Synthesis of indole-fused scaffolds via [3+3] cyclization reaction of 2-indolylmethanols with quinone imines

Article abstract of DOI:10.1016/j.tet.2020.131742

A formal [3 + 3] cyclization reaction of 2-indolylmethanols with quinones was realized to furnish indole-fused scaffolds in moderate to excellent yields. This protocol was proceeded smoothly under acid condition, with high high yields and broad substrate scope.

Full text of DOI:10.1016/j.tet.2020.131742

Journal Pre-proof
Synthesis of Indole-fused Scaffolds via [3+3] Cyclization Reaction of 2-
Indolylmethanols with Quinone Imines
Lu-Zhe Qin, Ya-Long Cheng, Xiaoan Wen, Qing-Long Xu, Le Zhen
PII:
S0040-4020(20)30968-6
https://doi.org/10.1016/j.tet.2020.131742
TET 131742
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 18 September 2020
Revised Date: 30 October 2020
Accepted Date: 2 November 2020
Please cite this article as: Qin L-Z, Cheng Y-L, Wen X, Xu Q-L, Zhen L, Synthesis of Indole-fused
Scaffolds via [3+3] Cyclization Reaction of 2-Indolylmethanols with Quinone Imines, Tetrahedron, https://
doi.org/10.1016/j.tet.2020.131742.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.
© 2020 Elsevier Ltd. All rights reserved.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Leave this area blank for abstract info.
Synthesis of Indole-fused Scaffolds via [3+3]
Cyclization Reaction of 2-Indolylmethanols
with Quinone Imines
Lu-Zhe Qing,Ya-Long Chen, Xiaoan Wen, Qing-Long Xu*, Le Zhen*
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic
Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China

Tetrahedron
journal homepage: www.elsevier.com
Synthesis of Indole-fused Scaffolds via [3+3] Cyclization Reaction of 2-
Indolylmethanols with Quinone Imines
Lu-Zhe Qin, Ya-Long Cheng, Xiaoan Wen, Qing-Long Xu*, Le Zhen*
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24
Tongjiaxiang, Nanjing 210009, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A formal [3+3] cyclization reaction of 2-indolylmethanols with quinones was realized to furnish
indole-fused scaffolds in moderate to excellent yields. This protocol was proceeded smoothly
under acid condition, with high high yields and broad substrate scope.
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved
.
[3+3] cyclization
2-indolulmethanol
Quinone imine
Indole
phosphine nucleophiles [7] et al. [8] were successfully added to the
Introduction
C3-position of the indole moiety, providing versatile indole
Among the numerous heterocyclic compounds, indole-fused
derivatives which serve as the core structures have been found in
biologically natural products and pharmaceuticals.[1] Thus the
development of novel and efficient methodologies to construct
structurally diverse indole-fused heterocycles has attracted
considerable attention from the chemistry community. Among
the various reported approaches, the synthesis of indole-fused
scaffolds from indole skeletons has been proved to be one of the
most straightforward procedure.
derivatives.
cycloaddition reaction, including [3+2],
cyclizations,
Second,
2-indolylmethanols
involved
[3+3],
in
[4+3]
[9]
[10]
[11]
have been recently developed to construct
indole-fused cyclic frameworks. However, among these reported
cyclization reactions, the C3 position of 2-indolylmethanols as
nucleophilic site has been very limited investigated to construct
indole-fused cyclic frameworks. To the best of our knowledge,
there are only two examples employing C3-position of 2-
indolylmethanols as nucleophilic site reported by the Shi group,
including [3+3] cyclization of 2-indolylmethanols with
vinylcyclopropanes10 and [4+3] cyclization of o-hydroxybenzyl
[11]
alcohols with 2-indolylmethanols.
In this regard, it is highly
desired to develop cyclization reaction of 2-indolylmethanols,
and C3-position of 2-indolylmethanols display nucleophilicity.
As a continuous work of our research towards the catalytic
[12]
reaction of quinone imines,
we designed the [3+3]
cycloaddition reaction of 2-indolylmethanols with quinone
imines, to construct indole-fused heterocycles. Herein, we report
the novel cyclization reaction, providing access to structurally
diverse indole-fused frameworks in high yield (up to 98%).
Scheme 1. Two reaction patterns of 2-indolylmethanols.
In recent years, 2-indolylmethanols which serve as versatile
reactants have been extensively explored in organic synthesis.
[2]
Result and Discussion
As shown in Scheme 1, two main reaction patterns of 2-
indolylmethanols have been developed to synthesize indole
derivatives or construct indole-fused scaffolds. First, nucleophilic
substitutions of 2-indolylmethanols have been well studied by the
At the outset, the reaction of 2-indolylmethanol 1a and
quinone imine 2a was examined as a model reaction to test our
hypothesis under acid condition (Table 1). However, initially, no
reaction occurred under weak acids condition, such as AcOH,
PhCO2H (entries 1-2, Table 1). Therefore, the stronger acids
were examined (entries 3-4, Table 1) and found that TsOH.H2O
[3]
Shi group. Nowadays, various nucleophiles including indoles,
[4]
[5]
[6]
cyclic enaminones,
pyrazol-5-ones,
2-naphthols,
1

catalyzed the [3+3] cycloaddition reaction smoothly and
generated the desired product 3a in 78% yield. Furthermore, the
structure of the product 3a was confirmed by X-ray single-crystal
analysis (see the supporting information for details). [13] Then, a
series of commonly used solvents were evaluated (entries 5-9,
Table 1), and CH2Cl2 was found to be the optimization reaction
medium as it could afford product 3a in 78% yield (entry 5,
Table 1). To improve the yield of the reaction, the reaction
temperature and the concentration of the reaction was further
investigated (entries 10-12, Table 1), lowering the temperature
had no influence on the reaction. However, when the
concentration of the reaction was decreased to 0.05 mol/L, the
yield could increase to 85%, then the concentration was further
lowered, the yield was almost be maintained. Thus, the optimal
reaction condition was confirmed as following: 1a (0.36 mmol),
2a (0.30 mmol), TsOH.H2O (5 mol%), CH2Cl2 (6.0 mL), 25 oC.
Table 1. Reaction Optimization. a
entry
acid
solvent
CH2Cl2
T (oC)
yield (%)b
1
2
3
4
5
6
7
8
9
AcOH
PhCO2H
(PhO)2PO2H
CF3SO3H
25
25
25
25
25
25
25
25
25
0
NR
NR
36
49
78
27
75
66
NR
75
85
87
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
DCE
EtOH
DMF
CH2Cl2
CH2Cl2
CH2Cl2
TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
Scheme 2. Substrate scope of 2-indolylmethanols. Reaction
conditions: 1 (0.36 mmol), 2a (0.3 mmol), TsOH.H2O (5 mol%),
CH2Cl2 (6.0 mL), 25 oC.
Table 2. Substrate scope of substituted quinone imines. a
10
11 c
12 d
25
25
a Reaction conditions: 1a (0.36 mmol), 2a (0.30 mmol), acid (5
mol%), solvent (3.0 mL), 25 C. b Isolated yield. using CH2Cl2
o
c
(6.0 mL). d using CH2Cl2 (12.0 mL).
With optimal reaction condition in hands, we next explored the
substrates with different substituted 2-indolylmethanols and
quinone imines. As illustrated in Scheme 2, a wide range of 2-
indolylmethanols 1 bearing different substituents on the indole
core could be proceeded smoothly, generating the cyclization
product 3 (3a-3o) in moderate to excellent yields (58-98%),
different electron-withdrawing and electron-donating substituents
were well tolerated in this transformation. It is worth noting that
N-Me-2-indolylmethanol 1p could serve as a suitable substrate to
give product 3p in excellent yield (91%). Meanwhile, 2-
indolylmethanols bearing other aromatic groups could be
participated in the [3+3] cyclization, affording the desire
products in good yields (77-92%).
entry
1
2
3
4
5
6
7
8
2
4
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
yield (%)b
81
2b, R’ = p-MeOC6H4SO2
2c, R’ = p-tBuC6H4SO2
2d, R’= p-PhC6H4SO2
2e, R’= p-ClC6H4SO2
2f, R’= m-BrC6H4SO2
2g, R’= o-ClC6H4SO2
2h R’= 3,4-Cl2C6H3SO2
2i, R’= m-FC6H4SO2
2j, R’= m-CNC6H4SO2
2k, R’= m-NO2C6H4SO2
2l, R’= m-CF3C6H4SO2
2m, R’= EtSO2
93
82
69
90
96
73
86
73
70
78
74
82
9
10
11
12
13
14
2n, R’= nPrSO2
2o, R’= cyclopropylSO2
94
Reaction conditions: 1a (0.36 mmol), 2 (0.3 mmol), TsOH.H2O
a
(5 mol%), CH2Cl2 (6.0 mL), 25 oC. b Isolated yield.
Moreover, a series of quinone imines bearing different Ar and
alkyl substituents were also employed in the [3+3] cyclization
reaction, affording the desired product 4b-4o in good yields (69-
96%) (Table 2). Substituted quinone imines bearing electron-
2

donating groups (Me, OMe, Ph) or an electron-withdrawing
group (Cl, Br, NO2, CN, CF3) on the aromatic ring, were obtained
with high to excellent yields (69-96% yields). Overall, the
substitution pattern and electronic effects of the substituents had
limited influence on the reactivity of this transformation. We also
examined the reactivity of the alkyl substituted quinone imines
(Et, n-Pr, cyclopropyl), pleasingly, the reaction proceeded
smoothly, affording the desired products in 74-94% yields.
However, the other protecting groups on the quinone imine (such
as Ac and Boc), the desired products could not be obtained under
optimized condition.
Experimental Section
1H and 13C NMR spectra were recorded on an ACF* 300Q
Bruker or ACF* 500Q Bruker spectrometer. Low- and high-
resolution mass spectra (LRMS and HRMS) were recorded in
electron impact mode. The mass analyzer type used for the
HRMS measurements was TOF. Reactions were monitored by
TLC on silica gel 60 F254 plates (Qingdao Ocean Chemical
Company, China). Column chromatography was carried out on
silica gel (200-300 mesh, Qingdao Ocean Chemical Company,
China). Data for 1H NMR are recorded as follows: chemical shift
(δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m =
multiplet or unresolved, br s = broad singlet, coupling constant
(s) in Hz, integration). Data for 13C NMR are reported in terms of
chemical shift (δ, ppm). Commercially available reagents and
solvents were used without further purification.
A
proposed reaction process to explain this
transformation of the [3+3] cyclization reaction was
depicted in Scheme 3. Initially, the 2-indolylmethanol 1a
utilized the nucleophilicity of the C3-position of the indole
to attack quinone imine 2a under acid condition, leading to
the intermediate Int-1, which could rapidly undergo proton
transfer and lose one molecular water to afford Int-2. Then
Int-2 could occur an intramolecular nucleophilic attack
General procedure for TsOH.H2O catalyzed [3+3] cyclization
reaction of 2-indolylmethanols and quinone imines.
To the mixture of 2-indolylmethanols 1 (0.36 mmol), quinone
imines 2 (0.30 mmol) in CH2Cl2 (6 mL) was added the catalyst
TsOH.H2O in one portion, which was stirred at 25 C for 2 h.
o
pathway to give cyclization product 3a
.
After the completion of the reaction indicated by TLC, the
reaction mixture was directly purified through flash column
chromatography on silica gel to afford pure products 3 and 4.
Scheme 3. Proposed reaction process.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-yl)-4-
methylbenzenesulfonamide (3a)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 85% yield (138.6 mg), white
o
1
solid; m.p. 280-281 C; H NMR (300 MHz, DMSO-d6) δ 11.29
(s, 1H), 9.91 (s, 1H), 7.71-7.57 (m, 3H), 7.48-7.41 (m, 1H), 7.40-
7.28 (m, 9H), 7.25-7.14 (m, 6H), 6.94 (d, J = 8.5 Hz, 1H), 6.75
(dd, J = 8.4, 1.8 Hz, 1H), 2.31 (s, 3H); 13C NMR (75 MHz,
DMSO-d6) δ 147.29, 143.51, 142.41, 137.46, 137.30, 136.52,
132.33, 130.03, 128.66, 128.57, 128.02, 127.22, 123.11, 122.93,
122.50, 121.04, 119.07, 118.97, 117.78, 115.49, 113.16, 105.78,
84.23, 21.37. HRMS (ESI) exact mass calcd. for
[C34H26N2O3S+Na]+ requires 565.1556, found 565.1556.
In addition, this [3+3] cyclization reaction of 2-
indolylmethanol 1a and quinone imine 2a could be carried
out at 2 mmol scale under the optimization condition,
affording the indole-fused framework 3a in 88% yield
(Scheme 4). This result revealed that this [3+3] cyclization
reaction could be scaled up.
4-methyl-N-(9-methyl-6,6-diphenyl-6,7-dihydrochromeno
[3,4-b]indol-2-yl)benzenesulfonamide (3b)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 83% yield (140.0 mg), white
o
1
solid; m.p. 252-255 C; H NMR (300 MHz, DMSO-d6) δ 11.13
(s, 1H), 9.88 (s, 1H), 7.65 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz,
1H), 7.42-7.28 (m, 9H), 7.26-7.16 (m, 5H), 7.02 (d, J = 8.1Hz,
1H), 6.92 (d, J = 8.4 Hz, 1H), 6.74 (dd, J = 8.4, 2.1 Hz, 1H), 2.41
(s, 3H), 2.32 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ 153.72,
146.74, 142.98, 142.02, 137.41, 136.85, 135.35, 131.78, 131.23,
129.51, 128.10, 128.02, 127.51, 126.70, 122.49, 122.14, 120.55,
118.27, 117.13, 114.86, 112.43, 105.20, 95.26, 91.63, 83.75,
21.30, 20.87. HRMS (ESI) exact mass calcd. for
[C35H28N2O3S+Na]+ requires 579.1718, found 579.1713.
Scheme 4. Two mmol scale reaction.
Conclusion
5-methyl-N-(10-methyl-6,6-diphenyl-6,7-dihydrochromeno
[3,4-b]indol-2-yl)benzenesulfonamide (3c)
In summary, a formal [3+3] cyclization reaction of 2-
indolylmethanols and quinone imines was developed and this
transformation provides an efficient method for the synthesis of
fused-indole scaffolds under acid condition. We next speculate
that 2-indolylmethanols as 1,3-dipole could be involved in other
cyclization reactions to give rapid access to fused-indole
heterocycles.
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 83% yield (140.0 mg), white
o
1
solid; m.p. 252-255 C; H NMR (300 MHz, DMSO-d6) δ 11.14
(s, 1H), 9.90 (s, 1H), 7.66 (d, J = 8.1 Hz, 2H), 7.44 (s, 1H), 7.41-
7.28 (m, 10H), 7.27-7.16 (m, 4H), 7.02 (d, J = 8.4 Hz, 1H), 6.94
(d, J = 8.4 Hz, 1H), 6.76 (dd, J = 8.4, 1.8 Hz, 1H), 2.47 (s, 3H),
2.30 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ 146.77, 142.98,
142.05, 136.95, 136.10, 135.37, 131.89, 129.55, 129.21, 128.15,
128.08, 127.55, 126.74, 123.51, 122.98, 122.69, 118.35, 118.20,
3

117.24, 114.97, 112.36, 104.93, 83.76, 21.45, 20.90. HRMS (ESI)
exact mass calcd. for [C35H28N2O3S+Na]+ requires 579.1718,
found 579.1713.
N-(8-chloro-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-
yl)-4-methylbenzenesulfonamid (3h)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 71% yield (128.5 mg), white
4-methyl-N-(11-methyl-6,6-diphenyl-6,7-dihydrochromeno
[3,4-b]indol-2-yl)benzenesulfonamide (3d)
o
1
solid; m.p. 246-248 C; H NMR (300 MHz, DMSO-d6) δ 11.76
(s, 1H), 9.91 (s, 1H), 7.65 (d, J = 8.1 Hz, 2H), 7.60 (d, J = 7.8 Hz,
1H), 7.44-7.18 (m, 15H), 6.97 (d, J = 8.4 Hz, 1H), 6.85-6.74 (m,
1H), 2.31 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ 147.01,
143.08, 141.50, 137.65, 136.82, 133.88, 131.90, 129.59, 128.25,
128.06, 127.93, 126.77, 124.60, 122.16, 121.68, 121.57, 119.13,
117.54, 117.35, 116.94, 115.13, 106.88, 91.68, 84.25, 20.92.
HRMS (ESI) exact mass calcd. for [C34H25ClN2O3S+Na]+
requires 599.1167, found 599.1164.
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 86% yield (145.5 mg), white
o
1
solid; m.p. 231-233 C; H NMR (300 MHz, DMSO-d6) δ 11.14
(s, 1H), 9.80 (s, 1H), 7.51 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 2.1 Hz,
1H), 7.38-7.30 (m, 6H), 7.30-7.23 (m, 3H), 7.22-7.13 (m, 4H),
7.03 (dd, J = 8.1, 7.8 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.88 (d, J
= 7.2 Hz, 1H), 6.73 (dd, J = 8.4, 2.1 Hz, 1H), 2.54 (s, 3H), 2.32 (s,
3H). 13C NMR (75 MHz, DMSO-d6) δ 147.69, 142.85, 141.51,
138.18, 137.44, 136.54, 131.66, 129.43, 129.32, 128.17, 128.00,
127.82, 126.58, 123.47, 122.61, 122.55, 122.04, 119.04, 118.92,
118.39, 110.24, 106.82, 83.56, 23.60, 20.89. HRMS (ESI) exact
mass calcd. for [C35H28N2O3S+Na]+ requires 579.1713, found
579.1711.
N-(9-chloro-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-
yl)-4-methylbenzenesulfonamide (3i)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 76% yield (131.0 mg), white
o
1
solid; m.p. 272-274 C; H NMR (300 MHz, DMSO-d6) δ 11.44
(s, 1H), 9.91 (s, 1H), 7.70-7.57 (m, 3H), 7.45 (s, 1H), 7.42-7.30
(m, 9H), 7.30-7.14 (m, 5H), 6.96 (d, J = 8.4 Hz, 1H), 6.83-6.73
(m, 1H), 2.31 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ 147.27,
143.54, 142.12, 137.92, 137.46, 137.24, 132.46, 130.04, 128.78,
128.65, 128.00, 127.22, 127.18, 122.31, 121.88, 121.40, 120.31,
119.23, 117.96, 115.41, 112.80, 106.06, 84.12, 21.37. HRMS
(ESI) exact mass calcd. for [C34H25ClN2O3S+Na]+ requires
599.1167, found 599.1165.
N-(10-methoxy-6,6-diphenyl-6,7-dihydrochromeno[3,4-
b]indol-2-yl)-4-methylbenzenesulfonamide (3e)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 62% yield (107.0mg), white
o
1
solid; m.p. 267-269 C; H NMR (300 MHz, DMSO-d6) δ 11.13
(s, 1H), 9.94 (s, 1H), 7.66 (d, J = 8.1 Hz, 2H), 7.47-7.26 (m,
10H), 7.26-7.15 (m, 5H), 6.93 (d, J = 8.4 Hz, 1H), 6.87 (d, J =
8.4 Hz, 1H), 6.77 (dd, J = 8.4, 1.8 Hz, 1H), 3.86 (s, 3H), 2.29 (s,
3H). 13C NMR (75 MHz, DMSO-d6) δ 154.43, 146.46, 143.01,
141.93, 136.70, 136.57, 132.00, 129.53, 128.11, 128.04, 127.48,
126.61, 123.01, 122.60, 117.41, 117.24, 114.18, 113.30, 111.49,
105.10, 101.12, 83.67, 55.46, 20.82. HRMS (ESI) exact mass
calcd. for [C35H28N2O4S+Na]+ requires 595.1662, found
595.1661.
N-(10-chloro-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-
2-yl)-4-methylbenzenesulfonamide (3j)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 98% yield (169.4 mg), white
o
1
solid; m.p. 266-269 C; H NMR (300 MHz, DMSO-d6) δ 11.52
(s, 1H), 9.89 (s, 1H), 7.76 (s, 1H), 7.65 (d, J = 8.1 Hz, 2H), 7.45-
7.30 (m, 10H), 7.27 (d, J = 1.8 Hz, 1H), 7.25-7.14 (m, 4H), 6.97
(d, J = 8.4 Hz, 1H), 6.82 (dd, J = 8.4, 2.1 Hz, 1H), 2.31 (s, 3H).
13C NMR (75 MHz, DMSO-d6) δ 147.15, 143.57, 142.05, 137.94,
137.14, 136.17, 132.52, 130.04, 128.78, 128.64, 128.00, 127.19,
125.06, 124.72, 122.23, 121.25, 118.98, 117.98, 115.21, 115.16,
113.56, 105.52, 84.13, 21.40. HRMS (ESI) exact mass calcd. for
[C34H25ClN2O3S+Na]+ requires 599.1163, found 599.1165.
N-(11-methoxy-6,6-diphenyl-6,7-dihydrochromeno[3,4-
b]indol-2-yl)-4-methylbenzenesulfonamide (3f)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 78% yield (136.0 mg), white
o
1
solid; m.p. 235-238 C; H NMR (300 MHz, DMSO-d6) δ 11.16
(s, 1H), 9.84 (s, 1H), 8.17 (d, J = 1.8 Hz, 1H), 7.59 (d, J = 8.1 Hz,
2H), 7.39-7.30 (m, 6H), 7.27 (d, J = 8.1 Hz, 2H), 7.23-7.15 (m,
4H), 7.13-6.98 (m, 2H), 6.85 (d, J = 8.4 Hz, 1H), 6.70-6.58 (m,
2H), 3.95 (s, 3H), 2.29 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ
153.58, 147.91, 143.17, 142.41, 139.01, 137.40, 135.92, 135.59,
132.04, 129.85, 128.59, 128.47, 128.15, 127.01, 123.54, 123.23,
120.51, 119.61, 117.86, 113.87, 106.93, 106.10, 101.36, 83.57,
55.32, 21.33. HRMS (ESI) exact mass calcd. for
[C35H28N2O4S+Na]+ requires 595.1662, found 595.1664.
N-(9,11-dichloro-6,6-diphenyl-6,7-dihydrochromeno[3,4-
b]indol-2-yl)-4-methylbenzenesulfonamide (3k)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 72% yield (132.0 mg), white
o
1
solid; m.p. 295-297 C; H NMR (300 MHz, DMSO-d6) δ 11.66
(s, 1H), 9.82 (s, 1H), 7.85 (d, J = 2.4 Hz, 1H), 7.49 (d, J = 8.1 Hz,
2H), 7.41 (d, J = 1.8 Hz, 1H), 7.39-7.30 (m, 6H), 7.29-7.21 (m,
3H), 7.21-7.11 (m, 4H), 6.96 (d, J = 8.4 Hz, 1H), 6.75 (dd, J =
8.4, 2.4 Hz, 1H), 2.31 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ
148.33, 143.29, 141.32, 140.84, 138.97, 137.14, 135.60, 132.06,
129.87, 128.91, 128.64, 128.26, 127.01, 126.89, 125.23, 122.04,
121.91, 121.27, 120.81, 120.53, 118.86, 111.75, 106.67, 83.74,
21.36. HRMS (ESI) exact mass calcd. for [C34H24Cl2N2O3S+Na]+
requires 633.0777, found 633.0779.
N-(10-fluoro-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-
2-yl)-4-methylbenzenesulfonamide (3g)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 83% yield (104.3 mg); white
o
1
solid; m.p. 282-285 C; H NMR (300 MHz, DMSO-d6) δ 11.42
(s, 1H), 9.86 (s, 1H), 7.66 (d, J = 8.1 Hz, 2H), 7.45 (dd, J = 8.7,
1.8 Hz, 1H), 7.42-7.25 (m, 10H), 7.25-7.16 (m, 4H), 7.12-7.02
(m, 1H), 6.97 (d, J = 8.4 Hz, 1H), 6.81 (dd, J = 8.4, 2.1 Hz, 1H),
2.31 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ 159.30, 156.20,
146.72, 143.10, 141.72, 137.93, 136.84, 133.68, 131.99, 129.58,
128.27, 128.16, 127.55, 126.76, 122.65 (d, J = 10.1 Hz), 121.99,
118.59, 117.44, 114.86, 113.85 (d, J = 9.7 Hz), 110.15 (d, J =
25.5 Hz), 105.63 (d, J = 4.5 Hz), 103.41 (d, J = 24.0 Hz), 95.32,
83.73, 20.86. HRMS (ESI) exact mass calcd. for
[C35H25FN2O3S+Na]+ requires 538.1462, found 538.1462.
N-(8-bromo-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-
2-yl)-4-methylbenzenesulfonamide (3l)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 70% yield (124.0 mg), white
o
1
solid; m.p. 242-245 C; H NMR (300 MHz, DMSO-d6) δ 11.56
(s, 1H), 9.90 (s, 1H), 7.70-7.60 (m, 3H), 7.45 (d, J = 7.6 Hz, 1H),
7.41-7.23 (m, 13H), 7.16 (dd, J = 7.8, 7.8 Hz, 1H), 6.97 (d, J =
8.4 Hz, 1H), 6.79 (dd, J = 8.4, 2.4 Hz, 1H), 2.31 (s, 3H). 13C
4

NMR (75 MHz, DMSO-d6) δ 147.47, 143.54, 141.91, 138.05,
137.23, 135.82, 135.59, 132.32, 130.04, 128.70, 128.55, 128.35,
127.21, 125.83, 124.86, 122.50, 122.02, 119.60, 118.43, 117.81,
115.58, 107.42, 105.53, 84.71, 21.37. HRMS (ESI) exact mass
calcd. for [C34H25BrN2O3S+H]+ requires 621.0842, found
621.0844.
N-(6,6-di-p-tolyl-6,7-dihydrochromeno[3,4-b]indol-2-yl)-4-
methylbenzenesulfonamide (3q)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 77% yield (132.9 mg), white
o
1
solid; m.p. 170-172 C; H NMR (300 MHz, DMSO-d6) δ 11.19
(s, 1H), 9.88 (s, 1H), 7.65 (d, J = 8.2 Hz, 2H), 7.60 (dd, J = 6.0,
2.9 Hz, 1H), 7.43 (dd, J = 6.0, 3.1 Hz, 1H), 7.39-7.30 (m, 3H),
7.22-7.11 (m, 6H), 7.07 (d, J = 8.1 Hz, 4H), 6.90 (d, J = 8.5 Hz,
N-(9-bromo-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-
2-yl)-4-methylbenzenesulfonamide (3m)
1H), 6.73 (dd, J = 8.5, 2.2 Hz, 1H), 2.31 (s, 3H), 2.27 (s, 6H). 13
C
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 58% yield (94.0 mg), white
NMR (75 MHz, DMSO-d6) δ 147.40, 143.48, 139.61, 137.90,
137.37, 136.92, 135.60, 132.19, 130.02, 129.05, 127.96, 127.21,
123.14, 123.03, 122.36, 120.94, 118.97, 117.75, 115.49, 113.12,
105.64, 84.02, 21.38, 21.06. HRMS (ESI) exact mass calcd. for
[C34H25BrN2O3S+Na]+ requires 593.1869, found 593.1869.
o
1
solid; m.p. 271-274 C; H NMR (300 MHz, DMSO-d6) δ 11.44
(s, 1H), 9.91 (s, 1H), 7.73-7.52 (m, 4H), 7.47-7.28 (m, 10H),
7.27-7.15 (m, 4H), 6.96 (d, J = 8.4 Hz, 1H), 6.82-6.73 (m, 1H),
2.31 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ 147.26, 143.53,
142.08, 138.33, 137.34, 137.26, 132.45, 130.03, 128.77, 128.64,
127.99, 127.21, 123.93, 122.28, 122.12, 120.67, 119.22, 117.94,
115.74, 115.43, 115.10, 106.10, 84.10, 21.35. HRMS (ESI) exact
mass calcd. for [C34H25BrN2O3S+H]+ requires 621.0842, found
621.0840.
N-(6,6-bis(4-chlorophenyl)-6,7-dihydrochromeno[3,4-b]indol-
2-yl)-4-methylbenzenesulfonamide (3r)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 92% yield (165.0 mg), white
o
1
solid; m.p. 155-156 C; H NMR (300 MHz, DMSO-d6) δ 11.33
(s, 1H), 9.91 (s, 1H), 7.70-7.60 (m, 3H), 7.50-7.38 (m, 6H), 7.31
(d, J = 8.1 Hz, 2H), 7.25-7.15 (m, 6H), 6.95 (d, J = 8.6 Hz, 1H),
6.76 (dd, J = 8.5, 2.2 Hz, 1H), 2.31 (s, 3H). 13C NMR (75 MHz,
DMSO) δ 146.40, 143.05, 140.39, 137.08, 136.82, 135.16,
133.25, 132.23, 129.52, 129.45, 128.31, 127.49, 126.75, 122.64,
122.38, 122.29, 120.75, 118.71, 118.61, 117.44, 115.09, 112.75,
105.61, 95.32, 82.89, 20.90. HRMS (ESI) exact mass calcd. for
[C34H24Cl2N2O3S+Na]+ requires 609.0812, found 609.0810.
N-(10-bromo-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-
2-yl)-4-methylbenzenesulfonamide (3n)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 89% yield (167.6 mg), white
o
1
solid; m.p. 280-282 C; H NMR (300 MHz, DMSO-d6) δ 11.49
(s, 1H), 9.88 (s, 1H), 7.66 (s, 1H), 7.64 (s, 1H), 7.63-7.56 (m,
2H), 7.45 (d, J = 8.7 Hz, 1H), 7.42-7.30 (m, 8H), 7.28 (d, J = 2.4
Hz, 1H), 7.26-7.15 (m, 5H), 6.97 (d, J = 8.6 Hz, 1H), 6.82 (dd, J
= 8.6, 2.3 Hz, 1H), 2.31 (s, 3H). 13C NMR (75 MHz, DMSO-d6)
δ 147.17, 143.57, 142.06, 138.13, 137.17, 135.94, 132.50, 130.05,
128.78, 128.64, 128.00, 127.19, 125.61, 124.03, 122.49, 122.24,
119.02, 118.21, 117.96, 115.27, 114.72, 105.63, 84.14, 21.36.
HRMS (ESI) exact mass calcd. for [C34H25BrN2O3S+H]+ requires
621.0842, found 621.0866.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-yl)-4-
methoxybenzenesulfonamide (4b)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 81% yield (135.8 mg), white
o
1
solid; m.p. 251-253 C; H NMR (300 MHz, DMSO-d6) δ 11.28
(s, 1H), 9.81 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.67-7.59 (m, 1H),
7.49-7.29 (m, 8H), 7.27-7.14 (m, 6H), 7.05 (d, J = 8.8 Hz, 2H),
6.94 (d, J = 8.5 Hz, 1H), 6.75 (dd, J = 8.5, 2.2 Hz, 1H), 3.77 (s,
3H). 13C NMR (75 MHz, DMSO-d6) δ 162.80, 147.25, 142.43,
137.46, 136.49, 132.46, 131.84, 129.35, 128.64, 128.56, 128.02,
123.13, 122.92, 122.50, 121.00, 119.11, 118.93, 117.74, 115.48,
114.75, 113.15, 105.81, 84.23, 56.01. HRMS (ESI) exact mass
calcd. for [C34H26N2O4S+Na]+ requires 581.1506, found
581.1506.
N-(11-bromo-6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-
2-yl)-4-methylbenzenesulfonamide (3o)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 96% yield (174.5 mg), white
o
1
solid; m.p. 262-263 C; H NMR (300 MHz, DMSO-d6) δ 11.58
(s, 1H), 9.80 (s, 1H), 7.90 (d, J = 1.9 Hz, 1H), 7.55-7.42 (m, 3H),
7.40-7.30 (m, 7H), 7.25 (d, J = 8.0 Hz, 2H), 7.22-7.14 (m, 4H),
7.07 (appt, J = 7.8 Hz, 1H), 6.98 (d, J = 8.5 Hz, 1H), 6.80 (dd, J
= 8.5, 2.0 Hz, 1H), 2.32 (s, 3H). 13C NMR (75 MHz, DMSO-d6)
δ 148.55, 143.25, 141.48, 140.67, 138.90, 137.24, 135.60, 131.59,
129.85, 128.80, 128.55, 128.31, 127.09, 125.91, 123.56, 123.16,
122.61, 122.55, 120.91, 118.76, 112.46, 106.56, 84.01, 21.37.
HRMS (ESI) exact mass calcd. for [C34H25BrN2O3S+H]+ requires
621.0842, found 621.0843.
4-(tert-butyl)-N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-
b]indol-2-yl)benzenesulfonamide (4c)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 93% yield (164.0 mg), white
o
1
solid; m.p. 260-262 C; H NMR (300 MHz, DMSO-d6) δ 11.29
(s, 1H), 9.95 (s, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.66-7.51 (m, 3H),
7.48-7.28 (m, 8H), 7.27-7.13 (m, 6H), 6.95 (d, J = 8.6 Hz, 1H),
6.79 (d, J = 7.4 Hz, 1H), 1.22 (s, 9H). 13C NMR (75 MHz,
DMSO-d6) δ 155.73, 146.76, 141.96, 137.02, 136.10, 131.94,
128.19, 128.10, 127.57, 126.58, 125.99, 122.67, 122.52, 122.03,
120.56, 118.61, 118.32, 117.36, 114.78, 112.70, 105.35, 83.78,
34.78, 30.69. HRMS (ESI) exact mass calcd for
[C37H32N2O3S+Na]+ requires 607.2026, found 607.2029.
5-methyl-N-(7-methyl-6,6-diphenyl-6,7-dihydrochromeno
[3,4-b]indol-2-yl)benzenesulfonamide (3p)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 91% yield (152.9 mg), white
solid; m.p. 218-220 oC; 1H NMR (300 MHz, DMSO-d6) δ 9.88 (s,
1H), 7.73-7.59 (m, 3H), 7.58-7.49 (m, 1H), 7.47-7.25 (m, 11H),
7.24-7.13 (m, 4H), 6.90 (d, J = 8.5 Hz, 1H), 6.80-6.69 (m, 1H),
3.05 (s, 3H), 2.32 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ
146.81, 143.49, 141.72, 138.40, 137.51, 137.29, 132.43, 130.01,
129.15, 128.76, 128.64, 127.19, 122.94, 122.73, 122.53, 121.45,
119.20, 119.12, 117.87, 115.56, 111.33, 106.56, 84.74, 31.77,
21.37. HRMS (ESI) exact mass calcd. for [C35H28N2O3S+Na]+
requires 579.1713, found 579.1711.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-yl)-[1,1'-
biphenyl]-4-sulfonamide (4d)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 82% (148.7 mg); white
o
1
solid; m.p. 213-232 C; H NMR (300 MHz, DMSO-d6) δ 11.29
(s, 1H), 10.05 (s, 1H), 7.85 (s, 4H), 7.72-7.62 (m, 3H), 7.52-7.40
(m, 5H), 7.39-7.28 (m, 6H), 7.26-7.09 (m, 6H), 6.97 (d, J = 8.5
5

Hz, 1H), 6.81 (dd, J = 8.5, 2.2 Hz, 1H). 13C NMR (126 MHz,
DMSO-d6) δ 147.44, 144.69, 142.44, 138.97, 138.75, 137.50,
136.64, 132.28, 129.51, 128.99, 128.72, 128.62, 128.08, 127.94,
127.83, 127.51, 123.17, 123.11, 122.55, 121.14, 119.10, 117.95,
115.59, 113.22, 105.81, 84.30. HRMS (ESI) exact mass calcd.
for (C39H28N2O3S+Na)+ requires m/z 627.1713, found m/z
627.1713.
exact mass calcd. for (C33H22Cl2N2O3S+Na)+ requires m/z
619.0620, found m/z 619.0625.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-yl)-3-
fluorobenzenesulfonamide (4i)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 86% (141.1 mg); white
o
1
solid; m.p. 244-246 C; H NMR (300 MHz, DMSO-d6) δ 11.32
(s, 1H), 10.10 (s, 1H), 7.67-7.54 (m, 4H), 7.53-7.43 (m, 2H),
7.42-7.39 (m, 1H), 7.39-7.29 (m, 6H), 7.27-7.16 (m, 6H), 6.97 (d,
J = 8.5 Hz, 1H), 6.76 (dd, J = 8.6, 2.2 Hz, 1H). 13C NMR (126
MHz, DMSO-d6) δ 163.14, 161.16, 147.72, 142.41, 142.18 (d, J
= 6.5 Hz), 137.52, 136.65, 132.13 (d, J = 7.8 Hz), 131.81, 128.75,
128.64, 128.08, 123.57 (d, J = 3.1 Hz), 123.16, 122.63, 121.16,
120.48 (d, J = 21.2 Hz), 119.49, 119.08, 118.00, 115.98, 114.25
(d, J = 24.2 Hz), 113.27, 105.73, 84.36. HRMS (ESI) exact mass
calcd. for (C33H23FN2O3S+Na)+ requires m/z 569.1306, found
m/z 569.1301.
4-chloro-N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-
yl)benzenesulfonamide (4e)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 69% yield (116.9 mg), white
o
1
solid; m.p. 292-295 C; H NMR (300 MHz, DMSO-d6) δ 11.30
(s, 1H), 10.04 (s, 1H), 7.76 (d, J = 8.5 Hz, 2H), 7.65-7.55 (m,
3H), 7.48-7.42 (m, 1H), 7.41-7.28 (m, 7H), 7.27-7.15 (m, 6H),
6.96 (d, J = 8.5 Hz, 1H), 6.79-6.70 (m, 1H). 13C NMR (75 MHz,
DMSO-d6) δ 147.66, 142.37, 138.93, 138.15, 137.48, 136.58,
131.82, 129.79, 129.13, 128.68, 128.58, 128.04, 123.12, 123.09,
122.53, 121.12, 119.51, 119.02, 117.92, 116.00, 113.19, 105.72,
84.30. HRMS (ESI) exact mass calcd. for [C33H23ClN2O3S+Na]+
requires 585.1010, found 585.1012.
3-cyano-N-(6,6-diphenyl-6,7-dihydro- chromeno[3,4-b]indol-
2-yl)benzene-Sulfonamide (4j)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 72% (121.0 mg); white
3-bromo-N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-
2-yl)benzenesulfonamide (4f)
o
1
solid; m.p. 259-262 C; H NMR (300 MHz, DMSO-d6) δ 11.32
(s, 1H), 10.14 (s, 1H), 8.23 (s, 1H), 8.10 (d, J = 7.8 Hz, 1H), 8.02
(d, J = 8.0 Hz, 1H), 7.75 (appt, J = 7.9 Hz, 1H), 7.67-7.57 (m,
1H), 7.51-7.41 (m, 1H), 7.41-7.29 (m, 7H), 7.28-7.15 (m, 6H),
6.98 (d, J = 8.6 Hz, 1H), 6.77 (dd, J = 8.6, 2.1 Hz, 1H). 13C NMR
(126 MHz, DMSO-d6) δ 147.87, 142.36, 141.33, 137.50, 136.86,
136.65, 131.72, 131.48, 131.26, 130.76, 128.77, 128.65, 128.06,
123.20, 123.11, 122.63, 121.19, 119.81, 119.04, 118.05, 117.87,
116.24, 113.27, 112.97, 105.64, 84.37. HRMS (ESI) exact mass
calcd. for (C34H23F3N2O3S-H)- requires m/z 552.1460, found m/z
552.1374.
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1, reaction time = 2 h, 90% yield (165.0 mg), white
o
1
solid; m.p. 220-223 C; H NMR (300 MHz, DMSO-d6) δ 11.30
(s, 1H), 10.06 (s, 1H), 7.97 (s, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.72
(d, J = 7.6 Hz, 1H), 7.66-7.57 (m, 1H), 7.53-7.42 (m, 2H), 7.41-
7.29 (m, 7H), 7.29-7.14 (m, 6H), 6.98 (d, J = 8.4 Hz, 1H), 6.83-
6.72 (m, 1H). 13C NMR (75 MHz, DMSO-d6) δ 147.76, 142.37,
142.10, 137.48, 136.53, 136.02, 131.87, 131.60, 129.57, 128.66,
128.56, 128.01, 126.23, 123.09, 122.53, 121.11, 119.78, 119.05,
117.90, 116.11, 113.18, 105.67, 84.33. HRMS (ESI) exact mass
calcd. for [C33H23BrN2O3S+NH4]+ requires 624.0951, found
624.0954.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-yl)-3-
nitrobenzenesulfonamide (4k)
2-chloro-N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-
yl)benzenesulfonamide (4g)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 70% (120.9 mg); white
o
1
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 96% (162.9 mg); white
solid; m.p. 208-210 C; H NMR (300 MHz, DMSO-d6) δ 11.32
(s, 1H), 10.29 (s, 1H), 8.60 (appt, J = 1.8 Hz, 1H), 8.48-8.37 (m,
1H), 8.19-8.08 (m, 1H), 7.82 (appt, J = 8.0 Hz, 1H), 7.71-7.58 (m,
1H), 7.51-7.41 (m, 2H), 7.41-7.28 (m, 6H), 7.28-7.14 (m, 6H),
6.98 (d, J = 8.5 Hz, 1H), 6.79 (dd, J = 8.5, 2.4 Hz, 1H). 13C NMR
(126 MHz, DMSO-d6) δ 148.31, 147.88, 142.33, 141.61, 141.59,
137.48, 136.63, 133.24, 131.82, 131.42, 131.40, 128.76, 128.64,
128.17, 128.03, 127.92, 123.21, 123.08, 122.63, 121.99, 121.12,
119.78, 118.97, 118.07, 116.22, 113.26, 105.59, 84.35. HRMS
(ESI) exact mass calcd. for (C33H23N3O5S+Na)+ requires m/z
592.1251, found m/z 592.1252.
o
1
solid; m.p. 270-272 C; H NMR (300 MHz, DMSO-d6) δ 11.30
(s, 1H), 10.30 (s, 1H), 8.06 (dd, J = 7.8, 1.6 Hz, 1H), 7.72-7.58
(m, 3H), 7.56-7.48 (m, 1H), 7.47-7.40 (m, 2H), 7.40-7.29 (m,
6H), 7.27-7.15 (m, 6H), 6.94 (d, J = 8.6 Hz, 1H), 6.77 (dd, J =
8.6, 2.4 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 147.25,
142.40, 137.47, 137.36, 136.62, 135.03, 132.36, 131.98, 131.60,
131.28, 128.74, 128.63, 128.25, 128.06, 128.05, 123.10, 123.08,
123.08, 122.57, 121.17, 119.06, 118.29, 117.90, 114.77, 113.24,
105.68, 84.28, 65.39, 15.65. HRMS (ESI) exact mass calcd. for
(C33H23ClN2O3S+Na)+ requires m/z 585.1010, found m/z
585.1012.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-yl)-3-
(trifluoromethyl)benzene sulfonamide (4l)
3,4-dichloro-N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-
b]indol-2-yl)benzenesulfonamide (4h)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 77% (139.1 mg); white
o
1
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 72% (130.3 mg); white
solid; m.p. 135-137 C; H NMR (300 MHz, DMSO-d6) δ 11.31
(s, 1H), 10.13 (s, 1H), 8.12 (s, 1H), 8.00 (d, J = 7.8 Hz, 2H), 7.77
(appt, J = 7.8 Hz, 1H), 7.57 (d, J = 7.3 Hz, 1H), 7.45 (d, J = 7.3
Hz, 1H), 7.42-7.30 (m, 7H), 7.29-7.13 (m, 6H), 6.98 (d, J = 8.5
Hz, 1H), 6.78 (dd, J = 8.5, 2.1 Hz, 1H). 13C NMR (126 MHz,
DMSO-d6) δ 147.95, 142.36, 141.13, 137.49, 136.61, 131.46,
131.31, 131.29, 130.38 (q, J = 32.7 Hz), 129.95 (q, J = 3.7 Hz),
128.74, 128.62, 128.05, 124.89, 123.81 (q, J = 273.4 Hz), 123.79
(q, J = 4.0 Hz), 123.10, 123.10, 122.60, 121.04, 120.09, 118.97,
118.02, 116.37, 113.24, 105.61, 84.36. HRMS (ESI) exact mass
o
1
solid; m.p. 283-284 C; H NMR (300 MHz, DMSO-d6) δ 11.33
(s, 1H), 10.12 (s, 1H), 7.98 (d, J = 1.8 Hz, 1H), 7.82 (d, J = 8.4
Hz, 1H), 7.67 (dd, J = 8.4, 1.9 Hz, 1H), 7.64-7.56 (m, 1H), 7.51-
7.42 (m, 1H), 7.42-7.30 (m, 7H), 7.29-7.16 (m, 6H), 7.00 (d, J =
8.5 Hz, 1H), 6.78 (dd, J = 8.5, 2.2 Hz, 1H). 13C NMR (126 MHz,
DMSO-d6) δ 170.82, 148.01, 142.36, 140.29, 137.53, 136.68,
136.48, 132.70, 132.11, 131.42, 128.99, 128.76, 128.64, 128.07,
127.41, 123.24, 123.14, 122.64, 121.24, 120.17, 118.98, 118.12,
116.44, 113.29, 105.67, 84.39, 60.25, 21.22, 14.54. HRMS (ESI)
6

calcd. for (C34H23F3N2O3S+Na)+ requires m/z 619.1274, found
m/z 619.1273.
ACKNOWLEDGMENT
Financial support from National Natural Science Foundation
of China (grants 21971256, 21977118 and 81773584) is
gratefully acknowledged. This project was also supported by
the National Science & Technology Major Project “Key
New Drug Creation and Manufacturing Program”, China
(2019ZX09301-151), the Jiangsu Provincial Key Research
and Development Project (BE2018710), the “Double First-
Class” University project (CPU2018GY01, CPU2018GY35,
CPU2018GY45) and the Program for Jiangsu Province
Innovative Research Team.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-
yl)ethanesulfonamide(4m)
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 74% (107.3 mg); white
o
1
solid; m.p. 142-145 C; H NMR (300 MHz, DMSO-d6) δ 11.31
(s, 1H), 9.48 (s, 1H), 7.92-7.84 (m, 1H), 7.69 (d, J = 2.2 Hz, 1H),
7.51-7.43 (m, 1H), 7.43-7.31 (m, 6H), 7.31-7.16 (m, 6H), 7.03 (d,
J = 8.6 Hz, 1H), 6.90 (dd, J = 8.5, 2.2 Hz, 1H), 3.06 (q, J = 7.2
Hz, 2H), 1.22 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, DMSO-d6)
δ 147.06, 142.62, 137.56, 136.61, 133.11, 128.74, 128.66, 128.12,
123.28, 123.27, 122.59, 121.15, 119.36, 117.94, 117.86, 114.82,
113.22, 105.91, 84.30, 45.26, 8.53. HRMS (ESI) exact mass
calcd. for (C29H24N2O3S+Na)+ requires m/z 503.1400, found m/z
579.1400.
References
[1] For reviews, see: a) G. R. Humphrey, J. T. Kuethe, Chem.
Rev. 2006, 106, 2875; b) M. Bandini, A. Eichholzer, Angew.
Chem. Int. Ed. 2009, 48, 9608; c) A. J. Kochanowska-
Karamyan, M. T. Hamann, Chem. Rev. 2010, 110, 4489.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-
yl)propane-1-sulfonamide (4n)
[2] For some reviews: a) A. Palmieri, M. Petrini, R. R. Shaikh,
Org. Biomol. Chem. 2010, 8, 1259; b) L. Wang, Y. Chen, J.
Xiao, Asian J. Org. Chem., 2014, 3, 1036; c) G.-J. Mei, F.
Shi, J. Org. Chem. 2017, 82, 7695.
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 82% (122.4 mg); white
o
1
[3] a) Y.-Y. He, X.-X. Sun, G.-H. Li, G.-J. Mei, F. Shi, J. Org.
Chem. 2017, 82, 2462; b) C. Ma, F. Jiang, F.-T. Sheng, Y.
Jiao, G.-J. Mei, F. Shi, Angew. Chem. Int. Ed. 2019, 58,
3014.
solid; m.p. 152-154 C; H NMR (300 MHz, DMSO-d6) δ 11.32
(s, 1H), 9.47 (s, 1H), 7.94-7.81 (m, 1H), 7.67 (s, 1H), 7.53-7.31
(m, 7H), 7.31-7.14 (m, 6H), 7.03 (d, J = 8.5 Hz, 1H), 6.89 (d, J =
7.7 Hz, 1H), 3.03 (t, J = 7.2 Hz, 2H), 1.84-1.60 (m, 2H), 0.93 (t,
J = 7.2 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 147.06,
142.59, 137.54, 136.62, 133.1, 128.74, 128.66, 128.10, 123.27,
123.24, 122.59, 121.14, 119.33, 117.95, 117.90, 114.84, 113.22,
105.91, 84.29, 52.54, 17.32, 13.08. HRMS (ESI) exact mass
calcd. for (C30H26N2O3S+Na)+ requires m/z 517.1556, found m/z
517.1555.
[4] C. Li, H. H. Zhang, T. Fan, Y. Shen, Q. Wu, F. Shi, Org.
Biomol. Chem. 2016, 14, 6932.
[5] Z. Q. Zhu, Y. Shen, J. X. Liu, J. Y. Tao, F. Shi, Org. Lett.
2017, 19, 1542.
[6] H. H. Zhang, C. S. Wang, C. Li, G. J. Mei, Y. Li, F. Shi,
Angew. Chem., Int. Ed. 2017, 56, 116.
N-(6,6-diphenyl-6,7-dihydrochromeno[3,4-b]indol-2-
yl)cyclopropanesulfonamide (4o)
[7] a) C. Hu, G. Hong, Y. He, C. Zhou, M. C. Kozlowski, L.
Wang, J. Org. Chem. 2018, 83, 4739; b) L. Chen, Y.-X. Zou,
X.-Y. Fang, J. Wu, X.-H. Sun, Org. Biomol. Chem. 2018, 16,
7417.
Flash column chromatography eluent, petroleum ether/ethyl
acetate = 5/1; reaction time = 2 h; yield: 94% ( 140.0 mg); white
o
1
solid; m.p. 150-152 C; H NMR (300 MHz, DMSO-d6) δ 11.31
(s, 1H), 9.40 (s, 1H), 7.93-7.83 (m, 1H), 7.69 (d, J = 2.5 Hz, 1H),
7.52-7.43 (m, 1H), 7.43-7.33 (m, 6H), 7.31-7.16 (m, 6H), 7.03 (d,
J = 8.5 Hz, 1H), 6.92 (dd, J = 8.6, 2.3 Hz, 1H), 2.66-2.54 (m, 1H),
0.93-0.88 (m, 4H). 13C NMR (126 MHz, DMSO-d6) δ 147.26,
142.57, 137.54, 136.63, 133.00, 128.73, 128.65, 128.25, 128.13,
123.30, 123.14, 122.56, 121.13, 119.35, 118.83, 117.86, 115.68,
113.21, 105.96, 84.29, 29.66, 5.40. HRMS (ESI) exact mass
calcd. for (C30H24N2O3S+Na)+ requires m/z 515.1400, found m/z
515.1399.
[8] a) C. Ma, J.-Y. Zhou, Y.-Z. Zhang, Y. Jiao, G.-J. Mei, F. Shi,
Chem. Asian J. 2018, 13, 2549; b) M.-M. Xu, H.-Q. Wang,
Y.-J. Mao, G.-J. Mei, S.-L. Wang, F. Shi, J. Org. Chem.
2018, 83, 502.
[9] a) Z.-Q. Zhu, Y. Shen, X.-X. Sun, J.-Y. Tao, J.-X. Liu, F. Shi,
Adv. Synth. Catal. 2016, 358, 3797; b) M.-M. Xu, H.-Q.
Wang, Y. Wan, S.-L. Wang, F. Shi, J. Org. Chem. 2017, 82,
10226; c) J. Mao, H. Zhang, X.-F. Ding, X. Luo, W.-P.
Deng, J. Org. Chem. 2019, 84, 11186.
[10] Z.-Q. Zhu, L. Yu, M. Sun, G.-J. Mei, F. Shi, Adv. Synth.
Catal. 2018, 360, 3109.
THE ASSOCIATED CONTENT
Supporting Information
[11] M. Sun, C. Ma, S.-J. Zhou, S.-F. Lou, J. Xiao, Y. Jiao, F. Shi,
Angew. Chem., Int. Ed. 2019, 58, 8703.
Experimental procedures, characterization data (PDF)
AUTHOR INFORMATION
Corresponding Author
[12] a) J.-Z. Wang, J. Zhou, C. Xu, H. Sun, L. Kürti, Q.-L. Xu, J.
Am. Chem. Soc. 2016, 138, 5202; b) L. Liu, K. Chen, W.-Z.
Wu, P.-F. Wang, H.-Y. Song, H. Sun, X. Wen, Q.-L. Xu,
Org. Lett. 2017, 19, 3823.
*i_m_zhenle@163.com
[13] CCDC
1983979 (3a) contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
*qlxu@cpu.edu.cn
Crystallographic
Data
Centre
via
Notes
www.ccdc.cam.ac.uk/data_request/cif.
The authors declare no competing financial interest.
7

Highlights
A formal [3+3] cyclization reaction of 2-indolylmethanols with quinone imines
was realized to afford fused-indole scaffolds in moderate to excellent yields. In this
transformation, the reaction was employing C3-position of 2-indolylmethanols as
nucleophilic site.

Declaration of interests
ꢀThe authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
ꢁ
The authors declare the following financial interests/personal relationships which may be
considered as potential competing interests: