Synthesis of substituted tetrahydron-1H-carbazol-1-one and analogs via PhI(OCOCF3)2-mediated oxidative C-C bond formation

Article abstract of DOI:10.1016/j.tet.2014.02.083

A variety of tetrahydro-1H-carbazol-1-ones and analogs were conveniently synthesized from the reaction of the corresponding 2-(phenylamino)cyclohex-2- enone with hypervalent iodine reagent PhI(OCOCF₃)₂ (PIFA), through a direct intramolecular oxidative C(sp²)-C(sp²) bond formation. This approach realized the construction of the biologically important tetrahydro-1H-carbazol-1-one and tetrahydrocyclohepta[b]indol-6(5H)- one skeletons. The mechanism of the process was proposed and briefly discussed.

Full text of DOI:10.1016/j.tet.2014.02.083

Tetrahedron 70 (2014) 2753e2760
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Tetrahedron
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Synthesis of substituted tetrahydron-1H-carbazol-1-one
and analogs via PhI(OCOCF3)2-mediated oxidative CeC bond
formation
,
b
,
a,
Hao Shi a, Tianjian Guo a, Daisy Zhang-Negrerie a, Yunfei Du a , Kang Zhao
*
*
a Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University,
Tianjin 300072, China
b China and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of tetrahydro-1H-carbazol-1-ones and analogs were conveniently synthesized from the re-
action of the corresponding 2-(phenylamino)cyclohex-2-enone with hypervalent iodine reagent PhI(O-
COCF3)2 (PIFA), through a direct intramolecular oxidative C(sp2)eC(sp2) bond formation. This approach
realized the construction of the biologically important tetrahydro-1H-carbazol-1-one and tetrahy-
drocyclohepta[b]indol-6(5H)-one skeletons. The mechanism of the process was proposed and briefly
discussed.
Received 10 December 2013
Received in revised form 18 February 2014
Accepted 27 February 2014
Available online 13 March 2014
Keywords:
Hypervalent iodine reagent
Metal-free coupling
Ó 2014 Elsevier Ltd. All rights reserved.
Oxidative annulation
C(sp2)eC(sp2) bond formation
Tetrahydro-1H-carbazol-1-one
1. Introduction
Nitrogen-containing heterocycles are structural constituents of
many natural products and medicinally important agents. Among
them, tetrahydro-1H-carbazol-1-one and its analogs have been
widely identified in many anti-virus and anti-cancer prodrugs. For
example, diketo acid I can act as an HIV integrase inhibitor by
specifically inhibiting the strand transfer step.1 Compound II was
found to be an active anti-prion agent by obstructing the accu-
mulation of PrPSc.2 Besides, significant activities against bacteria
have been observed in dispirooxindolopyrrolizidine III.3 What is
common for the above compounds IeIII is that they all bear a tet-
rahydro-1H-carbazole-1-one skeleton in their respective structure.
Furthermore, the R,R-diastereomer of compound IV, derived from
4-Br-tetrahydro-1H-carbazole-1-one was proven to be active
against HPV (human papillomaviruses) with low cytotoxicity and
suitable pharmacokinetic profile.4 Besides, tetrahydrocyclohepta[b]
indol-6(5H)-one, an analog of tetrahydro-1H-carbazol-1-one, can
also act as useful building blocks for the construction of some bi-
ologically important pharmaceutical agents. For example, penta-
cycle V represents a new class of aurora kinase inhibitors with
excellent oral availability and high potency against tumor (Fig. 1).5
Fig. 1. Biologically important pharmaceutical agents derived from tetrahydro-1H-
carbazol-1-ones or its analogs.
Owing to the significant biological activities, many methods
have been developed for the construction of tetrahydro-1H-car-
bazol-1-one skeletons. To the best of our knowledge, the existing
methods can generally be assorted into three categories, including
the well-known Fischer indole synthesis (Fig. 2, path a),6 oxidation
of the corresponding tetrahydro-1H-carbazol1,7 (Fig. 2, path b), and
intramolecular condensation through FriedeleCrafts reaction
(Fig. 2, path c).8 It is worth noting that in 2012, Bautista et al.9 tried
to synthesize tetrahydro-1H-carbazol-1-one 2b from 2-(phenyl-
amino)cyclohex-2-enone 1b through the classical Pd-mediated
* Corresponding authors. Tel./fax: þ86 (0)22 27404031; e-mail addresses:
duyunfeier@tju.edu.cn (Y. Du), kangzhao@tju.edu.cn (K. Zhao).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.083

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H. Shi et al. / Tetrahedron 70 (2014) 2753e2760
Table 1
CeH activation/CeC bond forming strategy. Unfortunately, what
they obtained was the aromatized product 3 rather than the de-
sired tetrahydro-1H-carbazol-1-one 2b (Scheme 1).
Optimization of reaction conditionsa
Entry Oxidant (1.1 equiv) Solvent Concn (mol/L) t (ꢁC) Time
Yieldb (%)
Tracec
1
2
3
4
5
6
7
8
PIDA
PIFA
PhIO
IBX
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
DCE
DCE
DCE
DMSO
DCE
TFE
MeOH
DMF
Dioxane 0.05
CH3CN 0.05
TFE
0.1
0.1
0.1
0.1
0.05
0.05
0.05
0.05
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
12 h
10 min 45
12 h
12 h
10 min 55
10 min 56
10 min trace
10 min ND
10 min ND
10 min 49
NR
NR
Fig. 2. Synthetic strategies for the construction of tetrahydro-1H-carbazol-1-one
skeletons.
9
10
11
12
13
0.05
0.05
0.05
ꢀ30 10 min 75
rt 10 min 86
ꢀ30 20 min 84
Ac2O
Ac2O
a
General condition: (1) for entries 1e4, 1a (0.6 mmol), oxidant (0.66 mmol) in
solvent (6 mL); for entries 5e13, 1a (0.6 mmol), oxidant (0.66 mmol) in solvent
(12 mL).
Scheme 1. Pd-mediated aromatization of compound 1b rather than the expected
oxidative CeC formation by Bautista.
b
Isolated yields.
c
Compound 1a was 60% recovered.
In 2009, we succeeded in the construction of indole product B
from N-aryl enamine A through PhI(OAc)2-mediated oxidative CeC
bond formation (Fig. 3, Eq. 1).10 Later on, when we applied the
method as an attempt for the synthesis of carbozolone C by sub-
jecting the cyclic enamine substrate D to the same reaction con-
the presence of PIFA, we implemented two strategies: (a) by car-
rying out the reaction at a lower temperature for the sake of hin-
dering possible side reactions; (b) switching the solvent to Ac2O for
the reason that the generated 2a could be simultaneously protected
by an acyl group. As expected, the reaction in TFE at ꢀ30 ꢁC greatly
improved the yield to 75% (Table 1, entry 11). And to our content-
ment, the same reaction run in Ac2O was found to give product 2a
in a satisfactory 86% yield, with no formation of the N-acylated
product (Table 1, entry 12). Further screening showed that oper-
ating the reaction in this solvent at lower temperature was not
necessary (Table 1, entry 13).
ditions, only the a-iodinated N-arylated product E was obtained
(Fig. 3, Eq. 2).11 In our continuation of search for new applications of
metal-free oxidative CeC bond formation, we were intrigued to
explore the possibility of forming the biologically important tet-
rahydro-1H-carbazol-1-one compound 2 via ring-closure reaction
of 1 mediated by a hypervalent iodine reagent.
With the optimal reaction conditions established (Table 1, entry
12), the scope and limitation of the method were explored by
testing out on the variously substituted anilines. The result in-
dicated that this method could be well applied to various N-aryl
enaminones bearing either electron-donating or electron-
withdrawing substituents (Table 2, entries 2e12). Notably, the
presence of para-nitro group in the phenyl ring of the substrate did
not prevent the occurrence of the cyclization, albeit a lower yield of
the desired product was obtained (Table 2, entry 4). meta-
Substituted substrates have the possibility of producing two
regioisomers. For the reaction regarding N-aryl enaminone 1h,
bearing a meta-CF3 group, two inseparable regioisomers were
generated. Comparably, the reaction of the substrate with a meta-
MeO group gave two separable isomers in relatively higher yield.
When applying this method to some other substrates such as those
bearing two substituents or having the phenyl ring replaced by
a naphthyl ring, the desired products were also achieved (Table 2,
entries 10e12).
Encouraged by the above results, we proceeded to investigate
whether the method was applicable to the analogous substrates
where the cyclohexene ring in 1 is turned into a cycloheptene ring.
However, when substrate 3a was subjected to the identical condi-
tions, only less than 5% yield of the desired product was isolated.
The low yield was mainly attributed to the fact that the enamine
substrate was unstable under the reaction conditions. It quickly
decomposed into aniline, which underwent a rapid acetylation and
led to the unexpected acetyl aniline (isolated in 51% yield). Inspired
by Boger’s work,15 we incorporated triethylamine (TEA) in the re-
action as a stabilizer of the sensitive substrates. To our satisfaction,
the desired product 4a was achieved in 60% yield after treating 3a
with 1.5 equiv of PIFA in the presence of 10 equiv of TEA in TFE
Fig. 3. Hypervalent iodine-mediated oxidations of different N-aryl enamine substrates.
2. Results and discussion
To begin with, 2-(phenylamino)cyclohex-2-enone 1a, which can
be easily prepared by the known methods from the commercially
available cyclohexane-1,2-dione in two steps,12,13 was selected as
the model substrate to test the feasibility of the proposed trans-
formation. We were pleased to find that the reaction of 1a with PIFA
in DCE (0.1 M) indeed led to the expected tetrahydro-1H-carbazol-
1-one 2a in 45% yield, although the reactions with PhI(OAc)2
(PIDA),14 PhIO, and IBX were unsuccessful (Table 1, entries 1e4).
When the concentration of 1a in DCE was lowered to 0.05 M from
0.1 M, an improved yield was achieved (Table 1, entry 5). Further
solvent screening showed that MeOH, DMF, and dioxane were not
effective for the reaction, while CH3CN and TFE were equally eli-
gible as solvents as DCE (Table 1, entries 5e10). Considering that the
free-NH moiety in product 2a was liable to further oxidization in

H. Shi et al. / Tetrahedron 70 (2014) 2753e2760
2755
Table 2
Synthesis of substituted tetrahydro-1H-carbazol-1-ones by PIFAa
Entry
1
Substrate
Product
Yieldb (%)
86
Entry
7
Substrate
Product
Yieldb (%)
55
2
3
4
63
51
36
8
9
55c
65d
71
10
5
67
30
11
12
46
36
6
a
Reaction conditions: 1 (0.6 mmol), PIFA (0.66 mmol) in Ac2O (12 mL).
b
c
Isolated yields.
An inseparable mixture, 2h/2h0¼0.45:0.55, the ratio was determined by 1H NMR.
d
Separable regioisomers, 2i: 26%, 2i0: 39%.
(trifluoroethanol) as the solvent.16 Similarly, various substituted
7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-ones bearing either
an electron-donating or electron-withdrawing substituent in the
phenyl ring were realized through this method (Table 3, entries
1e6). Although only moderate yields of the desired product were
obtained, the presented method serves as a more convenient access
to the various 7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-ones
while compared with the existing approaches, such as the well-
known Fischer indole synthesis,5,6e,17 oxidation of the corre-
sponding 5,6,7,8,9,10-hexahydrocyclohepta[b]in-dole,7b and con-
densation through FriedeleCrafts reaction.18
molecules. At the abstraction of a proton from I, aromatization was
realized and the desired indole skeleton 2a was achieved (Scheme
2, path a).
The reaction may also adopt an alternative pathway b. Initially,
the nucleophilic attack of the N atom on the iodine center20 of PIFA
afforded ammonium salt J, which was converted to enamine K via
proton transfer. Then K underwent electrocyclic ring-closure to
give iminium salt L, which was converted to M by loss of a proton.
Next, the release of one molecule of PhI and CF3CO2H from M
resulted in the formation of imine N. The final tautomerization of N
provided the title product 2a (Scheme 2, path b).
In our previous work, we found the reaction between the cyclic
enamine substrate D and PIDA could only lead to the a-iodinated N-
To gain further insight into the reaction mechanism, we carried
out a control experiment using 2-(methyl(phenyl)amino) cyclohex-
2-enone (10) as substrate, in which a methyl group was substituted
on the N atom. However, the reaction of 10 under the identical
conditions provided no desired cyclized product 20 (Scheme 3),
which clearly implied that the NeH moiety in the cyclic enamine
substrate is important for the cyclization to occur. In this regard, our
preliminary experiments show that the reaction might adopt the
mechanistic pathway described in path b. Further investigation on
the reaction mechanism is still in progress in our lab.
arylated product E (Fig. 3, Eq. 2).11 A reasonable explanation for the
formation of the CeI bond during the process is that the hyper-
valent iodine reagent reacts first with the double bond of the en-
amine substrate.19 Based on this, we proposed in path a that the
intermediate iminium salt F was first afforded after the nucleo-
philic attack on the iodine center of PIFA by the nucleophilic en-
amine, with the loss of one trifluoroacetate anion. With the
abstraction of one proton, the iminium salt F was converted to a-
iodo enamine G. Next, an intramolecular electrophilic aromatic
substitution reaction, facilitated by the electron-donating property
of the amino moiety and the electron-withdrawing effect of the
carbonyl moiety, took place, which resulted in iminium salt I via
intermediate H and the release of a PhI and a trifluoroacetic acid
3. Conclusion
In summary, we have demonstrated the first synthesis of tet-
rahydro-1H-carbazol-1-ones and 7,8,9,10-tetrahydrocyclohep-ta[b]

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H. Shi et al. / Tetrahedron 70 (2014) 2753e2760
Table 3
Synthesis of substituted 7,8,9,10-tetrahydrocyclohepta[b]-indol-6(5H)-ones via
PIFA-mediated CeC oxidative couplinga
Scheme 3. Further probe into the reaction mechanism.
Entry
Substrate
Product
Yieldb (%)
60
indol-6(5H)-ones through a metal-free oxidative CeC bond cou-
pling reaction mediated by PIFA, which has not been realized by any
of the well-known transition metal-mediated oxidation annulation
strategy. This general reaction tolerates a wide range of function
groups and can be conveniently and effectively applied to the
construction of the biologically important tetrahydro-1H-carbazol-
1
2
3
4
45
47
42
1-one
and
7,8,9,10-tetrahydrocyclohepta-[b]indol-6(5H)-one
skeletons.
4. Experimental section
4.1. General information
Unless otherwise noted, all the reagents were purchased from
commercial suppliers, used without further purification and all the
reaction mixtures were stirred magnetically without precaution of
contact with air. 1H and 13C NMR spectra were recorded on
5
6
51c
48c
13
a 600 MHz NMR instrument (150 MHz for C NMR) at 25 ꢁC. The
chemical shifts were recorded in parts per million (ppm) and re-
ferred as the internal standard to TMS: 0.00 ppm. The multiplicities
are defined as follows: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet; dd, doublet of doublets; and td, triplet of doublets. The
coupling constants J are reported in hertz (Hz). High resolution
mass spectra (HRMS) were obtained on
a Q-TOF micro-
a
Reaction condition: 1 (0.5 mmol), PIFA (0.75 mmol), TEA (5 mmol) in TFE
spectrometer. Melting points were determined with a micro
melting-point apparatus without correction. Unless otherwise
noted, flash column chromatography was performed over silica gel
200e300 mesh, and the eluent was a mixture of petroleum ether
(PE) and ethyl acetate (EA).
(10 mL).
b
c
Isolated yields.
Inseparable isomers, 4e/4e0¼0.55:0.45, 4f/4f0¼0.45:0.55, the ratios were de-
termined by 1H NMR.
4.2. General procedure for the synthesis of 2-(substituted
phenylamino)cyclohex-2-enone 1
A
mixture of substituted aniline (1.5 mmol), 2-
morpholinocyclohex-2-enone12 (1.5 mmol), and p-toluenesulfonic
acid monohydrate (1.5 mmol) in toluene (10 mL) was heated at
50 ꢁC under N2 for 2 h, during which time the solution became
homogeneous. The mixture was cooled down to room temperature,
diluted with EtOAc (30 mL), and washed with saturated aqueous
NaHCO3 (10 mLꢂ3). The separated organic layer was dried with
Na2SO4, filtered, and concentrated under vacuum. Purification of
the crude residue by column chromatography using a mixture of PE
and EA as eluent gave compounds 1ael.
Following the general procedure, the known compounds 1a,21
1b,9 1c,22 1g,22 and 1i,9 were prepared in 95%, 68%, 58%, 55% and
74% yields, respectively. The properties and 1H NMR data of 1a, 1b,
1c, 1g, and 1i were consistent with those in the literature. The novel
compounds 1def, 1h, and 1jel thus obtained were characterized as
follows:
4.2.1. 2-((4-Nitrophenyl)amino)cyclohex-2-enone (1d). Following
the general procedure,1d was purified by silica gel chromatography
(20% EA/PE). Yield: 226 mg, 65%, orange solid, mp 119e121 ꢁC. 1H
NMR (600 MHz, CDCl3)
2H), 6.93 (s,1H), 6.71 (t, J¼4.8 Hz,1H), 2.62e2.55 (m, 4H), 2.11e2.05
(m, 2H). 13C NMR (150 MHz, CDCl3)
195.0,148.2,140.1,134.4,125.9,
d
8.12 (d, J¼9.0 Hz, 2H), 7.01 (d, J¼9.0 Hz,
Scheme 2. Proposed mechanistic pathways.
d

H. Shi et al. / Tetrahedron 70 (2014) 2753e2760
2757
123.7, 115.2, 37.4, 24.8, 22.4. HRMS (ESI): calculated for [MþH]þ
37.8, 24.5, 23.2. HRMS (ESI): calculated for [MþH]þ C16H16NOþ
þ
C12H13N2O3 233.0921; found 233.0921.
238.1226; found 238.1227.
4.2.2. 2-((2-Bromophenyl)amino)cyclohex-2-enone (1e). Following
the general procedure, 1e was purified by silica gel chromatog-
raphy (10% EA/PE). Yield: 196 mg, 49%, yellow oil. 1H NMR
4.3. General procedure for the synthesis of substituted tet-
rahydro-1H-carbazol-1-one 2
(600 MHz, CDCl3)
d
7.52 (dd, J¼7.8, 1.2 Hz, 1H), 7.26 (dd, J¼7.8,
To a solution of 2-(substituted phenylamino)cyclohex-2-enone
1 (0.6 mmol) in Ac2O (10 mL) was added a solution of PIFA
(0.66 mmol) in Ac2O (2 mL) in a dropwise manner. The reaction
mixture was stirred at room temperature for 10 min, monitored by
TLC. Then the solution was poured into saturated NaHCO3 solution
(50 mL) and NaHCO3 (solid) was added portionwise while the
mixture was stirred vigorously until no more CO2 emerged. The
mixture was extracted with EA (20 mLꢂ3), and the combined or-
ganic layer was washed by brine (20 mL), dried with NaSO4, filtered,
and concentrated under vacuum. Purification of the crude residue
by column chromatography using PE and EA as eluent gave com-
pounds 2ael.
1.2 Hz, 1H), 7.20 (td, J¼7.2, 1.2 Hz, 1H), 6.75 (td, J¼7.8, 1.2 Hz, 2H),
6.43 (t, J¼4.8 Hz, 1H), 2.60e2.56 (m, 2H), 2.49e2.45 (m, 2H),
2.06e2.01 (m, 2H). 13C NMR (150 MHz, CDCl3)
d 195.1, 139.8,
135.7, 133.2, 127.9, 121.6, 118.8, 117.7, 114.3, 37.7, 24.7, 22.8. HRMS
(ESI): calculated for [MþH]þ C12H13BrNOþ 266.0175; found
266.0176.
4.2.3. 2-((2-Iodophenyl)amino)cyclohex-2-enone
(1f). Following
the general procedure, 1f was purified by silica gel chromatography
(10% EA/PE). Yield: 379 mg, 81%, yellow oil. 1H NMR (600 MHz,
CDCl3)
d
7.78 (dd, J¼7.8, 1.2 Hz, 1H), 7.26e7.20 (m, 2H), 6.64
(td, J¼8.4, 1.8 Hz, 1H), 6.54 (br s, 1H), 6.35 (t, J¼4.8 Hz, 2H),
2.60e2.57 (m, 2H), 2.47e2.44 (m, 2H), 2.06e2.01 (m, 2H). 13C NMR
4.3.1. 2,3,4,9-Tetrahydro-1H-carbazol-1-one23 (2a). Following the
general procedure, 2a was purified by silica gel chromatography
(20% EA/PE). Yield: 96 mg, 86%, white solid, mp 165e168 ꢁC. 1H
(150 MHz, CDCl3) d 195.1,142.4,139.8,136.1,128.8,122.7,118.3,118.1,
91.2, 37.7, 24.6, 22.9. HRMS (ESI): calculated for [MþH]þ
C12H13INOþ 314.0036; found 314.0035.
NMR (600 MHz, DMSO-d6)
d
11.58 (s,1H), 7.66 (d, J¼7.8 Hz,1H), 7.40
(d, J¼8.4 Hz, 1H), 7.30 (t, J¼7.8 Hz, 1H), 7.08 (t, J¼7.2 Hz, 1H),
2.96e2.93 (m, 2H), 2.57e2.55 (m, 2H), 2.17e2.14 (m, 2H). The 1H
NMR data were consistent with those in the literature.
4.2.4. 2-((3-(Trifluoromethyl)phenyl)amino)cyclohex-2-enone
(1h). Following the general procedure, 1h was purified by silica gel
chromatography (10% EA/PE). Yield: 230 mg, 60%, white solid,
mp 79e83 ꢁC. 1H NMR (600 MHz, CDCl3)
d
7.34 (t, J¼8.4 Hz, 1H),
4.3.2. 6-Methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one24
(2b). Following the general procedure, 2b was purified by silica gel
chromatography (20% EA/PE). Yield: 75 mg, 63%, white solid,
7.26 (s, 1H), 7.16 (dd, J¼7.8, 1.8 Hz, 1H), 7.13 (d, J¼7.2 Hz, 1H), 6.52
(br s, 1H), 6.46 (t, J¼4.8 Hz, 1H), 2.59e2.56 (m, 2H), 2.51e2.48
(m, 2H), 2.07e2.02 (m, 2H). 13C NMR (150 MHz, CDCl3)
d
195.3,
mp 189e191 ꢁC. 1H NMR (600 MHz, DMSO-d6)
d 11.43 (s, 1H), 7.43
142.6, 135.6, 131.6 (q, JFeC¼32 Hz), 129.8, 124.0 (q, JFeC¼270 Hz),
121.2, 118.2, 117.2 (q, JFeC¼4 Hz), 114.2 (q, JFeC¼4 Hz), 37.6, 24.6,
22.8. HRMS (ESI): calculated for [MþH]þ C13H13F3NOþ 256.0944;
found 256.0944.
(s, 1H), 7.28 (d, J¼8.4 Hz, 1H), 7.13 (d, J¼8.4 Hz, 1H), 2.93e2.90
(m, 2H), 2.55e2.52 (m, 2H), 2.37 (s, 3H), 2.16e2.11 (m, 2H). The 1H
NMR data were consistent with those in the literature.
4.3.3. 6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-one1
(2c). Following the general procedure, 2c was purified by silica gel
chromatography (20% EA/PE). Yield: 67 mg, 51%, yellowish solid,
4.2.5. 2-((2,4-Dimethylphenyl)amino)cyclohex-2-enone
(1j). Following the general procedure, 1j was purified by silica gel
chromatography (10% EA/PE). Yield: 271 mg, 84%, yellow oil. 1H
mp 220e223 ꢁC. 1H NMR (600 MHz, CDCl3)
d 9.01 (s, 1H), 7.63
NMR (600 MHz, CDCl3)
d
7.04 (d, J¼7.8 Hz, 1H), 6.99 (s, 1H), 6.95
(s, 1H), 7.36 (d, J¼9.0 Hz, 1H), 7.31 (d, J¼8.4 Hz, 1H), 2.99e2.96
(m, 2H), 2.68e2.65 (m, 2H), 2.30e2.25 (m, 2H). The 1H NMR data
were consistent with those in the literature.
(d, J¼7.8 Hz, 1H), 5.95 (br s, 1H), 5.92 (t, J¼4.8 Hz, 1H), 2.57e2.54
(m, 2H), 2.40e2.36 (m, 2H), 2.27 (s, 3H), 2.17 (s, 3H), 2.02e1.97
(m, 2H). 13C NMR (150 MHz, CDCl3)
d 195.7, 137.5, 137.3, 132.2,
131.6, 130.3, 127.1, 121.2, 115.0, 37.8, 24.5, 23.2, 20.7, 17.7. HRMS
(ESI): calculated for [MþH]þ C14H18NOþ 216.1383; found
216.1382.
4.3.4. 6-Nitro-2,3,4,9-tetrahydro-1H-carbazol-1-one24
(2d). Following the general procedure, 2d was purified by silica gel
chromatography (20% EA/PE). Yield: 50 mg, 36%, orange solid,
mp 252e255 ꢁC. 1H NMR (600 MHz, CDCl3)
d 9.33 (s, 1H), 8.68
4.2.6. Methyl 4-chloro-3-((6-oxocyclohex-1-enyl)amino)-benzoate
(1k). Following the general procedure, 1k was purified by silica gel
chromatography (10% EA/PE). Yield: 325 mg, 77%, white solid,
(s, 1H), 8.26 (dd, J¼9.0, 1.8 Hz, 1H), 7.50 (d, J¼9.0 Hz, 1H), 3.09e3.07
(m, 2H), 2.74e2.71 (m, 2H), 2.36e2.31 (m, 2H). The 1H NMR data
were consistent with those in the literature.
mp 43e46 ꢁC. 1H NMR (600 MHz, CDCl3)
d
7.92 (d, J¼1.8 Hz, 1H),
7.46 (dd, J¼7.8,1.8 Hz,1H), 7.40 (d, J¼8.4 Hz,1H), 6.91 (br s,1H), 6.56
(t, J¼4.8 Hz, 1H), 3.91 (s, 3H), 2.62e2.58 (m, 2H), 2.55e2.51 (m, 2H),
4.3.5. 8-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one24
(2e). Following the general procedure, 2e was purified by silica gel
chromatography (20% EA/PE). Yield: 106 mg, 67%, white solid,
2.09e2.04 (m, 2H). 13C NMR (150 MHz, CDCl3)
d 195.0, 166.5, 138.8,
135.1, 129.9, 129.3, 127.9, 121.6, 120.2, 117.3, 52.3, 37.6, 24.7, 22.7.
HRMS (ESI): calculated for [MþH]þ C14H15ClNO3þ 280.0735; found
280.0735.
mp 154e156 ꢁC. 1H NMR (600 MHz, DMSO-d6)
d 11.71 (s, 1H), 7.70
(dd, J¼10.8, 8.4 Hz, 1H), 7.54 (dd, J¼7.2, 4.8 Hz, 1H), 7.03 (dd, J¼14.4,
7.8 Hz, 1H), 2.97e2.93 (m, 2H), 2.60e2.57 (m, 2H), 2.18e2.14
(m, 2H). The 1H NMR data were consistent with those in the
literature.
4.2.7. 2-(Naphthalen-1-ylamino)cyclohex-2-enone (1l). Following
the general procedure, 1l was purified by silica gel chromatography
(10% EA/PE). Yield: 265 mg, 74%, yellow oil. 1H NMR (600 MHz,
4.3.6. 8-Iodo-2,3,4,9-tetrahydro-1H-carbazol-1-one (2f). Following
the general procedure, 2f was purified by silica gel chromatography
(20% EA/PE). Yield: 56 mg, 30%, white solid, mp 133e135 ꢁC. 1H
CDCl3)
d
7.98e7.95 (m, 1H), 7.84e7.81 (m, 1H), 7.53 (d, J¼7.8 Hz, 1H),
7.49e7.45 (m, 1H), 7.39 (t, J¼7.2 Hz, 1H), 7.30 (dd, J¼7.2, 1.2 Hz, 1H),
6.70 (s, 1H), 6.10 (t, J¼4.8 Hz, 1H), 2.62e2.59 (m, 2H), 2.40e2.36 (m,
NMR (600 MHz, CDCl3)
J¼8.4 Hz, 1H), 6.93 (t, J¼7.8 Hz, 1H), 3.01e2.99 (m, 2H), 2.69e2.66
(m, 2H), 2.31e2.26 (m, 2H). 13C NMR (150 MHz, DMSO-d6)
190.1,
d
8.67 (s, 1H), 7.73 (d, J¼7.8 Hz, 1H), 7.64 (d,
2H), 2.05e2.00 (m, 2H). 13C NMR (150 MHz, CDCl3)
d 195.7, 137.7,
137.6,134.7,128.5,128.0,126.1,125.8,125.6,123.1,122.0,116.9,116.6,
d

2758
H. Shi et al. / Tetrahedron 70 (2014) 2753e2760
139.9, 135.6, 131.7, 129.4, 125.9, 121.5, 121.2, 77.8, 38.4, 24.4, 21.0.
HRMS (ESI): calculated for [MþH]þ C12H11INOþ 311.9880; found
311.9880.
J¼8.4 Hz,1H), 7.94 (d, J¼7.8 Hz,1H), 7.69 (d, J¼8.4 Hz,1H), 7.58e7.50
(m, 3H), 3.04e3.01 (m, 2H), 2.61e2.58 (m, 2H), 2.21e2.16 (m, 2H).
13C NMR (150 MHz, DMSO-d6)
d 189.5, 134.0, 132.3, 130.3, 129.5,
128.5, 125.9, 122.4, 122.3, 121.1, 120.9, 119.8, 99.5, 38.1, 24.7, 20.9.
HRMS (ESI): calculated for [MþH]þ C16H14NOþ 236.1070; found
236.1069.
4.3.7. 8-Methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one24
(2g). Following the general procedure, 2g was purified by silica gel
chromatography (20% EA/PE). Yield: 66 mg, 55%, white solid,
mp 156e160 ꢁC. 1H NMR (600 MHz, DMSO-d6)
d
11.48 (s, 1H), 7.48
4.4. General procedure for the synthesis of 2-(substituted
phenylamino)cyclohept-2-enone 3
(d, J¼7.8 Hz, 1H), 7.09 (d, J¼6.6 Hz, 1H), 6.99 (t, J¼7.8 Hz, 1H),
2.95e2.92 (m, 2H), 2.58e2.55 (m, 2H), 2.48 (s, 3H), 2.17e2.12 (m,
2H). The 1H NMR data were consistent with those in the literature.
A
solution of cycloheptane-1,2-dione (2.4 mmol) and
substituted aniline (2 mmol) in toluene (5 mL) was heated to reflux
with a water condenser and DeaneStark trap under N2 for 5 h. The
solvent was removed under vacuum. Purification of the crude
residue by column chromatography using TEA (triethylamine) and
PE as eluent gave compounds 3aef. The 2-(substituted phenyl-
amino)cyclohept-2-enone 3 was unstable and characterized shortly
after being obtained.
4.3.8. 5-(Trifluoromethyl)-2,3,4,9-tetrahydro-1H-carbazol-1-one
(2h)/7-(trifluoromethyl)-2,3,4,9-tetrahydro-1H-carbazol-1-one
(2h0). Following the general procedure, 2h/2h0 was purified by
silica gel chromatography (10% EA/PE). Yield: 78 mg, 51%, white
solid, mp 160e164 ꢁC. 1H NMR (600 MHz, CDCl3) isomer 2h
d 9.34
(s, 1H), 7.70 (d, J¼8.4 Hz, 1H), 7.50 (d, J¼7.2 Hz, 1H), 7,40 (t, J¼7.8 Hz,
1H), 3.14e3.12 (m, 2H), 2.75e2.70 (m, 2H), 2.34e2.27 (m, 2H);
Isomer 2h0
d
9.86 (s, 1H), 7.78 (s, 1H), 7.76 (d, J¼8.4 Hz, 1H), 7.37 (d,
J¼8.4 Hz, 1H), 3.06e3.03 (m, 2H), 2.75e2.70 (m, 2H), 2.34e2.27 (m,
2H). 13C NMR (150 MHz, CDCl3)
192.4, 191.9, 138.4, 136.7, 133.1,
4.4.1. 2-(Phenylamino)cyclohept-2-enone (3a). Following the gen-
eral procedure, 3a was purified by silica gel chromatography (1%
TEA/PE). Yield: 163 mg, 40%, yellow oil. 1H NMR (600 MHz, DMSO-
d
132.5, 129.0, 128.7(q, JFeC¼32 Hz), 127.9, 127.2, 125.5, 125.3, 125.2,
123.7, 123.7, 123.5, 123.4, 122.1, 121.4, 118.8 (q, JFeC¼6 Hz), 117.0,
116.8, 110.4 (q, JFeC¼5 Hz), 38.3, 37.9, 24.9, 24.8, 22.7, 21.3. HRMS
(ESI): calculated for [MþH]þ C13H11F3NOþ 254.0787; found
254.0787.
d6)
d
7.15 (t, J¼7.8 Hz, 2H), 6.98 (s, 1H), 6.89 (d, J¼7.8 Hz, 2H), 6.73
(t, J¼7.2 Hz, 1H), 6.39 (t, J¼7.2 Hz, 1H), 2.66e2.62 (m, 2H),
2.43e2.38 (m, 2H), 1.75e1.67 (m, 4H). 13C NMR (150 MHz, DMSO-
d6)
d 200.1, 144.0, 140.1, 128.8, 122.5, 119.0, 116.8, 40.7, 24.8, 24.4,
20.5. HRMS (ESI): calculated for [MþH]þ C13H16NOþ 202.1226;
found 202.1223.
4.3.9. 5-Methoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one6h
(2i). Following the general procedure, 2i was purified by silica gel
chromatography (20% EA/PE). Yield: 33 mg, 26%, yellow solid,
4 . 4 . 2 . 2 - ( ( 4 - C h l o ro p h e nyl ) a m i n o ) c yc l o h e p t - 2 - e n o n e
(3b). Following the general procedure, 3b was purified by silica
gel chromatography (1% TEA/PE). Yield: 193 mg, 41%, yellow oil.
mp 150e152 ꢁC. 1H NMR (600 MHz, CDCl3)
d 9.10 (s, 1H), 7.24 (t,
J¼7.8 Hz, 1H), 6.99 (d, J¼8.4 Hz, 1H), 6.45 (d, J¼7.8 Hz, 1H),
3.23e3.20 (m, 2H), 2.63e2.60 (m, 2H), 2.25e2.20 (m, 2H). The 1H
NMR data was consistent with that in the literature.
1H NMR (600 MHz, DMSO-d6)
d
7.20 (s, 1H), 7.15 (d, J¼9.0 Hz, 2H),
6.87 (d, J¼8.4 Hz, 2H), 6.42 (t, J¼7.2 Hz, 1H), 2.65e2.62 (m, 2H),
2.44e2.40 (m, 2H), 1.76e1.67 (m, 4H). 13C NMR (150 MHz, DMSO-
d6)
d 200.0, 143.3, 139.8, 128.5, 124.8, 121.9, 117.7, 40.7, 24.8, 24.5,
4.3.9.1. 7-Methoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one6h
(2i0). Following the general procedure, 2i0 was purified by silica gel
chromatography (20% EA/PE). Yield: 50 mg, 39%, yellow solid,
20.5. HRMS (ESI): calculated for [MþH]þ C13H15ClNOþ 236.0837;
found 236.0836.
mp 139e142 ꢁC. 1H NMR (600 MHz, CDCl3)
d
9.04 (s, 1H), 6.83e6.79
4.4.3. 2-((4-Bromophenyl)amino)cyclohept-2-enone (3c). Following
the general procedure, 3c was purified by silica gel chromatog-
raphy (1% TEA/PE). Yield: 258 mg, 46%, yellow oil. 1H NMR
(600 MHz, DMSO-d6)
J¼9.0 Hz, 2H), 6.43 (t, J¼7.2 Hz, 1H), 2.65e2.62 (m, 2H), 2.44e2.40
(m, 2H), 1.75e1.68 (m, 4H). 13C NMR (150 MHz, DMSO-d6)
200.0,
143.8, 139.7, 131.4, 125.3, 118.1, 109.4, 40.8, 24.8, 24.6, 20.6. HRMS
(ESI): calculated for [MþH]þ C13H15BrNOþ 280.0332; found
280.0335.
(m, 2H), 3.87 (s, 1H), 2.98e2.95 (m, 2H), 2.65e2.62 (m, 2H),
2.27e2.22 (m, 2H). The 1H NMR data were consistent with those in
the literature.
d
7.27 (d, J¼9.0 Hz, 2H), 7.22 (s, 1H), 6.81 (d,
4.3.10. 6,8-Dimethyl-2,3,4,9-tetrahydro-1H-carbazol-1-one6h
(2j). Following the general procedure, 2j was purified by silica gel
chromatography (10% EA/PE). Yield: 91 mg, 71%, yellow solid,
d
mp 190e193 ꢁC. 1H NMR (600 MHz, CDCl3)
d 8.80 (s, 1H), 7.27 (s,
1H), 7.01 (s, 1H), 2.99e2.96 (m, 2H), 2.66e2.63 (m, 2H), 2.45 (s, 3H),
2.42 (s, 3H), 2.28e2.23 (m, 2H). The 1H NMR data were consistent
with those in the literature.
4.4.4. 2-(p-Methylamino)cyclohept-2-enone (3d). Following the
general procedure, 3d was purified by silica gel chromatography
(1% TEA/PE). Yield: 164 mg, 38%, yellow oil. 1H NMR (600 MHz,
4.3.11. Methyl 8-chloro-1-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-
carboxylate (2k). Following the general procedure, 2k was puri-
fied by silica gel chromatography (10% EA/PE). Yield: 77 mg, 46%,
DMSO-d6)
d
6.98 (d, J¼8.4 Hz, 2H), 6.83 (d, J¼8.4 Hz, 2H), 6.78 (s,
1H), 6.28 (t, J¼7.2 Hz, 1H), 2.64e2.61 (m, 2H), 2.40e2.36 (m, 2H),
2.19 (s, 3H), 1.73e1.66 (m, 4H). 13C NMR (150 MHz, DMSO-d6)
white solid, mp 109e112 ꢁC. 1H NMR (600 MHz, CDCl3)
d
9.11 (s,1H),
d 199.9, 141.1, 140.5, 129.3, 128.2, 119.5, 117.8, 40.6, 24.8, 24.3, 20.4,
7.71 (d, J¼8.4 Hz, 1H), 7.37 (d, J¼8.4 Hz, 1H), 3.97 (s, 3H), 3.26e3.23
20.2. HRMS (ESI): calculated for [MþH]þ C14H18NOþ 216.1383;
(m, 2H), 2.67e2.65 (m, 2H), 2.26e2.21 (m, 2H). 13C NMR (150 MHz,
found 216.1384.
CDCl3)
d 191.9, 167.0, 135.5, 133.2, 129.3, 125.4, 124.8, 124.7, 124.6,
122.7, 52.2, 37.8, 24.8, 24.7. HRMS (ESI): calculated for [MþH]þ
4.4.5. 2-((3-Fluorophenyl)amino)cyclohept-2-enone (3e). Following
the general procedure, 3e was purified by silica gel chromatography
(1% TEA/PE). Yield: 258 mg, 59%, yellow oil. 1H NMR (600 MHz,
þ
C14H13ClNO3 278.0578; found 278.0578.
4.3.12. 8,9-Dihydro-7H-benzo[a]carbazol-10(11H)-one
(2l). Following the general procedure, 2l was purified by silica gel
chromatography (10% EA/PE). Yield: 51 mg, 36%, white solid,
DMSO-d6)
d
7.32 (s, 1H), 7.13 (dd, J¼7.8, 1.8 Hz, 1H), 6.66 (dd, J¼7.8,
1.8 Hz, 1H), 6.59 (d, J¼12.6 Hz, 1H), 6.50 (t, J¼7.2 Hz, 1H), 6.46 (td,
J¼8.4, 2.4 Hz, 1H), 2.66e2.63 (m, 2H), 2.46e2.42 (m, 2H), 1.76e1.69
mp 230e232 ꢁC. 1H NMR (600 MHz, CDCl3)
d
12.57 (s, 1H), 8.69 (d,
(m, 4H). 13C NMR (150 MHz, DMSO-d6)
d 200.0, 163.0 (d,

H. Shi et al. / Tetrahedron 70 (2014) 2753e2760
2759
JFeC¼240 Hz), 146.8, 146.7 (d, JFeC¼11 Hz), 139.4, 130.2 (d,
JFeC¼10 Hz), 127.1 (d, JFeC¼2 Hz), 111.7, 104.5 (d, JFeC¼20 Hz), 102.1
(d, JFeC¼25 Hz), 40.8, 24.8, 24.6, 20.6. HRMS (ESI): calculated for
[MþH]þ C13H15FNOþ 220.1132; found 220.1131.
2.44 (s, 3H), 2.10e2.05 (m, 2H), 2.01e1.96 (m, 2H). The 1H NMR data
were consistent with those in the literature.
4.5.5. 1-Fluoro-7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-one
(4e)/3-fluoro-7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-one
(4e0). Following the general procedure, 4e/4e0 was obtained after
a reaction lasted for 1 h, purified by silica gel chromatography (10%
EA/PE). Yield: 55 mg, 51%, white solid, mp 122e128 ꢁC. 1H NMR
4.4.6. 2-((3-Chloro-4-fluorophenyl)amino)cyclohept-2-enone
(3f). Following the general procedure, 3f was purified by silica gel
chromatography (1% TEA/PE). Yield: 318 mg, 63%, yellow solid,
mp 57e60 ꢁC. 1H NMR (600 MHz, DMSO-d6)
d
7.23 (s, 1H), 7.17 (t,
(600 MHz, CDCl3) isomer 4e
d
9.46 (s, 1H), 7.56 (dd, J¼9.0, 5.4 Hz,
J¼9.0 Hz,1H), 6.99 (dd, J¼6.6, 2.4 Hz,1H), 6.86e6.82 (m,1H), 6.43 (t,
1H), 7.06e7.03 (m, 1H), 6.90e6.86 (m, 1H), 3.12e3.09 (m, 2H),
2.87e2.84 (m, 2H), 2.09e2.05 (m, 2H), 2.01e1.96 (m, 2H); isomer
J¼7.2 Hz, 1H), 2.65e2.63 (m, 2H), 2.45e2.41 (m, 2H), 1.75e1.69 (m,
4H). 13C NMR (150 MHz, DMSO-d6)
d
199.8, 150.0 (d, JFeC¼236 Hz),
4e0
d
9.46 (s, 1H), 7.23e7.19 (m, 1H), 7.16e7.12 (m, 1H), 6.73e6.69
(m, 1H), 3.36e3.33 (m, 2H), 2.87e2.84 (m, 2H), 2.09e2.05 (m, 2H),
2.01e1.96 (m, 2H). 13C NMR (150 MHz, CDCl3)
195.0, 194.6, 162.0
141.9 (d, JFeC¼2 Hz), 139.8, 125.3 (d, JFeC¼6 Hz), 119.2 (d, JFeC¼5 Hz),
117.3, 116.7 (d, JFeC¼22 Hz), 116.3 (d, JFeC¼7 Hz), 40.8, 24.8, 24.5,
20.5. HRMS (ESI): calculated for [MþH]þ C13H14ClFNOþ 254.0742;
found 254.0742.
d
(d, JFeC¼242 Hz), 159.0 (d, JFeC¼249 Hz), 139.0 (d, JFeC¼10 Hz), 137.1
(d, JFeC¼13 Hz), 133.4 (d, JFeC¼3 Hz), 132.9 (d, JFeC¼2 Hz), 127.0 (d,
JFeC¼7 Hz), 126.9 (d, JFeC¼8 Hz), 124.7 (d, JFeC¼32 Hz), 123.6 (d,
JFeC¼4 Hz), 122.6 (d, JFeC¼11 Hz), 117.2 (d, JFeC¼18 Hz), 109.6 (d,
JFeC¼25 Hz), 108.1 (d, JFeC¼4 Hz), 104.8 (d, JFeC¼19 Hz), 97.8 (d,
JFeC¼26 Hz), 42.8, 42.8, 27.3, 26.8, 26.6, 25.8, 22.8, 22.4. HRMS (ESI):
calculated for [MþH]þ C13H13FNOþ 218.0976; found 218.0976.
4.5. General procedure for the synthesis of substituted
7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-one 4
To a solution of 2-(substituted phenylamino)cyclohept-2-enone
3 (0.5 mmol) in TFE (10 mL) and TEA (5 mmol) was added PIFA
(0.75 mmol). The mixture was stirred at room temperature and
monitored by TLC. After the starting material was consumed, sat-
urated NaHCO3 solution (10 mL) was added with stirring. The
mixture was then extracted with EA (20 mLꢂ3). The combined
organic layer was washed with brine (20 mL), dried with NaSO4,
filtered, and concentrated under vacuum. Purification of the crude
residue by column chromatography using PE and EA as eluent gave
compounds 4aef.
4.5.6. 1-Chloro-2-fluoro-7,8,9,10-tetrahydrocyclohepta[b]indol-
6(5H)-one (4f)/3-chloro-2-fluoro-7,8,9,10-tetrahydrocyclohepta -[b]
indol-6(5H)-one (4f0). Following the general procedure, 4f/4f0 was
obtained after a reaction lasted for 1 h, purified by silica gel chro-
matography (10% EA/PE). Yield: 61 mg, 48%, white solid,
mp 153e157 ꢁC. 1H NMR (600 MHz, CDCl3) isomer 4f
d
9.51 (s, 1H),
7.23 (dd, J¼9.0, 3.6 Hz, 1H), 7.12 (t, J¼9.0 Hz, 1H), 3.55e3.52 (m, 2H),
2.88e2.85 (m, 2H), 2.11e1.93 (m, 4H); isomer 4f0
9.41 (s, 1H), 7.42
d
(d, J¼6.0 Hz, 1H), 7.33 (d, J¼9.0 Hz, 1H), 3.06e3.03 (m, 2H),
4.5.1. 7,8,9,10-Tetrahydrocyclohepta[b]indol-6(5H)-one17b
(4a). Following the general procedure, 4a was obtained after a re-
action for 2 h, purified by silica gel chromatography (10% EA/PE).
Yield: 60 mg, 60%, white solid, mp 140e143 ꢁC. 1H NMR (600 MHz,
2.88e2.85 (m, 2H), 2.11e1.93 (m, 4H). 13C NMR (150 MHz, CDCl3)
d
195.3, 194.9, 153.0 (d, JFeC¼237 Hz), 152.6 (d, JFeC¼239 Hz), 134.8,
134.3, 134.1, 133.0, 126.6 (d, JFeC¼8 Hz), 125.3 (d, JFeC¼6 Hz), 124.6,
124.3 (d, JFeC¼6 Hz), 121.0 (d, JFeC¼22 Hz), 115.7 (d, JFeC¼27 Hz),
114.2 (d, JFeC¼20 Hz), 113.3, 111.3 (d, JFeC¼9 Hz), 106.7 (d,
JFeC¼23 Hz), 42.9, 42.7, 27.02, 26.7, 26.5, 25.7, 22.6, 21.9. HRMS
(ESI): calculated for [MþH]þ C13H12ClFNOþ 252.0586; found
252.0585.
CDCl3)
d
8.85 (s, 1H), 7.66 (d, J¼8.4 Hz, 1H), 7.37e7.33 (m, 2H),
7.15e7.11 (m, 1H), 3.18e3.15 (m, 2H), 2.86e2.83 (m, 2H), 2.13e2.08
(m, 2H), 2.03e1.98 (m, 2H). The 1H NMR data were consistent with
those in the literature.
4.5.2. 2-Chloro-7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-one
(4b). Following the general procedure, 4b was obtained after a re-
action lasted for 1 h, purified by silica gel chromatography (10% EA/
PE). Yield: 53 mg, 45%, white solid, mp 181e184 ꢁC. 1H NMR
Acknowledgements
We acknowledge the National Natural Science Foundation of
China (_501100001809) (#21072148), Foundation (B) for Peiyang
Scholar e Young Core Faculty of Tianjin University (2013XR-
0144), the Innovation Foundation of Tianjin University (2013XJ-
0005) and the National Basic Research Project (2014CB932201) of
the Ministry of Science and Technology of the People’s Republic
of China (_501100002855) for financial support.
(600 MHz, CDCl3)
2H), 3.10e3.07 (m, 2H), 2.87e2.84 (m, 2H), 2.11e2.06 (m, 2H),
2.02e1.97 (m, 2H). 13C NMR (150 MHz, CDCl3)
194.9, 134.8, 133.7,
d
9.15 (s, 1H), 7.61 (d, J¼1.2 Hz, 1H), 7.32e7.25 (m,
d
128.9, 127.0, 125.7, 123.7, 120.6, 113.1, 42.9, 26.6, 25.7, 22.7. HRMS
(ESI): calculated for [MþH]þ C13H13ClNOþ 234.0680; found
234.0680.
Supplementary data
4.5.3. 2-Bromo-7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-one25
(4c). Following the general procedure, 4c was obtained after a re-
action lasted for 10 min, purified by silica gel chromatography (10%
EA/PE). Yield: 66 mg, 47%, white solid, mp 180e183 ꢁC. 1H NMR
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.02.083.
(600 MHz, CDCl3)
d
8.97 (s, 1H), 7.79 (d, J¼1.2 Hz, 1H), 7.41 (dd,
References and notes
J¼8.4, 1.8 Hz, 1H), 7.25 (d, J¼9.6 Hz, 1H), 3.11e3.08 (m, 2H),
2.86e2.83 (m, 2H), 2.11e2.07 (m, 2H), 2.02e1.97 (m, 2H). The 1H
NMR data were consistent with those in the literature.
1. Li, X.; Vince, R. Bioorg. Med. Chem. 2006, 14, 2942e2955.
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H
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1H), 7.17 (d, J¼8.4 Hz, 1H), 3.13e3.10 (m, 2H), 2.84e2.82 (m, 2H),
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2760
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