Expedient Iodocyclization Approach Toward Polysubstituted 3H-Benzo[e]indoles

Article abstract of DOI:10.1002/adsc.201500275

A facile and expedient iodocyclization of 4-(2-prop-1-ynylphenyl)-1H-pyrroles towards the synthesis of polysubstituted 3H-benzo[e]indoles is reported. The transformation was optimized and the best results were obtained by using iodine (1.2 equiv,) in dichloromethane, and potassium carbonate as base. The starting 1,2,3,4-tetrasubstituted pyrroles were efficiently obtained by means of a nickel(II) chloride-promoted four-component (nitromethane, amine, 2-alkynylbenzaldehyde and ethyl acetoacetate) reaction. Further functionalization of the resulting 5-iodoheterocycles was also explored.

Full text of DOI:10.1002/adsc.201500275

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DOI: 10.1002/adsc.201500275
Expedient Iodocyclization Approach Toward Polysubstituted
3H-Benzo[e]indoles
Guilherme M. Martins,a Gilson Zeni,a Davi F. Back,a Teodoro S. Kaufman,b
and Claudio C. Silveiraa,*
a
Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil
Fax: (+55)-55-3220-8754; phone: (+55)-55-3220-8754; e-mail: silveira@quimica.ufsm.br
Instituto de Química Rosario (CONICET-UNR), Suipacha 531, Rosario, SF, S2002LRK, Argentina
b
Received: March 19, 2015; Revised: July 22, 2015; Published online: September 28, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500275.
Abstract: A facile and expedient iodocyclization of el(II) chloride-promoted four-component (nitrome-
4-(2-prop-1-ynylphenyl)-1H-pyrroles towards the thane, amine, 2-alkynylbenzaldehyde and ethyl ace-
synthesis of polysubstituted 3H-benzo[e]indoles is re- toacetate) reaction. Further functionalization of the
ported. The transformation was optimized and the resulting 5-iodoheterocycles was also explored.
best results were obtained by using iodine
(1.2 equiv,) in dichloromethane, and potassium car-
bonate as base. The starting 1,2,3,4-tetrasubstituted Keywords: 3H-benzo[e]indoles; heterocycles; iodo-
pyrroles were efficiently obtained by means of a nick- cyclization; phenylacetylenes; pyrroles
Introduction
the production of organic electroluminescent devices
(OLEDs) and organic thin film transistors (OTFTs).[6]
There are three main groups of methods that have
The 3H-benzo[e]indoles are a small subfamily within
the indoles, which is one of the most important heter- been devised for accessing 3H-benzo[e]indoles. These
ocyclic ring systems among natural products and bio- involve (i) building the pyrrole ring on a naphthalene-
active compounds.
type precursor,[7] (ii) installing the benzo ring on
This tricyclic skeleton is found among enzymes
such as indoleamine 2,3-dioxygenase (IDO), mono-
amine oxidase (MAO) and 6-phosphofructo-2-kinase/
fructose-2,6-biphosphatase 3 (PFKFB3) inhibitors,[1]
intermediates toward antineoplastic agents, including
analogues of duocarmycin and the indole antibiotic
CC-1065, one of the most potent antineoplasic agents
known, and also in the DNA-intercalanting unit of
hybrid bifunctional antitumor agents (Figure 1).[2]
The 3H-benzo[e]indole motif is an integral part of
core-modified, p-extended, expanded porphyrins,
such as some naphthorubyrin and naphthosapphyrin
derivatives,[3a] being also found among fullerene deriv-
atives,[3b] drugs for treating Alzheimerꢀs disease[3c] and
antimicrobials.[3d,e]
In addition, some benzo[e]indoles have potential
technological applications, this core being embodied
in special photochromic materials[4] and fluorescent
multivalent carbocyanine molecular probes, useful for
biomonitoring, chemosensing and optical imaging.[5]
This tricyclic skeleton is also found in materials for
Figure 1. Selected examples of useful 3H-benzo[e]indole de-
rivatives.
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Guilherme M. Martins et al.
a pre-formed indole derivative,[8] and (iii) constructing
the required benzo ring from a pyrrole and an aryl
moiety directly bound to its C-3 position[9] or tethered
to C-2.[10] A variation of the latter alternative includes
the use of the starting aryl and pyrrole moieties as
separate chemical entities.[11]
Compounds with the 3H-benzo[e]indole core have
also resulted from the thermal rearrangement of 4,5-
dihydro-1H-benzo[g]indole, and other reactions.[12]
We have recently reported a multicomponent syn-
thesis of polyfunctionalized pyrroles.[13] We have also
studied the functionalization of indoles under eco-
Scheme 1. Proposed iodocyclization strategy for the synthe-
sis of polysubstituted 3H-benzo[e]indoles.
friendly conditions[14] and have been engaged in the to the best of our knowledge, the strategy proposed
synthesis of heterocycles attached to substituted herein represents the first iodocyclization approach
indole moieties.[15]
toward building the homocyclic ring of polysubstitut-
As part of our continued interest in the chemistry ed indoles and complements other recently developed
of pyrrole and indole derivatives, we focused our at- strategies, based on well-established p-activation cata-
tention on exploring the ability of conveniently 3-sub- lysts (Au, Pt).[17] Furthermore, the incorporation of an
stituted pyrroles to undergo intramolecular cyclization iodine atom into the products offers the possibility of
reactions, to afford more structurally complex prod- rapidly increasing their molecular complexity through
ucts. Therefore, in continuation of these studies, here the incorporation of more rings or additional func-
we wish to present the results of our iodocyclization- tionalities.[18]
mediated synthesis of polysubstituted 3H-benzo[e]in-
doles (1) from 4-(2-prop-1-ynylphenyl)-1H-pyrroles
(2), as shown in Scheme 1.
Results and Discussion
Indoles and fused indoles have been repeatedly ac-
cessed by means of iodocyclization reactions, mainly Initial attempts to access the required starting pyr-
involving the construction of the heterocyclic ring by roles (2), by use of our method,[13a] proved to be prob-
[16a–f]
À
C N bond formation
or by C-2 or C-3 functional- lematic. However, the target compounds could be
ization of preformed indole derivatives.[16g,h] However, conveniently obtained, in moderate yields, by a modi-
Table 1. Four-component synthesis of the starting 1,2,3,4-tetrasubstituted 4-(2-prop-1-ynyl-phenyl)-1H-pyrroles 2a–j.
Entry No,
Aldehyde
R1
R2
R3
Time [h]
Yield [%]
Product
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
H
F
MeO
MeO
H
H
H
H
H
H
H
H
MeO
H
Ph
8
6
6
12
12
5
6
5
47
41
40
40
38
35
32
42
40
31
45
2a
2b
2c
2d
2e
2f
2g
2h
2i
4-MeC6H4
3-MeC6H4
4-ClC6H4
2-ClC6H4
Ph
Ph
H
n-Bu
4-FC6H4
Ph
9
10
11
12
6
6
3j
3a
H
H
H
H
2j
2k[a]
[a]
b-Phenethylamine (5b) was employed as the amine component.
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Expedient Iodocyclization Approach Toward Polysubstituted 3H-Benzo[e]indoles
fication of the nickel(II)-mediated four-component re- room temperature in CH2Cl2 (entry 3). Lowering the
action [2-alkynylbenzaldehyde (3),[19] ethyl acetoace- reaction temperature to 08C resulted in a diminished
tate (4), primary amine (5) and MeNO2] disclosed by yield (entry 7), which was more noticeable when the
Khan et al.[20] Advantageously, this method avoided process was conducted at À308C (entry 8).
the need for the isolation and purification of the inter-
The use of K2CO3 as base (entries 9–11) afforded
mediates, thus minimizing the total reaction time, as still better results, being useful even when as little as
well as waste and costs (Table 1). 1.2 equiv. were employed (entry 9). It also confirmed
Next, the proposed iodocyclization reaction was op- that 2 equiv. furnished the optimal product yield
timized, employing 2a as model compound. The reac- (entry 11). On the other hand, the reaction did not
tion gave the expected compound 1a in 62% yield take place in non-chlorinated solvents (entries 12–16)
(Table 2, entry 1), along with 20% of 1’a, as confirmed and compound 1’a was isolated as the sole product
by comparison with an authentic sample (entry 17). when the cyclization was carried out under HI promo-
This suggested the need for an added base to remove tion at room temperature (41% yield, entry 17) or
the HI formed. Thus, the reaction conditions were op- when catalytic amounts of TsOH were added to the
timized by adjusting the relative amounts of iodine reaction and the system was refluxed (41% yield,
and base (entries 2–6).
entry 18).
After some experimentation, it was concluded that
The alkynylpyrroles 2a–l were cyclized under the
the use of NaHCO3 (2 equiv.) and I2 (1.2 equiv.) pro- optimized conditions (Table 3, entries 1–12), affording
vided the best results, when the cyclization was run at the expected products in good to excellent yields (61-
96%) and short reaction times (0.5–2 h).
Table 2. Optimization of the iodocyclization toward 1a.[a]
Small variations were observed among the yields of
these products. Those containing chlorine as an elec-
tron-withdrawing group on the phenyl moiety not at-
tached to the pyrrole ring (entries 4 and 5) were ac-
cessed in slightly lower yields than their analogues
carrying methyl groups on this phenyl ring (entries 2
and 3).
On the other side, compound 2f, which supports an
electron-withdrawing group on its phenyl moiety at-
tached to the pyrrole, cyclized more efficiently (90%
yield) than its congeners 2g and 2h with an electron-
donating group (entries 6–8), whereas the related 2j
which carries the fluoride on the other phenyl ring af-
forded 1j in good yield (65%, entry 10).
However, modifying the substituent attached to the
pyrrolic nitrogen to a b-phenethyl group (2k) and the
use of 1,2,4-trisubstituted pyrrole derivative 2l, which
lacks the 3-ethoxycarbonyl group, had essentially no
effect on the efficiency of the iodocyclization process
(entries 11 and 12, respectively).
Interestingly, compound 2i, which carries an ali-
phatic substituent, furnished only a 61% yield of 1i
(entry 9). This result underscores the relevance of the
structure of the disubstituted alkyne on the success of
the transformation.
Entry
No.
Solvent
Base
[equiv.]
Iodine
[equiv.]
Yield
[%]
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
THF
–
1.2
2.0
1.2
1.0
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
–
62[b]
80
84
81
82
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (2.0)
NaHCO3 (1.2)
NaHCO3 (2.0)
NaHCO3 (2.0)
K2CO3 (1.2)
K2CO3 (0.5)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
–
83
80[c]
63[d]
90
9
10
11
12
13
14
15
16
17
18
82
93
[e]
–
–
–
–
[e]
[e]
DMF
H2O
PEG-400
CH2Cl2
CH2Cl2
[e]
The single crystal X-ray analysis of compound 1a
(Figure 2) confirmed its structure and evidenced that
the 3H-benzo[e]indole skeleton forms an essentially
[e]
–
41[f,g]
41[g,h]
–
–
À
À
À
planar tricyclic core, where the C9’ C9’’ C3’ N3 di-
hedral angle measures 172.68.
[a]
Pyrrole 2a (0.25 mmol), base, I2, solvent (2 mL), 0.5 h,
room temperature.
Along with 20% 1’a (by H NMR).
Examination of the structure in Figure 2 also re-
vealed that the aromatic rings of the N-benzyl moiety
attached to C-4 are contained in quasi-parallel planes
adopting almost perpendicular positions with regard
[b]
[c]
[d]
[e]
[f]
1
At 08C.
At À308C.
No products were formed.
With HI at room temperature.
The yield of 1’a is given.
With TsOH under reflux.
À
À
À
to the tricyclic core, where the C26 C21 C4 C5,
C15 C14 N3 C2 and N3 C14 C15 C20 dihedral
[g]
[h]
À
À
À
À
À
À
angles are 95.58, 89.98 and 176.88, respectively.[21]
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Guilherme M. Martins et al.
Table 3. Synthesis of the 3H-benzo[e]indoles (1a–k) employing the iodocyclization of 4-(2-alkynylaryl)pyrroles (2a–k).[a]
Entry No.
Pyrrole
R1
R2
R3
Time [h]
Product
Yield [%][b]
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
H
H
H
H
F
MeO
MeO
H
H
H
H
H
H
H
H
MeO
H
Ph
0.5
1
1
1
2
0.5
2
2
2
1
1a
1b
1c
1d
1e
1f
1g
1h
1i
93
96
94
90
89
93
89
73
61
65
85[c]
90
4-MeC6H4
3-MeC6H4
4-ClC6H4
2-ClC6H4
Ph
Ph
Ph
n-Bu
4-FC6H4
Ph
9
10
11
12
2j
H
H
H
H
H
H
1j
1k
1l
2k
0.5
1
2l[d]
Ph
[a]
Pyrrole 2 (0.25 mmol), K2CO3 (2 equiv.), I2 (1.2 equiv.), CH2Cl2 (2 mL), room temperature.
After purification by column chromatography.
The N-substituent is PhCH2CH2.
[b]
[c]
[d]
Aldehyde 2l lacks the 3-CO2Et group.
pyrrole as a nucleophilic aryl[22] was advanced based
on those projected for analogous cyclizations involv-
ing I2, ICl[23] or organometallic (Au, Pt, Ga, In, Fe)
catalysis.[24]
In this proposal, it is assumed that iodine coordi-
nates with the triple bond, thereby generating the in-
termediate A. In turn, the loss of iodide anion affords
iodonium ion B, which is attacked intramolecularly by
the nucleophilic C-5 carbon of the pyrrole, resulting
in a 6-endo-digonal cyclization toward C.
Finally, elimination of HI from intermediate C and
subsequent aromatization would drive the formation
of the 3H-benzo[e]indole 1. Although the reaction
can take place with iodine alone, the addition of solid
K2CO3 as a mild base serves to scavenge the HI as it
is produced, preventing the formation of the acid-cat-
alyzed side products (1’).
It was considered that the resulting 5-iodo deriva-
tives 1 can be further functionalized for increasing
their structural complexity, thus favorably contribu-
ting to broaden the scope of the iodocyclization pro-
cess.
Luckily, it was observed that exposure of 1a to di-
phenylacetylene under Pd(OAc)2 catalysis in DMF
gave rise to an alkyne annulation (Scheme 3). The use
Figure 2. ORTEP projection of compound 1a.[21]
A reaction mechanism (Scheme 2), where the key of 1.0 equiv. LiCl and 2.0 equiv. NaOAc efficiently
iodocyclization step involves the ring closure of the provided the polycyclic derivative 6a in 98% yield.[25]
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Expedient Iodocyclization Approach Toward Polysubstituted 3H-Benzo[e]indoles
moderate yield, by a nickel(II)-promoted four-compo-
nent reaction.
The modular nature of the multicomponent trans-
formation enables the inclusion of multiple points of
diversification and, as demonstrated, the resulting io-
docyclization products can be further functionalized,
rapidly providing access to polycyclic compounds with
increased structural complexity.
Experimental Section
General Procedure for the Synthesis of the 1,2,3,4-
Tetrasubstituted Pyrroles 2a–k
Benzylamine (10 mmol) and ethyl acetoacetate (10 mmol)
were successively added to
a mixture of NiCl2·6H2O
(10 mol%) in MeNO2 (10 mL), magnetically stirred at room
temperature. After ~10 min, formation of a precipitate was
observed and the corresponding aldehyde (10 mmol) was
added. The open system was heated at 808C for 5–12 h.
After the reaction was completed, the system was cooled to
room temperature and the products were extracted with
EtOAc (3”100 mL), the organic phase was washed with
water and brine, and dried over anhydrous MgSO4 and fil-
tered. The solvent was evaporated under reduced pressure
and the residue was purified via column chromatography on
silica gel, eluting with EtOAc:hexane (5:95).
General Procedure for the Synthesis of the 3H-
Benzo[e]indoles 1a–l
Scheme 2. Proposed mechanism for the iodocyclization of
the 4-(2-alkynylaryl)pyrrole derivatives 2.
Solid K2CO3 (0.5 mmol) was added to a solution of the pyr-
role (0.25 mmol) in CH2Cl2 (2 mL) and the system was
stirred at room temperature for 10min. Then, it was treated
dropwise with a solution of iodine (0.3mmol) in CH2Cl2
(2 mL). After the reaction was completed, the product was
extracted with CH2Cl2 (3”50mL). The combined organic
extracts were successively washed with 15% aqueous
Na2S2O3 (50mL), water and brine, dried over MgSO4 and
filtered. The solvent was evaporated under reduced pressure
and the residue was purified via column chromatography on
silica gel eluting with EtOAc:hexane (10:90).
Ethyl 11-Benzyl-12-methyl-5,6-diphenyl-11H-
benzo[e]naphtho[2,1-g]indole-13-carboxylate (6a)
Diphenylacetylene (89 mg, 0.5 mmol), Pd(OAc)2 (5 mg,
5 mol%), NaOAc (41 mg, 0.5 mmol) and LiCl (10 mg,
0.25 mmol) were successively added to a stirred solution of
1a (139 mg, 0.25 mmol) in DMF (1 mL). The system was
heated at 1008C for 24 h. After the reaction was completed,
the products were extracted with EtOAc (4”25 mL) and
successively washed with water (30 mL) and brine (3”
10 mL). The extract was dried over MgSO4, filtered and con-
centrated under reduced pressure. The residue was purified
via column chromatography on silica gel, eluting with
hexane. The product was obtained as a yellow solid; yield:
145 mg (98%); mp 236–236.58C. 1H NMR (400 MHz,
CDCl3): d=8.73 (ddd, J=0.5, 1.4 and 8.3 Hz, 1H), 8.35–8.33
(m, 1H), 7.69–7.64 (m, 3H), 7.47–7.38 (m, 3H), 7.35–7.31
Scheme 3. Functionalization of the 3H-benzo[e]pyrrole 1a.
Conclusions
In conclusion, we have developed an efficient synthe-
sis of 3H-benzo[e]indoles by means of the iodocycliza-
tion of 4-(2-prop-1-ynylphenyl)-1H-pyrroles. The
latter were conveniently accessed, in one-pot and in (m, 2H), 7.22–7.17 (m, 2H), 7.07–7.06 (m, 4H), 7.01–6.90
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Guilherme M. Martins et al.
(m, 5H), 6.27 (d, J=7.2 Hz, 2H), 5.71 (d, J=15.6 Hz, 1H),
5.36 (d, J=15.6 Hz, 1H), 4.54–4.51 (m, 2H), 2.67 (s, 3H),
1.48 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
167.3, 143.6, 143.1, 139.5, 137.4, 136.4, 136.0, 132.5, 131.8,
131.5, 130.8, 130.5, 129.6, 128.8, 128.3, 128.1, 128.0, 127.5,
127.3, 126.9, 126.8, 126.6, 126.3, 126.1, 126.0, 125.9, 125.5,
125.0, 124.7, 123.1, 121.8, 121.5, 111.9, 60.5, 51.6, 14.4, 13.1;
MS: m/z (rel. int. %)=595 (M+, 17), 458 (10), 419 (23), 254
(14), 149 (13), 105 (100), 91 (84), 77 (45). HR-MS (ESI): m/
z=596.2583, calcd. for C43H33NO2 ([M+H]+): 596.2590.
Mirza, J. Heterocycl. Chem. 2012, 49, 413–416; d) T. D.
Lash, B. E. Smith, M. J. Melquist, B. A. Godfrey, J.
Org. Chem. 2011, 76, 5335–5345; e) G. W. Wang, H.-T.
Yang, C.-B. Miao, Y. Xu, F. Liu, Org. Biomol. Chem.
2006, 4, 2595–2599; f) S. Selvi, S.-C. Pu, Y.-M. Cheng,
J.-M. Fang, P. -T. Chou, J. Org. Chem. 2004, 69, 6674–
6678; g) D. W. Yue, T. L. Yao, R. C. Larock, J. Org.
Chem. 2006, 71, 62–69; h) K. R. Roesch, R. C. Larock,
J. Org. Chem. 2001, 66, 412–420; i) K. R. Roesch, R. C.
Larock, Org. Lett. 1999, 1, 1551–1553; j) R. C. Larock,
E. K. Yum, M. D. Refvik, J. Org. Chem. 1998, 63, 7652–
7662.
[8] a) A. Bej, A. Chakraborty, A. Sarkar, RSC Adv. 2013,
3, 15812–15819; b) S. M. Bronner, K. B. Bahnck, N. K.
Garg, Org. Lett. 2009, 11, 1007–1010; c) A. C. Kinsman,
V. Snieckus, Tetrahedron Lett. 1999, 40, 2453–2456.
[9] a) R. Y. Huang, P. T. Franke, N. Nicolaus, M. Lautens,
Tetrahedron 2013, 69, 4395–4402; b) D. G. Hulcoop, M.
Lautens, Org. Lett. 2007, 9, 1761–1764; c) L. M.
Hodges, M. L. Spera, M. W. Moody, W. D. Harman, J.
Am. Chem. Soc. 1996, 118, 7117–7127.
[10] a) H. Ohno, M. Iuchi, N. Kojima, T. Yoshimitsu, N.
Fujii, T. Tanaka, Chem. Eur. J. 2012, 18, 5352–5360;
b) A. K. Yadav, I. Ila, H. Junjappa, Eur. J. Org. Chem.
2010, 338–344; c) P. P. Singh, A. K. Yadav, I. Ila, H.
Junjappa, J. Org. Chem. 2009, 74, 5496–5501; d) M. E.
Hayes, H. Shinokubo, R. L. Danheiser, Org. Lett. 2005,
7, 3917–3920.
[11] S. Paria, O. Reiser, Adv. Synth. Catal. 2014, 356, 557–
562.
[12] a) B. B. Trofimov, A. M. Vasil’tsov, I. A. Ushakov, A. V.
Ivanov, E. Y. Schmidt, A. I. Mikhaleva, Mend.
Commun. 2007, 17, 296–298; b) A. Padwa, H. Ku, A.
Mazzu, J. Org. Chem. 1978, 43, 381–387.
[13] a) C. C. Silveira, S. R. Mendes, G. M. Martins, S. C.
Schlçsser, T. S. Kaufman, Tetrahedron 2013, 69, 9076–
9085; b) C. C. Silveira, M. P. Fortes, S. R. Mendes, Curr.
Org. Chem. 2012, 16, 1540–1548.
[14] a) J. B. Azeredo, M. Godoi, G. M. Martins, C. C. Sil-
veira, A. L. Braga, J. Org. Chem. 2014, 79, 4125–4130;
b) C. C. Silveira, S. R. Mendes, J. R. Soares, F. N. Victo-
ria, D. M. Martinez, L. Savegnago, Tetrahedron Lett.
2013, 54, 4926–4929; c) C. C. Silveira, S. R. Mendes, L.
Wolf, G. M. Martins, L. von Mühlen, Tetrahedron 2012,
68, 10464–10469.
Acknowledgements
The financial support by UFSM, CAPES and CNPq is grate-
fully acknowledged. TSK also thanks CONICET and
ANPCyT.
References
[1] a) M. Tanaka, X. Li, H. Hikawa, T. Suzuki, K. Tsutsu-
mi, M. Sato, O. Takikawa, H. Suzuki, Y. Yokoyama,
Bioorg. Med. Chem. 2013, 21, 1159–1165; b) P. Chand,
J. A. Chesney, B. F. Clem, G. H. Tapolsky, S. Telang,
J. O. Trent, WO Patent WO 2011/103557, 2011; c) M.
Kai, A. Noda, H. Noda, S. Goto, Chem. Pharm. Bull.
1988, 36, 3604–3608.
[2] a) A. G. Neo, C. López, A. López, L. Castedo, G. Tojo,
Tetrahedron 2013, 69, 11010–11016; b) L. Tietze, J. M.
von Hof, WO Patent WO 2011/054837, 2011; c) G. B.
Jones, J. E. Mathews, Tetrahedron 1997, 53, 14599–
14614.
[3] a) V. S. Shetti, S.-T. Kee, C.-H. Lee, Chem. Asian J.
2014, 9, 734–738; b) G. W. Wang, H.-T. Yang, C. B.
Miao, Y. Xu, F. Liu, Org. Biomol. Chem. 2006, 4, 2595–
2599; c) H. Bruderer, T. Godel, R. Imhof, R. Jakob-
Roetne, U.S. Patent 5,318,967, 1994; d) S. A. Samso-
niya, M. V. Trapaidze, N. A. Kuprashvili, Pharm. Chem.
J. 2009, 43, 92–94; e) S. A. Samsoniya, N. A. Esakiya,
S. V. Dolidze, M. V. Trapaidze, Z. S. Lomtatidze, N. N.
Suvorov, Pharm. Chem. J. 1991, 25, 40–43.
[4] S. Izumi, Y. Kawabata, Y. Takeda, J. Momoda, H.
Nagoh, European Patent EP 1184379, 2000.
[15] a) B. L. Kuhn, M. P. Fortes, T. S. Kaufman, C. C. Sil-
veira, Tetrahedron Lett. 2014, 55, 1648–1652; b) M. M.
Bassaco, M. P. Fortes, D. F. Back, T. S. Kaufman, C. C.
Silveira, RSC Adv. 2014, 4, 60785–60797; c) M. P.
Fortes, M. M. Bassaco, T. S. Kaufman, C. C. Silveira,
RSC Adv. 2014, 4, 34519–34530; d) M. M. Bassaco,
M. P. Fortes, T. S. Kaufman, C. C. Silveira, RSC Adv.
2015, 5, 21112–21124.
[16] a) B. Gabriele, R. Mancuso, R. C. Larock, Curr. Org.
Chem. 2014, 18, 341–358; b) H. Song, Y. Liu, Q. Wang,
Org. Lett. 2013, 15, 3274–3277; c) Z. He, H. Li, Z. Li, J.
Org. Chem. 2010, 75, 4636–4639; d) R. Halim, P. J.
Scammells, B. L. Flynn, Org. Lett. 2008, 10, 1967–1970;
e) T. Yao, D. Yue, R. C. Larock, J. Comb. Chem. 2005,
7, 809–812; f) T. Yao, D. Yue, R. C. Larock, J. Org.
Chem. 2005, 70, 9985–9989; g) S. D. Gawande, V.
Kavala, M. R. Zanwar, C.-W. Kuo, H.-N. Huang, C.-H.
[5] a) N. A. López, C. J. Abelt, J. Photochem. Photobiol.
A: Chem. 2012, 238, 35–40; b) Y. Ye, S. Bloch, J. Kao,
S. Achilefu, Bioconjugate Chem. 2005, 16, 51–61;
c) Y. H. Lin, R. Weissleder, C. H. Tung, Bioconjugate
Chem. 2002, 13, 605–610.
[6] a) F. Kakiuchi, J. Oguma, European Patent EP
2241563, 2009; b) J.-S. Lee, European Patent EP
2772493, 2014; c) O. Molt, C. Lennartz, E. Fuchs, K.
Dormann, N. Langer, C. Schildknecht, J. Rudolph, G.
Wagenblast, S. Watanabe, U.S. Patent 2011/0098473,
2011; d) A. Facchetti, H. Usta, J. Wang, C. Huang, M.
Denti, C. Newman, U.S. Patent 2013/0146851, 2013.
[7] a) H.-T. Yang, X.-C. Liang, Y.-H. Wang, Y. Yang, X.-Q.
Sun, C.-B. Miao, J. Org. Chem. 2013, 78, 11992–11998;
b) X. Wang, J. Liu, H. Guo, C. Ma, X. Gao, K. Zhou,
G. Huang, Synthesis 2012, 44, 1037–1042; c) J. Azizian,
F. Sheikholeslami, J. Hosseini, M. Mohammadi, B.
3260
asc.wiley-vch.de
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 3255 – 3261

FULL PAPERS
Expedient Iodocyclization Approach Toward Polysubstituted 3H-Benzo[e]indoles
He, T.-S. Kuo, C.-F. Yao, Adv. Synth. Catal. 2013, 355,
3022–3036; h) S. K. Sharma, A. K. Mandadapu, B.
Kumar, B. Kundu, J. Org. Chem. 2011, 76, 6798–6805.
[17] a) Y. Li, J. Waser, Angew. Chem. 2015, 127, ####–####;
Angew. Chem. Int. Ed. 2015, 54, 5438–5442; b) A. S. K.
Hashmi, W. B. Yang, F. Rominger, Chem. Eur. J. 2012,
18, 6576–6580; c) B. Alcaide, P. Almendros, J. M.
Alonso, M. T. Quiros, P. Gadzinski, Adv. Synth. Catal.
2011, 353, 1871–1876; d) Y. A. Qiu, W. Q. Kong, C. L.
Fu, S. M. Ma, Org. Lett. 2012, 14, 6198–6201.
[18] N. A. Danilkina, A. E. Kulyashova, A. F. Khlebnikov,
S. Bräse, I. A. Balova, J. Org. Chem. 2014, 79, 9018–
9045.
[19] P. C. Too, S. Chiba, Chem. Commun. 2012, 48, 7634–
7636.
[20] A. T. Khan, M. Lal, P. R. Bagdi, R. S. Basha, P. Sarava-
nam, S. Patra, Tetrahedron Lett. 2012, 53, 4145–4150.
[21] CCDC 1045258 (1a) contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
[22] a) S. Akbar, K. Srinivasan, Eur. J. Org. Chem. 2013, 9,
1663–1666; b) T. Yao, M. A. Campo, R. C. Larock, J.
Org. Chem. 2005, 70, 3511–3517; c) C. T. Bui, B. L.
Flynn, Mol. Diversity 2011, 15, 83–89.
[23] a) Y. Cheb, C. Huang, X. Liu, E. Perl, Z. Chen, J. Nam-
gung, G. Subramaniam, G. Zhang, W. H. Hersh, J. Org.
Chem. 2014, 79, 3452–3464; b) A. K. Verma, S. P.
Shukla, J. Singh, V. Rustagi, J. Org. Chem. 2011, 76,
5670–5684; c) S. A. Worlikar, R. C. Larock, Org. Lett.
2009, 11, 2413–2416; d) S. A. Worlikar, T. Kesharwani,
T. Yao, R. C. Larock, J. Org. Chem. 2007, 72, 1347–
1353; e) T. Kesharwani, S. A. Worlikar, R. C. Larock, J.
Org. Chem. 2006, 71, 2307–2312.
[24] a) V. Mamane, P. Hannen, A. Fürstner, Chem. Eur. J.
2004, 10, 4556–4575; b) M. T. Reetz, K. Sommer, Eur.
J. Org. Chem. 2003, 3485–3496; c) H. Inoue, N. Chatani,
S. Murai, J. Org. Chem. 2002, 67, 1414–1417; d) B. C.
Ranu, Eur. J. Org. Chem. 2000, 2347–2356.
[25] a) Z. Liu, R. C. Larock, Angew. Chem. 2007, 119, 2587–
2590; Angew. Chem. Int. Ed. 2007, 46, 2535–2538; b) T.
Yao, M. A. Campo, R. C. Larock, Org. Lett. 2004, 6,
2677–2680; c) R. C. Larock, M. J. Doty, Q. Tian, J. M.
Zenner, J. Org. Chem. 1997, 62, 7536–7537.
Adv. Synth. Catal. 2015, 357, 3255 – 3261
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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