Copper-Catalyzed Synthesis of 2-Aminocarbazoles through Cascade C–C and C–N Bond Formation and Aromatization

Article abstract of DOI:10.1002/ejoc.201801297

A novel transformation of 1-(1H-indole-3-yl)pentan-3-one into 2-aminocarbazoles in moderate yields using ammonium carbonate as a nitrogen source was achieved by copper catalysis. The method uses easily prepared starting materials with low cost and less to

Full text of DOI:10.1002/ejoc.201801297

A Journal of
Accepted Article
Title: Copper Salt Catalyzed Synthesis of 2-Aminocarbazoles via
Cascade C-C C-N Bond Formation and Aromatization
Authors: Xinlei Liu, Jiangkun Huang, Huibei Xu, Dandan Zhang, Qiu
Sun, and Ling He
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801297
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801297
Supported by

10.1002/ejoc.201801297
European Journal of Organic Chemistry
COMMUNICATION
Copper Salt Catalyzed Synthesis of 2-Aminocarbazoles via
Cascade C-C C-N Bond Formation and Aromatization
Xinlei Liu,a Jiangkun Huang,a Huibei Xu,a Dandan Zhang,a Qiu Sunb* and Ling Hea*
Abstract: A novel transformation of 1-(1H-indole-3-yl)pentan-3-one cyclization of diarylamines, transition metal free or rhodium
into 2-aminocarbazoles in moderate yields using ammonium catalyzed intramolecular C-H amination of anilides and nitrene
carbonate as a nitrogen source was achieved by copper catalysis. insertion of 2-azido-biphenyls, and Pd catalyzed one-pot Suzuki-
The method uses easily prepared starting materials with low cost Cadogan cascade reaction of o-halonitrobenzenes. Although
and less toxic reagents. The reaction proceeds in a one-pot manner, these methods are highly efficient and show good compatibility
giving rise to the homogeneous cleavage of C-H bonds, the with functional groups, for the synthesis of multifarious
formation of intramolecular C-C bonds, intermolecular C-N bonds, carbazoles derivatives, they require the preparation of complex
and aromatization.
starting materials, such as amino-, azido-, nitro- and halo-
substituted biaryls or indol-3-yl-3-yn-2-ols or N, N-biaryl amines
or require expensive reagents. Therefore, we have exploited the
Introduction
development of
a one-pot C-C/C-N bond formation and
dehydrogenative tandem reaction that utilizes easily prepared
starting materials with low cost and less toxic reagents. More
recently, there are reports on the direct carbon-carbon coupling
of indoles with alkenes and alkynes to provide carbazoles
(Scheme 2, b).[7] These synthesis of carbazoles via Pd-
catalyzed and copper(II)-mediated reactions of indoles with in-
situ generated aryl vinyl ketones using saturated β-chloroalkyl
aryl ketones as the olefins source.[7f] The preparation of
carbazoles via the Pd-catalyzed dehydrogenative cross-coupling
of indoles with in situ generated aryl vinyl ketones by using
statured ketones as the olefins source under the presence of
ligand PCy3, Ag2CO3, LiOAc, TEMPO, O2.[7g] However, the indole
to carbazole transformation via direct cross-coupling using
alkylketones are sparse in the literature. Especially, the direct
intramolecular C-C coupling of indoles with alkanes has not
been reported. Therefore, ongoing development of a greener
and more concise procedure to acquire substituted carbazoles is
still desirable.
Carbazoles as structural motifs have been widely applied in
material science such as organic electroluminescent materials,[1]
organic photorefractive materials,[2] solar cell materials.[3] In
addition, carbazoles derivatives are also unique structural units
in pharmaceuticals and natural products showing significant
biological activities. For example, staurosporine and its
derivatives have a variety of biological activities[4] including
antifungal,
antihypertensive
and
antitumor.
Moreover,
carbazoles was also used in dye industry and supramolecular
recognition. Based on carbazoles broad application and their
importance (Scheme 1), it is of great significance to propose
efficient methods for the construction of carbazole derivatives
with biological activity or specific function.[5]
Scheme 1. Carbazole derivatives with special functions
.
Over the past decades, some general strategies for the
synthesis of carbazoles have been developed[6]. These methods
include the formation of C-N / C-C bond and C-H cleavage
(Scheme
2,
a),
such
as
transition-metal-catalyzed
intramolecular dehydrogenative cross coupling, oxidative
[a]
[b]
X.L.Liu, J.K.Huang,H.B.Xu,D.D.Zhang, Prof. Dr. L.He
Sichuan Engineering Laboratory for Plant-Sourced Drug and
Sichuan Research Center for Drug Precision Industrial
Technology,Department of Medicinal Chemistry, West China School
of Pharmacy, Sichuan University,Chengdu, Sichuan, 610041(P. R.
China)
E-mail: lhe2001@sina.com
Dr. Q. Sun
West China Medical Center of Sichuan University, Chengdu,
Sichuan, 610041(P. R. China)
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201801297
European Journal of Organic Chemistry
COMMUNICATION
DMF and dimethylsulfoxide resulting in formation of traces of
carbazole under the same condition.
Table 1. Optimization of the reaction conditions.a
Scheme 2. Various strategies for the synthesis of carbazoles
Entry Catalyst
solvent
Time Yield
T(℃)
(h)
24
%
N.R
To take advantage of easily preparable starting materials with
tolerance of most organic functional groups for the preparation
of new pharmacologically active compounds, we developed a
copper-catalyzed oxidative cyclization based on easily available
indole saturated side-chain ketones and inexpensive ammonium
carbonate as nitrogen source, providing the novel 2-
aminocarbazoles derivatives with moderate yields. This reaction
completes the homogeneous cleavage of C-H bonds and the
formation of C-C and C-N bonds in one pot reaction, by a
sequence of free radical initiation, cyclization, Schiff base
formation, dehydrogenation, rearrangement and aromatization.
1
2
3
4
---
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3OH
80
80
80
80
80
80
80
80
r.t
CuI
24
24
24
24
24
24
24
24
48
24
24
24
24
24
24
40
Cu(CF3SO3)2
Cu(OAc)2
Cu(ClO4)2
Cu(acac)2
CuBr
56
trace
11
5
6
N.R
19
9
10
11
12
13
14
15
16
17
18
CuBr2
53
Cu(CF3SO3)2
Cu(CF3SO3)2
Cu(CF3SO3)2
Cu(CF3SO3)2
Pd(OAc)2
Yb(CF3SO3)3
(Cp*RhCl2)2
N.R
55
100
100
50
Results and Discussion
Toluene 120
53
CH3CN
CH3CN
CH3CN
80
80
80
80
N.R
N.R
N.R
N.R
To initiate the study, the reaction using 1-(1H-indole-3-
yl)pentan-3-one (1a) as the model substrate and (NH4)2CO3 as
nitrogen source was used to optimize the reaction conditions
(Table 1). In order to evaluate the catalytic efficiency of various
metal complexes including Yb(CF3SO3)3, Pd(OAc)2, Ru3(CO)12,
(CpRhCl2)2, [Rh(CH3(CH2)6CO2)2]2, Cu(OAc)2, CuCl2, CuBr2,
Cu(CF3SO3)2, the reaction of 1a with (NH4)2CO3 was studied by
using a catalyst with acetonitrile as solvent at 80oC. The results
were shown in Table 1. It was found that only copper salts could
be led to the formation of the desired carbazoles(3b) (Table 1,
Entries 1- 14). Other metal complexes, such as Pd, Yb,and Rh,
displayed poor catalytic activity (Entries 15- 18). At the same
time, the catalytic effect of bivalent copper is generally better
than that of univalent copper on this reaction. Among the
catalysts of various copper salts, Cu(CF3SO3)2 was the most
effective for the reaction (Table 1, entry 3).
[Rh(CH3(CH2)6CO2)2] CH3CN
2
aReaction conditions: 1 (0.4mmol), (NH4)2CO3 (8mmol), catalyst
(0.08mmol), CH3CN (2ml), 80oC, 24h. bIsolated yield, N.R: no
reaction.
Furthermore, the influence of the nitrogen source on the yield
was studied, when other nitrogen sources such as (NH4)2C2O4,
NH4Ac,etc. took the place of ammonium carbonate, no
carbazole products were obtained, And other alkyl primary
amine and aromatic primary amine were tried as well, but the
carbazole products were still not obtained. On the basis of these
results, we used the optimum condition in a molar ratio of
1a/ammonium carbonate/catalyst = 1.0 : 20 : 0.2 in acetonitrile
at 80oC for subsequent study.
After determining the optimum reaction conditions, in order to
investigate the universality of the reaction, we investigated the
substrate scope; the results are outlined in Scheme 3. A series
of 1-(1H-indole-3-yl)pentan-3-ones(R1=H, R3=Me, R4=H, Me, Ph)
can successfully provide the corresponding carbazole products
in moderate yields ( the structure of 3e was confirmed by X-ray
crystal structure CCDC 1589600) under identical conditions.
Unfortunately, when a carbon chain was extended at the end of
the indole side chain, the activity for the reactions was reduced
under strictly identical conditions, such as 3i, 3j, 3k, 3l,
3m(R3=Et). Meanwhile, we notice the substrate with the
electron-donating substituent on the indole nitrogen (R1=Me)
results in moderate yield, however, the substrate with the
electron-withdrawing groups on the indole nitrogen gave only
trace amount of corresponding products, such as R1=Ph, Bn, Ts,
Boc, Ac. The results showed that the reaction rate of indole
changed with the presence of the protective groups on the
nitrogen of indole.
Since this reaction involves aromatization, so we also studied
the effects of temperature, oxidants and solvents on the reaction
yields, and the results are listed in Table 1. Temperature also
affected the reaction. At room temperature, the formation of
carbazole was not observed. A further increase of temperature
(80–120oC) led to the increase of reaction yields (Table 1,
entries 3, 11, 13, 14). Meanwhile, the microwave irradiation has
advantages of short reaction time over the traditional heating
mode. But the yield was not obviously improved. Subsequently,
we screened a series of oxidants to promote the aromatization
via dehydrogenation process, such as PhI(OAc)2, I2, O2, NaIO4,
.
Mn(OAc)3 2H2O, DDQ, etc, and it was found that these oxidants
resulted in the formation of traces of carbazole products.
However, (E) 1- (1H-indol-3-yl) pent-1-en-3-one was obtained.
And then the resulting trans-1- (1H-indol-3-yl) pent-1-en-3-one
could not continue to cyclize and to form carbazoles under the
same conditions. In addition, we investigated the solvent effect
on the reaction. 1-(1H-indole-3-yl) pentan-3-one(1a) as model
was heated in different solvents. Acetonitrile and methanol were
the most effective for the reaction, but the reaction hardly
proceeded in xylene and decalin. The reaction carried out in
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10.1002/ejoc.201801297
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Scheme 4. Study on the reaction mechanism
the formation of 2-amonocarbazoles, as shown in Scheme 5.
The 1-(1H-indol-3-yl)pentan-3-one was oxidized to give radical
inter-mediates by Cu(II), which recombined with side chain and
cyclization. Then the cyclic ketones were condensed with
ammonia to give Schiff base. Finally, the double bonds occurred
rearrangement leading to aromatization and the formation of the
2-aminocarbazoles.
Scheme 3. Scope and yields of the carbazole synthesis
To understand the observed reactivity, we investigated the
reaction mechanism with deuterium-labeling experiments
(Scheme 4). No significant kinetic isotope effect (KIE) was
observed when the rate constants of the reaction of 1 and 1-D2
were measured, thus suggesting that C-H activation might not
be involved in the rate-determining step (reaction 1, 2). In order
to obtain more information about the reaction process, the
radical scavenger 2,2,6,6-tetra-methylpiperidino-oxy(TEMPO)
was added to the original reaction system, the products could
not be monitored completely under the same reaction conditions.
However, the peak of reactive intermediates could easily be
detected from the reaction
3
(Scheme 4) by liquid
chromatography-mass spectrometry, such as the peaks of
m/z=357.2, 355.2, 352.2. The reactive intermediates were
captured by radical scavengers, which suggests that the
formation reaction of aminocarbazoles might go through a
radical process. At the same time, potassium carbonate, cesium
carbonate, sodium tert-butanol and DBU were employed as
promoter for the reaction. However, these bases have no
obvious effect on the yield of the reaction. Thus, combined with
our experimental results and the literatures8, we propose a
possible reaction pathway for
Scheme 5. Possible reaction pathway
Conclusions
In summary, we report a simple and effective route to
synthesize 2-aminocarbazole derivatives by transition metal
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10.1002/ejoc.201801297
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COMMUNICATION
catalyzed conversion of indole side-chain ketones in a one pot
reaction with moderate yields. It uses easily made starting
materials and many functional groups are tolerated. The indoles
to carbazoles conversion protocol involves a cascade reaction
with free radical initiation, cyclization, condensation, dehydro-
genation, rearrangement and aromatization. Further studies of
the scope, limitations and applications of this process are
currently underway in our laboratory.
1,5-Dimethyl-9H-carbazol-2-amine(3b): Brown solid ， m.p. 210 oC
yield：50%.1H NMR（400 MHz，DMSO-d6） δ=10.65 (s, 1H), 7.61 (d,
J=8.8Hz, 1H), 7.20 (d, J=7.6Hz, 1H), 7.07 (t, J=7.6Hz, 1H), 6.80 (d,
J=7.2Hz, 1H), 6.57 (d, J=8.4Hz, 1H), 4.90 (s, 2H), 2.67 (s, 3H), 2.25 (s,
3H). 13C NMR (100 MHz, DMSO-d6) δ=144.8, 141.4, 139.9, 130.6, 123.1,
122.9, 120.2, 119.9, 114.4, 109.0, 108.3, 101.9, 20.8, 11.6; HR-MS(ESI) :
Calcd for C14H15N2 [M + H]+: 211.1228，found 211.1230.
6-Chloro-1-methyl-9H-carbazol-2-amine (3c): Brown solid ， m.p. 215
oC yield：46%. 1H NMR（400 MHz，DMSO-d6） δ=10.82 (s, 1H), 7.87
(d, J=0.8Hz, 1H), 7.62 (d, J=5.2Hz, 1H), 7.32 (d, J=5.6Hz, 1H), 7.15 (dd,
J=5.6Hz, 1H), 6.56 (d, J=5.2Hz, 1H), 5.03 (s, 2H), 2.23 (s, 3H). 13C NMR
(100 MHz, DMSO-d6) δ=145.9, 142.0, 138.1, 125.7, 122.6, 122.5, 118.5,
117.9, 112.4, 111.5, 109.3, 101.6, 11.3; HR-MS(ESI): Calcd for C13
H12ClN2 [M + H]+: 231.0689, found 231.0684.
Experimental Section
The Silica gel F254 plates were used for thin layer chromatography (TLC)
in which the spots were examined under UV light at 254 nm. Flash
chromatography was performed on silica gel(300-400 mesh). Anhydrous
solvents were purified according to standard procedures. All other
commercial reagents were purchased from commercial sources and
used without purification. NMR spectra were recorded on Varian Mercury
spectrometer(400 MHz and 600 MHz). 1H NMR spectra were recorded at
ambient temperature at 400 MHz or 600 MHz. 13C NMR spectra were
recorded at ambient temperature at 100 MHz or 150 MHz. For 1H NMR
spectra acquired in DMSO-d6 , chemical shifts are reported as δ values in
ppm and are calibrated according to internal DMSO (2.50 ppm) . For 1H
NMR spectra acquired in CDCl3 , chemical shifts are reported as δ values
in ppm and are calibrated according to internal CHCl3 (7.26 ppm) .For 13C
NMR spectra, chemical shifts are reported as δ values in ppm relative to
DMSO and CHCl3. The NMR data are reported as follows: chemical shift
in ppm on the δ scale, multiplicity (app = apparent, br = broad, s = singlet,
d = doublet, t = triplet, q = quartet, quin = quintet, m = multiplet), coupling
6-Methoxy-1-methyl-9H-carbazol-2-amine[9] (3d): Brown soli ， m.p.
240-242 oC yield ：30%.1H NMR（400 MHz，DMSO-d6 ） δ=10.43 (s,
1H), 7.57 (d, J=5.2Hz, 1H), 7.40 (s, 1H), 7.23 (d, J=5.6Hz, 1H), 6.80 (d,
J=5.6Hz, 1H), 6.53 (d, J=5.2Hz, 1H), 5.03 (s, 2H), 3.79 (s, 3H), 2.23 (s,
3H). 13C NMR (100 MHz, DMSO-d6) δ=153.0, 144.7, 142.0, 134.5, 124.7,
118.0, 113.7, 111.6, 110.9, 108.6, 102.1, 101.9, 55.7, 11.3; HR-MS(ESI):
Calcd for C14H15N2O [M + H]+: 227.1180，found 227.1179.
1,9-Dimethyl-9H-carbazol-2-amine(3e): Brown solid ， m.p. 151oC
yield：53% . 1H NMR (400 MHz, DMSO-d6) δ =7.83 (d, J = 7.6 Hz, 1H),
7.62 (d, J = 8.3 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.23 (t, J = 7.6 Hz, 1H),
7.05 (t, J = 7.4 Hz, 1H), 6.60 (d, J = 8.2 Hz, 1H), 5.04 (s, 2H), 4.00 (s,
3H), 2.49 (s, 3H). 13C NMR (100 MHz, CDCl3) δ=143.7, 142.0, 141.5,
123.8, 123.5, 118.8, 118.6, 118.3, 116.8, 109.6, 108.2, 104.2, 33.2, 12.4;
HR-MS(ESI) : Calcd for C14H15N2 [M + H]+: 211.1227，found 211.1230.
constants (Hz), and integration. LCMS/ HRMS were recorded on
Bruker Daltonics Data analysis 3.4 mass spectrometer. high performance
liquid chromatography (HPLC) was performed with YoungLin
a
a
7-Fluoro-1-methyl-9H-carbazol-2-amine (3f): Brown solid，m.p. 217 oC
yield: 65%.1H NMR（400 MHz，DMSO-d6） δ=10.84 (s, 1H), 7.79 (dd,
J=8.0Hz, 1H), 7.57 (d, J=8.4Hz, 1H), 7.10 (dd, J=6.4Hz, 1H), 6.84 (m,
1H), 6.58 (d, J=8.0Hz, 1H), 4.96 (s, 2H), 2.25 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ=159.9(d, J=234.0Hz), 144.9, 141.8, 140.2(d, J=13.0Hz),
121.1, 119.3, 117.8(d J=11Hz), 113.0, 109.2(d J=14.0Hz), 105.7, 102.1,
96.9(d J=29.0Hz), 11.4(d J=5.0Hz); HR-MS(ESI) : Calcd for C13H12N2F
[M + H]+: 215.0978，found 215.0979
instrument SP930D, one equipped with Dikma C18 columns using
methanol as an eluent. All reactions were carried out using inert
atmosphere operations under N2(g) passed through a Drierite drying
tube.X-Ray data were collected on a Bruker APEX-II equipped with a
CCD area detector using Mo/Kα radiation. The structures were solved by
direct method using SHELXL-97.
General procedure for synthesis of 3: To a 35 mL sealed tube (with a
Teflon cap) equipped with a magnetic stir bar was sequentially added
substrate 1 (0.20 mmol, for preparation, see supporting information),
Cu(CF3SO3)2 (0.02mmol, 7.2 mg), and Ammonium carbonate (4mmol,
384 mg), 2.0 mL of CH3CN was added and the tube was capped and
submerged into a pre-heated 80 °C oil bath. The reaction was stirred for
24 h and cooled to room temperature. The crude reaction mixture was
diluted with ethyl acetate (5 mL) and filtered through a short pad of Celite.
The sealed tube and Celite pad were washed with an additional 20 mL of
ethyl acetate. The filtrate was concentrated in vacuo, and the resulting
residue was purified by flash column chromatography or preparative TLC
using petroleum ether/EtOAc as the eluent.
6-Bromo-1-methyl-9H-carbazol-2-amine (3g): Brown solid ， m.p. 219
oC yield：76%。1H NMR（400 MHz，DMSO-d6） δ=10.85 (s, 1H), 8.02
(s, 1H), 7.63 (d, J=8.4Hz, 1H), 7.30 (d, J=8.0Hz, 1H), 7.27 (d, J=7.2Hz,
1H), 6.58 (d, J=8.4Hz, 1H), 5.04 (s, 2H), 2.24 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ=145.9, 141.8, 138.4, 126.4, 125.1, 120.9, 118.5, 112.3,
112.1, 110.4, 109.3, 101.6, 11.3; HR-MS(ESI) : Calcd for C13H12N2Br [M
+ H]+: 275.0177，found 275.0178.
7-Amino-8-methyl-9H-carbazole-3-carbonitrile(3h): Brown solid，m.p.
233 oC yield：44%。1H NMR（400 MHz，DMSO-d6） δ=11.30 (s, 1H),
8.32 (s, 1H), 7.70 (d, J=8.4Hz, 1H), 7.53 (dd, J=8.4Hz, 1H), 7.45 (d,
J=8.4Hz, 1H), 6.63 (d, J=8.8Hz, 1H), 5.16 (s, 2H), 2.25 (s, 3H). 13C NMR
(100 MHz, DMSO-d6) δ=146.6, 142.0,141.9, 137.7, 126.4, 124.6,124.4,
123.2, 121.3, 118.8, 112.2, 111.2, 110.0, 101.9, 99.8, 11.4; HR-
MS(ESI) : Calcd for C14H12N3 [M + H]+: 222.1026，found 222.1026.
1-Methyl-9H-carbazol-2-amine (3a): Brown solid，m.p. 205 oC yield：
56%.1H NMR (400 MHz, DMSO-d6) δ=10.72 (s, 1H), 7.83 (d, J = 7.6 Hz,
1H), 7.61 (d, J = 8.2 Hz, 1H), 7.35 (d, J = 7.9 Hz, 1H), 7.20 – 7.16 (m,
1H), 7.02 (t, J = 7.5 Hz, 1H), 6.60 (d, J = 8.2 Hz, 1H), 5.59 (s, 2H), 2.27
(s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 141.3, 140.0, 129.3, 128.7,
1-Ethyl-6-methoxy-9H-carbazol-2-amine (3i): Brown solid ， m.p. 245
oC yield：28%.1H NMR (400 MHz, DMSO-d6) δ=10.43 (s, 1H), 7.54 (d, J
= 8.2 Hz, 1H), 7.41 – 7.34 (m, 1H), 7.22 (d, J = 8.6 Hz, 1H), 6.79 (dd, J =
8.6, 2.1 Hz, 1H), 6.49 (d, J = 8.3 Hz, 1H), 4.89 (s, 2H), 3.79 (s, 3H), 2.74
(q, J = 7.2 Hz, 2H), 1.13 (t, J = 7.3 Hz, 3H). 13C NMR (151 MHz, DMSO-
127.1, 124.3, 123.4, 118.8, 118.5, 118.2, 110.6, 109.4, 11.6
. HR-
MS(ESI) : Calcd for C13 H13N2 [M + H]+: 197.1072，found 197.1073.
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10.1002/ejoc.201801297
European Journal of Organic Chemistry
COMMUNICATION
d6) δ= 153.2 , 144.5 , 141.6 , 134.7, 124.9 , 118.4 , 113.9 , 111.7 ,
111.0 ,109.2 , 108.4 , 102.3 , 55.9, 18.8 , 13.4 ; HR-MS(ESI) : Calcd for
C15H17N2O [M + H]+: 241.1263，found 241.1262.
7-fluoro-1,4-dimethyl-9H-carbazol-2-amine(3q): Brown soild，m.p.
232 oC yield：61%. 1H NMR (400 MHz, DMSO-d6) δ=10.82 (s, 1H),
7.79 (dd, J = 8.4, 5.6 Hz, 1H), 7.08 (dd, J = 10.0, 2.0 Hz, 1H), 6.85 (t, J
= 9.2 Hz, 1H), 6.36 (s, 1H), 4.92 (s, 2H), 2.57 (s, 3H), 2.20 (s, 3H). 13
C
NMR (100 MHz, DMSO-d6) δ 164.8 (d, J = 233.0Hz), 144.7 , 142.0 ,
Ethyl-9-methyl-9H-carbazol-2-amine (3j): Brown solid，yield：43% 1H
NMR（400 MHz，CDCl3 ） δ=7.91 (d, J=7.6Hz, 1H), 7.74 (d, J=8.0Hz,
1H), 7.36 (d, J=7.6Hz, 1H), 7.32 (d, J=8.0Hz, 1H), 7.16 (d, J=6.4Hz, 1H),
6.66 (d, J=8.0Hz, 1H), 4.04 (s, 3H), 3.06 (m, 2H), 1.37 (t, J=7.6Hz, 3H).
HR-MS(ESI) : Calcd for C15H17N2 [ M + H]+: 225.1513，found 225.1549 .
140.5 (d, J=13.0Hz) ,129.6 , 121. 8 , 121.2 (d, J=10.0Hz) , 112.0 , 110.8 ,
105.9 (d, J=23.0Hz) , 99.8 , 96.9(d, J=26.0Hz) , 20.5 , 11.3. HR-MS(ESI) :
Calcd for C14H14N2F［M + H］+ : 229.1143，found 229.1136.
Acknowledgements
6-Bromo-1-ethyl-9H-carbazol-2-amine (3k): Brown solid, m.p. 233 oC
yield：51%.1H NMR（400 MHz，DMSO-d6） δ=10.84 (s, 1H), 7.99 (s,
1H), 7.60 (d, J=8.4Hz, 1H), 7.30 (d, J=4.8Hz, 1H), 7.27 (d, J=4.0Hz, 1H),
6.54 (d, J=8.4Hz, 1H), 5.04 (s, 2H), 2.75 (m, 2H), 1.13 (t, J=7.2Hz, 3H).
13C NMR(100 MHz, DMSO-d6) δ=145.2, 141.2, 138.4, 126.3, 125.0,
120.9, 118.7, 112.4, 112.1, 110.3, 109.7, 108.0, 18.5, 13.2; HR-MS(ESI) :
Calcd for C14H14BrN2［M + H］+: 289.0163，found 289.0164.
We sincerely thank Prof. Dr. Burkhard Koenig (Institut für
Organische Chemie, Universität Regensburg, Germany) for his
revisions and suggestions to this paper. We gratefully
acknowledge the financial support from the National Science
Foundation of China (No. 21072131, 21702141) and Sichuan
Universit–Lu Zhou Strategic Cooperation Projects (No. 2017
CDLZ-S34)
1-Ethyl-7-fluoro-9H-carbazol-2-amine(3l): Brown solid，m.p. 225 o
C
yield：45%. 1H NMR (400 MHz, DMSO-d6) δ=10.82 (s, 1H), 7.78 (dd, J
= 8.3, 5.7 Hz, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.09 – 7.01 (m, 1H), 6.86 –
6.77 (m, 1H), 6.53 (d, J = 8.2 Hz, 1H), 4.93 (s, 2H), 2.75 (q, J = 7.1 Hz,
2H), 1.14 (t, J = 7.4 Hz, 3H).13C NMR (150 MHz, DMSO-d6) δ 160.1(d,
J=234.0Hz) , 144.4, 141.3 , 140.0 (d, J=13.5Hz), 121.2 , 119.4 (d,
J=10.5Hz) , 118.1 , 113.2 , 109.7 , 108.7 , 105.8 (d, J=24.0Hz), 97.1(d,
J=25.5Hz) , 18.79 , 13.44 . HR-MS(ESI) : Calcd for C14H14N2F ［M + H］
+: 229.1135，found 229.1136
Keywords: carbazoles • amination • C-C coupling • cyclization •
domino reaction• radical reactions
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Copper Salt Catalyzed Synthesis of 2-
Aminocarbazoles via Cascade C-C C-
N Bond Formation and Aromatization
One pot synthesis of 2-aminocarbanoles from 1-(1H-indole-3-yl)pentan-3-one via cascade C-
C/C-N bond formation using ammonium carbonate as a nitrogen source and copper salt as a
catalysis is reported.
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