Regioselective synthesis of 2,3′-biindoles mediated by an NBS-induced homo-coupling of indoles

Article abstract of DOI:10.1039/c7ob02312j

Mild conditions have been developed to achieve NBS-induced homodimerization of indole derivatives with excellent regioselectivity at 15 °C in high efficiency. This method provides a simple route to a 2,3′-linked biindolyl scaffold from the electron-rich to moderately electron-poor indoles. In addition, [3,2-a]carbazole derivatives can also be prepared through this method.

Full text of DOI:10.1039/c7ob02312j

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DOI: 10.1039/C7OB02312J
Regioselective Synthesis of 2,3′-Biindoles Mediated by an
NBS-Induced Homo-coupling of Indoles
Panpan Huang,a Xiangjun Peng,b Dan Hu,a Huiwu Liao,a Shaobin Tang,*a Liangxian Liu*a
a Department of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou,
Jiangxi 341000, P. R. China
b School of Pharmaceutical Science, Gannan Medical University, Ganzhou, Jiangxi 341000, P. R.
China
E-mail: lxliu@xmu.edu.cn
Abstract: Mild conditions have been developed to achieve NBS-induced homo dimerization of
indole derivatives with excellent regioselectivity at 15 oC in high efficiency. This method provides
a simple route to 2,3'-linked biindolyl scaffold from the electron-rich to moderately electron-poor
indoles. In addition, [3,2-a]carbazole derivatives can also be prepared through this method.
Keywords: Bisindole; Indole; Carbazole; NBS
Introduction
2,3'-Biindolyl (1) scaffolds are important motifs in many natural products and the synthetic
world.1 For example, the red-purple indirubin (2) is an isomer of the blue indigo. Indirubins can be
found in various indigo dye-producing plants (more than 200 species).2 In addition, indirubin is
the active ingredient of a Traditional Chinese Medicine recipe, “Danggui Longhui Wan”, used to
treat various diseases including chronic myelocytic leukemia.3 Their excellent bioactivities
inspired great interest in their structure diversification by chemical and biosynthetic methods. To
date, more than 250 naturally occurring or chemo(bio)synthetic bisindole alkaloid family members
have been described.4
Figure 1. Bioactive alkaloids and compounds containing the biindolyl scaffold.
Thus, the development of new methods for accessing unique 2,3'-biindole derivatives for new
leads in drug and material discovery is still highly desirable. However, the direct formation of C-C
bonds of indole derivatives is particularly challenging because of the poor control of both the
chemo- and regioselectivities.5a Among the existing approaches for preparation of biindoles,5-7 the
oxidative dimerization of indoles has been well investigated.5a-c On the other hand, the methods
based on the transition-metal-catalyzed coupling of aryl halides with aryl-metals have emerged as
versatile tools for the synthesis of biaryls over the past decades,8 and biindolyls have been
constructed facilely by Stille reaction and Suzuki reaction.9 However, most of these procedures
require the prefunctionalization of indoles to their halide, boronic or metallic derivatives, or
require expensive metal catalysts and high loading of metal oxidants. From both scientific and
environmental points of view, the development of methodology for direct activation of C-H bonds

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DOI: 10.1039/C7OB02312J
is of great significance. Therefore, a new and effective practical synthetic strategy, involving mild,
atom economic, environmently benign, and metal-free conditions, for the regioselective
construction of C-C bonds of indoles is still of high demand in modern organic synthesis.
NH
HN
R
R
8
Pd(OTFA)2 3,3'-linked
Shi's work7a
2,2'-linked
2,3'-linked
R
Hao's work6c
NH
Zhang's work5b
R
R
N
N
N
1) TFA
2) DDQ
N
H
H
Pd(OTFA)2
R
H
5
H
R
7
6
Scheme 1. Representative methods for preparation of biindole derivatives.
As part of a continuing program, our group developed a range of transformations that enable the
direct functionalization of indole derivatives via TEMPO catalysis.10 Based on our previous
studies10 and related reports,5 we envisioned that the direct transformation of indoles to
2,3'-biindole derivatives could be achieved by employing NBS-promoted homo-coupling. Herein,
we report a new synthetic strategy for the synthesis of 2,3'-biindole and [3,2-a]carbazole
derivatives from indoles using NBS under aerobic conditions. Very few methods report the
self-condensation of indole to generate [3,2-a]carbazole derivatives. To the best of our knowledge,
this work represents the first example of one-step synthesis of 2,3'-biindole and [3,2-a]carbazole
derivatives via oxidative homodimerization of indoles.
Results and discussion
With the hypothesis mentioned above, our optimization studies began with indole 5a as model
substrate. Representative results are shown in Table 1. On the outset of our study, a low yield of
the desired product 6a was obtained when NBS was used as an essential additive. It was found
that the dimerization reaction occurred by use of 100 mol % NBS to give the 2,3'-dimer of indole
1H,1'H-2,3′-biindole in 26% yield in 1,4-dioxane at room temperature (Table 1, entry 1). However,
NCS and NIS diminished the reaction (Table 1, entries 2 and 3). The derivatives of 2,2′- and
3,3′-biindolyls were not observed under the reaction conditions, showing excellent regioselectivity.
The solvent was also found to have a dramatic impact on the efficiency of the reaction. CHCl3 was
found to be the best choice (Table 1, entry 10). A lower yield of 6a was obtained when other
commonly used solvents such as benzene, toluene, CH3CO2C2H5, CH3CN, CH2Cl2, and
ClCH2CH2Cl were employed (Table 1, entries 4-9). Interestingly, DME and CH3CO2H proved to
be inefficient for the formation of 6a (Table 1, entries 11-12). Further investigations revealed that
there was obvious increase in yield when NBS loading was decreased to 80 mol % (Table 1, entry
15). The influence of temperature was also studied. When temperature was decreased to 15 °C, the
yield increased from 83% to 87%; however, lowering the temperature to 10 °C only dramatically
reduced the yields of desired product 6a to 52% (Table 1, entries 17 and 18).
On the basis of our screening experiments, the best results were obtained using a treatment of 0.8
equiv of NBS in CHCl3 at 15 °C for 6 h, which afforded the desired product 6a in high yield (87%,
entry 17).
Table 1. Selected optimization of the reaction conditionsa

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entry
1
additive (equiv)
solvent
1,4-dioxane
1,4-dioxane
1,4-dioxane
benzene
toluene
temp. (oC)
yield (%)b
NBS (1)
NCS (1)
NIS (1)
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
15
10
26
15
2
3
12
4
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NBS (1.2)
NBS (0.9)
NBS (0.8)
NBS (0.7)
NBS (0.8)
NBS (0.8)
24
5
30
6
CH3CO2C2H5
CH3CN
51
7
56
8
CH2Cl2
68
9
ClCH2CH2Cl
CHCl3
61
10
11
12
13
14
15
16
17
18
75
DME
trace
trace
62
CH3CO2H
CHCl3
CHCl3
79
CHCl3
83
CHCl3
76
CHCl3
87
CHCl3
52
a Conditions: 5a (0.3 mmol) and solvent (1 mL), 6 h, under open air. b Isolated yield.
With the optimal reaction conditions available, the protocol was extended to different indoles. The
results are shown in Table 2. In general, the reaction proceeded smoothly to give the desired
products in generally good yields (56 to 90%) and can tolerate a variety of functional groups at the
1, 4, 5, 6, and 7 positions of indoles, such as F, Cl, Br, I, CH3, CH3O, CH2CH3, OBn and CO2H.
The substituent effect on the indole ring was then investigated. The results have shown that
electronegativities of substituents played a major role in governing the reactivity of the substrates.
Electron-donating substitutents showed better results than electron-withdrawing substitutents in
this transformation. For example, 5-substituted indole derivatives with electron-donating
substituents (CH3 and OCH3) afforded the desired 6f and 6g in 89% and 90% yields, respectively
(Table 2, entries 6 and 7). While 5-substituted indole derivatives with electron-withdrawing
substituents (F, Cl, Br and I) provided the desired products 6b-6e in yields ranging from 60% to
70% (Table 2, entries 2-4). Substrate with a strong electron-withdrawing substituent at C5-position,
such as CO2H, was also suitable (Table 2, entry 9). Notably, 4-methyl- and 4-benzyloxy-indole
gave also excellent yield even due to the steric hindrance (Table 2, entries 16 and 17).5b
Furthermore, we were pleased to find that indoles bearing an halogen atom including fluoro,
chloro, bromo, and iodo worked well and desired products were obtained in good yields.
Tolerance to the halogen functional groups is especially noteworthy since they are useful for
subsequent cross-coupling reactions.
Table 2. Substrate scope of the homocoupling a

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entry
1
R1
H
R2
H
product
6a
6b
6c
yield (%)b
87
60
62
66
70
89
90
81
56
57
64
88
83
86
85
87
78
79
2
5-F
H
3
5-Cl
H
4
5-Br
H
6d
6e
5
5-I
H
6
5-CH3
5-OCH3
5-OBn
5-CO2H
6-F
H
6f
7
H
6g
6h
6i
8
H
9
H
10
11
12
13
14
15
16
17
18
H
6j
6-Cl
H
6k
6l
6-CH3
7-CH3
7-OCH3
7-CH2CH3
4-CH3
4-OBn
H
H
H
6m
6n
6o
6p
6q
6r
H
H
H
H
CH3
a Conditions: 5 (0.3 mmol) and NBS (0.24 mmol), in CHCl3 (1 mL), 6 h, under open air. b Isolated
yield.
Nevertheless, when using 3-methyl-1H-indole as the substrate, the reaction yielded
3-methylindolin-2-one 9 in 83% yield without desired product (Scheme 2). In addition, no desired
product was obtained when other heterocyclic scaffolds such as 1H-pyrrolo[2,3-c]pyridine and
1H-pyrrolo[3,2-c]pyridine were used as the substrates.
Scheme 2. Reaction of 5c with NBS.
During the screening of reaction conditions for this homocoupling reaction, we isolated a small
amount of carbazole derivative 10a. Carbazole alkaloids, both naturally occurring as well as
synthetically made, are of great interest not only as attractive targets for synthetic chemists, but
especially because of the promising pharmacological properties that many of these compounds
confer.11 However, the synthesis of [3,2-a]carbazole derivatives from indoles via direct C-H
transformation is very limited.12 We investigated the reaction conditions for selective formation of
2-(5,12-dihydroindolo[3,2-a]carbazol-6-yl)anilines 10 (Table S1, Supporting Information). It was
found that reaction temperature played the key role for the formation of 10. For example, only a

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o
trace of 10b was detected when the reaction was performed at 15 C, but the yield of 10b
o
increased to 66% when the reaction was performed at higher temperature (35 C). Similar results
were obtained for electron-deficient indoles such as 7-chloro-1H-indole and 7-bromo-1H-indole
under the reaction conditions (Scheme 3). Significant electronic effects of the phenyl substituents
were observed in the process. The electron-withdrawing groups delivered a higher yield than the
electron-donating groups (10a, 10b, 10c, and 10d vs 10e and 10f). Unfortunately, the
electron-donating groups, such as 5-CH3, 5-OCH3, 6-CH3, and 7-CH3, deactivated the reaction. No
desired product was obtained under the optimized conditions. The structure of 10b was confirmed
by X-ray single-crystal diffraction, and the molecular structure is given in the Supporting
Information.
Scheme 3. Synthesis of 2-(5,12-dihydroindolo[3,2-a]carbazol-6-yl)anilines 10.
In order to prove the practicality of this approach, a gram-scale synthesis of the 6a (1.021 g, 88%
yield) and 6m (1.105 g, 85% yield) was performed, respectively, which suggested that such
methodology could also be efficiently scaled up (Scheme 4).
Scheme 4. Gram-scale synthesis of 6a and 6m.
Scheme 5. Control experiments.
We further performed several control experiments under the standard conditions in order to probe
the reaction mechanism. First, the reaction proceeded well in argon instead of air (Scheme 5).
Second, a radical trapping reagent (for example, TEMPO and BHT) had little effect on the
reaction efficiency, suggesting that free radical intermediate is not involved in this reaction. Third,
considering that this type of coupling reaction may involve the 3-bromo-1H-indole intermediate
11, which was often detected in the reaction mixtures, we attempted to treat 11 with
5-methy-1H-indole. However, no formation of product 12 was observed under the standard

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conditions, suggesting that 11 might not be an intermediate in this reaction and the reaction
mechanism is different from the iodine-induced previously reported one.5a
Based on these observations and previous literature reports, a mechanism can tentatively be
proposed (Scheme 6).13 First, nucleophilic attack of indole on the bromine atom of NBS forms an
intermediate 13. Then, an intermolecular nucleophilic addition takes place to give an intermediate
14. Finally, 14 gives 6a upon elimination of a molecule of hydrogen bromide.
Scheme 6. Proposed mechanism for the formation of 6a.
Conclusions
In summary, a new NBS-induced homo-coupling of indoles was first developed, which provides a
convenient and efficient approach to prepare a variety of 2,3'-biindole and [3,2-a]carbazole
derivatives. This transition meta-free synthetic process works well with a wide range of indoles
and can be safely conducted on a gram scale. The features such as generality, high efficiency and
regioselectivity, and air- and moisture-insensitive reaction conditions make the present method an
attractive alternative for the preparation of 2,3'-biindole.
Experimental Section
General
1H and 13C NMR spectra were recorded on a Bruker spectrometers at 400 and 100 MHz,
respectively. Mass spectra were recorded with Bruker Dalton Esquire 3000 plus LC-MS apparatus.
Elemental analysis were carried out on a Perkin-Elmer 240B instrument. HRFABMS spectra were
recorded on a FTMS apparatus. Silica gel (300-400 mesh) was used for flash column
chromatography, eluting (unless otherwise stated) with an ethyl acetate/petroleum ether (PE)
(60-90 °C) mixture.
General Procedure for the Preparation of 6.
To a solution of indole (0.3 mmol) in CHCl3 (1 mL) was added NBS (0.24 mmol) under an air
o
atmosphere and the mixture was stirred at 15 C for 6 h. The reaction mixture was concentrated
under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent:
EtOAc/PE = 1:1) to yield the corresponding product 6.
1
1H,1'H-2,3′-Biindole (6a): Yellow amorphous solid. H NMR (400 MHz, DMSO-d6): δ 11.38 (s,
1H), 11.18 (s, 1H), 8.00 (d, J = 7.5 Hz, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.48 (dd, J = 11.8, 7.6 Hz,
2H), 7.35 (d, J = 7.8 Hz, 1H), 7.19 – 7.14 (m, 2H), 7.02 (dd, J = 11.0, 4.0 Hz, 1H), 6.96 (dd, J =
10.8, 3.9 Hz, 1H), 6.75 (d, J = 1.5 Hz, 1H). 13C NMR (101 MHz, DMSO-d6): δ 137.1, 136.5,
134.6, 129.7, 125.1, 123.6, 122.2, 120.7, 120.2, 120.1, 119.5, 119.3, 112.4, 110.9, 108.9, 97.3. MS
(ESI): 233 (M+H+, 100). These assignments matched with those previously published.14
5,5′-Difluoro-1H,1'H-2,3′-biindole (6b): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 11.56 (s, 1H), 11.31 (s, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.71 (dd, J = 10.3, 2.3 Hz,

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1H), 7.48 (dd, J = 8.8, 4.7 Hz, 1H), 7.32 (dd, J = 8.6, 4.6 Hz, 1H), 7.22 (dd, J = 10.0, 2.4 Hz, 1H),
7.04 (dt, J = 2.4, 9.1 Hz, 1H), 6.85 (dt, J = 2.5, 9.4 Hz, 1H), 6.75 (d, J = 1.4 Hz, 1H). 13C NMR
(101 MHz, DMSO-d6): δ 158.0 (d, J = 231.4 Hz), 157.5 (d, J = 230.5 Hz), 136.1, 133.8, 133.2,
130.0 (d, J = 10.5 Hz), 125.9, 125.1 (d, J = 10.2 Hz), 113.5 (d, J = 9.9 Hz), 111.6 (d, J = 9.9 Hz),
110.5 (d, J = 26.0 Hz), 108.9 (d, J = 4.6 Hz), 108.5 (d, J = 25.8 Hz), 104.8 (d, J = 24.0 Hz), 104.2
(d, J = 23.2 Hz), 97.6 (d, J = 4.5 Hz). MS (ESI): 269 (M+H+, 100). Anal calcd for C16H10F2N2: C,
71.64; H, 3.76; N, 10.44. Found C, 71.37; H, 4.13; N, 10.18.
5,5′-Dichloro-1H,1'H-2,3′-biindole (6c): Yellow amorphous solid.1H NMR (400 MHz, DMSO-d6):
δ 11.65 (s, 1H), 11.43 (s, 1H), 8.08-7.81 (m, 2H), 7.49 (d, J = 10.7 Hz, 2H), 7.35 (d, J = 8.5 Hz,
1H), 7.19 (dd, J = 8.6, 1.4 Hz, 1H), 7.02 (dd, J = 8.5, 1.6 Hz, 1H), 6.76 (s, 1H). 13C NMR (101
MHz, DMSO-d6): δ 137.6, 137.0, 135.1, 128.4, 127.0, 125.4, 125.0, 123.8, 121.4, 120.8, 120.6,
119.7, 112.1, 110.5, 108.8, 97.7. MS (ESI): 301 (M+H+, 100), 303 (M+H+, 30). These assignments
matched with those previously published.15
5,5′-Dibromo-1H,1'H-2,3′-biindole (6d): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 11.66 (s, 1H), 11.43 (s, 1H), 8.10 (s, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.66 (d, J = 1.7
Hz, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.38-7.26 (m, 2H), 7.13 (dd, J = 8.5, 1.9 Hz, 1H), 6.75 (d, J =
1.2 Hz, 1H). 13C NMR (101 MHz, DMSO-d6): δ 135.9, 135.4, 135.3, 131.6, 126.7, 125.7, 124.9,
123.3, 122.1, 121.8, 114.5, 113.1, 112.9, 111.9, 108.2, 97.3. MS (ESI): 391 (M+H+, 100). These
assignments matched with those previously published.15
1
5,5'-Diiodo-1H,1'H-2,3′-biindole (6e): Yellow amorphous solid. H NMR (400 MHz, DMSO-d6):
δ 11.64 (s, 1H), 11.42 (s, 1H), 8.26 (s, 1H), 7.86 (d, J = 7.9 Hz, 2H), 7.45 (d, J = 8.5 Hz, 1H), 7.33
(d, J = 8.5 Hz, 1H), 7.28 (d, J = 8.3 Hz, 1H), 7.20 (d, J = 8.3 Hz, 1H), 6.71 (s, 1H). 13C NMR (101
MHz, DMSO-d6): δ 136.2, 135.7, 134.9, 132.5, 130.4, 128.8, 128.2, 128.1, 127.6, 125.2, 115.0,
113.4, 107.8, 96.9, 84.4, 83.0. MS (ESI): 485 (M+H+, 100). Anal calcd for C16H10I2N2: C, 39.70;
H, 2.08; N, 5.79. Found C, 40.05; H, 2.30; N, 5.48.
5,5'-Dimethyl-1H,1'H-2,3′-biindole (6f): Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6):
δ 11.21 (s, 1H), 10.99 (s, 1H), 7.77 (d, J = 2.7 Hz, 2H), 7.33 (d, J = 8.2 Hz, 1H), 7.26 (s, 1H), 7.21
(d, J = 8.1 Hz, 1H), 6.99 (dd, J = 8.3, 1.1 Hz, 1H), 6.83 (dd, J = 8.2, 1.2 Hz, 1H), 6.64 (d, J = 1.4
Hz, 1H), 2.45 (s, 3H), 2.36 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 135.5, 134.9, 134.8, 130.0,
128.8, 127.5, 125.4, 123.7, 123.5, 122.2, 119.7, 119.2, 112.0, 110.5, 108.6, 96.8, 21.8, 21.7. MS
(ESI): 261 (M+H+, 100). Anal calcd for C18H16N2: C, 83.04; H, 6.19; N, 10.76. Found C, 82.87; H,
6.01; N, 10.83.
5,5'-Dimethoxy-1H,1'H-2,3′-biindole (6g): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 11.22 (s, 1H), 10.97 (s, 1H), 7.76 (d, J = 2.7 Hz, 1H), 7.36 (dd, J = 14.7, 5.6 Hz, 2H),
7.21 (d, J = 8.7 Hz, 1H), 7.01 (d, J = 2.4 Hz, 1H), 6.82 (dd, J = 8.8, 2.3 Hz, 1H), 6.69-6.61 (m,
2H), 3.83 (s, 3H), 3.74 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 154.5, 153.8, 135.4, 132.2,
131.6, 130.2, 125.5, 124.1, 113.1, 112.3, 111.4, 110.3, 110.2, 108.9, 101.9, 97.1, 60.2, 55.9. MS
(ESI): 293 (M+H+, 100). These assignments matched with those previously published.15
1
5,5'-Bis(benzyloxy)-1H,1'H-2,3′-biindole (6h): Yellow amorphous solid. H NMR (400 MHz,
DMSO-d6): δ 11.25 (d, J = 2.0 Hz, 1H), 11.01 (s, 1H), 7.80 (d, J = 2.6 Hz, 1H), 7.56-7.50 (m, 3H),
7.47 (d, J = 7.2 Hz, 2H), 7.39 (dd, J = 14.2, 7.5 Hz, 5H), 7.32 (dd, J = 7.3, 4.6 Hz, 2H), 7.25 (d, J
= 8.6 Hz, 1H), 7.10 (d, J = 2.2 Hz, 1H), 6.92 (dd, J = 8.8, 2.3 Hz, 1H), 6.76 (dd, J = 8.6, 2.4 Hz,
1H), 6.64 (d, J = 1.1 Hz, 1H), 5.19 (s, 2H), 5.10 (s, 2H). 13C NMR (101 MHz, DMSO-d6): δ 153.6,
152.9, 138.5, 138.3, 135.5, 132.4, 131.8, 130.2, 129.0, 128.9, 128.8, 128.7, 128.2, 128.1, 128.0,

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127.9, 125.5, 124.2, 113.1, 112.9, 111.4, 111.1, 108.9, 103.8, 103.5, 97.2, 70.6, 70.4. MS (ESI):
445 (M+H+, 100). Anal calcd for C30H24N2O2: C, 81.06; H, 5.44; N, 6.30. Found C, 80.73; H, 5.46;
N, 6.51.
1H,1′H-[3, 3′-Biindole]-5,5′-dicarboxylic acid (6i): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 12.50 (s, 2H), 11.81 (d, J = 2.2 Hz, 1H), 11.68 (d, J = 1.2 Hz, 1H), 8.64 (s, 1H),
8.27-8.24 (m, 1H), 7.99 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 8.6, 1.5 Hz, 1H), 7.71 (dd, J = 8.5, 1.6
Hz, 1H), 7.55 (d, J = 8.6 Hz, 1H), 7.43 (d, J = 8.5 Hz, 1H), 6.89 (d, J = 1.4 Hz, 1H). 13C NMR
(101 MHz, DMSO-d6): δ 168.9, 168.7, 139.6, 139.2, 135.4, 129.2, 125.6, 124.7, 123.6, 123.0,
122.6, 122.5, 122.4, 122.0, 112.3, 110.7, 109.7, 98.8. MS (ESI): 321 (M+H+, 100). Anal calcd for
C18H12N2O4: C, 67.50; H, 3.78; N, 8.75. Found C, 67.84; H, 3.60; N, 9.02.
6,6′-Difluoro-1H,1'H-2,3′-biindole (6j): Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6):
δ 11.46 (s, 1H), 11.34 (s, 1H), 7.96 (dd, J = 8.6, 5.4 Hz, 1H), 7.84 (d, J = 2.3 Hz, 1H), 7.47 (dd, J
= 8.4, 5.5 Hz, 1H), 7.25 (dd, J = 9.9, 2.1 Hz, 1H), 7.10 (d, J = 10.0 Hz, 1H), 7.03-6.97 (m, 1H),
6.83 (dd, J = 13.2, 5.3 Hz, 1H), 6.77 (s, 1H). 13C NMR (101 MHz, DMSO-d6): δ 159.5 (d, J =
235.4 Hz), 159.0 (d, J = 233.3 Hz), 137.1 (d, J = 12.6 Hz), 136.4 (d, J = 12.7 Hz), 134.8 (d, J =
3.5 Hz), 126.4, 124.2 (d, J = 3.1 Hz), 121.9, 121.1 (d, J = 10.2 Hz), 120.4 (d, J = 10.0 Hz), 108.9,
108.7 (d, J = 24.3 Hz), 107.5 (d, J = 24.0 Hz), 98.4 (d, J = 25.5 Hz), 97.4, 97.1 (d, J = 25.6 Hz).
MS (ESI): 269 (M+H+, 100). Anal calcd for C16H10F2N2: C, 71.64; H, 3.76; N, 10.44. Found C,
71.79; H, 3.92; N, 10.25.
6,6′-Dichloro-1H,1'H-2,3′-biindole (6k): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 11.56 (s, 1H), 11.41 (s, 1H), 7.98 (d, J = 8.6 Hz, 1H), 7.90 (d, J = 2.5 Hz, 1H), 7.51
(dd, J = 14.9, 5.0 Hz, 2H), 7.35 (s, 1H), 7.16 (dd, J = 8.4, 1.5 Hz, 1H), 6.98 (dd, J = 8.3, 1.6 Hz,
1H), 6.79 (s, 1H). 13C NMR (101 MHz, DMSO-d6): δ 137. 5, 137.0, 135.0, 128.4, 127.0, 125.4,
125.0, 123.8, 121.4, 120.8, 120.6, 119.6, 112.1, 110.5, 108.8, 97.7. MS (ESI): 301 (M+H+, 100),
303 (M+H+, 30). Anal calcd for C16H10Cl2N2: C, 63.81; H, 3.35; N, 9.30. Found C, 64.20; H, 3.48;
N, 9.17.
6,6'-Dimethyl-1H,1'H-2,3′-biindole (6l): Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6):
δ 11.18 (s, 1H), 10.98 (s, 1H), 7.84 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 2.6 Hz, 1H), 7.35 (d, J = 7.9
Hz, 1H), 7.23 (s, 1H), 7.12 (s, 1H), 6.96 (dd, J = 8.2, 1.0 Hz, 1H), 6.78 (dd, J = 8.0, 0.9 Hz, 1H),
6.65 (d, J = 1.4 Hz, 1H), 2.42 (s, 3H), 2.39 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 137.6,
136.9, 134.1, 131.2, 129.6, 127.6, 123.1, 122.6, 121.9, 120.9, 119.8, 119.2, 112.1, 110.8, 109.0,
97.0, 22.0, 21.8. MS (ESI): 261 (M+H+, 100). Anal calcd for C18H16N2: C, 83.04; H, 6.19; N,
10.76. Found C, 82.96; H, 5.82; N, 10.49.
7,7'-Dimethyl-1H,1'H-2,3′-biindole (6m): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 11.36 (s, 1H), 10.78 (s, 1H), 8.03 (d, J = 2.7 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.32
(d, J = 7.6 Hz, 1H), 7.05 (t, J = 7.8 Hz, 1H), 6.98 (d, J = 7.0 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H),
6.81 (d, J = 7.0 Hz, 1H), 6.75 (t, J = 2.0 Hz, 1H), 2.51 (s, 3H), 2.49 (s, 3H). 13C NMR (101 MHz,
DMSO-d6): δ 136.6, 135.8, 134.6, 129.4, 125.0, 123.8, 122.6, 121.6, 121.4, 120.3, 120.1, 119.5,
117.8, 117.2, 109.3, 98.0, 17.6, 17.2. MS (ESI): 261 (M+H+, 100). These assignments matched
with those previously published.15
7,7'-Dimethoxy-1H,1'H-2,3′-biindole (6n): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 11.41 (s, 1H), 11.13 (s, 1H), 8.00 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.12-7.00 (m,
2H), 6.90 – 6.83 (m, 1H), 6.72 (d, J = 6.8 Hz, 2H), 6.60 (d, J = 7.5 Hz, 1H), 3.92 (s, 6H). 13C
NMR (101 MHz, DMSO-d6): δ 146.8, 146.1, 134.6, 131.2, 127.2, 126.8, 126.2, 123.7, 120.8,

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119.8, 112.9, 112.7, 109.2, 102.6, 101.9, 98.0, 55.7, 55.5. HRESIMS calcd for [C18H16N2O2 + H]+
293.12900, found 293.12859.
7,7'-Diethyl-1H,1'H-2,3′-biindole (6o): Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6):
δ 11.35 (s, 1H), 10.76 (s, 1H), 8.02 (d, J = 2.5 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.32 (d, J = 7.5
Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 7.0 Hz, 1H), 6.95-6.79 (m, 2H), 6.74 (d, J = 1.6 Hz,
1H), 2.94 (q, J = 7.5 Hz, 2H), 2.90 (q, J = 7.5 Hz, 2H), 1.31 (t, J = 7.5 Hz, 3H), 1.30 (t, J = 7.5 Hz,
3H). 13C NMR (101 MHz, DMSO-d6): δ 135.8, 135.1, 134.6, 129.6, 127.8, 126.6, 125.3, 123.8,
120.8, 120.5, 119.65 (d, J = 8.4 Hz), 117.8, 117.2, 109.3, 98.1, 24.2, 24.1, 15.1, 14.9. MS (ESI):
289 (M+H+, 100). Anal calcd for C20H20N2: C, 83.30; H, 6.99; N, 9.71. Found C, 83.04; H, 6.83;
N, 9.39.
4,4'-Dimethyl-1H,1'H-2,3′-biindole (6p): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 11.31 (s, 1H), 11.09 (s, 1H), 7.44 (d, J = 2.5 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.16
(d, J = 8.1 Hz, 1H), 7.07-6.99 (m, 1H), 6.97-6.88 (m, 1H), 6.78 (dd, J = 9.5, 7.2 Hz, 2H), 6.40 (d,
J = 1.5 Hz, 1H), 2.47 (s, 3H), 2.32 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 136.8, 136.3, 134.1,
130.3, 128.8, 128.4, 125.9, 125.7, 122.0, 121.2, 120.8, 119.3, 110.1, 109.4, 108.9, 100.4, 20.3,
19.1. MS (ESI): 261 (M+H+, 100). Anal calcd for C18H16N2: C, 83.04; H, 6.19; N, 10.76. Found C,
82.87; H, 5.95; N, 10.38.
1
4,4′-Bis(benzyloxy)- 1H,1'H-2,3′-biindole (6q): Yellow amorphous solid. H NMR (400 MHz,
DMSO-d6) δ 11.53 (d, J = 2.2 Hz, 1H), 10.65 (d, J = 1.5 Hz, 1H), 7.84 (d, J = 2.6 Hz, 1H),
7.58-7.55 (m, 2H), 7.48 (d, J = 7.2 Hz, 2H), 7.40-7.33 (m, 5H), 7.10 (d, J = 4.1 Hz, 2H), 6.81-6.76
(m, 4H), 6.49 (d, J = 7.8 Hz, 1H), 6.32 (d, J = 8.0 Hz, 1H), 5.27 (s, 2H), 5.18 (s, 2H), 3.37 (s, 2H).
13C NMR (101 MHz, DMSO-d6): δ 152.5, 151.4, 139.0, 138.3, 137.4, 137.0, 133.3, 129.1, 129.0,
128.8, 128.6, 128.0, 127.8, 124.2, 122.8, 120.8, 120.1, 114.8, 108.7, 106.4, 104.8, 101.9, 101.2,
95.3, 70.6, 69.5. MS (ESI): 445 (M+H+, 100). Anal calcd for C30H24N2O2: C, 81.06; H, 5.44; N,
6.30. Found C, 80.91; H, 5.28; N, 6.03.
1,1'-Dimethyl-1H,1'H-2,3′-biindole (6r): Yellow amorphous solid. 1H NMR (400 MHz,
DMSO-d6): δ 7.71 (s, 1H), 7.68 (s, 1H), 7.53 (s, 1H), 7.44 (s, 1H), 7.24 (d, J = 7.3 Hz, 2H), 7.14
(d, J = 4.6 Hz, 2H), 7.04 (t, J = 7.4 Hz, 2H), 3.87 (s, 3H), 3.76 (s, 3H). 13C NMR (101 MHz,
DMSO-d6): δ 138.0, 137.2, 135.4, 129.7, 128.4, 127.3, 122.4, 121.0, 120.5, 120.0, 119.9, 119.7,
110.6, 110.1, 106.2, 100.6, 33.1, 31.3. MS (ESI): 261 (M+H+, 100). Anal calcd for C18H16N2: C,
83.04; H, 6.19; N, 10.76. Found C, 82.76; H, 5.84; N, 10.59.
1
3-Methylindolin-2-one (9): White amorphous solid. H NMR (400 MHz, DMSO-d6): δ 10.31 (s,
1H), 7.22 (d, J = 7.4 Hz, 1H), 7.15 (t, J = 7.7 Hz, 1H), 6.93 (t, J = 7.4 Hz, 1H), 6.81 (d, J = 7.7 Hz,
1H), 3.38 (q, J = 7.6 Hz, 1H), 1.30 (d, J = 7.6 Hz, 3H). 13C NMR (101 MHz, DMSO-d6): δ 180.1,
142.8, 131.8, 128.0, 124.1, 121.7, 109.6, 40.6, 15.5. MS (ESI): 148 (M+H+, 100).
1
2-(5,12-Dihydroindolo[3,2-a]carbazol-6-yl)aniline (10a): Yellow amorphous solid. H NMR (400
MHz, DMSO-d6): δ 11.74 (s, 1H), 10.81 (s, 1H), 8.66 (d, J = 7.8 Hz, 1H), 8.11 (d, J = 7.7 Hz, 1H),
8.02 (s, 1H), 7.62 (dd, J = 14.1, 8.0 Hz, 2H), 7.32-7.14 (m, 6H), 6.90 (dd, J = 8.1, 1.0 Hz, 1H),
6.75 (dt, J = 1.2, 7.4 Hz,1H), 4.64 (s, 2H). 13C NMR (101 MHz, DMSO-d6): δ 149.5, 139.9, 139.6,
137.7, 133.7, 131.5, 128.6, 124.5, 124.2, 124.1, 123.9, 122.0, 121.5, 119.5, 119.4, 119.3, 119.1,
117.1, 115.7, 115.6, 115.4, 111.9, 111.5, 107.1. MS (ESI): 348 (M+H+, 100). These assignments
matched with those previously published.16
3-Chloro-2-(1,8-dichloro-5,12-dihydroindolo[3,2-a]carbazol-6-yl)aniline
(10b):
Yellow
1
amorphous solid. H NMR (400 MHz, DMSO-d6): δ 11.39 (s, 1H), 10.93 (s, 1H), 8.38 (s, 1H),

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7.92 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.44-7.26 (m, 5H), 7.25-7.15 (m, 2H), 4.64 (s,
2H). 13C NMR (101 MHz, DMSO-d6): δ 149.4, 141.1, 140.4, 138.7, 135.0, 133.8, 130.1,
125.9,125.8, 125.1, 124.8, 122.9, 121.0, 120.5, 120.4, 120.3, 119.8, 117.0, 115.2, 113.8, 113.0,
111.7, 111.1, 105.5. MS (ESI): 450 (M+H+, 100). Anal calcd for C24H14Cl3N3: C, 63.95; H, 3.13;
N, 9.32. Found C, 64.07; H, 3.28; N, 9.01.
2-Chloro-6-(4,11-dichloro-5,12-dihydroindolo[3,2-a]carbazol-6-yl)aniline
(10c):
Yellow
amorphous solid. 1H NMR (400 MHz, DMSO-d6): δ 11.74 (s, 1H), 10.94 (s, 1H), 9.05 (d, J = 7.8
Hz, 1H), 8.20-8.10 (m, 2H), 7.48 (dd, J = 7.7, 0.8 Hz, 1H), 7.42 (dd, J = 7.7, 0.9 Hz, 1H), 7.36 (dd,
J = 8.0, 1.4 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 7.24-7.17 (m, 2H), 6.77 (t, J = 7.8 Hz, 1H), 4.69 (s,
2H). 13C NMR (101 MHz, DMSO-d6): δ 142.9, 138.6, 136.9, 136.4, 134.3, 130.7, 129.0, 126.5,
125.9, 124.8, 124.3, 124.1, 121.8, 121.1, 121.0, 120.3, 118.8, 118.5, 117.7, 116.9, 116.7, 116.1,
115.7, 108.4. MS (ESI): 450 (M+H+, 100). Anal calcd for C24H14Cl3N3: C, 63.95; H, 3.13; N, 9.32.
Found C, 63.80; H, 3.32; N, 8.96.
2-Bromo-6-(4,11-dibromo-5,12-dihydroindolo[3,2-a]carbazol-6-yl)aniline
(10d):
Yellow
amorphous solid. 1H NMR (400 MHz, DMSO-d6): δ 11.54 (s, 1H), 10.53 (s, 1H), 9.07 (d, J = 7.8
Hz, 1H), 8.43-7.94 (m, 2H), 7.63 (d, J = 7.7 Hz, 1H), 7.60-7.47 (m, 2H), 7.33-7.19 (m, 2H), 7.15
(t, J = 7.7 Hz, 1H), 6.72 (t, J = 7.7 Hz, 1H), 4.70 (s, 2H). 13C NMR (101 MHz, DMSO-d6): δ
143.7, 138.5, 138.3, 137.8, 134.4, 132.2, 131.4, 127.9, 127.5, 126.4, 125.9, 123.9, 122.5, 121.5,
121.2, 120.8, 119.0, 118.5, 117.2, 116.9, 109.5, 108.6, 104.3, 103.9. MS (ESI): 584 (M+H+, 100).
Anal calcd for C24H14Br3N3: C, 49.35; H, 2.42; N, 7.19. Found C, 49.69; H, 2.16; N, 6.83.
1
3-Bromo-1H-indole (11): White amorphous solid. H NMR (400 MHz, DMSO-d6): δ 11.45 (s,
1H), 7.52 (d, J = 2.6 Hz, 1H), 7.40 (t, J = 8.2 Hz, 2H), 7.18-7.14 (m, 1H), 7.11-7.07 (m, 1H). 1H
NMR (400 MHz, DMSO-d6): δ 135.8, 126.5, 125.2, 122.6, 120.3, 118.3, 112.5, 89.1.
2-(4,11-Dimethoxy-5,12-dihydroindolo[3,2-a]carbazol-6-yl)-6-methoxyaniline (10e): Yellow
1
amorphous solid. H NMR (400 MHz, DMSO-d6): δ 11.40 (s, 1H), 10.39 (s, 1H), 8.14 (s, 1H),
7.77 (d, J = 7.8 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.00-7.92 (m, 4H), 6.90
(dd, J = 7.8, 1.0 Hz, 1H), 6.78 (t, J = 7.8 Hz, 1H), 4.33 (s, 2H), 4.04 (s, 3H), 3.95 (s, 3H), 3.89 (s,
3H). 13C NMR (101 MHz, DMSO-d6): δ 147.5, 146.1, 145.8, 137.7, 135.2, 131.9, 131.2, 128.0,
124.8, 124.3, 124.2, 124.1, 122.7, 121.3, 120.7, 117.4, 117.1, 117.0, 112.4, 110.2, 107.4, 106.6,
105.5, 104.0, 56.3, 56.1, 56.0. MS (ESI): 438 (M+H+, 100). Anal calcd for C27H23N3O3: C, 74.13;
H, 5.30; N, 9.60. Found C, 73.85; H, 5.21; N, 9.29.
2-(Benzyloxy)-6-(4,11-bis(benzyloxy)-5,12-dihydroindolo[3,2-a]carbazol-6-yl)aniline
(10f):
1
Yellow amorphous solid. H NMR (400 MHz, DMSO-d6): δ 11.50 (s, 1H), 11.15 (s, 1H), 8.12
(dd, J = 5.0, 2.6 Hz, 1H), 7.60-7.55 (m, 8H), 7.44-7.33 (m, 9H), 7.12 (t, J = 8.1 Hz, 1H), 7.06 (d, J
= 8.1 Hz, 2H), 6.88-6.85 (m, 2H), 6.77 (d, J = 1.9 Hz, 1H), 6.67 (d, J = 7.8 Hz, 1H), 5.35-5.27 (m,
8H). 13C NMR (101 MHz, DMSO-d6): δ 145.9, 145.8, 145.0, 144.6, 138.1, 137.8, 137.7, 137.6,
135.8, 134.7, 131.4, 128.9, 128.8, 128.3, 128.2, 128.1, 128.0, 127.9, 127.4, 127.0, 126.9, 126.5,
124.8, 124.2, 121.1, 120.8, 119.8, 113.1, 112.8, 109.2, 108.4, 104.9, 104.0, 103.4, 98.1, 97.6, 70.0,
69.7, 69.6. MS (ESI): 666 (M+H+, 100). Anal calcd for C45H35N3O3: C, 81.18; H, 5.30; N, 6.31.
Found C, 80.83; H, 5.09; N, 6.12.
1
3-Bromo-1H-indole (11): White amorphous solid. H NMR (400 MHz, DMSO-d6): δ 11.45 (s,
1H), 7.52 (d, J = 2.6 Hz, 1H), 7.40 (t, J = 8.2 Hz, 2H), 7.18-7.14 (m, 1H), 7.11-7.07 (m, 1H). 1H
NMR (400 MHz, DMSO-d6): δ 135.8, 126.5, 125.2, 122.6, 120.3, 118.3, 112.5, 89.1.
Acknowledgments

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DOI: 10.1039/C7OB02312J
The authors are grateful to the National Natural Science Foundation of China (No: 21462002),
Natural Science Foundation of Jiangxi Province in China (No: 20161BAB203096) for financial
support.
Supporting Information Available. 1H and 13C NMR spectra of compounds 6, 9, 10 and 11; and
X-ray crystallographic files (CIF) for 10b.
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C7OB02312J
Table of Contents Entry
An efficient method for the synthesis of 2,3'-biindole and [3,2-a]carbazole derivatives via a
NBS-induced homo-coupling of indoles with high regioselectivity.