Synthesis of complex dispirocyclopentanebisoxindoles via cycloaddition reactions of 4-dimethylamino-1-alkoxycarbonylmethylpyridinium bromides with 2-oxoindolin-3-ylidene derivatives

Article abstract of DOI:10.1016/j.tet.2014.02.050

The cycloaddition reactions of 4-dimethylamino-1- alkoxycarbonylmethylpyridinium bromides with various 2-oxoindolin-3-ylidene derivatives in ethanol in the presence of triethylamine afforded the unprecedented dispirocyclopentanebisoxindole derivatives in

Full text of DOI:10.1016/j.tet.2014.02.050

Tetrahedron 70 (2014) 2537e2545
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of complex dispirocyclopentanebisoxindoles
via cycloaddition reactions of 4-dimethylamino-1-
alkoxycarbonylmethylpyridinium bromides with 2-oxoindolin-
3-ylidene derivatives
*
Li-Juan Lu, Qin Fu, Jing Sun, Chao-Guo Yan
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The cycloaddition reactions of 4-dimethylamino-1-alkoxycarbonylmethylpyridinium bromides with
various 2-oxoindolin-3-ylidene derivatives in ethanol in the presence of triethylamine afforded the
unprecedented dispirocyclopentanebisoxindole derivatives in good yields and in high diaster-
eoselectivity. Under similar reaction conditions, the reactions of 1-alkoxycarbonylmethylpyridinium
bromides with 3-phenacylideneoxindoles only resulted in 4-oxo-3-(2-oxoindolin-3-ylidene)-4-
arylbutanoates. The stereochemistry of the complex spirooxindoles was established by 1H NMR data
and single crystal structures.
Received 18 November 2013
Received in revised form 28 January 2014
Accepted 20 February 2014
Available online 2 March 2014
Keywords:
1,3-Dipolar cycloaddition
Dimethylaminopyridine
Pyridinium N-ylide
Spirooxindole
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
N-phenacylquinolinium ylides with 2-oxoindolin-3-ylidene
derivatives.15 The formation of spiro[cyclopropane-1,30-indolines]
The spirooxindole unit is a privileged heterocyclic motif that
forms the core structure of a large family of natural alkaloids and
many pharmacological agents with important bioactivity and
interesting structural properties.1,2 The unique structures and the
highly pronounced pharmacological activity displayed by the
spirooxindoles have made them attractive synthetic targets.3,4 In
versatile synthetic methods of spirooxindole system, the 1,3-
dipolar cycloaddition of azomethine ylides with isatin and its
functionalized derivatives might be the most convenient
procedure.5e9 However, there have been few reports about the
synthesis of spirooxindole system by 1,3-cycloaddition of hetero-
aromatic N-ylides with functionalized oxindole derivatives. As one
kind of reactive azomethine ylides, heteroaromatic N-ylides such as
pyridinium, quinolinium, and isoquinolinium methylides are
readily available from the alkylations of aza-aromatic heterocycles
and sequential deprotonation reactions. The heteroaromatic
N-ylides have been used extensively in cycloadditions for
the synthesis of the various nitrogen-containing heterocycles.10e13
by the reactions of N-phenacylpyridinium salts with phenacylide-
neoxindoles was also briefly reported.16 Recently, we found
that the reactions of N-benzylbenzimidazolium salts, isatylidene
malononitrile gave a series of the novel zwitterionic salts.17
We also reported that the 1,3-cycloaddition reactions of 3-
phenacylideneoxindoles with aza-aromatic N-ylides generated
from isoquinolinium, N-phenacylquinolinium, and 1,10-phenan
throlinium salts afforded a series of polycyclic system such as
spiro[indoline-3,30-pyrrolo[1,2-a]quinolines], spiro[indoline-3,10-
pyrrolo[2,1-a]isoquinolines]
and spiro[benzo[h]pyrrolo[1,2-a]
quinoline-3,30-indolines].18 On the other hand, the similar cyclo-
addition reactions of pyridinium salts and 4-dimethylamino
pyridinium salts with 3-phenacylideneoxindoles produced the
functionalized spiro[cyclopropane-1,30-indolines], and 3-(furan-
3(2H)-ylidene)indolin-2-ones depending upon the structures of
the pyridinium salts and reaction conditions.19 Thus, the very in-
teresting molecular diversity of the cycloaddition of heteroaromatic
N-ylides with 3-phenacylideneoxindoles so far promoted us
to examine the reactivity of other pyridinium salts in this
reaction. Here we wish to report the cycloaddition reactions of
€
L. Toke and co-workers reported the 1,3-cycloadditions of dihy-
droisoquinolinium salts with 2-oxoindolin-3-ylidene derivatives.14
A.B. Serov and co-workers successfully developed the reactions of
4-dimethylamino-1-alkoxycarbonylmethylpyridinium
bromides
with 3-phenacylideneoxindoles for the efficient synthesis of the
* Corresponding author. E-mail address: cgyan@yzu.edu.cn (C.-G. Yan).
complex dispirocyclopentanebisoxindole derivatives.
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.050

2538
L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
2. Results and discussion
compound 3a and the Z/E isomers with ratio of 25:1 existed in
compound 3d. From the crystal structure of compound 3a, it can be
seen that the benzoyl group and phenyl group of oxindole moiety
existed in trans-configuration, which also suggested that the Z-iso-
mer of compounds 3aej was the major isomer. 1H NMR spectra of
compounds 3gej clearly indicated only one diastereoisomer exists
in these samples, which might be due to the large steric hindrance of
tert-butyl group in molecule. It should be pointed out that there is
one exocyclic C]C double bond in the 3-(2-oxoindolin-3-ylidene)
butanoates 3aej, which is very similar to the structure of starting
3-phencaylideneoxindole. No further cycloadditions of 3-(2-
oxoindolin-3-ylidene)butanoates 3aej were observed by using
more than 2 M pyridinium bromides 1a or 1b in the experiments.
In order to develop the scope of this reaction, the reaction
of 3-phenacylideneoxindoles with 4-dimethylamino-1-ethoxy
carbonylmethylpyridinium bromide (1c) was examined under
same reaction condition. To our surprise, the reaction resulted in
a complex dispirocyclopentanebisoxindole derivative (4a) in 53%
yield. The structure of the compound 4a is very interesting, in which
the two oxindole units exist in 1,2-positions of the newly formed
cyclopentyl ring. A literature survey indicated there are only very few
known examples of dispirocyclopentanebisoxindoles with two
oxindole units in 1,2-positions of cylcopentyl ring,20 while the sim-
ilar dispirocyclopentanebisoxindoles with two oxindole units in 1,3-
positions of cylcopentyl ring are more popular.21 Due to two mole-
cules of 3-phenacylideneoxindole took part in the reaction, the yield
of the compound 4a increased to 80% by using two equal 3-
phenacylideneoxindoles in the reaction. Then, the similar reactions
of other 3-phenacylideneoxindoles with 4-dimethylamino-1-alkoxy
carbonylmethylpyridinium bromide (1c: R¼Et; 1d: R¼t-Bu) also
gave a series of functionalized dispirocyclopentanebisoxindoles
(4aek) in very good yields. The substituent on the 3-phena
cylideneoxindoles did not show very important role in the re-
action. On the other hand, the bulky tert-butyl group also did not
affect the yields of products (Table 2, entries 5e11).
According to the previously established reaction conditions for
the cycloaddition of N-phenacylpyridinium bromide with
3-phenacyclideneoxindoles,19
a mixture of slightly excess of
N-ethoxycarbonylmethylpyridinium bromide (1a) and 3-
phenacylideneoxindoles 2 in ethanol with triethylamine as base
catalyst was stirred at 50e60 ꢀC for several hours. After workup,
instead ofisolating theexpectedspiro[cyclopropane-1,30-indolines],
the reaction afforded a series of 3-(2-oxoindolin-3-ylidene)buta-
noates (3aef) in satisfactory yields (Table 1, entries 1e6). It looks
likely that this kind of products come from the substitution reaction
of ethoxycarbonylmethyl group at the exocyclic carbon atom of 3-
phenacylideneoxindoles. To determine the scope and limits of this
reaction, the reactions of N-tert-butoxycarbonylmethylpyridinium
bromide (1b) with 3-phenacylideneoxindoles under same condi-
Table 1
Synthesis of 3-(2-oxoindolin-3-ylidene)butanoates 3aeja
Entry
Compd
R
R0
Ar
Yieldb (%, Z/E ratio)
1
2
3
4
5
6
7
8
9
10
3a
3b
3c
3d
3e
3f
3g
3h
3i
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C(CH3)3
C(CH3)3
C(CH3)3
C(CH3)3
H
p-ClC6H4
C6H5
p-CH3C6H4
p-ClC6H4
C6H5
p-ClC6H4
C6H5
p-CH3C6H4
p-ClC6H4
C6H5
88 (4:1)
71 (6:1)
89
80 (25:1)
65 (10:3)
74 (5:1)
70
82
76
80
CH3
CH3
CH3
F
F
H
CH3
Cl
F
The structures of the prepared dispirocyclopentane
bisoxindoles (4aek) were characterized with spectroscopic
methods. Because there are two oxindole moieties, two benzoyl
groups, and one esteric group in the newly formed cyclopentyl
ring in dispirocyclopentanebisoxindoles 4aek, a couple of di-
astereoisomers could exist for each product. In 1H NMR spectra of
spiro compounds 4aed, the one CH unit connecting ethox-
ycarbonyl group and the two CH units connecting phenacyl
groups in the newly formed cyclopentyl ring usually displays
different absorption patterns. Thus, it is difficult to determine the
diastereochemistry of these complex dispiro compounds barely
with 1H NMR spectra. On the other hand, in the 1H NMR spectra
of spiro compounds 4eek, the CH unit connecting tert-butox-
ycarbonyl group always displays one triplet at about 5.20 ppm
and the two CH units connecting benzoyl groups displays one
doublet at about 5.10 ppm. The other characteristic groups also
show only one set of absorption peaks. This fact strongly in-
dicated that a high symmetric stereoisomer exists in each sample
of the compounds 4eek. The single crystal structures of com-
pounds 4b, 4e and 4h were determined by X-ray diffraction
(Figs. 2e4). In the molecule structure of 4b (Fig. 2) it can be seen
that the two oxindole moieties exist in opposite orientation and
the two benzoyl groups also exist in trans-configuration. Thus,
we can tentatively suggest that compounds 4aed all exist in this
unsymmetrical isomer based on the NMR data and single crystal
determination. On the other hand, the two oxindole moieties
exist in cis-orientation and the two benzoyl groups exist in cis-
configuration in the molecule structure of 4e and 4h (Figs. 3
and 4). The tert-butoxycarbonyl group is in the trans-position
to the two neighboring benzoyl groups. There is one C2v sym-
metric plane in the molecules of 4e and 4h, which is concordance
3j
a
Reaction conditions: pyridinium salts (1.1 mmol), 3-phenacylideneoxindole
(1.0 mmol), triethylamine (0.2 mmol), EtOH (15 mL), 50e60 ꢀC, 6 h.
b
Isolated yields.
tions were also examined. All reactions proceeded smoothly to give
the corresponding substituted products (3gej) in high yields (Table
1, entries 7e10). The structures of the prepared 3-(2-oxoindolin-3-
ylidene)butanoates (3aej) were characterized by 1H and 13C NMR,
MS, IR spectra and were further confirmed by single crystal X-ray
diffraction performed for the representative compound 3a (Fig. 1).
1H NMR spectra of compounds 3aef indicated that a mixture of
major isomer and minor isomer existed in the most samples. For
examples, the Z/E isomers with about 4:1 molecular ratio existed in
Fig. 1. Molecular structure of compound 3a.

L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
2539
Table 2
Synthesis of dispirocyclopentanebisoxindoles 4aeka via cycloaddition reaction
Entry
Comp
R
R0
R00
Ar
Yieldb (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
CH2CH3
CH2CH3
CH2CH3
CH2CH3
C(CH3)3
C(CH3)3
C(CH3)3
C(CH3)3
C(CH3)3
C(CH3)3
C(CH3)3
H
H
Cl
Cl
F
Cl
Cl
F
Bn
Bn
H
H
H
H
H
H
H
C6H5
85
80
82
58
49
80
65
71
74
78
79
p-CH3C6H4
p-CH3C6H4
p-ClC6H4
p-ClC6H4
p-CH3C6H4
C6H5
C6H5
9
10
11
H
F
H
p-ClC6H4
p-CH3C6H4
C6H5
4j
4k
H
Bn
a
Reaction conditions: pyridinium salts (1.1 mmol), 3-phenacylideneoxindole (2.0 mmol), triethylamine (0.2 mmol), EtOH (15.0 mL), 50e60 ꢀC, 12 h.
Isolated yields.
b
Fig. 2. Molecular structure of compound 4b.
Fig. 4. Molecular structure of compound 4h.
with the analytical result of 1H NMR data. Thus, we can get
a conclusion that compounds 4eek are in this kind of symmetric
isomer. It is known that the benzoyl group and the aryl group of
the oxindole moiety exist in the cis-position in the starting 3-
phenacylideneoxindoles.21 Thus, even this cis-configuration is
retained in all compounds 4aek, two different isomers were
obtained in the reactions due to the two moieties of 3-
phenacylideneoxindoles connecting with each other in opposite
direction.
In order to further develop the applicability of this reaction,
another typical 3-methyleneoxindoles, ethyl (2-oxo-1,2-dihydro-
indol-3-ylidene)acetates were also used to react with 4-
dimethylamino-1-alkoxycarbonylmethylpyridinium
bromides.
The results are summarized in Table 3. It can be seen that the ex-
pected dispirocyclcopentanebisoxindoles 5aej were successfully
obtained in good yields. Their structures have also been fully de-
termined by the spectroscopic methods. 1H NMR spectra of com-
pounds 5aej clearly indicated one set of absorptions for the
Fig. 3. Molecular structure of compound 4e.

2540
L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
Table 3
Synthesis of dispirocyclopentanebisoxindoles 5ae5ja
Entry
Product
R
R0
R00
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
5a
5b
5c
5d
5e
5f
5g
5h
5i
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
C(CH3)3
C(CH3)3
C(CH3)3
C(CH3)3
C(CH3)3
CH3
F
H
H
H
H
Bn
Bn
H
H
H
70
80
65
71
55
95
93
91
75
75
F
Cl
CH3
F
H
Cl
F
H
Bn
5j
a
Reaction conditions: pyridinium salts (1.1 mmol), 3-phenacylideneoxindole (2.0 mmol), triethylamine (0.2 mmol), EtOH (15.0 mL), 50e60 ꢀC, 12 h.
Isolated yields.
b
characterized groups, which suggested only one diastereoisomer
5aej all exist in the same symmetric isomer as the spiro com-
pounds 4eek based on the 1H NMR data and single crystal de-
termination (Fig. 6).
In order to explain the reaction mechanism, a plausible mech-
anism for the formation of the two kinds of products is proposed in
existing in each sample. For examples, in the 1H NMR spectrum of
5a the three CH units in cyclopentyl ring display one singlet at
4.58 ppm and one doublet at 3.94 ppm. The three ethyl groups also
show two quartets at 4.17, and 3.79 ppm for CH2 units and two
triplets at 1.19, and 0.68 ppm for methyl group, which clearly in-
dicates the molecule has high symmetry. 1H NMR spectra of 5g
displays one triplet at 4.42 ppm for the CH unit connecting tert-
butoxycarbonyl group, and one doublet at 3.93 ppm for the two CH
units connecting ethoxycarbonyl groups. The tert-butyl group
shows one singlet at 1.42 ppm and the two ethyl groups also display
one set of signs at 3.87e3.82 ppm for methylene units and
0.76 ppm for methyl groups, which cleanly indicated this com-
pound has very high symmetry. The single crystal determination of
compounds 5e and 5g clearly indicated that the two oxindole
moieties exist in same orientation and the two ethoxycarbonyl
groups also exist in cis-configuration, while the ethoxycarbonyl or
tert-butoxycarbonyl group oriented in the trans-position to the two
neighboring two ethoxycarbonyl groups (Fig. 5). Thus, compounds
Fig. 6. Molecular structure of compound 5g.
Scheme 1 based on the similar cycloaddition reactions of aza-
aromatic nitrogen ylides. Firstly, deprotonation of pyridinium salt
1 with triethylamine afforded the desired pyridinium ylide (A).
Secondly, Michael addition of pyridinium ylide (A) to the exocyclic
carbon atom of 3-phenacylideneoxindole 2 gives addition in-
termediate (B). Two reactions existed for the further reaction
depending on the properties of the pyridinium salts. In the path a,
the elimination of pyridine and rearrangement of carbonium ion
resulted a alkene intermediate (C), which is similar to our recently
reported reactions of N-phenacylidenepyridinium ylide.19 Then 1,3-
H shift in the alkene (C) gave the Z/E isomers of compound 3 as final
Fig. 5. Molecular structure of compound 5e.

L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
2541
yields and with high diastereoselectivity was successfully developed.
The stereochemistry of reaction and the reaction mechanism were
briefly discussed. It is interesting to find that the dimethylamino
group significantly affects the reactivity of pyridinium ylides, which
would be found high potential applications in organic and medical
synthesis. Further expansion of the reaction scope and synthetic
applications of this methodology are in progress in our laboratory.
4. Experimental section
4.1. General procedure for the preparation of 3-(2-oxoindolin-
3-ylidene)butanoates 3aej from the reactions of N-alkox-
ycarbonylmethylpyridinium salts with 3-phenacylideneoxin
doles
A
mixture of N-ethoxycarbonylmethylpyridinium bromide
or N-tert-butoxycarbonylmethylpyridinium chloride (1.1 mmol),
3-phenacylideneoxindoles (1.0 mmol), and triethylamine
(0.2 mmol) in ethanol (15.0 mL) was stirred at about 50e60 ꢀC for
6 h. The resulting precipitates were collected by filtration, which
were recrystallized in a mixture of chloroform and ethanol to give
pure product for analysis.
4.1.1. Ethyl 4-(4-chlorophenyl)-4-oxo-3-(2-oxoindolin-3-ylidene)bu-
tanoate (3a). Yellow solid, yield: 88%. Mp 146e148 ꢀC. IR (KBr):
3224, 2979, 1736, 1707, 1668, 1614, 1586, 1464, 1397, 1342, 1270,
1232, 1185, 1092, 1035, 966. 1H NMR (600 MHz, CDCl3)
d (ppm):
Z-isomer: 8.56 (s, 1H, NH), 7.98 (d, J¼7.8 Hz, 2H, ArH), 7.57
(d, J¼7.8 Hz, 1H, ArH), 7.40 (d, J¼8.4 Hz, 2H, ArH), 7.29 (t, J¼7.8 Hz,
1H, ArH), 7.07 (t, J¼7.8 Hz, 1H, ArH), 6.72e6.67 (m, 1H, ArH),
4.15e4.07 (m, 2H, CH2), 3.89 (s, 2H, CH2), 1.14 (t, J¼7.2 Hz,
3H, CH3). E-isomer: 8.08 (d, J¼8.4 Hz, 2H, ArH), 7.45 (d, J¼8.4 Hz,
2H, ArH), 7.12 (t, J¼7.2 Hz, 1H, ArH), 4.27 (s, 2H, CH2), 1.19
(t, J¼7.2 Hz, 3H, CH3); ratio Z/E¼4:1. 13C NMR (150 MHz, CDCl3)
Scheme 1. The proposed formation mechanism of compounds 3 and 4.
product. The ratio of Z/E isomers was clearly affected by the effect
of the nuleophiles. Thus, the reaction of N-ethoxycarbonylmethyl
pyridinium bromide (1a) usually afforded a mixture of major iso-
mer and minor isomer, whiles the bulky N-tert-buyox-
ycarbonylmethylpyridinium bromide (1b) predominately resulted
in one isomer. When 4-dimethylamino-1-alkoxycarbonylmethyl
pyridinium bromides (1c,d) were used in the reaction, the corre-
sponding 4-dimethylaminopyridnium ylide is much more stable
due the stronger electron-donating effect of dimethylamino
group.22 The further reaction was outlined in path b. The carbanion
of the intermediate (B) added to the second molecular 3-
phenacylideneoxindole to gave a double addition adduct (D). The
intramolecular nucleophilic substitution in intermediate (D) pro-
duced the dispirocyclopentanebisoxindoles 4. The formation pro-
cess for the dispirocyclopentanebisoxindoles 4 is very similar to the
base promoted dimerization reactions between two molecules of 3-
phenacylideneoxindoles to give the dispirocyclopentane-1,3-
bisoxindoles,21b in which the two oxindole moieties exist in 1,3-
position of the newly formed cyclopentyl ring. Because the
formation of dispirocyclcopentanebisoxindoles 4 contains several
equilibrium reaction processes, the most thermodynamically stable
diastereoisomer would be preferentially formed in this sequential
reaction. The different reactivity of the pyridinium ylides plays key
role on the reaction path and the steric effect of the substituents
greatly affects the stereochemistry of the reaction.
d
(ppm): 196.9, 168.1, 167.7, 142.9, 140.3, 139.6, 134.4, 130.9,
130.3, 128.8, 124.3, 122.4, 121.1, 110.9, 61.8, 38.4, 13.9. HRMS
(ESI) calcd for C20H16ClNNaO4 ([MþNa]þ): 392.0660. Found:
392.0667.
4.1.2. Ethyl 3-(5-methyl-2-oxoindolin-3-ylidene)-4-oxo-4-
phenylbutanoate (3b). Yellow solid, yield: 71%. Mp 144 ꢀC. IR
(KBr): 3445, 3179, 3070, 2984, 1733, 1702, 1668, 1619, 1483, 1445,
1321,1275, 1219,1190,1153, 1097,1031, 952, 813. 1H NMR (600 MHz,
CDCl3)
d
(ppm): Z-isomer: 8.21 (s, 1H, NH), 8.02 (d, J¼7.2 Hz, 2H,
ArH), 7.54 (t, J¼7.2 Hz, 1H, ArH), 7.43 (t, J¼7.2 Hz, 2H, ArH), 7.41
(s, 1H, ArH), 7.08 (d, J¼7.2 Hz, 1H, ArH), 6.62 (d, J¼7.2 Hz, 1H, ArH),
4.11e4.08 (m, 2H, CH2), 3.88 (s, 2H, CH2), 2.36 (s, 3H, CH3), 1.11
(t, J¼7.2 Hz, 3H, CH3). E-isomer: 8.13 (d, J¼7.2 Hz, 2H, ArH), 7.61
(t, J¼7.2 Hz, 1H, ArH), 7.48 (t, J¼7.2 Hz, 2H, ArH), 6.54 (s, 1H, ArH),
6.89 (d, J¼7.8 Hz, 1H, ArH), 6.57 (d, J¼7.8 Hz, 1H, ArH), 4.27 (s, 2H,
CH2), 1.98 (s, 3H, CH3), 1.18 (t, J¼7.2 Hz, 3H, CH3); ratio Z/E¼6:1. 13
C
NMR (150 MHz, CDCl3)
d (ppm): 198.0, 168.0, 167.8, 140.7, 140.5,
135.9, 133.2, 131.6, 131.1, 130.2, 128.9, 128.4, 124.9, 121.3, 110.6, 61.7,
38.5, 21.3, 13.9. HRMS (ESI) calcd for C21H19NNaO4 ([MþNa]þ):
372.1220. Found: 372.1216.
4.1.3. Ethyl 3-(5-methyl-2-oxoindolin-3-ylidene)-4-oxo-4-p-tolylbu-
tanoate (3c). Yellow solid, yield: 89%. Mp 150e152 ꢀC. IR (KBr):
3445, 2990, 2921, 1733, 1704, 1654, 1608, 1485, 1407, 1317, 1182,
3. Conclusion
1034, 811. 1H NMR (600 MHz, CDCl3)
d
(ppm): 8.03 (d, J¼7.8 Hz, 2H,
In summary, we systematically investigated the cycloaddition
reactions of alkoxycarbonylmethylpyridinium bromides with
3-phenacylideneoxindoles and ethyl (2-oxo-1,2-dihydro-indol-3-
ylidene)acetates. An efficient synthetic protocol for the un-
precedented dispirocyclopentanebisoxindole derivatives in good
ArH), 7.29 (d, J¼7.8 Hz, 2H, ArH), 6.92 (d, J¼7.8 Hz, 1H, ArH), 6.69
(d, J¼7.8 Hz, 1H, ArH), 6.61 (s, 1H, ArH), 4.25 (s, 2H, CH2), 4.11
(q, J¼7.2 Hz, 2H, CH2), 2.42 (s, 3H, CH3), 2.01 (s, 3H, CH3), 1.20
(t, J¼7.2 Hz, 3H, CH3). 13C NMR (150 MHz, CDCl3)
d (ppm): 196.9,
169.2, 169.1, 145.7, 142.4, 138.5, 132.0, 131.3, 130.5, 130.0, 129.8,

2542
L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
127.2, 125.4, 120.9, 109.6, 61.1, 36.1. 21.9, 21.0, 14.1. HRMS (ESI) calcd
3448,1730, 1699,1664,1627,1484, 1416,1317, 1249, 1195, 1170,1125,
816. 1H NMR (600 MHz, CDCl3)
(ppm): 8.11 (s, 1H, NH), 8.02
(d, J¼7.2 Hz, 2H, ArH), 7.28 (d, J¼7.2 Hz, 2H, ArH), 6.91 (d, J¼7.2 Hz,
1H, ArH), 6.69 (d, J¼7.2 Hz, 1H, ArH), 6.61 (s, 1H, ArH), 4.16 (s, 2H,
CH2), 2.42 (s, 3H, CH3), 2.01 (s, 3H, CH3), 1.38 (s, 9H, CH3). 13C NMR
for C22H21NNaO4 ([MþNa]þ): 386.1376. Found: 386.1379.
d
4.1.4. Ethyl 4-(4-chlorophenyl)-3-(5-methyl-2-oxoindolin-3-
ylidene)-4-oxobutanoate (3d). Yellow solid, yield: 80%. Mp
162e164 ꢀC. IR (KBr): 3233, 2977, 1734, 1701, 1665, 1622, 1586, 1486,
1394, 1326, 1269, 1214, 1179, 1091, 1035, 951, 858. 1H NMR (600 MHz,
(150 MHz, CDCl3)
d (ppm): 196.9, 169.4, 168.1, 145.6, 143.0, 138.6,
132.1, 131.2, 130.4, 130.0, 129.8, 127.1, 125.2, 121.0, 109.7, 81.6, 37.5,
28.0, 27.8, 21.9, 21.0. HRMS (ESI) calcd for C24H25NNaO4 ([MþNa]þ):
414.1676. Found: 414.1682.
CDCl3)
d
(ppm): Z isomer: 7.98 (d, J¼8.4 Hz, 2H, ArH), 7.40 (d, J¼8.4 Hz,
2H, ArH), 7.39 (s,1H, ArH), 7.11 (d, J¼7.8 Hz,1H, ArH), 6.62 (d, J¼7.8 Hz,
1H, ArH), 4.12e4.09 (m, 2H, CH2), 3.89 (s, 2H, CH2), 2.37 (s, 3H, CH3),
1.15 (t, J¼7.2Hz, 3H, CH3);E isomer: 7.95 (d, J¼8.4 Hz, 2H, ArH), 7.46 (d,
J¼8.4 Hz, 2H, ArH), 6.93 (d, J¼7.8 Hz, 1H, ArH), 6.59 (d, J¼7.8 Hz, 1H,
ArH), 6.51 (s, 1H, ArH), 4.26 (s, 2H, CH2), 2.01 (s, 3H, CH3), 1.20
(t, J¼7.2 Hz, 3H, CH3); Z/E ratio¼25:1. 13C NMR (150 MHz, CDCl3)
4.1.9. tert-Butyl 3-(5-chloro-2-oxoindolin-3-ylidene)-4-(4-
chlorophenyl)-4-oxobutanoate (3i). Yellow solid, yield: 76%. Mp
192e194 ꢀC. IR (KBr): 3446, 2977, 1719, 1647, 1588, 1470,1444, 1306,
1196, 1148, 1088, 1015, 982, 821. 1H NMR (600 MHz, CDCl3)
d (ppm):
d
(ppm): 197.0, 168.1, 167.6, 140.2, 140.1, 139.7, 134.5, 131.9, 131.4, 130.3,
8.48 (s, 1H, NH), 7.97 (d, J¼8.4 Hz, 2H, ArH), 7.58 (s, 1H, ArH), 7.41
(d, J¼8.4 Hz, 2H, ArH), 7.26 (d, J¼8.4 Hz, 1H, ArH), 6.59 (d, J¼8.4 Hz,
1H, ArH), 3.76 (s, 2H, CH2), 1.40 (s, 9H, CH3). 13C NMR (150 MHz,
130.2, 128.8, 125.1, 121.2, 110.4, 61.8, 38.5, 21.3, 14.0. HRMS (ESI) calcd
for C21H18ClNNaO4 ([MþNa]þ): 406.0817. Found: 406.0819.
CDCl3)
d (ppm): 196.5, 167.5, 166.6, 143.1, 140.8, 140.0, 133.9, 130.4,
4.1.5. Ethyl 3-(5-fluoro-2-oxoindolin-3-ylidene)-4-oxo-4-
phenylbutanoate (3e). Yellow solid, yield: 65%. Mp 138 ꢀC. IR
(KBr): 3185, 3079, 2986, 2874, 1705, 1672, 1628, 1476, 1467, 1313,
1270, 1193, 1159, 1114, 1033, 1001, 953, 818. 1H NMR (600 MHz,
129.2, 129.0, 127.8, 124.5, 122.5, 111.7, 83.3, 39.6, 28.0, 27.9. HRMS
(ESI) calcd for C22H19Cl2NNaO4 ([MþNa]þ): 454.0583. Found:
454.0586.
CDCl3)
d
(ppm): Z isomer: 8.48 (s, 1H, NH), 8.01 (d, J¼7.8 Hz, 2H,
4.1.10. tert-Butyl 3-(5-fluoro-2-oxoindolin-3-ylidene)-4-oxo-4-
phenylbutanoate (3j). Yellow solid, yield: 80%. Mp 124e126 ꢀC.
IR (KBr): 3193, 3079, 2980, 1735, 1708, 1664, 1626, 1477, 1368,
1299, 1230, 1154, 1008, 951, 860. 1H NMR (600 MHz, CDCl3)
ArH), 7.56 (t, J¼7.2 Hz, 1H, ArH), 7.44 (t, J¼7.2 Hz, 2H, ArH), 7.35
(dd, J1¼8.4 Hz, J2¼3.6 Hz, 1H, ArH), 6.70 (td, J1¼8.4 Hz, J2¼3.6 Hz,
1H, ArH), 6.65 (dd, J1¼8.4 Hz, J2¼4.2 Hz, 1H, ArH), 4.14e4.09 (m, 2H,
CH2), 3.83 (s, 2H, CH2), 1.13 (t, J¼7.2 Hz, 3H, CH3). E isomer: 8.40
(s, 1H, NH), 8.11 (d, J¼7.2 Hz, 2H, ArH), 7.65 (t, J¼7.2 Hz, 1H, ArH),
7.51 (t, J¼7.8 Hz, 2H, ArH), 6.48 (dd, J1¼8.4 Hz, J2¼3.6 Hz, 1H, ArH),
6.82 (t, J¼8.4 Hz, 1H, ArH), 6.61 (dd, J1¼8.4 Hz, J2¼4.2 Hz, 1H, ArH),
4.26 (s, 2H, CH2), 1.18 (t, J¼7.2 Hz, 3H, CH3); ratio Z/E¼10:3. 13C NMR
d
(ppm): 8.62 (s, 1H, NH), 8.12 (d, J¼8.4 Hz, 2H, ArH), 7.65 (t,
J¼7.2 Hz, 1H, ArH), 6.84 (td, J1¼8.4 Hz, J2¼1.8 Hz, 1H, ArH), 6.76
(dd, J1¼8.4 Hz, J2¼4.2 Hz, 1H, ArH), 6.52 (dd, J1¼9.0 Hz, J2¼3.6 Hz,
1H, ArH), 4.19 (s, 2H, CH2), 1.38 (s, 9H, CH3). 13C NMR (150 MHz,
CDCl3)
d
(ppm): 196.6, 169.3, 167.8, 158.3 (d, J¼237.5 Hz), 144.9,
(150 MHz, CDCl3)
d
(ppm): 197.5, 167.7, 167.6, 158.7 (d, J¼238.2 Hz),
137.1, 134.9, 134.1, 129.9, 129.3, 127.0, 121.7 (d, J¼8.7 Hz), 116.5 (d,
J¼23.9 Hz), 111.8 (d, J¼26.1 Hz), 110.7 (d, J¼8.1 Hz), 82.0, 28.0, 27.9.
HRMS (ESI) calcd for C22H20FNNaO4 ([MþNa]þ): 404.1269. Found:
404.1269.
142.7, 138.6, 135.4, 133.6, 129.6, 128.9, 128.6, 122.0 (d, J¼8.7 Hz),
117.0 (d, J¼23.5 Hz), 111.8 (d, J¼25.8 Hz), 111.3 (d, J¼7.8 Hz), 61.9,
38.3, 13.9. HRMS (ESI) calcd for
376.0969. Found: 376.0967.
C
20H16FNNaO4 ([MþNa]þ):
4.2. General procedure for the preparation of dispirocyclo
pentanebisoxindoles 4aek and 5aej from the reactions of 4-
dimethylamino-1-alkoxycarbonylmethylpyridinium salts
with 3-phenacylideneoxindoles or ethyl (2-oxo-1,2-dihydro-
indol-3-ylidene)acetates
4.1.6. Ethyl 4-(4-chlorophenyl)-3-(5-fluoro-2-oxoindolin-3-ylidene)-
4-oxobutanoate (3f). Yellow solid, yield: 74%. Mp 158e160 ꢀC. IR
(KBr): 3462, 3081, 2982, 1708, 1663, 1630, 1588, 1749, 1396, 1307,
1273, 1192, 1161, 1092, 1033, 1006, 953, 821. 1H NMR (600 MHz,
CDCl3)
d
(ppm): Z isomer: 8.58 (br s, 1H, NH), 7.96 (d, J¼8.4 Hz, 2H,
ArH), 7.41 (d, J¼8.4 Hz, 2H, ArH), 7.32 (d, J¼9.0 Hz, 1H, ArH), 7.02
(t, J¼9.0 Hz, 1H, ArH), 6.63e6.61 (m, 1H, ArH), 4.14e4.09 (m, 2H,
CH2), 3.84 (s, 2H, CH2), 1.67 (t, J¼7.2 Hz, 3H, CH3); E isomer: 8.07
(d, J¼8.4 Hz, 2H, ArH), 7.48 (d, J¼8.4 Hz, 1H, ArH), 6.44 (d, J¼9.0 Hz,
1H, ArH), 6.85 (d, J¼9.0 Hz, 1H, ArH), 4.25 (s, 2H, CH2), 1.20
(t, J¼7.2 Hz, 3H, CH3); ratio Z/E¼5:1. 13C NMR (150 MHz, CDCl3)
A
mixture
of
4-dimethylamino-1-alkoxycarbonylmethyl
pyridinium bromide (1.1 mmol), 3-phenacylideneoxindoles or ethyl
(2-oxo-1,2-dihydro-indol-3-ylidene)acetates (2.0 mmol), and
triethylamine (0.2 mmol) in ethanol (15 mL) was stirred at about
50e60 ꢀC for 12 h. The resulting precipitates were collected by fil-
tration, which were recrystallized in a mixture of chloroform and
ethanol to give pure product for analysis.
d
(ppm): 196.4, 168.9, 167.6, 158.7 (d, J¼238.2 Hz), 142.1, 140.0, 138.6,
134.0, 131.2, 130.2, 128.9, 121.8 (d, J¼8.6 Hz),117.2 (d, J¼23.7 Hz),111.9
(d, J¼26.1 Hz), 111.3 (d, J¼7.95 Hz), 62.0, 38.3, 14.0. HRMS (ESI) calcd
for C20H15FClNNaO4 ([MþNa]þ): 410.0566. Found: 410.0568.
4.2.1. Compound 4a. White solid, yield: 85%. Mp 288 ꢀC, IR (KBr)
3401, 3055, 2981, 1739, 1704, 1606, 1490, 1459, 1356, 1299, 1174,
1079, 1005, 982, 857, 754 cmꢁ1. 1H NMR (600 MHz, CDCl3)
(ppm):
n:
d
4.1.7. tert-Butyl 4-oxo-3-(2-oxoindolin-3-ylidene)-4-
phenylbutanoate (3g). Yellow solid, yield: 70%. Mp 130e132 ꢀC. IR
(KBr): 3446, 3077, 3022,1733,1703,1657,1615,1464,1318,1276,1156,
8.05 (d, J¼7.2 Hz, 2H, ArH), 7.60 (d, J¼7.2 Hz, 1H, ArH), 7.52
(t, J¼7.2 Hz, 1H, ArH), 7.46 (t, J¼7.8 Hz, 2H, ArH), 7.43 (t, J¼7.8 Hz,
2H, ArH) 7.27 (br s, 1H, ArH), 7.25 (m, 5H, ArH), 7.19e7.14 (m, 4H,
ArH), 7.05 (t, J¼7.8 Hz, 2H, ArH), 6.95 (t, J¼7.8 Hz, 1H, ArH), 6.90
(t, J¼7.8 Hz, 1H, ArH), 6.87 (d, J¼7.2 Hz, 2H, ArH), 6.77 (t, J¼7.8 Hz,
1H, ArH), 6.63 (t, J¼7.8 Hz, 1H, ArH), 6.41 (d, J¼7.8 Hz, 1H, ArH), 5.91
(d, J¼11.4 Hz, 1H, CH), 5.81 (d, J¼6.6 Hz, 1H, CH), 5.17e5.14 (m, 1H,
CH), 5.07 (d, J¼15.6 Hz, 1H, CH), 4.94 (d, J¼16.2 Hz, 1H, CH), 4.74
(d, J¼16.2 Hz, 1H, CH), 4.20 (d, J¼15.6 Hz, 1H, CH), 3.93 (q, J¼7.2 Hz,
2H, CH2), 6.77 (d, J¼7.2 Hz, 3H, CH3). 13C NMR (150 MHz, CDCl3)
983, 794. 1H NMR (600 MHz, CDCl3)
d (ppm): 8.41 (s,1H, NH), 8.13 (d,
J¼6.0 Hz, 2H, ArH), 7.62 (br s, 1H, ArH), 7.49 (br s, 2H, ArH), 7.12 (br s,
1H, ArH), 6.82 (d, J¼6.6 Hz, 1H, ArH), 6.79 (d, J¼6.6 Hz,1H, ArH), 6.68
(br s,1H, ArH), 4.20 (s, 2H, CH2), 1.37 (s, 9H, CH3). 13C NMR (150 MHz,
CDCl3)
d (ppm): 197.2, 169.2, 168.0, 143.2, 141.0, 134.6, 134.4, 129.9,
129.2,127.1,124.5,122.0,120.9,110.1, 81.8, 37.4, 28.0, 27.8. HRMS (ESI)
calcd for C22H21NNaO4 ([MþNa]þ): 386.1376. Found: 386.1375.
d
(ppm): 197.9, 195.3, 177.5, 175.3, 171.5, 144.2, 143.2, 137.4, 136.9,
4.1.8. tert-Butyl 3-(5-methyl-2-oxoindolin-3-ylidene)-4-oxo-4-p-tol-
ylbutanoate (3h). Yellow solid, yield: 82%. Mp 176e178 ꢀC. IR (KBr):
135.8, 134.9, 132.8, 132.6, 129.2, 129.0, 128.6, 128.3, 128.1, 127.7,
127.5, 127.3, 127.2, 125.5, 125.0, 123.7, 122.8, 122.3, 109.3, 109.1, 61.2,

L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
2543
61.1, 61.0, 56.8, 54.6, 46.6, 44.3, 43.8, 13.7. HRMS (ESI) calcd for
C
HRMS (ESI) calcd for
Found: 731.1704.
C
40H34Cl2N2NaO6 ([MþNa]þ): 731.1686.
50H40N2NaO6 ([MþNa]þ): 787.2779. Found: 787.2777.
4.2.2. Compound 4b. White solid, yield: 80%. Mp 251 ꢀC, IR (KBr)
3450, 1716, 1677, 1641, 1612, 1490, 1462, 1413, 1361, 1303, 1181, 1089,
1032, 833, 752 cmꢁ1. 1H NMR (600 MHz, CDCl3)
(ppm): 7.50e7.46
n
:
4.2.7. Compound 4g. Yellow solid, yield: 65%. Mp 272 ꢀC. IR (KBr)
3421, 1726, 1690, 1621, 1597, 1478, 1449, 1392, 1234, 1188, 1155,
1085, 1008, 843 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
(ppm): 10.59
n:
d
d
(m, 5H, ArH), 7.20 (d, J¼7.8 Hz, 1H, ArH), 7.06 (t, J¼7.8 Hz, 1H, ArH),
7.00 (t, J¼7.2 Hz, 1H, ArH), 6.96 (d, J¼7.8 Hz, 4H, ArH), 6.94
(t, J¼7.2 Hz, 2H, ArH), 6.89e6.81 (m, 5H, ArH), 6.50 (t, J¼7.8 Hz, 1H,
ArH), 6.45 (d, J¼7.8 Hz, 2H, ArH), 6.29 (t, J¼7.8 Hz, 3H, ArH),
6.00e5.95 (m, 2H, ArH, CH), 5.45e5.14 (m, 1H, CH), 4.98e4.95
(m, 2H, CH), 4.72 (d, J¼15.6 Hz, 1H, CH), 4.31 (d, J¼15.6 Hz, 1H, CH),
4.12e4.06 (m, 2H, CH2), 3.83 (d, J¼16.2 Hz, 1H, CH), 2.28 (s, 3H,
CH3), 2.27 (s, 3H, CH3), 1.04 (t, J¼7.2 Hz, 3H, CH3). 13C NMR
(s, 2H, NH), 7.61 (s, 4H, ArH), 7.53 (s, 2H, ArH), 7.38 (s, 4H, ArH), 7.04
(s, 2H, ArH), 6.86 (s, 2H, ArH), 6.50 (s, 2H, ArH), 5.23 (s, 1H, CH), 5.14
(s, 2H, CH), 1.22 (s, 9H, 3CH3). 13C NMR (150 MHz, DMSO-d6)
d
(ppm): 196.5, 175.6, 170.6, 156.0, 140.8, 136.1, 133.8, 129.0, 128.7,
127.8, 127.1, 125.6, 124.6, 110.7, 81.4, 63.4, 51.5, 48.0, 27.3. HRMS
(ESI) calcd for C38H30Cl2N2NaO6 ([MþNa]þ): 703.1317. Found:
703.1385.
(150 MHz, CDCl3)
d
(ppm): 196.8, 196.7, 176.2, 175.8, 171.6, 143.6,
4.2.8. Compound 4h. Yellow solid, yield: 71%. Mp 241 ꢀC. IR (KBr)
3420,1724,1690, 1633, 1600,1487, 1452, 1235,1190, 1157, 1111,1049,
1004, 816 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
(ppm): 10.50 (s, 2H,
n:
143.0, 142.6, 142.5, 135.2, 134.9, 134.7, 129.7, 129.6, 128.9, 128.8,
128.7, 128.6, 128.5, 128.4, 127.1, 126.4, 125.3, 124.0, 122.2, 121.9,
108.5, 108.1, 63.8, 62.9, 60.7, 55.4, 53.0, 49.1, 43.6, 43.4, 21.5, 13.9.
HRMS (ESI) calcd for C52H44N2NaO6 ([MþNa]þ): 815.3092. Found:
815.3090.
d
NH), 7.62 (d, J¼7.2 Hz, 4H, ArH), 7.53 (t, J¼6.6 Hz, 2H, ArH), 7.38
(t, J¼7.2 Hz, 4H, ArH), 6.84 (t, J¼8.4 Hz, 2H, ArH), 6.67 (d, J¼8.4 Hz,
2H, ArH), 6.51e6.49 (m, 2H, ArH), 5.24 (t, J¼9.6 Hz, 1H, CH), 5.15
(d, J¼9.0 Hz, 2H, CH), 1.22 (s, 9H, 3CH3). 13C NMR (150 MHz, DMSO-
4.2.3. Compound 4c. Yellow solid, yield: 82%. Mp 210 ꢀC, IR (KBr)
3423, 1735, 1679, 1606, 1479, 1411, 1352, 1303, 1281, 1233, 1186,
1120, 816. 1H NMR (600 MHz, DMSO-d6)
(ppm): 10.62 (s, 2H, NH),
n
:
d6)
d
(ppm): 196.6, 175.9, 170.7, 156.5 (d, J¼234.6 Hz), 138.3, 136.1,
133.8, 128.6, 127.8, 125.3 (d, J¼7.5 Hz), 115.7 (d, J¼22.5 Hz), 114.5
(d, J¼25.6 Hz), 110.1 (d, J¼5.7 Hz), 81.4, 63.3, 51.6, 48.0, 27.3. HRMS
(ESI) calcd for C38H30F2N2NaO6 ([MþNa]þ).
d
7.50 (d, J¼7.8 Hz, 4H, ArH), 7.17 (d, J¼7.8 Hz, 4H, ArH), 7.03
(d, J¼8.4 Hz, 2H, ArH), 6.85 (s, 2H, ArH), 6.49 (d, J¼8.4 Hz, 2H, ArH),
5.30 (t, J¼9.6 Hz, 1H, CH), 5.10 (d, J¼10.2 Hz, 2H, CH), 4.03
(q, J¼7.2 Hz, 2H, CH2), 2.18 (s, 6H, 2CH3), 0.97 (t, J¼7.2 Hz, 3H, CH3).
4.2.9. Compound 4i. Yellow solid, yield: 74%. Mp 245 ꢀC, IR (KBr)
3432, 3288, 1739, 1709, 1620, 1590, 1475, 1401, 1232, 1156, 1115,
1091, 1003, 841, 756 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
(ppm):
n:
13C NMR (150 MHz, DMSO-d6)
d
(ppm): 195.8, 175.7, 171.4, 144.3,
d
140.8, 133.6, 129.2, 128.9, 128.0, 127.2, 125.6, 124.6, 110.6, 63.4, 61.0,
10.39 (s, 2H, NH), 7.54 (d, J¼6.6 Hz, 4H, ArH), 7.42 (d, J¼6.6 Hz, 4H,
ArH), 6.94 (br s, 2H, ArH), 6.81 (d, J¼5.4 Hz, 2H, ArH), 6.56 (br s, 2H,
ArH), 6.47 (d, J¼6.0 Hz, 2H, ArH), 5.30 (t, J¼8.4 Hz, 1H, CH), 5.07
(d, J¼9.0 Hz, 2H, CH), 1.24 (s, 9H, 3CH3). 13C NMR (150 MHz, DMSO-
51.4, 46.8, 21.0, 13.8. HRMS (ESI) calcd for
C38H30Cl2N2O6
([MþNa]þ): 681.1554. Found: 681.1553.
4.2.4. Compound 4d. Yellow solid, yield: 58%. Mp 212 ꢀC, IR (KBr)
: 3440, 1728, 1686, 1622, 1591, 1478, 1402, 1385, 1218, 1183, 1092,
1044, 1015, 818 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
(ppm):
d6) d (ppm): 195.7, 176.3, 170.9, 141.9, 138.4, 135.0, 129.6, 129.1,
n
128.6, 127.0, 124.0, 120.3, 109.3, 81.2, 63.3, 52.1, 47.6, 27.4. HRMS
(ESI) calcd for C38H30Cl2N2NaO6 ([MþNa]þ): 703.1373. Found:
703.1381.
.
d
10.51 (s, 1H, NH), 10.23 (s, 1H, NH), 8.07 (d, J¼7.8 Hz, 2H, ArH),
7.81 (s, 1H, ArH), 7.61 (d, J¼7.2 Hz, 2H, ArH), 7.46 (d, J¼7.8 Hz, 2H,
ArH), 7.40 (d, J¼7.2 Hz, 2H, ArH), 7.26 (d, J¼7.8 Hz, 1H, ArH), 7.03
(d, J¼7.8 Hz, 1H, ArH), 6.69 (d, J¼7.8 Hz, 1H, ArH), 6.43 (d,
J¼7.8 Hz, 1H, ArH), 5.99 (s, 1H, ArH), 5.59 (d, J¼6.0 Hz, 1H, CH),
5.17e5.14 (m, 1H, CH), 4.97 (d, J¼10.8 Hz, 1H, CH), 3.96e3.94 (m,
1H, CH), 3.84e3.81 (m, 1H, CH), 0.92 (t, J¼6.6 Hz, 3H, CH3). HRMS
(ESI) calcd for C36H24Cl4N2NaO6 ([MþNa]þ): 721.0448. Found:
721.0461.
4.2.10. Compound 4j. Yellow solid, yield: 78%. Mp 234e235 ꢀC. IR
(KBr)
n
: 3437, 1725, 1685, 1632, 1607, 1487, 1412, 1237, 1188, 1156,
(ppm):
1115, 1047, 1013, 844 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
d
10.49 (s, 2H, NH), 7.52 (d, J¼8.4 Hz, 4H, ArH), 7.18 (d, J¼8.4 Hz, 4H,
ArH), 6.84 (td, J1¼8.4 Hz, J2¼2.4 Hz, 2H, ArH), 6.71 (d, J¼8.4 Hz, 2H,
ArH), 6.50e6.48 (m, 2H, ArH), 5.21 (t, J¼9.6 Hz, 1H, CH), 5.10
(d, J¼9.6 Hz, 2H, CH), 2.28 (s, 6H, 2CH3), 1.20 (s, 9H, 3CH3). 13C NMR
(150 MHz, DMSO-d6)
d (ppm): 195.9, 176.0, 170.8, 156.5
4.2.5. Compound 4e. Yellow solid, yield: 49%. Mp 240 ꢀC, IR (KBr)
3447, 1740, 1702,1635, 1489,1406,1387, 1231,1154, 1094,1047,1010,
817. 1H NMR (600 MHz, DMSO-d6)
(ppm): 10.55 (s, 1.84H, NH),
n
:
(d, J¼234.3 Hz), 144.3, 138.3, 133.7, 129.2, 128.0, 125.4 (d, J¼8.3 Hz),
115.6 (d, J¼23.1 Hz), 114.6 (d, J¼26.1 Hz), 110.0 (d, J¼8.6 Hz), 81.2,
63.6, 56.0, 51.4, 48.1, 27.4, 21.0, 18.5. HRMS (ESI) calcd for
d
7.60 (br s, 4H, ArH), 7.47 (br s, 4H, ArH), 6.88 (br s, 2H, ArH), 6.61 (br
C
40H34F2N2NaO6 ([MþNa]þ): 699.2277. Found: 699.2288.
s, 2H, ArH), 6.53 (br s, 2H, ArH), 5.21 (br s, 1H, CH), 5.11 (d, J¼6.0 Hz,
2H, CH), 1.24 (s, 9H, 3CH3). 13C NMR (150 MHz, DMSO-d6)
d
(ppm):
4.2.11. Compound 4k. White solid, yield: 79%. Mp 218 ꢀC, IR (KBr)
3448, 2978,1708,1642,1461,1366, 1271,1229,1162,1085,1002, 847,
757 cmꢁ1. 1H NMR (600 MHz, CDCl3)
(ppm): 8.04 (d, J¼7.8 Hz, 2H,
n:
196.1, 176.2, 171.0, 157.8, 156.3,139.4,138.8, 135.1, 130.2,129.4,125.6,
116.5 (d, J¼5.1 Hz), 116.3, 115.0, 114.8, 110.9 (d, J¼4.2 Hz), 82.1, 63.9,
d
52.2, 48.3, 27.8. HRMS (ESI) calcd for
C38H28Cl2F2N2NaO6
ArH), 7.61 (d, J¼7.8 Hz, 1H, ArH), 7.53 (d, J¼7.8 Hz, 2H, ArH), 7.50
(d, J¼7.2 Hz, 1H, ArH), 7.44 (t, J¼7.2 Hz, 2H, ArH) 7.28e7.27 (m, 4H,
ArH), 7.26e7.24 (m, 2H, ArH), 7.20e7.16 (m, 4H, ArH), 7.10
(t, J¼7.8 Hz, 2H, ArH), 6.96e6.93 (m, 3H, ArH), 6.90 (t, J¼7.8 Hz, 1H,
ArH), 6.76 (t, J¼7.8 Hz, 1H, ArH), 6.63 (t, J¼7.8 Hz, 1H, ArH), 6.41
(d, J¼7.8 Hz, 1H, ArH), 6.11 (d, J¼7.8 Hz, 1H, ArH), 5.98 (d, J¼7.2 Hz,
1H, CH), 5.88 (d, J¼11.4 Hz, 1H, CH), 5.08 (d, J¼16.2 Hz, 1H, CH),
5.04e5.01 (m, 1H, CH), 4.98 (d, J¼16.2 Hz, 1H, CH), 4.79
(d, J¼15.6 Hz, 1H, CH), 4.35 (d, J¼15.6 Hz, 1H, CH), 1.04 (s, 9H, 3CH3).
([MþNa]þ): 739.1171. Found: 739.1185.
4.2.6. Compound 4f. Yellow solid, yield: 80%. Mp 270e271 ꢀC. IR
(KBr) : 3434, 1740, 1709, 1683, 1609, 1479, 1441, 1388, 1296, 1237,
1185, 1156, 1123, 1013, 815. 1H NMR (600 MHz, DMSO-d6)
(ppm):
n
d
10.60 (s, 2H, NH), 7.52 (d, J¼7.8 Hz, 4H, ArH), 7.19 (d, J¼8.4 Hz, 4H,
ArH), 7.04e7.03 (m, 2H, ArH), 6.90 (s, 2H, ArH), 6.50 (d, J¼8.4 Hz,
2H, ArH), 5.20 (t, J¼10.2 Hz, 1H, CH), 5.07 (d, J¼9.6 Hz, 2H, CH), 2.28
(s, 6H, 2CH3), 1.20 (s, 9H, 3CH3). 13C NMR (150 MHz, DMSO-d6)
13C NMR (150 MHz, CDCl3)
d (ppm): 198.2, 195.0, 177.3, 175.4, 170.3,
d
(ppm): 195.9, 175.8, 170.9, 144.3, 140.8, 133.7, 129.2, 128,9, 128.0,
144.2, 143.2, 137.2, 137.1, 136.0, 135.0, 132.8, 132.6, 129.0, 128.8,
128,6, 128.4, 127.8, 127.5, 127.4, 127.2, 125.4, 125.1, 124.8, 123.8,
127.3, 125.7, 124.6, 110.6, 81.3, 63.5, 56.0, 51.4, 48.3, 27.4, 21.0, 18.5.

2544
L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
122.6, 122.2, 109.1, 109.0, 82.2, 61.0, 60.8, 56.2, 55.3, 47.8, 44.2.
HRMS (ESI) calcd for C52H44N2NaO6 ([MþNa]þ): 815.3092. Found:
815.3089.
13.2. HRMS (ESI) calcd for C42H38Cl2N2NaO8 ([MþNa]þ): 791.1897.
Found: 791.1890.
4.2.17. Compound 5f. White solid, yield: 95%. Mp 239 ꢀC, IR (KBr)
3451, 3249, 3038, 2979, 1739, 1691, 1627, 1496, 1457, 1371, 1294,
1177, 1096, 960, 853, 760 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
n:
4.2.12. Compound 5a. White solid, yield: 70%. Mp 270 ꢀC, IR (KBr)
3443, 2986,1738,1627,1548,1495,1374,1319,1218,1171,1094,1027,
858, 818 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
(ppm): 10.30 (s, 2H,
n:
.
d
d
(ppm): 10.27 (s, 2H, NH), 6.92 (d, J¼7.8 Hz, 2H, ArH), 6.71 (s, 2H,
NH), 6.93 (d, J¼7.8 Hz, 2H, ArH), 6.67 (s, 2H, ArH), 6.53 (d, J¼7.8 Hz,
2H, ArH), 4.58 (t, J¼9.6 Hz, 1H, CH), 4.17 (q, J¼7.2 Hz, 2H, CH2), 3.94
(d, J¼9.6 Hz, 2H, 2CH), 3.79 (q, J¼7.2 Hz, 4H, 2CH2), 2.06 (s, 6H,
ArH), 6.51 (d, J¼7.8 Hz, 2H, ArH), 4.50 (t, J¼9.6 Hz, 1H, CH), 3.89
(d, J¼9.6 Hz, 2H, 2CH), 3.79 (q, J¼7.2 Hz, 4H, 2OCH2), 2.06 (s, 6H,
2CH3), 1.42 (s, 9H, 3CH3), 0.71 (t, J¼7.8 Hz, 6H, 2CH3). 13C NMR
2CH3), 1.19 (t, J¼7.2 Hz, 3H, CH3), 0.68 (t, J¼7.2 Hz, 6H, 2CH3). 13
C
(150 MHz, DMSO-d6) d (ppm): 176.2,170.5,170.0,140.0,129.0,128.8,
NMR (150 MHz, DMSO-d6)
d
(ppm): 176.2, 171.3, 169.9, 140.0, 129.1,
126.8, 125.0, 108.8, 80.9, 61.9, 60.4, 51.2, 47.4, 20.6, 13.3. HRMS (ESI)
128.9, 126.7, 124.9, 108.9, 62.0, 60.9, 60.6, 51.0, 46.4, 20.6, 14.0, 13.2.
HRMS (ESI) calcd for C30H32N2NaO8 ([MþNa]þ): 571.2051. Found:
571.2050.
calcd for C32H36N2NaO8 ([MþNa]þ): 599.2364. Found: 599.2362.
4.2.18. Compound 5g. White solid, yield: 93%. Mp 265 ꢀC. IR (KBr)
3449, 3085, 2979, 1738, 1696, 1632, 1489, 1456, 1372, 1283, 1217,
1158, 1095, 921, 871, 760 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
n:
4.2.13. Compound 5b. White solid, yield: 80%. Mp 235 ꢀC, IR (KBr)
.
n
: 3444, 3086, 2986, 2880, 1702, 1635, 1492, 1399, 1375, 1295, 1170,
1094, 1021, 927, 868, 772 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
(ppm): 10.59 (s, 2H, NH), 7.08e7.05 (m, 2H, ArH), 6.73e6.71
d
(ppm): 10.56 (s, 2H, NH), 6.72e6.69 (m, 4H, ArH), 4.42 (t, J¼9.6 Hz,
.
1H, CH), 3.93 (d, J¼10.2 Hz, 2H, 2CH), 3.87e3.82 (m, 4H, 2OCH2),
d
1.42 (s, 9H, 3CH3), 0.76 (t, J¼7.2 Hz, 6H, 2CH3). 13C NMR (150 MHz,
(m, 2H, ArH), 6.67e6.66 (m, 2H, ArH), 4.50 (t, J¼9.6 Hz, 1H, CH),
4.18 (q, J¼7.2 Hz, 2H, CH2), 3.99 (d, J¼9.6 Hz, 2H, 2CH), 3.85 (q,
J¼7.2 Hz, 4H, 2CH2), 1.19 (t, J¼7.2 Hz, 3H, CH3), 0.74 (t, J¼7.2 Hz, 6H,
DMSO-d6) d (ppm): 175.8, 170.0, 169.8, 156.5, 156.0, 138.9, 125.8
(d, J¼8.1 Hz), 115.9 (d, J¼23.0 Hz), 113.2 (d, J¼26.0 Hz), 110.4
(d, J¼8.0 Hz), 81.3, 62.0, 60.8, 51.2, 47.4, 27.4, 13.3. HRMS (ESI) calcd
for C30H30F2N2NaO8 ([MþNa]þ): 607.1862. Found: 607.1856.
2CH3). 13C NMR (150 MHz, DMSO-d6)
d (ppm): 175.7, 170.8, 169.8,
157.5, 156.0, 138.9, 127.8 (d, J¼8.1 Hz), 116.0 (d, J¼23.0 Hz), 113.2 (d,
J¼26.0 Hz), 110.4 (d, J¼8.1 Hz), 62.1, 61.1, 61.0, 51.0, 46.4, 13.9, 13.2.
HRMS (ESI) calcd for C28H26 F2N2NaO8 ([MþNa]þ): 579.1549.
Found: 579.1547.
4.2.19. Compound 5h. White solid, yield: 91%. Mp 246 ꢀC. IR (KBr)
3450, 3095, 2978, 1730, 1694, 1620, 1473, 1397, 1373, 1288, 1156,
1095, 1024, 903, 848, 751 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
n:
.
d
(ppm): 10.42 (s, 2H, NH), 7.11 (t, J¼7.8 Hz, 2H, ArH), 6.90
4.2.14. Compound 5c. White solid, yield: 65%. Mp 230 ꢀC, IR (KBr)
3456, 2988, 1737, 1692, 1623, 1474, 1373, 1339, 1295, 1222, 1173,
1096, 1022, 858, 748 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
(ppm):
n
:
(d, J¼7.8 Hz, 2H, ArH), 6.73 (t, J¼7.8 Hz, 2H, ArH), 6.65 (d, J¼7.8 Hz,
2H, ArH), 4.50 (t, J¼10.2 Hz, 1H, CH), 3.91 (d, J¼7.8 Hz, 2H, 2CH),
3.80e3.72 (m, 4H, 2OCH2), 1.41 (s, 9H, 3CH3), 0.70 (t, J¼7.2 Hz, 6H,
d
10.44 (s, 2H, NH), 7.12 (t, J¼7.8 Hz, 2H, ArH), 6.87 (d, J¼7.2 Hz, 2H,
ArH), 6.73 (t, J¼7.2 Hz, 2H, ArH), 6.66 (d, J¼7.8 Hz, 2H, ArH), 4.57
(t, J¼9.6 Hz, 1H, CH), 4.17 (q, J¼7.2 Hz, 2H, CH2), 3.96 (d, J¼9.6 Hz,
2H, 2CH), 3.80e3.73 (m, 4H, 2CH2), 1.18 (t, J¼7.2 Hz, 3H, CH3), 0.67
2CH3). 13C NMR (150 MHz, DMSO-d6)
d (ppm): 176.3, 170.4, 170.0,
142.4, 129.2, 125.8, 124.8, 120.3, 109.3, 81.0, 61.8, 60.5, 51.4, 47.4,
27.5,13.3. HRMS (ESI) calcd for C30H32N2NaO8 ([MþNa]þ): 571.2051.
Found: 571.2047.
(t, J¼7.2 Hz, 6H, 2CH3). 13C NMR (150 MHz, DMSO-d6)
d (ppm):
176.2, 171.2, 169.8, 142.5, 129.2, 125.7, 124.8, 120.4, 109.3, 61.8, 61.0,
60.6, 51.2, 46.4, 13.9, 13.2. HRMS (ESI) calcd for C28H28N2NaO8
([MþNa]þ): 543.1738. Found: 543.1738.
4.2.20. Compound 5i. White solid, yield: 75%. Mp 235 ꢀC, IR (KBr)
n:
3467, 3120, 2982, 2900, 2728, 1734, 1620, 1479, 1395, 1371, 1220,
1161, 1090, 1022, 892, 802, 736 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
d
(ppm): 10.70 (s, 2H, NH), 7.26 (br s, 1H, ArH), 7.25 (br s, 1H, ArH),
4.2.15. Compound 5d. White solid, yield: 71%. Mp 167 ꢀC, IR (KBr)
6.88 (br s, 2H, ArH), 6.72 (d, J¼8.4 Hz, 2H, ArH), 4.43 (t, J¼9.6 Hz, 1H,
CH), 3.92 (d, J¼9.6 Hz, 2H, 2CH), 3.88e3.83 (m, 4H, 2OCH2), 1.42
(s, 9H, 3CH3), 0.77 (t, J¼7.2 Hz, 6H, 2CH3). 13C NMR (150 MHz,
n
: 3071, 2984, 2934, 1742, 1606, 1492, 1450, 1370, 1271, 1178, 1023,
941, 887 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
.
d
(ppm): 7.17e7.15
(m, 4H, ArH), 7.10 (t, J¼7.2 Hz, 4H, ArH), 6.92 (d, J¼7.2 Hz, 4H, ArH),
6.75e6.72 (m, 4H, ArH), 4.99 (d, J¼16.2 Hz, 2H, 2CHPh), 4.65
(d, J¼16.2 Hz, 2H, 2CHPh), 4.60 (t, J¼9.6 Hz, 1H, CH), 4.22
(q, J¼6.6 Hz, 2H, OCH2), 4.18 (d, J¼9.6 Hz, 2H, 2CH), 3.83 (q,
J¼6.6 Hz, 4H, 2OCH2), 1.21 (t, J¼6.6 Hz, 3H, CH3), 0.68 (t, J¼6.6 Hz,
DMSO-d6) d (ppm): 175.5, 169.7, 141.4, 129.3, 126.2, 125.8, 124.7,
110.9, 81.4, 61.9, 60.9, 51.5, 47.4, 27.5, 13.4. HRMS (ESI) calcd for
C
30H30Cl2N 2NaO8 ([MþNa]þ): 639.1271. Found: 639.1267.
4.2.21. Compound 5j. White solid, yield: 75%. Mp 169 ꢀC, IR (KBr)
2977, 2931, 1738, 1724, 1606, 1494, 1451, 1369, 1344, 1282, 1176,
1090, 941, 887 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
(ppm):
n:
6H, 2CH3). 13C NMR (150 MHz, DMSO-d6)
d (ppm): 174.2, 170.7,
169.4, 158.1, 156.6, 139.4, 135.0, 128.3, 127.2, 126.6, 125.1
(d, J¼8.1 Hz), 116.2 (d, J¼23.1 Hz), 113.2 (d, J¼26.4 Hz), 110.6
(d, J¼7.6 Hz), 61.6, 61.3, 61.1, 51.6, 46.5, 43.0, 13.9, 13.2. HRMS (ESI)
.
d
7.17e7.12 (m, 4H, ArH), 7.09 (t, J¼7.2 Hz, 4H, ArH), 6.92 (d, J¼7.2 Hz,
4H, ArH), 6.76e6.73 (m, 4H, ArH), 5.01 (d, J¼15.6 Hz, 2H, 2CHPh),
4.64 (d, J¼16.2 Hz, 2H, 2CHPh), 4.54 (t, J¼9.6 Hz, 1H, CH), 4.11
(d, J¼9.6 Hz, 2H, 2CH), 3.83 (q, J¼6.6 Hz, 4H, 2OCH2), 1.44 (s, 9H,
3CH3), 0.70 (t, J¼7.2 Hz, 6H, 2CH3). 13C NMR (150 MHz, DMSO-d6)
calcd for
759.2504.
C
42H38F2N 2NaO8 ([MþNa]þ): 759.2488. Found:
4.2.16. Compound 5e. White solid, yield: 55%. Mp 188 ꢀC, IR (KBr)
3065, 2981, 2932, 1744, 1729, 1608, 1485, 1367, 1344, 1216, 1177,
1023, 889, 854 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
(ppm): 7.36
n
:
d (ppm): 174.2, 169.9, 169.6, 158.1, 156.5, 139.4, 135.0, 128.3, 127.2,
126.6, 125.0 (d, J¼8.2 Hz), 116.2 (d, J¼22.4 Hz), 113.2 (d, J¼26.8 Hz),
110.6 (d, J¼7.6 Hz), 81.6, 61.6, 61.0, 51.7, 47.5, 43.0, 27.5, 13.3. HRMS
(ESI) calcd for C44H42F2 N2NaO8 ([MþNa]þ): 787.2801. Found:
787.2817.
d
(d, J¼7.2 Hz, 2H, ArH), 7.14e7.11 (m, 6H, ArH), 6.90 (br s, 6H, ArH),
6.76 (d, J¼7.2 Hz, 2H, ArH), 4.98 (d, J¼15.6 Hz, 2H, 2CHPh), 4.65
(d, J¼15.6 Hz, 2H, 2CHPh), 4.61 (t, J¼8.4 Hz, 1H, CH), 4.22 (br s, 2H,
OCH2), 4.16 (d, J¼8.4 Hz, 2H, 2CH), 3.85e3.84 (m, 4H, 2OCH2), 1.22
(br s, 3H, CH3), 0.69 (br s, 6H, 2CH3). 13C NMR (150 MHz, DMSO-d6)
Acknowledgements
d
(ppm): 173.9, 170.6, 169.4, 141.9, 134.8, 129.6, 128.3, 127.2, 126.6,
This work was financially supported by the National Natural
125.9, 125.6, 125.3, 111.1, 61.5, 61.3, 61.2, 51.5, 46.5, 43.0, 40.1, 13.9,
Science Foundation of China (Grant No. 21172189) and the Priority

L.-J. Lu et al. / Tetrahedron 70 (2014) 2537e2545
2545
7. (a) Liu, H.; Dou, D. L.; Shi, D. Q. J. Comb. Chem. 2010, 12, 633e637; (b) Liu, H.;
Dou, G. L.; Shi, D. Q. J. Comb. Chem. 2010, 12, 292e294; (c) Li, Y. L.; Chen, H.; Shi,
C. L.; Shi, D. Q.; Ji, S. J. J. Comb. Chem. 2010, 12, 231e237.
Academic Program Development of Jiangsu Higher Education
Institutions.
8. (a) Shanmugam, P.; Viswambharan, B.; Madhavan, S. Org. Lett. 2007, 9,
4095e4098; (b) Lakshmi, N. V.; Thirumurugan, P.; Perumal, P. T. Tetrahedron
Lett. 2010, 51, 1064e1068; (c) Badillo, J. J.; Arevalo, G. E.; Fettinger, J. C.; Franz, A.
K. Org. Lett. 2011, 13, 418e421.
Supplementary data
9. (a) Lanka, S.; Thennarasu, S.; Perumal, P. T. Tetrahedron Lett. 2012, 53,
7052e7055; (b) Rao, J. N. S.; Raghunathan, R. Tetrahedron Lett. 2013, 54,
6568e6573; (c) Purushothaman, S.; Prasanna, R.; Lavanya, S.; Raghunathan, R.
Tetrahedron Lett. 2013, 54, 5744e5747; (d) Singh, S. N.; Regati, S.; Paul, A. K.;
Layek, M.; Jayaprakash, S.; Reddy, K. V.; Deora, G. S.; Mukherjee, S.; Pal, M.
Tetrahedron Lett. 2013, 54, 5448e5452.
Crystallographic data 3a (CCDC 904922), 4b (CCDC 971841), 4e
(CCDC 971842), 4h (CCDC 971843), 5e (CCDC 983652), and 5g
(CCDC 971844) have been deposited at the Cambridge Crystallo-
graphic Database Centre. Supplementary data associated with this
article can be found in the online version, at http://dx.doi.org/
10.1016/j.tet.2014.02.050.
€
10. (a) Krohnke, F.; Zecher, W. Angew. Chem., Int. Ed. Engl. 1962, 1, 626e632; (b)
€
Krohnke, F. Angew. Chem., Int. Ed. Engl. 1963, 2, 225e238.
11. (a) Yan, C. G.; Cai, X. M.; Wang, Q. F.; Wang, T. Y.; Zheng, M. Org. Biomol. Chem.
2007, 5, 945e951; (b) Yan, C. G.; Song, X. K.; Wang, Q. F.; Sun, J.; Siemeling, U.;
Bruhn, C. Chem. Commun. 2008, 1440e1442; (c) Wang, Q. F.; Song, X. K.; Chen, J.;
Yan, C. G. J. Comb. Chem. 2009, 11, 1007e1010; (d) Wang, Q. F.; Hou, H.; Hui, L.;
Yan, C. G. J. Org. Chem. 2009, 74, 7403e7406; (e) Yan, C. G.; Wang, Q. F.; Song, X.
K.; Sun, J. J. Org. Chem. 2009, 74, 710e718.
12. (a) Wang, Q. F.; Hui, L.; Hou, H.; Yan, C. G. J. Comb. Chem. 2010, 12, 260e265; (b)
Han, Y.; Chen, J.; Hui, L.; Yan, C. G. Tetrahedron 2010, 66, 7743e7748; (c) Hou, H.;
Zhang, Y.; Yan, C. G. Chem. Commun. 2012, 4492e4494.
References and notes
1. (a) Koch, M. A.; Schuffenhauer, A.; Scheck, M.; Wetzel, S.; Casaulta, M.; Oder-
matt, A.; Ertl, P.; Waldmann, H. Proc. Natl. Acad. Sci. U.S.A. 2005, 102,
17272e17277; (b) Ashimori, A.; Bachand, B.; Overman, L. E.; Poon, D. J. J. Am.
Chem. Soc. 1998, 120, 6477e6487.
2. (a) Sebahar, P. R.; Williams, R. M. J. Am. Chem. Soc. 2000, 122, 5666e5667; (b)
Abdel-Rahman, A. H.; Keshk, E. M.; Hanna, M. A.; El-Bady, Sh. M. Bioorg. Med.
Chem. 2004, 12, 2483e2488.
3. (a) iKotha, S. B.; Deb, A. C.; Lahiri, K.; Manivannan, E. Synthesis 2009, 165e193;
(b) Singh, G. S.; Desta, Z. Y. Chem. Rev. 2012, 112, 6104e6155; (c) Liu, Y. Y.; Wang,
H.; Wan, J. P. Asian J. Org. Chem. 2013, 2, 374e386.
4. (a) Trost, B. M.; Brennan, M. K. Synthesis 2009, 3003e3025; (b) Ball-Jones, N. R.;
Badillo, J. J.; Franz, A. K. Org. Biomol. Chem. 2012, 10, 5165e5181; (c) Hong, L.;
Wang, R. Adv. Synth. Catal. 2013, 355, 1023e1052.
5. (a) Bazgir, A.; Tisseh, T. Z.; Mirzaei, P. Tetrahedron Lett. 2008, 49, 5165e5168; (b)
Jadidi, K.; Ghahremanzadeh, R.; Bazgir, A. Tetrahedron 2009, 65, 2005e2009; (c)
Dabiri, M.; Azimi, S. C.; Khavasi, H. R.; Bazgir, A. Tetrahedron 2008, 64,
7307e7311; (d) Jadidi, K.; Ghahremanzadeh, R.; Bazgir, A. J. Comb. Chem. 2009,
11, 341e344.
6. (a) Gao, S. J.; Tsai, C. H.; Tseng, C.; Yao, C. F. Tetrahedron 2008, 64, 9143e9149;
(b) Litvinov, Y. M.; Mortikov, V. Y.; Shestopalov, A. M. J. Comb. Chem. 2008, 10,
741e745; (c) Liang, B.; Kalidindi, S.; Porco, J. A., Jr.; Stephenson, C. R. J. Org. Lett.
2010, 12, 572e575; (d) Chen, W. B.; Wu, Z. J.; Pei, Q. L.; Cun, N. F.; Zhang, X. M.;
Yuan, W. C. Org. Lett. 2010, 12, 3132e3135.
13. Jacobs, J.; Van Hende, E.; Claessens, S.; De Kimpe, N. Curr. Org. Chem. 2011, 15,
1340e1362.
€
€
€
14. (a) Nyerges, M.; Gajdics, L.; Szollosy, A.; Toke, L. Synlett 1999, 111e113; (b) Fejes,
€
I.; Toke, L.; Nyerges, M.; Pak, C. S. Tetrahedron 2000, 56, 639e644; (c) Fejes, I.;
€
Nyerges, M.; Szollosy, A.; Blasko, G.; Toke, L. Tetrahedron 2001, 57, 1129e1137.
15. (a) Serov, A. B.; kartsev, V. G.; Aleksandrov, A. Yu; Dolgushin, F. M. Russ. Chem.
Bull. 2005, 54, 2432e2436; (b) Velikorodov, A. V.; Imasheva, N. M.; Kuancha-
lieva, A. K.; Poddubnyi, O. Yu Russ. J. Org. Chem. 2010, 46, 971e975.
16. El-Ahl, A. A. S. Pol. J. Chem. 1997, 71, 27e31.
17. Hui, L.; Li, H. Y.; Yan, C. G. Eur. J. Org. Chem. 2012, 3157e3164.
18. Wu, L.; Sun, J.; Yan, C. G. Org. Biomol. Chem. 2012, 10, 9452e9463.
19. Fu, Q.; Yan, C. G. Tetrahedron 2013, 69, 5841e5849.
20. (a) Basavaiah, D.; Reddy, K. R. Org. Lett. 2007, 9, 57e60; (b) Shanthi, G.; Perumal,
P. T. Tetrahedron Lett. 2008, 49, 7139e7142; (c) Lingam, K.; Shanmugam, P.;
Selvakumar, K. Synlett 2012, 278e284.
21. (a) Tan, B.; Candeias, N. R.; Barbas, C. F., III. Nat. Chem. 2011, 3, 473e477; (b) Sun,
J.; Xie, Y. J.; Yan, C. G. J. Org. Chem. 2013, 78, 8354e8365; (c) Wu, H.; Zhang, L. L.;
Tian, Z. Q.; Huang, Y. D.; Wang, Y. M. Chem.dEur. J. 2013, 19, 1747e1753.
22. Sarkunam, K.; Nallu, M. J. Heterocycl. Chem. 2005, 42, 5e11.