A novel allylic substitution strategy to four-component synthesis of pyrazole-substituted fused pyrroles

Article abstract of DOI:10.1016/j.tet.2013.05.063

The selective formation of pyrazole-substituted fused pyrroles through HOAc-mediated multicomponent reactions of enaminones with arylglyoxal monohydrates and generated in situ pyrazole-3-carboxylates was developed. It constructed a variety of bis-heterocyclic pairs under mild conditions in a domino process. Reaction driving tandem cyclization/allylic esterification/ allylic substitution was achieved through the formation of in situ generation of allyl esters and pyrazole-3-carboxylates from readily available starting materials. Up to two new five-membered heterocyclic rings and five new sigma bonds including a C(sp3)-C(sp2) bond were formed in a single reaction without isolated intermediates.

Full text of DOI:10.1016/j.tet.2013.05.063

Tetrahedron 69 (2013) 6100e6107
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A novel allylic substitution strategy to four-component synthesis
of pyrazole-substituted fused pyrroles
*
*
Xing-Chao Tu, Wei Fan, Bo Jiang , Shu-Liang Wang, Shu-Jiang Tu
School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials,
Jiangsu Normal University, Xuzhou 221116, Jiangsu, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The selective formation of pyrazole-substituted fused pyrroles through HOAc-mediated multicomponent
reactions of enaminones with arylglyoxal monohydrates and generated in situ pyrazole-3-carboxylates
was developed. It constructed a variety of bis-heterocyclic pairs under mild conditions in a domino
process. Reaction driving tandem cyclization/allylic esterification/allylic substitution was achieved
through the formation of in situ generation of allyl esters and pyrazole-3-carboxylates from readily
available starting materials. Up to two new five-membered heterocyclic rings and five new sigma bonds
including a C(sp3)eC(sp2) bond were formed in a single reaction without isolated intermediates.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 21 February 2013
Received in revised form 4 May 2013
Accepted 17 May 2013
Available online 23 May 2013
Keywords:
Multicomponent domino reactions
Pyrazole-substituted fused pyrroles
Microwave heating
Allylic pyrazolization
1. Introduction
Recently, we have been engaging in the development of unique
MDRs that can provide easy access to new core structures of
The direct and selective allylic substitution with carbon nucle-
ophiles constitutes one of the most important and useful carbon-
ecarbon bond-forming reactions in organic synthesis, and a variety
of transition metal complexes have been explored as catalysts for
this regio- and stereoselective reactions.1,2 Thus, the design of new
allylic substitution generated in situ, especially those of metal-free
conditions, remains challenging, and continues to attract interest to
synthetic community.
chemical and pharmaceutical interest.9 During our study of this
topic, we now discovered a novel Brønsted acid-promoted multi-
component N-heteroannulations of enaminones 1 with arylglyoxal
monohydrates 2, phenylhydrazine 3, and acetylenedicarboxylates 4
selectively providing multifunctionalized fused pyrrole derivatives
through the control of charging sequence (Scheme 1). The great
features of the present domino strategy are shown by the fact
that the construction of two new rings including pyrrole and pyr-
azole rings and five new sigma bonds formation containing the
direct C(sp3)eC(sp2) bond were readily achieved via Brønsted
Fused pyrroles are common structural motifs in many bi-
ologically active molecules and pharmaceutical substances.3 Owing
to their biological importance, these derivatives attract the atten-
tion of synthetic chemists. In the past several decades, many
methodologies for the synthesis of fused pyrroles have been de-
veloped, which involved cycloketone annulations,4 rearrangement-
cyclization of alkynol,5a alkynyl ketones,5b metal-catalyzed cascade
cyclization of alkynes,6 and 1,3-dipolar cycloadditions of
7
€
munchnone derivatives. Despite these limited construction of
fused pyrroles, an exploration of a versatile strategy for the direct
formation of fused pyrrole framework would be highly favorable.
To our best of knowledge, the utilization of allylic substitution
generated in situ combined with multicomponent domino re-
actions (MDRs)8 for the construction of pyrazole-substituted fused
pyrrole skeleton has not been published so far.
* Corresponding authors. Tel./fax: þ86 516 83500065; e-mail addresses: jiang-
Scheme 1. The domino synthesis of fused pyrroles 5.
chem@jsnu.edu.cn (B. Jiang), laotu@jsnu.edu.cn (S.-J. Tu).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.063

X.-C. Tu et al. / Tetrahedron 69 (2013) 6100e6107
6101
acid-mediated domino reaction, and allylic substitution generated
in situ occurred in a one-pot operation. The present work repre-
sents the special examples for synthesizing such important types of
bis-heterocyclic pairs containing pyrazole and pyrrole motifs.
2. Results and discussion
We have planned to link two biologically important nuclei, pyr-
azoles and fused pyrroles, to generate a new set of compounds,
pyrazole-substituted fused pyrroles, using allylic substitution-based
heterocyclization of enaminones 1 with arylglyoxal monohydrates
2, phenylhydrazine 3, and acetylenedicarboxylates 4. Here, it should
be mentioned that the chemistry of enaminones, consisting of 1,3-
bisnucleophilic centers, has a wide application on the synthesis of
heterocyclic compounds.9a,b,10 We previously developeda new three-
component domino reaction of enaminones for the synthesis of
multifunctionalized fused pyrroles C through allylic esterification.9a
So, we reasoned that new type of allylic substitution could be ach-
ievedundersuitablereactionconditionsusingallylestersCgenerated
in situ as allylating agents and pyrazole-3-carboxylates generated in
situascarbonnucleophilesinone-potoperation,basedonthesuccess
of allylic substitution between allyl esters and carbon nucleophiles.2
With this notion in mind, we started this study by subjecting
a preformed 3-((4-bromophenyl)amino)-5,5-dimethylcyclo-hex-2-
enone 1a and phenylglyoxal monohydrate 2a to the reaction with
phenylhydrazine 3 and dimethyl acetylenedicarboxylate 4a (DMAD)
in HOAc under microwave heating conditions (Scheme 2). As we
expected, pyrazole-substituted fused pyrroles 5a with 15% chemical
yield was sustained, supported by NMR analysis and X-ray diffraction
of single crystal 5a (Fig. 1). In further steps, possible options were
considered to improve yield of expected product 5a. (a) Charging
sequence. The mixture of enaminones 1a and glyoxal monohydrate
2a in HOAc was firstly heated at 120 ꢀC for 10 min under microwave
irradiation, and then phenylhydrazine 3 and dimethyl acetylenedi-
carboxylate 4a (DMAD) were added into the mixed system at 150 ꢀC
for 15 min. The product 5a was obtained in 83% isolated yield by flash
chromatography (Table 1, entry 5). (b) Acidic solvents. Both HCOOH
and propionic acid were used within the same experimental pro-
cedures. The product 5a was not observed in HCOOH while the pro-
pionic acidgave the 61%yield of5a. Also, HOAcwaschosen for further
study. It turned out that in this reaction acetic acid behaves as nu-
cleophile, reaction media, and Brønsted acid promoter for the allylic
pyrazolization simultaneously.
Fig. 1. X-ray structure of 5a.11
substituents, such as fluoro, bromo, and chloro groups at the para
position of the benzene ring, but also 1dee having electron-
donating substituents, such as methyl and methoxy groups pro-
duced the corresponding pyrazole-substituted fused pyrroles 5 in
good to high yields, respectively. Both electron-deficient and
electron-rich groups on the arylglyoxal monohydrates were suitable
for the multicomponent domino reactions. Similarly, the diethyl
acetylenedicarboxylate 4b was another appropriate partner in the
multicomponent domino reactions and worked well, providing the
corresponding products 5 in good yields of 77e85%. With no ex-
ceptions, the reaction of secondary allylic acetates with different
substitution patterns resulted in the direct displacement of the
acetoxy group with pyrazole-3-carboxylates generated in situ. The
results exhibit the scope and generality of the novel allylic
substitution-based multicomponent domino reaction with respect
to a range of enaminones and arylglyoxal monohydrate substrates,
although 5,5-unsubstituted enaminones failed totake place in allylic
substitution with pyrazole-3-carboxylates since it was converted
into the polysubstituted bis-indoles.9a
In all cases, the complexity of resulting products from this new
reaction illustrates the remarkable regioselectivity of the sequence
starting from verycommon and easily accessible inexpensive starting
materials. Ingeneral, thereactionoccurredataveryfastspeed withall
cases finished within 25e32 min. Water and alcohols were formed as
the major by-products, which make the work-up convenient. In most
cases, the products can precipitate out after cold water was poured
into the reaction mixture. During these domino processes, up to two
new rings (pyrrole and pyrazole rings) and five new sigma bonds
including a C(sp3)eC(sp2) bond were formed accompanied by cleav-
age of one C]O and three CeO bonds of the arylglyoxal mono-
hydrates and acetylenedicarboxylates, and direct allylic pyrazolation
of fused pyrroles C was simultaneously achieved via intermolecular
allylicsubstitutionbetweenallylestersCandpyrazole-3-carboxylates
E;12 both of them were generated in situ (Table 1). This observation is
very interesting and useful in organic chemistry.
O
O
O
CO2Me
Ph
NH
HO
AcOH
120-150 oC
CO2Me
4a
Ph
Ph +
+
+
H3N
N
NH
Ph-p-Br
OH
2a
Ph-p-Br
H
1a
MeO2C
OH
3
N N
single step, yield 15%
Ph
O
O
5a
AcOH 120 o
C
Ph
3 and 4a
5a
N
150 oC
two-step, yield 83%
Ph-p-Br
O
C1
Scheme 2. The optimized synthesis of fused pyrroles 5a.
The mechanism for formation of products 5 was proposed
and shown in Scheme 3. The reactioninvolves the dominocyclization
to give allylic acetates C,9a which is followed by subsequent in-
termolecular nucleophilic substitution with pyrazole-3-carboxylates
E,12 derived from phenylhydrazine 3 and acetylenedicarboxylates 4,
yielding final products 5. This mechanism was supported by the fact
that the isolated allylic acetates C1 was employed to subject with
isolated pyrazole-3-carboxylates E in HOAc, generating pyrroles 5a in
82% yield (Scheme 4).
With the optimized multicomponent protocol in hand, we next
set out to explore its scope using various readily available starting
materials. The reactions of various arylglyoxal monohydrates 1 with
N-substituted 3-aminocyclohex-2-enones (2aef) in acetic acid were
performed for a short period, following with addition of both phe-
nylhydrazine 3 and dimethyl acetylenedicarboxylate 4a were added
into the mixed system under the conditions described above
(25e32 min). The results are summarized in Table 1. Obviously, not
only N-aryl enaminones 1aec, which possess electron-withdrawing

6102
X.-C. Tu et al. / Tetrahedron 69 (2013) 6100e6107
Table 1
Multicomponent domino synthesis of pyrazole-substituted fused pyrroles 5
Entry
5
R
Ar
R1
Timea/min
Yieldb (%)
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
p-BrC6H4 (1a)
p-BrC6H4 (1a)
p-BrC6H4 (1a)
p-BrC6H4 (1a)
p-BrC6H4 (1a)
p-BrC6H4 (1a)
p-BrC6H4 (1a)
p-FC6H4 (1b)
p-FC6H4 (1b)
p-FC6H4 (1b)
p-FC6H4 (1b)
p-FC6H4 (1b)
p-ClC6H4 (1c)
p-ClC6H4 (1c)
p-ClC6H4 (1c)
p-ClC6H4 (1c)
p-ClC6H4 (1c)
p-ClC6H4 (1c)
p-CH3C6H4 (1d)
p-CH3C6H4 (1d)
p-CH3C6H4 (1d)
p-CH3C6H4 (1d)
p-CH3C6H4 (1d)
p-CH3C6H4 (1e)
p-CH3C6H4 (1e)
p-CH3C6H4 (1e)
p-CH3C6H4 (1e)
p-CH3C6H4 (1e)
p-CH3C6H4 (1e)
C6H5 (2a)
Me (4a)
Me (4a)
Me (4a)
Me (4a)
Et (4b)
Et (4b)
Et (4b)
Me (4a)
Me (4a)
Me (4a)
Me (4a)
Et (4b)
Me (4a)
Me (4a)
Me (4a)
Me (4a)
Et (4b)
Et (4b)
Me (4a)
Me (4a)
Me (4a)
Me (4a)
Et (4b)
Me (4a)
Me (4a)
Me (4a)
Me (4a)
Et (4b)
Et (4b)
25
27
26
29
28
31
27
25
29
27
30
31
29
25
27
28
32
28
27
25
26
27
29
25
28
26
28
29
32
83
84
87
88
82
81
85
83
86
87
89
84
79
85
83
81
87
86
78
87
86
82
83
79
86
89
78
77
81
p-ClC6H4 (2b)
p-BrC6H4 (2c)
p-CH3C6H4 (2d)
C6H5 (2a)
p-ClC6H4 (2b)
p-BrC6H4 (2c)
C6H5 (2a)
p-ClC6H4 (2b)
p-BrC6H4 (2c)
p-CH3C6H4 (2d)
p-BrC6H4 (2c)
C6H5 (2a)
p-ClC6H4 (2b)
p-BrC6H4 (2c)
p-CH3C6H4 (2d)
p-ClC6H4 (2b)
p-BrC6H4 (2c)
C6H5 (2a)
p-ClC6H4 (2b)
p-BrC6H4 (2c)
p-CH3C6H4 (2d)
p-ClC6H4 (2b)
C6H5 (2a)
p-ClC6H4 (2b)
p-BrC6H4 (2c)
p-CH3C6H4 (2d)
C6H5 (2a)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
5s
5t
5u
5v
5w
5x
5y
5z
5aa
5ab
5ac
p-CH3C6H4 (2d)
a
Total reaction time of two steps.
Isolated yield.
b
O
O
O
O
O
OH
Ar
Ar
Ar
Ar
H+
H+
HO
2
O
OH
OH2
N
O
N
-2H2O
NH
R
NH
R
R
O
R
Ar
H
N
A
AcO
Ph
C
B
1
-AcOH
R
O
R1O2C
OH
OH
O
CO2R1
H2N
HN Ph
R1
N N
Ph
O
N
-R1OH
N
Ph
HN
5
R1O2C
N
N
H
NH
Ph
CO2R1
CO2R1
CO2R1
E
3
D
Scheme 3. The proposed mechanism for the formations of fused pyrroles 5.
3. Conclusion
In conclusion, we have developed HOAc-mediated multicom-
ponent reactions that enable metal-free allylic substitution of in
situ generation of both pyrazole-3-carboxylates and allyl esters.
This domino strategy provides a facile and efficient method for
construction of structurally diverse bis-heterocyclic pairs contain-
ing pyrazole and pyrrole motifs. Notable features of these reactions
Scheme 4. The supporting reaction for the proposed mechanism.

X.-C. Tu et al. / Tetrahedron 69 (2013) 6100e6107
6103
include short reaction times, convenient one-pot operation, high
regioselectivity, and atom-economical process with a broad range
of starting materials. Future work will focus on an expansion of the
reaction’s scope and on the use of this methodology in its asym-
metric version.
CH3), 2.89 (d, J¼17.6 Hz, 1H, CH2), 2.10 (d, J¼20.0 Hz, 1H, CH2), 1.25
(s, 3H, CH3), 0.97 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
, ppm):
197.8, 163.0, 149.5, 148.7, 139.7, 137.7, 136.0, 136.0, 133.3, 132.7, 132.1,
129.9, 129.6, 129.4, 129.0, 128.5, 128.0, 123.9, 122.9, 119.6, 106.3,
105.6, 51.9, 48.8, 38.5, 38.1, 28.9, 27.3, 20.6. HRMS (ESI) m/z: calcd
for C33H27BrClN3O4: 642.0795 [MꢁH]ꢁ; found: 642.0794.
d
4. Experimental section
4.1. General
4.5. Methyl 4-(1,2-bis(4-bromophenyl)-4,5,6,7-tetrahydro-
6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-hydroxy-1-phenyl-1H-
pyra-zole-3-carboxylate (5c)
Microwave irradiation was carried out with Initiator 2.5 Mi-
crowave Synthesizers from Biotage, Uppsala, Sweden. Melting
points were determined in open capillaries and were uncorrected.
IR spectra were taken on a FT-IR-Tensor 27 spectrometer in KBr
White solid, mp: 257e259 ꢀC.
IR (KBr,
n
, cmꢁ1): 2955, 1720, 1708, 1621, 1575, 1467, 1446, 1402,
1218, 1171, 1043, 1011, 827, 807, 799, 753. 1H NMR (400 MHz, CDCl3)
pellets and reported in cmꢁ1
.
1H NMR spectra were measured on
d
: 7.69 (d, J¼7.6 Hz, 2H, AreH), 7.52 (s, 1H, AreH), 7.44 (t, J¼7.6 Hz,
a Bruker DPX 400 MHz spectrometer in DMSO-d6 with chemical
shift ( ) given in parts per million relative to TMS as internal
2H, AreH), 7.35 (t, J¼7.6 Hz, 1H, AreH), 7.29e7.22 (m, 3H, AreH),
7.09 (s, 1H, AreH), 6.81 (d, J¼8.4 Hz, 2H, AreH), 6.47 (d, 2H, AreH),
4.65 (s, 1H, CH), 3.82 (s, 3H, CH3), 2.89 (d, J¼17.6 Hz, 1H, CH2), 2.10
(d, J¼19.2 Hz, 1H, CH2), 1.25 (s, 3H, CH3), 0.96 (s, 3H, CH3). 13C NMR
d
standard [(s¼singlet, d¼doublet, t¼triplet, br s¼broad singlet,
m¼multiplet), coupling constant (Hertz)]. HRMS (ESI) was de-
termined by using microTOF-Q II HRMS/MS instrument (BRUKER).
X-ray crystallographic analysis was performed with a Siemens P4
diffractometer.
(100 MHz, CDCl3) (d, ppm): 197.9, 163.0, 149.6, 148.8, 139.7, 137.7,
136.0,136.0,132.7,132.1,131.5,130.1,129.9,129.7,129.0,128.0,124.0,
122.9, 121.5, 119.6, 106.4, 105.6, 51.9, 48.8, 38.5, 38.1, 28.9, 27.3.
HRMS (ESI) m/z: calcd for C33H27Br2N3O4: 688.0267 [MꢁH]ꢁ;
found: 688.0268.
4.2. Typical procedure for the preparation of 5
In a 10-mL reaction vial, enaminones (1, 1 mmol, 1.0 equiv),
phenylglyoxal monohydrates (2, 1 mmol, 1.0 equiv), and acetic
acid (2.0 mL) were mixed equally and then heated to 120 ꢀC for
10e12 min under microwave irradiation. Acetylenedicarbox-
ylates (4, 1.0 mmol, 1.0 equiv) was then added into the mixture
system, and phenylhydrazine (3, 1.0 mmol, 1.0 equiv) was filled
slowly (within 2 min) under constantly stirring conditions. The
reaction temperature was raised to 150 ꢀC for 15e18 min under
microwave irradiation. Upon completion as shown by TLC mon-
itoring, the reaction mixture diluted with cold water. The
resulting mixture was purified by flash column chromatography
on silica gel (n-hexane/diethyl ether¼7/1) to give the desired
product 5.
4.6. Methyl 4-(1-(4-bromophenyl)-4,5,6,7-tetrahydro-6,6-
dimeth-yl-4-oxo-2-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-
phenyl-1H-pyrazole-3-carboxylate (5d)
White solid, mp: 246e247 ꢀC.
IR (KBr,
1219, 1173, 1121, 1043, 1015, 959, 824, 807, 755, 696. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2955, 1716, 1624, 1575, 1492, 1470, 1402, 1285,
d: 7.70 (d, J¼8.0 Hz, 2H, AreH), 7.50 (s, 1H, AreH),
7.43 (t, J¼7.6 Hz, 2H, AreH), 7.34 (t, J¼7.2 Hz, 1H, AreH), 7.24 (s, 1H,
AreH), 7.11 (s, 1H, AreH), 6.91 (d, J¼8.0 Hz, 2H, AreH), 6.86 (d,
J¼7.6 Hz, 2H, AreH), 6.62e6.43 (m, 2H, AreH), 4.65 (s, 1H, CH), 3.83
(s, 3H, CH3), 2.89 (d, J¼17.2 Hz, 1H, CH2), 2.23 (s, 3H, CH3), 2.17 (d,
J¼17.2 Hz, 1H, CH2), 1.27 (s, 3H, CH3), 0.98 (s, 3H, CH3). 13C NMR
(100 MHz, CDCl3) (d, ppm): 197.4, 163.0, 149.6, 148.0, 139.7, 137.7,
4.3. Methyl 4-(1-(4-bromophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-2-phenyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyr-azole-3-carboxylate (5a)
137.4, 137.0, 136.4, 129.0, 129.0, 128.3, 128.3, 127.8, 123.8, 122.6,
119.6, 106.1, 104.9, 51.9, 48.9, 38.6, 38.1, 28.9, 27.3, 21.2. HRMS (ESI)
m/z: calcd for C34H30BrN3O4: 624.1321 [MꢁH]ꢁ; found: 624.1321.
White solid, mp: 269e271 ꢀC.
4.7. Ethyl 4-(1-(4-bromophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-2-phenyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5e)
IR (KBr,
1395, 1218, 1172, 1044, 1015, 958, 830, 808, 756. 1H NMR
(400 MHz, DMSO-d6)
: 10.04 (s, 1H, OH), 7.62 (d, J¼7.2 Hz, 1H,
n
, cmꢁ1): 2955, 1719, 1709, 1622, 1598, 1575, 1491,
d
AreH), 7.55 (d, J¼8.0 Hz, 2H, AreH), 7.48 (t, J¼7.6 Hz, 2H),
7.45e7.36 (m, 2H, AreH), 7.26e7.17 (m, 3H, AreH), 7.17e7.10 (m,
3H, AreH), 6.67 (s, 1H, AreH), 6.40 (d, J¼7.4 Hz, 1H, AreH), 4.55
(s, 1H, CH), 3.71 (s, 3H, CH3), 2.85 (d, J¼16.0 Hz, 1H, CH2), 2.09
(d, J¼5.4 Hz, 1H, CH2), 1.24 (s, 3H, CH3), 0.87 (s, 3H, CH3). HRMS
(ESI) m/z: calcd for C33H28BrN3O4: 608.1185 [MꢁH]ꢁ; found:
608.1153.
White solid, mp: 209e210 ꢀC.
IR (KBr,
n
, cmꢁ1): 2957, 1703, 1626, 1557, 1490, 1456, 1397, 1375,
1287, 1218, 1041, 1014, 822, 756, 689. 1H NMR (400 MHz, DMSO-d6)
d
: 9.99 (s,1H, OH), 7.60 (d, J¼7.6 Hz,1H, AreH), 7.55 (d, J¼8.0 Hz, 2H,
AreH), 7.49 (t, J¼7.6 Hz, 2H, AreH), 7.44e7.37 (m, 2H, AreH),
7.31e7.08 (m, 6H, AreH), 6.66 (s, 1H, AreH), 6.44 (d, J¼7.2 Hz, 1H),
AreH, 4.56 (s, 1H, CH), 4.24e4.01 (m, 2H, CH2), 2.83 (d, J¼16.0 Hz,
1H, CH2), 2.06 (d, J¼16.4 Hz, 1H, CH2), 1.28 (t, J¼7.0 Hz, 3H, CH3),
1.22 (s, 3H, CH3), 0.86 (s, 3H, CH3). HRMS (ESI) m/z: calcd for
C34H30BrN3O4: 623.1243; found: 623.1265.
4.4. Methyl 4-(1-(4-bromophenyl)-2-(4-chlorophenyl)-
4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-
hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (5b)
4.8. Ethyl 4-(1-(4-bromophenyl)-2-(4-chlorophenyl)-4,5,6,7-
tetrahydro-6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-hydroxy-1-
phenyl-1H-pyrazole-3-carboxylate (5f)
White solid, mp: 267e269 ꢀC.
IR (KBr,
1397, 1218, 1172, 1043, 1015, 958, 831, 808, 756, 696. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2955, 1719, 1708, 1622, 1596, 1575, 1491, 1469,
d
: 7.69 (d, J¼7.6 Hz, 2H, AreH), 7.52 (s, 1H, AreH),
White solid, mp: 245e246 ꢀC.
7.44 (t, J¼7.6 Hz, 2H, AreH), 7.35 (t, J¼7.2 Hz, 1H, AreH), 7.26 (s, 1H,
AreH), 7.10 (d, J¼8.4 Hz, 3H, AreH), 6.88 (d, J¼8.4 Hz, 2H, AreH),
6.50 (s, 1H, AreH), 6.44 (s, 1H, AreH), 4.65 (s, 1H, CH), 3.83 (s, 3H,
IR (KBr,
1216, 1094, 1042, 1014, 831, 803, 757, 695, 640. 1H NMR (400 MHz,
CDCl3)
: 7.69 (d, J¼8.0 Hz, 2H, AreH), 7.52 (d, J¼6.4 Hz, 1H, AreH),
n
, cmꢁ1): 2958, 1716, 1704, 1622, 1575, 1491, 1469, 1417,
d

6104
X.-C. Tu et al. / Tetrahedron 69 (2013) 6100e6107
7.44 (t, J¼7.6 Hz, 2H, AreH), 7.40e7.28 (m, 2H, AreH), 7.15e7.02 (m,
3H, AreH), 6.90 (d, J¼8.4 Hz, 2H, AreH), 6.59e6.47 (m, 2H, AreH),
4.68 (s,1H, CH), 4.40e4.20 (m, 2H, CH2), 2.87 (d, J¼17.2 Hz,1H, CH2),
2.36e2.19 (m, 1H, CH2), 1.37 (t, J¼7.2 Hz, 3H, CH3), 1.26 (s, 3H, CH3),
4.12. Methyl 4-(2-(4-bromophenyl)-1-(4-fluorophenyl)-
4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-
hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (5j)
0.98 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
d, ppm): 197.6, 162.6,
White solid, mp: 245e246 ꢀC.
149.4, 148.6, 140.0, 137.7, 136.1, 136.0, 133.3, 132.1, 129.6, 129.3,
129.0, 128.6, 127.9, 123.9, 122.9, 119.7, 105.9, 105.7, 61.0, 48.8, 38.8,
38.2, 28.8, 27.3, 14.4. HRMS (ESI) m/z: calcd for C34H29BrClN3O4:
657.0850 [MꢁH]ꢁ; found: 657.0854.
IR(KBr,
n
, cmꢁ1):2956,1721,1710,1622,1511,1471,1415,1284,1219,
1197,1170,1043, 853, 809, 748, 650.1H NMR (400 MHz, CDCl3)
d: 9.30
(s, 1H, OH), 7.69 (d, J¼7.6 Hz, 2H, AreH), 7.44 (t, J¼7.6 Hz, 2H, AreH),
7.35 (t, J¼7.2 Hz, 1H, AreH), 7.28e7.16 (m, 3H, AreH), 7.08 (s, 1H,
AreH), 6.82 (d, J¼8.4 Hz, 3H, AreH), 6.61 (s, 1H, AreH), 6.48 (s, 1H,
AreH), 4.66 (s, 1H, CH), 3.79 (s, 3H, CH3), 2.88 (d, J¼17.2 Hz, 1H, CH2),
2.16 (d, J¼17.2 Hz,1H, CH2),1.26 (s, 3H, CH3), 0.97 (s, 3H, CH3).13C NMR
4.9. Ethyl 4-(1,2-bis(4-bromophenyl)-6,6-dimethyl-4-oxo-
4,5,6,7-tetrahydro-1H-indol-7-yl)-5-hydroxy-1-phenyl-1H-
pyrazole-3-carboxylate (5g)
(100 MHz, CDCl3) (
d
, ppm): 197.7, 163.0, 162.3 (1JCF¼250.0 Hz), 149.5,
148.9, 139.7, 137.7, 136.2, 133.0 (4JCF¼3.2 Hz),131.5,130.1 (3JCF¼9.4 Hz),
129.6, 129.0, 127.9, 123.9, 121.4, 119.5, 116.1 (d, J¼22.4 Hz, 1H), 106.2,
105.5, 51.7, 48.8, 38.6, 38.1, 28.9, 27.3. HRMS (ESI) m/z: calcd for
C33H27BrFN3O4: 628.1071 [MꢁH]ꢁ; found: 628.1069.
White solid, mp: 235e237 ꢀC.
IR (KBr,
n
, cmꢁ1): 2957, 1716, 1703, 1622, 1594, 1490, 1469, 1402,
1217, 1174,1043, 1010, 828, 802, 753, 695. 1H NMR (400 MHz, CDCl3)
d
: 7.70 (d, J¼7.6 Hz, 2H, AreH), 7.51 (d, J¼7.6 Hz, 1H, AreH), 7.44 (t,
4.13. Methyl 4-(1-(4-fluorophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-2-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5k)
J¼7.6 Hz, 2H, AreH), 7.35 (t, J¼7.2 Hz, 1H, AreH), 7.31e7.22 (m, 3H,
AreH), 7.06 (d, J¼7.6 Hz, 1H, AreH), 6.78 (d, J¼8.4 Hz, 2H, AreH),
6.57 (d, J¼8.0 Hz, 1H, AreH), 6.37 (s, 1H, AreH), 4.66 (s, 1H, CH),
4.38e4.18 (m, 2H, CH2), 2.89 (d, J¼17.6 Hz, 1H, CH2), 2.09 (d,
J¼17.2 Hz, 1H, CH2), 1.37 (t, J¼7.2 Hz, 3H, CH3), 1.22 (s, 3H, CH3), 0.94
White solid, mp: 228e229 ꢀC.
IR (KBr,
1219, 1179, 1170, 1043, 853, 819, 798, 753, 695. 1H NMR (400 MHz,
CDCl3)
n
, cmꢁ1): 2956, 1716, 1624, 1598, 1596, 1510, 1446, 1379,
(s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
d, ppm): 197.4, 162.9, 159.6,
149.5, 148.9, 139.9, 137.8, 136.2, 132.9, 130.1, 129.6, 129.3, 128.9,
128.8, 128.3, 127.8, 123.9, 119.3, 114.6, 113.8, 106.2, 105.2, 55.4, 51.5,
48.9, 38.6, 38.2, 28.8, 27.3, 14.3. HRMS (ESI) m/z: calcd for
C34H29Br2N3O4: 702.0424 [MꢁH]ꢁ; found: 702.0424.
d
: 7.67 (d, J¼7.2 Hz, 2H, AreH), 7.43 (t, J¼7.2 Hz, 2H, AreH),
7.34 (t, J¼7.2 Hz,1H, AreH), 7.25e7.04 (m, 2H, AreH), 6.97e6.89 (m,
4H, AreH), 6.78 (s, 1H, AreH), 6.70e6.48 (m, 2H, AreH), 4.68 (s, 1H,
CH), 3.80 (s, 3H, CH3), 2.83 (d, J¼15.6 Hz, 1H, CH2), 2.37e2.23 (m,
4H, CH2, CH3),1.30 (s, 3H, CH3),1.00 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3) (
d
, ppm): 163.0, 162.2 (1JCF¼249.6 Hz), 149.6, 139.7, 137.7,
4.10. Methyl 4-(1-(4-fluorophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-2-phenyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5h)
137.6, 137.0, 133.3 (4JCF¼3.2 Hz), 129.0, 128.9 (3JCF¼9.6 Hz), 128.9,
128.4, 128.2, 127.8, 123.7, 123.7, 119.5, 116.1 (2JCF¼22.4 Hz), 113.2,
104.8, 51.7, 48.9, 38.7, 38.2, 28.9, 27.3, 21.2. HRMS (ESI) m/z: calcd
for C34H30FN3O4: 562.2142 [MꢁH]ꢁ; found: 562.2130.
White solid, mp: 230e231 ꢀC.
IR (KBr,
n
, cmꢁ1): 2956, 1716, 1622, 1598, 1540, 1472, 1398, 1217,
1173,1093,1044, 806, 753, 695. 1H NMR (400 MHz, CDCl3)
d
: 7.68 (d,
4.14. Ethyl 4-(2-(4-bromophenyl)-1-(4-fluorophenyl)-6,6-
dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-7-yl)-5-hydroxy-
1-phenyl-1H-pyrazole-3-carboxylate (5l)
J¼7.2 Hz, 2H, AreH), 7.43 (t, J¼7.2 Hz, 2H, AreH), 7.34 (t, J¼7.2 Hz,
2H, AreH), 7.26 (s, 1H, AreH), 7.16e6.97 (m, 6H, AreH), 6.80 (s, 1H,
AreH), 6.67e6.50 (m, 2H, AreH), 4.69 (s, 1H, CH), 3.80 (s, 3H, CH3),
2.86 (d, J¼17.2 Hz, 1H, CH2), 2.23 (d, J¼17.6 Hz, 1H, CH2), 1.30 (s, 3H,
White solid, mp: 229e231 ꢀC.
CH3), 1.00 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
d, ppm): 197.7,
IR (KBr,
1283, 1217, 1190, 1174, 1043, 1009, 853, 824, 797, 747. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2958, 1715, 1704, 1621, 1595, 1510, 1469, 1402,
163.0, 162.2 (1JCF¼249.4 Hz), 149.6, 148.5, 139.7, 137.8, 137.4, 133.3
(4JCF¼3.2 Hz), 131.3, 129.6 (3JCF¼7.6 Hz), 129.0, 128.3, 128.1, 127.8,
127.2, 123.9, 119.5, 115.9 (2JCF¼23.6 Hz), 106.3, 105.3, 51.7, 48.9, 38.6,
38.1, 28.9, 27.3. HRMS (ESI) m/z: calcd for C33H28FN3O4: 548.1986
[MꢁH]ꢁ; found: 548.2000.
d: 10.14 (s, 1H, OH), 7.71 (d, J¼7.6 Hz, 2H, AreH),
7.43 (t, J¼7.2 Hz, 2H, AreH), 7.34 (t, J¼7.2 Hz, 1H, AreH), 7.23 (d,
J¼8.0 Hz, 2H, AreH), 7.17 (s, 1H, AreH), 7.07 (t, J¼7.6 Hz, 1H, AreH),
6.85 (t, J¼7.6 Hz,1H, AreH), 6.78 (d, J¼7.6 Hz, 2H, AreH), 6.68 (s,1H,
AreH), 6.37 (s, 1H, AreH), 4.65 (s, 1H, CH), 4.37e4.15 (m, 2H, CH2),
2.89 (d, J¼17.6 Hz, 1H, CH2), 2.08 (d, J¼17.2 Hz, 1H, CH2), 1.34 (t,
J¼7.0 Hz, 3H, CH3), 1.23 (s, 3H, CH3), 0.94 (s, 3H, CH3). 13C NMR
4.11. Methyl 4-(2-(4-chlorophenyl)-1-(4-fluorophenyl)-
4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-
hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (5i)
(100 MHz, CDCl3) (
d
, ppm): 196.9, 162.28 (1JCF¼249.8 Hz), 148.3,
140.0, 137.7, 136.3, 132.9 (4JCF¼3.2 Hz), 130.1, 129.9 (3JCF¼9.6 Hz),
129.6, 123.0, 127.9, 123.7, 121.5, 119.6, 116.1 (2JCF¼24.4 Hz), 105.6,
60.8, 48.9, 38.8, 38.2, 28.7, 27.2, 14.3. HRMS (ESI) m/z: calcd for
C34H29BrFN3O4: 642.1227 [MꢁH]ꢁ; found: 642.1227.
White solid, mp: 240e241 ꢀC.
IR (KBr,
1353, 1234, 1204, 1164, 1099, 1046, 730, 688, 613, 555. 1H NMR
(400 MHz, CDCl3)
2H, AreH), 7.35 (t, J¼7.2 Hz, 1H, AreH), 7.20 (s, 1H, AreH), 7.10 (d,
J¼8.4 Hz, 3H, AreH), 6.89 (d, J¼8.4 Hz, 2H, AreH), 6.83 (s, 1H,
AreH), 6.59 (s, 1H, AreH), 6.52 (s, 1H, AreH), 6.52 (s, 1H, AreH),
4.67 (s, 1H, CH), 3.80 (s, 3H, CH3), 2.87 (d, J¼17.2 Hz, 1H, CH2),
2.25e2.17 (m, 1H, CH2), 1.27 (s, 3H, CH3), 0.98 (s, 3H, CH3). 13C NMR
n
, cmꢁ1): 2959, 2929, 2873, 1740, 1713, 1650, 1531, 1384,
d
: 7.69 (d, J¼7.6 Hz, 2H, AreH), 7.44 (t, J¼7.6 Hz,
4.15. Methyl 4-(1-(4-chlorophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-2-phenyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5m)
White solid, mp: 262e263 ꢀC.
(100 MHz, CDCl3) (
d
, ppm): 163.0, 162.3 (1JCF¼250.0 Hz), 149.5,
IR (KBr,
1441, 1376, 1284, 1217, 1711, 1043, 841, 810, 758, 696. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2956, 1717, 1707, 1624, 1598, 1560, 1495, 1468,
139.7, 137.7, 136.2, 133.2 (4JCF¼3.6 Hz), 133.0, 129.7 (3JCF¼8.8 Hz),
129.4, 129.0, 128.5, 127.9, 123.8, 119.5, 116.1 (2JCF¼23.6 Hz), 105.5,
51.7, 48.8, 38.6, 38.1, 28.9, 27.3. HRMS (ESI) m/z: calcd for
C33H27ClFN3O4: 582.1596 [MꢁH]ꢁ; found: 582.1595.
d
: 8.50 (s, 1H, OH), 7.68 (d, J¼7.1 Hz, 2H, AreH),
7.48e7.31 (m, 4H, AreH), 7.23e6.99 (m, 7H, AreH), 6.64e6.46 (m,
2H, AreH), 4.68 (s, 1H, CH), 3.82 (s, 3H, CH3), 2.87 (d, J¼16.9 Hz, 1H,

X.-C. Tu et al. / Tetrahedron 69 (2013) 6100e6107
6105
CH2), 2.22 (d, J¼17.7 Hz, 1H, CH2), 1.29 (s, 3H, CH3), 0.99 (s, 3H, CH3).
13C NMR (100 MHz, CDCl3) (
, ppm): 197.7, 163.0, 149.6, 148.4, 139.7,
137.7,137.3,135.8,134.6,131.2,129.0,128.3,128.2,127.9,127.2,123.9,
119.6, 106.3, 105.3, 51.8, 48.9, 38.5, 38.1, 29.0, 27.3. HRMS (ESI) m/z:
calcd for C33H28ClN3O4: 564.1690 [MꢁH]ꢁ; found: 564.1689.
CH2), 2.86 (d, J¼17.2 Hz, 1H, CH2), 2.36e2.22 (m, 1H, CH2), 1.36 (t,
J¼7.2 Hz, 3H, CH3), 1.26 (s, 3H, CH3), 0.99 (s, 3H, CH3). 13C NMR
d
(100 MHz, CDCl3) (d, ppm): 162.6, 149.3, 140.0, 137.7, 136.2, 135.5,
134.9, 133.3, 129.6, 129.5, 129.3, 129.1, 129.0, 128.6, 127.9, 123.8,
119.7, 105.7, 60.9, 48.9, 38.8, 38.2, 28.7, 27.2, 14.4. HRMS (ESI) m/z:
calcd for C34H29Cl2N3O4: 612.1457 [MꢁH]ꢁ; found: 612.1460.
4.16. Methyl 4-(1,2-bis(4-chlorophenyl)-4,5,6,7-tetrahydro-
6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-hydroxy-1-phenyl-1H-
pyrazole-3-carboxylate (5n)
4.20. Ethyl 4-(2-(4-bromophenyl)-1-(4-chlorophenyl)-6,6-
dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-7-yl)-5-hydroxy-
1-phenyl-1H-pyrazole-3-carboxylate (5r)
White solid, mp: 265e267 ꢀC.
IR (KBr,
1217, 1197, 1172, 1092, 1043, 831, 800, 753, 695, 642. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2956, 1720, 1709, 1622, 1597, 1548, 1470, 1398,
White solid, mp: 231e233 ꢀC.
IR (KBr,
n
, cmꢁ1): 2958, 1716, 1703, 1622, 1594, 1402, 1282, 1217,
d
: 7.67 (d, J¼8.0 Hz, 2H, AreH), 7.48e7.33 (m, 4H,
1172,1091,1043, 1009, 827, 801, 756, 730. 1H NMR (400 MHz, CDCl3)
AreH), 7.22e7.06 (m, 4H, AreH), 6.91 (d, J¼8.4 Hz, 2H, AreH), 6.56 (s,
2H, AreH), 4.67 (s, 1H, CH), 3.82 (s, 3H, CH3), 2.89 (d, J¼17.2 Hz, 1H,
d
: 9.87 (s, 1H, OH), 7.71 (d, J¼7.6 Hz, 2H, AreH), 7.44 (t, J¼7.6 Hz, 2H,
AreH), 7.40e7.31 (m, 2H, AreH), 7.25 (d, J¼8.4 Hz, 2H, AreH), 7.13
(s, 2H, AreH), 6.78 (d, J¼8.0 Hz, 2H, AreH), 6.62 (d, J¼6.8 Hz, 1H,
AreH), 6.39 (s, 1H, AreH), 4.66 (s, 1H, CH), 4.42e4.18 (m, 2H, CH2),
2.89 (d, J¼17.2 Hz, 1H, CH2), 2.11 (d, J¼17.2 Hz, 1H, CH2), 1.36 (t,
J¼6.8 Hz, 3H, CH3), 1.23 (s, 3H, CH3), 0.95 (s, 3H, CH3). 13C NMR
CH2), 2.14e2.08 (m, 1H, CH2), 1.28 (s, 3H, CH3), 0.99 (s, 3H, CH3). 13
C
NMR (100 MHz, CDCl3) (d, ppm): 197.9, 163.0, 149.5, 148.8, 139.7,
137.7, 136.0, 135.5, 134.9, 133.2, 129.6, 129.4, 129.2, 129.0, 128.5, 128.0,
123.9, 119.6, 106.4, 105.6, 51.8, 48.8, 38.5, 38.1, 28.9, 27.3. HRMS (ESI)
m/z: calcd for C33H27Cl2N3O4: 598.1300 [MꢁH]ꢁ; found: 598.1300.
(100 MHz, CDCl3) (d, ppm): 197.4, 162.6, 149.4, 148.5, 140.0, 137.7,
136.1,135.5,134.9, 131.5, 130.0, 129.6, 129.0, 127.9,123.9, 121.5,119.7,
105.7, 60.9, 48.9, 38.8, 38.2, 28.8, 27.2, 14.4. HRMS (ESI) m/z: calcd
for C34H29BrClN3O4: 658.0928 [MꢁH]ꢁ; found: 658.0929.
4.17. Methyl 4-(2-(4-bromophenyl)-1-(4-chlorophenyl)-
4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-
hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (5o)
4.21. Methyl 4-(4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-2-
phenyl-1-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-1H-pyr-
azole-3-carboxylate (5s)
White solid, mp: 267e268 ꢀC.
IR (KBr,
1378, 1217, 1711, 1042, 1010, 827, 808, 799, 730. 1H NMR (400 MHz,
CDCl3)
n
, cmꢁ1): 2955, 1720, 1708, 1621, 1596, 1545, 1494, 1468,
d
: 7.68 (d, J¼8.0 Hz, 2H, AreH), 7.43 (t, J¼7.6 Hz, 2H, AreH),
White solid, mp: 251e253 ꢀC.
7.35 (t, J¼7.2 Hz, 1H, AreH), 7.26e7.17 (m, 3H, AreH), 7.08 (s, 1H,
AreH), 6.83 (d, J¼8.0 Hz, 3H, AreH), 6.61 (s, 1H, AreH), 6.49 (s, 1H,
AreH), 4.66 (s, 1H, CH), 3.79 (s, 3H, CH3), 2.89 (d, J¼17.2 Hz, 1H, CH2),
IR (KBr,
1151, 1044, 1018, 847, 807, 772, 750, 699. 1H NMR (400 MHz, DMSO-
d6)
n
, cmꢁ1): 2957, 1709, 1625, 1503, 1435, 1402, 1237, 1198,
d
: 10.01 (s,1H, OH), 7.56 (d, J¼7.6 Hz, 2H, AreH), 7.48 (t, J¼7.6 Hz,
2.15 (d, J¼16.8 Hz, 1H, CH2), 1.26 (s, 3H, CH3), 0.97 (s, 3H, CH3). 13
C
2H, AreH), 7.38 (t, J¼7.6 Hz, 1H, AreH), 7.26e7.08 (m, 7H, AreH),
6.82 (d, J¼6.0 Hz, 1H, AreH), 6.65 (s, 1H, AreH), 6.33 (d, J¼7.6 Hz,
1H, AreH), 4.50 (s, 1H, CH), 3.65 (s, 3H, CH3), 2.86 (d, J¼16.8 Hz, 1H,
CH2), 2.26 (s, 3H, CH3), 2.15e2.10 (m,1H, CH2), 1.22 (s, 3H, CH3), 0.86
NMR (100 MHz, CDCl3) (d, ppm): 197.9, 163.0, 149.5, 148.9, 139.7,
137.7, 136.0, 135.5, 134.9, 131.5, 130.1, 129.6, 129.2, 129.0, 128.0, 123.9,
121.5, 119.6, 106.4, 105.6, 51.8, 48.8, 38.5, 38.1, 28.9, 27.3. HRMS (ESI)
m/z: calcd for C33H27BrClN3O4: 644.0712 [MꢁH]ꢁ; found: 644.0727.
(s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
d, ppm): 162.9, 149.5, 139.8,
138.6, 137.7, 137.6, 134.6, 131.5, 128.9, 128.2, 128.1, 127.8, 127.0, 123.8,
119.3, 105.1, 51.5, 49.1, 38.8, 38.2, 28.8, 27.3, 21.2. HRMS (ESI) m/z:
calcd for C34H31N3O4: 544.2236 [MꢁH]ꢁ; found: 544.2239.
4.18. Methyl 4-(1-(4-chlorophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-2-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5p)
4.22. Methyl 4-(2-(4-chlorophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-1-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5t)
White solid, mp: 255e257 ꢀC.
IR (KBr,
1285, 1218, 1198, 1172, 1090, 1043, 1019, 824, 800, 727, 684. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2957, 1716, 1708, 1631, 1594, 1495, 1446, 1402,
d
: 8.36 (s, 1H, OH), 7.68 (d, J¼7.6 Hz, 2H, AreH),
White solid, mp: 256e258 ꢀC.
7.43 (t, J¼7.3 Hz, 2H, AreH), 7.40e7.29 (m, 2H, AreH), 7.21e7.05 (m,
2H, AreH), 6.98e6.85 (m, 4H, AreH), 6.69e6.35 (m, 2H, AreH), 4.66
(s, 1H, CH), 3.81 (s, 3H, CH3), 2.85 (d, J¼17.1 Hz, 1H, CH2), 2.30e2.18
(m, 4H, CH3, CH2), 1.29 (s, 3H, CH3), 0.99 (s, 3H, CH3). 13C NMR
IR(KBr,
n
, cmꢁ1): 2957, 1719,1711, 1622,1597, 1543,1515,1458,1397,
1216,1172,1120,1043, 831, 808, 752, 695.1H NMR (400 MHz, CDCl3)
d:
7.69 (d, J¼7.6 Hz, 2H, AreH), 7.43 (t, J¼7.6 Hz, 2H, AreH), 7.34 (t,
J¼7.2 Hz, 1H, AreH), 7.17 (s, 1H, AreH), 7.07 (d, J¼8.4 Hz, 3H, AreH),
6.91(d, J¼8.4Hz,3H, AreH), 6.50(s, 2H, AreH),4.64(s,1H, CH),3.76(s,
3H, CH3), 2.88 (d, J¼17.6 Hz, 1H, CH2), 2.33 (s, 3H, CH3), 2.20e2.13 (m,
1H, CH2),1.26 (s, 3H, CH3), 0.97 (s, 3H, CH3).13C NMR (100 MHz, CDCl3)
(100 MHz, CDCl3) (d): 197.5, 163.0, 149.6, 148.1, 139.7, 137.7, 137.4,
137.0, 135.9, 134.5, 129.0, 128.9, 128.3, 128.3, 127.8, 123.8, 119.5,
106.2, 104.9, 51.8, 48.8, 38.6, 38.1, 28.9, 27.3, 21.2. HRMS (ESI) m/z:
calcd for C34H30ClN3O4: 578.1847 [MꢁH]ꢁ; found: 578.1847.
(d, ppm): 197.5, 162.9, 149.5, 148.9, 139.8, 138.8, 137.8, 136.1, 134.4,
132.9, 130.1, 129.8, 129.5, 129.3, 128.9, 128.3, 128.0, 127.8, 127.5, 123.9,
119.4,106.4,105.3, 51.5, 48.9, 38.5, 38.2, 28.9, 27.3, 21.2. HRMS (ESI) m/
z: calcd for C34H30ClN3O4: 578.1847 [MꢁH]ꢁ; found: 578.1846.
4.19. Ethyl 4-(1,2-bis(4-chlorophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-1H-indol-7-yl)-5-hydroxy-1-phenyl-1H-pyr-
azole-3-carboxylate (5q)
4.23. Methyl 4-(2-(4-bromophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-1-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5u)
White solid, mp: 242 ꢀC.
IR (KBr,
1458, 1396, 1217, 1176, 1092, 1043, 959, 908. 1H NMR (400 MHz,
CDCl3)
n
, cmꢁ1): 2958, 1716, 1704, 1647, 1622, 1576, 1542, 1495,
d
: 7.68 (d, J¼7.6 Hz, 2H, AreH), 7.44 (t, J¼7.6 Hz, 2H, AreH),
White solid, mp: 248e249 ꢀC.
7.41e7.32 (m, 2H, AreH), 7.22e7.08 (m, 4H, AreH), 6.91 (d, J¼7.6 Hz,
2H, AreH), 6.57 (s, 2H, AreH), 4.68 (s, 1H, CH), 4.38e4.20 (m, 2H,
IR (KBr,
n
, cmꢁ1): 2956, 1719, 1711, 1596, 1543, 1459, 1418, 1378,
1283, 1216, 1172, 1092, 1043, 1008, 959, 799, 754. 1H NMR (400 MHz,

6106
X.-C. Tu et al. / Tetrahedron 69 (2013) 6100e6107
CDCl3)
d
: 7.68 (d, J¼8.0 Hz, 2H, AreH), 7.49e7.40 (m, 2H, AreH), 7.35
4.27. Methyl 4-(2-(4-chlorophenyl)-1-(4-methoxyphenyl)-6,6-
dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-7-yl)-5-hydroxy-
1-phenyl-1H-pyrazole-3-carboxylate (5y)
(t, J¼7.2 Hz, 1H, AreH), 7.25e7.07 (m, 4H, AreH), 6.92 (d, J¼7.2 Hz,
1H, AreH), 6.87 (d, J¼8.4 Hz, 2H, AreH), 6.55 (s, 1H, AreH), 6.45 (d,
J¼7.2 Hz, 1H, AreH), 4.65 (s, 1H, CH), 3.77 (s, 3H, CH3), 2.86 (d,
J¼16.8 Hz,1H, CH2), 2.33 (s, 3H, CH3), 2.19 (d, J¼17.6 Hz,1H, CH2),1.27
White solid, mp: 272e274 ꢀC.
(s, 3H, CH3), 0.98 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
d, ppm):
IR (KBr,
n
, cmꢁ1): 2966, 1704, 1617, 1514, 1493, 1458, 1416, 1313,
197.5, 162.9, 149.5, 148.8, 139.8, 138.8, 137.8, 136.1, 134.4, 131.3, 130.5,
129.8, 129.6, 128.9, 128.0, 127.8, 127.5, 123.9, 121.1, 119.4, 106.2, 105.4,
51.5, 48.9, 38.6, 38.2, 28.8, 27.3, 21.2. HRMS (ESI) m/z: calcd for
C34H30BrN3O4: 624.1322 [MꢁH]ꢁ; found: 622.1324.
1263, 1155, 1040, 1014, 759, 696. 1H NMR (400 MHz, CDCl3)
d: 7.72
(d, J¼8.0 Hz, 2H, AreH), 7.44 (t, J¼7.6 Hz, 2H, AreH), 7.35 (t,
J¼7.2 Hz, 1H, AreH), 7.14e7.01 (m, 3H, AreH), 6.88 (d, J¼8.0 Hz, 3H,
AreH), 6.64 (d, J¼8.4 Hz, 1H, AreH), 6.56 (d, J¼8.4 Hz, 1H, AreH),
6.40 (s, 1H, AreH), 4.63 (s, 1H, CH), 3.79 (s, 3H, CH2), 3.76 (s, 3H,
CH2), 2.92 (d, J¼17.6 Hz, 1H, CH2), 2.13 (d, J¼17.2 Hz, 1H, CH2), 1.25
(s, 3H, CH3), 0.96 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
d, ppm):
4.24. Methyl 4-(4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-1,2-
dip-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-1H-pyrazole-3-
carboxylate (5v)
197.4, 162.9, 159.6, 149.5, 148.9, 137.8, 136.2, 132.9, 130.1, 129.6,
129.3, 128.9, 128.8, 128.3, 127.8, 123.7, 119.3, 114.6, 113.8, 106.2,
105.2, 55.4, 51.5, 48.9, 38.6, 38.2, 28.8, 27.3. HRMS (ESI) m/z: calcd
for C34H30ClN3O4: 594.1796 [MꢁH]ꢁ; found: 594.1796.
White solid, mp: 228e229 ꢀC.
IR (KBr,
1377, 1284, 1216, 1171, 1043, 823, 800, 754. 1H NMR (400 MHz,
CDCl3)
n
, cmꢁ1): 2956, 1715, 1623, 1597, 1558, 1515, 1458, 1471,
4.28. Methyl 4-(2-(4-bromophenyl)-4,5,6,7-tetrahydro-1-(4-
methoxyphenyl)-6,6-dimethyl-4-oxo-1H-indol-7-yl)-5-
hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (5z)
d
: 7.68 (d, J¼7.7 Hz, 2H, AreH), 7.49e7.38 (m, 2H, AreH), 7.33
(t, J¼7.2 Hz, 1H, AreH), 7.14 (d, J¼11.2 Hz, 2H, AreH), 6.96e6.86 (m,
5H, AreH), 6.56 (s, 1H, AreH), 6.46 (s, 1H, AreH), 4.64 (s, 1H, CH),
3.76 (s, 3H, CH3), 2.87 (d, J¼17.2 Hz, 1H, CH2), 2.32 (s, 3H, CH3),
White solid, mp: 268e270 ꢀC.
2.27e2.14 (m, 4H, CH3, CH2), 1.28 (s, 3H, CH3), 0.98 (s, 3H, CH3). 13
C
IR (KBr,
1283, 1216, 1172, 1092, 1043, 1008, 959, 799, 754. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2956, 1719, 1711, 1596, 1543, 1459, 1418, 1378,
NMR (100 MHz, CDCl3) (d, ppm): 197.2, 162.9, 149.6, 148.1, 139.8,
138.4, 137.8, 137.5, 136.6, 134.8, 129.6, 129.4, 128.0, 128.8, 128.1,
127.7, 127.5, 123.9, 119.3, 106.1, 104.7, 77.4, 77.1, 76.8, 51.5, 49.0, 38.6,
38.2, 28.9, 27.3, 21.2. HRMS (ESI) m/z: calcd for C35H33N3O4:
558.2393 [MꢁH]ꢁ; found: 558.2395.
d
: 7.69 (d, J¼8.0 Hz, 2H, AreH), 7.43 (t, J¼7.2 Hz,
2H, AreH), 7.33 (t, J¼7.2 Hz, 1H, AreH), 7.20e7.01 (m, 6H, AreH),
6.88 (s, 1H, AreH), 6.69e6.44 (m, 3H, AreH), 4.66 (s, 1H, CH), 3.77
(s, 6H, CH3), 2.88 (d, J¼17.2 Hz, 1H, CH2), 2.22 (d, J¼17.6 Hz, 1H,
CH2), 1.29 (s, 3H, CH3), 1.00 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3)
(d, ppm): 197.4, 162.9, 159.6, 149.5, 149.0, 139.9, 137.8, 136.2, 131.3,
4.25. Ethyl 4-(2-(4-chlorophenyl)-4,5,6,7-tetrahydro-6,6-
dimethyl-4-oxo-1-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5w)
130.5, 129.5, 129.3, 129.0, 128.8, 127.8, 123.9, 121.1, 119.3, 114.6,
113.9, 106.2, 105.3, 55.5, 51.6, 48.9, 38.6, 38.2, 28.8, 27.3. HRMS
(ESI) m/z: calcd for C34H30BrN3O4: 638.1270 [MꢁH]ꢁ; found:
638.1290.
White solid, mp: 219 ꢀC.
IR (KBr,
1313, 1263, 1166, 1155, 1039, 1014, 866, 758, 696. 1H NMR
(400 MHz, CDCl3)
n
, cmꢁ1): 2964, 1707, 1619, 1595, 1514, 1493, 1458, 1416,
4.29. Methyl 4-(4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-6,6-
dimethyl-4-oxo-2-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5aa)
d: 7.68 (d, J¼8.0 Hz, 2H, AreH), 7.43 (t, J¼7.6 Hz,
2H, AreH), 7.34 (t, J¼7.2 Hz, 1H, AreH), 7.21e7.05 (m, 4H, AreH),
7.01e6.87 (m, 3H, AreH), 6.63 (s, 1H, AreH), 6.47 (s, 1H, AreH),
4.66 (s, 1H, CH), 4.33e4.15 (m, 2H, CH2), 2.84 (d, J¼17.2 Hz, 1H,
CH2), 2.32 (s, 3H, CH3), 2.28e2.21 (m, 1H, CH2), 1.32 (t, J¼7.2 Hz,
3H, CH3), 1.27 (s, 3H, CH3), 0.99 (s, 3H, CH3). 13C NMR (100 MHz,
White solid, mp: 245e247 ꢀC.
IR (KBr,
n
, cmꢁ1): 2957, 1712, 1622, 1598, 1596, 1513, 1463, 1383,
1248,1217,1170,1042, 907, 808, 759, 654. 1H NMR (400 MHz, CDCl3)
d
: 7.69 (d, J¼8.4 Hz, 2H, AreH), 7.43 (t, J¼7.6 Hz, 2H, AreH), 7.33 (t,
CDCl3) (d, ppm): 197.2, 162.5, 149.4, 148.6, 140.1, 138.8, 137.8, 136.2,
J¼7.2 Hz, 1, AreH H), 7.14 (s, 1H, AreH), 6.99e6.84 (m, 5H, AreH),
6.64e6.52 (m, 2H, AreH), 6.48 (s, 1H, AreH), 4.64 (s, 1H, CH), 3.77
(s, 6H, CH3), 2.85 (d, J¼17.6 Hz, 1H, CH2), 2.28e2.19 (m, 4H, CH3,
CH2), 1.28 (s, 3H, CH3), 0.99 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3)
134.4, 132.9, 130.0, 129.9, 129.6, 129.3, 128.9, 128.4, 127.9, 127.8,
127.5, 123.9, 119.4, 105.4, 60.6, 48.9, 38.8, 38.3, 28.7, 27.3, 21.2, 14.3.
HRMS (ESI) m/z: calcd for C35H32ClN3O4: 592.2003 [MꢁH]ꢁ;
found: 592.2021.
(d, ppm): 197.0, 163.0, 159.4, 149.6, 148.2, 139.9, 137.8, 137.7, 136.7,
130.0,129.4,128.9,128.8,128.7,128.2,127.7,123.8,119.2,114.4,113.7,
105.9, 104.6, 55.4, 51.5, 49.0, 38.7, 38.2, 28.9, 27.3, 21.2. HRMS (ESI)
m/z: calcd for C35H33N3O5: 574.2342 [MꢁH]ꢁ; found: 574.2343.
4.26. Methyl 4-(4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-6,6-
dimethyl-4-oxo-2-phenyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5x)
4.30. Ethyl 4-(4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-6,6-
dimethyl-4-oxo-2-phenyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5ab)
White solid, mp: 255e257 ꢀC.
IR (KBr,
n
, cmꢁ1): 2958, 1716, 1620, 1598, 1512, 1471, 1442, 1381,
1246, 1216, 1171, 1035, 841, 809, 759, 652. 1H NMR (400 MHz, CDCl3)
d
: 7.69 (d, J¼7.8 Hz, 2H, AreH), 7.43 (t, J¼7.2 Hz, 2H, AreH), 7.33 (t,
White solid, mp: 213e215 ꢀC.
J¼7.2 Hz, 1H, AreH), 7.19e6.99 (m, 6H, AreH), 6.88 (s, 1H, AreH),
6.67e6.58 (m, 1H, AreH), 6.50 (s, 1H, AreH), 4.66 (s, 1H, CH), 3.77 (s,
6H, CH3), 2.88 (d, J¼17.2 Hz, 1H, CH2), 2.22 (d, J¼17.6 Hz, 1H, CH2),
IR (KBr,
1384, 1247, 1215, 1171, 1041, 841, 776, 652. 1H NMR (400 MHz,
CDCl3)
n
, cmꢁ1): 2959, 1714, 1703, 1621, 1599, 1512, 1470, 1440,
d
: 7.68 (d, J¼8.0 Hz, 2H, AreH), 7.42 (t, J¼7.6 Hz, 2H, AreH),
1.29 (s, 3H, CH3), 1.00 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) (
d,
7.33 (t, J¼6.8 Hz, 1H, AreH), 7.19e7.00 (m, 6H, AreH), 6.87 (s, 1H,
AreH), 6.72 (s, 1H, AreH), 6.60 (s, 1H, AreH), 6.47 (s, 1H, AreH),
4.66 (s, 1H, CH), 4.24 (q, J¼7.6 Hz,1H, CH2), 3.76 (s, 3H, CH3), 2.80 (d,
J¼17.2 Hz,1H, CH2), 2.25 (d, J¼17.6 Hz,1H, CH2),1.31 (t, J¼7.2 Hz, 3H,
CH3), 1.28 (s, 3H, CH3), 1.01 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3)
ppm): 197.2, 163.0, 159.4, 149.6, 148.5, 139.9, 137.8, 137.5, 131.6, 129.9,
129.4, 128.9, 128.2, 128.1, 127.8, 126.9, 123.8, 119.3, 114.4, 113.8, 106.0,
105.0, 55.4, 51.5, 49.0, 38.6, 38.22, 28.9, 27.3. HRMS (ESI) m/z: calcd
for C34H31N3O5: 560.2185 [MꢁH]ꢁ; found: 560.2184.

X.-C. Tu et al. / Tetrahedron 69 (2013) 6100e6107
6107
(d
, ppm): 196.5, 162.5, 159.4, 149.4, 147.9, 140.2, 137.8, 137.7, 131.5,
References and notes
129.8, 128.9, 128.2, 128.1, 127.7, 127.0, 123.7, 119.3, 114.5, 113.8, 105.0,
104.9, 60.7, 55.4, 49.1, 39.0, 38.3, 28.7, 27.3, 14.3. HRMS (ESI) m/z:
calcd for C35H33N3O5: 574.2342 [MꢁH]ꢁ; found: 574.2342.
1. (a) Sundararaju, B.; Achard, M.; Bruneau, C. Chem. Soc. Rev. 2012, 41,
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dimethyl-4-oxo-2-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-
1H-pyrazole-3-carboxylate (5ac)
White solid, mp: 193e195 ꢀC.
IR (KBr,
n
, cmꢁ1): 2966, 1703, 1615, 1593, 1513, 1497, 1445, 1385,
1253,1214,1118,1035, 830, 807, 770, 650. 1H NMR (400 MHz, CDCl3)
€
€
2438e2440; (e) Gartner, M.; Jakel, M.; Achatz, M.; Sonnenschein, C.; Tverskoy,
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O.; Helmchen, G. Org. Lett. 2011, 13, 2810e2813.
7.38e7.28 (m, 2H, AreH), 7.04e6.90 (m, 4H, AreH), 6.91e6.68 (m,
2H, AreH), 6.59 (s, 1H, AreH), 6.43 (s, 1H, AreH), 4.65 (s, 1H, CH),
4.35e4.16 (m, 2H, CH2), 3.76 (s, 3H, CH3), 2.79 (d, J¼17.2 Hz, 1H,
CH2), 2.32e2.22 (m, 4H, CH2, CH3), 1.39e1.20 (m, 6H, CH3), 1.01 (s,
3. (a) Pyrroles, The Synthesis, Reactivity, and Physical Properties of Substituted Pyr-
roles, Part II; Jones, R. A., Ed.; Wiley: New York, NY, 1992; (b) Jacobi, P. A.; Coults,
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3H, CH3). 13C NMR (100 MHz, CDCl3) (
d, ppm): 196.6, 162.5, 159.4,
149.5, 147.9, 140.2, 137.8, 137.8, 136.7, 129.9, 128.9, 128.8, 128.6,
128.1, 127.6, 123.7, 119.2, 114.4, 105.1, 104.6, 60.6, 55.4, 49.0, 38.9,
38.3, 28.7, 27.3, 21.1, 14.2. HRMS (ESI) m/z: calcd for C36H35N3O5:
588.2498 [MꢁH]ꢁ; found: 588.2502.
4.32. The supporting experimental for proposed mechanism
6. Nagafuji, P.; Cushman, M. J. Org. Chem. 1996, 61, 4999e5003.
7. (a) Hershenson, F. M. J. Org. Chem. 1972, 37, 3111e3113; (b) Hershenson, F. M. J.
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8. (a) Tietze, L. F. Chem. Rev. 1996, 96, 115e136; (b) Tietze, L. F.; Brasche, G.; Gerike,
K. Domino Reactions in Organic Chemistry; Wiley-VCH: Weinheim, Germany,
1-(4-Bromophenyl)-4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-2-
phenyl-1H-indol-7-yl acetate C1 (1 mmol, 1.0 equiv) was in-
troduced in a 10 mL vial, and methyl 5-hydroxy-1-phenyl-1H-
pyrazole-3-carboxylate E (1.0 mmol, 1.0 equiv) and HOAc (2.0 mL)
were added. The reaction vial was closed and pre-stirred for 20 s.
The mixture was irradiated at 150 ꢀC until the conversion of the
starting material C1 was complete, as shown by TLC. The reaction
mixture was cooled to room temperature and diluted with cold
€
ꢁ
2006; (c) Domling, A. Chem. Rev. 2006, 106, 17e89; (d) Zhu, J.; Bienayme, H.
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€
Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168e3210; (f) Ruijter, E.;
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Chem. 2010, 12, 1357e1361.
€
water (50 mL). The solid product was collected by Buchner filtration
and was purified by flash column chromatography (silica gel,
mixtures of n-hexane/diethyl ether¼7/1, v/v) to afford the desired
pure products 5a in 82% yield.
Acknowledgements
We are grateful for financial support from the National Science
Foundation of China (21072163, 21232004, 21272095, and
21102124), PAPD of Jiangsu Higher Education Institutions, the NSF
of Jiangsu Education Committee (11KJB150016), Jiangsu Science
and Technology Support Program (No. BE2011045), the Qing Lan
Project (12QLG006), and the National Science Foundation of Xuz-
hou Normal Univ. (XZNU, No. 12XLA05).
10. (a) Stanovnik, B.; Svete, J. Chem. Rev. 2004, 104, 2433e2480; (b) White, J. D.;
Ihle, D. C. Org. Lett. 2006, 8, 1081e1084; (c) Tu, S.-J.; Jiang, B.; Jia, R.-H.; Zhang, J.-
Y.; Zhang, Y.; Yao, C. S.; Shi, F. Org. Biomol. Chem. 2006, 4, 3664e3668; (d)
Huang, J.; Liang, Y.; Pan, W.; Dong, D. Org. Lett. 2007, 9, 5345e5348; (e) Yavari,
I.; Hossaini, Z.; Sabbaghan, M. Tetrahedron Lett. 2008, 49, 844e846; (f) Wang,
G.-W.; Miao, C.-B. Green Chem. 2006, 8, 1080e1085; (g) Wu, X. J.; Jiang, R.; Wu,
B.; Su, X. M.; Xu, X. P.; Ji, S. J. Adv. Synth. Catal. 2009, 351, 3150e3156; (h) Jiang,
B.; Li, Q.-Y.; Zhang, H.; Tu, S.-J.; Pindi, S.; Li, G. Org. Lett. 2012, 14, 700e703.
11. The single crystal growth was carried out in co-solvent of EtOH and DMF at
room temperature. Crystal data for 5a (CCDC-922114): C33H28BrN3O4, crystal
ꢂ
dimension 0.42 ꢂ 0.20 ꢂ 0.13 mm, Triclinic, space group P-1, a¼9.1630(10) A,
ꢂ
ꢂ
b¼18.8682(16) A, c¼7.3157(6) A,
a
¼25.570(2)ꢀ,
b
¼97.6530(10)ꢀ,
g
¼94.
Supplementary data
3
ꢂ
3680(10)ꢀ, V¼2925.7(5) A , Mr¼610.49, Z¼4,
l
¼0.71073 A,
m
(Mo
K
a
)¼1.
ꢂ
447 mmꢁ1, F(000)¼1256, R1¼0.0441, wR2¼0.0547.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.05.063.
12. Tu, X.-C.; Feng, H.; Tu, M.-S.; Jiang, B.; Wang, S.-L.; Tu, S.-J. Tetrahedron Lett.
2012, 53, 3169e3172.