown oil. H NMR (500 MHz, CDCl3)  1.56–1.69 (m, 6
H), 2.03–2.14 (m, 2 H), 3.74–3.93 (m, 2 H), 6.04 (s, 1 H),
7.30–7.37 (m, 2 H), 7.51–7.57 (m, 1 H), 7.74–7.81 (m, 1
H); 13C NMR (125 MHz, CDCl3)  24.4, 33.6, 56.4, 95.2,
119.3, 123.2, 123.3, 124.6, 133.0, 139.1, 140.9. HRMS
(FI) Calcd for C13H15NS: M, 217.0925. Found: m/z
217.0947.
N-Benzylbenzo[b]thiophen-3-amine (3aaf): The title
compound was synthesized using the following reagents
and conditions: 1aa (67.0 mg, 0.625 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (71.6 mg, 75.0 mol), PhCl (1.0
mL), 130 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc/Et3N =
100/1/5). Compound 3aaf has already appeared in the
literature,[54] and its spectral and analytical data are in good
agreement with those reported. Accordingly, 13C NMR
data are omitted here. A pale blue oil. 1H NMR (400 MHz,
CDCl3)  4.22 (bs, 1 H), 4.44 (s, 2 H), 6.07 (s, 1 H), 7.28–
7.41 (m, 5 H), 7.43–7.48 (m, 2 H), 7.56–7.61 (m, 1 H),
N-(2-Methylindol-5-yl)benzo[b]thiophen-3-amine (3vf):
The title compound was synthesized using the following
reagents and conditions: 1v (91.4 mg, 0.625 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 110 °C, 3 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 5/1). A
brown solid, mp 154–156 ºC. 1H NMR (400 MHz, CDCl3)
 2.43 (s, 3 H), 5.70 (bs, 1 H), 6.13 (s, 1 H), 6.70 (s, 1 H),
6.95 (dd, J = 8.5, 2.1 Hz, 1 H), 7.22 (d, J = 8.5 Hz, 1 H),
7.26 (d, J = 2.1 Hz, 1 H), 7.33–7.40 (m, 2 H), 7.67–7.73
(m, 1 H), 7.77 (bs, 1 H), 7.79–7.86 (m, 1 H); 13C NMR
(100 MHz, CDCl3)  13.8, 100.2, 102.7, 109.5, 110.8,
14
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
7.76–7.82 (m, 1 H). HRMS (FD) Calcd for C15H13NS: M,
239.0769. Found: m/z 239.0790.
 6.13 (bs, 1 H), 6.80 (s, 2 H), 7.38–7.44 (m, 4 H), 7.71–
7.78 (m, 2 H), 7.82–7.89 (m, 2 H); 13C NMR (100 MHz,
CDCl3)  105.5, 120.1, 123.3, 123.9, 124.9, 133.4, 136.1,
139.0. HRMS (FD) Calcd for C16H11NS2: M, 281.0333.
Found: m/z 281.0354.
N-[2-(1-Cyclohexen-1-yl)ethyl]benzo[b]thiophen-3-
amine (3abf): The title compound was synthesized using
the following reagents and conditions: 1ab (78.3 mg, 0.625
mmol), 2f (41.1 mg, 0.250 mmol), In(NTf2)3 (71.6 mg,
75.0 mol), PhCl (0.25 mL), 130 °C, 48 h, and was
isolated by column chromatography on silica gel
(hexane/EtOAc = 100/1). Compound 3abf has already
appeared in the literature,[55] and its spectral and analytical
data are in good agreement with those reported.
Accordingly, 13C NMR data are omitted here. A brown oil.
1H NMR (400 MHz, CDCl3)  1.54–1.68 (m, 4 H), 1.95–
2.09 (m, 4 H), 2.38 (t, J = 6.5 Hz, 2 H), 3.28 (t, J = 6.8 Hz,
2 H), 3.90 (bs, 1 H), 5.60 (tt, J = 4.9, 1.6 Hz, 1 H), 6.05 (s,
1 H), 7.31–7.37 (m, 2 H), 7.49–7.55 (m, 1 H), 7.75–7.81
(m, 1 H). HRMS (FI) Calcd for C16H19NS: M, 257.1238.
Found: m/z 257.1260.
Indium-Catalyzed
Reaction
of
3-
Methoxybenzothiophene with Cyclic Diarylamine 1af
(Scheme 7)
Synthesis of 3’aff was carried out in a similar way to the
procedure described in “Indium-Catalyzed SNAr
Amination of Thiophene Electrophiles with Secondary
Amines: A General Procedure for Table 2”. As shown
below, product 3’aff was fully characterized by 1H and 13
NMR spectroscopy, and HRMS.
C
2-(Benzo[b]thien-3-yl)-10,11-dihydro-5H-
dibenz[b,f]azepine (3’aff): The title compound was
synthesized using the following reagents and conditions:
1af (146 mg, 0.750 mmol), 2f (41.1 mg, 0.250 mmol),
In(NTf2)3 (71.6 mg, 75.0 mol), PhCl (0.25 mL), 110 °C,
24 h, and was isolated by column chromatography on silica
gel (hexane/EtOAc = 20/1). A pale yellow solid, mp 62–64
ºC. 1H NMR (500 MHz, CDCl3)  3.14 (s, 4 H), 6.11 (bs, 1
H), 6.75–6.85 (m, 3 H), 7.05–7.13 (m, 2 H), 7.26–7.34 (m,
3 H), 7.34–7.42 (m, 2 H), 7.87–7.98 (m, 2 H); 13C NMR
(100 MHz, CDCl3)  34.9, 35.1, 118.0, 118.2, 119.7, 122.2,
122.9, 123.0, 124.2, 124.3, 126.9, 127.07, 127.09, 128.6,
128.8, 130.7, 130.9, 137.7, 138.1, 140.6, 141.9, 142.2.
HRMS (FD) Calcd for C22H17NS: M, 327.1082. Found:
m/z 327.1096.
N-Phenylbenzo[b]thiophen-2-amine (3ig): The title
compound was synthesized using the following reagents
and conditions: 1i (27.9 mg, 0.300 mmol), 2g (41.1 mg,
0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol), PhCl (1.0
mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 30/1). A
1
salmon pink solid, mp 133–134 ºC. H NMR (400 MHz,
CDCl3)  5.93 (bs, 1 H), 6.82 (s, 1 H), 6.95 (tt, J = 7.3, 1.1
Hz, 1 H), 7.07–7.13 (m, 2 H), 7.17–7.24 (m, 1 H), 7.26–
7.33 (m, 3 H), 7.53–7.59 (m, 1 H), 7.63–7.69 (m, 1 H); 13
C
NMR (100 MHz, CDCl3)  109.2, 116.2, 121.1, 121.9,
122.9, 124.5, 129.4, 134.4, 139.5, 143.7, 146.3 (One
carbon signal is missing due to overlapping). HRMS (FD)
Calcd for C14H11NS: M, 225.0612. Found: m/z 225.0615.
Indium-Catalyzed SNAr Amination of Furan,
Benzofuran, Pyrrole, and Indole Electrophiles (Table 4)
Indium-Catalyzed
SNAr
Amination
of
3-
Methoxybenzothiophene with Small Molecular Weight
Amines (Scheme 6)
Synthesis of 3eh–3ek was carried out in a similar way to
the procedure described in “Indium-Catalyzed SNAr
Amination of Thiophene Electrophiles with Secondary
Amines: A General Procedure for Table 2”. As shown
Synthesis of 3acf–3aeff was carried out in a similar way to
the procedure described in “Indium-Catalyzed SNAr
Amination of Thiophene Electrophiles with Secondary
Amines: A General Procedure for Table 2”. As shown
below, products 3acf–3aeff were fully characterized by 1H
and 13C NMR spectroscopy, and HRMS.
1
below, products 3eh–3ek were fully characterized by H
and 13C NMR spectroscopy, and HRMS.
2,3-Dihydro-1-(5-phenyl-2-furanyl)-1H-indole
(3eh):
The title compound was synthesized using the following
reagents and conditions: 1e (74.5 mg, 0.625 mmol), 2h
(43.5 mg, 0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 90 °C, 10 min, and was isolated by column
chromatography on silica gel (hexane/CHCl3 = 8/1). A
N,N-Dimethylbenzo[b]thiophen-3-amine (3acf): The
title compound was synthesized using the following
reagents and conditions: 1ac (101 mg, 0.750 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 130 °C, 72 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 15/1). A
1
brown oil. H NMR (400 MHz, CDCl3)  3.22 (t, J = 8.7
Hz, 2 H), 3.98 (t, J = 8.7 Hz, 2 H), 5.53 (d, J = 3.4 Hz, 1
H), 6.67 (d, J = 3.4 Hz, 1 H), 6.83 (td, J = 7.4, 0.8 Hz, 1 H),
7.15–7.22 (m, 3 H), 7.34–7.41 (m, 3 H), 7.57–7.64 (m, 2
H); 13C NMR (100 MHz, CDCl3)  28.1, 50.1, 88.3, 106.9,
109.7, 119.9, 122.3, 124.8, 125.9, 127.7, 128.7, 130.0,
131.1, 145.0, 145.9, 152.2. HRMS (FI) Calcd for
C18H15NO: M, 261.1154. Found: m/z 261.1183.
1
colorless oil. H NMR (400 MHz, CDCl3)  2.89 (s, 6 H),
6.54 (s, 1 H), 7.30–7.40 (m, 2 H), 7.75–7.86 (m, 2 H); 13C
NMR (100 MHz, CDCl3)  44.4, 105.6, 122.2, 123.2,
123.6, 124.4, 134.7, 139.4, 148.0. HRMS (FD) Calcd for
C10H11NS: M, 177.0612. Found: m/z 177.0604.
N-Methylbenzo[b]thiophen-3-amine (3adf): The title
compound was synthesized using the following reagents
and conditions: 1ad (50.6 mg, 0.750 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (47.8 mg, 50.0 mol), PhCl (1.0
mL), 130 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 15/1). A
pale brown oil. 1H NMR (400 MHz, CDCl3)  3.00 (s, 3 H),
3.90 (bs, 1 H), 6.06 (s, 1 H), 7.31–7.38 (m, 2 H), 7.52–7.57
(m, 1 H), 7.75–7.81 (m, 1 H); 13C NMR (100 MHz,
CDCl3)  32.4, 94.6, 119.3, 123.2, 123.4, 124.7, 132.7,
139.3, 142.7. HRMS (FD) Calcd for C9H9NS: M, 163.0456.
Found: m/z 163.0452.
N-Methyl-N,5-diphenyl-2-furanamine (3kh): The title
compound was synthesized using the following reagents
and conditions: 1k (67.0 mg, 0.625 mmol), 2h (43.5 mg,
0.250 mmol), In(NTf2)3 (4.78 mg, 5.00 mol), PhCl (1.0
mL), 110 °C, 2 h, and was isolated by column
chromatography on silica gel (hexane/CHCl3 = 8/1). A pale
yellow solid, mp 30–31 ºC. 1H NMR (500 MHz, CDCl3) 
3.35 (s, 3 H), 5.84 (d, J = 3.4 Hz, 1 H), 6.63 (d, J = 3.4 Hz,
1 H), 6.90–6.94 (m, 1 H), 6.99–7.04 (m, 2 H), 7.19 (t, J =
7.4 Hz, 1 H), 7.24–7.30 (m, 2 H), 7.31–7.37 (m, 2 H),
7.57–7.61 (m, 2 H); 13C NMR (100 MHz, CDCl3)  38.8,
97.6, 106.4, 116.5, 120.4, 122.9, 126.6, 128.6, 129.0, 130.9,
147.1, 147.7, 154.3. HRMS (FD) Calcd for C17H15NO: M,
249.1154. Found: m/z 249.1174.
N-Benzo[b]thien-3-ylbenzo[b]thiophen-3-amine (3aeff):
The title compound was synthesized using the following
reagents and conditions: 1ae (38.5 mg, 0.500 mmol), 2f
(41.1 mg, 0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol),
PhCl (1.0 mL), 130 °C, 48 h, and was isolated by column
chromatography on silica gel (hexane/CHCl3 = 4/1). A pale
brown solid, mp 104–106 ºC. 1H NMR (400 MHz, CDCl3)
1-(Benzo[b]furan-2-yl)-2,3-dihydro-1H-indole (3ei): The
title compound was synthesized using the following
reagents and conditions: 1e (35.8 mg, 0.300 mmol), 2i
(37.0 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
15
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
PhCl (1.0 mL), 50 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/Et3N = 20/1). A
CDCl3)  0.88 (t, J = 6.9 Hz, 3 H), 1.20–1.38 (m, 12 H),
1.38–1.48 (m, 2 H), 1.71–1.82 (m, 2 H), 4.02 (t, J = 6.6 Hz,
2 H), 6.19 (dd, J = 3.9, 1.6 Hz, 1 H), 6.53 (dd, J = 5.7, 1.6
Hz, 1 H), 6.71 (dd, J = 5.5, 3.7 Hz, 1 H). HRMS (FI) Calcd
for C14H24OS: M, 240.1548. Found: m/z 240.1525.
1
white solid, mp 96–98 ºC. H NMR (400 MHz, CDCl3) 
3.25 (t, J = 8.7 Hz, 2 H), 4.04 (td, J = 8.7, 0.6 Hz, 2 H),
5.72 (d, J = 0.9 Hz, 1 H), 6.87 (td, J = 7.3, 0.9 Hz, 1 H),
7.08 (td, J = 7.6, 1.5 Hz, 1 H), 7.13–7.24 (m, 3 H), 7.34–
7.42 (m, 2 H), 7.46–7.56 (m, 1 H); 13C NMR (100 MHz,
CDCl3)  28.0, 49.8, 80.9, 109.8, 110.8, 118.3, 120.5,
120.6, 123.0, 124.9, 127.7, 130.1, 130.4, 144.2, 150.6,
154.7. HRMS (FI) Calcd for C16H13NO: M, 235.0997.
Found: m/z 235.0988.
2-[2-(2-Ethoxyethoxy)ethoxy]thiophene (7ba): The title
compound was synthesized using the following reagents
and conditions: 5b (134 mg, 1.00 mmol), 2a (28.5 mg,
0.250 mmol), In(NTf2)3 (7.16 mg, 7.50 mol), PhCl (1.0
mL), 80 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 4/1). A
1
4-(1-Phenylpyrrol-2-yl)morpholine (3aj): The title
compound was synthesized using the following reagents
and conditions: 1a (54.5 mg, 0.625 mmol), 2j (43.3 mg,
0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0
mL), 90 °C, 46 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 20/1). A
pale yellow oil. H NMR (500 MHz, CDCl3)  1.22 (t, J =
6.9 Hz, 3 H), 3.54 (q, J = 6.9 Hz, 2 H), 3.62 (dd, J = 5.7,
4.0 Hz, 2 H), 3.71 (dd, J = 5.7, 4.0 Hz, 2 H), 3.85 (dd, J =
5.7, 4.0 Hz, 2 H), 4.20 (dd, J = 5.2, 4.0 Hz, 2 H), 6.23 (dd,
J = 3.7, 1.4 Hz, 1 H), 6.55 (dd, J = 5.7, 1.7 Hz, 1 H), 6.70
(dd, J = 5.7, 3.4 Hz, 1 H); 13C NMR (100 MHz, CDCl3) 
15.2, 66.7, 69.4, 69.9, 70.9, 73.1, 105.1, 112.2, 124.6,
165.3. HRMS (FD) Calcd for C10H16O3S: M, 216.0820.
Found: m/z 216.0813.
1
white solid, mp 87–88 ºC. H NMR (400 MHz, CDCl3) 
2.75–2.81 (m, 4 H), 3.61–3.68 (m, 4 H), 5.76 (dd, J = 3.5,
1.9 Hz, 1 H), 6.17 (t, J = 3.4 Hz, 1 H), 6.63 (dd, J = 3.2,
1.8 Hz, 1 H), 7.23–7.30 (m, 1 H), 7.38–7.45 (m, 2 H),
7.53–7.58 (m, 2 H); 13C NMR (100 MHz, CDCl3)  52.3,
66.9, 95.2, 107.3, 117.7, 124.3, 126.2, 128.9, 139.8, 142.9.
HRMS (FI) Calcd for C14H16N2O: M, 228.1263. Found:
m/z 228.1287.
2-(n-Decylthio)thiophene (8aa): The title compound was
synthesized using the following reagents and conditions:
6a (52.3 mg, 0.300 mmol), 2a (28.5 mg, 0.250 mmol),
In(NTf2)3 (2.39 mg, 2.50 mol), PhCl (1.0 mL), 50 °C, 5 h,
and was isolated by column chromatography on silica gel
1
3-(Morpholin-4-yl)-1H-indole (3ak): The title compound
was synthesized using the following reagents and
conditions: 1a (54.5 mg, 0.625 mmol), 2k (43.8 mg, 0.250
mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (0.50 mL),
110 °C, 6 h, and was isolated by column chromatography
on silica gel (hexane/EtOAc = 2/1). A yellow-brown solid,
(hexane). A colorless oil. H NMR (400 MHz, CDCl3) 
0.88 (t, J = 6.9 Hz, 3 H), 1.22–1.33 (m, 12 H), 1.33–1.44
(m, 2 H), 1.55–1.65 (m, 2 H), 2.79 (t, J = 7.6 Hz, 2 H),
6.97 (dd, J = 5.3, 3.4 Hz, 1 H), 7.10 (dd, J = 3.4, 1.1 Hz, 1
H), 7.32 (dd, J = 5.3, 1.1 Hz, 1 H); 13C NMR (100 MHz,
CDCl3)  14.1, 22.7, 28.4, 29.2, 29.3, 29.4, 29.50, 29.54,
31.9, 39.0, 127.4, 128.8, 133.2, 135.0. HRMS (FI) Calcd
for C14H24S2: M, 256.1319. Found: m/z 256.1333.
1
mp 140–142 ºC. H NMR (400 MHz, CDCl3)  3.05–3.14
(m, 4 H), 3.89–3.99 (m, 4 H), 6.74 (d, J = 2.7 Hz, 1 H),
7.09 (ddd, J = 8.2, 6.9, 0.9 Hz, 1 H), 7.19 (ddd, J = 8.4, 6.8,
1.3 Hz, 1 H), 7.28–7.35 (m, 1 H), 7.60–7.66 (m, 1 H), 7.71
(bs, 1 H); 13C NMR (100 MHz, CDCl3)  53.1, 67.1, 110.2,
111.4, 119.0, 122.0, 122.4, 132.5, 135.7 (One carbon
signal is missing due to overlapping). HRMS (FI) Calcd
for C12H14N2O: M, 202.1106. Found: m/z 202.1119.
3,4-Bis(n-dodecylthio)thiophene (8bd):
The title
compound was synthesized using the following reagents
and conditions: 6b (202 mg, 1.00 mmol), 2d (36.0 mg,
0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0
mL), 100 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane). Compound 8bd has
already appeared in the literature,[28c] and its spectral and
analytical data are in good agreement with those reported.
Accordingly, 13C NMR data are omitted here. A colorless
oil. 1H NMR (500 MHz, CDCl3)  0.88 (t, J = 7.0 Hz, 6 H),
1.20–1.33 (m, 32 H), 1.41 (quint, J = 7.0 Hz, 4 H), 1.64
(quint, J = 7.6 Hz, 4 H), 2.86 (t, J = 7.4 Hz, 4 H), 7.08 (s, 2
H). HRMS (FD) Calcd for C28H52S3: M, 484.3231. Found:
m/z 484.3247.
2,3-Dihydro-1,3’-bi-1H-indole (3ek): The title compound
was synthesized using the following reagents and
conditions: 1e (74.5 mg, 0.625 mmol), 2k (43.8 mg, 0.250
mmol), In(NTf2)3 (11.9 mg, 12.5 mol), PhCl (0.50 mL),
100 °C, 4 h, and was isolated by column chromatography
on silica gel (hexane/EtOAc = 5/1). A brown solid, mp 84–
86 ºC. 1H NMR (500 MHz, CDCl3)  3.17 (t, J = 8.6 Hz, 2
H), 3.91 (t, J = 8.6 Hz, 2 H), 6.52 (d, J = 8.0 Hz, 1 H), 6.69
(t, J = 7.4 Hz, 1 H), 6.99 (t, J = 7.7 Hz, 1 H), 7.08 (t, J =
7.4 Hz, 1 H), 7.14–7.19 (m, 2 H), 7.22 (t, J = 7.4 Hz, 1 H),
7.37 (d, J = 8.6 Hz, 1 H), 7.53 (d, J = 8.0 Hz, 1 H), 7.90
(bs, 1 H); 13C NMR (100 MHz, CDCl3)  28.9, 55.4, 108.3,
111.5, 116.9, 117.8, 119.3, 119.7, 122.4, 123.1, 123.5,
124.5, 127.3, 129.7, 135.2, 151.4. HRMS (FI) Calcd for
C16H14N2: M, 234.1157. Found: m/z 234.1139.
Indium-Catalyzed
SNAr
Reaction
of
3-
Methoxybenzothiophene in the Presence of Phenol
(Scheme 8)
Synthesis of 9 was carried out in a similar way to the
procedure described in “Indium-Catalyzed SNAr
Amination of Thiophene Electrophiles with Secondary
Amines: A General Procedure for Table 2”. As shown
Indium-Catalyzed SNAr Alkoxylation and Thiolation of
(Di)methoxythiophenes (Table 5)
1
below, product 9 was fully characterized by H and 13C
NMR spectroscopy, and HRMS.
Synthesis of 7aa, 7ba, 8aa, and 8bd was carried out in a
similar way to the procedure described in “Indium-
Catalyzed SNAr Amination of Thiophene Electrophiles
with Secondary Amines: A General Procedure for
Table 2”. Unless otherwise noted, products 7 and 8
prepared in this section were fully characterized by 1H and
13C NMR spectroscopy, and HRMS.
3-Methoxy-2,3’-bibenzo[b]thiophene (9): The title
compound was synthesized using the following reagents
and conditions: 5c (58.8 mg, 0.625 mmol), 2f (41.1 mg,
0.250 mmol), In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0
mL), 90 °C, 24 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 200/1). A
1
pale yellow solid, mp 96–97 ºC. H NMR (400 MHz,
2-(n-Decyloxy)thiophene (7aa): The title compound was
synthesized using the following reagents and conditions:
5a (158 mg, 1.00 mmol), 2a (28.5 mg, 0.250 mmol),
In(NTf2)3 (23.9 mg, 25.0 mol), PhCl (1.0 mL), 50 °C, 4 h,
and was isolated by column chromatography on silica gel
(hexane). Compound 7aa has already appeared in the
literature,[56] and its spectral and analytical data are in good
agreement with those reported. Accordingly, 13C NMR
data are omitted here. A colorless oil. 1H NMR (400 MHz,
CDCl3)  3.71 (s, 3 H), 7.36–7.47 (m, 4 H), 7.73 (s, 1 H),
7.76–7.80 (m, 1 H), 7.82–7.86 (m, 1 H), 7.89–7.95 (m, 1
H), 8.06–8.12 (m, 1 H); 13C NMR (100 MHz, CDCl3) 
60.7, 117.7, 121.1, 122.5, 122.7, 123.6, 124.3, 124.7, 124.8,
125.1, 126.7, 128.1, 134.0, 136.4, 138.3, 139.8, 148.1.
HRMS (FD) Calcd for C17H12OS2: M, 296.0330. Found:
m/z 296.0355.
16
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
Synthetic Application: Copper-Catalyzed Coupling of
(C11), 125.6 (C11), 125.7 (C11), 127.2 (C6), 127.3 (C6),
127.4 (C6), 130.4 (C3), 146.97 (C8), 147.05 (C8), 148.3
(C9), 148.4 (C9). HRMS (FI) Calcd for C12H10DNS: M,
202.0675. Found: m/z 202.0697.
3uf with 4,4’-Diiodobiphenyl (Scheme 9)
According to the reported procedure,[32] the coupling of
3uf with 4,4’-diiodobiphenyl (10) was performed, as
follows: A flame-dried 20 mL Schlenk tube was charged
with CuI (4.76 mg, 25.0 mol), 1,10-phenanthroline (13.5
mg, 75.0 mol), t-BuOK (84.2 mg, 0.750 mmol) and
toluene (1.0 mL). The resulting solution was degassed by
three freeze-pump-thaw cycles, and the Schlenk tube was
then filled with argon. After stirring at room temperature
for 5 min, to this solution were successively added 3uf
(175 mg, 0.550 mmol) and 10 (102 mg, 0.250 mmol), and
the mixture was stirred at room temperature for 20 min,
and then heated at 120 ºC for 15 h. The resulting mixture
was diluted with CH2Cl2 (5 mL). Filtration through a pad
of Celite and evaporation of the solvent followed by
recycling GPC after column chromatography on silica gel
(hexane/CH2Cl2 = 1/1) gave N,N’-bis(benzo[b]thiophen-3-
yl)-N,N’-bis[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]-[1,1’-
biphenyl]-4,4’-diamine (11) in 43% yield (84.7 mg) as a
yellow solid (mp 290–292 °C; decomp.). Compound 11
Kinetic Isotope Effect Experiments (Scheme 12)
The reaction shown in Scheme 12 was carried out similarly
as the general procedure described in “Indium-Catalyzed
SNAr Amination of Thiophene Electrophiles with
Secondary Amines: A General Procedure for Table 2”.
The amination of 2-methoxythiophene (2a) with indoline
(1e) or indoline-1-d (1e-1-d) was thus performed using the
following reagents and conditions: 1e or 1e-1-d (74.5 or
75.1 mg, 0.625 mmol), 2a (28.5 mg, 0.250 mmol),
In(NTf2)3 (2.39 mg, 2.50 mol), PhCl (1.0 mL), 90 °C, 10–
60 min, and the yields of product 3ea including 3ea-3-d
and 3ea-5-d after 10, 20, 30, 40, 50 and 60 min were
determined by GC using n-decane as an internal standard.
Compound 3ea has already emerged in this Experimental
Section, and their spectral and analytical data are thus
collected there (vide supra). The reaction rate at the early
stage of each reaction was obtained by plotting the yield of
3ea against the reaction time. Figure ES1 indicates the
result for the reaction of 1e or 1e-1-d with 2a. The slope
value of each line in Figure ES1 is 0.38 or 0.37,
respectively, thus showing that the value of the kH/kD is
approximately 1.0 (= 0.38/0.37).
1
was fully characterized by H and 13C NMR spectroscopy
1
and elemental analysis, as follows: H NMR (400 MHz,
CDCl3)  2.06 (s, 12 H), 5.88 (s, 4 H), 7.05 (dt, J = 9.4, 2.5
Hz, 4 H), 7.14 (dt, J = 9.3, 2.5 Hz, 4 H), 7.20 (dt, J = 9.2,
2.3 Hz, 4 H), 7.23 (s, 2 H), 7.23–7.28 (m, 2 H), 7.36 (ddd,
J = 7.6, 7.1, 0.9 Hz, 2 H), 7.41 (dt, J = 8.0, 0.8 Hz, 2 H),
7.48 (dt, J = 9.2, 2.3 Hz, 4 H), 7.87 (dt, J = 8.1, 0.7 Hz, 2
H); 13C NMR (125 MHz, CDCl3)  13.0, 105.4, 120.8,
121.5, 122.5, 122.8, 123.3, 124.2, 124.8, 127.4, 128.8,
128.9, 132.7, 134.9, 135.3, 139.2, 139.5, 145.9, 146.8.
Anal. Calcd for C52H42N4S2: C, 79.36; H, 5.38; N, 7.12; S,
8.15. Found: C, 78.97; H, 5.16; N, 6.86; S, 8.52.
A Confirmation Experiment of a Released Alcohol
(Scheme 10)
The reaction shown in Scheme 10 was carried out similarly
as the general procedure described in “Indium-Catalyzed
SNAr Amination of Thiophene Electrophiles with
Secondary Amines: A General Procedure for Table 2”.
Reagents and conditions: 1e (74.5 mg, 0.625 mmol), 7aa
(60.1 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
PhCl (1.0 mL), 90 °C, 24 h. Compounds 3ea and n-decanol
(5a) were isolated by column chromatography on silica gel
(hexane/EtOAc = 10/1 to 5/1). Compound 3ea has already
emerged in this Experimental Section, and the spectral and
analytical data are thus collected there (vide supra).
Compound 5a is commercially available, and spectral and
analytical data of 5a are in good agreement with those of
the commercial n-decanol. Accordingly, only 1H NMR
Figure ES1. Plots of the yield of 3ea against the reaction
time for the indium-catalyzed SNAr amination of 2a with
1e or 1e-1-d.
1
data of 5a are provided here. H NMR (400 MHz, CDCl3)
 0.88 (t, J = 6.9 Hz, 3 H), 1.19–1.40 (m, 14 H), 1.57
(quint, J = 7.1 Hz, 2 H), 3.64 (t, J = 6.6 Hz, 2 H).
A Deuterium Labelling Study: Reaction of MeOD with
3ea (Scheme 14)
A Deuterium Labelling Study: Reaction of 1e-1-d with
2a (Scheme 11)
The reaction shown in Scheme 14 was carried out similarly
as the general procedure described in “Indium-Catalyzed
SNAr Amination of Thiophene Electrophiles with
Secondary Amines: A General Procedure for Table 2”.
Reagents and conditions: MeOD (20.7 mg, 0.625 mmol),
3ea (50.3 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50
mol), PhCl (1.0 mL), 90 °C, 24 h. Product 3ea-3-d was
isolated by column chromatography on silica gel
(hexane/EtOAc = 20/1) in 91% yield (46.1 mg) with a total
The reaction shown in Scheme 11 was carried out similarly
as the general procedure described in “Indium-Catalyzed
SNAr Amination of Thiophene Electrophiles with
Secondary Amines: A General Procedure for Table 2”.
Reagents and conditions: 1e-1-d (75.1 mg, 0.625 mmol),
2a (28.5 mg, 0.250 mmol), In(NTf2)3 (2.39 mg, 2.50 mol),
PhCl (1.0 mL), 90 °C, 24 h. A mixture of products 3ea-3-d
and 3ea-5-d was isolated by column chromatography on
silica gel (hexane/EtOAc = 20/1) in 76% yield (38.4 mg)
with a total deuterium content of 50%, which was
1
deuterium content of 23%, which was determined by H
1
NMR. A white solid, mp 72–73 ºC. H NMR (400 MHz,
CDCl3)  3.16–3.23 (m, 2 H), 3.96 (t, J = 8.6 Hz, 2 H),
6.50 (dd, J = 3.7, 1.4 Hz, 0.78 H), 6.74–6.83 (m, 2 H),
6.89–6.95 (m, 1 H), 7.12–7.18 (m, 3 H);
1
1
determined by H NMR. A white solid, mp 72–74 ºC. H
NMR (500 MHz, CDCl3)  3.20 (t, J = 8.6 Hz, 2 H), 3.97
(t, J = 8.6 Hz, 2 H), 6.47–6.55 (m, 0.80 H), 6.71–6.85 (m,
1.70 H), 6.88–6.96 (m, 1 H), 7.09–7.20 (m, 3 H);
13C NMR (125 MHz, CDCl3) 28.2
6
5
(C1), 54.1 (C2), 108.4 (C7), 109.7 (C10),
109.9 (C10), 110.1 (C10), 113.5 (C12),
119.3 (C5), 124.8 (C4), 125.6 (C11),
125.7 (C11), 127.4 (C6), 130.4 (C3),
147.0 (C8), 148.3 (C9), 148.4 (C9).
HRMS (FD) Calcd for C12H10DNS: M,
7(H)D
13C NMR (125 MHz, CDCl3)  28.2
6
4
5
10
8
11
12
7(H)D
(C1), 54.1 (C2), 108.4 (C7), 110.1
3
2
N
4
9
(C10), 110.2 (C10), 113.5 (C12),
10
8
11
12
S
3
2
1
113.6 (C12), 119.4 (C5), 124.7 (C4),
124.8 (C4), 125.4 (C11), 125.5
N
9
S
D(H)
1
202.0675. Found: m/z 202.0667.
17
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
Acknowledgements
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2016, 22, 14186–14189 (Pd); k) M. S. Oderinde, N. H.
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We thank Mr. Toshiyuki Katsumata for experimental assistance.
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18
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
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system is also applicable to the amination of 2-
methoxynaphthalene, as the following scheme shows:
[24] The reaction of 2f with 9,10-dihydroacridine as
another example of the cyclic diarylamine was also
examined but resulted in the dehydrogenative oxidation
of 9,10-dihydroacridine to give acridine preferentially
and thus in no formation of the desired C–N bond.
In(NTf2)3 (20 mol%)
NH2
2.5:1
+
O
HN
74% yield
PhCl, 130 ºC, 48 h
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19
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701452
Advanced Synthesis & Catalysis
[29] For a representative review, see: Y. Shirota, H.
procedure. Therefore, In(NTf2)3 is stable to H2O but
highly hygroscopic, and thus is recommended to be
pre-dried as shown in the Experimental Section, in
which catalyst In(NTf2)3 as well as substrates and
solvent PhCl are pre-dried. However, the amination of,
for instance, 2f with 1i performed without pre-drying
In(NTf2)3 or without pre-drying all of 1i, 2f, In(NTf2)3
and PhCl gave 93% NMR yield of 3if in either case and
thus resulted in no significant decrease of the yield,
compared to the 99% yield of 3if obtained by the
reaction based on the general procedure (see Table 3).
These results clearly show that the high performance of
the heteroaryl amination is attributed to the anhydrous
conditions but, on the other hand, that its good
performance is maintained even without the precaution.
Kageyama, Chem. Rev. 2007, 107, 953–1010.
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Advanced Synthesis & Catalysis
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21
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10.1002/adsc.201701452
Advanced Synthesis & Catalysis
FULL PAPER
A Heteroarylamine Library: Indium-Catalyzed
Nucleophilic Aromatic Substitution of
Alkoxyheteroarenes with Amines
cat.
R1R2NH
+
In
R1R2N Het
Adv. Synth. Catal. Year, Volume, Page – Page
– HOMe
MeO
Het
Kyohei Yonekura, Yasuhiro Yoshimura, Mizuri
Akehi, Teruhisa Tsuchimoto*
22
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