Tosyl Hydrazine-Promoted Tandem Condensation and Cyclization of Acyl Azobenzenes Enabling Access to 2H-Indazoles under Metal-Free Aerobic Conditions

Article abstract of DOI:10.1002/adsc.201801055

Tosyl hydrazine-promoted tandem condensation and cyclization of 2-acyl azobenzenes under metal-free aerobic conditions was demonstrated to give 2-aryl-2H-indazoles having alkyl- or aryl groups at the 3-position in quantitative yields through the release o

Full text of DOI:10.1002/adsc.201801055

Title: Tosyl Hydrazine-Promoted Tandem Condensation and
Cyclization of Acyl Azobenzenes Enabling Access to 2<i>H</i>-
Indazoles under Metal-Free Aerobic Conditions
Authors: Jeong-Yu Son, Hyunseok Kim, Yonghyeon Baek, Kyusik Um,
Gi Hoon Ko, Gi Uk Han, Sang Hoon Han, Kooyeon Lee, and
Phil Ho Lee
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801055
Link to VoR: http://dx.doi.org/10.1002/adsc.201801055

10.1002/adsc.201801055
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Tosyl Hydrazine-Promoted Tandem Condensation and
Cyclization of Acyl Azobenzenes Enabling Access to 2H-
Indazoles under Metal-Free Aerobic Conditions
Jeong-Yu Son,a,† Hyunseok Kim, a,† Yonghyeon Baek,a Kyusik Um,a Gi Hoon Ko,a Gi
Uk Han,a Sang Hoon Han,a Kooyeon Lee,b and Phil Ho Leea,*
a
Department of Chemistry, Kangwon National University, Chuncheon 24341, Republic of Korea
E-mail : phlee@kangwon.ac.kr
Department of Bio-Health Technology, Kangwon National University, Chuncheon 24341, Republic of Korea
b
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. Tosyl hydrazine-promoted tandem condensation corresponding 2H-indazoles in quantitative yields. The
and cyclization of 2-acyl azobenzenes under metal-free present reaction was determined to have a wide substrate
aerobic conditions was demonstrated to give 2-aryl-2H- scope and good functional group tolerance.
indazoles having alkyl- or aryl groups at the 3-position in
quantitative yields through the release of water, molecular Keywords:
Metal-free,
Azobenzene,
2H-indazole,
nitrogen, and sulfinic acid. All of the examples produced the Condensation, Cyclization
position 3 of 2-aryl-2H-indazoles has been mainly
reported to date.[9] Therefore, the high difficulty of
preparing 2-aryl-2H-indazoles bearing 3-alkyl or 3-
aryl groups has drawn a considerable attention from
organic chemists.[10] Although the conversion of 2-
acyl azobenzenes to 2-aryl-2H-indazoles having alkyl
or aryl groups at the 3-position through the
corresponding 2o-alcohols was recently reported, this
transformation requires stoichiometric quantities of
metallic reducing agents, such as NaBH4/Cu2Cl2 and
Zn/NH4Cl, for the reduction of acyl azobenzene and
the reaction also suffers from limited functional
group tolerance (eq 1 and 2).[11] In addition, the
reduction of 2-acylated azoxybenzene was promoted
by Pd/C catalyst under H2 atmosphere affording the
indazole (eq 3).[12] For this reason, the introduction of
a variety of alkyl or aryl substituents at the 3-position
of 2-aryl-2H-indazoles is strongly needed.
Introduction
2H-indazoles occupy an important position in
medicinal chemistry.[1] Because these compounds
have been identified as a priviledged structure in drug
discovery,[2] the 2H-indazole scaffold makes up an
essential moiety in many drugs and active
pharmaceutical ingredients (APIs) with a large
number of biological activities, such as anticancer,[3]
anti-HIV,[4] antidepressant,[5] anti-inflammatory,[6]
and contraceptive activities (Figure 1).[7] However,
because 2H-indazoles are thermodynamically
unfavorable in comparison with 1H-indazoles, their
Figure 1. Biologically active molecules containing 2H-
indazoles.
Recently, a transition metal-free methodology for
the construction of an important structure in drug
discovery has attracted attention.[13] In this regard, we
envisioned that the treatment of 2-acyl azobenzenes
with tosyl hydrazine would produce the
preparation has been much less investigated, and the
reported synthetic approaches afford mixtures of 1H-
and 2H-indazoles with poor regioselectivity.[8]
Moreover, the introduction of acyl and ester groups at
1
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10.1002/adsc.201801055
Advanced Synthesis & Catalysis
corresponding tosyl hydrazones along with the
release of water, and then, the hydrozones would be
easily transformed to 2-aryl-2H-indazoles having 3-
alkyl- or 3-aryl groups through intramolecular
cyclization with concomitant release of molecular
A variety of bases (1.2 equiv), including LiOt-Bu,
NaH, K2CO3, and Cs2CO3, were examined in toluene,
and Cs2CO3 provided 2-phenyl-3-propyl-2H-indazole
(2a) in 90% yield (entries 1-4). An increase in the
reaction temperature to 80 oC gave the desired
nitrogen and sulfinic acid under metal-free conditions. product 2a in quantitative yield (entry 5). Although
o
Herein, we describe an efficient synthetic method for
2-aryl-2H-indazoles having alkyl- or aryl groups at
the 3-position through intramolecular cyclization of
tosyl hydrazone having an azobenzene moiety, which
is generated in situ from the condensation of 2-acyl
azobenzene with tosyl hydrazine together with the
release of water, molecular nitrogen, and sulfinic acid
under metal-free aerobic conditions (Scheme 1).
the same reaction conducted in toluene at 110 C for
4 h without Cs2CO3 provided 2a in 64% yield (entry
6), the desired 2H-indazole (2a) was gratifyingly
obtained in 95% yield in ethanol after reaction at 110
oC for 4 h (entry 8).
Since the preparation of hydrazone 1a was
straightforward, we next examined the feasibility of
performing this cyclization directly from 2-butyryl
azobenzene (3a) and tosyl hydrazine in one-pot (eq 4).
The best result was achieved from the treatment of 3a
(0.2 mmol, 1.0 equiv) with tosyl hydrazine (1.1 equiv)
in EtOH at 110 °C for 1 h without base under metal-
free aerobic conditions, providing 2H-indazole 2a in
99% yield. A control experiment in the absence of
tosyl hydrazine was carried out. Refluxing 3a in
ethanol at 110 oC for 12 h was totally ineffective and
then, 3a was recoverd in 90% yield (eq 5).
Scheme 1. Synthetic method for 3-alkyl- and 3-aryl-2H-
indazoles.
Results and Discussion
First, the intramolecular cyclization of hydrazone-
substituted azobenzene 1a, which was easily obtained
from 2-butyryl azobenzene (3a) and tosyl hydrazine,
was attempted (Table 1).
Table 1. Reaction optimization.[a]
Encouraged by these results, we attempted the
direct synthesis of 2H-indazoles from the tandem
reaction of 2-acyl azobenzenes with tosyl hydrazine
o
Entry Base
Solvent
T
t [h]
Yield
[%][b]
in ethanol (110 C, 4 h) under metal-free aerobic
[oC]
conditions. First, a variety of azobenzenes having a
wide range of acyl groups at the 2-position were
investigated under the optimized metal-free aerobic
conditions (Scheme 2). Azobenzenes having alkanoyl
substituents, such as 2-acetyl and 2-cyclohexanoyl,
were smoothly converted to the corresponding 2H-
indazoles (2b and 2c) in quantitative yields. Next, the
metal-free aerobic cyclization of a variety of 2-aroyl
azobenzenes was examined. 2-Benzoyl-substituted
azobenzene was reacted with tosyl hydrazine,
affording 2,3-diphenyl-2H-indazole (2d) in 99%
yield. Electronic variations in the substituents on the
aryl group of the 2-aroyl azobenzenes did not
influence the reaction efficiency. Electron-donating
groups, including 2-methyl, 3-methyl, and 4-methyl,
1
2
3
4
5
LiOt-Bu
toluene
toluene
toluene
toluene
toluene
60
10
10
10
6
45
40
70
90
NaH
60
60
60
80
K2CO3
Cs2CO3
Cs2CO3
2
99
(99)[c]
64
6
7
8
-
-
-
toluene
DCE
110
110
110
4
4
1
77
EtOH
95
(94)[c]
[a]
Reactions were carried out with 1a (0.15 mmol, 1.0
equiv) and base (1.2 equiv) in solvent (0.3 mL) under N2. produced the corresponding 2H-indazoles (2e, 2f, and
[b]
NMR yield using dibromomethane as an internal
standard.
2g) in quantitative yields. Likewise, a strong electron-
donating 4-methoxy group gave the desired 2H-
indazole (2h) in 99% yield. Moreover, azobenzenes
having 3,5-dimethyl and 2,5-dimethoxybenzoyl
group took part in the tandem reaction to afford the
[c] Isolated yield.
2
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10.1002/adsc.201801055
Advanced Synthesis & Catalysis
corresponding 2H-indazoles (2i and 2j) in
quantitative yields. The metal-free aerobic conditions
of the condensation reaction followed by cyclization
were compatible with a number of electron-
withdrawing groups, including 2-chloro, 4-chloro, 2-
compatible with the reaction conditions. The present
method worked equally well with an azobenzene
bearing a thiophen-2-carbonyl group to give 2s in
99% yield.
Scheme 3. Substrate scope of azobenzenes having
substituent on two aryl rings.[a]
[a] Reactions were carried out with 5 (0.2 mmol, 1.0 equiv)
o
and 4 (1.1 equiv) in EtOH (0.4 mL) at 110 C for 1 h
under air.
On the basis of these results, we next examined
the scope and limitations of 2-benzoyl azobenzenes
having substituents on two aryl rings of the
azobenzenes under the optimal reaction conditions
(Scheme 3). Both electron-donating and electron-
withdrawing groups on the benzoyl azobenzenes
were compatible, thus equally affording the
corresponding 2H-indazole products in quantitative
yields (6a–6h). The electronic and steric effects of
the substituents on the benzoyl azobenzenes were
also studied. When a 2-benzoyl azobenzene with
methyl substituents on each phenyl ring (5a) was
treated with tosyl hydrazine, the desired 2H-indazole
6a was obtained in 99% yield. The transformation of
azobenzenes 5b and 5c having 3- and 4-methyl
groups was also highly facile (6b and 6c). The
strongly electron-donating 3,3’- and 4,4’-dimethoxy
groups did not influence the tandem condensation and
cyclization reaction, and the desired products 6d and
6e were obtained in quantitative yields. 4,4’-
Scheme 2. Substrate scope of 2-acyl azobenzenes.[a]
[a] Reactions were carried out with 3 (0.2 mmol, 1.0 equiv)
o
and 4 (1.1 equiv) in EtOH (0.4 mL) at 110 C for 1 h
under air.
bromo, 3-bromo, 4-methoxycarbonyl, and 4-nitro
groups, providing the corresponding 2H-indazoles
(2k, 2l, 2m, 2n, 2o, and 2p) in quantitative yields.
When
3-bromo-4-chloro-substituted
benzoyl
azobenzene was employed, the desired 2H-indazole
2q was obtained in 99% yield. 2-Fluoro-4-methoxy-
substituted benzoyl azobenzene was found to be
Dichloro-,
3,3’-dibromo-,
and
4,4’-dibromo-
substituted 2-benzoyl azobenzenes (5f, 5g, and 5h)
were applicable in the present reaction, providing the
3
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10.1002/adsc.201801055
Advanced Synthesis & Catalysis
corresponding 2H-indazoles (6f, 6g, and 6h) in
quantitative yields. These results indicate that both
electronic and steric effects were negligible. We
subsequently investigated the scope of azobenzenes
having one substituent on two aryl rings.
Azobenzenes (5i and 5j) bearing 4-methoxy and 4-
ethoxycarbonyl groups on the benzoyl-substituted
aryl ring (A) underwent the tandem reaction under
metal-free aerobic conditions, furnishing the
corresponding 2H-indazoles (6i and 6j) in
quantitative yields. When azobenzenes (5k, 5l, and
5m) bearing 4-chloro, 4-bromo, and 4-
ethoxycarbonyl groups on the phenyl ring (B) were
subjected to tosyl hydrazine, the condensation
reaction followed by cyclization occurred smoothly,
providing the corresponding 2H-indazoles (6k, 6l,
and 6m) in quantitative yields.
and 5) and tosyl hydrazine (4) is shown in Scheme 4.
The reaction of 2-acylazobenzene with tosyl
hydrazine
provided
hydrazone-substituted
azobenzene 1, which was heated to produce the
cyclized intermediate G. Then, elimination of the
tosyl group followed by the evolution of a nitrogen
molecule afforded the 2H-indazoles (2 and 6).
Conclusion
In summary, we have developed an efficient synthetic
method for 2-aryl-2H-indazoles bearing alkyl- or aryl
groups at the 3-position through intramolecular
cyclization of tosyl hydrazone having an azobenzene
moiety generated in situ from the condensation of 2-
acyl azobenzenes with tosyl hydrazine along with the
release of water, molecular nitrogen, and sulfinic acid
under metal-free aerobic conditions. All of the
examples afforded the corresponding 2H-indazoles in
quantitative yields. The observed excellent functional
group tolerance enables practical application of this
method in the synthesis of complex molecules.
A
plausible reaction mechanism for the
intramolecular cyclization of hydrazone-substituted
azobenzene 1a in the presence of Cs2CO3 is shown in
Scheme 4.
Experimental Section
General: Commercial available reagents were used
without purification. All reaction mixtures were stirred
magnetically and were monitored by thin-layer
chromatography using silica gel pre-coated glass plates,
which were visualized with UV light and then, developed
using either iodine or a solution of anisaldehyde. Flash
column chromatography was carried out using silica gel
(230-400 mesh). 1H NMR (400 MHz), 13C{1H} NMR (100
MHz), and 19F NMR (377 MHz) spectra were recorded on
NMR spectrometer. Deuterated chloroform was used as the
solvent and chemical shift values () are reported in parts
per million relative to the residual signals of this solvent [δ
7.26 for 1H (chloroform-d),
δ
77.2 for 13C{1H}
(chloroform-d)]. Infrared spectra were recorded on FT-IR
spectrometer as either a thin film pressed between two
sodium chloride plates or as a solid suspended in a
potassium bromide disk. High resolution mass spectra
(HRMS) were obtained by fast atom bombardment (FAB)
using a double focusing magnetic sector mass spectrometer
and electron impact (EI) ionization technique (magnetic
sector - electric sector double focusing mass analyzer)
from the KBSI (Korea Basic Science Institute Daegu
Center). Melting points were determined in open capillary
tube.
Scheme 4. Plausible mechanisms.
General Procedure for Preparation of Hydrazone[14]
When 1a was treated with Cs2CO3, intermediate A
was produced. Then, elimination of the tosyl group
followed by cyclization provided C. Finally, the
evolution of a nitrogen molecule from C generated
intermediate D, and subsequent resonance delivered
2H-indazole 2a. On the other hand, the carbene
intermediate F could be involved through the
evolution of a nitrogen molecule from E, which is a
resonance structure of B. Then, nucleophilic attack of
the azo nitrogen atom on the electrophilic carbene
Acylazobenzene (5.0 mmol, 1.0 equiv) and TsNHNH2 4
(1.0 equiv) were stired in EtOH (5.0 mL) at 40 oC for 12 h
under air. After cooling to room temperature and
evaporation of the solvents in vacuo, the crude product was
purified by column chromatography on silica gel using
CH2Cl2:Hexane = 1:5.
(E)-4-Methyl-N’-(1-(2-((E)-phenyldiazenyl)phenyl)
butylidene)benzenesulfonohydrazide (1a): Yield : 1.5g
(70%); Rf = 0.4 (CH2Cl2:Hexane = 1: 5); Brown solid;
o
1
Melting point: 60-62 C; H NMR (400 MHz, CDCl3) δ
7.83-7.81 (m, 1H), 7.69 (d, J = 8.3 Hz, 2H), 7.57-7.54 (m,
4H), 7.51-7.47 (m, 1H), 7.43-7.39 (m, 2H), 7.27 (s, 1H),
7.19-7.17 (m, 1H), 7.11 (d, J = 8.0 Hz, 2H), 2.53 (t, J = 7.6
Hz, 2H), 2.33 (s, 3H), 1.50-1.44 (m, 2H), 0.82 (t, J = 7.4
Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 158.0, 152.3,
carbon of
F
generated intermediate D, and
subsequent resonance furnished the 2H-indazole 2a.
A proposed reaction pathway for the formation of
2H-indazoles (2 and 6) from 2-acyl azobenzenes (3
4
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10.1002/adsc.201801055
Advanced Synthesis & Catalysis
148.7, 143.7, 135.7, 133.0, 132.0, 131.8, 130.6, 129.5,
129.2, 128.2, 127.9, 123.4, 117.9, 41.0, 21.8, 19.6, 13.8; IR
(film): 3230, 3030, 1510, 1322, 1150, 1030, 730 cm-1;
HRMS (FAB): (M+H)+: m/z calcd for C23H14N2O3:
421.1698; found: 421.1696.
7.13 (ddd, J = 8.5, 6.6, 0.8 Hz, 1H), 2.39 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3)  149.1, 140.5, 138., 135.7,
129.7, 129.6, 129.1, 128.3, 127.1, 126.2, 126.1, 122.4,
121.8, 120.8, 117.8, 21.5.
3-(4-Methoxyphenyl)-2-phenyl-2H-indazole
(2h)[11a]
:
General procedure for reaction of acylated azobenzenes
with tosyl hydrazine[10, 11]
Yield: 59.5 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
Ivory solid; 1H NMR (400 MHz, CDCl3)  7.79 (d, J = 8.8
Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.46-7.34 (m, 6H), 7.29
(d, J = 8.8 Hz, 2H), 7.13 (ddd, J = 8.5, 6.6, 0.8 Hz, 1H),
6.93 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3)  159.7, 149.1, 140.5, 135.5, 131.1, 129.1,
128.3, 127.1, 126.2, 126.1, 122.4, 121.7, 120.8, 117.8,
114.4, 55.5.
Acylazobenzene (3 and 5, 0.2 mmol, 1.0 equiv) and
TsNHNH2 4 (1.1 equiv) were stired in EtOH (0.4 mL) at
110 oC for 1 h under air. After cooling to room temperature
and evaporation of the solvents in vacuo, the crude product
was purified by column chromatography on silica gel using
EtOAc:Hexane = 1: 5.
3-(3,5-Dimethylphenyl)-2-phenyl-2H-indazole
(2i):
2-Phenyl-3-propyl-2H-indazole (2a)[11a]: Yield : 46.7 mg
Yield: 59.0 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
o
1
1
Yellow solid; Melting point: 115-117 C H NMR (400
MHz, CDCl3)  7.79 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.5
Hz, 1H), 7.74-7.46 (m, 2H), 7.40-7.34 (m, 4H), 7.13 (ddd,
J = 8.5, 6.6, 0.9 Hz, 1H), 7.00 (s, 1H), 7.96 (d. J = 0.5 Hz,
2H), 2.28 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) 
149.1, 140.5, 138.4, 135.9, 130.2, 129.9, 129.0, 128.3,
127.6, 127.1, 126.1, 122.4, 121.9, 120.9, 117.8, 21.4.; IR
(film): 3059, 2917, 1625, 1599, 1360, 1072, 763 cm-1;
HRMS (EI) m/z: [M]+ Calcd for C21H18N2 298.1470;
Found 298.1470.
(99%); Rf = 0.3 (EtOAc:Hexane = 1:5); Yellow solid; H
NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.7 Hz, 1H), 7.68
(d, J = 8.5 Hz, 1H), 7.57-7.50 (m, 5H), 7.32 (ddd, J = 8.5,
6.6, 1.1 Hz, 1H), 7.08 (ddd, J = 8.5, 6.6, 0.9 Hz, 1H), 3.02
(t, J = 7.7 Hz, 2H), 1.74-1.64 (m, 2H), 0.90 (t, J = 7.4 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 148.7, 140.3,
136.9, 129.3, 129.0, 126.8, 126.4, 121.3, 121.0, 120.4,
117.7, 27.4, 23.0, 14.1.
3-Methyl-2-phenyl-2H-indazole (2b)[10h]: Yield : 41.2 mg
1
(99%); Ivory solid; Rf = 0.3 (EtOAc:Hexane = 1:5); H
3-(2,5-Dimethoxyphenyl)-2-phenyl-2H-indazole
(2j):
NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.8 Hz, 1H), 7.63
(d, J = 8.5 Hz, 1H), 7.59-7.53 (m, 4H), 7.51-7.48 (m, 1H),
7.33 (ddd, J = 8.7, 6.6, 1.0 Hz, 1H), 7.09 (dd, J = 8.1, 7.0
Hz, 1H), 2.66 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
148.8, 140.1, 132.1, 129.3, 128.8, 126.9, 125.9, 121.8,
121.1, 120.1, 117.7, 11.3.
Yield: 66.0 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
o
1
Yellow solid; Melting point: 140-142 C; H NMR (400
MHz, CDCl3)  7.80 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 8.5
Hz, 1H), 7.46-7.44 (m, 2H), 7.36-7.26 (m, 4H), 7.10 (ddd,
J = 8.5, 6.6, 0.7 Hz, 1H), 7.02 (d, J = 3.1 Hz, 1H), 6.93 (dd,
J = 9.0, 3.1 Hz, 1H), 6.80 (d, J = 9.0 Hz, 1H), 3.78 (s, 3H),
3.27 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)  153.7,
151.1, 149.1, 141.5, 132.3, 128.7, 127.9, 126.9, 124.7,
122.6, 122.2, 120.8, 119.9, 117.9, 117.1, 115.6, 112.8, 55.9,
55.4; IR (film): 3061, 1626, 1597, 1361, 1045, 768 cm-1;
HRMS (EI) m/z: [M]+ Calcd for C21H18N2O2 330.1368;
Found 330.1368.
3-Cyclohexyl-2-phenyl-2H-indazole (2c)[10h]: Yield : 54.7
mg (99%); Ivory solid; Rf = 0.3 (EtOAc:Hexane = 1:5); 1H
NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.6 Hz, 1H), 7.71
(d, J = 8.8 Hz, 1H), 7.57-7.47 (m, 5H), 7.30 (ddd, J = 8.7,
6.6, 1.0 Hz, 1H), 7.05 (ddd, J = 8.5, 6.6, 0.9 Hz, 1H), 3.01-
2.93 (m, 1H), 2.04-1.74 (m, 7H), 1.38-1.25 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 149.0, 141.3, 140.3,
129.3, 129.1, 126.6, 126.4, 121.4, 120.7, 119., 118.0, 37.4,
32.7, 26.7, 26.0.
3-(2-Chlorophenyl)-2-phenyl-2H-indazole
(2k)[11a]
:
Yield: 60.3 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
Yellow solid; H NMR (400 MHz, CDCl3)  7.83 (d, J =
8.8 Hz, 1H), 7.51-7.48 (m, 2H), 7.44-7.32 (m, 9H), 7.14
(ddd, J = 8.5, 6.6, 0.8 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)  148.9, 140.4, 134.7, 132.8, 132.7, 130.6, 130.4,
129.6, 129.1, 128.3, 127.1, 125.2, 122.8, 122.6, 120.7,
118.0.
2,3-Diphenyl-2H-indazole (2d)[10i]: Yield : 53.3 mg
1
(99%); Ivory solid; Rf = 0.3 (EtOAc:Hexane = 1:5); H
NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.8 Hz, 1H), 7.72
(d, J = 8.5 Hz, 1H), 7.46-7.35 (m, 11H), 7.15 (ddd, J = 8.5,
6.6, 0.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
149.1, 140.4, 135.6, 130.1, 129.8, 129.1, 128.9, 128.5,
128.4, 127.1, 126.2, 122.7, 121.9, 120.7, 117.9.
3-(4-Chlorophenyl)-2-phenyl-2H-indazole
(2l)[10h]
:
Yield: 60.3 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
Yellow solid; H NMR (400 MHz, CDCl3)  7.31 (d, J =
2-Phenyl-3-(o-tolyl)-2H-indazole (2e)[11a]: Yield : 56.2
mg (99%); Ivory solid; Rf = 0.3 (EtOAc:Hexane = 1:5); 1H
NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.8 Hz, 1H), 7.45
(dt, J = 8.5, 1.0 Hz, 1H), 7.43-7.45 (m, 2H), 7.39-7.30 (m,
6H), 7.26 (t, J = 6.9 Hz, 2H), 7.10 (ddd, J = 8.5, 6.6, 0.8
Hz, 1H), 1.95 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
148.9, 140.5, 137.9, 135.4, 131.3, 130.8, 129.7, 129.4,
129.0, 128.0, 127.1, 126.2, 124.9, 122.7, 122.2, 120.9,
117.8, 20.1.
8.8 Hz, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.42-7.36 (m, 8H),
7.29 (d, J = 8.7 Hz, 2H), 7.17 (ddd, J = 8.5, 6.6, 0.8 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3)  149.1, 140.1,
134.6, 134.2, 131.0, 129.3, 129.2, 128.6, 128.5, 127.2,
126.2, 123.0, 121.9, 120.3, 118.1.
3-(2-Bromophenyl)-2-phenyl-2H-indazole
(2m)[10h]
:
Yield: 69.1 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
Yellow solid; H NMR (400 MHz, CDCl3)  7.83 (d, J =
8.8 Hz, 1H), 7.70-7.67 (m, 1H), 7.48 (d, J = 8.5 Hz, 1H),
7.45-7.43 (m, 2H), 7.40-7.30 (m, 7H), 7.13 (ddd, J = 8.5,
6.6, 0.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) 
148.8, 140.4, 134.4, 133.5, 133.1, 131.7, 130.8, 129.1,
128.3, 127.6, 127.1, 125.3, 124.9, 122.7, 122.6, 120.8,
118.0.
2-Phenyl-3-(m-tolyl)-2H-indazole (2f)[10h]: Yield: 56.1
mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5); Ivory solid; 1H
NMR (400 MHz, CDCl3)  7.80 (d, J = 8.8 Hz, 1H), 7.72
(d, J = 8.5 Hz, 1H), 7.46-7.35 (m, 6H), 7.27 (t, J = 7.6 Hz,
1H), 7.22 (s, 1H), 7.18 (d, J = 7.6 Hz, 1H), 7.14 (ddd, J =
8.5, 6.7, 0.8 Hz, 1H), 7.11 (d, J = 7.6 Hz, 1H), 2.34 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3)  149.1, 140.4,
138.6, 135.7, 130.4, 130.0, 129.2, 129.1, 128.8, 128.3,
127.1, 127.0, 126.1, 122.5, 121.9, 120.8, 117.9, 21.6.
3-(3-Bromophenyl)-2-phenyl-2H-indazole
(2n)[10h]
:
Yield: 69.1 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
Yellow solid; H NMR (400 MHz, CDCl3)  7.81 (d, J =
8.8 Hz, 1H), 7.71 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.50 (dt,
J = 7.5, 1.8 Hz, 1H), 7.44-7.37 (m, 6H), 7.26-7.16 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3)  149.1, 140.0, 133.7,
132.5, 132.1, 131.5, 130.4, 129.3, 128.7, 128.5, 127.3,
126.2, 123.2, 122.9, 121.9, 120.2, 118.1.
2-Phenyl-3-(p-tolyl)-2H-indazole (2g)[10h]: Yield: 56.1 mg
1
(99%); Rf = 0.3 (EtOAc:Hexane = 1:5); Ivory solid; H
NMR (400 MHz, CDCl3)  7.79 (d, J = 8.8 Hz, 1H), 7.71
(d, J = 8.5 Hz, 1H), 7.46-7.34 (m, 6H), 7.25-7.19 (m, 4H),
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801055
Advanced Synthesis & Catalysis
Methyl 4-(2-phenyl-2H-indazol-3-yl)benzoate (2o)[10h]
:
5-Methyl-3-phenyl-2-(p-tolyl)-2H-indazole
(6c)[10h]
:
Yield: 65.0 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
Yield: 59.6 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
1
Yellow solid; H NMR (400 MHz, CDCl3)  8.06 (d, J =
Yellow solid; H NMR (400 MHz, CDCl3)  7.70 (d, J =
8.1 Hz, 2H), 7.83 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 8.5 Hz,
1H), 7.45-7.38 (m, 8H), 7.21-7.18 (m, 1H), 3.94 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3)  166.7, 149.2, 140.1,
134.5, 134.3, 130.1, 129.8, 129.7, 129.4, 128.8, 127.3,
126.2, 123.3, 122.1, 120.3, 118.2, 52.5.
8.9 Hz, 1H), 7.45 (s, 1H), 7.41-7.34 (m, 5H), 7.30 (d, J =
8.4 Hz, 2H), 7.20 (dd, J = 8.9, 1.5 Hz, 1H), 7.17 (d, J = 8.2
Hz, 2H), 2.43 (d, J = 0.7 Hz, 3H), 2.38 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3)  148.0, 138.2, 138.0, 134.5,
132.0, 130.4, 129.9, 129.8, 129.7, 128.8, 128.2, 125.8,
122.0, 118.6, 117.5, 22.0, 21.3.
3-(4-Nitrophenyl)-2-phenyl-2H-indazole (2p) [10g]: Yield:
62.4 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5); Yellow
6-Methoxy-2-(3-methoxyphenyl)-3-phenyl-2H-indazole
1
solid; Melting point: 120-122 oC H NMR (400 MHz,
(6d)[10h]: Yield: 62.7 mg (99%); Rf = 0.3 (EtOAc:Hexane =
1
CDCl3)  8.26 (d, J = 8.9 Hz, 2H), 7.85 (d, J = 8.8 Hz, 1H), 1:5); Yellow solid; H NMR (400 MHz, CDCl3)  7.56 (d,
7.73 (d, J = 8.5 Hz, 1H), 7.53 (d, J = 9.0 Hz, 2H), 7.46-
J = 9.1 Hz, 1H), 7.42-7.36 (m, 5H), 7.24 (t, J = 8.2 Hz,
7.40 (m, 6H), 7.26-7.22 (m, 1H); 13C{1H} NMR (100 MHz, 1H), 7.02 (d, J = 7.1 Hz, 2H), 6.94 (d, J = 7.4 Hz, 1H),
CDCl3)  149.3, 147.3, 139.8, 136.5, 132.8, 130.3, 129.6,
6.89 (dd, J = 8.3, 2.4 Hz, 1H), 6.83 (dd, J = 9.2, 1.5 Hz,
1H), 3.91 (s, 3H), 3.72 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3)  160.0, 159.7, 150.1, 141.3, 135.7, 130.1, 129.7,
128.9, 128.5, 121.6, 118.2, 117.8, 117.7, 114.6, 111.1, 94.5,
55.5, 55.4.
129.2, 127.5, 126.2, 124.2, 124.1, 122.2, 119.7, 118.4.
3-(3-Bromo-4-chlorophenyl)-2-phenyl-2H-indazole
(2q): Yield: 76.7 mg (99%); Rf = 0.3 (EtOAc:Hexane =
o
1
1:5); Yellow solid; Melting point: 120-122 C; H NMR
(400 MHz, CDCl3)  7.82 (d, J = 8.8 Hz, 1H), 7.70 (d, J =
2.0 Hz, 1H), 7.69 (d, J = 8.6 Hz, 1H), 7.45-7.43 (m, 6H),
7.39 (ddd, J = 8.8, 6.6, 1.0 Hz, 1H), 7.20 (ddd, J = 8.5, 6.6,
0.8 Hz, 1H), 7.14 (dd, J = 8.3, 2.0 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3)  149.1, 139.9, 134.7, 134.4, 132.7,
130.8, 130.1, 129.6, 129.4, 128.9, 127.3, 126.2, 123.5,
123.1, 121.9, 119.9, 118.2; IR (film): 3059, 1711, 1627,
1597, 1382, 1024, 763, 621 cm-1; HRMS (EI) m/z: [M]+
Calcd for C19H1279BrClN2 381.9872, C19H1281BrClN2
383.9872; Found 381.9872, 383.9878.
5-Methoxy-2-(4-methoxyphenyl)-3-phenyl-2H-indazole
(6e)[10h]: Yield: 62.7 mg (99%); Rf = 0.3 (EtOAc:Hexane =
1
1:5); Yellow solid; H NMR (400 MHz, CDCl3)  7.69 (d,
J = 9.3 Hz, 1H), 7.43-7.31 (m, 7H), 7.07 (dd, J = 9.3, 2.4
Hz, 1H), 6.90-6.87 (m, 3H), 3.83 (s, 3H), 3.82 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3)  159.3, 155.9, 145.8,
134.3, 133.6, 130.6, 129.7, 128.9, 128.1, 127.1, 121.9,
121.6, 119.3, 114.2, 96.5, 55.6, 55.5.
5-Chloro-2-(4-chlorophenyl)-3-phenyl-2H-indazole
(6f)[10h]: Yield: 67.2 mg (99%); Rf = 0.3 (EtOAc:Hexane =
1:5); Yellow solid; 1H NMR (400 MHz, CDCl3)  7.72 (dd,
J = 9.2, 0.6 Hz, 1H), 7.67 (dd, J = 1.9, 0.7 Hz, 1H), 7.46-
7.43 (m, 3H), 7.37 (s, 4H), 7.34-7.29 (m, 3H); 13C{1H}
NMR (100 MHz, CDCl3)  147.6, 138.6, 135.4, 134.5,
129.7, 129.4, 129.3, 129.2, 129.0, 128.8, 128.5, 127.1,
122.4, 119.5, 119.4.
3-(2-Fluoro-4-methoxyphenyl)-2-phenyl-2H-indazole
(2r): Yield: 63.5 mg (99%); Rf = 0.3 (EtOAc:Hexane =
o
1
1:5); Yellow solid; Melting point: 134-136 C; H NMR
(400 MHz, CDCl3)  7.81 (d, J = 8.8 Hz, 1H), 7.58 (dd, J =
8.5, 1.1 Hz, 1H), 7.47-7.44 (m, 2H), 7.40-7.34 (m, 4H),
7.26 (t, J = 8.4 Hz, 1H), 7.13 (ddd, J = 8.5, 6.6, 0.8 Hz,
1H), 6.76 (ddd, J = 8.6, 2.6, 0.5 Hz, 1H), 6.66 (dd, J = 11.5,
2.5 Hz, 1H), 3.84 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3)  161.2, 160.6 (d, J = 260.2 Hz), 149.1, 140.7,
132.5 (d, J = 4.5 Hz), 129.8, 129.1, 128.3, 127.0, 125.3,
122.8, 122.5, 120.6 (d, J = 1.2 Hz), 118.0, 110.7 (d, J = 2.9
Hz), 110.2 (d, J = 15.6 Hz), 102.4 (d, J = 25.2 Hz), 55.8;
19F NMR (376 MHz, CDCl3) δ -109.6; IR (film): 3062,
1712, 1682, 1363, 1072, 1031, 635 cm-1; HRMS (EI) m/z:
[M]+ Calcd for C20H15FN2O 318.1168; Found 318.1168.
6-Bromo-2-(3-bromophenyl)-3-phenyl-2H-indazole
(6g): Yield: 84.8 mg (99%); Rf = 0.3 (EtOAc:Hexane =
o
1
1:5); Yellow solid; Melting point: 143-145 C; H NMR
(400 MHz, CDCl3)  7.96 (d, J = 0.9 Hz, 1H), 7.72 (t, J =
1.8 Hz, 1H), 7.57 (dd, J = 8.9, 0.6 Hz, 1H), 7.52 (dt, J =
7.5, 1.7 Hz, 1H), 7.45-7.43 (m, 3H), 7.35-7.32 (m, 2H),
7.25-7.19 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) 
149.8, 141.1, 136.4, 131.7, 130.3, 129.8, 129.3, 129.2,
129.1, 129.0, 126.7, 124.6, 122.8, 122.2, 121.6, 120.6,
120.2.; IR (film): 3061, 1621, 1590, 1350, 1067, 783, 699
cm-1; HRMS (EI) m/z: [M]+ Calcd for C19H1279Br2N2
425.9367, C19H1281Br2N2 427.9367; Found 425.9368,
427.9375.
2-Phenyl-3-(thiophen-2-yl)-2H-indazole (2s)[10h]: Yield:
55.3 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5); Yellow
1
solid; H NMR (400 MHz, CDCl3)  7.86 (d, J = 8.5 Hz,
1H), 7.79 (d, J = 8.8 Hz, 1H), 7.52-7.45 (m, 5H), 7.42-7.36
(m, 2H), 7.21-7.17 (m, 1H), 7.07 (dd, J = 5.1, 3.6 Hz, 1H),
7.01 (dd, J = 3.6, 1.2 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)  149.0, 140.2, 130.6, 129.8, 129.2, 129.1, 128.3,
127.6, 127.5, 127.2, 126.7, 123.0, 121.9, 120.7, 118.0.
5-Bromo-2-(4-bromophenyl)-3-phenyl-2H-indazole
(6h)[10h]: Yield: 84.8 mg (99%); Rf = 0.3 (EtOAc:Hexane =
1:5); Yellow solid; 1H NMR (400 MHz, CDCl3)  7.84 (dd,
J = 1.8, 0.7 Hz, 1H), 7.67 (dd, J = 9.2, 0.7 Hz, 1H), 7.52 (d,
J = 8.9 Hz, 2H), 7.45-7.41 (m, 4H), 7.33-7.30 (m, 4H);
13C{1H} NMR (100 MHz, CDCl3)  147.6, 139.0, 135.2,
132.4, 131.1, 129.7, 129.3, 129.1, 129.0, 127.4, 123.2,
122.8, 122.6, 119.7, 116.4.
7-Methyl-3-phenyl-2-(o-tolyl)-2H-indazole
(6a)[10h]
:
Yield: 59.6 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
Yellow solid; H NMR (400 MHz, CDCl3)  7.63 (d, J =
8.4 Hz, 1H), 7.37-7.28 (m, 8H), 7.24 (d, J = 7.5 Hz, 1H),
7.15 (d, J = 6.6 Hz, 1H), 7.11-7.07 (m, 1H), 2.70 (s, 3H),
1.94 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)  149.4,
139.7, 137.0, 135.4, 131.1, 130.1, 129.4, 129.2, 128.7,
128.4, 128.2, 128.1, 126.7, 125.8, 122.8, 120.5, 118.2, 17.7,
17.4.
5-Methoxy-2,3-diphenyl-2H-indazole (6i)[10e]
:
Yield:
59.5 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5); Yellow
1
solid; H NMR (400 MHz, CDCl3)  7.70 (dd, J = 9.3, 0.6
Hz, 1H), 7.44-7.34 (m, 10H), 7.08 (dd, J = 9.3, 2.4 Hz, 1H),
6.90 (d, J = 2.1 Hz, 1H), 3.84 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3)  156.0, 146.0, 140.4, 134.4, 130.5, 129.7,
129.1, 129.0, 128.2, 128.1, 126.0, 122.2, 121.7, 119.4, 96.4,
55.6.
6-Methyl-3-phenyl-2-(m-tolyl)-2H-indazole
(6b)[10h]
:
Yield: 59.6 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
Yellow solid; H NMR (400 MHz, CDCl3)  7.60 (d, J =
8.7 Hz, 1H), 7.54 (d, J = 1.0 Hz, 1H), 7.39-7.33 (m, 6H),
7.22-7.15 (m, 2H), 7.08 (d, J = 7.6 Hz, 1H), 6.98 (dd, J =
8.7, 1.3 Hz, 1H), 2.49 (d, J = 0.8 Hz, 3H), 2.35 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3)  149.7, 140.4, 139.3,
137.0, 135.3, 130.3, 129.8, 129.0, 128.8, 128.7, 128.3,
126.7, 125.6, 123.2, 120.3, 120.2, 116.1, 22.4, 21.5.
Ethyl 2,3-diphenyl-2H-indazole-5-carboxylate (6j):
Yield: 67.7 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
o
1
Yellow solid; Melting point: 130-132 C; H NMR (400
MHz, CDCl3)  8.53 (dd, J = 1.5, 0.9 Hz, 1H), 8.00 (dd, J
= 9.1, 1.6 Hz, 1H), 7.80 (dd, J = 9.1, 0.8 Hz, 1H), 7.45-
7.38 (m, 10H), 4.40 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3)  167.1, 150.2,
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801055
Advanced Synthesis & Catalysis
140.0, 138.2, 129.9, 129.3, 129.2, 129.1, 129.0, 128.8,
127.0, 126.1, 125.5, 124.9, 121.4, 117.7, 61.1, 14.6; IR
(film): 3062, 2978, 1624, 1597, 1365, 1078, 722 cm-1;
HRMS (EI) m/z: [M]+ C22H18N2O2 342.1368; Found
342.1368.
Schmidt, A. Beutler, B. Snovydovych, Eur. J. Org.
Chem. 2008, 4073.
[3] a) B. K. Keppler, M. Hartmann, Met.-Based Drugs
1994, 1, 145; b) P. G. Baraldi, G. Balboni, M. G.
Pavani, G. Spalluto, M. A. Tabrizi, E. Clercq, De J.
Balzarini, T. Bando, H. Sugiyama, R. Romagnoli, J.
Med. Chem. 2001, 44, 2536.
2-(4-Chlorophenyl)-3-phenyl-2H-indazole
(6k)[10i]
:
Yield: 60.3 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
1
Yellow solid; H NMR (400 MHz, CDCl3)  7.79 (d, J =
8.8 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.43-7.35 (m, 10H),
7.15 (ddd, J = 8.5, 6.6, 0.7 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3)  149.2, 138.9, 135.6, 134.2, 129.8, 129.7,
129.4, 129.1, 128.7, 127.4, 127.3, 122.9, 122.0, 120.6,
117.9.
[4] a) J. D. Rodgers, B. L. Johnson, H. Wang, R. A.
Greenberg, S. Erickson-Viitanen, R. M. Klabe, B. C.
Cordova, M. M. Rayner, G. N. Lam, C.-H. Chang,
Bioorg. Med. Chem. Lett. 1996, 6, 2919; b) J.-H. Sun,
C. A. Teleha, J.-S. Yan, J. D. Rodgers, D. A. Nugiel, J.
Org. Chem. 1997, 62, 5627; c) W. Han, C. Pelletier J.
C. N. Hodge, Bioorg. Med. Chem. Lett. 1998, 8, 3615 .
2-(4-Bromophenyl)-3-phenyl-2H-indazole (6l): Yield:
69.1 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5); Yellow
o
1
solid; Melting point: 120-122 C; H NMR (400 MHz,
CDCl3)  7.79 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H),
7.51 (d, J = 8.8 Hz, 2H), 7.44-7.32 (m, 7H), 7.15 (ddd, J =
8.5, 6.6, 0.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) 
149.3, 139.4, 135.6, 132.3, 129.8, 129.7, 129.1, 128.7,
127.5, 127.4, 122.9, 122.3, 122.0, 120.6, 117.9; IR (film):
3058, 1713, 1600, 1363, 1184, 1012, 744, 574 cm-1;
HRMS (EI) m/z: [M]+ Calcd for C19H1379BrN2 348.0262,
C19H1381BrN2 350.0262; Found 348.0265, 350.0268.
[5] Y. Ykeda, N. Takano, H. Matsushita, Y. Shiraki, T.
Koide, R. Nagashima, Y. Fujimura, M. Shindo, S.
Suzuki, T. Iwasaki, Arzneim.-Forsch. 1979, 29, 511.
[6] a) G. A. Bistochi, G. De Meo, M. Pedini, A. Ricci, H.
Brouilhet, S. Bucherie, M. Rabaud, P. Jacquignon,
Farmaco, Ed. Sci. 1981, 36, 315; b) G. Picciola, F.
Ravenna, G. Carenini, P. Gentili, M. Riva, Farmaco Ed.
Sci. 1981, 36, 1037.
Ethyl
4-(3-phenyl-2H-indazol-2-yl)benzoate
(6m):
Yield: 67.7 mg (99%); Rf = 0.3 (EtOAc:Hexane = 1:5);
o
1
Yellow solid; Melting point: 135-137 C; H NMR (400
MHz, CDCl3)  8.07 (d. J =8.8 Hz, 2H), 7.80 (d, J = 8.8
Hz, 1H), 7.70 (d, J = 8.6 Hz, 1H), 7.53 (d, J = 8.8 Hz, 2H),
7.43-7.34 (m, 6H), 7.15 (ddd, J = 8.5, 6.6, 0.8 Hz, 1H),
4.39 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3)  165.9, 149.4, 143.8, 135.8,
130.5, 130.1, 129.8, 129.7, 129.1, 128.8, 127.6, 125.8,
123.0, 122.2, 120.7, 117.9, 61.5, 14.4; IR (film): 3061,
2980, 1625, 1606, 1304, 1273, 1018, 772 cm-1; HRMS (EI)
m/z: [M]+ Calcd for C22H18N2O2 342.1368; Found
342.1366.
[7] G. Corsi, G. Palazzo, C. Germani, P. S. Barcellona, B.
Silvestrini, J. Med. Chem. 1976, 19, 778.
[8] a) R. M. Claramunt, J. Elguero, R. Garceran,
Heterocycles 1985, 23, 2895; b) P. Y. S. Lam, C. G.
Clark, S. Saubern, J. Adams, M. P. Winters, D. M. T.
Chan, A. Combs, Tetrahedron Lett. 1998, 39, 2941; c)
P. López-Alvarado, C. Avendaño, J. C. Menéndez, J.
Org. Chem. 1995, 60, 5678; d) A. Y. Fedorov, J.-P.
Finet, Tetrahedron Lett. 1999, 40, 2747; e) D. J. Slade,
N. F. Pelz, W. Bodnar, J. W. Lampe, P. S. Watson, J.
Org. Chem. 2009, 74, 6331.
Acknowledgements
This work was supported by the National Research Foundation of
Korea (NRF) grant, funded by the Korean government (2011-
0018355) and BRL (2017R1A4A1015405).
[9] a) C.-D. Wang, R.-S. Liu, Org. Biomol. Chem. 2012,
10, 8948; b) W.-S. Yong, S. Park, H. Yun, P. H. Lee,
Adv. Synth. Catal. 2016, 358, 1958; c) T. Jeong, S. H.
Han, S. Han, S. Sharma, J. Park, J. S. Lee, J. H. Kwak,
Y. H. Jung, I. S. Kim, Org. Lett. 2016, 18, 232; d) H.
Oh, S. Han, A. K. Pandey, S. H. Han, N. K. Mishra, R.
Chun, H. S. Kim, J. Park, I. S. Kim, J. Org. Chem.
2018, 83, 4070; e) Z. Long, Z. Wang, D. Zhou, D. Wan,
J. You, Org. Lett. 2017, 19, 2777.
†These authors (J.-Y. S and H.K.) contributed equally to this work.
References
[1] a) J. Elguero, in Comprehensive Heterocyclic
Chemistry, ed. A. R. Katritzky, C. W. Rees, Pergamon
Press, New York, 1984, vol. 5, p. 167; b) M. Akazome,
T. Kondo, Y. Watanabe, J. Org. Chem. 1994, 59, 3375;
c) S. Andreonati, V. Sava, S. Makan, G. Kolodeev,
Pharmazie 1999, 54, 99; d) J. C. Antilla, J. M. Baskin,
T. E. Barder, S. L. Buchwald, J. Org. Chem. 2004, 69,
5578; e) M. V. Peters, R. S. Stoll, R. Goddard, G. Buth,
S. Hecht, J. Org. Chem. 2006, 71, 7840.
[10] a) N. Halland, N. M. Nazaré, O. R’kyek, J. Alonso, M.
Urmann, A. Lindenschmidt, Angew. Chem., Int. Ed.
2009, 48, 6879; b) C. Wu, Y. Fang, R. C. Larock, F.
Shi, Org. Lett. 2010, 12, 2234; c) B. J. Stokes, C. V.
Vogel, L. K. Urnezis, M. Pan, T. G. Driver, Org. Lett.
2010, 12, 2884; d) J. Hu, Y. Cheng, Y. Yang, Y. Rao,
Chem. Commun. 2011, 47, 10133; e) Y. Lian, Y. R.
Bergman, L. D. Lavis, J. A. Ellman, J. Am. Chem. Soc.
2013, 135, 7122; f) N. E. Genung, L. Wei, G. E.
Aspnes, Org. Lett. 2014, 16, 3114; g) J. R. Hummel, J.
A. Ellman, J. Am. Chem. Soc. 2015, 137, 490; h) X.
Geng, C. Wang, Org. Lett. 2015, 17, 2434; i) W. Hu,
J.-T. Yu, S. Liu, Y. Jiang, J. Cheng, Org. Chem. Front.,
2017, 4, 22; j) S. Cai, S. Lin, X. Yi, C. Xi, J. Org.
Chem. 2017, 82, 512. k) R. Fusco, A. Marchesini, F.
Sannicoló, J. Heterocyclic Chem. 1987, 24, 773. l) X.
[2] a) W. Stadlbauer, in Science of Synthesis, vol. 12,
Georg Thieme, Stuttgart, 2002, pp. 227; b) V. Minkin,
D. Garnovskii, J. Elguero, A. Katritzky, O. Denisko,
Adv. Heterocycl. Chem. 76, 157; c) H. Cerecetto, A.
Gerpe, M. González, A. J. Arán, C. O. de Ocáriz, Mini-
Rev. Med. Chem. 2005, 5, 869; d) L. Sorbera, J. Bolos,
N. Serradell, Drugs Future 2006, 31, 585; e) A.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801055
Advanced Synthesis & Catalysis
Yi, L. Jiao, C. Xi. Org. Biomol. Chem. 2016, 14, 9912.
m) X. Yi, C. Xi. Tetrahedron 2017, 73, 1311.
Potavathri, R. A. Barham, K. M. Romano, B. DeBoef, J.
Am. Chem. Soc. 2011, 133, 19960; e) T. Froehr, C. P.
Sindlinger, U. Kloeckner, P. Finkbeiner, B. J.
Nachtsheim, Org. Lett. 2011, 13, 3754; f) Q. Xiao, L.
Tian, R. Tan, Y. Xia, D. Qiu, Y. Zhang, J. Wang, Org.
Lett. 2012, 14, 4230; g) C.-L. Sun, Z.-J. Shi, Chem. Rev.
2014, 114, 9219; h) Y. R. Kim, S. Cho, P. H. Lee, Org.
Lett. 2014, 16, 3098; i) S. W. Youn, E. M. Lee, Org.
Lett. 2016, 18, 5728. 14, 4230.
[11] a) H. Li, P. Li, L. Wang, Org. Lett. 2013, 15, 620; b)
F. Xiong, C. Qian, D. Lin, W. Zeng, X. Lu, Org. Lett.
2013, 15, 5444; c) H. Li, P. Li, H. Tan, L. Wang, Chem.
Eur. J. 2013, 19, 14432.
[12] a) M. Sun, L.-K. Hou, X.-X. Chen, X.-Y. Yang, W.
Sun, Y.-S. Zang. Adv. Synth. Catal. 2014, 356, 3789; b)
H. Li, P. Li, Q. Zhao, L. Wang. Chem. Commun., 2013,
49, 9170; c) G. Hong, A. N. Aruma, X. Zhu, S. Wu, L.
Wang, Synthesis 2016, 48, 1147.
[14] a) Z. X. Liu, H. C. Tan, L. Wang, T. R. Fu, Y. Xia, Y.
Zhang, J. Wang, Angew. Chem., Int. Ed. 2015, 54,
3056; b) Q. Xiao, J. Ma, Y. Yang, Y. Zhang, J. Wang,
Org. Lett. 2009, 11, 4732; c) Y. Xia, J. Wang, Chem.
Soc. Rev. 2017, 46, 2306.
[13] a) C.-J. Li, B. M. Trost, Proc. Natl. Acad. Sci. U. S. A.
2008, 105, 13197; b) A. P. Antonchick, R. Samanta, K.
Kulikov, J. Lategahn, Angew. Chem., Int. Ed. 2011, 50,
8605; c) H. J. Kim, J. Kim, S. H. Cho, S. Chang, J. Am.
Chem. Soc. 2011, 133, 16382; d) A. A. Kantak, S.
8
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FULL PAPER
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