Dual enantioselective Diels-Alder process in the cyclization of chiral acrylamide with dienes

Article abstract of DOI:10.1002/poc.828

Diels-Alder cycloadditions of chiral acrylamides with cyclopentadiene or 2, 3-dimethyl butadiene proceed with high diastereofacial selectivity. Either endo-R or endo-S products have been obtained depending upon the structures of acrylamides and Lewis acids used. The endo form was exclusively obtained over the exo form. The dependence of the mechanism of formation of opposite configurations of endo-R or endo-S products on the Lewis acids is discussed. Copyright 2004 John Wiley & Sons, Ltd.

Full text of DOI:10.1002/poc.828

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2004; 17: 1017–1022
Published online 13 August 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.828
Dual enantioselective Diels–Alder process in
the cyclization of chiral acrylamide with dienesy
Doo Young Jung,1 Doo Han Park,2 Sung Han Kim1 and Yong Hae Kim1*
1Department of Chemistry, Center for Molecular Design and Synthesis, Korea Advanced Institute of Science and Technology,
Daejon, 305-701, South Korea
2Department of Chemistry, Sam Youk University, Seoul, 139-742, South Korea
Received 8 September 2003; revised 6 April 2004; accepted 13 April 2004
ABSTRACT: Diels–Alder cycloadditions of chiral acrylamides with cyclopentadiene or 2, 3-dimethyl butadiene
proceed with high diastereofacial selectivity. Either endo-R or endo-S products have been obtained depending upon
the structures of acrylamides and Lewis acids used. The endo form was exclusively obtained over the exo form. The
dependence of the mechanism of formation of opposite configurations of endo-R or endo-S products on the Lewis
acids is discussed. Copyright # 2004 John Wiley & Sons, Ltd.
KEYWORDS: dual enantioselective; Diels–Alder cyclization; diastereofacial selectivity; endo-R; endo-S; Lewis acids
INTRODUCTION
with dienes in the presence of various Lewis acids. Here
we describe the intriguing results obtained during devel-
opment of Lewis acid dependent stereocontrol toward
both endo-R and endo-S configurations with high diaster-
eofacial selectivity. We reported the preliminary results
on dual enantioselective control in asymmetric Diels–
Alder cyclization.6 In order to generalize the results, the
requisite dienophiles 1–3 were synthesized from (S)-
indoline-2-carboxylic acid.7 They were purified and their
optical purities (>99.8% ee) were determined by HPLC
(Daicel chiral OD column, i-PrOH-n-hexane, 5:95). The
preliminary studies involved reaction of 1–3 with 4 and 5,
as shown in Fig. 1.
Asymmetric Diels–Alder cyclization is one of the most
effective methods of creating a chiral center during the
formation of six-membered rings (for reviews see Ref. 1).
Various types of chiral dienophiles such as chiral esters,1
N-acyloxazole derivatives,2 N-acylsultams,3 acrylates4
and acrylamides5 have been developed. Metal coordina-
tion is important for diastereofacial selectivity in the
asymmetric synthesis. Lewis acids have been used for
chelate formation in Diels–Alder cyclizations to obtain
high diastereofacial selectivities.1–5 In general, the S-
form of the chiral dienophile (auxiliary) exclusively
affords the endo-R adduct over the endo-S, and the R-
form exclusively gives the S-adduct over the endo-R.
Issues associated with this absolute stereochemical con-
trol dependence upon Lewis acids and the structures of
dienophiles provide an important challenge in the area of
practical Diels–Alder reaction designs.4a,5b
Extremely high levels of asymmetric induction can be
achieved in Diels–Alder cycloadditions of 3 with 4. The
results obtained are summarized in Table 1.
Table 1 shows extremely high diastereoselectivities
[endo-R (8a):endo-S (8b) ¼ 99:1] in the Diels–Alder
cyclizations of 3 with 4 in the presence of various Lewis
acids such as Et2AlCl, EtAlCl2, AlCl3, BF3ꢀEt2O, ZnCl2,
TiCl4, Ti(O-i-Pr)4, SnCl4 and ZrCl4. All Lewis acids
resulted in the endo-form with the R-form of absolute
configuration. In contrast to these results, when 1 was
reacted with 4 in the presence of aluminum chlorides,
ZnCl2 or BF3ꢀEt2O, the opposite configuration of endo-S
(6b) with high diastereoselectivity [endo-R (6a):endo-S
(6b) ¼ 1:>99] as shown in Table 2.
RESULTS AND DISCUSSION
In anticipation of obtaining the opposite configuration of
the endo adduct and understanding the mechanism, three
different dienophiles 1, 2 and 3 were prepared and reacted
*Correspondence to: Y. H. Kim, Department of Chemistry, Center for
Molecular Design and Synthesis, Korea Advanced Institute of Science
and Technology, Daejon, 305-701, South Korea.
E-mail: kimyh@kaist.ac.kr
yPaper presented at the 9th European Symposium on Organic
Reactivity, 12–17 July 2003, Oslo, Norway.
In particular, 3, which contains a diphenyl substituted
tertiary alcohol moiety, affords exceptionally high dia-
stereofacial selectivities (8a:8b ꢁ 99:1, yield ꢁ 90%;
Table 1) regardless of the nature of the Lewis acid. The
endo configurations were readily ascertained by iodolac-
tonization of 6a–8a with I2 in DME.5b The exo compound
Contract/grant sponsor: Korea Science and Engineering Foundation;
Contract/grant number: R02-2002-000-00097-0.
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 1017–1022

1018
D. Y. JUNG ET AL.
mined by reductive cleavage of 6a to the known norbor-
nene-2-methanol and subsequent comparison of [ꢀ]D
values.8
The variously configured adducts produced can be
rationalized by the intermediates formed between 1–3
and the metals of the Lewis acids. Compounds 1–3 react
with 4 to favor the formation of endo-R species 6a or 8a
with TiCl4, Ti(O-i-Pr)4, SnCl4 or ZrCl4 probably via
formation of seven-membered ring chelates with the
acryloyl moiety of 10 or 11 having a cisoid conforma-
tion.4a,5b (Fig. 2). Helmchen and co-workers reported the
first evidence of formation of a seven-membered ring
chelate complex.4a It is worth noting that even in the
absence of any Lewis acid, 3 reacts with 4 to give an
excellent chemical yield and high stereofacial selectivity
(endo:exo ꢁ 99:1, endo-R:endo-S ꢁ 99:1; entry 1 in Table
1) at 25 ꢂC after a long reaction time (48 h, in Table 1).
The results can be attributed to the hydrogen bond cisoid
conformation intermediate 11 where the hydrogen acts as
a Lewis acid. On the other hand, 1 or 2 prefer endo-S
formation 6b or 7b with ZnCl2, AlEtCl2 or BF3ꢀEt2O,
with high diastereofacial selectivity probably resulting
from intermediates 9, as shown in Fig. 2. In contrast to Ti
or Sn Lewis acids, relatively weaker Lewis acids such as
Zn, Al or B may not form a seven-membered ring
complex, instead forming a weak coordination with the
amide carbonyl group (9).4a,5b In dienophile 2, the same
trend as for 7b was observed, but in a less diastereose-
lective manner than for 1 [Ti(O-i-Pr)4; 90%, endo-
R:endo-S ¼ 94:6, SnCl4; 92%, endo-R:endo-S ¼ 99:1).
Dienophile 1 and 3 also reacted with less reactive 2,3-
dimehylbutadiene 5 or methylbutadiene 50 at 25 ꢂC, re-
sulting in the same trend as shown in Table 3 and Figure 3.
Figure 1. Diels–Alder cyclizations
cannot be lactonized under the same reaction conditions.
The ratio of endo-R and endo-S was determined by HPLC
with the crude 6a–8a and 6b–8b without purification.
The absolute configuration of 6a, 7b or 8a was deter-
Table 1. Asymmetric Diels–Alder cyclization of 3 with 4
Lewis acid
Temp. ( ꢂC)
Time (h)
Yield (%)a
endo:exob
endo dsb
Config.c
None
rt
48
10
7
8
5
12
7
15
10
5
92
95
94
88
91
90
90
89
91
93
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
98:2
>99:1
>99:1
>99:1
>99:1
99:1
>99:1
99:1
>99:1
98:2
>99:1
R
R
R
R
R
R
R
R
R
R
Et2AlCl
EtAlCl2
AlCl3
ꢃ40
ꢃ78
ꢃ40
ꢃ78
rt
BF3ꢀEt2O
ZnCl2
TiCl4
rt
rt
Ti(O-i-Pr)4
SnCl4
ZrCl4
ꢃ78
ꢃ40
>99:1
a
Isolated yield.
Determined by HPLC with silica column. ds: diastereoselectivity.
Confirmed by [ꢀ]D of norbornene-2-methanol.
b
c
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 1017–1022

DUAL ENANTIOSELECTIVE DIELS–ALDER PROCESS
Table 2. Asymmetric Diels–Alder cyclization of 1 with 4
1019
Lewis acid
Temp. ( ꢂC)
Time (h)
Yield (%)a
endo:exob
endo dsb
Config.c
None
rt
ꢃ78
ꢃ78
ꢃ20
ꢃ78
rt
72
10
8
8
5
12
10
12
5
90
95
87
87
90
90
92
87
92
90
73:27
90:10
88:12
80:20
94:6
83:17
95:5
72:28
95:5
93:7
73:7
>99:1
90:10
81:19
>99:1
99:1
99:1
94:6
99:1
94:6
S
S
S
S
S
S
R
R
R
R
Et2AlCl
EtAlCl2
AlCl3
BF3ꢀEt2O
ZnCl2
TiCl4
0
rt
Ti(O-i-Pr)4
SnCl4
ZrCl4
ꢃ78
ꢃ40
5
a
Isolated yield.
Determined by HPLC with silica column.
b
c Confirmed by [ꢀ]D of norbornene-2-methanol.
In the case of Evans’ model dienophile, an ꢀ,ꢁ-
unsaturated S-oxazolidinone, the endo-R form was obtai-
ned2a and explained by formation of a six-membered ring
intermediate with Et2AlCl, which was clarified by a 13C
NMR study2c (Fig. 4.) However, in contrast to a signifi-
cant chemical shift change in the 1–SnCl4 chelation
complex 11, 13C NMR measurement of the 1–Et2AlCl
mixture did not show significant changes in the chemical
shifts for either of the amide or ester carbonyl peaks,
which can be explained by a weak coordination (9)
between 1 and Et2AlCl.
Species 1 and 3 also reacted with the less reactive
acyclic diene 5 at 25 ꢂC resulting in the same trend: for 1
with TiCl4 the ratio of endo-R:endo-S was 97:3, while
with EtAlCl2 the ratio was reversed to 3:97, which is
comparable to entry 1; for 3 with both TiCl4 and Et2AlCl,
endo-R:endo-S ¼ 97:3 and 94:6, respectively.
However, octahydroindoline dienophile gave the simi-
lar trends through an intermediate 13 with Et2AlCl (endo-
R:endo-S ¼ 7:93) and an intermediate 14 with TiCl4
(endo-R:endo-S ¼ 93:7).
EXPERIMENTAL
Instruments and measurements
Melting points were taken on a Electrothermal melting
point apparatus (Electrothermal Engineering). Infrared
spectra were taken on a Bomen MB-100 FT-IR spectro-
meter. NMR spectra were determined on Brucker AC-200
and AM-300. The chemical shifts are reported in ppm
relative to internal tetramethylsilane. HPLC was per-
formed on a Waters Associates Model 44 instrument
Figure 2. Mechanism of Diels–Alder cyclizations
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 1017–1022

1020
D. Y. JUNG ET AL.
Table 3. Asymmetric Diels–Alder cyclization of 1 and 3 with 5 or methylbutadiene (50)
Lewis acid
Dienophile
Diene
Temp. ( ꢂC)
Time (h)
Yield (%)a
ds (R:S)b
TiCl4
EtAlCl2
TiCl4
EtAlCl2
TiCl4
EtAlCl2
TiCl4
EtAlCl2
1
1
1
1
3
3
3
3
5
0 ! 25
0 ! 25
0 ! 25
0 ! 25
0 ! 25
0 ! 25
0 ! 25
0 ! 25
8
10
14
18
24
30
24
24
85
80
78
76
75
72
68
67
97:3
97:3
95:5
10:90
97:3
94:6
95:5
94:6
5
50
50
5
5
50
50
a Isolated yield.
b Determined by HPLC analysis.
and benzophenone for at least 5 h under an argon atmo-
sphere and distilled prior to use. Methylene chloride was
refluxed over calcium hydride. Some compounds were
prepared by known procedures and spectral and physical
data of the products were in accord with reported data.
Synthesis of chiral dienophile 1
Figure 3. Diels–Alder cyclizations of 1 with 5
In an ice bath, thionyl chloride (0.1 mol) was dropped
into a solution of (S)-indoline-2-carboxylic acid (0.1 mol)
in CH2Cl2 (150 ml) and stirred for 30 min. MeOH
(0.8 mol) was dropped into the solution at 0 ꢂC for
30 min and refluxed for 1 h. The mixture was dissolved
in water and neutralized with NH4OH from pH 1–2 to pH
7–8 and then extracted with CH2Cl2 three times. The
organic layer was washed off with brine, dried over
MgSO4 and concentrated under reduced pressure to
give the crude product, which was chromatographed on
a silica gel column (ether:n-hexane ¼ 1:2) to yield (S)-
indoline-2-carboxylic acid methyl ester. This (S)-indo-
line-2-carboxylic acid methyl ester was dissolved in
CH2Cl2 and cooled to 0 ꢂC, and subsequently treated
with 2 equiv. of Et3N and 2 equiv. of acryloyl chloride.
The mixture was stirred for 1 h, diluted with ether, filtered
thorough Celite, washed with brine and dried over
MgSO4 and then concentrated under reduced pressure,
and chromatographed on a silica gel column to give chiral
dienophile 1.
[ꢀ]D ꢃ127.85 ꢂ (c 1.07, CHCl3). H NMR (CDCl3)
ꢂ3.20 (m, 1H), 3.51 (m, 1H), 3.66 (s, 3H), 5.03 (m, 1H),
5.75 (m, 1H), 6.36 (m, 2H), 6.96–7.15 (m, 4H). 13C NMR
(CDCl3) ꢂ171.62, 164.22, 141.71, 139.97, 130.56,
128.64, 125.30, 117.23, 114.60, 59.69, 53.02, 32.91. IR
(NaCl) 1745, 1658, 1481, 1415, 1374, 1271, 1204, 756
cmꢃ1. Anal. Calcd for C13H13NO3: C, 67.52; H, 5.66; N,
6.05. Found: C, 66.98; H, 5.74; N, 5.81.
Figure 4. Evans’ model dienophile
equipped with ultraviolet detectors. GLC analyses were
performed on a Hewlett Packard 5890A gas chromato-
graph using a flame ionization detector and nitrogen as a
carrier with a Hewlett Packard 3390A integrator. The
column used for analysis was an SE-30, 10% OV101 and
capillary OV-17. Mass spectra were obtained on Hewlett
Packard 5980A GC/MS system using the electron impact
(EI) method. Optical rotations were taken on an Autopoll
III automatic polarimeter. Analytical thin layer chroma-
tography (TLC) was performed on a glass plate
(0.25 mm) coated with silica gel 60 F 254 (E. Merck).
Preparative thin layer chromatography was carried out on
Merck silica gel GF254, on a 20 ꢄ 20 cm glass plate of
1.0 mm thickness. The plates were activated by heating in
an oven at 125 ꢂC overnight. Also, silica gel 60 (E.
Merck) was used for column chromatography.
20
1
Materials
All the reagent grade chemicals, purchased from Aldrich,
Fluka, Merck and Wako and, were used without further
purification. All the organic solvents were obtained from J.
T. Baker and Duksan Pharmaceutical Compound. Tetra-
hydrofuran and diethyl ether were refluxed over sodium
Synthesis of chiral dienophile 2
In a 50 ml, two necked, round-bottom flask equipped
with an oil-bath, a reflux condenser with a drying tube
packed with CaCl2, and a stopper were placed 25 ml of
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 1017–1022

DUAL ENANTIOSELECTIVE DIELS–ALDER PROCESS
1021
anhydrous THF and LiAlH4 (591 mg, 15.6 mmol). The
suspension was heated under reflux for 15 min, the
heating oil-bath was switched off, and 1.63 g
(10 mmol) of powdered (S)-indoline-2-carboxylic acid
were added in small portions to the boiling mixture at
such a rate to maintain reflux. The contents of the flask
were kept boiling for an additional 1 h. Excess LAH was
then decomposed by cautiously adding a solution of
280 mg of KOH in 1.2 ml of water (without external
heating) through a syringe to the boiling mixture. Upon
hydrolysis, white salts precipitate and stirring became
difficult. After the addition was complete, the mixture
was refluxed for 15 min and the hot solution was filtered
by suction through a Buchner funnel. The precipitate was
pressed dry with a beaker. Any remaining indoline was
extracted from the precipitate by refluxing with 15 ml of
THF for 1 h under mechanical stirring, followed again by
suction filtration. The combined filters were concen-
trated at 30 ꢂC under reduced pressure to yield the crude
product. The crude hydroxymethyl indoline derivative,
along with a magnetic stirring bar, was cooled to 0 ꢂC.
Methyl formate (5 ml, excess) was added gradually and
stirring was continued overnight. Excess methyl formate
was evaporated at 30 ꢂC, which was taken up in CH2Cl2
and dried over sodium sulfate. The filtrates were con-
centrated under reduced pressure to yield the crude N-
formyl derivative. This was placed in a two-necked flask
in 15 ml of anhydrous THF and flushed with argon. The
solution was cooled to ꢃ50 ꢂC to ꢃ60 ꢂC, the cooling
bath was removed, and methyl iodide (4.00 mmol) was
added, followed by NaH (3.7 mmol) added in one por-
tion. The apparatus was flushed again with argon and
allowed to warm to rt. During this period hydrogen gas
evolved and a gray solid precipitated, which caused
stirring to become difficult. At about 0 ꢂC, the precipitate
dissolves exothericmally with strong evolution of hydro-
gen. The solution was refluxed for 15 min, and quenched
by slow addition of HCl, without external heating. THF
was removed under reduced pressure to yield the crude
O-methylated compound. To this compound, a solution
of KOH (650 mg of KOH in 4 ml of water) was added
and the mixture stirred overnight under an argon atmo-
sphere. Addition of potassium carbonate (1.5 g) caused a
precipitate of potassium salts to form, which were
filtered off and washed with ether. The Organic layer
was dried over MgSO4. The solvent was evaporated on a
rotary evaporator under reduced pressure. The residue
was chromatographed on silica column (ether:n-
hexane ¼ 1:2) to yield (S)-2-methoxymethyl indoline.
This indoline was treated with Et3N and acryloyl
chloride as described previously to yield chiral
dienophile 2.
117.72, 73.74, 58.92, 57.53, 31.57. IR (NaCl) 2894,
1655, 1615, 1480 cmꢃ1
.
Synthesis of chiral dienophile 3
To a THF (150 ml) solution of (S)-indoline-2-carboxylic
acid methyl ester (21.2 mmol) and formic acid (0.88 ml,
23.3 mmol) was added DCC (4.81 g, 23.3 mmol) in THF
(35 ml) at 0 ꢂC. The mixture was stirred at 0 ꢂC for 4 h.
The precipitate was filtered off. The filtrate was concen-
trated under reduced pressure. The residue was chroma-
tographed on a silica gel column (ether:n-hexane ¼ 2:1)
to yield (S)-N-formylindoline-2-carboxylic acid methyl
ester. Phenyl magnesium bromide (91.02 mmol) in THF
was added to a THF solution of (S)-N-formylindoline-2-
carboxylic acid methyl ester at 0 ꢂC and the mixture was
stirred at 0 ꢂC for an additional 4 h. Brine was added to
quench the reaction. The mixture was extracted with
CH2Cl2. The organic layer was dried and concentrated
under reduced pressure and passed through a column of
silica gel to give (S)-2-(diphenylhydroxymethyl)indoline.
Again, this was treated with Et3N and acryloyl chloride as
described previously and purified by column chromato-
graphy to give chiral dienophile 3.
20
1
[ꢀ]D ꢃ428.13 ꢂ (c 0.96, CHCl3). H NMR (CDCl3)
ꢂ3.00 (dd, 1H), 3.55 (dd, 1H), 5.66 (d, 1H), 5.75 (m, 1H),
6.49 (d, 1H), 6.60 (m, 1H), 6.79–7.42 (m, 14H). 13C
NMR (CDCl3) ꢂ167.09, 144.57, 141.47, 132.52, 129.43,
128.08, 127.68, 127.62, 127.41, 126.87, 126.66, 124.25,
124.04, 116.75. IR (NaCl) 3309, 1641, 1592, 1268 cmꢃ1
M.p. 167–169 ꢂC. Anal. Calcd for C24H21NO2: C, 81.10;
H, 5.95; N, 3.94. Found: C, 81.75; H, 5.90; N, 4.00.
.
General procedures for Diels–Alder cycloaddition
Lewis acid (1 equiv.) was added to a solution of chiral
dienophiles 1–3 and 10 in CH2Cl2 under argon at the
indicated temperature. After 5 min, freshly distilled cy-
clopentadiene (5 equiv.) was added to the solution. The
reaction mixture was stirred according to the TLC proce-
dure, quenched with saturated aqueous NaHCO3 solution
and extracted with ethyl acetate. The organic layer was
dried over MgSO4 and concentrated in vacuo. The dia-
stereomers were separated by preparative TLC. The ratio
of diastereomers was determined by HPLC [Hibar Pre-
packed Column RT 250-4, LiChrosorb Si 60 (10 mM)].
Reductive cleavage of Diels–Alder cycloadducts
LiAlH4 (0.6 equiv.) was added to the Diels–Alder adduct
in THF at ꢃ78 ꢂC. The reaction mixture was stirred at
ꢃ78 ꢂC and slowly allowed to attain rt, and then
quenched with water, 15% NaOH and water. The mixture
was filtered and washed with ether, and the crude pro-
ducts were separated by chromatography on silica gel to
give norbornene-2-methanol.
20
1
[ꢀ]D ꢃ100.32 ꢂ (c 1.24, CHCl3). H NMR (CDCl3)
ꢂ2.94 (t, 1H), 3.28 (m, 2H), 3.30 (s, 3H), 3.43 (m, 1H),
4.69 (d, 1H), 5.76 (dd, 1H), 6.74 (dd, 1H), 6.72 (dd, 1H),
6.97–8.16 (m, 4H). 13C NMR (CDCl3) ꢂ163.91, 141.77,
130.53, 129.01, 128.40, 127.16, 125.68, 123.99, 122.34,
Copyright # 2004 John Wiley & Sons, Ltd.
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1022
D. Y. JUNG ET AL.
Int. Ed. Engl. 1984; 23: 876–889; Waldmann H. Synthesis. 1994;
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Iodolactonization of cycloadducts
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Iodine (1.2 equiv.) was added to a solution of cycloadduct
in H2O–DME (1:1) at rt and the mixture was stirred for
5 h. The resultant solution was diluted with ethyl acetate
and washed with saturated Na2S2O3 and with 0.5 mol
dmꢃ3 HCl. The organic layer was further washed with
saturated NaHCO3, dried over MgSO4 and concentrated.
The residue was subjected to preparative TLC (ether:n-
hexane ¼ 1:1) to give iodolactone.
CONCLUSION
Asymmetric Diels–Alder cycloadditions of 1, or 3 with 4
proceed with absolute stereocontrolled diastereofacial
selectivities in both endo-S and endo-R (up to >99%
de) depending upon Lewis acids used and the structures
of chiral dienophiles.
4. (a) Poll T, Metter JO, Helmchen G. Angew. Chem., Int. Ed. Engl.
1985; 24: 112–114; (b) Poll T, Helmchen G, Bauer B. Tetrahedron
Lett. 1984; 25: 2191–2194; (c) Choy W, Reed LA III, Masamune
S. J. Org. Chem. 1983; 48: 1137–1139.
5. (a) Kawanami Y, Katsuki T, Yamaguchi M. Bull. Chem. Soc. Jpn.
1987; 60: 4190–4192; (b) Waldmann H. J. Org. Chem. 1988; 53:
6133–6136; (c) Bueno MP, Cativiela CA, Mayoral JA, Avenoza A.
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Acknowledgement
This work was supported by Grant No. R02-2002-000-
00097-0 from Korea Science and Engineering Foundation.
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