Ethylenediamine diacetate-catalyzed three-component reaction for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones and their spirooxindole derivatives

Article abstract of DOI:10.1016/j.tet.2011.08.018

Ethylenediamine diacetate (EDDA)-catalyzed one-pot syntheses of biologically interesting 2,3-dihydroquinazolin-4(1H)-ones and their spirooxindole derivatives from isatoic anhydride, amines, and benzaldehydes or isatins via a three-component condensation in aqueous media have been described. This method is of great value because of high yields and ease of handling.

Full text of DOI:10.1016/j.tet.2011.08.018

Tetrahedron 67 (2011) 9627e9634
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ethylenediamine diacetate-catalyzed three-component reaction for the synthesis
of 2,3-dihydroquinazolin-4(1H)-ones and their spirooxindole derivatives
*
Manchala Narasimhulu, Yong Rok Lee
School of Chemical Engineering and Technology, Yeungnam University, Gyeongsan 712-749, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 July 2011
Received in revised form 4 August 2011
Accepted 5 August 2011
Available online 24 September 2011
Ethylenediamine diacetate (EDDA)-catalyzed one-pot syntheses of biologically interesting 2,3-
dihydroquinazolin-4(1H)-ones and their spirooxindole derivatives from isatoic anhydride, amines, and
benzaldehydes or isatins via a three-component condensation in aqueous media have been described.
This method is of great value because of high yields and ease of handling.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Three-component reaction
2,3-Dihydroquinazolin-4(1H)-one
Spirooxindole
1. Introduction
O
O
O
R2
R1
R2
+
path a
N
path b
O
+ R1CHO+ R2NH2
O
N
H
R1CHO
2,3-Dihydroquinazolinone derivatives are an important class of
fused heterocycles that display a wide range of biological, pharma-
cological, and medicinal properties involving antitumor, antibiotic,
antipyretic, analgesic, antihypertonic, diuretic, antihistamine, anti-
depressant, and vasodilating activities.1 In addition 2,3-dihy-
droquinazolinones have been shown to act as potent tubulin
inhibitors with impressive antiproliferative activity against several
human cancer cell lines.2 Furthermore, these compounds can act
analogously to the antimitotic agent colchicine.3 Given the impor-
tance of such activities, a number of synthetic methods for their
synthesis from isatoic anhydride (path a) and anthranilamide (path
b) have been reported (Scheme 1). Three-component condensation
of an isatoic anhydride, a primary amine, and an aromatic aldehyde
has been widely described under a variety of catalysts such (path a)
as [bmim]BF4,4 p-TsOH,5 silica sulfuric acid,6 Al(H2PO4)3,7 KAl-
(SO4)2$12H2O (alum),8 montmorillonite K-10,9 zinc perfluo-
rooctanoate,10 gallium triflate,11 and Amberlyst-15/microwave.12
N
H
N
H
NH2
2,3-Dihydroquinazolinones
Scheme 1.
Spirooxindole derivatives also represent an important class of
naturally occurring substances with highly pronounced biological
activities and properties.20,21 The unique structural array and
highly prominent pharmacological activities have subsequently
stimulated interest in the synthesis of spirooxindole derivatives.
Thus, development of new and simple synthetic methods for the
preparation of such derivatives bearing the biologically active
dihydroquinazolinone ring has become an interesting challenge.
Very recently, two methods for the synthesis of spirooxindoles
bearing the dihydroquinazolinone ring through multicomponent
reactions have been developed (Scheme 2). The typical procedure
involves the condensation of isatoic anhydride with isatins and
amines using KAl(SO4)2$12H2O as a catalyst (path c).22 Another
method has shown formation of a spirooxindole derivative from 2-
aminobenzamide with isatin in the presence of chiral phosphoric
acid (path d).18a
The method through path
b includes condensation of 2-
aminobenzamides with aldehydes in the presence of p-TsOH/
DDQ,13 I2,14 FeCl3,15 CuCl2,16 TiCl4/Zn,17 chiral phosphoric acid,18 and
ionic liquid/water.19
Although several methods for the synthesis of 2,3-
dihydroquinazolinones and spirooxindole derivatives have been
reported, there is still a demand for simple and cost effective
methods. Recently, the Brønsted acids and bases have demon-
strated their potential to serve as active catalysts for a variety of
* Corresponding author. Tel.: þ82 53 810 2529; fax: þ82 53 810 4631; e-mail
address: yrlee@yu.ac.kr (Y.R. Lee).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.018

9628
M. Narasimhulu, Y.R. Lee / Tetrahedron 67 (2011) 9627e9634
O
O
R1
N
O
O
O
O
R1
+
path c
path d
O
1
N
H
+
O
+
O
R NH2
O
N
H
NH
N
N
H
N
NH2
H
H
Scheme 2.
synthetically useful reactions in organic synthesis.23 In particular,
we developed a new and useful methodology for a variety of ben-
zopyrans using ethylenediamine diacetate (EDDA) as effective
Brønsted acid and base catalyst.24 We also developed an environ-
mentally benign method for the synthesis of a variety of pyrans
Importantly, the use of water as a solvent offers environmental
benefits as well as significant rate enhancements, due likely to
select factors, including the hydrophobic effect, a large dielectric
constant, extensive hydrogen bonding, high heat capacity, and
optimum oxygen solubility.28 By comparing with reported results,
EDDA in water revealed itself a much better catalyst for the for-
mation of 4a than [bmim]BF4 (80%),4 p-TsOH/ethanol (65%),5 silica
sulfuric acid/H2O (85%),6 alum/H2O (65%),8 montmorillonite K-10/
ethanol (80%),9 zinc perfluorooctanoate/H2O (60%),10 gallium tri-
flate/ethanol (79%),11 and Amberlyst-15/microwave (81%).12 In
particular, this protocol is convincingly superior to the recently
reported catalytic methods, such as other Brønsted acid (TsOH/
ethanol, 65%),5 or solvent free conditions (Amberlyst-15/micro-
wave, 81%).12
After optimizing the conditions, the generality toward various
amines and benzaldehydes was next explored. The results obtained
are listed in Table 2. The direct three-component reactions worked
well with a variety of arylamines bearing either electron-donating
(entries 1e5) or -withdrawing groups (entries 6 and 7), phene-
thylamine (entries 8 and 9) and 4-phenylbutylamine (entry 10).
Also the reactions with arylamines and a range of benzaldehydes
carrying either electron-donating or -withdrawing groups on the
benzene ring afforded desired products 4beh in high yields. With
other primary amines having an aromatic ring, desired products
4iek were produced in 88e92% yield (entries 8e10). These re-
actions provided rapid access to various 2,3-dihydroquinazolin-
4(1H)-one derivatives 4aek.
starting from cyclic 1,3-dicarbonyls and a,b-unsaturated aldehydes
in water.25 As a part of an ongoing study into the synthetic efficacy
of EDDA as a catalyst for organic reactions, this study examines
EDDA-catalyzed three-component reactions of isatoic anhydride,
amines, and benzaldehydes to afford 2,3-dihydroquinazolin-4(1H)-
one derivatives. We also examine EDDA-catalyzed three-compo-
nent reactions of isatoic anhydride, amines, and isatins to afford
spirooxindole derivatives bearing dihydroquinazolinone rings. We
report herein an efficient and convenient one-pot synthesis of
a variety of biologically interesting 2,3-dihydroquinazolin-4(1H)-
ones and spirooxindole derivatives with dihydroquinazolinone
rings in aqueous medium.
2. Results and discussion
Presently, the development of environmental friendly tech-
niques is one of the priority goals of chemical research, with water
emerging as a versatile solvent for organic chemistry in recent
years.26 Water as a solvent is not only inexpensive and environ-
mentally benign, but also gives completely new reactivities.27
Therefore, we investigated a EDDA-catalyzed, three-component
reaction of isatoic anhydride (1), aniline (2a), and benzaldehyde
(3a) to afford 4a, under several solvents, including ethanol, aceto-
nitrile, methylene chloride, toluene, and water (Table 1). When the
reaction was carried out in the presence of 20 mol % EDDA in water,
the expected product (4a) was obtained in high yield (94%) and
with better reaction times compared with other organic solvents.
With nonpolar methylene chloride and toluene, the desired adduct
was not produced, likely due to insolubility of the isatoic anhydride.
As an application of this methodology to synthesize spiroox-
indole derivatives bearing dihydroquinazolinone ring, EDDA-
catalyzed three-component reactions of isatoic anhydride (1), an-
iline (2a), and isatin (5a) were next carried out. Treatment of 1 with
2a and 5a in the presence 20 mol % EDDA in water at reflux for 5 h
provided compound 6a in 94% yield (Scheme 3). The assignment of
6a was easily defined by observing the chemical shifts of the
characteristic protons and comparison with reported data in the
1
literature.22 The H NMR spectrum of 6a showed an amide proton
Table 1
at
d
¼10.39 ppm as a singlet and one amine proton at ¼7.30 ppm as
d
Reaction of 1 with 2a and 3a in the presence of EDDA under several solvents
a singlet. In the IR spectrum, the absorption bands at 1721 and
1644 cmꢀ1, corresponding to two carbonyls of the amide, con-
firmed the presence of this structure.
O
O
O
NH2
+
EDDA
N
O
To explore generality and scope, additional reactions of isatoic
anhydride (1) with various amines and several isatins were next
attempted. The results obtained are listed in Table 3. Reactions
with anilines bearing both electron-donating (entries 1 and 2) and
-withdrawing groups (entry 3) on the benzene ring provided
products 6bed in 89e96% yield. With other primary amines
having an aromatic ring, desired products 6eei were produced in
82e92% yield (entries 4e8). Interestingly, when employing ali-
phatic amines with a chain and cyclic ring, the expected cyclo-
adducts 6j and 6k were obtained in 91 and 89% yields,
respectively. With ammonium acetate, 6l was also produced
(93%). In addition, reactions of 5-bromoisatin (5b) and 1-
methylisatin (5c) with several anilines successfully afforded
products 6meq in 82e93% yield (entries 12e16). These reactions
provided rapid access to various spirooxindole derivatives 6beq
with the dihydroquinazolinone moiety.
H
+
O
solvent
N
H
N
H
1
2a
3a
4a
Entry
EDDA (mol %)
Solvent
Condition
Yield (%)
1
2
3
4
5
6
7
8
d
Ethanol
Ethanol
Ethanol
Ethanol
Acetonitrile
Acetonitrile
Acetonitrile
Methylene chloride
Toluene
Water
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
Reflux, 5 h
25
50
55
60
<5
20
30
No reaction
No reaction
36
80
94
10
20
40
d
20
40
20
20
d
9
10
11
12
10
20
Water
Water

M. Narasimhulu, Y.R. Lee / Tetrahedron 67 (2011) 9627e9634
9629
Table 2
EDDA catalyzed one-pot synthesis of 2,3-dihydroquinazolinones in water
Time (h)
Yield (%)
Amine
Entry
Isatoic
anhydride
Aldehyde
Product
O
NH2
CHO
CHO
10
7
N
86
93
91
90
1
MeO
N
H
NH2
4b
O
OMe
2
N
Cl
N
H
4c
Cl
NH2
NH2
O
CHO
CHO
8
7
3
4
N
MeO
N
H
O
4d
OMe
OMe
N
O
O
O
N
H
NH2
O
4e
CHO
O
6
5
6
MeO
F
O
O
N
92
90
MeO
MeO
O
N
H
F
O
NH2
NH2
N
H
O
4f
CHO
CHO
OMe
F
1
N
6
7
N
H
O
OMe
4g
N
7
O
O
89
88
N
H
F
O
4h
O
NH2
8
7
CHO
CHO
N
8
9
MeO
N
H
4i
O
NH2
OMe
N
87
92
O
O
O
N
H
O
NH2
4j
O
CHO
6
10
N
Cl
N
H
4k
Cl
catalyzed by Brønsted acid and Lewis acid, EDDA could act as
a Brønsted acid. The carbonyl group of isatoic anhydride (1) could
be protonated by EDDA to give intermediate 7, which could fa-
cilitate nucleophilic attack of aniline (2a) on the carbonyl unit.
Nucleophilic addition of aniline (2a) to 7, followed by de-
carboxylation, produced 2-aminobenzamide 8. Condensation of 8
with protonated benzaldehyde gave imine 9, which underwent
intramolecular cyclization to afford final product 4a. Similarly,
condensation of 8 with protonated isatin, prepared using EDDA,
gave imine 10, which underwent intramolecular cyclization to
afford product 6a.
O
O
N
O
NH2
+
EDDA
O
O
+
O
(20 mol%)
O
H2O
reflux, 5 h
94%
N
H
N
N
H
NH
H
1
2a
5a
6a
Scheme 3.
In summary, the one-pot three-component condensation of
isatoic anhydride with various amines and benzaldehydes provided
2,3-dihydroquinazolin-4(1H)-one derivatives in an aqueous
The formation of 4a and 6a can be explained by the mecha-
nism as shown in Scheme 4. According to observation of evolu-
tion in the reaction mixture and other reported mechanisms

9630
M. Narasimhulu, Y.R. Lee / Tetrahedron 67 (2011) 9627e9634
Table 3
EDDA catalyzed one-pot synthesis of spirooxindole derivatives with dihydroquinazolinones in water
Time (h)
Isatin
Isatoic
anhydride
Amine
Product
Entry
Yield (%)
O
NH2
92
96
O
N
7
1
2
6b
N
H
NH
O
NH2
O
N
6
9
6c
F
N
H
NH
O
NH2
89
O
N
3
6d
F
O
N
H
NH
O
N
O
O
NH2
NH2
O
90
82
7
4
5
N
H
NH
6e
O
N
N
H
O
O
H
1
5a
O
N
10
10
N
H
NH
OMe
O
6f
NH2
O
N
88
92
MeO
6
N
H
NH
6g
O
NH2
6
7
O
N
7
8
N
H
NH
6h
O
O
N
92
91
NH2
N
H
NH
6i
O
O
N
7
7
NH2
9
O
N
H
NH
6j
O
N
N
H
NH2
NH
89
93
10
6k
O
O
NH
NH4OAc
11
6
N
H
NH
6l

M. Narasimhulu, Y.R. Lee / Tetrahedron 67 (2011) 9627e9634
9631
Table 3 (continued)
Yield (%)
Product
Entry
Amine
Isatin
Time (h)
Isatoic
anhydride
O
O
Br
NH2
O
N
8
O
93
82
12
13
N
N
H
F
NH
H
5b
6m
O
NH2
Br
O
O
N
10
O
N
F
N
H
NH
O
O
6n
O
H
1
NH2
O
N
10
Br
90
92
88
O
14
15
N
H
N
N
5c
6o
O
NH2
NH2
O
N
8
8
F
N
H
N
6p
O
O
16
N
N
H
F
N
6q
EDDA
H
NH2
O
+
+
OH
O
O
HO
2a
Ph
O
Ph
EDDA
O
N
H
N
H
N
H
O
-CO2
-H2O
N
H
O
NH2
N
1
7
8
9
Ph
+
OH
O
-H2O
EDDA
O
O
N
N
O
N
H
N
H
O
Ph
4a
N
:
H
O
N
NH
N
H
10
N
6a
H
Scheme 4. A possible mechanism for the formation of 4a and 6a.
medium. Also, three-component reaction of isatoic anhydride with
a variety of amines and several isatins was successfully applied to
the synthesis of biologically interesting spirooxindole derivatives
bearing the dihydroquinazolinone moiety in aqueous media. This
methodology offers several advantages, including high product
yield, ease of experimental procedure, and amenability to large-
scale operations.
3. Experimental
3.1. General
All the experiments were carried out in aqueous medium. Isa-
toic anhydride, aldehydes, Isatins, and amines were obtained from
Aldrich chemicals. Merck, pre-coated silica gel plates (Art. 5554)

9632
M. Narasimhulu, Y.R. Lee / Tetrahedron 67 (2011) 9627e9634
with a fluorescent indicator were used for analytical TLC. 1H NMR
and 13C NMR spectra were recorded on a Bruker Model ARX (300
and 75 MHz, respectively) spectrometer in DMSO-d6 as the solvent
chemical shift. IR spectra were recorded on a Jasco FTIR 5300
spectrophotometer. HRMS were carried out at the Korea Basic
Science Institute.
113.6, 72.8, 55.1, 55.0; IR (KBr) 3426, 2936, 2837, 1636, 1510, 1394,
1441,1243,1174,1025, 996, 830, 762 cmꢀ1; HRMS m/z (Mþ) calcd for
C22H20N2O3: 360.1474. Found: 360.1477.
3.2.7. Compound 4g. Mp 259e260 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
7.74 (1H, d, J¼7.8 Hz), 7.49 (1H, s), 7.29e7.12 (7H, m), 6.86 (2H,
d, J¼8.7 Hz), 6.76 (2H, t, J¼7.8 Hz), 6.23 (1H, s), 3.70 (3H, s); 13C NMR
3.2. Typical procedure for 4aek
(75 MHz, DMSO-d6) d 162.5, 159.2, 146.8, 133.7, 132.2, 128.8, 128.7,
128.09, 127.9, 117.4, 115.4, 115.1, 115.0, 114.6, 113.6, 72.6, 55.0; IR
(KBr) 3427, 3302, 1643, 1504, 1390, 1305, 1245, 1026, 994, 832,
760 cmꢀ1; HRMS m/z (Mþ) calcd for C21H17FN2O2: 348.1274. Found:
348.1272.
To a solution of isatoic anhydride (1) (1.0 mmol), amines
(1.0 mmol), and benzaldehydes (1.0 mmol) in water (10 mL) was
addedEDDA(36mg, 0.2mmol)andthereactionmixturewasrefluxed
for 5e10 h under nitrogen atmosphere. After completion of the re-
action, the reactionmixturewascooledtoroomtemperature, filtered,
and recrystallized in ethanol to afford the pure product.
3.2.8. Compound 4h. Mp 252e253 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
(2H, m), 6.95 (1H, s), 6.86e6.72 (5H, m), 6.21 (1H, s), 5.98 (2H, s); 13C
NMR (75 MHz, DMSO-d6) 162.4, 147.3, 147.2, 136.7, 134.1, 133.7,
d
7.74 (1H, d, J¼7.5 Hz), 7.55 (1H, s), 7.31e7.26 (2H, m), 7.22e7.14
3.2.1. Compound 4a. Mp 205e206 ꢁC; 1H NMR (300 MHz, DMSO-
d
d6)
d
7.77 (1H, d, J¼7.8 Hz), 7.64 (1H, s), 7.42e7.18 (11H, m), 6.79 (1H,
128.8, 128.7, 127.8, 120.5, 117.5, 115.4, 115.1, 114.9, 114.6, 107.7, 106.9,
101.1, 72.7; IR (KBr) 3426, 1641, 1501, 1447, 1393, 1248, 1027, 996,
758 cmꢀ1; HRMS m/z (Mþ) calcd for C21H15FN2O3: 362.1067. Found:
362.1064.
d, J¼8.1 Hz), 6.74 (1H, t, J¼7.2 Hz), 6.30 (1H, s); 13C NMR (75 MHz,
DMSO-d6) d 162.2, 146.5, 140.7, 140.6, 133.7, 128.5, 128.3, 128.2, 127.9,
126.5, 126.2, 125.9, 117.4, 115.3, 114.7, 72.6; IR (KBr) 3427, 3294, 3061,
2832, 1633, 1511, 1392, 1332, 1257, 1158, 1025, 754 cmꢀ1; HRMS m/z
(Mþ) calcd for C20H16N2O: 300.1263. Found: 300.1265.
3.2.9. Compound 4i. Mp 183e185 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
7.72 (1H, d, J¼7.8 Hz), 7.35e7.17 (9H, m), 6.93 (2H, d, J¼8.7 Hz),
3.2.2. Compound 4b. Mp 209e210 ꢁC; 1H NMR (300 MHz, DMSO-
6.75e6.67 (2H, m), 5.82 (1H, s), 4.06e3.97 (1H, m), 3.73 (3H, s),
d6)
d
7.75 (1H, d, J¼7.5 Hz), 7.54 (1H, s), 7.33e7.19 (5H, m), 7.14 (1H,
3.05e2.87 (2H, m), 2.76e2.52 (1H, m); 13C NMR (75 MHz, DMSO-
s), 7.03 (2H, t, J¼8.7 Hz), 6.88e6.85 (2H, m), 6.77 (1H, t, J¼8.1 Hz),
d6)
d 162.3, 159.4, 146.5, 139.0, 133.1132.9, 128.6, 128.5, 128.3, 127.7,
6.22 (1H, s), 3.71 (3H, s), 2.27 (3H, s); 13C NMR (75 MHz, DMSO-d6)
127.4, 126.2, 117.0, 114.7, 114.2, 113.8, 70.3, 55.1, 46.0; IR (KBr) 3426,
d
162.2, 159.0, 146.5, 140.8, 137.8, 133.6, 132.7, 128.3, 127.9, 127.8,
3299, 1629, 1509, 1408, 1299, 1249, 1173, 1025, 997, 763 cmꢀ1
;
126.8, 126.6, 123.2, 117.4, 115.4, 114.7, 113.6, 72.3, 55.0, 20.8; IR (KBr)
3424, 3301, 2961, 2833, 1634, 1507, 1393, 1301, 1248, 1170, 1026,
830, 766 cmꢀ1; HRMS m/z (Mþ) calcd for C22H20N2O2: 344.1525.
Found: 344.1525.
HRMS m/z (Mþ) calcd for C23H22N2O2: 358.1681. Found: 358.1679.
3.2.10. Compound 4j. Mp 147e148 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
6.69e6.62 (3H, m), 5.98 (2H, s), 5.76 (1H, s), 4.04e3.88 (1H, m),
3.01e2.84 (2H, m), 2.77e2.67, (1H, m); 13C NMR (75 MHz, DMSO-
d
7.65 (1H, d, J¼7.8 Hz) 7.29e7.16 (6H, m), 6.88e6.78 (3H, m),
3.2.3. Compound 4c. Mp 190e192 ꢁC; 1H NMR (300 MHz, DMSO-d6)
d
7.95(1H,d,J¼8.4Hz), 7.74(1H,d, J¼6.9 Hz), 7.68(1H, d, J¼2.4Hz), 7.59
d6) d 162.1, 147.4, 147.3, 146.3, 139.0, 134.9, 133.1, 128.5, 128.3, 127.3,
(1H, d, J¼8.4 Hz), 7.37e7.17 (7H, m), 6.78e6.71 (2H, m), 6.29 (1H, d,
126.1, 119.7, 117.0, 114.6, 114.1, 107.9, 106.4, 101.1, 70.2, 46.0, 33.5; IR
(KBr) 3427, 1634, 1484, 1411, 1248, 1026, 994, 756 cmꢀ1; HRMS m/z
(Mþ) calcd for C23H20N2O3: 372.1474. Found: 372.1471.
J¼2.4 Hz), 2.93e2.84 (1H, m),1.18 (6H, d, J¼6.9 Hz); 13C NMR (75 MHz,
DMSO-d6) d 162.05, 146.2, 139.9, 138.4, 133.7, 132.8, 130.1, 128.9, 128.3,
127.02, 126.5, 121.04, 117.6, 115.4, 114.8, 71.8, 32.9, 23.7; IR (KBr) 3425,
3282, 2960, 1645, 1511, 1390, 1327, 1240, 990, 8826, 754 cmꢀ1; HRMS
m/z (Mþ) calcd for C23H21ClN2O: 376.1342. Found: 376.1339.
3.2.11. Compound 4k. Mp 129e130 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
5.83 (1H, d, J¼2.1 Hz), 3.41e3.35 (2H, m), 2.53 (2H, t, J¼6.9 Hz),
1.58e1.45 (4H, m); 13C NMR (75 MHz, DMSO-d6)
162.2, 145.9,
d
7.65 (1H, d, J¼7.8 Hz), 7.39e7.11 (11H, m), 6.81e6.61 (2H, m),
3.2.4. Compound 4d. Mp 171e172 ꢁC; 1H NMR (300 MHz, DMSO-d6)
d
d
7.75 (1H, d, J¼7.5 Hz), 7.55 (1H, s), 7.32e7.21 (7H, m), 6.86 (2H, d,
142.03, 140.2, 133.2, 132.9, 128.4, 128.26, 128.21, 127.9, 127.4, 125.6,
117.3, 115.0, 114.3, 69.4, 44.3, 34.8, 28.3, 27.1; IR (KBr) 3426, 3297,
J¼8.4 Hz), 6.74 (2H, t, J¼8.4 Hz), 6.19 (1H, s), 3.70 (3H, s), 2.91e2.82
(1H, m), 1.19 (6H, d, J¼6.9 Hz); 13C NMR (75 MHz, DMSO-d6)
d
162.1,
2938, 2859, 1630, 1489, 1437, 1413, 1320, 1089, 996, 826, 749 cmꢀ1
;
159.05, 146.4, 145.9, 138.6, 133.5, 132.8, 127.8, 127.6, 126.3, 125.9,
117.3, 115.4, 114.7, 113.6, 72.2, 54.9, 32.9, 23.7; IR (KBr) 3420, 3298,
2956, 1630, 1508, 1392, 1332, 1249, 1177, 1027, 833, 700 cmꢀ1; HRMS
m/z (Mþ) calcd for C24H24N2O2: 372.1838. Found: 372.1840.
HRMS m/z (Mþ) calcd for C24H23ClN2O: 390.1499. Found: 390.1499.
3.3. Typical procedure for 6aeq
3.2.5. Compound 4e. Mp 210e212 ꢁC; 1H NMR (300 MHz, DMSO-
To a solution of isatoic anhydride (1) (1.0 mmol), amines
(1.0 mmol), and isatins (1.0 mmol) in water (10 mL) was added
EDDA (36 mg, 0.2 mmol) and the reaction mixture was refluxed for
5e10 under nitrogen atmosphere. After completion of the reaction,
the reaction mixture was cooled to room temperature, filtered, and
recrystallized in ethanol to afford the pure product.
d6)
d
7.74 (1H, d, J¼7.5 Hz), 7.58 (1H, s), 7.28e7.18 (5H, m), 6.94 (1H,
s), 6.83e6.63 (4H, m), 6.18 (1H, s), 5.98 (2H, s), 2.92e2.85 (1H, m),
1.19 (6H, d, J¼6.6 Hz); 13C NMR (75 MHz, DMSO-d6)
d 162.1, 147.3,
147.1, 146.3, 146.0, 138.5, 134.9, 133.6, 127.9, 126.4, 125.8, 119.9, 117.4,
115.4, 114.8, 107.8, 106.6, 101.1, 72.2, 32.9, 23.7; IR (KBr) 3437, 2960,
1644, 1509, 1401, 1237, 1028, 755 cmꢀ1; HRMS m/z (Mþ) calcd for
C24H22N2O3: 386.1630. Found: 386.1629.
3.3.1. Compound 6a. Mp 264e266 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
10.39 (1H, s), 7.68 (1H, d, J¼7.5 Hz), 7.60 (1H, s), 7.53 (1H, d,
3.2.6. Compound 4f. Mp 227e228 ꢁC; 1H NMR (300 MHz, DMSO-
J¼7.5 Hz), 7.30 (1H, t, J¼7.8 Hz) 7.24e7.12 (4H, m), 7.01e6.98 (2H,
d6)
d, J¼8.7 Hz), 6.89e6.84 (4H, m) 6.75 (2H, t, J¼7.8 Hz), 6.16 (1H, s),
3.73 (3H, s), 3.70 (3H, s); 13C NMR (75 MHz, DMSO-d6)
162.3,159.1,
157.2, 146.6, 133.5, 132.7, 127.9, 127.8, 127.4, 117.3, 115.2, 114.6, 113.7,
d
7.74 (1H, d, J¼7.8 Hz), 7.44 (1H, s), 7.31e7.23 (3H, m), 7.15 (2H,
m), 6.92 (1H, t, J¼7.5 Hz), 6.78e6.70 (2H, m), 6.64 (1H, d, J¼7.5 Hz);
13C NMR (75 MHz, DMSO-d6)
d 175.6, 163.8, 146.3, 141.4, 138.3,
d
134.2, 134.0, 129.9, 129.7, 129.2, 128.3, 127.9, 118.4, 115.0, 114.6, 114.1,
112.6, 76.8; IR (KBr) 3447, 3303, 1721, 1644, 1615, 1486, 1358, 1194,

M. Narasimhulu, Y.R. Lee / Tetrahedron 67 (2011) 9627e9634
9633
1105, 1012, 964, 865, 752 cmꢀ1; HRMS m/z (Mþ) calcd for
C21H15N3O2: 341.1164. Found: 341.1161.
(1H, t, J¼11.4 Hz), 2.86e2.68 (2H, m), 2.57 (1H, t, J¼7.2 Hz); 13C NMR
(75 MHz, DMSO-d6) d 175.2, 163.3, 145.7, 142.2, 138.6, 133.2, 131.3,
128.4, 128.0, 127.2, 127.1, 126.2, 125.9, 122.4, 117.5, 114.3, 113.7, 110.6,
75.3, 44.9, 34.2; IR (KBr) 3279, 3062, 2956, 2873, 1723, 1639, 1513,
1477, 1394, 1325, 1272, 1234, 1189, 1023, 944, 751 cmꢀ1; HRMS m/z
(Mþ) calcd for C23H19N3O2: 369.1477. Found: 369.1479.
3.3.2. Compound 6b. Mp 274e276 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
10.40 (1H, s), 7.66 (1H, d, J¼7.8 Hz), 7.59 (1H, s), 7.53 (1H, d,
J¼7.2 Hz), 7.30 (1H, t, J¼7.8 Hz), 7.15 (1H, t, J¼7.5 Hz), 7.07 (1H, t,
J¼7.2 Hz), 6.98e6.90 (3H, m), 6.82 (1H, s), 6.75 (1H, t, J¼8.4 Hz),
6.70 (1H, d, J¼8.1 Hz), 6.64 (1H, d, J¼7.5 Hz), 2.15 (3H, s); 13C NMR
3.3.9. Compound 6i. Mp 173e175 ꢁC; 1H NMR (300 MHz, DMSO-d6)
(75 MHz, DMSO-d6)
d
174.3, 163.9, 146.5, 143.6, 138.3, 134.1, 131.4,
d
10.50 (1H, s), 7.62 (1H, d, J¼7.5 Hz), 7.43 (1H, d, J¼7.5 Hz), 7.37 (1H,
128.8, 128.7, 127.9, 127.1, 126.6, 123.1, 118.2, 115.1, 114.6, 109.3, 76.6,
21.2 IR (KBr) 3298, 3206, 3093, 1724, 1643, 1616, 1485, 1361, 1236,
1193, 1100, 1048, 963, 751 cmꢀ1; HRMS m/z (Mþ) calcd for
C22H17N3O2: 355.1321. Found: 355.1318.
d, J¼8.1 Hz), 7.35 (1H, s), 7.25e7.20 (3H, m), 7.14 (1H, d, J¼6.9 Hz),
7.09e7.02 (3H, m), 6.92 (1H, d, J¼7.8 Hz), 6.70 (1H, t, J¼7.2 Hz), 6.60
(1H, d, J¼8.1 Hz), 3.20 (1H, t, J¼9.3 Hz), 2.81 (1H, t, J¼9.0 Hz), 2.33
(2H, t, J¼6.6 Hz), 1.37e1.25 (4H, m); 13C NMR (75 MHz, DMSO-d6)
d
175.7, 163.8, 146.1, 142.6, 142.3, 133.6, 131.7, 128.6, 127.8, 127.5,
3.3.3. Compound 6c. Mp 276e278 ꢁC; 1H NMR (300 MHz, DMSO-
126.2, 126.0, 122.8, 117.9, 115.0, 114.2, 111.1, 75.6, 43.1, 35.0, 28.8,
28.1; IR (KBr) 3260, 2935, 1726, 1689, 1624, 1400, 1365, 1325, 1191,
1030, 749 cmꢀ1; HRMS m/z (Mþ) calcd for C25H23N3O2: 397.1790.
Found: 397.1794.
d6)
d
10.36 (1H, s), 7.66 (1H, d, J¼7.5 Hz), 7.56 (1H, s), 7.52 (1H, d,
J¼7.5 Hz), 7.29 (1H, t, J¼8.1 Hz), 7.15 (1H, t, J¼7.5 Hz), 7.08e6.87 (5H,
m), 6.77e6.63 (3H, m), 2.79e2.73 (1H, m),1.09 (6H, d, J¼6.9 Hz); 13C
NMR (75 MHz, DMSO-d6)
d 175.3, 163.6, 147.4, 146.0, 141.5, 135.6,
133.5, 130.6, 129.0, 127.5, 127.4, 126.3, 126.2, 122.1, 117.6, 114.5, 114.0,
110.0, 76.3, 32.7, 23.6, 23.5; IR (KBr) 3311, 3066, 2961, 1725, 1632,
1511, 1484, 1359, 1214, 1190, 1105, 1051, 955, 817, 752 cmꢀ1; HRMS
m/z (Mþ) calcd for C24H21N3O2: 383.1634. Found: 383.1630.
3.3.10. Compound 6j. Mp 170e171 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
10.53, (1H, s),7.66 (1H, d, J¼7.8 Hz), 7.52 (1H, d, J¼7.5 Hz), 7.42
(1H, d, J¼7.8 Hz), 7.37 (1H, s), 7.26 (1H, t, J¼7.5 Hz) 7.12 (1H, t,
J¼7.5 Hz), 6.95 (1H, d, J¼7.8 Hz), 6.72 (1H, t, J¼7.2 Hz), 6.62 (1H, d,
J¼8.1 Hz), 3.17e3.07 (1H, m), 2.83e2.74 (1H, m), 1.40e1.22 (2H, m),
1.13e1.00 (6H, m), 0.74 (3H, t, J¼6.9 Hz); 13C NMR (75 MHz, DMSO-
3.3.4. Compound 6d. Mp 295e296 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
(1H, t, J¼7.2 Hz), 7.18 (1H, t, J¼7.5 Hz), 7.09e6.92 (5H, m), 6.78e6.65
(3H, m); 13C NMR (75 MHz, DMSO-d6)
175.4, 163.9, 146.3, 141.4,
d
10.47 (1H, s), 7.67 (2H, t, J¼3.3 Hz), 7.59 (1H, d, J¼10.5 Hz), 7.31
d6) d 175.8, 163.8, 146.1, 142.6, 133.5, 131.7, 127.8, 127.5, 126.3, 122.8,
117.9, 115.0, 114.2, 111.0, 75.6, 43.3, 30.9, 28.0, 26.3, 22.1, 14.2; IR
(KBr) 3261, 2952, 2930, 2860, 1727, 1690, 1624, 1479, 1325, 1109,
1024, 943, 749 cmꢀ1; HRMS m/z (Mþ) calcd for C21H23N3O2:
349.1790. Found: 349.1793.
d
134.4, 134.3, 134.1, 129.8, 129.7, 127.9, 118.4, 116.2, 115.9, 114.8, 114.6,
114.2, 112.6, 76.9 IR (KBr) 3272, 3066, 1726, 1642, 1616, 1509, 1483,
1360, 1328, 1221, 1197, 1154, 1099, 961, 827, 750 cmꢀ1; HRMS m/z
(Mþ) calcd for C21H14FN3O2: 359.1070. Found: 359.1068.
3.3.11. Compound 6k. Mp 190e192 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
10.54 (1H, s), 7.66 (1H, d, J¼7.5 Hz) 7.52 (1H, d, J¼7.5 Hz), 7.39
3.3.5. Compound 6e. Mp 210e211 ꢁC; 1H NMR (300 MHz, DMSO-
(1H, t, J¼7.5 Hz), 7.33 (1H, s), 7.24 (1H, t, J¼7.2 Hz), 7.11 (1H, t,
J¼7.5 Hz), 6.94 (1H, d, J¼7.8 Hz), 6.73 (1H, t, J¼7.2 Hz), 6.64 (1H, d,
J¼7.8 Hz), 3.18e3.11 (1H, dd, J¼6.9 and 13.8 Hz), 2.79e2.71 (1H, dd,
J¼7.5 and 13.5 Hz), 1.58e1.27 (6H, m), 1.06e0.68 (5H, m); 13C NMR
d6)
d
10.34 (1H, s), 7.72 (1H, d, J¼7.8 Hz), 7.45 (1H, s), 7.36e7.24 (3H,
m), 7.17e7.15 (3H, m), 6.93e6.88 (3H, m), 6.83 (1H, d, J¼7.8 Hz), 6.76
(1H, t, J¼7.5 Hz), 6.67 (1H, d, J¼7.5 Hz), 4.48 (1H, d, J¼15.3 Hz), 4.15
(1H, d, J¼15.3 Hz); 13C NMR (75 MHz, DMSO-d6)
d
175.4, 164.5,
(75 MHz, DMSO-d6) d 175.7, 164.6, 146.2, 142.6, 133.5, 131.7, 127.7,
146.4, 142.9, 137.8, 133.8, 131.7, 128.2, 127.8, 127.2, 126.8, 126.7,
122.4, 118.1, 115.1, 114.4, 110.9, 75.5, 46.3. IR (KBr) 3297, 3090, 2944,
1727, 1625, 1483, 1383, 1323, 1242, 1191, 968. 750 cmꢀ1; HRMS m/z
(Mþ) calcd for C22H17N3O2: 355.1321. Found: 355.1318.
127.6,126.6,122.6,117.9,115.3,114.2,110.9, 75.7, 48.9, 37.4, 31.1, 31.0,
26.3, 26.0, 25.9; IR (KBr) 3265, 2925, 2851, 1732, 1622, 1483, 1440,
1391, 1322, 1189, 1111, 951, 750 cmꢀ1; HRMS m/z (Mþ) calcd for
C22H23N3O2: 361.1790. Found: 361.1791.
3.3.6. Compound 6f. Mp 257e258 ꢁC; 1H NMR (300 MHz, DMSO-
3.3.12. Compound 6l. Mp 261e263 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
10.26 (1H, s), 7.70 (1H, d, J¼7.8 Hz), 7.39 (1H, s), 7.35e7.22 (3H,
d6)
d
10.25 (1H, s), 8.30 (1H, s), 7.60 (1H, d, J¼7.5 Hz), 7.46 (1H, d,
m), 6.95e6.89 (3H, m), 6.81e6.71 (4H, m), 6.64 (1H, d, J¼8.1 Hz),
J¼6.9 Hz), 7.33 (1H, t, J¼7.5 Hz), 7.24 (1H, s), 7.20 (1H, d, J¼8.4 Hz),
7.05 (1H, t, J¼6.9 Hz), 6.84 (1H, d, J¼8.1 Hz), 6.68 (1H, t, J¼7.5 Hz),
4.35 (1H, d, J¼15.0 Hz), 4.18 (1H, d, J¼15.3 Hz), 2.22 (3H, s); 13C NMR
(75 MHz, DMSO-d6)
d
174.9, 163.9, 145.9, 142.4, 135.7, 134.1, 133.2,
6.61 (1H, d, J¼8.1 Hz); 13C NMR (75 MHz, DMSO-d6)
d 176.4, 164.3,
131.1, 128.2, 127.4, 127.3, 126.2, 121.8, 117.5, 114.6, 113.8, 110.3, 74.9,
45.4, 20.6; IR (KBr) 3322, 3092, 2946, 1726, 1625, 1482, 1435, 1379,
1324, 1242, 1198, 1113, 1027, 963, 747 cmꢀ1; HRMS m/z (Mþ) calcd
for C23H19N3O2: 369.1477. Found: 369.1475.
147.2, 142.5, 133.7, 131.2, 129.9, 127.3, 125.7, 122.7, 117.6, 114.8, 114.3,
110.5, 71.4; IR (KBr) 3474, 3288, 3066, 1708, 1621, 1519, 1478, 1326,
1266, 1192, 1151, 1105, 1048, 960, 750 cmꢀ1; HRMS m/z (Mþ) calcd
for C15H11N3O2: 265.0851. Found: 265.0847.
3.3.7. Compound 6g. Mp 227e228 ꢁC; 1H NMR (300 MHz, DMSO-
3.3.13. Compound 6m. Mp 277e279 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
10.20 (1H, s), 7.71 (1H, d, J¼7.8 Hz), 7.37e7.22 (4H, m), 6.95
d6)
d
10.54 (1H, s), 7.74 (1H, s), 7.68 (1H, d, J¼8.4 Hz), 7.66 (1H, s),
(1H, t, J¼7.8 Hz), 6.81e6.62 (7H, m), 4.28 (2H, s), 3.68 (3H, s); 13C
7.35e7.18 (5H, m), 7.03 (2H, d, J¼7.8 Hz), 6.77 (1H, t, J¼6.9 Hz), 6.70
NMR (75 MHz, DMSO-d6)
d 174.9, 163.9, 158.1, 145.9, 142.5, 133.2,
(1H, d, J¼8.1 Hz), 6.60 (1H, d, J¼8.1 Hz); 13C NMR (75 MHz, DMSO-
131.1, 128.9, 127.3, 126.3, 121.9, 117.5, 114.7, 113.8, 113.1, 110.4, 74.8,
54.9, 45.1; IR (KBr) 3280, 3062, 2957, 1723, 1640, 1477, 1326, 1118,
1024, 944, 752 cmꢀ1; HRMS m/z (Mþ) calcd for C23H19N3O3:
385.1426. Found: 385.1423.
d6) d 175.08, 163.2, 145.7, 140.9, 137.8, 133.7, 133.5, 129.4, 129.2,
128.7, 127.7, 127.4, 117.8, 117.6, 114.5, 114.09, 113.6, 112.09, 76.3; IR
(KBr) 3372, 3324, 3247, 1742, 1619, 1484, 1361, 1276, 1190, 1067, 873,
814, 750 cmꢀ1; HRMS m/z (Mþ) calcd for C21H14BrN3O2: 419.0269.
Found: 419.0272.
3.3.8. Compound 6h. Mp 287e288 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
7.46e7.41 (2H, m), 7.28e7.10 (5H, m), 6.96 (1H, d, J¼7.8 Hz), 6.80
(2H, d, J¼8.1 Hz), 6.73 (1H, t, J¼7.2 Hz), 6.63 (1H, d, J¼7.8 Hz), 3.36
d
10.56 (1H, s), 7.68 (1H, d, J¼7.5 Hz), 7.53 (1H, d, J¼7.2 Hz),
3.3.14. Compound 6n. Mp 275e277 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
m), 7.14e7.08 (4H, m), 6.78 (1H, t, J¼7.2 Hz), 6.70 (1H, d, J¼8.4 Hz),
d 10.60 (1H, s), 7.80 (1H, s), 7.70e7.66 (2H, m), 7.38e7.30 (2H,

9634
M. Narasimhulu, Y.R. Lee / Tetrahedron 67 (2011) 9627e9634
6.64 (1H, d, J¼8.4 Hz); 13C NMR (75 MHz, DMSO-d6)
d 173.6, 163.6,
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Int. Ed. 1999, 38, 3186; (c) Ashimori, A.; Bachand, B.; Overman, L. E.; Poon, D. J. J.
Am. Chem. Soc. 1998, 120, 6477; (d) Matsuura, T.; Overman, L. E.; Poon, D. J. J. Am.
Chem. Soc. 1998, 120, 6500.
22. Mohammadi, A. A.; Dabiri, M.; Qaraat, H. Tetrahedron 2009, 65, 3804.
23. (a) Bolm, C.; Rantanen, T.; Schiffers, I.; Zani, L. Angew. Chem., Int. Ed. 2005, 44,
1758; (b) Berrisford, D. J.; Bolm, C.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
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146.0, 143.0, 134.0, 133.7, 131.0, 127.4, 126.4, 126.1, 122.8, 117.8, 115.5,
115.3, 114.3, 114.1, 108.9, 76.2. IR (KBr) 3269, 1732, 1641, 1618, 1510,
1482, 1359, 1225, 1195, 954, 823, 750 cmꢀ1; HRMS m/z (Mþ) calcd
for C21H13BrFN3O2: 437.0175. Found: 437.0174.
3.3.15. Compound 6o. Mp 238e240 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
7.70 (1H, d, J¼7.5 Hz), 7.61 (2H, d, J¼7.8 Hz), 7.34e7.13 (5H, m),
7.01 (1H, t, J¼6.9 Hz), 6.93 (2H, d, J¼7.5 Hz), 6.85 (1H, d, J¼8.1 Hz),
6.78 (1H, t, J¼7.5 Hz), 6.72 (1H, d, J¼8.1 Hz), 3.02 (3H, s); 13C NMR
(75 MHz, DMSO-d6)
d 173.8, 163.5, 146.0, 143.1, 137.9, 133.6, 130.9,
128.6, 127.6, 127.4, 126.6, 126.1, 122.7, 117.8, 116.2, 114.5, 114.1, 108.9,
76.1, 25.9; IR (KBr) 3265, 1728, 1636, 1616, 1491, 1362, 1274, 1172,
1128, 1093, 942, 884, 751 cmꢀ1; HRMS m/z (Mþ) calcd for
C22H17N3O2: 355.1321. Found: 355.1318.
3.3.16. Compound 6p. Mp 232e234 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
7.71 (1H, d, J¼8.1 Hz), 7.60 (1H, d, J¼7.5 Hz), 7.58 (1H, s),
7.36e7.25 (2H, m), 7.09e6.94 (3H, m), 6.87 (1H, d, J¼7.5 Hz),
6.81e6.71 (4H, m), 3.03 (3H, s), 2.15 (3H, s); 13C NMR (75 MHz,
DMSO-d6) d 173.7,163.4,146.0,143.1,137.8,133.5,130.8,129.5,128.2,
128.1, 127.3, 126.6, 126.0, 122.6, 117.7, 114.5, 114.0, 108.8, 76.07, 25.8,
20.5; IR (KBr) 3283, 3059, 2935, 1727, 1643, 1612, 1487, 1356, 1244,
1167,1125,1090,1038, 965, 872, 751 cmꢀ1; HRMS m/z (Mþ) calcd for
C23H19N3O2: 369.1477. Found: 369.1475.
3.3.17. Compound 6q. Mp 220e222 ꢁC; 1H NMR (300 MHz, DMSO-
d6)
d
7.68 (1H, d, J¼7.8 Hz), 7.64e7.60 (2H, m), 7.34e7.25 (2H, m),
7.05e6.95 (5H, m), 6.86 (1H, d, J¼7.8 Hz), 6.77 (1H, t, J¼7.8 Hz), 6.69
(1H, d, J¼7.5 Hz), 3.01 (3H, s); 13C NMR (75 MHz, DMSO-d6)
d 174.1,
164.1, 146.5, 143.5, 134.6, 134.5, 134.2, 131.5, 127.9, 126.9, 126.6,
123.3, 118.3, 116.1, 115.8, 114.8, 114.6, 109.5, 76.7, 26.4; IR (KBr) 3274,
3061, 2943,1727,1640,1613,1510,1354,1219,1155,1130,1093,1033,
961, 799, 752 cmꢀ1; HRMS m/z (Mþ) calcd for C22H16FN3O2:
373.1227. Found: 373.1227.
24. (a) Lee, Y. R.; Choi, J. H.; Yoon, S. H. Tetrahedron Lett. 2005, 46, 7539; (b) Lee, Y.
R.; Lee, W. K.; Noh, S. K.; Lyoo, W. S. Synthesis 2006, 853; (c) Lee, Y. R.; Kim, D. H.
Synthesis 2006, 603; (d) Lee, Y. R.; Kim, J. H. Synlett 2007, 2232; (e) Wang, X.;
Lee, Y. R. Tetrahedron Lett. 2007, 48, 6275; (f) Wang, X.; Lee, Y. R. Synthesis 2007,
3044; (g) Lee, Y. R.; Xia, L. Synthesis 2007, 3240; (h) Lee, Y. R.; Kim, Y. M. Helv.
Chim. Acta 2007, 90, 2401; (i) Lee, Y. R.; Li, X.; Kim, J. H. J. Org. Chem. 2008, 73,
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Acknowledgements
This study was supported by grant No. RTI04-01-04 from the
Regional Technology Innovation Program of the Ministry of
Knowledge Economy (MKE).
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