Facile one-pot synthesis of 2-aminoindoles from simple anilines and ynamides

Article abstract of DOI:10.1039/d0cc06490d

A highly effective and straightforward one-pot synthesis of diversely substituted 2-aminoindoles has been developed, involving sequential Au(i)-catalyzed regioselective hydroamination and CuCl2-mediated oxidative cyclization. This protocol offers an operationally easy, simple, robust, and sustainable approach with the use of readily available starting materials, good functional group tolerance, and high practicality and efficiency. This journal is

Full text of DOI:10.1039/d0cc06490d

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DOI: 10.1039/D0CC06490D
COMMUNICATION
Facile One-Pot Synthesis of 2-Aminoindoles from Simple Anilines
and Ynamides
Young Ho Kim, Huen Ji Yoo, and So Won Youn*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A highly effective and straightforward one-pot synthesis of Common limitations of these methods include requisite use of
diversely substituted 2-aminoindoles has been developed, prefunctionalized arenes and generation of only 3-
involving sequential Au(I)-catalyzed regioselective hydroamination unsubstituted indoles. On the other hand, Skrydstrup and co-
and CuCl2-mediated oxidative cyclization. This protocol offers an workers developed a two-step process consisting of 1) Au-
operationally easy, simple, robust, and sustainable approach with catalyzed hydroamination of ynamides with 2-haloanilines and
the use of readily available starting materials, good functional 2) Pd-catalyzed cyclization of the so-generated amidine
group tolerance, and high practicality and efficiency.
precursors (B) for synthesis of 2-amidoindoles (Scheme 1Bb,
upper).5a This cyclization step required purified intermediates;
thus, an attempt to perform a one-pot reaction directly using
ynamides and 2-haloanilines failed. Interestingly, however, they
found that the Pd-catalyzed Larock indole protocol gave a
mixture of 2- and 3-aminoindole isomers with opposite
regioselectivity, which has been wisely utilized for synthesis of
δ-carbolines from ynamides and 2-haloanilines through Pd-
catalyzed sequential reactions by Cao and Lai.6 As a one-step
protocol, Au-catalyzed intermolecular reactions of ynamides
with various nitrene transfer reagents have been employed for
sequential C-N and C-C bond formation (Scheme 1Bb, middle),7
which is mechanistically similar but based on a different bond
disconnection from that shown in Scheme 1A. In this reaction,
N-heterocycles such as anthranils, benzotriazoles, and
Among indoles referred to as “privileged structures,” 2-
aminoindoles are important structural motifs found in a wide
range of bioactive compounds.1 While numerous methods for
construction of indoles have been developed, synthetic
methods to produce 2-aminoindoles have remained limited. In
recent years, various synthetic approaches toward 2-
aminoindoles using ynamides2 as versatile building blocks have
been developed.3-7 Ynamides are useful precursors as a source
of either the N1 atom or C2-amino substituent for regioselective
formation of the 2-aminoindole scaffold.
In 2003, Witulski and co-workers reported a Pd-catalyzed
annulative cross-coupling reaction of N-(o-haloaryl)ynamides
with primary and secondary amines as a source of the C2-amino
substituent to afford 2-aminoindoles through a one-pot C-N/C-
C bond forming sequence (Scheme 1A).3a Later, leading
researchers in gold catalysis, Ye,3b Liu,3c and Hashmi3d
independently demonstrated Au-catalyzed intermolecular
reactions of ynamides with various nitrene transfer reagents
(azides, benzisoxazoles, sulfilimines, respectively) as precursors
of α-imino gold carbene intermediates as well as a source of C2-
amino substituent, relying on the same bond disconnection
approach. One of the most common synthetic strategies for 2-
aminoindole synthesis is use of ynamides as a source of C2-
amino substituents and C2 building blocks (C2-C3 bond) for the
pyrrole nucleus of indoles (Scheme 1B). Some examples of Pd-
and/or Cu-catalyzed one-pot processes involving in situ
formation of o-aminoaryl-substituted ynamides (A) as a
common intermediate have been reported (Scheme 1Ba).4
A) Ynamides as a building block for indole skeleton & amine derivatives as a source of 2-amino substituent
C-N C-C
bonds
: Intermolecular annulative coupling of ynamides with external N source :
&
R2
I or H
R2
R3
[Pd] or [Au]
(ref. 3)
R
N
1 from ynamide Csp-N
+
N
N
R4
R
N
R1
N
C2- from external N source
N
R1
B) Ynamides as a C2 building block (C2-C3 bond) & anilines derivatives as a N1 source
C-N
a) Intramolecular cyclization of ynamide intermediates :
R3
& C-N/C-C bonds
[Cu]
R3
N
R4
and/or
various
precursors
N
R4
R
[Pd]
(ref. 4)
N
R1
R
1
A
N
HR
C-N C-C
bonds
b) Intermolecular annulative coupling of aniline derivatives with ynamides :
&
[Pd]
R2
3-aminoindoles
only or mixture of 3- & 2-isomers
(refs. 5a, 6)
I
R
+
I
R2
[Pd]
[Au]
N
H2
R
N
R3
N
1 from N atom of anilines
R4
R3
(ref. 5)
N
B
N
R4
N
C2- from ynamide Csp-N
R2
R2
H
H
R3
N
R4
Ph
S
[Au]
R
R
R
or
+
R
(ref. 7)
N
Ph
N
R1
N
N
R4
X = O, N
Y = N, C
R3
Y
X
R2
Center for New Directions in Organic Synthesis, Department of Chemistry and
Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
E-mail: sowony73@hanyang.ac.kr
R2
H
R
R3
[Cu]
[Au]
+
N
N
R4
N
H2
N
one-pot cascade
(this work)
R4
C
R3
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
Scheme 1 Synthesis of 2-aminoindoles employing ynamides.
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Table 1. Optimization studies: Stepwise process
benzofurazan N-oxides used as nitrene transfer reagents
provide indole products, which have a certain substituent such
as acyl,7a pyrazolyl,7b and nitro7c-d group, respectively, mostly at
the C7 position. In contrast, Hashmi successfully utilized
sulfilimines as a nitrene transfer reagent with a traceless leaving
group (i.e., sulfide) to afford diversely substituted 2-
aminoindoles.7f Despite significant advances, several drawbacks
such as requirement of prefunctionalized substrates and, thus,
several steps or limited commercially available reagents for
preparation of starting materials, use of costly ligands, and a
stepwise process limit the practicality of these reactions.
Therefore, development of a simple, cost-effective, and
sustainable protocol for regioselective formation of such
compounds is highly desirable. The use of low cost, diverse, and
widely available anilines would be more efficient and attractive
to improve the practicality and synthetic utility of this
transformation.
Considering the regioselective reactivity of ynamides2 and
inspired by literature precedents of oxidative cyclization of N-
aryl enamines8a-d/imines8e for indole synthesis, we envisaged
regioselective addition of anilines to ynamides and subsequent
oxidative cyclization of the ensuing amidines (C) to afford 2-
aminoindoles (Scheme 1Bb, lower). Realization of this proposal
would be a significant advance, providing a straightforward
route to such compounds, overcoming the aforementioned
deficiencies of the precedent syntheses.
View Article Online
DOI: 10.1039/D0CC06490D
Ph
Ph
Ts
Ts
10 mol% catalyst
oxidant
+
NH2
Ph
N
N
Ts
toluene (0.1 M)
100 o
toluene (0.1 M)
120 o
N
N
Me
N
H
Me
C
2d
(1 equiv)
C
Me
3ad
1a
4ad
Step 1 : Hydroamination
Step 2 : Oxidative annulation
Entry
Catalyst
HNTf2
3ad (%)a
55
Entry
Oxidant (equiv)
CuCl2 (3)
4ad (%)a
39
1
2
3
4
5
6
7
8
9
AgOTf
63
10
Cu(OAc)2 (3)
CuI (3)
trace
0
ZnBr2
71b
31
11
CuCl2
12
I2 (3) or NIS (3)
NCS (1)
20 or 24
27
Cu(OTf)2
PPh3AuCl
PPh3AuCl/AgNTf2
71
13
38
14d
15d-e
16d, f
CuCl2 (2)
34
93b
90b
CuCl2 (2)
5-21
73b
c
PPh3AuCl/AgOTfc
CuCl2 (2)
a 1H NMR yields. b Isolated yields. c 5 mol% each ([Au]:[Ag] = 1:1). d At 100 °C. e In
the presence of 10 mol% AgSbF6, Cu(OTf)2, FeCl3, or PPh3AuCl/ AgOTf (1/1). f Using
3aa (derived from 2a) instead of 3ad and isolated yield of 4aa.
Table 2. Optimization studies: One-pot domino processa
: R1 = Ms, R2 = Bn
: R1 = Ms, R2 = Me
: R1 = Ts, R2 = Bn
: R1 = Ts, R2 = Me
Ph
5 mol% catalyst
solvent (0.1 M)
100 oC, 2 h, then
2 equiv oxidant
100 oC, Ar
2a
2b
2c
2d
2e
R1
R2
R1
R2
+
Ph
N
N
N
NH2
H
2
1
: R -R2 = CO2(CH2)2
1a
4
(1 equiv)
Entry
1
2
Catalysta
Oxidant
Solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
Time (h)b
Yield (%)c
(60) (4aa)
(45)
2a
PPh3AuCl/AgOTf
PPh3AuCl/AgNTf2
AgOTf
CuCl2
CuCl2
CuCl2
CuCl2
I2
4
2
2a
2a
2a
2a
2a
2a
2a
2a
2a
4
As part of our continued interest in oxidative annulation and
one-pot reactions in heterocycle synthesis,9 we herein report a
highly effective and facile synthesis of diversely substituted 2-
aminoindoles directly from anilines and ynamides (Scheme 1Bb,
lower). This one-pot sequential process consists of 1) C-N bond
3
10
3
17
4
Cu(OTf)2
2
5
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
PPh3AuCl/AgOTf
2
6
6
NIS
2
12
formation
through
Au(I)-catalyzed
regioselective
7
NCSd
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
6
30
hydroamination of ynamides with anilines and 2) C-C bond
formation through CuCl2-mediated cyclization of the so-
generated amidine intermediates.
8
4
(44)
9
DMF
4
13
10
11
12
13
14
15e
THF
4
(73)
To test the viability of the one-pot sequential process in forming
2-aminoindoles, 1a and 2d were employed as test substrates to
investigate the stepwise hydroamination and oxidative
cyclization reactions (Table 1).10 First, we examined a variety of
Brønsted/Lewis acids for hydroamination to form amidines 3.
Although most of the catalysts surveyed promoted
hydroamination to give 3ad in low to moderate yields, the
combination of PPh3AuCl and Ag salts such as AgNTf2 or AgOTf
2b
2c
2d
2e
2a
THF
6
35 (4ab)
(69) (4ac)
30 (4ad)
- (4ae)
12
THF
6
THF
6
THF
6
THF
24
Reaction conditions: 1a (1 equiv), 2 (1 equiv), 5 mol% catalyst in solvent (0.1 M) at
100 °C for 2 h under Ar. Subsequently, oxidant (2 equiv) was added to the reaction
mixture and stirred at 100 °C under Ar. a [Au]:[Ag] = 1:1. b Reaction time after the
11
was most effective for this transformation (entries 7-8).5,
c
addition of oxidant. Determined by 1H NMR. Values in parentheses indicate
isolated yields. d Using 1 equiv NCS. e All the catalysts, oxidant, and reagents were
added at the outset of the reaction.
Having identified successful conditions for amidine formation,
oxidative annulation of 3ad was investigated under previously
reported conditions for related processes of N-aryl enamines.8
After initial findings that the desired indole product 4ad was
formed in 45% yield under Liang’s protocol using FeCl3 as a
catalyst and Cu(OAc)2·CuCl2 complex as an oxidant,8c further
examination of the reaction parameters was undertaken. We
found that a comparable yield of 4ad could be obtained using
only CuCl2 (entry 9). Hoping to improve the reactivity as well as
to examine compatibility with this cyclization condition, a
variety of metal catalysts, including those that could promote
the 1st step, were subjected to the CuCl2-mediated reaction of
3ad. Unfortunately, the presence of other metal catalysts
exerted a deleterious effect on the reaction (entries 14 vs. 15).
A substantial effect of N-substituents of amidines was observed
in the oxidative cyclization reaction, and N-benzyl-N-mesyl-
substituted amidines (e.g., 3aa) proved to be optimal (entry 16).
Having established optimal conditions for the stepwise process,
we investigated a one-pot domino reaction (Table 2).10
Considering the preliminary results regarding the detrimental
effect of metal catalysts including Au(I) on oxidative annulation,
the presence of Au(I) in the same reaction vessel could influence
the outcome of the 2nd step due to compatibility issues. Very
2 | J. Name., 2012, 00, 1-3
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R
5 mol% PPh3AuCl
5 mol% AgOTf
regardless of substituent position, while stronVgileyw AertlieclcetOrnolinne-
withdrawing substituents, such as NO2D, OreI:s1u0l.1t0e3d9/iDn0CreCl0a6t4iv9e0lDy
lower yields of the desired products (4aj, 4am) (Scheme 2b).
Furthermore, reaction of bis(ynamide) 2s proceeded
uneventfully to afford the desired bisindole 4as. In contrast, the
reaction failed with heteroaryl- and alkyl-substituted ynamides.
This process can tolerate various functional groups such as
halogen, ketone, ester, and nitro groups. In particular, both 2-
haloanilines (1o-r→4oa-ra) and 2-haloaryl-substituted
ynamides (2o→4ao, 2r→4ar/4fr) afforded products with an
intact halogen substituent. This functional group tolerance
could be advantageous compared to other transition metal-
Ms
N
Bn
Ms
N
Bn
R'
R'
+
R
THF, 100 oC, 2 h
then, 2 equiv CuCl2
N
H
NH2
2
1
4
(1 equiv)
1
2a
a) Anilines ( ) - Reaction with
R' = H (
OMe (
(R = Ph)
Ph
4aa
) : 4 h, 73%
4ba
4ma
R' = Me (
) : 4 h, 66%
) : 4 h, 69%
) : 4 h, 62%
) : 6 h, 61%
Ph
Ms
) : 4 h, 62%
4na
4oa
4pa
Ph (
Br (
I (
R'
Ms
N
4ca
Me (
) : 4 h, 68%
) : 4 h, 61%
) : 4 h, 66%
N
N
Bn
4da
F (
H
N
Bn
H
R'
4ea
Cl (
Ph
Ph
Ms
N
4fa
Br ( ) : 6 h, 87%
Ms
N
Bn
4ga
) : 8 h, 75%
I (
4ha
Ac (
) : 6 h, 56%
CO2Me ( ) : 4 h, 61%
N
N
Bn
4ia
H
H
Br
Br
4ra
R'
a
a
Ph
Ph
4qa
: 3 h, 65%
Ph
: 6 h, 67%
Ms
Ms
N
Bn
N
+
Ms
N
Bn
N
N
Bn
R'
H
H
N
H
5-6
catalyzed synthetic methods to prepare 2-aminoindoles3a,
4ja
R' = Me ( ) : 6 h, 66% (2.5:1)
4ka
Br (
) : 8 h, 54% (1.7:1)
4la
( ) : 6 h, 57% (1:1)
4sa
: 2 h, 68%
and makes this method particularly appealing, since it should
permit further elaboration and enable greater structural
diversity.
NO2
2
1a
b) Ynamides ( ) - Reaction with aniline ( , R' = H)
R
R
R =
4af
Me ( ) : 4 h, 72%
R = OMe (4ak) : 6 h, 76%
4ag
4ah
Cl (
Br (
) : 6 h, 57%
) : 6 h, 65%
4ai
CO2Me ( ) : 6 h, 71%
4al
Me ( ) : 4 h, 66%
4am
) : 4 h, 50%
Ms
Ph
Ph
Br
Ph
NO2
(
tBuO2C
Br
N
Ms
Ms
4aj
NO2
(
) : 6 h, 46%
N
H
Heck reaction
N
Bn
R'
N
N
N
(a)
N
N
N
N
H
Bn
H
Br
Buchwald-
6a
6b
4fr
X
R
Ms
Suzuki reaction
Hartwig amination
N
Ms
Ms
N
Bn
Ms
N
Ph
N
N
H
N
Ph
N
Ph
H
N
N
H
N
N
Bn
Bn
H
H
Br
R' = H (4ar) : 6 h, 58%
[Pd]
N
N
R
4an
N
R = Me (
) : 4 h, 68%
N
N
4ap
4aq
: 6 h, 59%
: 6 h, 70%
6d
(from
)
Ts
4ao
Br (
) : 5 h, 71%
4fr
Br ( ) : 6 h, 85%
Ms
Ms
6e
6f
6c
6d
(X = CH)
(X = N)
(R = H)
(R = NHTs)
Bn
Bn
N
N
6g
Ph
HN
NH
Ph
Ms
Ms
Ph
Ms
Bn
N
N
b
Ms
2s
4as
N
N
R1
: 6 h, 43%
Bn
Bn
N
(b)
(c)
Ms
N
N
N
H
Bn
R2
Bn
N
Br
(R1 = H, R2 = Ph)
(R1 = allyl, R2 = H)
Scheme 2 Substrate scope. Reaction conditions: 1 (1 equiv), 2 (1 equiv), 5 mol%
PPh3AuCl, 5 mol% AgOTf in THF (0.1 M) at 100 °C for 2 h under Ar. Subsequently,
CuCl2 (2 equiv) was added to the reaction mixture and stirred at 100 °C for the
provided time under Ar. Isolated yields are given. After 3 h, CuCl2 was added.
Using 2.1 equiv 1a, 1 equiv 2s, and twice amount of catalysts and reagents.
7b
7e
4oa
N
N
8
Bn
Ph
Ph
Ph
Ts
Ts
metathesis
N
Ts
a
b
N
N
N
N
N
Bn
H
4ac
7h
9
interestingly, in sharp contrast to the stepwise reaction, the 2nd
step, CuCl2-mediated cyclization, proceeded smoothly in the
presence of the Au(I) catalyst used in the 1st step (entry 1). To
find the optimal conditions for this sequence, diverse variations
of the reaction parameters were explored. In this one-pot
process, AgOTf and THF were more effective than AgNTf2 and
toluene as Ag salt and solvent, respectively (entries 1-2 and 10).
Replacing any component with alternatives significantly
reduced the conversion and efficiency (entries 1-9 vs. entry 10).
For ynamide, benzyl (Bn) and mesyl (Ms) were identified as
optimal N-substituents (entry 10 vs. entries 11-14). Encouraged
by these results, we attempted this reaction by adding all the
catalysts and reagents into the same pot from the outset;
however, a low yield of 4aa was obtained (entry 15). In contrast
to related prior work,5-6 the one-pot reaction successfully
achieved regioselective construction of 2-aminoindoles directly
from ynamides and simple anilines.
With establishment of a viable one-pot reaction system, we set
out to explore the scope of this domino process. A wide range
of anilines (1) underwent domino amidine formation/oxidative
cyclization smoothly to afford the corresponding 2-
aminoindoles (4) in good yields irrespective of the electronic
properties and position of substituents (Scheme 2a). In general,
a variety of aryl-substituted ynamides (2) was well tolerated
Scheme 3 Synthetic application.
To highlight the synthetic utility of this one-pot reaction, further
transformation of the indoles obtained from this process was
undertaken.10 First, intramolecular N-arylation of 4fr, which has
an ortho-bromo substituent on the N-benzyl group, proceeded
smoothly to give indoloquinazoline 6a (Scheme 3a).4c Further
elaboration of bromo-substituted 6a was readily accomplished
through Heck (6b), Suzuki (6c-d), and Buchwald-Hartwig
amination (6e-f) reactions, leading to diversely substituted
indoloquinazolines 6b-f in good yields. Subsequent Pd-
catalyzed oxidative C-H amidation of 6d successfully installed
the carbazole skeleton to afford 6g in 91% yield. 7-Bromo-
substituted 4oa was transformed into 7-triazole-substituted
indole 7b or 7e via Sonogashira reaction followed by Ru- or Cu-
catalyzed cycloaddition of the so-generated 7-alkynyl indoles
with benzyl azide (Scheme 3b). In addition, pyrroloquinoline 8
was constructed by N-allylation of 4oa followed by Heck-type
cyclization. In addition, facile removal of the N-Bn group led to
NH-free indole, which could be transformed into 7h by
bisallylation. 7h was further subjected to a metathesis reaction
to form diazepinoindole 9 in 96% yield (Scheme 3c).
Although clearly detailed mechanistic studies are needed to
clarify the mechanism especially for the Cu-mediated
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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R
There are no conflicts to declare.
R
[Au]+
View Article Online
DOI: 10.1039/D0CC06490D
R
[Au]
Ms
Ms
N
Bn
N
R'
R'
Bn
Ms
N
N
H
NH2
Bn
2
1
I
[Au]+
Notes and references
4
R
R
1
2
3
(a) J. Landwehr, S. George, E.-M. Karg, D. Poeckel, D.
Cu(0)
R'
Ms
N
Bn
Ms
Ms
Steinhilber, R. Troschuetz, and O. Werz, J. Med. Chem., 2006,
49, 4327; (b) M. Tichy, R. Pohl, H. Y. Xu, Y. L. Chen, F.
Yokokawa, P. Y. Shi, and M. Hocek, Bioorg. Med. Chem.,
2012, 20, 6123.
R'
N
N
N
3aa
(e.g.,
)
Bn
3
Cu
R
N
V
R'
Ms
CuCl2
N
HCl
R
N
Bn
HCl
IV
R'
Cl
R
N
Selected reviews: (a) G. Evano, A. Coste, and K. Jouvin,
Angew. Chem. Int. Ed., 2010, 49, 2840; (b) K. A. DeKorver, H.
Li, A. G. Lohse, R. Hayashi, Z. Lu, Y. Zhang, and R. P. Hsung,
Chem. Rev., 2010, 110, 5064; (c) R. H. Dodd, and K. Cariou,
Chem. Eur. J., 2018, 24, 2297.
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N
H
R'
path b
Cl
Ms
Bn
N
Cu
R
3'
CuCl2
path a
Bn
R'
III
HCl
Ms
N
N
Cu(0)
Bn
II
Cl
Ph
Cl
Ph
N
Cl
Ph
R1
O
O
2b
or
2d
hydrolysis
R1
Ph
Ph
Cl
R1
R1
Ph
1a
+
+
N
N
N
N
N
N
N
H
H
H
Me
Cl
Me
Me
Me
(R1 = Ms, Ts)
III-1
III-2
III-3
D
E
Scheme 4 Proposed mechanism.
annulation step, a plausible mechanism for this one-pot
reaction is proposed as outlined in Scheme 4. By analogy with
mechanisms established for related Au(I)-catalyzed
hydroamination of ynamides with anilines,5,
4
5
11
amidine
intermediate 3 is formed by the reaction of 1 and 2. 3′ resulting
from tautomerization of 3 undergoes electrophilic attack by
CuCl2 to provide II with loss of HCl. Reductive elimination
followed by intramolecular nucleophilic attack by the ortho
carbon of the aniline moiety to the chlorinated αC atom of
intermediate III leads to the formation of V (path a). Subsequent
isomerization of V produces the final product 4. Alternatively,
IV could be formed through nucleophilic attack of the ortho
carbon of the aniline moiety of II to Cu,8a-b,e which is promoted
by the electron-donating effect of the amide (-NMsBn) group
(path b). The indole product 4 is generated by reductive
elimination followed by isomerization of the resulting V. In the
case of reactions with ynamides 2b and 2d, formation of α-
chlorinated amides D and E was observed,10 which might form
via hydrolysis of the tautomers III-1 and III-3, respectively.
These findings suggest that this reaction more likely proceeds
through path a, involving intermediate III.
In summary, we have developed a highly efficient and facile
one-pot reaction for the synthesis of diversely substituted 2-
aminoindoles from anilines and ynamides. In this one-pot
sequential process, the two metal salts, Au(I) and CuCl2, operate
in two distinct reactions in series. To the best of our knowledge,
this represents the first example using simple anilines as a N1
source for the pyrrole nucleus of indoles, offering new and
straightforward access to synthetically valuable 2-
aminoindoles.
6
7
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8
9
This work was supported by both the Basic Science Research
Program and Nano·Material Technology Department Program
through the National Research Foundation of Korea (NRF)
funded by the Korea government (MSIT) (Nos.
2012M3A7B4049644, 2018R1A2A2A05018392, and 2014-
011165).
10 For details, see the Supporting Information.
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Conflicts of interest
4 | J. Name., 2012, 00, 1-3
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