Iodine-Catalyzed C-H Amidation and Imination at the 2α-Position of 2,3-Disubstituted Indoles with Chloramine Salts

Article abstract of DOI:10.1021/acs.joc.8b00286

A novel iodine-catalyzed amidation and imination at the 2α-position of 2,3-disubstituted indoles in the presence of chloramine salts with high regioselectivity has been achieved. The protocol is applicable to a wide range of substrates to deliver the corresponding 2α-nitrogen-containing indole derivatives. Furthermore, to demonstrate the synthetic value of this established transformation, a concise assembly of the bridged tetracyclic framework of akuammiline alkaloids from the 2α-amidated product has been accomplished in five steps.

Full text of DOI:10.1021/acs.joc.8b00286

Subscriber access provided by UNIVERSITY OF TOLEDO LIBRARIES
Iodine-Catalyzed C-H Amidation and Imination at 2#-
Position of 2,3-Disubstituted Indoles with Chloramine Salts
Xiaozu Liu, Yuxiang Zhou, Zhongqin Yang, Qin Li, Liang Zhao, and Peijun Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00286 • Publication Date (Web): 28 Mar 2018
Downloaded from http://pubs.acs.org on March 28, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 11
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
IodineꢀCatalyzed CꢀH Amidation and Imination at 2αꢀPosition of
2,3ꢀDisubstituted Indoles with Chloramine Salts
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Xiaozu Liu, Yuxiang Zhou, Zhongqin Yang, Qin Li, Liang Zhao, and Peijun Liu*
Pharmacy School, Zunyi Medical University, Zunyi 563003, P. R. China
Supporting Information Placeholder
R3
R3
R3
I2 (cat.)
R2
R2
(
)
n
1,4-dioxane
rt
1,4-dioxane R2
rt
( )
n
NSO2R
+
N
R1
N
R1
N
R1
R4
R4
Na
SO2R
NHSO2R
N
Cl
10 examples
up to 91% yield
R4 = CH3 or H
n = 1-4
33 examples
up to 90% yield
5 steps
OHC
O
External oxidant free
PhO2S
N
N
High regioselectivity
Ambient condition
Me
PMB
HN
N
H
Excellent atom economy
Readily avilable substrates
CO2Me
O
aspidophylline A
[
]
ABSTRACT: A novel iodineꢀcatalyzed amidation and imination at 2αꢀposition of 2,3ꢀdisubstituted indoles in the presence of chloꢀ
ramine salts with high regioselectivity has been achieved. The protocol is applicable to a wide range of substrates to deliver the
corresponding 2αꢀnitrogenꢀcontaining indole derivatives. Furthermore, to demonstrate the synthetic value of this established transꢀ
formation, a concise assembly of the bridged tetracyclic framework of akuammiline alkaloids from the 2αꢀamidated product has
been accomplished in five steps.
atom economy and limiting the practical applications. Noticeꢀ
■ INTRODUCTION
ably, 2αꢀfunctionalized indoles are not only privileged scafꢀ
folds in some bioactive compounds such as antiꢀHPV agents,6
Indoles are among the most privileged structures that are
NPY receptor antagonists,7 and PGD2 receptor antagonists,8
widely found in naturally occurring alkaloids, organic materiꢀ
but also found as the core structures of some indole alkaloids
(Figure 1).9 Therefore, it is of great significance to develop
new methods that allow for easy access to these attractive
compounds, particularly the 2αꢀnitrogenꢀcontaining ones that
could serve as key intermediates for the total synthesis of akuꢀ
ammiline alkaloids.10
als, biologically active compounds, and medicinally relevant
molecules.1 Hence, considerable effort has been directed toꢀ
ward the development of efficient methods for their synthesis
and functionalization.2 Meanwhile, The direct functionalizaꢀ
tion of CꢀH bonds, which has been studied extensively in reꢀ
cent years, has become a powerful tool in the formation of Cꢀ
C and Cꢀheteroatom bonds owing to its inherent atom and step
economy.3 Consequently, this approach has attracted growing
attention in indole functionalization and many impressive reꢀ
sults have been documented.4 In contrast, the methods for diꢀ
rect CꢀH bond functionalization of side chains of 2,3ꢀ
disubstituted indoles are quite limited.5 For instance, in 2011,
Kawasaki and coꢀworkers described an efficient procedure for
CꢀH functionalization at indole 2αꢀposition mediated by
acyloxythionium species.5a Several similar transformations
have been achieved via an oxidative coupling approach using
different oxidants later.5bꢀ5d Despite the merits of these methꢀ
ods, most of them suffer from drawbacks such as the relatively
narrow scope of substrates and inevitable requirement of stoiꢀ
chiometric external oxidants to regenerate the active catalytic
species or yield the reactive intermediates, thus lowering the
Figure 1. Representative natural products and biologically active
molecules with 2αꢀsubstituted indole motifs.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Table 2. Scope of 2,3ꢀDisubstituted Indolesa,b
Page 2 of 11
Table 1. Optimization of Reaction Conditionsa
1
2
3
4
O
R2
R2
O
O
O
I2
S
Cl
+
n
n
N
S
Cl
iodine source
solvent
N
1,4-dioxane
N
N
Na
N
+
NHSO2Ph
HN
Na
S
R1
1
R1
Me
N
O
H
O
Me
1a
2a
3
5
2a
3a
n = 1-4
n = 1-4
6
7
8
9
Entry
1
Iodine source
Solvent
Yield [%]b
I2
CH3CN
71
68
44
85
31
28
nd
56
12
10
66
81
nd
2
I2
THF
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
I2
toluene
4
I2
1,4ꢀdioxane
DCM
5
I2
6
I2
MeOH
7
8c
I2
H2O
I2
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
9
NaI
KI
TBAI
NIS
ꢀ
10
11
12
13
aReaction conditions: 1a (0.5 mmol), 2a (1.1 mmol), iodine
b
source (10 mol%), solvent (3 mL), room temperature, 9 h.
Isolated yield. c2a (0.6 mmol).
Recently, iodineꢀbased catalytic systems in CꢀH bond funcꢀ
tionalization have been significantly developed featuring the
atom economy and the mild and ecoꢀfriendly conditions.11
Furthermore, These protocols are efficient at promoting the
synthetically challenging C(sp3)ꢀH amination.12 Inspired by
the above achievements, and in continuation of our interest in
iodineꢀcatalyzed functionalization of indoles,13 we herein
would like to disclose a novel iodineꢀcatalyzed regioselective
2αꢀamidation and imination of 2,3ꢀdisubstituted indoles emꢀ
ploying chloramine salts as both oxidants and nitrogen sources.
aReaction conditions: 1 (0.5 mmol), chloramineꢀB (1.1 mmol), I2
(10 mol%), 1,4ꢀdioxane (3 mL), room temperature, 9 h. bIsolated
yield. cAt 50 oC. dThe reaction time was 17 h.
■ RESULTS AND DISCUSSION
Initially, we utilized Nꢀmethyltetrahydrocarbazole 1a and
chloramineꢀB 2a as the model substrates to optimize the reacꢀ
tion conditions (Table 1). Gratifyingly, when the reaction was
conducted in the presence of a catalytic amount of molecular
iodine in acetonitrile at room temperature for 9 h, the desired
compound 3a was isolated in 71% yield (Table 1, entry 1).
Encouraged by this promising result, further screening of the
reaction conditions was performed. Among various potential
solvents examined, 1, 4ꢀdioxane gave the best result to afford
3a in 85% yield (entries 2ꢀ6), whereas water as solvent did not
provide any desired product (entry 7). Decreasing the amount
of chloramineꢀB to 0.6 mmol resulted in a significant reducꢀ
tion in yield (56%, entry 8). Next, several other iodine sources
were also tested for their efficiency, but they were found to be
inferior to molecular iodine under the given conditions (entries
9ꢀ12). Moreover, no target compound was observed in the
absence of iodine (entry 13).
reacted smoothly with chloramineꢀB 2a, affording the correꢀ
sponding products in moderate to excellent yields (Table 2).
The introduction of various protecting groups such as methyl,
benzyl, PMB, MOM, allyl, and TBDMS for Nꢀprotection had
only marginal influence on performance of the reaction (67ꢀ
90%, 3aꢀf). Among the products, the structure of 3d was deꢀ
termined by Xꢀray diffraction of a single crystal.14 Substrates
with both electronꢀdonating and electronꢀwithdrawing groups
on the indole core were engaged in this transformation, furꢀ
nishing the corresponding products in good to excellent yields
(3gꢀr). The tolerance of the Br substituent enables further
transformation through classical crossꢀcoupling reactions.
Notably, the reaction worked well under the standard condiꢀ
tions when cyclic systems of different ring sizes were emꢀ
ployed (3tꢀw). Most importantly, more hindered 1ꢀmethyl
tetrahydrocarbazole derivative 1z also reacted efficiently with
excellent regioselectivity to give the desired 2αꢀamidated
product 3z in 55% yield. Likewise, the reaction of 2ꢀethylꢀ3ꢀ
methylindole derivative 1aa proceeded smoothly to give the
With the optimized conditions in hand, we next explored the
substrate scope. Initially, a wide range of indole derivatives
ACS Paragon Plus Environment

Page 3 of 11
The Journal of Organic Chemistry
Table 3: Scope of 2ꢀMethylꢀ3ꢀsubstituted Indolesa,b
Scheme 1: Assembly of a Tetracyclic Motif Present in
Akuammiline Alkaloids from the Product 3c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To further explore the potential of our methodology, several
other chloramine salts were examined to react with Nꢀmethyl
tetrohydrocarbazole 1a under the optimized reaction condiꢀ
tions. The reaction proceeded smoothly to deliver the correspꢀ
onding 2αꢀamidated products in good to excellent yields (Taꢀ
ble 4).
aReaction conditions: 1 (0.5 mmol), chloramineꢀB (1.1 mmol), I2
(10 mol%), 1,4ꢀdioxane (3 mL), room temperature. bIsolated
yield. cAt 50 oC.
In order to verify the synthetic utility of these CꢀH amidated
products, a concise assembly of the bridged tetracyclic core of
akuammiline alkaloids starting from 3c was performed
(Scheme 1). A sequence of Nꢀpropargylation and desilylation
of 3c afforded compound 6 with good overall efficiency.
Treatment of 6 with DDQ furnished ketone 7 in 88% yield,
without deprotecting the PMB group. Finally, goldꢀcatalyzed
intramolecular cyclization of the silyl enol ether generated
from 7 provided the desired 6ꢀexoꢀdig cyclization product 810c,
16 in 57% overall yield (76% based on recovered starting mateꢀ
rial 7).
Table 4: Scope of Chloramine Saltsa,b
To gain insight into the mechanism of the reaction, the folꢀ
lowing experiments were carried out. As illustrated in Scheme
2, the reaction was not suppressed when the radical scavenger
2,2,6,6ꢀtetramethylpiperidineꢀ1ꢀoxyl (TEMPO) or 2,6ꢀdiꢀtertꢀ
butylꢀ4ꢀmethylphenol (BHT) was added under the standard
reaction conditions. This means that a radical pathway is not
involved in this reaction.
On the basis of these observations and the literature reꢀ
ports,5b, 17 a plausible mechanism is proposed in Scheme 3.
Initially, the interaction of chloramineꢀB and iodine generates
the active species Nꢀiodoꢀchlorobenzenesulfonamide 9, which
subsequently activates the indole moiety 1 to give iminium
intermediate 10. Elimination of a hydrogen atom at the 2αꢀ
position provides enamine 11. Subsequent SN2’displacement
of 11 by the chloramineꢀB results in the formation of chloraꢀ
mine 12, which then reacts with iodide ion to give the amidatꢀ
ed product 3. Finally, the resulting iodine monochloride oxiꢀ
dizes NaI to regenerate iodine. As for 2ꢀmethylꢀ3ꢀsubstituted
indoles, the intermediate 2αꢀamidated indole 13 continues to
react with another molecule of 9, which produces the final
iminated product 4 along with the release of benzene sulfonaꢀ
mide and iodine monochloride. The latter then oxidizes NaI to
regenerate iodine.
aReaction conditions: 1a (0.5 mmol), 2 (1.1 mmol), I2 (10
b
mol%), 1,4ꢀdioxane (3 mL), room temperature, 9 h. Isolated
yield.
desired 2αꢀamidated product 3aa in good yield with excellent
regioselectivity. These results indicated the regioselectivity
might be thermodynamically controlled rather than kinetically.
Interestingly, reaction between chloramineꢀB and various 2ꢀ
methylꢀ3ꢀsubstituted indoles led to the formation of the correꢀ
sponding 2αꢀiminated products instead of amidated ones in
moderated to excellent yields (Table 3).14 It is noteworthy that
NꢀEWGꢀprotected aldimines represent a valuable structural
motif due to their capacity to serve as versatile building blocks
for the synthesis of a wide range of nitrogenꢀcontaining comꢀ
pounds.15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 11
Scheme 2: Radical Scavenger Experiment
hertz (Hz). High resolution mass spectra were obtained on
Agilent 6210 ESI/TOF spectrometer.
1
2
3
4
5
6
7
8
9
General procedure for the synthesis of 3. A 25 mL round
bottom flask with a magneton was charged with 2,3ꢀ
disubstituted indole 1 (0.5 mmol), chloramine salt 2 (1.1
mmol), and 1,4ꢀdioxane (3 mL) under air at room temperature,
and then I2 (13 mg, 0.05 mmol) was added. The mixture was
stirred vigorously for 9 h. After that, the reaction mixture was
filtered. The filtrate was concentrated under reduced pressure.
Purification of the residue by flash column chromatography on
silica gel using petroleum ether/ethyl acetate as eluent
afforded the desired product 3.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3: Plausible Reaction Mechanism
General procedure for the synthesis of 4. A 25 mL round
bottom flask with a magneton was charged with 2ꢀmethylꢀ3ꢀ
substituted indole 1 (0.5 mmol), chloramineꢀB 2a (0.24 g, 1.1
mmol), and 1, 4ꢀdioxane (3 mL) under air at room temperature,
and then I2 (13 mg, 0.05 mmol) was added. The mixture was
vigorously stirred and monitored by thin layer chromatogꢀ
raphy. After completion, the reaction mixture was filtered. The
filtrate was concentrated under reduced pressure. Purification
of the residue by flash column chromatography on silica gel
using petroleum ether/ethyl acetate as eluent afforded the deꢀ
sired product 4.
Procedures for the synthesis of bridged tetracycle 8. Alꢀ
kyne 6: To a stirred solution of benzenesulfonamide 3c (0.60
g, 1.35 mmol) in dry THF (18 mL) were added dropwise LDA
(1.35 mL, 2.70 mmol, 2.0 M in THF) at ꢀ78 °C. The reaction
mixture was stirred at that temperature for 30 min and then
warmed up to 0 °C. TMSꢀpropargylbromide 5 (0.45 mL, 2.76
mmol) and (nꢀBu)4NI (0.51 mg, 1.35 mmol) were added. The
reaction mixture was warmed to room temperature and stirred
for further 12 h. After completion, the resultant mixture was
quenched with saturated NH4Cl (30 mL), extracted with ethyl
acetate (3 x 30 mL), dried over Na2SO4 and the solvent was
evaporated under reduced pressure. The obtained brown oil
was dissolved in dry THF (3 mL), and then cooled to 0 oC. To
the stirred solution was added dropwise TBAF (2 mL, 2.0
mmol, 1 M in THF). The resultant mixture was warmed to
room temperature and stirred for 30 min before it was
quenched with brine (10 mL). The resultant mixture was exꢀ
tracted with ethyl acetate (3 x 10 mL). The combined organic
phases were dried over anhydrous Na2SO4, filtered, and conꢀ
centrated under vacuum. The residue was purified by flash
column chromatography with EtOAc/petroleum ether (1:6) to
give the alkyne 6 (0.383g, 58%, 2 steps) as a colorless oil
which was solidified on standing.
■ CONCLUSIONS
In summary, we have developed a general and practical methꢀ
od for iodineꢀcatalyzed regioselective CꢀH amidation and imiꢀ
nation at the 2αꢀposition of 2,3ꢀdisubstituted indoles with
chloramine salts, which enables the facile and direct construcꢀ
tion of various 2αꢀnitrogenꢀcontaining indoles. The reaction
features mild and environmentally benign reaction conditions,
broad substrate scope, and good functional group compatibilꢀ
ity. Furthermore, the products are important synthetic interꢀ
mediates which have been demonstrated by a concise assemꢀ
bly of the bridged tetracyclic core of akuammiline alkaloids,
providing a powerful tool for the total synthesis of natural
molecules in this family.
Ketone 7: To the stirred solution of alkyne 6 (99 mg, 0.20
mmol) in THF/water (11 mL, 10:1) was added DDQ (93 mg,
0.41 mmol) at 0 °C. The resultant mixture was allowed to
warm to room temperature and stirred at that temperature for 3
h before it was quenched with saturated aq. NaHCO3 (10 mL)
and extracted with EtOAc (3 × 15 mL). The combined organic
phases were washed with brine (10 mL) and dried over anhyꢀ
drous Na2SO4. After filtration and evaporation of the solvent
under vacuum, the residue was subjected to flash column
chromatography for purification using EtOAc/petroleum ether
(1:2) as eluent to give the ketone 7 (90 mg, 88%) as a brown
solid.
■ EXPERIMENTAL SECTION
General Methods. Unless otherwise noted, all commercial
materials and solvents were used without further purification.
Commercially available chemicals were obtained from Energy
Chemical, TCI, Alfa Aesar and J&K. Thin layer chromatogꢀ
raphy (TLC) was carried out on GF254 plates (0.25 mm layer
thickness) and visualized under UV light (254 nm). The silica
gel (200ꢀ300 meshes) was used for column chromatography.
1H NMR and 13C NMR were recorded on Agilent 400 MHz
spectrometer using TMS as internal standard. Spin multipliciꢀ
ties are given as s (singlet), d (doublet), t (triplet), q (quartet),
m (multiplet), dd (doublet of doublet), td (triplet of doublet),
as well as brs (broad). Coupling constants (J) are given in
Terminal alkene 8: To a stirred solution of ketone 7 (0.10
g, 0.20 mmol) in dry CH2Cl2 (10 mL) were sequentially added
Et3N (0.11 mL, 0.80 mmol) and TIPSOTf (0.22 mL, 0.80
mmol) at room temperature. The reaction mixture was stirred
ACS Paragon Plus Environment

Page 5 of 11
The Journal of Organic Chemistry
at that temperature for 2 h. The resultant mixture was concenꢀ
73.3, 56.0, 46.1, 29.8, 20.6, 17.8. HRMSꢀESI (m/z): calcd for
C20H22N2NaO3S [M + Na]+: 393.1243, found 393.1241.
1
2
3
4
5
6
7
8
trated under vacuum, and the residue was purified by flash
column chromatography with EtOAc/petroleum ether (1:5) to
give the silyl enol ether (0.121 g, 92%) as a brown oil. The oil
was then dissolved in dry CH2Cl2 (5 mL). To the stirred soluꢀ
tion were sequentially added iꢀPrOH (0.38 mL), 4 Å molecular
sieves (0.2 g), Ph3PAuCl (5 mg, 5 mol%), AgSbF6 (4 mg, 5
mol%), and 2,4,6ꢀtriꢀtertꢀbutylpyrimidine (5 mg, 10 mol%) at
room temperature. The resultant mixture was allowed to stir at
that temperature for 13 h. After that, the resultant mixture was
directly subjected to flash column chromatography for purifiꢀ
cation using EtOAc/petroleum ether (1:3) as eluent to give the
cyclization product 8 (59 mg, 57%, 76% brsm, 2 steps) as a
white solid and ketone 7 (25 mg) was recovered.
Nꢀ(9ꢀallylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)benzenesulfꢀ
onamide (3e): Brown solid, 162 mg, 89% yield, m.p. 116.0ꢀ
o
118.6 C. 1H NMR (400 MHz, CDCl3) δ 8.03 – 7.90 (m, 2H),
7.71 – 7.41 (m, 4H), 7.21 (d, J = 5.7 Hz, 2H), 7.08 (ddd, J =
7.9, 5.9, 2.0 Hz, 1H), 5.89 – 5.72 (m, 1H), 5.15 – 5.00 (m, 1H),
4.78 – 4.45 (m, 5H), 2.80 (dd, J = 15.7, 3.6 Hz, 1H), 2.56 (ddd,
J = 16.3, 11.1, 6.5 Hz, 1H), 1.90 – 1.66 (m, 4H). 13C NMR
(101 MHz, DMSOꢀd6) δ 142.9, 136.7, 134.9, 132.9, 132.5,
129.8, 126.7, 126.4, 122.2, 119.1, 118.8, 116.4, 112.3, 110.3,
45.7, 45.0, 29.9, 20.8, 17.8. HRMSꢀESI (m/z): calcd for
C21H23N2O2S [M + H]+: 367.1475, found 367.1476.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(9ꢀ(tertꢀbutyldimethylsilyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbaꢀ
Characterization Data of Products. Nꢀ(9ꢀmethylꢀ2,3,4,9ꢀ
tetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)benzenesulfonamide (3a): White
solid, 144 mg, 85% yield, m.p. 231.2ꢀ232.8 oC. 1H NMR (400
MHz, DMSOꢀd6) δ 8.14 (dd, J = 8.2, 2.6 Hz, 1H), 7.98 – 7.79
(m, 2H), 7.64 (tdd, J = 9.5, 4.9, 2.2 Hz, 3H), 7.37 (ddd, J =
22.7, 8.2, 2.5 Hz, 2H), 7.19 – 7.05 (m, 1H), 6.97 (td, J = 7.4,
2.4 Hz, 1H), 4.68 (dd, J = 8.2, 3.5 Hz, 1H), 3.44 (s, 3H), 2.73
– 2.56 (m, 1H), 2.45 – 2.33 (m, 1H), 1.89 – 1.71 (m, 1H), 1.67
– 1.50 (m, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 142.9,
137.2, 133.0, 132.9, 129.7, 126.8, 126.2, 122.1, 118.9, 118.6,
111.9, 109.7, 45.6, 30.2, 29.2, 20.8, 17.8. HRMSꢀESI (m/z):
calcd for C19H21N2O2S [M + H]+: 341.1318, found 341.1317.
zolꢀ1ꢀyl)benzenesulfonamide (3f): Brown solid, 147 mg, 65%
o
1
yield, m.p. 68.6ꢀ71.3 C,. H NMR (400 MHz, CDCl3) δ 7.87
(dq, J = 7.1, 1.2 Hz, 2H), 7.62 – 7.52 (m, 2H), 7.53 – 7.44 (m,
2H), 7.40 (dq, J = 7.7, 1.1 Hz, 1H), 7.21 – 7.11 (m, 1H), 7.12
– 7.03 (m, 1H), 5.04 (dd, J = 5.9, 3.0 Hz, 1H), 4.57 (dd, J =
5.9, 2.5 Hz, 1H), 2.81 – 2.70 (m, 1H), 2.55 (ddd, J = 16.4, 11.2,
7.2 Hz, 1H), 2.11 – 2.00 (m, 1H), 1.67 – 1.53 (m, 1H), 1.49 –
1.35 (m, 2H), 0.88 (d, J = 1.1 Hz, 9H), 0.81 (dd, J = 12.3, 1.0
Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 143.1, 142.3, 136.7,
132.4, 129.8, 129.0, 126.5, 122.4, 119.7, 118.3, 117.4, 115.0,
49.2, 28.7, 27.1, 20.8, 20.7, 15.6, ꢀ0.4, ꢀ0.7. HRMSꢀESI (m/z):
calcd for C24H33N2O2S Si [M + H]+: 441.2027, found 441.2030.
Nꢀ(9ꢀbenzylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)benzenesꢀ
Nꢀ(6,9ꢀdimethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)benzeꢀ
nesulfonamide (3g): Brown solid, 128 mg, 72% yield, m.p.
212.0ꢀ214.0 oC. 1H NMR (400 MHz, CDCl3) δ 8.04 – 7.90 (m,
2H), 7.71 – 7.44 (m, 3H), 7.26 (dd, J = 2.2, 1.2 Hz, 1H), 7.13
(dd, J = 8.3, 1.5 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 4.85 – 4.60
(m, 2H), 3.48 (t, J = 1.2 Hz, 3H), 2.85 – 2.70 (m, 1H), 2.57 –
2.36 (m, 4H), 1.89 – 1.60 (m, 4H). 13C NMR (101 MHz,
CDCl3) δ 141.7, 135.8, 132.8, 131.6, 129.3, 128.3, 126.9,
126.2, 124.0, 118.4, 112.3, 108.8, 46.1, 30.2, 29.1, 21.4, 20.6,
18.0. HRMSꢀESI (m/z): calcd for C20H23O2N2S [M + H]+:
355.1475, found 355.1476.
ulfonamide (3b): White solid, 182 mg, 87% yield, m.p. 216.1ꢀ
1
218.0 . H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.7 Hz,
2H), 7.66 – 7.38 (m, 4H), 7.29 – 7.04 (m, 6H), 6.89 – 6.72 (m,
2H), 5.17 (d, J = 2.8 Hz, 2H), 4.78 (d, J = 8.6 Hz, 1H), 4.66 (d,
J = 8.4 Hz, 1H), 2.96 – 2.77 (m, 1H), 2.61 (dd, J = 10.6, 4.9
Hz, 1H), 1.93 – 1.64 (m, 4H). 13C NMR (101 MHz, CDCl3) δ
141.4, 137.9, 137.1, 132.7, 131.5, 129.2, 128.6, 127.1, 126.9,
126.4, 125.9, 122.7, 119.4, 118.8, 113.6, 109.9, 46.1, 45.8,
30.1, 20.7, 17.7. HRMSꢀESI (m/z): calcd for C25H25N2O2S [M
+ H]+: 417.1631, found 417.1637.
Nꢀ(9ꢀ(4ꢀmethoxybenzyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀ
yl)benzenesulfonamide (3c): White solid, 202 mg, 90% yield,
m.p. 137.7ꢀ140.1 oC. 1H NMR (400 MHz, DMSOꢀd6) δ 8.29 (d,
J = 8.7 Hz, 1H), 7.97 – 7.81 (m, 2H), 7.71 – 7.52 (m, 3H),
7.49 – 7.37 (m, 1H), 7.32 – 7.21 (m, 1H), 7.05 (ddd, J = 8.2,
7.0, 1.2 Hz, 1H), 6.99 – 6.88 (m, 3H), 6.80 (d, J = 8.7 Hz, 2H),
5.33 (d, J = 16.4 Hz, 1H), 5.10 (d, J = 16.4 Hz, 1H), 4.69 –
4.54 (m, 1H), 3.68 (s, 3H), 2.79 – 2.62 (m, 1H), 2.48 – 2.36 (m,
1H), 1.84 (dd, J = 14.5, 8.3 Hz, 1H), 1.64 – 1.47 (m, 3H). 13C
NMR (101 MHz, DMSOꢀd6) δ 158.7, 142.9, 136.8, 132.9,
132.7, 130.7, 129.7, 128.1, 126.7, 126.6, 122.3, 119.2, 118.8,
114.2, 112.5, 110.6, 55.4, 45.9, 45.3, 29.8, 20.8, 17.6. HRMSꢀ
ESI (m/z): calcd for C26H27N2O3S [M + H]+: 447.1737, found
447.1738.
Nꢀ(6ꢀethylꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)bꢀ
enzenesulfonamide (3h): Brown solid, 160 mg, 87% yield, m.p.
157.6ꢀ159.6 oC. 1H NMR (400 MHz, CDCl3) δ 7.99 – 7.93 (m,
2H), 7.67 – 7.59 (m, 1H), 7.56 (dd, J = 8.4, 6.6 Hz, 2H), 7.31
(dd, J = 6.1, 3.0 Hz, 1H), 7.02 – 6.96 (m, 2H), 4.79 (d, J = 8.5
Hz, 1H), 4.68 (d, J = 8.5 Hz, 1H), 3.76 (s, 3H), 3.15 – 3.00 (m,
2H), 2.83 – 2.71 (m, 1H), 2.60 – 2.43 (m, 1H), 1.86 – 1.62 (m,
4H), 1.37 – 1.27 (m, 3H). 13C NMR (101 MHz, CDCl3) δ
141.8, 135.4, 132.8, 132.1, 129.3, 127.9, 127.3, 126.9, 123.9,
119.3, 116.6, 113.3, 46.2, 32.0, 30.2, 25.9, 20.6, 17.7, 16.8.
HRMSꢀESI (m/z): calcd for C21H25N2O2S [M + H]+: 369.1631,
found 369.1636.
Nꢀ(6ꢀmethoxyꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀ
yl)benzenesulfonamide (3i): White solid, 132 mg, 71% yield,
m.p. 174.7ꢀ175.8 oC. 1H NMR (400 MHz, CDCl3) δ 7.94 (ddd,
J = 8.7, 3.2, 1.5 Hz, 2H), 7.70 – 7.48 (m, 3H), 7.13 (dd, J = 8.8,
3.3 Hz, 1H), 6.89 (ddt, J = 10.2, 3.7, 1.9 Hz, 2H), 4.77 (t, J =
4.2 Hz, 2H), 3.84 (s, 3H), 3.47 (s, 3H), 2.73 (dd, J = 15.3, 3.6
Hz, 1H), 2.57 – 2.41 (m, 1H), 1.89 – 1.64 (m, 4H). 13C NMR
(101 MHz, CDCl3) δ 153.8, 141.7, 132.7, 132.7, 132.2, 129.2,
126.9, 126.2, 112.5, 112.3, 109.8, 100.7, 56.0, 46.1, 30.2, 29.2,
20.7, 18.0. HRMSꢀESI (m/z): calcd for C20H23N2O3S [M + H]+:
371.1424, found 371.1429.
Nꢀ(9ꢀ(methoxymethyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀ
yl)benzenesulfonamide (3d): White solid, 135 mg, 71% yield,
m.p. 146.6ꢀ148.4 oC. 1H NMR (400 MHz, CDCl3) δ 7.96 (dt, J
= 6.9, 1.5 Hz, 2H), 7.67 – 7.60 (m, 1H), 7.55 (ddt, J = 8.6, 7.1,
1.5 Hz, 2H), 7.47 (dt, J = 7.8, 1.3 Hz, 1H), 7.43 – 7.34 (m, 1H),
7.29 – 7.18 (m, 1H), 7.12 (ddt, J = 8.5, 7.1, 1.3 Hz, 1H), 5.35
– 5.05 (m, 3H), 4.81 – 4.73 (m, 1H), 3.24 (s, 3H), 2.83 – 2.70
(m, 1H), 2.60 – 2.43 (m, 1H), 2.02 – 1.87 (m, 1H), 1.84 – 1.64
(m, 3H). 13C NMR (101 MHz, CDCl3) δ 141.1, 137.6, 132.8,
131.4, 129.2, 127.1, 126.8, 123.1, 120.1, 118.9, 115.4, 109.6,
Nꢀ(5,8,9ꢀtrimethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)beꢀ
nzenesulfonamide (3j): Yellow solid, 161 mg, 87% yield, m.p.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 11
o
1
150.0ꢀ150.7 C. H NMR (400 MHz, CDCl3) δ 7.96 (dd, J =
7.2, 1.8 Hz, 2H), 7.70 – 7.48 (m, 3H), 6.76 (d, J = 7.2 Hz, 1H),
6.64 (d, J = 7.2 Hz, 1H), 4.80 – 4.54 (m, 2H), 3.76 (s, 3H),
3.17 – 3.03 (m, 1H), 2.85 – 2.72 (m, 1H), 2.68 (s, 3H), 2.57 (s,
3H), 1.86 – 1.72 (m, 2H), 1.69 – 1.60 (m, 2H). 13C NMR (101
MHz, DMSOꢀd6) δ 143.1, 136.0, 132.9, 132.7, 129.7, 128.3,
126.7, 126.0, 124.9, 120.4, 118.7, 112.6, 45.7, 32.1, 29.3, 23.5,
20.3, 20.1, 17.8. HRMSꢀESI (m/z): calcd for C21H25N2O2S [M
+ H]+: 369.1631, found 369.1637.
Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 4.97 – 4.72 (m, 2H), 3.58 (s,
1
2
3
4
5
6
7
8
3H), 2.78 (dt, J = 15.9, 2.6 Hz, 1H), 2.54 (td, J = 10.4, 4.9 Hz,
1H), 1.90 – 1.63 (m, 4H). 13C NMR (101 MHz, CDCl3) δ
141.5, 138.6, 133.6, 132.9, 129.3, 126.8, 125.4, 124.0(q, J =
269.5 Hz), 121.3 (q, J = 31.8 Hz), 119.0 (q, J = 3.5 Hz), 116.4
(q, J = 4.2 Hz), 113.9, 109.3, 45.9, 29.9, 29.4, 20.4, 17.8.
HRMSꢀESI (m/z): calcd for C20H20O2N2F3S [M + H]+:
409.1192, found 409.1194.
Nꢀ(6ꢀcyanoꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)ꢀ
benzenesulfonamide (3p): White solid, 143 mg, 77% yield,
m.p. 275.3ꢀ277.7 oC. 1H NMR (400 MHz, DMSOꢀd6) δ 8.16 (d,
J = 8.2 Hz, 1H), 7.95 (d, J = 1.5 Hz, 1H), 7.91 – 7.82 (m, 2H),
7.63 (tt, J = 8.9, 6.1 Hz, 3H), 7.54 (d, J = 8.6 Hz, 1H), 7.45
(dd, J = 8.5, 1.6 Hz, 1H), 4.70 (dd, J = 8.0, 3.9 Hz, 1H), 3.49
(s, 3H), 2.78 – 2.63 (m, 1H), 2.43 – 2.31 (m, 1H), 1.82 – 1.71
(m, 1H), 1.58 (q, J = 7.7 Hz, 3H). 13C NMR (101 MHz,
DMSOꢀd6) δ 142.7, 138.7, 135.8, 133.0, 129.8, 126.8, 126.0,
124.8, 124.4, 121.2, 113.3, 111.1, 100.8, 45.4, 30.0, 29.6, 20.5,
17.5. HRMSꢀESI (m/z): calcd for C20H20O2N3S [M + H]+:
366.1271, found 366.1273.
Nꢀ(6ꢀfluoroꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)
9
benzenesulfonamide (3k): Brown solid, 155 mg, 85% yield,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
m.p. 218.6ꢀ220.2 C. 1H NMR (400 MHz, CDCl3) δ 8.09 –
o
7.86 (m, 2H), 7.69 – 7.47 (m, 3H), 7.13 (ddd, J = 19.7, 9.2, 3.4
Hz, 2H), 6.96 (td, J = 9.1, 2.5 Hz, 1H), 4.91 – 4.60 (m, 2H),
3.53 (s, 3H), 2.80 – 2.65 (m, 1H), 2.58 – 2.40 (m, 1H), 1.87 –
1.60 (m, 4H). 13C NMR (101 MHz, DMSOꢀd6) δ 157.2 (d, J =
231.7 Hz), 142.9, 135.0, 133.9, 132.9, 129.7, 126.8, 126.2 (d,
J = 9.8 Hz), 112.0 (d, J = 4.8 Hz), 110.8 (d, J = 9.7 Hz), 110.0
(d, J = 25.9 Hz), 103.5 (d, J = 23.0 Hz), 45.6, 30.1, 29.5, 20.7,
17.7. HRMSꢀESI (m/z): calcd for C19H20FN2O2S [M + H]+:
359.1224, found 359.1221.
Methyl 9ꢀmethylꢀ1ꢀ(phenylsulfonamido)ꢀ2,3,4,9ꢀtetrahydroꢀ
Nꢀ(6ꢀchloroꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)
1Hꢀcarbazoleꢀ6ꢀcarboxylate (3q): Pale yellow solid, 164 mg,
o
1
benzenesulfonamide (3l): Brown solid, 144 mg, 76% yield,
82% yield, m.p. 199.3ꢀ200.1 C. H NMR (400 MHz, CDCl3)
δ 8.22 (d, J = 1.7 Hz, 1H), 8.01 – 7.92 (m, 2H), 7.89 (dd, J =
8.7, 1.7 Hz, 1H), 7.71 – 7.49 (m, 3H), 7.23 (d, J = 8.8 Hz, 1H),
4.95 – 4.74 (m, 2H), 3.91 (s, 3H), 3.58 (s, 3H), 2.80 (dt, J =
16.3, 3.1 Hz, 1H), 2.54 (ddd, J = 16.0, 10.4, 5.2 Hz, 1H), 1.89
– 1.63 (m, 4H). 13C NMR (101 MHz, cdcl3) δ 168.2, 141.6,
139.8, 133.2, 132.8, 129.3, 126.8, 125.6, 123.6, 121.7, 120.8,
114.5, 108.6, 51.8, 45.9, 30.0, 29.4, 20.5, 17.8. HRMSꢀESI
(m/z): calcd for C21H23O4N2S [M + H]+: 399.1373, found
399.1373.
o
m.p. 210.0ꢀ212.6 C. 1H NMR (400 MHz, DMSOꢀd6) δ 8.15
(ddd, J = 8.3, 3.8, 2.4 Hz, 1H), 8.02 – 7.84 (m, 2H), 7.73 –
7.57 (m, 3H), 7.45 (dd, J = 3.9, 1.9 Hz, 1H), 7.43 – 7.31 (m,
1H), 7.11 (ddd, J = 8.8, 4.0, 1.9 Hz, 1H), 4.68 (dd, J = 8.1, 4.0
Hz, 1H), 3.45 (s, 3H), 2.65 (dq, J = 15.6, 3.3 Hz, 1H), 2.37 (dd,
J = 15.6, 11.3 Hz, 1H), 1.79 (d, J = 10.5 Hz, 1H), 1.64 – 1.48
(m, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 142.9, 135.7,
134.8, 132.9, 129.7, 127.2, 126.8, 123.6, 121.9, 118.0, 111.8,
111.4, 45.5, 30.1, 29.5, 20.6, 17.7. HRMSꢀESI (m/z): calcd for
C19H20ClN2O2S [M + H]+: 375.0929, found 375.0931.
Nꢀ(8ꢀfluoroꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)ꢀ
Nꢀ(6ꢀbromoꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)
benzenesulfonamide (3m): Brown solid, 150 mg, 71% yield,
m.p. 210.4ꢀ210.7 oC. 1H NMR (400 MHz, DMSOꢀd6) δ 8.15 (d,
J = 8.1 Hz, 1H), 7.90 (dt, J = 8.0, 1.4 Hz, 2H), 7.72 – 7.53 (m,
4H), 7.35 (d, J = 8.7 Hz, 1H), 7.22 (dt, J = 8.7, 1.5 Hz, 1H),
4.68 (dt, J = 7.8, 3.5 Hz, 1H), 3.45 (d, J = 1.2 Hz, 3H), 2.73 –
2.57 (m, 1H), 2.37 (ddd, J = 15.8, 10.9, 5.1 Hz, 1H), 1.78 (q, J
= 7.8, 5.4 Hz, 1H), 1.58 (q, J = 7.8, 6.2 Hz, 3H). 13C NMR
(101 MHz, DMSOꢀd6) δ 142.8, 135.9, 134.6, 132.9, 129.7,
127.9, 126.8, 124.4, 121.0, 111.9, 111.7, 111.5, 45.5, 30.1,
29.4, 20.6, 17.7. HRMSꢀESI (m/z): calcd for
C19H19BrN2NaO2S [M + Na]+: 441.0243, found 441.0247.
benzenesulfonamide (3r): White solid, 140 mg, 78% yield, m.p.
o
184.3ꢀ185.4 C. 1H NMR (400 MHz, CDCl3) δ 7.91 (dt, J =
8.5, 1.3 Hz, 2H), 7.65 – 7.56 (m, 1H), 7.52 (ddd, J = 8.5, 6.7,
1.4 Hz, 2H), 7.17 (d, J = 7.7 Hz, 1H), 6.91 (tdd, J = 7.9, 4.5,
1.3 Hz, 1H), 6.87 – 6.78 (m, 1H), 4.80 (d, J = 8.7 Hz, 1H),
4.72 (q, J = 4.9, 3.9 Hz, 1H), 3.66 (s, 3H), 2.73 (dd, J = 16.6,
4.5 Hz, 1H), 2.49 (td, J = 10.1, 5.0 Hz, 1H), 1.93 – 1.53 (m,
4H). 13C NMR (101 MHz, CDCl3) δ 150.1 (d, J = 243.9 Hz),
141.5, 132.8, 132.8, 130.0 (d, J = 5.7 Hz), 129.3, 126.8, 125.1
(d, J = 8.9 Hz), 119.1 (d, J = 6.5 Hz), 114.4 (d, J = 3.4 Hz),
113.7 (d, J = 1.7 Hz), 108.1 (d, J = 18.3 Hz), 45.7, 31.6 (d, J =
6.4 Hz), 30.1, 20.7, 17.6. HRMSꢀESI (m/z): calcd for
C19H20FN2O2S [M + H]+: 359.1224, found 359.1227.
Nꢀ(5,7ꢀdichloroꢀ9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1
ꢀyl)benzenesulfonamide (3n): Pale yellow solid, 157 mg, 76%
yield, m. p. 235.3ꢀ237.5 oC. 1H NMR (400 MHz, DMSOꢀd6) δ
8.18 (d, J = 8.2 Hz, 1H), 7.94 – 7.84 (m, 2H), 7.73 – 7.58 (m,
3H), 7.53 (d, J = 1.6 Hz, 1H), 7.05 (d, J = 1.6 Hz, 1H), 4.68
(dd, J = 8.0, 3.9 Hz, 1H), 3.46 (s, 3H), 3.08 – 2.93 (m, 1H),
2.61 (ddd, J = 16.4, 11.0, 5.5 Hz, 1H), 1.76 (dd, J = 12.2, 6.9
Hz, 1H), 1.53 (dt, J = 10.4, 3.6 Hz, 3H). 13C NMR (101 MHz,
DMSOꢀd6) δ 142.8, 138.4, 135.5, 133.0, 130.0, 126.8, 126.5,
126.0, 122.0, 119.3, 112.0, 109.3, 45.4, 30.0, 29.3, 22.6, 17.6.
HRMSꢀESI (m/z): calcd for C19H18O2N2Cl2NaS [M + Na]+:
431.0358, found 431.0359.
Nꢀ(3,3,9ꢀtrimethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)beꢀ
nzenesulfonamide (3s): White solid, 121 mg, 66% yield, m.p.
223.3ꢀ226.3 oC. 1H NMR (400 MHz, CDCl3) δ 8.11 – 7.90 (m,
2H), 7.68 – 7.62 (m, 1H), 7.58 (ddd, J = 8.5, 6.5, 1.6 Hz, 2H),
7.44 (dt, J = 7.9, 1.0 Hz, 1H), 7.28 (dt, J = 8.1, 1.0 Hz, 1H),
7.22 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.08 (ddd, J = 7.9, 6.8, 1.2
Hz, 1H), 4.84 (dt, J = 11.5, 6.0 Hz, 1H), 4.57 (d, J = 9.9 Hz,
1H), 3.71 (s, 3H), 2.61 – 2.37 (m, 2H), 1.61 (dd, J = 13.6, 6.0
Hz, 1H), 1.36 (dd, J = 13.6, 6.1 Hz, 1H), 0.97 (s, 3H), 0.88 (s,
3H). 13C NMR (101 MHz, DMSOꢀd6) δ 142.9, 138.0, 133.0,
131.6, 129.7, 126.8, 126.5, 121.9, 118.9, 118.5, 111.2, 109.7,
47.0, 44.5, 34.9, 31.7, 30.5, 30.4, 26.5. HRMSꢀESI (m/z):
calcd for C21H25O2N2S [M + H]+: 369.1631, found 369.1634.
Nꢀ(9ꢀmethylꢀ6ꢀ(trifluoromethyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarꢀ
bazolꢀ1ꢀyl)benzenesulfonamide (3o): White solid, 154 mg, 76%
o
1
yield, m.p. 182.4ꢀ184.0 C. H NMR (400 MHz, CDCl3) δ
8.04 – 7.90 (m, 2H), 7.75 (s, 1H), 7.61 (dd, J = 7.3, 1.7 Hz,
1H), 7.54 (ddd, J = 8.8, 6.7, 1.7 Hz, 2H), 7.44 (dd, J = 8.7, 1.8
Nꢀ(4ꢀmethylꢀ1,2,3,4ꢀtetrahydrocyclopenta[b]indolꢀ3ꢀyl)benꢀ
zenesulfonamide (3t): White solid, 106 mg, 63% yield, m.p.
180.6ꢀ181.2 oC. 1H NMR (400 MHz, CDCl3) δ 7.99 – 7.88 (m,
ACS Paragon Plus Environment

Page 7 of 11
The Journal of Organic Chemistry
o
1
2H), 7.62 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.6 Hz, 2H), 7.43 (d,
76% yield, m.p. 249.3ꢀ250.8 C. H NMR (400 MHz, CDCl3)
δ 7.96 (dt, J = 8.6, 1.5 Hz, 2H), 7.68 – 7.61 (m, 1H), 7.57 (ddd,
J = 8.7, 6.6, 1.7 Hz, 2H), 7.47 – 7.41 (m, 1H), 7.33 – 7.26 (m,
1H), 7.25 – 7.19 (m, 1H), 7.09 (ddt, J = 7.9, 6.8, 1.1 Hz, 1H),
5.83 – 5.71 (m, 1H), 4.98 (dd, J = 10.5, 4.8 Hz, 1H), 4.02 (ddd,
J = 7.4, 5.4, 1.8 Hz, 1H), 3.89 (td, J = 6.6, 5.7, 1.8 Hz, 2H),
3.74 – 3.55 (m, 4H), 3.07 – 2.78 (m, 2H), 2.02 (ddd, J = 13.9,
5.0, 1.7 Hz, 1H), 1.61 (dd, J = 13.9, 2.0 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ 141.7, 138.0, 132.8, 130.8, 129.3, 127.0,
125.7, 122.5, 119.2, 118.5, 109.3, 109.3, 109.1, 64.6, 64.5,
46.8, 36.4, 32.1, 29.5. HRMSꢀESI (m/z): calcd for
C21H23N2O4S [M + H]+: 399.1373, found 399.1373.
1
2
3
4
5
6
7
8
J = 7.9 Hz, 1H), 7.27–7.26 (m, 2H), 7.12 – 7.05 (m, 1H), 5.03
(t, J = 8.5 Hz, 1H), 4.67 (d, J = 9.9 Hz, 1H), 3.61 (s, 3H), 2.84
(t, J = 8.6 Hz, 1H), 2.73 – 2.52 (m, 2H), 1.96 (t, J = 10.0 Hz,
1H). 13C NMR (101 MHz, DMSOꢀd6) δ 143.1, 142.2, 142.1,
132.9, 129.7, 127.0, 123.4, 121.5, 119.31, 119.30, 119.1,
110.5, 52.2, 37.3, 30.3, 22.7. HRMSꢀESI (m/z): calcd for
C18H19N2O2S [M + H]+: 327.1162, found 327.1166.
Nꢀ(5ꢀmethylꢀ5,6,7,8,9,10ꢀhexahydrocyclohepta[b]indolꢀ6ꢀy
l)benzenesulfonamide (3u): White solid, 180 mg, 83% yield,
m.p. 140.7ꢀ141.8 oC. 1H NMR (400 MHz, CDCl3) δ 7.81 (dt, J
= 8.3, 1.2 Hz, 2H), 7.56 – 7.34 (m, 4H), 7.24 – 7.13 (m, 2H),
7.11 – 6.99 (m, 1H), 4.96 (td, J = 6.7, 6.1, 3.4 Hz, 1H), 4.78 (d,
J = 7.2 Hz, 1H), 3.46 (s, 3H), 2.93 (ddd, J = 15.7, 6.6, 2.4 Hz,
1H), 2.64 (ddd, J = 15.5, 11.3, 2.6 Hz, 1H), 2.19 – 2.06 (m,
1H), 1.99 – 1.71 (m, 4H), 1.65 – 1.57 (m, 1H). 13C NMR (101
MHz, CDCl3) δ 141.1, 136.0, 135.0, 132.5, 128.9, 127.0,
126.7, 122.1, 119.0, 118.5, 115.6, 109.2, 49.4, 31.8, 29.2, 28.1,
24.0, 23.5. HRMSꢀESI (m/z): calcd for C20H23N2O2S [M + H]+:
355.1475, found 355.1478.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(1,9ꢀdimethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)benzeꢀ
nesulfonamide (3z): White solid, 97 mg, 55% yield,
o
1
m.p.165.8ꢀ168.0 C. H NMR (400 MHz, CDCl3) δ 7.92 –
7.78 (m, 2H), 7.61 – 7.38 (m, 4H), 7.28 – 7.15 (m, 2H), 7.13 –
7.01 (m, 1H), 4.87 (s, 1H), 3.64 (s, 3H), 2.74 – 2.56 (m, 2H),
2.36 – 2.20 (m, 1H), 1.93 – 1.64 (m, 6H). 13C NMR (101 MHz,
CDCl3) δ 142.6, 137.6, 135.4, 132.5, 128.9, 127.0, 125.9,
122.4, 119.2, 118.8, 112.4, 108.9, 56.7, 40.4, 31.4, 25.7, 21.4,
20.4. HRMSꢀESI (m/z): calcd for C20H23N2O2S [M + H]+:
355.1475, found 355.1473.
Nꢀ(2ꢀethylꢀ5ꢀmethylꢀ5,6,7,8,9,10ꢀhexahydrocyclohepta[b]ꢀ
indolꢀ6ꢀyl)benzenesulfonamide (3v): Yellow solid, 148 mg, 76%
o
1
yield, m.p. 170.1ꢀ172.2 C. H NMR (400 MHz, CDCl3) δ
7.92 – 7.79 (m, 2H), 7.64 – 7.48 (m, 1H), 7.48 – 7.36 (m, 2H),
7.31 (dt, J = 7.5, 1.1 Hz, 1H), 7.08 – 6.91 (m, 2H), 4.97 (t, J =
6.5 Hz, 1H), 4.74 (d, J = 7.3 Hz, 1H), 3.71 (s, 3H), 3.03 (q, J =
7.5 Hz, 2H), 2.93 – 2.82 (m, 1H), 2.68ꢀ2.58 (m, 1H), 2.17 –
2.07 (m, 1H), 1.94 – 1.70 (m, 4H), 1.60 (dd, J = 5.7, 2.9 Hz,
1H), 1.31 (td, J = 7.5, 0.9 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 141.2, 135.5, 134.3, 132.5, 128.9, 128.0, 127.5,
126.8, 123.8, 119.2, 116.5, 116.2, 49.5, 32.0, 31.6, 27.9, 26.2,
23.8, 23.3, 16.7. HRMSꢀESI (m/z): calcd for C22H26N2NaO2S
[M + Na]+: 405.1607, found 405.1609.
Nꢀ(1ꢀ(1,3ꢀdimethylꢀ1Hꢀindolꢀ2ꢀyl)ethyl)benzenesulfonamide
o
(3aa): White solid, 116 mg, 71% yield, m.p. 114.8ꢀ117.6 C.
1H NMR (400 MHz, CDCl3) δ 7.49 (dq, J = 8.5, 1.3 Hz, 2H),
7.44 – 7.35 (m, 1H), 7.31 – 7.24 (m, 1H), 7.20 – 7.13 (m, 1H),
7.12 – 7.00 (m, 4H), 5.16 (d, J = 4.7 Hz, 1H), 5.03 – 4.93 (m,
1H), 3.50 (s, 3H), 2.16 (s, 3H), 1.61 (dt, J = 7.2, 1.2 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 139.6, 136.7, 133.2, 132.1,
128.3, 127.7, 126.6, 121.8, 118.9, 118.6, 108.7, 108.6, 45.8,
30.3, 21.1, 8.8. HRMSꢀESI (m/z): calcd for C18H21O2N2S [M +
H]+: 329.1318, found 329.1318.
4ꢀmethylꢀNꢀ(9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)
benzenesulfonamide (3ab): Brown solid, 120 mg, 68% yield,
m.p. 186.1ꢀ186.9 oC. 1H NMR (400 MHz, CDCl3) δ 7.82 (dt, J
= 8.3, 1.9 Hz, 2H), 7.54 – 7.42 (m, 1H), 7.33 (d, J = 8.0 Hz,
2H), 7.25 (dtt, J = 7.9, 3.0, 1.5 Hz, 2H), 7.08 (ddd, J = 8.0, 6.5,
1.7 Hz, 1H), 4.78 (dd, J = 8.6, 3.0 Hz, 1H), 4.69 (dd, J = 8.7,
3.7 Hz, 1H), 3.55 (s, 3H), 2.86 – 2.73 (m, 1H), 2.60 – 2.43 (m,
4H), 1.86 – 1.64 (m, 4H). 13C NMR (101 MHz, CDCl3) δ
143.5, 138.8, 137.3, 131.8, 129.8, 126.9, 126.1, 122.3, 119.0,
118.7, 112.8, 109.1, 46.0, 30.1, 29.1, 21.6, 20.6, 18.0. HRMSꢀ
ESI (m/z): calcd for C20H23N2O2S [M + H]+: 355.1475, found
355.1479.
Nꢀ(5ꢀmethylꢀ6,7,8,9,10,11ꢀhexahydroꢀ5Hꢀcycloocta[b]indol
ꢀ6ꢀyl)benzenesulfonamide (3w): Pale yellow solid, 123 mg, 67%
o
1
yield, m.p. 170.8ꢀ172.6 C. H NMR (400 MHz, CDCl3) δ
7.67 (dd, J = 8.5, 2.2 Hz, 2H), 7.50 – 7.37 (m, 2H), 7.34 – 7.24
(m, 2H), 7.18 (d, J = 7.9 Hz, 2H), 7.07 (ddt, J = 7.7, 3.9, 1.6
Hz, 1H), 5.17 – 5.03 (m, 1H), 5.02 – 4.87 (m, 1H), 3.56 (s,
3H), 3.10 – 2.88 (m, 1H), 2.77 – 2.61 (m, 1H), 2.11 (d, J =
11.7 Hz, 1H), 1.90 (ddd, J = 14.0, 6.8, 3.5 Hz, 1H), 1.76 –
1.65(m, 1H), 1.62ꢀ1.43 (m, 3H), 1.31 – 1.08 (m, 2H). 13C
NMR (101 MHz, CDCl3) δ 140.3, 136.9, 132.5, 132.5, 128.7,
126.8, 126.8, 121.6, 118.8, 118.2, 113.4, 108.8, 50.3, 34.8,
30.1, 29.4, 25.6, 23.2, 22.2. HRMSꢀESI (m/z): calcd for
C21H25O2N2S [M + H]+: 369.1631, found 369.1631.
2ꢀmethylꢀNꢀ(9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)
benzenesulfonamide (3ac): Brown solid, 160 mg, 90% yield,
o
1
Nꢀ(5ꢀmethylꢀ2ꢀtosylꢀ2,3,4,5ꢀtetrahydroꢀ1Hꢀpyrido[4,3ꢀb]inꢀ
m.p. 208.5ꢀ210.8 C. H NMR (400 MHz, CDCl3) δ 8.22 –
8.02 (m, 1H), 7.61 – 7.44 (m, 2H), 7.42 – 7.31 (m, 2H), 7.30 –
7.17 (m, 2H), 7.09 (ddd, J = 7.9, 6.5, 1.4 Hz, 1H), 4.84 – 4.70
(m, 2H), 3.55 (s, 3H), 2.87 – 2.74 (m, 1H), 2.64 (s, 3H), 2.54
(dt, J = 10.4, 4.2 Hz, 1H), 1.92 – 1.62 (m, 4H). 13C NMR (101
MHz, CDCl3) δ 139.5, 137.3, 136.8, 132.9, 132.6, 131.7,
129.2, 126.4, 126.0, 122.4, 119.1, 118.7, 112.8, 109.1, 45.9,
30.1, 29.0, 20.6, 20.3, 18.1. HRMSꢀESI (m/z): calcd for
C20H23N2O2S [M + H]+: 355.1475, found 355.1477.
dolꢀ4ꢀyl)benzenesulfonamide (3x): White solid, 143 mg, 58%
o
1
yield, m.p. 112.9ꢀ114.2 C. H NMR (400 MHz, CDCl3) δ
8.12 – 7.98 (m, 2H), 7.74 – 7.68 (m, 1H), 7.65 (ddd, J = 8.5,
6.4, 1.5 Hz, 2H), 7.57 – 7.49 (m, 2H), 7.40 (dd, J = 7.9, 1.3 Hz,
1H), 7.32 – 7.28 (m, 3H), 7.27 – 7.23 (m, 1H), 7.10 (ddd, J =
8.0, 6.8, 1.4 Hz, 1H), 5.27 (dd, J = 10.1, 1.8 Hz, 1H), 4.83 (d,
J = 13.7 Hz, 1H), 4.75 (d, J = 10.2 Hz, 1H), 3.78ꢀ3.66 (m, 4H),
3.47 (d, J = 12.4 Hz, 1H), 2.58 (dt, J = 12.4, 2.0 Hz, 1H), 2.41
(s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 144.1, 142.0, 137.4,
133.4, 133.1, 130.5, 130.3, 129.8, 127.8, 127.1, 123.9, 122.6,
119.6, 118.7, 110.1, 107.6, 50.5, 45.6, 43.2, 29.1, 21.4.
HRMSꢀESI (m/z): calcd for C25H26O4N3S2 [M + H]+: 496.1359,
found 496.1360.
4ꢀfluoroꢀNꢀ(9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)
benzenesulfonamide (3ad): White solid, 159 mg, 89% yield,
o
m.p. 183.1ꢀ184.2 C. 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J
= 8.1 Hz, 1H), 8.07 – 7.90 (m, 2H), 7.61 – 7.28 (m, 4H), 7.13
(ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 6.99 (ddd, J = 7.9, 7.0, 1.0 Hz,
1H), 4.71 (dt, J = 7.4, 3.4 Hz, 1H), 3.47 (s, 3H), 2.69 (ddd, J =
15.7, 5.4, 2.2 Hz, 1H), 2.49 – 2.32 (m, 1H), 1.93 – 1.76 (m,
Nꢀ(9ꢀmethylꢀ1,2,4,9ꢀtetrahydrospiro[carbazoleꢀ3,2'ꢀ[1,3]diꢀ
oxolan]ꢀ1ꢀyl)benzenesulfonamide (3y): White solid, 152 mg,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 11
1H), 1.64 (q, J = 6.8, 5.6 Hz, 3H). 13C NMR (101 MHz, HRMSꢀESI (m/z): calcd for C18H19N2O2S [M + H]+: 327.1162,
1
2
3
4
5
6
7
8
DMSOꢀd6) δ 151.0 (d, J = 152.8 Hz), 139.5, 137.3, 132.9,
129.9, 129.8, 126.2, 122.1, 118.8 (d, J = 22.1 Hz), 116.9 (d, J
= 22.7 Hz), 112.0, 109.7, 45.7, 30.3, 29.3, 20.8, 17.8. HRMSꢀ
ESI (m/z): calcd for C19H19FN2NaO2S [M + Na]+: 381.1043,
found 381.1036.
found 327.1165.
(E)ꢀNꢀ((1ꢀmethylꢀ3ꢀpropylꢀ1Hꢀindolꢀ2ꢀyl)methylene)benzenꢀ
esulfonamide (4c): Yellow solid, 110 mg, 64% yield, m.p.
o
1
112.8ꢀ115.0 C. H NMR (400 MHz, CDCl3) δ 9.13 (s, 1H),
8.04 – 7.96 (m, 2H), 7.66 (dt, J = 8.4, 1.0 Hz, 1H), 7.62 – 7.56
(m, 1H), 7.53 (ddd, J = 8.3, 6.8, 1.2 Hz, 2H), 7.40 (ddd, J =
8.1, 6.8, 1.1 Hz, 1H), 7.29 (d, J = 8.7 Hz, 1H), 7.11 (ddd, J =
7.7, 6.9, 0.9 Hz, 1H), 4.03 (s, 3H), 2.99 (t, J = 7.5 Hz, 2H),
1.69 (q, J = 7.4 Hz, 2H), 0.99 – 0.90 (m, 3H). 13C NMR (101
MHz, CDCl3) δ 158.0, 141.7, 139.4, 135.3, 133.1, 129.1,
128.2, 128.0, 127.5, 126.6, 121.5, 120.4, 110.4, 32.4, 26.4,
25.3, 14.0. HRMSꢀESI (m/z): calcd for C19H21N2O2S [M + H]+:
341.1318, found 341.1323.
4ꢀchloroꢀNꢀ(9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)
benzenesulfonamide (3ae): Pale brown solid, 155 mg, 83%
o
1
yield, m.p. 169.9ꢀ172.8 C. H NMR (400 MHz, CDCl3) δ
7.85 (d, J = 8.4 Hz, 2H), 7.48 (dd, J = 14.4, 8.1 Hz, 3H), 7.31
– 7.16 (m, 2H), 7.12 – 6.96 (m, 1H), 4.87 – 4.66 (m, 2H), 3.56
(s, 3H), 2.87 – 2.67 (m, 1H), 2.53 (ddd, J = 15.6, 10.2, 4.7 Hz,
1H), 1.86 – 1.59 (m, 4H). 13C NMR (101 MHz, CDCl3) δ
140.3, 139.2, 137.3, 131.3, 129.5, 128.3, 126.0, 122.5, 119.1,
118.7, 112.9, 109.1, 46.2, 30.2, 29.2, 20.6, 17.9. HRMSꢀESI
(m/z): calcd for C19H20ClN2O2S [M + H]+: 375.0929, found
375.0925.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(E)ꢀNꢀ((3ꢀisopropylꢀ1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methylene)benꢀ
zenesulfonamide (4d): Brown solid, 146 mg, 84% yield, m.p.
133.2ꢀ134.9 oC. 1H NMR (400 MHz, CDCl3) δ 9.27 (d, J = 1.5
Hz, 1H), 8.09 – 7.96 (m, 2H), 7.85 (d, J = 8.3 Hz, 1H), 7.68 –
7.50 (m, 3H), 7.44 – 7.36 (m, 1H), 7.32 (d, J = 8.6 Hz, 1H),
7.11 (t, J = 7.6 Hz, 1H), 4.04 (s, 3H), 3.72 – 3.45 (m, 1H),
1.52 (d, J = 7.0 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 157.9,
142.1, 140.9, 139.4, 133.1, 129.1, 127.9, 127.5, 126.7, 124.9,
123.0, 120.2, 110.6, 32.6, 26.4, 23.9. HRMSꢀESI (m/z): calcd
for C19H21N2O2S [M + H]+: 341.1318, found 341.1314.
Nꢀ(9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)ꢀ4ꢀ(trifluꢀ
oromethoxy)benzenesulfonamide (3af): White solid, 189 mg,
o
1
89% yield, m.p. 150.8ꢀ152.5 C. H NMR (400 MHz, CDCl3)
δ 7.97 (d, J = 8.5 Hz, 2H), 7.54 – 7.44 (m, 1H), 7.37 (d, J =
8.4 Hz, 2H), 7.29 – 7.20 (m, 2H), 7.11 (ddd, J = 8.1, 5.4, 2.6
Hz, 1H), 4.98 (d, J = 8.5 Hz, 1H), 4.81 (d, J = 8.7 Hz, 1H),
3.54 (s, 3H), 2.81 (dd, J = 15.4, 4.3 Hz, 1H), 2.57 (dd, J = 15.1,
9.4 Hz, 1H), 1.88 – 1.62 (m, 4H). 13C NMR (101 MHz, CDCl3)
δ 152.2, 140.2, 137.4, 131.3, 129.0, 126.0, 122.6, 121.1, 119.2,
118.7, 113.1, 109.1, 46.2, 30.3, 29.1, 20.6, 17.9. HRMSꢀESI
(m/z): calcd for C20H20F3N2O3S [M + H]+: 425.1147, found
425.1141.
(E)ꢀNꢀ((3ꢀisobutylꢀ1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methylene)benzꢀ
enesulfonamide (4e): Brown solid, 162 mg, 91% yield, m.p.
o
1
143.3ꢀ144.5 C. H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H),
8.04 – 7.97 (m, 2H), 7.70 – 7.58 (m, 2H), 7.55 (ddt, J = 8.4,
6.7, 1.3 Hz, 2H), 7.41 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.31 (dq,
J = 8.6, 1.2 Hz, 1H), 7.12 (ddd, J = 8.0, 6.8, 1.0 Hz, 1H), 4.05
(s, 3H), 2.89 (d, J = 7.2 Hz, 2H), 1.94 (dt, J = 13.5, 6.7 Hz,
1H), 0.94 (d, J = 6.6 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ
158.2, 141.6, 139.3, 134.3, 133.1, 129.1, 128.4, 128.2, 127.6,
127.0, 121.7, 120.4, 110.3, 33.5, 32.5, 31.0, 22.7. HRMSꢀESI
(m/z): calcd for C20H23N2O2S [M + H]+: 355.1475, found
355.1469.
Nꢀ(9ꢀmethylꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀyl)methanesꢀ
ulfonamide (3ag): Pale yellow solid, 103 mg, 74% yield, m.p.
118.0ꢀ118.9 oC. 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.9
Hz, 1H), 7.25 (dt, J = 14.6, 8.1 Hz, 2H), 7.15 – 6.99 (m, 1H),
4.89 (dt, J = 7.8, 3.5 Hz, 1H), 4.60 (d, J = 8.6 Hz, 1H), 3.72 (s,
3H), 3.04 (s, 3H), 2.84 (ddd, J = 16.0, 5.6, 2.4 Hz, 1H), 2.61
(ddd, J = 16.1, 11.0, 5.6 Hz, 1H), 2.28 – 2.09 (m, 1H), 2.08 –
1.92 (m, 2H), 1.82 (dddd, J = 13.4, 10.8, 5.3, 3.0 Hz, 1H). 13C
NMR (101 MHz, CDCl3) δ 137.3, 131.7, 126.0, 122.4, 119.1,
118.7, 112.7, 109.1, 45.9, 43.0, 31.3, 29.4, 20.7, 18.1. HRMSꢀ
ESI (m/z): calcd for C14H19N2O2S [M + H]+: 279.1162, found
279.1157.
(E)ꢀNꢀ((3ꢀ(2ꢀ((tertꢀbutyldimethylsilyl)oxy)ethyl)ꢀ1ꢀmethylꢀ1
Hꢀindolꢀ2ꢀyl)methylene)benzenesulfonamide (4f): Yellow solꢀ
o
1
id, 185 mg, 81% yield, m.p. 105.9ꢀ107.2 C. H NMR (400
MHz, CDCl3) δ 9.22 – 9.11 (m, 1H), 8.09 – 7.97 (m, 2H), 7.69
(d, J = 8.2 Hz, 1H), 7.64 – 7.57 (m, 1H), 7.54 (t, J = 7.8 Hz,
2H), 7.42 (t, J = 7.7 Hz, 1H), 7.32 (d, J = 8.6 Hz, 1H), 7.14 (t,
J = 7.5 Hz, 1H), 4.06 (s, 3H), 3.83 (t, J = 6.6 Hz, 2H), 3.25 (t,
J = 6.6 Hz, 2H), 0.79 (s, 9H), 0 (s, 6H). 13C NMR (101 MHz,
CDCl3) δ 158.6, 141.5, 139.5, 133.0, 131.4, 129.0, 128.8,
128.1, 127.5, 126.8, 121.4, 120.5, 110.3, 63.7, 32.5, 28.2, 25.9,
18.3, ꢀ5.5. HRMSꢀESI (m/z): calcd for C24H33N2O3SSi [M +
H]+: 457.1976, found 457.1977.
(E)ꢀNꢀ((1ꢀbenzylꢀ3ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methylene)benzenꢀ
esulfonamide (4a): Pale yellow solid, 120 mg, 62% yield, m.p.
146.5ꢀ148.5 oC. 1H NMR (400 MHz, CDCl3) δ 9.16 (d, J = 1.2
Hz, 1H), 7.75 (dt, J = 8.5, 1.3 Hz, 2H), 7.69 (dt, J = 8.1, 1.2
Hz, 1H), 7.52 (td, J = 7.4, 1.3 Hz, 1H), 7.39 (td, J = 7.5, 6.8,
1.2 Hz, 3H), 7.33 (dd, J = 8.5, 1.2 Hz, 1H), 7.20 – 7.12 (m,
1H), 7.12 – 7.00 (m, 3H), 6.86 (dd, J = 6.9, 1.6 Hz, 2H), 5.80
(s, 2H), 2.63 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 157.6,
141.6, 139.4, 137.7, 132.8, 131.2, 128.9, 128.7, 128.4, 127.8,
127.4, 127.3, 127.0, 126.3, 121.5, 120.7, 110.7, 48.2, 9.6.
HRMSꢀESI (m/z): calcd for C23H21N2O2S [M + H]+: 389.1318,
found 389.1319.
(E)ꢀNꢀ((3ꢀbenzylꢀ1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methylene)benzenꢀ
esulfonamide (4g): Yellow solid, 137 mg, 70% yield, m.p.
185.4ꢀ187.1 oC. 1H NMR (400 MHz, CDCl3) δ 9.21 (d, J = 1.0
Hz, 1H), 7.91 (dt, J = 8.3, 1.2 Hz, 2H), 7.65 – 7.54 (m, 2H),
7.50 (ddd, J = 8.3, 6.7, 1.2 Hz, 2H), 7.44 – 7.37 (m, 1H), 7.31
(dd, J = 8.5, 1.1 Hz, 1H), 7.25 – 7.13 (m, 5H), 7.10 (ddt, J =
8.0, 6.8, 1.1 Hz, 1H), 4.40 (s, 2H), 4.05 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 158.5, 141.6, 140.0, 139.1, 133.1, 132.2,
129.1, 128.6, 128.2, 128.2, 128.2, 127.6, 126.7, 126.4, 121.7,
120.9, 110.4, 32.4, 30.3. HRMSꢀESI (m/z): calcd for
C23H21N2O2S [M + H]+: 389.1318, found 389.1322.
(E)ꢀNꢀ((3ꢀethylꢀ1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methylene)benzeneꢀ
sulfonamide (4b): Pale green solid, 118 mg, 72% yield, m.p.
113.9ꢀ116.8 oC. 1H NMR (400 MHz, CDCl3) δ 9.17 (d, J = 3.0
Hz, 1H), 8.09 – 7.93 (m, 2H), 7.69 (dd, J = 8.1, 3.1 Hz, 1H),
7.65 – 7.52 (m, 3H), 7.42 (dt, J = 7.4, 4.9 Hz, 1H), 7.31 (dd, J
= 8.5, 3.1 Hz, 1H), 7.18 – 7.08 (m, 1H), 4.04 (s, 3H), 3.24 –
2.91 (m, 2H), 1.42 – 1.18 (m, 3H). 13C NMR (101 MHz,
CDCl3) δ 157.8, 141.7, 139.4, 137.0, 133.1, 129.1, 128.3,
127.5, 127.3, 126.1, 121.4, 120.4, 110.4, 32.4, 17.9, 17.0.
(E)ꢀNꢀ((3ꢀ(4ꢀmethoxyphenyl)ꢀ1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methꢀ
ylene)benzenesulfonamide (4h): Yellow solid, 137 mg, 68%
yield, m.p. 136.0ꢀ137.7 C. H NMR (400 MHz, CDCl3) δ
o
1
ACS Paragon Plus Environment

Page 9 of 11
The Journal of Organic Chemistry
7.35 (m, 1H), 7.34 – 7.27 (m, 2H), 7.12 – 7.01 (m, 2H), 6.84
8.95 (s, 1H), 8.00 – 7.92 (m, 2H), 7.69 (d, J = 8.2 Hz, 1H),
1
2
3
4
5
6
7
8
7.58 (d, J = 7.3 Hz, 1H), 7.52 (dd, J = 8.4, 6.7 Hz, 2H), 7.49 –
7.42 (m, 1H), 7.39 – 7.31 (m, 3H), 7.15 (t, J = 7.5 Hz, 1H),
7.05 (d, J = 8.5 Hz, 2H), 4.13 (s, 3H), 3.89 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 160.7, 159.8, 141.5, 139.2, 135.1, 133.1,
131.8, 129.1, 128.4, 127.8, 127.6, 126.1, 124.1, 122.3, 121.3,
114.5, 110.4, 55.4, 32.7. HRMSꢀESI (m/z): calcd for
C23H21N2O3S [M + H]+: 405.1267, found 405.1261.
(dt, J = 8.7, 1.8 Hz, 2H), 5.61 (d, J = 16.3 Hz, 1H), 5.46 (d, J
= 16.5 Hz, 1H), 5.38 (s, 1H), 4.99 (s, 1H), 4.87 (d, J = 2.2 Hz,
1H), 4.23 (d, J = 16.4 Hz, 1H), 3.77 (t, J = 1.9 Hz, 4H), 3.18 (s,
1H), 2.28 – 2.17 (m, 1H), 1.72 – 1.59 (m, 1H). 13C NMR (101
MHz, CDCl3) δ 191.1, 159.2, 144.7, 140.2, 137.7, 137.6,
133.1, 129.4, 128.4, 127.6, 127.2, 124.6, 123.9, 123.3, 122.2,
114.4, 114.4, 114.1, 110.7, 55.3, 51.4, 46.5, 46.2, 45.4, 33.2.
HRMSꢀESI (m/z): calcd for C29H27N2O4S [M + H]+: 499.1686,
found 499.1683.
(E)ꢀNꢀ((3ꢀ(4ꢀchlorophenyl)ꢀ1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methylꢀ
ene)benzenesulfonamide (4i): Yellow solid, 164 mg, 80%
9
o
1
yield, m.p. 185.3ꢀ187.5 C. H NMR (400 MHz, CDCl3) δ
8.91 (s, 1H), 7.99 – 7.92 (m, 2H), 7.62 (dd, J = 16.3, 7.7 Hz,
2H), 7.57 – 7.43 (m, 5H), 7.37 (dd, J = 19.2, 8.3 Hz, 3H), 7.18
(t, J = 7.5 Hz, 1H), 4.15 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 160.1, 141.3, 138.8, 134.5, 133.3, 133.3, 131.8, 130.3, 129.2,
129.1, 128.5, 127.8, 127.7, 125.9, 121.8, 121.7, 110.5, 32.8.
HRMSꢀESI (m/z): calcd for C22H18ClN2O2S [M + H]+:
409.0772, found 409.0779.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Single Crystal Data for 3d
Single Crystal Data for 4d
Copies of 1H and 13C NMR spectra for all products (PDF)
CIF data for 3d (CIF)
(E)ꢀNꢀ((3ꢀ(4ꢀbromophenyl)ꢀ1,5ꢀdimethylꢀ1Hꢀindolꢀ2ꢀyl)meꢀ
thylene)benzenesulfonamide (4j): Yellow solid, 133 mg, 56%
CIF data for 4d (CIF)
o
1
yield, m.p. 164.6ꢀ166.5 C. H NMR (400 MHz, CDCl3) δ
8.89 (d, J = 1.0 Hz, 1H), 8.11 – 7.91 (m, 2H), 7.68 – 7.63 (m,
2H), 7.62 – 7.58 (m, 1H), 7.57 – 7.48 (m, 2H), 7.40 (q, J = 1.2
Hz, 1H), 7.33 – 7.27 (m, 4H), 4.13 (s, 3H), 2.41 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 160.0, 140.0, 138.9, 133.2, 132.7,
132.1, 132.1, 131.3, 131.0, 130.7, 129.1, 127.7, 127.6, 126.0,
122.6, 120.7, 110.3, 32.9, 21.4. HRMSꢀESI (m/z): calcd for
C23H20BrN2O2S [M + H]+: 467.0429, found 467.0422.
■ AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: pjliu@zmc.edu.cn
ORCID
Peijun Liu: 0000ꢀ0001ꢀ9507ꢀ8238
Notes
The authors declare no competing financial interest.
Nꢀ(9ꢀ(4ꢀmethoxybenzyl)ꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbazolꢀ1ꢀ
yl)ꢀNꢀ(propꢀ2ꢀynꢀ1ꢀyl)benzenesulfonamide (6): White solid,
m.p. 114.2ꢀ114.6 oC. 1H NMR (400 MHz, CDCl3) δ 7.99 (dt, J
= 8.4, 1.1 Hz, 2H), 7.61 – 7.52 (m, 2H), 7.51 – 7.42 (m, 2H),
7.28 – 7.15 (m, 2H), 7.15 – 7.07 (m, 1H), 6.86 (d, J = 8.7 Hz,
2H), 6.80 – 6.74 (m, 2H), 5.46 – 5.34 (m, 2H), 5.28 (d, J =
16.9 Hz, 1H), 3.82 (dt, J = 18.6, 1.7 Hz, 1H), 3.75 (d, J = 0.8
Hz, 3H), 3.54 (ddd, J = 18.6, 2.5, 0.9 Hz, 1H), 2.84 (dt, J =
15.9, 5.2 Hz, 1H), 2.65 (ddd, J = 15.2, 8.4, 6.2 Hz, 1H), 2.09 –
1.98 (m, 1H), 1.98 – 1.87 (m, 2H), 1.84 – 1.65 (m, 2H). 13C
NMR (101 MHz, CDCl3) δ 158.6, 140.9, 137.8, 132.8, 130.0,
129.1, 128.8, 128.0, 127.3, 126.5, 122.8, 119.3, 118.7, 116.7,
113.8, 110.1, 79.5, 72.7, 55.2, 51.4, 45.8, 33.8, 29.3, 20.8,
20.5. HRMSꢀESI (m/z): calcd for C29H29N2O3S [M + H]+:
485.1893, found 485.1888.
■ ACKNOWLEDGMENTS
Financial support from the National Natural Science Foundation
of China (No. 21562052 and 21462055), the Guizhou Provincial
Department of Education (No. KY[2012]078), and the Guizhou
Provincial Department of Science and Technology (No.
G[2013]7036, LH[2014]7547, and LH[2014]7554) is gratefully
acknowledged.
■ REFERENCES
(1) For reviews on indoles, see: (a) Somei, M.; Yamada, F. Nat. Prod.
Rep. 2005, 22, 73ꢀ103. (b) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005,
105, 2873ꢀ2920. (c) Chen, F. E.; Huang, J. Chem. Rev. 2005, 105,
4671ꢀ4706. (d) Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106,
2875ꢀ2911. (e) KochanowskaꢀKaramyan, A. J.; Hamann, M. T.
Chem. Rev. 2010, 110, 4489ꢀ4497. (f) Sharma, V.; Kumar, P.; Pathak,
D. J. Heterocycl. Chem. 2010, 47, 491ꢀ502. (g) Cacchi, S.; Fabrizi, G.
Chem. Rev. 2011, 111, PR215ꢀ PR283. (h) Ishikura, M.; Abe, T.;
Choshi, T.; Hibino, S. Nat. Prod. Rep. 2013, 30, 694ꢀ752. (i) Kaushik,
N. K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.; Verma, A. K.;
Choi, E. H. Molecules 2013, 18, 6620ꢀ6662. (j) Zhang, M.ꢀZ.; Chen,
Q.; Yang, G.ꢀF. Eur. J. Med. Chem. 2015, 89, 421ꢀ441. (k) Gu, L. J.;
Wang, Y. S.; Zhang, H. T.; Tang, H. J.; Li, G. P.; Yuan, M. L. Chemꢀ
CatChem, 2016, 8, 2206ꢀ2209.
Nꢀ(9ꢀ(4ꢀmethoxybenzyl)ꢀ4ꢀoxoꢀ2,3,4,9ꢀtetrahydroꢀ1Hꢀcarbꢀ
azolꢀ1ꢀyl)ꢀNꢀ(propꢀ2ꢀynꢀ1ꢀyl)benzenesulfonamide (7): Brown
solid, m.p. 168.6ꢀ171.0 oC. 1H NMR (400 MHz, CDCl3) δ 8.46
– 8.20 (m, 1H), 7.96 (ddd, J = 8.5, 2.7, 1.3 Hz, 2H), 7.69 –
7.57 (m, 1H), 7.50 (tq, J = 7.2, 1.5 Hz, 2H), 7.34 – 7.17 (m,
3H), 6.97 – 6.86 (m, 2H), 6.80 (dd, J = 8.9, 2.3 Hz, 2H), 5.61
– 5.51 (m, 1H), 5.42 (dd, J = 6.0, 2.0 Hz, 2H), 4.06 – 3.94 (m,
1H), 3.80 – 3.72 (m, 3H), 3.67 – 3.56 (m, 1H), 2.96 (dddd, J =
17.5, 11.5, 5.8, 2.2 Hz, 1H), 2.50 – 2.35 (m, 1H), 2.26 – 2.07
(m, 2H), 2.08 – 1.98 (m, 1H). 13C NMR (101 MHz, CDCl3) δ
193.1, 159.0, 143.1, 140.0, 137.9, 133.3, 129.0, 128.0, 127.9,
127.2, 124.7, 124.2, 123.2, 122.3, 116.3, 114.2, 110.6, 78.4,
73.6, 55.2, 49.5, 46.4, 34.8, 34.4, 28.1. HRMSꢀESI (m/z):
calcd for C29H27N2O4S [M + H]+: 499.1686, found 499.1681.
(2) For reviews on the synthesis and functionalization of indoles, see:
(a) Balme, G.; Bouyssi, D.; Lomberget, T.; Monteiro, N. Synthesis
2003, 2115ꢀ2134. (b) Zeni, G.; Larock, R. C. Chem. Rev. 2004, 104,
2285ꢀ2310. (c) Seregin, I. V.; Gevorgyan, V. Chem. Soc. Rev. 2007,
36, 1173ꢀ1193. (d) Dalpozzo, R. Chem. Soc. Rev. 2015, 44, 742ꢀ778.
(e) Sandtorv, A. H. Adv. Synth. Catal. 2015, 357, 2403ꢀ2435. (f)
Leitch, J. A.; Bhonoah, Y.; Frost, C. G. ACS Catal. 2017, 7, 5618ꢀ
5627.
(1S,5S)ꢀ11ꢀ(4ꢀmethoxybenzyl)ꢀ4ꢀmethyleneꢀ2ꢀ(phenylsulfonꢀ
yl)ꢀ2,3,4,5ꢀtetrahydroꢀ1Hꢀ1,5ꢀmethanoazocino[3,4ꢀb]indolꢀ6ꢀ
1
(11H)ꢀone (8): White solid, m.p. 97.6ꢀ100.5 oC. H NMR (400
MHz, CDCl3) δ 8.28 – 8.17 (m, 1H), 7.89 – 7.78 (m, 2H), 7.58
(dt, J = 6.5, 1.7 Hz, 1H), 7.50 (tt, J = 6.1, 1.5 Hz, 2H), 7.42 –
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 11
(3) For recent reviews, see: (a) Souillart, L.; Cramer, N. Chem. Rev.
Chen, W.; Cai, Q.; Liu, P.; Sun, P. Eur. J. Org. Chem. 2017, 4773ꢀ
4777.
(14) CCDC 1550605 (3d) and 1580692 (4d) contain the supplemenꢀ
tary crystallographic data for this paper. These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
2015, 115, 9410ꢀ9464. (b) Vanjari, R.; Singh, K. N. Chem. Soc. Rev.
2015, 44, 8062ꢀ8096. (c) Mo, J. Y.; Wang, L. H.; Liu, Y. Q.; Cui, X.
L. Synthesis 2015, 47, 439ꢀ459. (d) Yang, Q.; Wang, Q.; Yu, Z. Chem.
Soc. Rev. 2015, 44, 2305ꢀ2329. (e) Yang, L.; Huang, H. Chem. Rev.
2015, 115, 3468ꢀ3517. (f) Liu, C.; Yuan, J.; Gao, M.; Tang, S.; Li, W.;
Shi, R.; Lei, A. Chem. Rev. 2015, 115, 12138ꢀ12204. (g) Song, G.; Li,
X. Acc. Chem. Res. 2015, 48, 1007ꢀ1020. (h) Huang, Z.; Lim, H. N.;
Mo, F.; Young, M. C.; Dong, G. Chem. Soc. Rev. 2015, 44, 7764ꢀ
7786. (i) Cheng, C.; Hartwig, J. F. Chem. Rev. 2015, 115, 8946ꢀ8975.
(j) Gensch, T.; Hopkinson, M. N.; Glorius, F.; WencelꢀDelord, J.
Chem. Soc. Rev. 2016, 45, 2900ꢀ2936. (k) Zheng, Q. Z.; Jiao, N.
Chem. Soc. Rev. 2016, 45, 4590ꢀ4627.
(4) For reviews involving C−H activation of indoles, see: (a) Bandini,
M.; Eichholzer, A. Angew. Chem., Int. Ed. 2009, 48, 9608ꢀ9644. (b)
Joucla, L.; Djakovitch, L. Adv. Synth. Catal. 2009, 351, 673ꢀ714. (c)
Sandtorv, A. H. Adv. Synth. Catal. 2015, 357, 2403ꢀ2435.
(5) (a) Higuchi, K.; Tayu, M.; Kawasaki, T. Chem. Commun. 2011,
47, 6728ꢀ6730. (b) Zaimoku, H.; Hatta, T.; Taniguchi, T.; Ishibashi,
H. Org. Lett. 2012, 14, 6088ꢀ6091. (c) Tayu, M.; Higuchi, K.; Inaba,
M.; Kawasaki, T. Org. Biomol. Chem. 2013, 11, 496ꢀ502. (d) Gulzar,
N.; Klussmann, M. Org. Biomol. Chem. 2013, 11, 4516ꢀ4520. (e)
Nakano, Y.; Lupton, D. W. Chem. Commun. 2014, 50, 1757ꢀ1760. (f)
Jiang, L.; Xie, x.; Zu, L. RSC Adv. 2015, 5, 9204ꢀ9207.
1
2
3
4
5
6
7
8
(15) (a) Moriyama, K.; Kuramochi, M.; Fujii, K.; Morita, T.; Togo, H.
Angew. Chem., Int. Ed. 2016, 55, 14546ꢀ14551. (b) Wang, G.; Fu, Z.;
Huang, W. Org. Lett. 2017, 19, 3362ꢀ3365. (c) Park, J.; Choi, S.; Lee,
Y.; Cho, S. H. Org. Lett. 2017, 19, 4054ꢀ4057. (d) Hatano, M.; Nishiꢀ
kawa, K.; Ishihara, K. J. Am. Chem. Soc. 2017, 139, 8424ꢀ8427. (e)
AliceaꢀMatías, E.; Soderquist, J. A. Org. Lett. 2017, 19, 336ꢀ339.
(16) (a) Staben, S. T.; KennedyꢀSmith, J. J.; Huang, D.; Corkey, B.
K.; LaLonde, R. L.; Toste, F. D. Angew. Chem., Int. Ed. 2006, 45,
5991ꢀ5994. (b) Linghu, X.; KennedyꢀSmith, J. J.; Toste, F. D. Angew.
Chem., Int. Ed. 2007, 46, 7671ꢀ7673. (c) Nicolaou, K. C.; Tria, G. S.;
Edmonds, D. J.; Kar, M. J. Am. Chem. Soc. 2009, 131, 15909ꢀ15917.
(d) Zhang, X.; Zhou, Y.; Zuo, J.; Yu, B. Nat. Commun. 2015, 6, 5879.
(17) (a) Minakata, S.; Hayakawa, J. Chem. Commun. 2011, 47, 1905ꢀ
1907. (b) Kiyokawa, K.; Kojima, T.; Hishikawa, Y.; Minakata, S.
Chem. Eur. J. 2015, 21, 15548ꢀ15552.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6) (a) Boggs, S. D.; Cobb, J. D.; Gudmundsson, K. S.; Jones, L. A.;
Matsuoka, R. T.; Millar, A.; Patterson, D. E.; Samano, V.; Trone, M.
D.; Xie, S.; Zhou, X. Org. Process Res. Dev. 2007, 11, 539ꢀ545. (b)
Gudmundsson, K. S.; Sebahar, P. R.; Richardson, L. D.; Catalano, J.
G.; Boggs, S. D.; Spaltenstein, A.; Sethna, P. B.; Brown, K. W.; Harꢀ
vey, R.; Romines, K. R. Bioorg. Med. Chem. Lett. 2009, 19, 3489ꢀ
3492. (c) Gudmundsson, K. S.; Boggs, S. D.; Sebahar, P. R.; Richardꢀ
son, L. D.; Spaltenstein, A.; Golden, P.; Sethna, P. B.; Brown, K. W.;
Moniri, K.; Harvey, R.; Romines, K. R. Bioorg. Med. Chem. Lett.
2009, 19, 4110ꢀ4114.
(7) Fabio, R. D.; Giovannini, R.; Bertani, B.; Borriello, M.; Bozzoli,
A.; Donati, D.; Falchi, A.; Ghirlanda, D.; Leslie, C. P.; Pecunioso, A.;
Rumboldt, G.; Spada, S. Bioorg. Med. Chem. Lett. 2006, 16, 1749ꢀ
1752.
(8) Li, L.; Beaulieu, C.; Carriere, M.ꢀC.; Denis, D.; Greig, G.; Guay,
D.; O’Neill, G.; Zamboni, R.; Wang, Z. Bioorg. Med. Chem. Lett.
2010, 20, 7462ꢀ7465.
(9) (a) Miranda, E. C.; Blechert, S. Tetrahedron Lett. 1982, 23, 5395ꢀ
5398. (b) Jiricek, J.; Blechert, S. J. Am. Chem. Soc. 2004, 126, 3534ꢀ
3538. (c) Cai, X. H.; Du, Z. Z.; Luo, X. D. Org. Lett. 2007, 9, 1817ꢀ
1820. (d) Gerfaud, T.; Xie, C.; Neuville, L.; Zhu, J. Angew. Chem.,
Int. Ed. 2011, 50, 3954ꢀ3957.
(10) (a) Li, Q.; Li, G.; Ma, S.; Feng, P.; Shi, Y. Org. Lett. 2013, 15,
2601ꢀ2603. (b) Ren, W.; Wang, Q.; Zhu, J. Angew. Chem., Int. Ed.
2014, 53, 1818ꢀ1821. (c) Li, Y.; Zhu, S.; Li, J.; Li, A. J. Am. Chem.
Soc. 2016, 138, 3982ꢀ3985. (d) Wang, D.; Hou, M.; Ji, Y.; Gao, S. H.
org. lett. 2017, 19, 1922ꢀ1925. (e) Wang, T.; Duan, X.; Zhao, Hua.;
Zhai, S.; Tao, C.; Wang, H.; Li, Y.; Cheng, B.; Zhai, H. Org. Lett.
2017, 19, 1650ꢀ1653.
(11) For reviews, see: (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev.
2008, 108, 5299ꢀ5358. (b) Dohi, T.; Kita, Y. Chem. Commun. 2009,
2073ꢀ2085. (c) Parvatkar, P. T.; Parameswaran, P. S.; Tilve, S. G.
Chem. Eur. J. 2012, 18, 5460ꢀ5489. (d) Finkbeiner, P.; Nachtsheim, B.
J. Synthesis 2013, 45, 979ꢀ999. (e) Ren, Y.ꢀM.; Cai, C.; Yang, R.ꢀC.
RSC Adv. 2013, 3, 7182ꢀ7204. (f) Liu, D.; Lei, A.ꢀW. Chem. Asian J.
2015, 10, 806ꢀ823.
(12) For recent examples, see: (a) Yan, Y.; Zhang, Y.; Feng, C.; Zha,
Z.; Wang, Z. Angew. Chem., Int. Ed. 2012, 51, 8077ꢀ8081. (b) Luo,
W.ꢀK.; Shi, X.; Zhou, W.; Yang, L. Org. Lett. 2016, 18, 2036ꢀ2039.
(c) Zhu, D.; Luo, W.ꢀK.; Yang, L.; Ma, D.ꢀY. Org. Biomol. Chem.
2017, 15, 7112ꢀ7116. (d) Zhang, H.; Muñiz, K. ACS Catal. 2017, 7,
4122ꢀ4125. (e) Takeda, Y.; Hayakawa, J.; Yano, K.; Minakata, S.
Chem. Lett. 2012, 41, 1672ꢀ1674.
(13) (a) Liu, X.; Hu, Q.; Yuan, Z.; Liu, P. Org. Biomol. Chem. 2014,
12, 7494ꢀ7497. (b) Liu, P.; Guo, J.; Wei, W.; Liu, X.; Sun, P. Eur. J.
Org. Chem. 2016, 2105ꢀ2109. (c) Guo, J.; Chen, S.; Liu, J.; Guo, J.;
ACS Paragon Plus Environment

Page 11 of 11
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11
ACS Paragon Plus Environment