Novel, one-pot, three-component route to indol-3-yl substituted spirooxindole derivatives

Article abstract of DOI:10.1021/cc100064c

A simple and efficient approach to the synthesis of a novel series of polysubstituted 6′-(1H-indol-3-yl)-1′,7′- dihydrospiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2-one derivatives in high yields was developed from a one-pot, three-component reaction of 3-cyanoacetyl indoles, isatins, and 1H-pyrazol-5-amines in H₂O/HOAc.

Full text of DOI:10.1021/cc100064c

J. Comb. Chem. 2010, 12, 659–663
659
Novel, One-Pot, Three-Component Route to Indol-3-yl Substituted
Spirooxindole Derivatives
Tao Chen, Xiao-Ping Xu, and Shun-Jun Ji*
Key Laboratory of Organic Synthesis of Jiangsu ProVince, College of Chemistry, Chemical Engineering
and Materials Science, Soochow UniVersity, Suzhou 215123, China
ReceiVed April 15, 2010
A simple and efficient approach to the synthesis of a novel series of polysubstituted 6′-(1H-indol-3-yl)-
1′,7′-dihydrospiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2-one derivatives in high yields was developed from
a one-pot, three-component reaction of 3-cyanoacetyl indoles, isatins, and 1H-pyrazol-5-amines in H2O/
HOAc.
Introduction
focused on the development of new methodologies to
synthesize many kinds of pyrazolopyridine ring systems
because of their interesting biological and pharmacological
properties, such as vasodilatory, hypoglycemic, anti-inflam-
matory, analgesic, and antipyretic activities.17,18 Furthermore,
spiro[indoline-3,4′-pyrazolo[3,4-b]pyridines] seem to be
promising candidates for biological responses because it has
been reported that sharing of the indole 3-carbon atom in
the formation of spirooxindole derivatives highly enhances
biological activity.19-21
A wide range of advantages offered by multicomponent
reactions (MCRs), such as high degree of atom economy,
convergence, ease of execution, and access to complex
molecules has been recognized in the past decade. The utility
of MCRs in preparing libraries to screen for biologically
active compounds and potent drug candidates is well-
appreciated.1 Thus, the search and discovery of new MCRs
is still of considerable current interest.
The indole ring system is probably the most ubiquitous
heterocycle in nature. Because of the great structural diversity
of biologically active indoles, it is not surprising that the
indole ring system has become an important structural
component in many pharmaceutical agents.2 Furthermore,
indoles substituted with heterocyclic rings at the 3-position
have been found in a fascinating array of bioactive natural
products and pharmaceutical compounds (Figure 1). New
indole alkaloids with a broad spectrum of biological proper-
ties are being discovered rapidly as marine invertebrate
metabolites.3-6 For example, nortopsentins A-C exhibit in
vitro cytotoxicity against P388 cells;7 hamacanthin B reveals
cytotoxic activities against a wide range of human tumor
cell lines with GI50 values at micromolar concentration;8
meridianins A-E show cytotoxicity toward murine tumor
cell lines and have potent inhibition against several protein
kinases.9 Moreover, many other analogous indole deriva-
tives10-13 demonstrate strong inhibitory effects against a
variety of tumor cell lines, including leukemia, non-small-
cell lung cancer, ovarian cancer, colon cancer, renal cancer,
and breast cancer.
Despite the potent and diverse biological activities of
indoles and spiro[indoline-3,4′-pyrazolo[3,4-b]pyridines], no
report is yet available on the synthesis of substituted indoles
containing spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine] struc-
tures at the 3-position. Out of our interest in the multicom-
ponent synthesis and in continuation of our work on the
synthesis of indole and spirooxindole derivatives,22 guided
by the observation that the presence of two or more different
heterocyclic moieties in a single molecule often enhances
the biocidal profile remarkably and that water is a nontoxic,
cheap, abundantly available and environmentally benign
solvent,23 herein, we report the synthesis of various polysub-
stituted 6′-(1H-indol-3-yl)-1′,7′-dihydrospiro[indoline-3,4′-
pyrazolo[3,4-b]pyridine]-2-one derivatives via a facile, atom-
economical, one-pot, three-component condensation reaction
in H2O/HOAc.
Results and Discussion
The reaction of 3-(1H-indol-3-yl)-3-oxopropanenitrile 1a
(0.5 mmol) with an equimolar amount of 5-bromoindoline-
2,3-dione 2a and 3-methyl-1-phenyl-1H-pyrazol-5-amine 3a
as a simple model system was examined to establish the
feasibility of the strategy and optimize the reaction condi-
tions. It is well-known that the choice of an appropriate
reaction medium is of crucial importance for successful
synthesis. The growing demand for clean and efficient eco-
friendly chemical synthesis has been increasing our interest
in synthesizing indole derivatives. So, to begin with, the
model reaction was employed in water without any catalyst
at 100 °C (Table 1, entry 1). To our delight, the saffron
On the other hand, spirooxindole derivatives occupy a
special place in organic and medicinal chemistry because
these compounds are well-known as microtubule assembly
inhibitors (spirotryprostatin A and B),14 muscarinic M1, and
serotonin receptor modulators (pteropodine and isopteropo-
dine)15 and nonpeptidyl growth-hormone secretagogues
(MK-0677).16 Similarly, considerable attention has been
* To whom correspondence should be addressed. E-mail: chemjsj@
suda.edu.cn.
10.1021/cc100064c  2010 American Chemical Society
Published on Web 07/01/2010

660 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 5
Chen et al.
Figure 1. Representatives of important indol-3-yl substituted heterocycles and spirooxindoles.
Table 1. Model Reaction, Conditions, and Yieldsa
Scheme 1. Synthesis of the Intermediate 5a
solvent
(H2O/HOAc)
(v/v)
temperature
time
(h)
yield
(%)
entry
(°C)
4a was not obtained. Instead, compound 5a, which is a
Baylis-Hillman type adduct of 2a and 3a was isolated even
when the reaction time was prolonged to 24 h (Scheme 1).24
The intermediate 5a was characterized by spectroscopic
methods. Considering the above observation, a variety of
Lewis and Brønsted acid catalysts, such as CeCl3 · 7H2O,
Yb(OTf)3, InCl3, HOAc, p-toluenesulfonic acid, and HCl
were tested (Table 1, entries 2-7), but the results was also
disappointing because the desired product 4a was only
obtained in trace amount. Although the yield was very low,
we were encouraged to examine other reaction conditions
to increase the yield. Thus, H2O/HOAc was employed as
solvent in this reaction considering that intermediate 5a was
obtained in excellent yield when the solvent was water and
that HOAc can be used as both catalyst and solvent because
of the very low solubility of 1a and 5a. The volume ratio
1:1 (H2O/HOAc) gave the better result at 100 °C, as shown
in Table 1, entry 9. Then, the synthesis of 4a was performed
at temperatures ranging from 120 to 140 °C and reaction
times ranging from 6 to 12 h in H2O/HOAc (1:1 v/v) (Table
1, entries 11-13). The yield of 4a was highest (80%) when
the reaction was carried out at 140 °C for 12 h in the mixed
1
2b
3b
4b
5b
6b
7b
8
1:0
1:0
1:0
1:0
1:0
1:0
1:0
2:1
1:1
1:2
1:1
1:1
1:1
0:1
100
100
100
100
100
100
100
100
100
100
120
140
140
120
140
140
24
12
12
12
12
12
12
12
12
12
12
12
6
0
trace
trace
trace
trace
trace
trace
38
48
50
66
80
9
10
11
12
13
14
15c
16d
52
61
30
37
12
12
12
a Isolated yield.
b The reaction was catalyzed by 10 mol
%
CeCl3 · 7H2O, Yb(OTf)3, InCl3, HOAc, p-toluenesulfonic acid or HCl
respectively. c The reaction was carried out in H2O/(CH2OH)2 (1:1 v/v).
d The reaction was catalyzed by 10 mol % HOAc in H2O/(CH2OH)2 (1:1
v/v).
yellow color of 2a faded out during the reaction. After
heating for 2 h, 2a and 3a almost disappeared according to
thin layer chromatography analysis. Unfortunately, product

Indol-3-yl Substituted Spirooxindole Derivatives
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 5 661
Scheme 2. Synthesis of 6′-(1H-Indol-3-yl)-1′,7′-dihydrospiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2-one Derivatives 4
Table 2. 6′-(1H-Indol-3-yl)-1′,7′-dihydrospiro[indoline-3,4′-
pyrazolo[3,4-b]pyridine]-2-one Derivatives 4
observation, compound 4 could be formed from the inter-
mediate 5 via nucleophilic substitution and condensation with
3-cyanoacetyl indole 1, followed by tautomerization (Scheme
3). Evidence supporting this proposed mechanism came from
the observation that when the intermediate 5a was prepared
as a separate exercise and subsequently reacted with 1a under
the same conditions, the expected product 4a was obtained
in a yield similar to that obtained in the one-pot reaction
(Scheme 4).
entry
R1
R2
R3
X
product
yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
H
H
H
H
6-CH3
6-CH3
6-CH3
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
5-Br
5-Cl
6-Br
H
5-Br
5-Cl
6-Br
5-Br
5-Cl
6-Br
H
5-Br
6-Br
H
5-Br
5-Cl
6-Br
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
80
82
81
87
83
86
81
78
80
81
86
88
85
82
90
86
81
92
80
88
87
84
82
88
90
83
H
H
H
In summary, we have demonstrated a simple, atom-
economical, and efficient approach for synthesis of highly
functionalized indole-containing spirooxindole derivatives via
one-pot, three-component reactions using readily available
starting materials. This method incorporates both indole and
spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine] moieties into a
single molecule. In view of those molecules having either
functionality, these novel compounds may potentially have
enhanced biological activities. Prominent among the advan-
tages of this new method are novelty, operational simplicity,
high yields, and easy workup procedures employed. Further
reactivity studies and synthetic applications of this methodol-
ogy are in progress in our laboratory.
7-CH3
7-CH3
7-CH3
5-Br
5-Br
5-Br
5-Br
H
Ph
Ph
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
5-Br
6-Br
H
5-Br
6-Br
H
H
H
4t
4u
4v
4w
4x
4y
4z
6-CH3
6-CH3
6-CH3
5-Br
5-Br
H
H
5-Br
6-Br
a Isolated yield.
Experimental Section
Typical Procedure for the Synthesis of 5-Bromo-6′-(1H-
indol-3-yl)-3′-methyl-2-oxo-1′-phenyl-1′,7′-dihydrospiro[in-
doline-3,4′-pyrazolo[3,4-b]pyridine]-5′-carbonitrile 4a. A mix-
ture of 3-(1H-indol-3-yl)-3-oxopropanenitrile 1a (0.5 mmol)
with an equimolar amount of 5-bromoindoline-2,3-dione 2a
and 3-methyl-1-phenyl-1H-pyrazol-5-amine 3a in 4 mL of
H2O/HOAc (1:1 v/v) at 140 °C was stirred for 12 h (the
progress was monitored by TLC). After completion, the
reaction mixture was neutralized by the freshly prepared
saturated solution of NaHCO3; then, it was filtered. The
precipitate was washed with water (10 mL) and ethanol (5
mL) to afford the pure 4a as a white solid (yield 80%). mp:
243-245 °C. IR (KBr): ν 3425, 3356, 3090, 2195, 1730,
solvent (Table 1, entry 12), in contrast with HOAc as sole
solvent (Table 1, entry 14) or H2O/(CH2OH)2 as mixed
solvent (Table 1, entries 15 and 16).
Encouraged by this success, we extended this reaction to
commercially available isatins, 1H-pyrazol-5-amines and a
range of 3-(1H-indol-3-yl)-3-oxopropanenitriles with both
electron withdrawing and electron releasing substituents in
indole heterocycles under the same conditions, resulting in
high yields of the corresponding 6′-(1H-indol-3-yl)-1′,7′-
dihydrospiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2-one de-
rivatives (Scheme 2). We have shown that the use of a range
of substituents in 3-(1H-indol-3-yl)-3-oxopropanenitriles 1,
isatins 2 and 1H-pyrazol-5-amines 3 in this three-component
reaction makes possible the synthesis of libraries under the
same circumstances. The results are summarized in Table
2. In this work, the products were characterized by melting
point, IR, NMR, HRMS (or LC-MS) and combustion
analysis. Furthermore, the structure of 4d was established
by X-ray crystallographic analysis (see Supporting Informa-
tion).
1
1629, 1529, 1472, 1394, 1217, 752 cm-1. H NMR (400
MHz, DMSO-d6) (δ, ppm): 11.70 (s, 1H, NH), 10.81 (s, 1H,
NH), 10.06 (s, 1H, NH), 7.86 (d, J ) 1.6 Hz, 1H, ArH),
7.71 (d, 1H, J ) 7.2 Hz, ArH), 7.65 (d, J ) 8.0 Hz, 2H,
ArH), 7.47-7.55 (m, 4H, ArH), 7.36-7.41 (m, 2H, ArH),
7.16-7.22 (m, 2H, ArH), 6.94 (d, J ) 8.4 Hz, 1H, ArH),
1.61 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) (δ, ppm):
177.8, 147.2, 144.3, 140.4, 138.3, 138.2, 136.9, 136.0, 132.0,
129.2, 128.4, 127.9, 127.1, 125.4, 123.4, 122.0, 120.1, 120.0,
Although the detailed mechanism of the above reaction
remains to be fully clarified, according to the experimental

662 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 5
Scheme 3. Possible Mechanism for the Synthesis of Product 4
Chen et al.
Scheme 4. Synthesis of 4a According to the Reaction of 1a
and 5a
crystallography for compounds 4d. This material is available
free of charge via the Internet at http://pubs.acs.org.
References and Notes
(1) (a) Wender, P. A.; Handy, S. T.; Wright, D. L. Chem. Ind.
1997, 765. (b) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995,
34, 259. (c) Weber, L.; Illgen, K.; Almstetter, M. Synlett 1999,
366. (d) Bienayme´, H.; Hulme, C.; Oddon, G.; Schmitt, P.
Chem.sEur. J. 2000, 6, 3321. (e) Terrett, N. K. Combinatorial
Chemistry; Oxford University Press: New York, 1998.
(2) (a) Sundberg, R. J. The Chemistry of Indoles; Academic Press:
New York, 1970. (b) Sundberg, R. J. Pyrroles and Their
Benzoderivatives: Synthesis and Applications. In Compre-
hensiVe Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Eds.; Pergamon: Oxford, U.K., 1984; Vol. 4, pp 313-376.
(c) Sundberg, R. J. In Best Synthetic Methods, Indoles;
Academic Press: New York, 1996; pp 7-11. (d) Joule, J. A.
Indole and its Derivatives. In Science of Synthesis: Houben-
Weyl Methods of Molecular Transformations; Thomas, E. J.,
Ed.; George Thieme Verlag: Stuttgart, Germany, 2000;
Category 2, Vol. 10, Chapter 10.13. (e) Brown, R. K. In
Indoles; Houlihan, W. J., Ed.; Wiley-Interscience: New York,
1972. (f) Sundberg, R. J. In ComprehensiVe Heterocyclic
Chemistry II; Katritzky, A. R., Ress, C. W., Scriven, E. F. V.,
Bird, C. W., Eds.; Pergamon Press: Oxford, 1996; Vol. 2, p
119. (g) Gribble, G. W. ComprehensiVe Heterocyclic Chem-
istry II; Katritzky, A. R., Ress, C. W., Scriven, E. F. V., Bird,
C. W., Eds.; Pergamon Press: Oxford, 1996; Vol. 2, p 207.
(h) Indoles; Sundberg, R. J., Ed.; Academic Press: London,
1996.
119.6, 114.4, 112.2, 111.8, 107.9, 98.5, 78.8, 51.3, 11.4.
HRMS: calculated for C29H19BrN6O [MH+]: 547.0876; found
547.0867.
Acknowledgment. The work was partially supported by
the National Natural Science Foundation of China (No.
20672079, 20910102041), Natural Science Foundation of
Jiangsu Province (No. BK 2006048), Nature Science Key
Basic Research of Jiangsu Province for Higher Education
(No. 06KJ A15007), the Specialized Research Fund for the
Doctoral Program of Higher Education (No. 20060285001),
and Key Project in Science and Technology Innovation
Cultivation Program of Soochow University.
Supporting Information Available. Experimental details
and characterization data including IR, MS, 1H, and 13C NMR
spectra for compounds 4a-z and 5a, as well as X-ray
(3) Sundberg, R. J. The Chemistry of Indoles; Academic Press:
New York, 1996.

Indol-3-yl Substituted Spirooxindole Derivatives
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 5 663
(4) (a) Casapullo, A.; Bifulco, G.; Bruno, I.; Riccio, R. J. Nat.
Prod. 2000, 63, 447. (b) Bao, B.; Sun, Q.; Yao, X.; Hong, J.;
Lee, C. O.; Sim, C. J.; Im, K. S.; Jung, J. H. J. Nat. Prod.
2005, 68, 711.
(5) Skibo, E. B.; Xing, C.; Dorr, R. T. J. Med. Chem. 2001, 44,
3545.
(6) (a) Gupta, L.; Talwar, A.; Palne, N. S.; Gupta, S.; Chauhan,
P. M. S. Bioorg. Med. Chem. Lett. 2007, 17, 4075. (b) Kaniwa,
K.; Arai, M. A.; Li, X.; Ishibashi, M. Bioorg. Med. Chem.
Lett. 2007, 17, 4254.
(15) Kang, T. H.; Matsumoto, K.; Murakami, Y.; Takayama, H.;
Kitajima, M.; Aimi, N.; Watanabe, H. Eur. J. Pharmacol.
2002, 444, 39.
(16) (a) Maligres, P. E.; Houpis, I.; Rossen, K.; Molina, A.; Sager,
J.; Upadhyay, V.; Wells, K. M.; Reamer, R. A.; Lynch, J. E.;
Askin, D.; Volante, R. P.; Reider, P. J. Tetrahedron 1997,
53, 10983. (b) Palucki, B. L.; Feighner, S. D.; Pong, S. S.;
McKee, K. K.; Hrenuik, D. L.; Tan, C.; Howard, A. D.; Van
der Ploeg, L. H. Y.; Patchett, A. A.; Nargund, R. P. Bioorg.
Med. Chem. Lett. 2001, 11, 1955.
(17) (a) Gein Stein, R.; Biel, J. H.; Singh, T. J. Med. Chem. 1979,
13, 153. (b) Farghaly, A. M.; Habib, N. S.; Khalil, M. A.;
El-Sayed, O. A. Alexandria J. Pharm. Sci. 1989, 3, 90. (c)
Gatta, F.; Pomponi, M.; Marta, M. J. Heterocycl. Chem. 1991,
28, 1301. (d) Kohara, T.; Fukunaga, K.; Fujimura, M.;
Hanano, T.; Okabe, H. U. S. Patent 0052822, 2004.
(18) (a) Elnagdi, M. H.; Al-awadi, N.; Erian, A. N.; In Compen-
satiVe Heterocyclic Chemistry II, 1st ed.; Katritzky, A. R.,
Rees, C. W., Scriven, E. F. V., Eds.; Pergamon Press, Oxford,
U.K., 1996; Vol. 7, p 431. (b) Ghahremanzadeh, R.; Sayyafi,
M.; Ahadi, S.; Bazgir, A. J. Comb. Chem. 2009, 11, 393. (c)
Ahadi, S.; Ghahremanzadeh, R.; Mirzaei, P.; Bazgir, A.
Tetrahedron 2009, 65, 9316.
(19) Da-Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J. Braz. Chem.
Soc. 2001, 12, 273.
(20) (a) Joshi, K. C.; Chand, P. Pharmazie 1982, 37, 1. (b) Joshi,
K. C.; Jain, R.; Sharma, K. J. Indian Chem. Soc. 1988, 115,
202.
(21) Abdel-Rahman, A. H.; Keshk, E. M.; Hanna, M. A.; El-Bady,
Sh. M. Bioorg. Med. Chem. 2004, 12, 2483.
(7) (a) Sakemi, S.; Sun, H. H. J. Org. Chem. 1991, 56, 4304. (b)
Kawasaki, I.; Yamashita, M.; Ohta, S. Chem. Pharm. Bull.
1996, 44, 1831.
(8) (a) Kouko, T.; Matsumura, K.; Kawasaki, T. Tetrahedron
2005, 61, 2309. (b) Higuchi, K.; Takei, R.; Kouko, T.;
Kawasaki, T. Synthesis 2007, 669.
(9) (a) Jiang, B.; Yang, C.-G.; Xiong, W.-N.; Wang, J. Bioorg.
Med. Chem. 2001, 9, 1149. (b) Gompel, M.; Leost, M.; Joffe´,
E. B. K.; Puricelli, L.; Franco, L. H.; Palermo, J.; Meijer, L.
Bioorg. Med. Chem. Lett. 2004, 14, 1703.
(10) (a) Jiang, B.; Xiong, X.; Yang, C. Bioorg. Med. Chem. Lett.
2001, 11, 475. (b) Jiang, B.; Gu, X. Bioorg. Med. Chem. Lett.
2000, 10, 363. (c) Gu, X.; Wan, X.; Jiang, B. Bioorg. Med.
Chem. Lett. 1999, 9, 569. (d) Jiang, B.; Xiong, X.; Yang, C.
Bioorg. Med. Chem. 2001, 9, 1149. (e) Xiong, W.; Yang, C.;
Jiang, B. Bioorg. Med. Chem. 2001, 9, 1773. (f) Diana, P.;
Carbone, A.; Barraja, P.; Montalbano, L.; Martorana, A.;
Dattolo, G.; Gia, O.; Via, D. L.; Cirrincione, G. Bioorg. Med.
Chem. Lett. 2007, 17, 2342. (g) Kawasaki, Y.; Yamashita,
M.; Otha, S. J. Chem. Soc., Chem. Commun. 1994, 2085. (h)
Kawasaki, Y.; Yamashita, M.; Otha, S. Chem. Pharm. Bull.
1996, 44, 1831. (i) Kawasaki, Y.; Katsuma, H.; Nakayama,
Y.; Yamashita, M.; Otha, S. Heterocycles 1998, 48, 1887.
(11) (a) Sun, H. H.; Sakemi, J. J. Org. Chem. 1991, 56, 4307. (b)
Vervoort, H. C.; Richards-Gross, S. E.; Fenical, W.; Lee,
A. Y.; Clardy, J. J. Org. Chem. 1997, 62, 1486. (c) Takahashi,
S.; Matsunaga, T.; Hasegawa, C.; Saito, H.; Fujita, D.; Kiuchi,
F.; Tsuda, Y. Chem. Pharm. Bull. 1998, 46, 1527.
(12) (a) N’Diaye, Y.; Guella, G.; Chiasera, G.; Mancini, Y.; Pietra,
F. Tetrahedron Lett. 1994, 50, 4147. (b) Guella, G.; Mancini,
Y.; N’Diaye, Y.; Pietra, F. HelV. Chim. Acta 1999, 77, 1994.
(13) (a) Bergmann, T.; Schories, D.; Steffan, B. Tetrahedron 1997,
53, 2055. (b) Kohmoto, S.; Kashman, Y.; McConnell, O. J.;
Rinehart, K. L.; Wright, A., Jr.; Koehn, F. J. Org. Chem. 1988,
53, 3116.
(14) (a) Khafagy, M. M.; El-Wahas, A. H. F. A.; Eid, F. A.; El-
Agrody, A. M. Farmaco 2002, 57, 715. (b) Sebahar, P. R.;
Williams, R. M. J. Am. Chem. Soc. 2000, 122, 5666.
(22) (a) Ji, S.-J.; Wang, S.-Y. Synlett 2003, 2074. (b) Ji, S.-J.;
Wang, S.-Y.; Zhang, Y.; Loh, T.-P. Tetrahedron 2004, 60,
2051. (c) Gu, D.-G.; Ji, S.-J.; Jiang, Z.-Q.; Zhou, M.-F.; Loh,
T.-P. Synlett 2005, 959. (d) Wang, S.-Y.; Ji, S.-J. Tetrahedron
2006, 62, 1527. (e) Sun, C.; Ji, S.-J. Tetrahedron Lett. 2007,
48, 8987. (f) Wang, S.-Y.; Ji, S.-J. Synlett 2007, 2222. (g)
Zhu, S.-L.; Ji, S.-J.; Zhang, Y. Tetrahedron 2007, 63, 9365.
(h) Zhu, S.-L.; Ji, S.-J.; Su, X.-M.; Sun, C.; Liu, Y.
Tetrahedron Lett. 2008, 49, 1777. (i) Zhu, S.-L.; Ji, S.-J.; Zhao,
K.; Liu, Y. Tetrahedron Lett. 2008, 49, 2578. (j) Zhao, K.;
Xu, X.-P.; Zhu, S.-L.; Shi, D.-Q.; Zhang, Y.; Ji, S.-J. Synthesis
2009, 2697. (k) Zhao, K.; Zhu, S.-L.; Shi, D.-Q.; Zhang, Y.;
Xu, X.-P.; Ji, S.-J. Synthesis 2010, 1793.
¨
(23) (a) LindstrOm, U. M. Chem. ReV. 2002, 102, 2751. (b)
Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35, 209.
(24) Pushechnikov, A; Volochnyuk, D.; Tolmachev, A. Synlett
2002, 1140.
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