An efficient four-component synthesis of spiro[indoline-pyrazolo[4′, 3′:5,6]pyrido[2,3-d]pyrimidine]triones

Article abstract of DOI:10.1002/cjoc.201180471

A four-component reaction in the presence of Alum [KAl(SO₄) ₂middot;12H₂O] as an inexpensive and reusable catalyst using the ionic liquid as an effective green reaction media is reported. Copyright

Full text of DOI:10.1002/cjoc.201180471

FULL PAPER
DOI: 10.1002/cjoc.201180471
An Efficient Four-component Synthesis of Spiro[indoline-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]triones
Ghahremanzadeh, Ramin*,a
Bazgir, Ayoobb
Moghaddam, Mojtaba Mirhosseinia
Akhondi, Mohammad Mehdic
a Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
b Department of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396-4716, Tehran, Iran
c Reproductive Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
A four-component reaction in the presence of Alum [KAl(SO4)2•12H2O] as an inexpensive and reusable catalyst
using the ionic liquid as an effective green reaction media is reported.
Keywords catalysis, condensation, cyclization, green chemistry, ionic liquids, multicomponent reaction, spiro
compounds
Introduction
dole ring systems are the central structural framework
that are present in numerous bioactive natural products
such as spirotryprostatin A and pteropodine (Figure
1).[16] Accordingly, the development of new and simple
synthetic methods for the preparation of spirooxindole
derivatives is an interesting challenge. Consequently,
many synthetic methodologies have been developed for
constructing these spirooxindole derivatives, most of
which are based on cycloaddition or condensation reac-
tions.[17]
Multicomponent reactions (MCRs) are one-pot
processes in which three or more reactants come to-
gether in a single reaction vessel to form a product con-
taining substantial elements of all the reactants.[1] This
methodology allows molecular diversity and complexity
to create facile formation of several new covalent bonds
in a one-pot transformation, which is quite closely ap-
proaching the concept of an ideal synthesis.[2] Multi-
component reactions have been provd to be a valuable
asset in medicinal chemistry, drug design, and drug
discovery because of their simplicity, efficiency and
high selectivity. Such protocols can reduce the number
of steps and present advantages, such as low energy
consumption and little to no waste production, leading
to desired environmentally friendly processes. They
lead to interesting heterocyclic scaffolds, which are par-
ticularly useful for the combinatorial chemistry as pow-
erful tools[3] because of their valuable features such as
atom-economy, environmental concerns, straightfor-
ward reaction design, and the opportunity to construct
target compounds by the introduction of several diver-
sity elements in a single chemical operation.[4]
The indole nucleus is probably the most well-known
heterocycle, a common and important feature of a vari-
ety of natural products and medicinal agents.[5] Com-
pounds carrying the indole moiety exhibit antibacterial
and antifungal activities.[6] Furthermore, it has been re-
ported that sharing of the indole 3-carbon atom in the
formation of spiroindoline derivatives highly enhances
biological activity.[7-9] The spirocyclic oxindole core is
featured in a number of natural alkaloids as well as
medicinally relevant compounds.[10-15] The spirooxin-
N
Me
H
O
O
N
N
H
O
H
O
Me
Me
N
O
OMe
N
MeO
H
H
Pteropodine
Spirotryprostatin A
Figure 1 Structure of spirotryprostatin A and pteropodine.
Heterocycles containing the pyrazole ring are im-
portant targets in synthetic and medicinal chemistry be-
cause this fragment is a key moiety in numerous bio-
logically active compounds.[18] Among them are such
prominent drug molecules as Viagra, Celebrex, Analgi-
num, and many others. On the other hand, pyra-
zolopyridines have received more and more attention in
the recent years. Pharmaceutical researches of this kind
of compounds have been reported, such as a potent cy-
clin dependent Kinase 1 (CDK1) inhibitor,[19] human
immunodeficiency virus (HIV) reverse transcriptase
*
E-mail: r.ghahremanzadeh@yahoo.com
Received May 23, 2011; accepted September 24, 2011.
Chin. J. Chem. 2012, 30, 321—326
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
321

Ghahremanzadeh et al.
FULL PAPER
inhibitors, CCR1 antagonists, protein kinase inhibi-
tors,[20] and inhibitors of cGMP degradation, together
with studies of several herbicidal and fungicidal activi-
ties.[21] Numerous methods for the synthesis of pyra-
zolopyridines in the past 20 years have been reported
with respect to their different structures.[22]
Pyrimidopyrimidines are annulated uracils that have
attracted considerable attention in recent years. Their
derivatives are known to display a wide range of phar-
macological activities,[23] and their potent inhibitory
properties regarding the tyrosine kinase domain of epi-
dermal growth factor receptor,[24] 5-phosphoribosyl-
1-pyrophosphate synthetase,[25] and dihydrofolate re-
ductase[26] have been fully demonstrated. Therefore, for
the preparation of these complex molecules, significant
efforts were directed toward the synthetic manipulation
of uracils.[27]
In continuation of our previous works on the
synthesis of heterocyclic compounds,[28-33] recently, for
the first time, we reported novel three-component syn-
thesis of spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]-
pyrimidine]triones.[34] In order to improve our synthetic
strategy for the synthesis of spiro[indoline-pyra-
zolo[4',3':5,6]pyrido[2,3-d]pyrimidine]triones, herein,
we report a simple four-component method in ionic liq-
uid media using Alum as an inexpensive and reusable
catalyst in short reaction times for the synthesis of these
compounds.
10.69 (s, 1H, NH).
5-Bromo-1',3'-diphenyl-spiro[indoline-3,4'-pyrazolo-
[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'(6'H,8'H,9'H)-
1
trione (5b): White powder (92%), m.p.＞300 ℃; H
NMR (DMSO-d6, 300 MHz) δ: 6.40—7.69 (m, 13H,
ArH), 9.40 (s, 1H, NH), 10.14 (s, 1H, NH), 10.17 (s, 1H,
NH), 10.78 (s, 1H, NH).
5-Nitro-1',3'-diphenyl-spiro[indoline-3,4'-pyrazolo-
[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'(6'H,8'H,9'H)-
1
trione (5c): White powder (93%), m.p.＞300 ℃; H
NMR (DMSO-d6, 300 MHz) δ: 6.63—8.06 (m, 13H,
ArH), 9.53 (s, 1H, NH), 10.30 (s, 1H, NH), 10.71 (s, 1H,
NH), 10.80 (s, 1H, NH).
1-Methyl-1',3'-diphenyl-spiro[indoline-3,4'-pyrazolo-
[4′,3′:5,6]pyrido[2,3-d]pyrimidine]-2,5',7'(6'H,8'H,9'H)-
1
trione (5d): White powder (88%), m.p.＞300 ℃; H
NMR (DMSO-d6, 300 MHz) δ: 2.66 (s, 3H, CH3),
6.62—7.70 (m, 14H, ArH), 9.43 (s, 1H, NH), 10.27 (s,
1H, NH), 10.70 (s, 1H, NH).
5-Methyl-1',3'-diphenyl-spiro[indoline-3,4'-pyrazolo-
[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'(6'H,8'H,9'H)-
1
trione (5e): White powder (82%), m.p.＞300 ˚C; H
NMR (DMSO-d6, 300 MHz) δ: 2.22 (s, 3H, CH3),
6.44—7.71 (m, 13H, ArH), 9.40 (s, 1H, NH), 9.88 (s,
1H, NH), 10.21 (s, 1H, NH), 10.69 (s, 1H, NH).
1-Ethyl-1',3'-diphenyl-spiro[indoline-3,4'-pyrazolo-
[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'(6'H,8'H,9'H)-
1
trione (5f): White powder (80%), m.p.＞300 ℃; H
NMR (DMSO-d6, 300 MHz) δ: 0.79 (t, JHH＝6.93 Hz,
3
3H, CH3), 3.11—3.37 (m, 2H, CH2), 6.54—7.68 (m,
14H, ArH), 9.42 (s, 1H, NH), 10.25 (s, 1H, NH), 10.71
(s, 1H, NH).
1-Methyl-5-nitro-1',3'-diphenyl-spiro[indoline-3,4'-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'-
(6'H,8'H,9'H)-trione (5g): White powder (83%), m.p.＞
300 ℃; 1H NMR (DMSO-d6, 300 MHz) δ: 2.78 (s, 3H,
CH3), 6.68—8.11 (m, 13H, ArH), 9.59 (s, 1H, NH),
10.27 (s, 1H, NH), 10.81 (s, 1H, NH).
1-Methyl-5-bromo-1',3'-diphenyl-spiro[indoline-3,4'-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'-
(6'H,8'H,9'H)-trione (5h): White powder (82%), m.p.＞
300 ℃; 1H NMR (DMSO-d6, 300 MHz) δ: 2.67 (s, 3H,
CH3), 6.56—7.73 (m, 13H, ArH), 9.47 (s, 1H, NH),
10.17 (s, 1H, NH), 10.81 (s, 1H, NH).
Experimental
All the products 5a—5t are known compounds and
were characterized by comparison of their H NMR
1
spectrum with authentic samples that were synthesized
by reported procedures.[34] 1H NMR spectra were re-
corded on a BRUKER DRX-300 AVANCE spectrome-
ter at 300.13 MHz and obtained in CD3SOCD3 solutions
using TMS as internal standard. The chemicals used in
this work were obtained from Fluka and Merck and
were used without purification.
Typical procedure for preparation of compounds 5
Take compound 5a as the example. To a magneti-
cally stirred mixture of phenyl hydrazine (1 mmol),
3-oxo-3-phenylpropanenitrile (1 mmol), [Bmim]PF6
(0.2 g) and Alum (10 mol%) at 100 ℃ for 5 min were
added barbituric acid (1 mmol) and isatin (1 mmol). The
mixture was finally stirred for 40 min (the progress of
the reaction was monitored by TLC). After cooling, the
water (10 mL) was added to the reaction mixture and
filtered. The precipitate was washed with water (10 mL)
and EtOH (10 mL) to afford the pure product 5a as
white powder.
1',3'-Diphenyl-spiro[indoline-3,4'-pyrazolo-
[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'(6'H,8'H,9'H)-
trione (5a): Yield 90%, m.p. ＞ 300 ℃ ; 1H NMR
(DMSO-d6, 300 MHz) δ: 6.51—7.71 (m, 14H, ArH),
9.35 (s, 1H, NH), 9.91 (s, 1H, NH), 10.19 (s, 1H, NH),
1-Ethyl-5-bromo-1',3'-diphenyl-spiro[indoline-3,4'-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5',7'-
(6'H,8'H,9'H)-trione (5i): White powder (81%), m.p.＞
1
300 ℃; H NMR (DMSO-d6, 300 MHz) δ: 0.80 (t,
3JHH＝6.90 Hz, 3H, CH3), 3.11—3.37 (m, 2H, CH2),
6.60—7.69 (m, 13H, ArH), 9.45 (s, 1H, NH), 10.23 (s,
1H, NH), 10.80 (s, 1H, NH).
5-Bromo-6',8'-dimethyl-1',3'-diphenyl-spiro[indoli-
ne-3,4'-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]-
2,5',7'(6'H,8'H,9'H)-trione (5j): White powder (85%),
1
m.p.＞300 ℃; H NMR (DMSO-d6, 300 MHz) δ: 3.05
(s, 3H, CH3), 3.52 (s, 3H, CH3), 6.42—7.85 (m, 13H,
ArH), 9.75 (s, 1H, NH), 10.12 (s, 1H, NH).
5-Nitro-6',8'-dimethyl-1',3'-diphenyl-spiro[indoline-
322
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 321—326

Synthesis of Spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]triones
3,4'-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]2,5',7'-
1-Methyl-1',3'-diphenyl-7'-thioxo-spiro[indoline-3,4'-
(6'H,8'H,9'H)-trione (5k): White powder (87%), m.p.＞
300 ℃; 1H NMR (DMSO-d6, 300 MHz) δ: 3.04 (s, 3H,
CH3), 3.57 (s, 3H, CH3), 6.62—8.09 (m, 13H, ArH),
9.88 (s, 1H, NH), 10.73 (s, 1H, NH).
1,6',8'-Trimethyl-1',3'-diphenyl-spiro[indoline-3,4'-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]2,5',7'-
(6'H,8'H,9'H)-trione (5l): White powder (79%), m.p.＞
300 ℃; 1H NMR (DMSO-d6, 300 MHz) δ: 2.69 (s, 3H,
CH3), 3.05 (s, 3H, CH3), 3.59 (s, 3H, CH3), 6.62—7.83
(m, 14H, ArH), 9.79 (s, 1H, NH).
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5'-
(6'H,8'H,9'H)dione (5t): White powder (86%), m.p.＞
300 ℃; 1H NMR (DMSO-d6, 300 MHz) δ: 2.67 (s, 3H,
CH3), 6.64—7.73 (m, 14H, ArH), 9.48 (s, 1H, NH),
11.79 (s, 1H, NH), 12.21 (s, 1H, NH).
Results and Discussion
In our initial study, the one-pot reaction was con-
ducted by stirring the mixture of phenyl hydrazine 3a
and 3-oxo-3-phenylpropanenitrile 4 in ionic liquid,
[Bmim]PF6, in the presence of catalytic amount of
Alum (10 mol%) at 100 ℃ for 5 min. Then isatin 1a
and barbituric acid 2a were added to the reaction mix-
ture. The progress of the reaction was monitored by
TLC. After completion of the reaction the desired prod-
uct 5a was obtained in 90% yield (Table 1). Using
lower amount of catalyst resulted in lower yields, while
higher amount of catalyst did not affected reaction time
and yield (Table 1). When this reaction was carried out
with other catalysts such as silica sulfuric acid (SSA),
SnCl4, p-TSA, and CAN, the yield of the expected
product was low to moderate amounts (Table 1).
1'-Phenyl-3'-(4-nitrophenyl)-spiro[indoline-3,4'-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]2,5',7'-
(6'H,8'H,9'H)trione (5m): White powder (83%), m.p.＞
1
300 ℃; H NMR (DMSO-d6, 300 MHz) δ: 6.47—7.97
(m, 9H, ArH), 7.98 (d, 3JHH＝9.0 Hz, 2H, ArH), 8.47 (d,
3JHH＝9.0 Hz, 2H, ArH), 9.67 (s, 1H, NH), 9.97 (s, 1H,
NH), 10.50 (s, 1H, NH), 10.79 (s, 1H, NH).
5-Bromo-1'-phenyl-3'-(4-nitrophenyl)-spiro[indoline-
3,4'-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]2,5',7'-
(6'H,8'H,9'H)-trione (5n): White powder (82%), m.p.＞
1
300 ℃; H NMR (DMSO-d6, 300 MHz) δ: 6.66—7.96
(m, 8H, ArH), 7.95 (d, 3JHH＝8.8 Hz, 2H, ArH), 8.47 (d,
3JHH＝8.7 Hz, 2H, ArH), 9.65 (s, 1H, NH), 10.16 (s, 1H,
NH), 10.47 (s, 1H, NH), 10.83 (s, 1H, NH).
We also tested the reaction in different ionic liquid
media such as [Bmim]Br, [Bmim]Cl, [Bmim]CF3COO,
[Bmim]BF4 and [Bmim]PF6. Table 1 demonstrates that
[Bmim]PF6 is the best choice of media and the use of
Alum in [Bmim]PF6 improves the yield of the product.
After optimizing conditions, in order to establish the
generality of the method, a wide variety of suitable sub-
strates were employed in this methodology. Five sub-
stituted isatins 1a—1e, three commercially available
barbituric acids 2a—2c, two available phenyl hydra-
zines 3a, 3b, and 3-oxo-3-phenylpropanenitrile were
chosen for the library validation (Table 2). Correspond-
ing spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]pyri-
midine]triones 5a—5t were synthesized by the one-pot,
four-component condensation reaction in excellent
yields at 100 ℃ in the presence of Alum (10 mol%)
for 45 min. The results are summarized in Table 2.
The recovery and recycling of the catalyst is a key
factor in catalytic processes, especially, in industry. An
important advantage of this catalyst is the easy separa-
tion from the reaction mixture, as well as the fact that it
could be recycled a number of times. We checked the
reusability of the catalyst by recovering the Alum in the
reaction. Apparently, recycling of catalyst is possible
for three successive times without significant loss of
activity (Table 2, 3c).
5-Nitro-1'-phenyl-3'-(4-nitrophenyl)-spiro[indoline-
3,4'-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]2,5',7'-
(6'H,8'H,9'H)-trione (5o): White powder (85%), m.p.＞
300 ℃; H NMR (DMSO-d6, 300 MHz) δ: 6.62—8.48
(m, 12H, ArH), 9.78 (s, 1H, NH), 10.57 (s, 1H, NH),
10.73 (s, 1H, NH), 10.89 (s, 1H, NH).
1
1-Methyl-1'-phenyl-3'-(4-nitrophenyl)-spiro[indoline-
3,4'-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]2,5',7'-
(6'H,8'H,9'H)-trione (5p): White powder (78%), m.p.＞
300 ℃; 1H NMR (DMSO-d6, 300 MHz) δ: 2.68 (s, 3H,
3
CH3), 6.63—7.32 (m, 9H, ArH), 7.99 (d, JHH＝9.0 Hz,
2H, ArH), 8.48 (d, J＝9.0 Hz, 2H, ArH), 9.72 (s, 1H,
NH), 10.57 (s, 1H, NH), 10.78 (s, 1H, NH).
1',3'-Diphenyl-7'-thioxo-spiro[indoline-3,4'-pyrazolo-
[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5'(6'H,8'H,9'H)-
1
dione (5q): White powder (80%), m.p.＞300 ℃; H
NMR (DMSO-d6, 300 MHz) δ: 6.52—7.71 (m, 14H,
ArH), 9.43 (s, 1H, NH), 10.07 (s, 1H, NH), 11.77 (s, 1H,
NH), 12.15 (s, 1H, NH).
5-Bromo-1',3'-diphenyl-7'-thioxo-spiro[indoline-
3,4'-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5'-
(6'H,8'H,9'H)-dione (5r): White powder (81%), m.p.＞
1
300 ℃; H NMR (DMSO-d6, 300 MHz) δ: 6.45—7.68
(m, 13H, ArH), 9.46 (s, 1H, NH), 10.23 (s, 1H, NH),
11.74 (s, 1H, NH), 12.27 (s, 1H, NH).
We have not established an exact mechanism for the
formation of 5, however, a reasonable possibility is
shown in Scheme 1. The one-pot four-component proc-
ess consists of an initial formation of 1,3-diphenyl-
1H-pyrazol-5-amine 6 via cyclocodensation reaction of
3 and 4. Then condensation reaction of 1, 2 and 6, fol-
5-Nitro-1',3'-diphenyl-7'-thioxo-spiro[indoline-3,4'-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]-2,5'-
(6'H,8'H,9'H)dione (5s): White powder (83%), m.p.＞
300 ℃; H NMR (DMSO-d6, 300 MHz) δ: 6.66—8.05
(m, 13H, ArH), 9.58 (s, 1H, NH), 10.80 (s, 1H, NH),
11.78 (s, 1H, NH), 12.31 (s, 1H, NH).
1
Chin. J. Chem. 2012, 30, 321—326
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
323

Ghahremanzadeh et al.
FULL PAPER
Table 1 Model reaction, conditions and yieldsa
Entry
Condition
[Bmim]PF6
[Bmim]PF6
[Bmim]PF6
[Bmim]PF6
[Bmim]BF4
[Bmim]Br
Catalyst
Time/min
Yield/%
＜50
55
1
2
CAN (10 mol%)
p-TSA (10 mol%)
SnCl4 (10 mol%)
SSA (10 mol%)
Alum (10 mol%)
Alum (10 mol%)
Alum (10 mol%)
Alum (10 mol%)
Alum (10 mol%)
Alum (5 mol%)
Alum (15 mol%)
60
60
60
60
45
45
45
45
45
45
45
3
52
4
58
5
70
6
65
7
[Bmim]CF3CO2
[Bmim]Cl
78
8
62
9
[Bmim]PF6
[Bmim]PF6
[Bmim]PF6
90
10
11
83
90
a Isatin (1 mmol), barbituric acid (1 mmol), 3-oxo-3-phenylpropanenitrile (1 mmol), phenyl hydrazine (1 mmol), catalyst (10 mol%) and
ionic liquid (0.2 g) at 100 ℃.
Table 2 Synthesis of spiro[indoline-pyrazolopyrido[2,3-d]pyrimidine]triones
Compound 5a
R1
H
R2
H
X
H
Y
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
Z
H
Yieldb/%
5a
5b
5c
5d
5e
5f
90
H
H
Br
NO2
H
H
92
H
H
H
93 (93, 91, 91)c
Me
H
H
H
88
82
80
83
82
81
85
87
79
83
82
85
78
80
H
Me
H
H
Et
Me
Me
Et
H
H
H
5g
5h
5i
H
NO2
Br
Br
Br
NO2
H
H
H
H
H
H
5j
Me
Me
Me
H
H
5k
5l
H
H
Me
H
H
5m
5n
5o
5p
5q
H
NO2
NO2
NO2
NO2
H
H
H
Br
NO2
H
H
H
Me
H
H
H
H
324
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 321—326

Synthesis of Spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]triones
Continuted
Compound 5a
R1
H
R2
H
H
H
X
Br
Y
S
S
S
Z
H
H
H
Yieldb/%
5r
5s
5t
81
83
86
H
NO2
H
Me
a
1
All the products are known compounds and were characterized by comparison of their H NMR spectrum with authentic samples syn-
thesized by reported procedures.[36] b Isolated yields. c Isolated yield after recycling of catalyst.
Scheme 1 Proposed mechanism of the reaction
[13] Kang, T. H.; Matsumoto, K.; Murakami, Y.; Takayama, H.;
lowed by intramolecular cyclization afforded the corre-
sponding product 5.
Kitajima, M.; Aimi, N.; Watanabe, H. Eur. J. Pharmacol. 2002, 444,
39.
[14] (a) Lin, H.; Danishefsky, S. J. Angew. Chem. 2003, 115, 38; (b) Lin,
H.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2003, 42, 36.
[15] Venkatesan, H.; Davis, M. C.; Altas, Y.; Snyder; Liotta, D. C. J. Org.
Chem. 2001, 66, 3653.
[16] Da Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J. Braz. Chem. Soc.
2001, 273.
Acknowledgement
We gratefully acknowledge financial support from
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