Iodobenzene Dichloride/Zinc Chloride-Mediated Synthesis of N-Alkoxyindole-3-carbonitriles from 3-Alkoxyimino-2-arylalkylnitriles via Intramolecular Heterocyclization

Article abstract of DOI:10.1002/adsc.201701111

A series of N-alkoxyindole-3-carbonitriles were synthesized, under mild conditions, via intramolecular heterocyclization of the readily available 3-alkoxyimino-2-arylalkylnitriles mediated by iodobenzene dichloride/zinc chloride. The mechanism of the reaction proposes the formation of a key intermediate of nitrenium cation from a chlorination and dechlorination process facilitated by the hypervalent iodine reagent and Lewis acid respectively. (Figure presented.).

Full text of DOI:10.1002/adsc.201701111

Title: Iodobenzene Dichloride/Zinc Chloride-Mediated Synthesis of N-
Alkoxyindole-3-carbonitriles from 3-Alkoxyimino-2-arylalkylnitriles
via Intramolecular Heterocyclization
Authors: Yunfei Du, Zhongxiang Yun, Ran Cheng, Jiyun Sun, and
Daisy Zhang-Negrerie
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701111
Link to VoR: http://dx.doi.org/10.1002/adsc.201701111

10.1002/adsc.201701111
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Iodobenzene Dichloride/Zinc Chloride-Mediated Synthesis of
N-Alkoxyindole-3-carbonitriles from 3-Alkoxyimino-2-
arylalkylnitriles via Intramolecular Heterocyclization
Zhongxiang Yun,a Ran Cheng,a Jiyun Sun,a Daisy Zhang-Negrerie,a and Yunfei Dua,b*
a
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and
Technology, Tianjin University, Tianjin 300072, China.
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
b
Fax: +86-22-27404031; Tel: +86-22-27404031; duyunfeier@tju.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A series of N-alkoxyindole-3-carbonitriles
were synthesized, under mild conditions, via
intramolecular heterocyclization of the readily
available 3-alkoxyimino-2-arylalkylnitriles mediated
by iodobenzene dichloride/zinc chloride. The
mechanism of the reaction proposes the formation of a
key intermediate of nitrenium cation from a
chlorination and dechlorination process facilitated by
the hypervalent iodine reagent and Lewis acid
respectively.
Keywords: N-alkoxyindole; hypervalent iodine(III)
reagent;
intramolecular
heterocyclization; one-pot;
nitrenium ion
Figure 1. Representative Natural products and
Pharmaceutical agents containing the N-alkoxyinodole
framework.
The N-alkoxyinodole framework bearing
a
characteristic N-alkoxy moiety is often found in
natural products.1 For instances, 9-methoxycarbazole-
3-carbaldehyde, isolated from Murraya euchrestifolia
HAYATA (Rutaceae),[1b] paniculidine B, isolated
from Murraya paniculata (Linn.) Jack,[2] and
phytoalexin, produced by wasabi (Wasabia japonica.
syn. Eutrema wasab)[3] (Figure 1) all possess the N-
alkoxyindole motif in their respective chemical
structure. Furthermore, N-alkoxyinodole compounds
can also be used as a pharmacophore in drug
discoveries.[4] For examples, indole-3-carbinol,
isolated from Brassica, has shown to have
anticarcinogenic effects.[5] N-methoxylated indole-3-
carbinol showed stronger inhibition to the colon
cancer cell lines DLD-1 and HTC-115 and higher
efficiency as an inducer of cytochrome P-450 1A1 in
cultured cells than unsubstituted indole-3-carbinol.[5,6]
Similarly, functionalization of the indole nitrogen
with a methoxy moiety in melatonin led to an
increase of activity to nearly five folds.[7] Moreover,
N-alkoxyindoles are used to serve as precursors of
other indole derivatives by dealkoxylation through
nucleophilic substitution reactions[8] with 1-alkoxy as
the leaving group[9] and hydrogenation reaction.[10]
Though N-alkoxyindole derivatives have received
considerable attention from organic and medicinal
chemists, only a few approaches have been explored
to achieve the N-alkoxyindole skeleton compared to
the existing plethora syntheses of many other types of
substituted indoles. This is mainly due to the
requirement of specific starting materials and/or
reagents for constructing the N-alkoxyindole
framework. The most common strategy is
methylation of N-hydroxyindoles, via Somei’s
method,
to
produce
N-methoxyindole
derivatives.[8d,9a,11] Intramolecular cyclization is
another commonly adopted approach. Selvakumar et
al
reported
the
cyclization
of
2-(2-
nitrophenyl)malonate or 2-(2-nitrophenyl)cyanoester
mediated by NaCl/DMSO at high temperatures.[12]
Penoni’s group also reported a one-pot strategy for
the preparation of N-methoxyindoles via base-
promoted cycloaddition of nitrosoarenes with alkynes
followed by methylation with Me2SO4.[13] In 2003,
Creary and co-workers realized a DMSO facilitated
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701111
Advanced Synthesis & Catalysis
intramolecular
cyclization
of
2-chloro-2,2-
chlorination-dechlorination process facilitated by a
diphenylacetaldehyde O-methyloxime during their
research on carbocation-forming reactions.[14] Our
group also realized the synthesis of N-alkoxyindole-
3-carbonitrile through an intramolecular oxidative
combination of a hypervalent iodine reagent,
iodobenzene dichloride (PhICl2), and Lewis acid, zinc
chloride (ZnCl2), and followed by intramolecular
hetrocyclization reaction (Scheme 1c).
cyclization
of
3-alkoxyimino-2-arylalkylnitriles
3-(Methoxyimino)-2-phenylbutanenitrile 1a, which
can be easily prepared from the commercially
available β-ketonitrile in two steps according to the
known procedures,[20,21] was selected as the model
substrate to test the feasibility of the proposed
transformation. When substrate 1a was treated with
1.5 equiv of PhICl2 in 1,2-dichloroethane (DCE) at
room temperature, a chlorinated imine product 1a′
was obtained in nearly quantitative yield (Scheme 2).
mediated by FeCl3 in which FeCl3 functioned as a
single electron oxidant.[15]
Scheme 2. PhICl2-Mediated Chlorination of 3-
Methoxyimino-2-phenylbutanenitrile
After the formation of 1a′, additive BF3Et2O was
added into the reaction mixture to investigate whether
the reaction could deliver the desired N-
methoxyindole product with satisfactory results such
as in a one-pot fashion. We were very pleased to find
that the second step went to completion 24 h later,
Scheme 1. Proposed Route to Access N-Alkoxyindoles
Based on Our Previously Reported Approaches for Indole
Synthesis
Hypervalent iodine(III) reagents have attracted
extensive interests from synthetic chemists during the
past several decades due to their easy-to-handle, non-
toxic and environmental benign properties compared
to other oxidative reagents involving heavy metals
such as Pb(IV), Hg(II) and Ti(III).[16] Being
recognized these desirable properties, hypervalent
iodine(III) reagents have been widely applied in
many oxidative reactions leading to the formation of
N-containing heterocycles.[17] In 2006, we utilized
phenyliodine bis(trifluoroacetate) (PIFA) as an
oxidant to realize an intramolecular cyclization
protocol for the synthesis of N-substituted indole
derivatives from N-aryl or N-alkyl enamine substrates
(Scheme 1a).[18] However, shortly afterwards we
realized the protocol did not work for 3-alkoxyimino-
2-arylalkylnitriles, an N-alkoxyimine substrate, to
afford the desired N-alkoxyindole products.[15]
Table 1. Conditions Optimization for the PhICl2/Lewis
Acid-mediated One-pot Synthesis of 3-(Methoxyimino)-2-
phenylbutanenitrile 1aa
Entrya Additive (equiv)
Solvent Time/hb Yieldc(%)
1
BF3•Et2O (2.0)
DCE
DCE
24
12
12
12
3.5
5
20
2
AlCl3 (1.0)
73
3
Zn(OAc)2•2H2O (1.0) DCE
0
4
CoCl2•6H2O (1.0)
ZnBr2 (1.0)
ZnCl2 (1.0)
ZnCl2 (2.0)
ZnCl2 (0.5)
ZnCl2 (0.5)
ZnCl2 (0.5)
ZnCl2 (0.5)
ZnCl2 (0.5)
DCE
DCE
DCE
DCE
DCE
THF
DMF
0
In 2011, we reported an alternative approach for
the formation of N-arylindoles from N-aryl enamine
substrate, the process of which involved NBS or
5
73
6
91
NCS-mediated halogenation followed by
a
7
4
81
Zn(OAc)22H2O-mediated
dehalogenation
and
8
6
93
subsequent C-N bond formation (Scheme 1b).[19]
Inspired by this work, we launched an investigation
of whether 3-alkoxyimino-2-arylalkylnitriles could
9
12
12
<5%
<5%
<5%
<5%
10
11
12
undergo
a
similar halogenation-dehalogenation
CH3CN 12
toluene 12
process to give the N-alkoxyindole product. However,
the reaction failed as neither NBS or NCS was able to
convert 3-alkoxyimino-2-arylalkylnitrile to its
halogenated product.
aReaction conditions: 1a (2.0 mmol), PhICl2 (3.0 mmol),
b
additive in solvent (20 mL). Time for the second step.
Here in this communication, we report the
cIsolated yield.
formation of N-alkoxyindole products via
a
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701111
Advanced Synthesis & Catalysis
and the desired N-methoxy-indole-3-carbonitrile 2a
was obtained in 20% (Table 1, entry 1). This
preliminary result, albeit low in yield, encouraged us
to carry out further screenings of variables to identify
seemed to be more favored than para-substituted (2d
vs. 2b in 83% vs. 63%, respectively), while those
with R1 being fluorine, both o- and p-substituted gave
the same satisfactory yield of 82% (Table 2, 2c & 2e).
In contrast, for substrates bearing electron-donating
methyl or methoxy group, the para-substituted gave
higher yields than relatively to the ortho counterpart
(Table 2, 98% vs. 81% for 2f and 2g, respectively;
and 70% vs. 61% for 2h and 2i, respectively). As
expected, for substrates bearing substituents at the
meta position, separable regioisomeric products were
obtained in a nearly equal amount (2j/2j′ and 2k/2k′).
Interestingly, for the substrate bearing a methoxy
group at meta position, only 5-methoxy indole 2l was
formed regioselectively in a 72% yield. A lower yield
of the desired product was obtained for dimethoxy
substituted imine 1m due to formation of additional
byproducts. It is worthy to note that this method is
also applicable to substrate bearing a naphthalenyl
ring, which enables the synthesis of the desired indole
compound 2n.
the
optimal
conditions
for this
one-pot
process.
dechlorination-and-hetreocyclization
Screening of various Lewis acids showed that ZnCl2
was the most effective for this transformation, which
agreed with the previous reactions[19] (Table 1, entries
2-6). The use of two-fold dosage of ZnCl2 resulted
into a lower yield (Table 1, entry 7), although the
reaction time was shortened. Reducing the amount of
ZnCl2 to 0.5 equiv increased the yield up to 93%
(Table 1, entry 8). Finally, other solvents including
THF, DMF, CH3CN and toluene were tested, but
none of them gave a better yield compared to DCE
(Table 1, entries 9-12).
Table 2. PhICl2/ZnCl2-Mediated Synthesis of N-
Methoxyindole-3-carbonitriles from 3-Methoxyimino-2-
arylalkylnitrilesa
Concerning R2, substrates carrying bulkier (than
methyl) groups such as phenyl or benzyl all afforded
the desired products 2o-q in similar moderate yields
between 66-69%.
The methoxy group in the substrate could also be
replaced with other alkoxy groups. For example,
when substrate 1r-t was subjected to the standard
conditions, the desired N-benzyloxyindole products
2r-t could be obtained in acceptable to satisfactory
yields.
Scheme 3. Derivatization of N-Alkoxyindole 2.
The obtained N-alkoxy-indole-3-carbonitriles 2
could be converted to other indole derivatives via
known methods. For examples, the methoxy group in
compound 2a could be straightforwardly removed
aReaction conditions: 1 (2.0 mmol), PhICl2 (3.0 mmol),
b
c
ZnCl2 (1.0 mmol) in DCE (20 mL). Isolated yield. Time
for the first step. dTime for the second step.
o
upon treatment with NaH in DMF at 60 C[10,23] to
provide NH-free 2-methyl-1H-indole-3-carbonitrile
3a in 58% yield. In addition, the cyano group in N-
methoxyindole 2a could be conveniently converted to
N-methoxyindole 3-carboxamide 4a in the presence
of K2CO3/H2O2 in DMSO with a modest yield of 64%,
according to a known method.[24] Furthermore, the
benzyl group in 2r could be removed by
hydrogenation over Pd/C to afford the N-OH-free N-
hydroxyindole product 5a, which is also a crucial
Under the optimized conditions,[22] studies of
feasibility and scope of this one-pot reaction were
carried out. Results summarized in Table 2 show that
a range of substituents of R1 electron-withdrawing
(fluoro, trifluoromethyl, and chloro) and electron-
donating (methoxy and methyl) groups, 2a-m were
all formed in acceptable yields between 60-98%. For
chlorine substituted substrates, ortho-substituted
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701111
Advanced Synthesis & Catalysis
skeleton found in natural products or employed as a
key intermediate in natural products syntheses[1e]
(Scheme 3).
temperature. After consumption of the 1, ZnCl2 (1.0
mmol, 0.5 equiv) was added in a portion-wise manner.
The resulting mixture was maintained at room
temperature and the reaction was monitored by TLC.
Upon completion, the residue was mixed with water
(20 mL) and extracted with DCM (3 x 20 mL). The
organic phase was washed with brine (1 x 20 mL),
dried over anhydrous Na2SO4 and solvent was
removed by rotary evaporation. The product was
isolated by flash column chromatography on silica
gel (EtOAc/PE) to afford the desired compound 2.
In the mechanistic studies, we ran the reaction in
the present of radical scavenger TEMPO. The
negative result ruled out a radical path of the reaction.
A plausible mechanistic sequence is proposed in
Scheme 4. First, nucleophilic attack of the iodine
center of PhICl2 by the nitrogen atom in substrate 1
affords the ammonium salt intermediate 6, which can
be converted to enamine 7[25] by the loss of a proton.
Then the nucleophilic addition of chloride anion to
the carbon double bond in 7 followed by the
reductive elimination of phenyl iodine in 7 gives α-
chloro imine intermediate 1′.[25c] Assisted by ZnCl2,
dechlorination occurs to convert imine 1′ to the
enamine/oxonium 8, with a resonance structure of the
highly reactive species nitrenium ion intermediate
9.[19,26] Then electrophilic cyclization occurs in 9,
followed by deprotonation/aromatization to give the
target product N-alkoxyindole 2.
Acknowledgements
We acknowledge the National Science Foundation of China
(#21472136), Tianjin Research Program of Application
Foundation and Advanced Technology (#15JCZDJC32900) for
financial support.
References
[1] a) Y. Konda, M. Onda, A. Hirano, S. Omura, Chem.
Pharm. Bull. 1980, 28, 2987-2993; b) C. Ito, T.-S. Wu,
H. Furukawa, Chem. Pharm. Bull. 1988, 36, 2377-2380;
c) D. L. Boger, H. Keim, B. Oberhauser, E. P.
Schreiner, C. A. Foster, J. Am. Chem. Soc. 1999, 121,
6197-6205; d) T. Kinoshita, S. Tatara, U. Sankawa,
Chem. Pharm. Bull. 1985, 33, 1770-1773; e) T.
Kawasaki, M. Tabata, K. Nakagawa, K. Kobayashi, A.
Kodama, T. Kobayashi, M. Hasegawa, K. Tanii, M.
Somei, Heterocycles 2015, 90, 1038-1071.
[2] T. Kinoshita, S. Tatara, F.-C. Ho, U. Sankawa,
Phytochemistry 1989, 28, 147-151, and references
cited therein.
[3] M. Soledade, C. Pedras, J. L. Sorenson, Phytochemistry
1998, 49, 1959-1965.
Scheme 4. Proposed Mechanistic Pathway
[4] a) Y. Chen, Y. Wang, Z. Sun, D. Ma, Org. Lett. 2008,
10, 625-628; b) A. Brancale, R. Silvestri, Med. Res.
Rev. 2007, 27, 209-238; c) Q. V. Vo, C. Trenerry, S.
Rochfort, J. Wadeson, C. Leyton, A. B. Hughes, Bioorg.
Med. Chem. 2014, 22, 856-864.
In summary, we have developed an efficient
PhICl2/ZnCl2-mediated synthesis of N-alkoxyindole-
3-carbonitriles
from
via
3-alkoxyimino-2-
intramolecular
arylbutanenitriles
heterocyclization. The main feature of the current
method is one-pot, and the main role of the
hypervalent iodine reagent is chlorinating the
substrate which facilitates the formation of the
cyclization through forming the key nitrenium ion
intermediate. The widespread existence of the
biologically and pharmacologically significant N-
alkoxyindole compounds will render this protocol a
valuable synthetic tool in organic chemistry.
[5] A. S. Neave, S. M. Sarup, M. Seidelin, F. Duus, O.
Vang, Toxicol. Sci. 2005, 83, 126-135.
[6] P. U. Stephensen, C. Bonnesen, C. Schaldach, O.
Andersen, L. F. Bjeldances, O. Vang, Nutr. Cancer
2000, 36, 112-121.
[7] A. Tsotinis, A. Eleutheriades, K. Hough, D. Sugden,
Chem. Commun. 2003, 382-383.
[8] a) M. Somei, Yakugaku Zasshi 2008, 128, 527-563, and
references cited therein; b) M. Somei, Topics in
Heterocyclic Chemistry, Vol. 6, ed. by S. Eguchi,
Springer-Verlag, Berlin, 2006, pp. 77-111; c) M. Somei,
Advances in Heterocyclic Chemistry, Vol. 82, ed. by A.
R. Katritzky, Elsevier Science (USA), 2002, pp. 101-
155; d) M. Somei, Heterocycles 1999, 50, 1157-1211; e)
M. Somei, J. Synth. Org. Chem. Jpn. 1991, 49, 205-217.
Experimental Section
General One-pot Procedure for the Preparation of
N-Alkoxyindole-3-carbonitriles 2.
To a solution of the prepared 3-alkoxyimino-2-
aryl-alkylnitrilles 1 (2.0 mmol, 1.0 equiv) in DCE (20
mL) was added PhICl2 (3.0 mmol, 1.5 equiv) at room
[9] M. Somei, F. Yamada, T. Kurauchi, Y. Nagahama, M.
Hasegawa, K. Yamada, S. Teranishi, H. Sato, C.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701111
Advanced Synthesis & Catalysis
Kaneko, Chem. Pharm. Bull. 2001, 49, 87-96, and
[19] Q. Yan, J. Luo, D. Zhang-Negrerie, H. Li, X. Qi, K.
references cited therein.
Zhao, J. Org. Chem. 2011, 76, 8690-8697.
[10] a) H. Zhong, D. Yang, S. Wang, J. Huang, Chem.
Commun. 2012, 48, 3236-3238; b) S. Manna, A. P.
Antonchick, Angew. Chem. Int. Ed. 2014, 53, 7324-
7327; c) X. Zhang, D. Zhang-Negrerie, J. Deng, Y.
Du, K. Zhao, J. Org. Chem. 2013, 18, 12750-12759.
[20] a) H. R. Snyder, E. L. Eliel, J. Am. Chem. Soc. 1948,
70, 1703-1705; b) P. J. Gilligan, C. Baldauf, A.
Cocuzza, D. Chidester, R. Zaczek, L. W. Fitzgerald, J.
McElroy, M. A. Smith, H. L. Shen, J. A. Saye, D.
Christ, G. D. Trainor, W. Robertson, P. Hartig, Bioorg.
Med. Chem. 2000, 8, 181-189.
[11] a) T. Kawasaki, A. Kodama, T. Nishida, K. Shimizu,
M. Somei, Heterocycles 1991, 32, 221-227; b) M.
Somei, T. Shoda, Heterocycles 1981, 16, 1523-1525;
c) M. Somei, S. Inoue, S. Tokutake, F. Yamada, C.
Kaneko, Chem. Pharm. Bull. 1981, 29, 726-738; d) M.
Somei, T. Kawasaki, Heterocycles 1989, 29, 1251-
1254.
[21] T. Q. Dinh, R. W. Armstrong, Tetrahedron Lett. 1996,
37, 1161-1164.
[22] We also studied the reaction by adding ZnCl2 together
with PhICl2 at the same time. The reaction provided
the final product 2a in 75% with longer time (12 h).
[23] Some other Lewis acids were also tested but gave
relatively low yields: 1) LiAlH4 (0.3 equiv), THF, 40
[12] a) N. Selvakumar, Y. Reddy, A. M. Azhagan, M. K.
Khera, J. M. Babu, J. Iqbal, Tetrahedron Lett. 2003,
44, 7065-7069; b) N. Selvakumar, M. K. Khera, Y.
Reddy, D. Srinivas, M. Azhagan, J. Iqbal,
Tetrahedron Lett. 2003, 44, 7071-7074; c) N.
Selvakumar, G. G. Rajulu, J. Org. Chem. 2004, 69,
4429-4432.
o
oC, 1 h, 54%; 2) BBr3 (3 equiv), DCM, 25 C, 24 h,
49%.
[24] a) M. Noè, A. Perosa, M. Selva, Green Chem. 2013,
15, 2252-2260; b) D. Kovács, J. Wölfling, N. Szabó,
M. Szécsi, I. Kovács, I. Zupkó, É. Frank, Eur. J. Med.
Chem. 2013, 70, 649-660; c) N. Saemian, G. Shirvani,
H. Matloubi, J. Label. Compd. Radiopharm. 2006, 49,
71-76.
[13] a) A. Penoni, G. Palmisano, G. Broggini, A.
Kadowaki, K. M. Nicholas, J. Org. Chem. 2006, 71,
823-825; b) G. Ieronimo, A. Mondelli, F. Tibiletti, A.
Maspero, G. Palmisano, S. Galli, S. Tollari, N.
Masciocchi, K. M. Nicholas, S. Tagliapietra, G.
Cravotto, A. Penoni, Tetrahedron 2013, 69, 10906-
10920.
[25] a) X. Li, Y. Du, Z. Liang, X. Li, K. Zhao, Org. Lett.
2009, 11, 2643-1646; b) N. Zhang, R. Cheng, D.
Zhang-Negrerie, Y. Du, K. Zhao, J. Org. Chem. 2014,
79, 10581-10587; c) L. Tang, D. Zhang-Negrerie, Y.
Du, K. Zhao, Synthesis 2014, 46, 1621-1629.
[14] X. Creary, E. A. Burtch, Z. Jiang, J. Org. Chem. 2003,
68, 1117-1127.
[26] a) D. E. Falvey, J. Phys. Org. Chem. 1999, 12, 589-
596; b) A. Liard, T. H. Nguyen, A. I. D. Smir, M.
Vaultier, A. Derdour, J. Mortier, Chem. Eur. J. 2003,
9, 1000-1007; c) G. Boche, P. Andrews, K. Harms, M.
Marsch, K. S. Rangappa, M. Schimeczek, C. Willeke,
J. Am. Chem. Soc. 1996, 118, 4925-4930; d) D.
Chiapperino, S. McIlroy, D. E. Falvey, J. Am. Chem.
Soc. 2002, 124, 3567-3577.
[15] Y. Du, J. Chang, J. Reiner, K. Zhao, J. Org. Chem.
2008, 73, 2007-2010.
[16] For selected reviews, see: a) A. Yoshimura, V. V.
Zhdankin, Chem. Rev. 2016, 116, 3328-3435; b) M. S.
Yusubov, V. V. Zhdankin, Curr. Org. Synth. 2012, 9,
247-272; c) V. V. Zhdankin, Arkivoc 2009 (i), 1-62. f)
V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008, 108,
5299-5358; d) T. Wirth, Angew. Chem. Int. Ed. 2005,
44, 3656-3665; e) P. J. Stang, J. Org. Chem. 2003, 68,
2997-3008; f) V. V. Zhdankin, P. J. Stang, Chem. Rev.
2002, 102, 2523-2584.
[17] For selected examples, see: a) S. Maiti, T. K. Achar, P.
Mai, Org. Lett. 2017, 19, 2006-2009; b) S. Manna, A.
P. Antonchick, Angew. Chem. Int. Ed. 2014, 53, 7324-
7327; c) W. Yuan, K. Szabo, Angew. Chem. Int. Ed.
2015, 54, 8533-8537; d) A. Correa, I. Tellitu, E.
Dominguez, R. SanMartin, Tetrahedron 2006, 62,
11100-11105; e) F. Churruca, R. SanMartin, I. Tellitu,
E. Dominguez, Eur. J. Org. Chem. 2005, 2481-2490; f)
X. Wang, J. Gallardo-Donaire, R. Martin, Angew.
Chem. Int. Ed. 2014, 53, 11084-11087; g) H. J. Kim,
S. H. Cho, S. Chang, Org. Lett. 2012, 14, 1424-1427;
h) S. Suzuki, T. Kamo, K. Fukushi, T. Hiramatsu, E.
Tokunaga, T. Dohi, Y. Kita, N. Shibata, Chem. Sci.
2014, 5, 2754-2760.
[18] Y. Du, R. Liu, G. Linn, K. Zhao, Org. Lett. 2006, 8,
5919-5922.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701111
Advanced Synthesis & Catalysis
COMMUNICATION
Iodobenzene Dichloride/Zinc Chloride-Mediated
Synthesis of N-Alkoxyindole-3-carbonitriles from
3-Alkoxyimino-2-arylalkylnitriles
Intramolecular Heterocyclization
via
Adv. Synth. Catal. Year, Volume, Page – Page
Zhongxiang Yun,a Ran Cheng,a Jiyun Sun,a Daisy
Zhang-Negrerie,a and Yunfei Dua,b*
6
This article is protected by copyright. All rights reserved.