Synthesis and spectroscopic NMR studies of a highly stable cross-ozonide product derived from a carbohydrate system

Article abstract of DOI:10.1016/j.tetasy.2006.06.006

Ozonolysis of a carbohydrate derived norbornene system afforded a stable intramolecular cross-ozonide through a stereocontrolled pathway involving a regioselective fragmentation of the primary ozonide.

Full text of DOI:10.1016/j.tetasy.2006.06.006

Tetrahedron: Asymmetry 17 (2006) 1780–1785
Synthesis and spectroscopic NMR studies of a highly stable
cross-ozonide product derived from a carbohydrate system
a
a
a
´
´
´
Marıa I. Mangione, Sebastian A. Testero, Alejandra G. Suarez,
Rolando A. Spanevelloa,* and Jean-Pierre Tuchaguesb
aInstituto de Quı´mica Orga´nica de Sı´ntesis, Facultad de Ciencias Bioquı´micas y Farmace´uticas—Universidad Nacional de
Rosario-CONICET, Suipacha 531, S2002LRK Rosario, Argentina
bLaboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 Route de Narbonne, 31077 Toulouse Cedex, France
Received 10 April 2006; accepted 5 June 2006
Available online 18 July 2006
Abstract—Ozonolysis of a carbohydrate derived norbornene system afforded a stable intramolecular cross-ozonide through a stereo-
controlled pathway involving a regioselective fragmentation of the primary ozonide.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
More recently, a new drug candidate named OZ 277 2
has strongly emerged as a new antimalarial agent.5 The un-
ique structural similarity that this synthetic ozonide exhib-
its with artemisinin is the peroxide bridge, which is critical
for the pharmacological activity.
The chemistry of endoperoxides and trioxolane systems has
gained much popularity over the last decade because they
were recognized as structures widely distributed in nature,
mostly due to their inherent biological properties.1 A great
deal of effort has been directed towards studying the chem-
istry and biological mode of action of artemisinin 1 (Fig. 1)
and a plethora of analogues. Artemisinin2 is a natural
product from a traditional Chinese herbal remedy and
has shown a potent antimalarial activity.3 The fact that this
type of compound has been used as a model for the design
of new therapeutic agents against resistant forms of Plas-
modium falciparum led to the development of simpler cyclic
peroxide structures with important antimalarial activity.4
The synthesis of 1,2,4-trioxolane rings is usually achieved
through ozonolysis of a carbon–carbon double bond. The
mechanism of the ozonolysis reaction proposed by Criegee
consists of three steps: (i) a [3+2] cycloaddition reaction of
ozone with the alkene leading to the formation of a pri-
mary ozonide or 1,2,3-trioxolane 3, (ii) a cycloreversion
process providing the transient carbonyl oxide and a stable
carbonyl compound, which may proceed in two different
ways in the case of unsymmetrically substituted alkenes
4a and 4b, (iii) recombination of the carbonyl oxide and
the newly formed carbonyl group derivative to give 1,2,4-
trioxolane 5.6 In the case where the transient carbonyl
oxide is trapped by another carbonyl derivative present in
the reaction medium, the product is a cross-ozonide 6a
and 6b7 (see Scheme 1).
H
O
O
O
O
O
O
H
NH2
O
NH
Alternatively, when the ozonolysis reaction is performed in
a participating solvent, such as an alcohol, the carbonyl
oxide can react with the solvent to give an alkoxy hydro-
peroxide, which upon the appropriate workup yields the
corresponding ester.8 In the last two cases, the reaction
products provide useful information regarding the regio-
selectivity of the primary ozonide cleavage.9
O
O
1: Artemisinin
2: OZ 277
Figure 1.
*
Corresponding author. Tel./fax: +54 341 4370477; e-mail: rspaneve@
fbioyf.unr.edu.ar
0957-4166/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.06.006

M. I. Mangione et al. / Tetrahedron: Asymmetry 17 (2006) 1780–1785
1781
O
O
R
R
CH(OR2)OOH
R1
OHC
O
OHC
R
R2OH
R1CHO
R
7a
6a
CHO
O
-
O
+
R
R
O
5
4a
O
O
O3
O
O
O
R
3
+
O
-
O
CHO
4b
O
O
R1CHO
R2OH
CH(OR2)OOH
R1
OHC
OHC
O
R
R
7b
6b
Scheme 1.
6
2. Results and discussion
OCH3
CHO
5
4
O
1
2
OCH3
CHO
O
O
O
In this context, we report the synthesis of an enantiomeri-
cally pure and highly stable intramolecular cross-ozonide
structure. The product was obtained by means of a non-
symmetric ozonolysis of a norbornene type skeleton
derived from a carbohydrate system.
H5C6
H5C6
O
O
3
H
10
11
Scheme 3. Reagents and conditions: LiClO4 anhydrous 5 M in Et2O,
cyclopentadiene, rt.
Our enantiospecific route relies on the use of D-glucose as
source of chirality and employed the pyranoside ring as
the initial scaffolding for constructing a dienophile with
an exocyclic electron withdrawing group. In a simple and
efficient synthetic sequence, methyl-a-D-glucopyranoside 8
was converted into a cyclic a,b-unsaturated aldehyde 10
(Scheme 2).10
cally assigned by using homo and heteronuclear 2D NMR
techniques and NOE experiments.
The proton spectrum showed four sharp singlets at 3.42,
4.84, 5.51, and 9.53 ppm that were assigned as the methoxy
group, the anomeric proton H-3, the benzylic proton H-8,
and the aldehyde proton, respectively. Two broad singlets
at 2.96 and 3.14 ppm correspond to the bridge head pro-
tons H-1 and H-12. A well defined double doublet at
4.33 ppm was attributed to the equatorial H-6 and two
other double doublets centered at 6.08 and 6.19 ppm were
assigned to the vinylic protons H-13 and H-14. Another
characteristic multiplet that integrated for two protons
appeared at 1.63 ppm and was attributed to the methylene
group C-15. A coupling constant of 9.18 Hz between the
vicinal protons H-10 and H-11 clearly showed a trans rela-
tionship, suggesting that the product was formed by the
approach of the cyclopentadiene from the b face of the
The reaction of aldehyde 10 with freshly cracked cyclopent-
adiene afforded the cycloadduct 11 in 26% yield as the
major adduct (Scheme 3). The product was the result of
the diene approach from the b face of dienophile 10 in an
endo manner. We were surprised with the outcome and
low yield of this reaction, since the isomeric dienophile
(with the carbonyl group attached at C-3) afforded the
corresponding b-exo adduct in 85% yield as a single prod-
uct under similar reaction conditions.11,12
The structure assignment of 11 was based on spectroscopic
1
evidence. All its H and 13C NMR signals were unequivo-
HO
O
OCH3
OH
O
OCH3
O
OCH3
CHO
O
O
a, b, c, d
e, f, g
H5C6
HO
H5C6
O
O
OH
NO2
8
9
10
Scheme 2. Reagents and conditions: (a) NaIO4, H2O, pH 5–6; (b) CH3NO2, NaOCH3, CH3OH; (c) C6H5CH(OCH3)2, CSA, CHCl3; (d) MsCl, Et3N,
CH2Cl2; (e) KCN, H2O, Amberlite, CH3CN; (f) Et3N, acetone/H2O; (g) DiBAL-H, CH2Cl2.

1782
M. I. Mangione et al. / Tetrahedron: Asymmetry 17 (2006) 1780–1785
dienophile. The NOE observed between H-5MH-11 and H-
1MH-3 also corroborated the attack of the diene from the
b face of the dienophile. The NOE observed between H-
11MH-13 and H-14MH–CHO showed the endo character
of the addition. The NOE between H-3MH-15 also con-
firmed that compound 12 is a b-endo adduct (Fig. 2).
Due to the number of oxygen atoms that are part of the ring
system, it was difficult to establish a complete proton/car-
bon connectivity in the structure. For this reason, in order
to confirm the presence and regioselective formation of
the 1,2,4-trioxolane ring we performed selected gradient
experiments of heteronuclear multiple bond correlation
2
3
(HMBC). The J and J coupling constants correlations
were of great utility in providing the following evidence:
H
H
4
O
OCH3
CHO
6
O7
8
3
2
5
(a) The cross-peaks between C-1/H-11, C-1/H-15, and C-3/
H-1 allowed the C-1 signal to be identified; (b) the cross
peaks between C-1/H-15, C-15/H-13a, and C-15/H-13b
determined the remaining carbon peak of the trioxolane
ring; (c) the cross-peaks between C-2/H-14, C-14/H-3,
and C-15/H-14 were used to assign the signal for C-14;
(d) the cross-peaks between C-11/H-12, C-12/H-10, C-14/
H-12, and C-19/H-12 helped to establish the chemical shift
of C-12.
H
10
9
O
11
H
H5C6
1
15
12
H
14
H
13
H
11
Figure 2. Significant NOE correlations.
The ozonolysis reaction of cycloadduct 11 was carried out
in a dichloromethane–methanol solution with solid NaH-
CO3 in suspension. The crude reaction mixture was then
treated with acetic anhydride and triethylamine in dichloro-
methane. The TLC analysis of the crude material showed
only one product, which after flash chromatography puri-
fication afforded product 12 in 54% yield.
The NOESY experiments were useful to corroborate part
of the chemical shift assignments and provide extra stereo-
chemical information. The correlation found between H-
3MH-14 and H-10MH-14 showed that the ozonide ring
is located on the a face of the fused ring system; the corre-
lation between H-1MH-11 and H-1MOCH3 also corrobo-
rated this ring system and confirmed that the signal at
111.4 ppm corresponded to the carbon adjacent to C-2;
the correlation between H-13aMH-15 helped to clearly
identify the H-13a; the correlation between H-3MH-14
and H-10MH-14 defined the orientation of H-14 towards
the b face of the molecule and the correlation between
H-10MH-12 and H-11MH-19 demonstrated that there
was no epimerization of the C-12 configuration during
the treatment with triethylamine.
The IR spectrum of 12 showed typical absorption bands at
1733 and 1761 cmꢀ1 assigned to the carbonyl of the acetate
group and the peroxide linkage, respectively. The 1H NMR
spectrum showed five distinctive sharp singlets at 4.63,
4.92, 5.55, 5.94, and 6.50 ppm that integrated for one pro-
ton each and correspond to protons attached at carbon
atoms bearing two oxygenated functions. There were also
three other neat singlets that integrated for three protons
each at 2.11, 3.43, and 3.51 ppm, which were assigned to
a methyl group from the acetate and two methoxy groups,
respectively. No aldehyde proton signal was observed at
low fields. The pyranose backbone was confirmed by the
signals of the methoxy group at 3.43 ppm and the anomeric
proton at 4.92 ppm. The benzylidene acetal structure was
evident from the aromatic protons between 7.38 and
7.53 ppm, the presence of the acetal proton at 5.55 ppm
and the characteristic coupling constant of the geminal
protons H-6eq and H-6ax plus the vicinal coupling constant
with H-5 (Fig. 3). The signals of the 13C NMR spectrum
also denoted the existence of a methyl group at 21.3 ppm,
a carbonyl carbon at 169.6 ppm both from the acetate
group, two methoxyl carbons at 55.2 and 57.5 ppm and five
acetal carbons at 97.3, 102.4, 106.6, 107.8, and 111.4 ppm.
The complete set of signals in the 1H and 13C NMR spectra
were assigned by using homo and heteronuclear 2D NMR
techniques and NOE experiments.
The stereochemistry of C-1 and C-15 was proposed based
on the value of 1H NMR coupling constants between
H-14 and H-15 in comparison with computer-generated
3D structures obtained by CHEM 3DTM Pro V.4.0, with
MM2 force-field calculations for energy minimization for
the two possible orientations of the 1,2,4-trioxolane ring.
The calculated dihedral angle between H-14/C-14/C-15/
H-15 for the model with the peroxide bridge oriented
toward the b face is U = 78.3°, while for the other isomer
it is U = 44.4°. The coupling constants calculated accord-
ing to the Karplus equation13 for both dihedral angles were
JH-14/H-15 = 0.1 and 4.1 Hz, respectively. Considering that
the signal of H-15 is a singlet, the only model that showed
a good agreement between the calculated and the observed
coupling constant is the diastereoisomer with the peroxide
bridge oriented toward the b face. Similar results were
obtained with the corresponding epimers at C-19.
Unfortunately, no spectroscopic evidence was found to
establish the configuration of C-19 and we were unable
to obtain a crystalline material suitable for X-ray diffrac-
tion analysis. For this reason, the stereochemistry of C-19
is not shown in Figure 3. It is worth to mention that the
reaction afforded only one of the two possible diastereo-
isomers at C-19. The HRMS showed a peak for the
[M+NH4]+ = 482.2032 that is in agreement with the
C23H28O10 calculated molecular formula.
4
O
6
H
H
OCH3
1H
7 O
O17
3
2
5
10
O16
18
9
O
11
O
8
H5C6
14
15
H
19
H
12
H
13
AcO
CH3O
H
12
Figure 3. Compound 12 rings numbering.

M. I. Mangione et al. / Tetrahedron: Asymmetry 17 (2006) 1780–1785
1783
In addition to the spectroscopic studies, the positive perox-
ide test using the iodide method14 was chemical evidence
for the peroxide structure. All these data were consistent
with the structure of ozonide 12 (Scheme 4).
nation with the carbonyl group generated at the other
termini of the double bond to generate ozonide 19. Further
diastereoselective reaction of the carbonyl group at C-19
with methanol afforded hemiacetal 16, which upon acetyla-
tion yielded the final product 12. The fact that the reaction
afforded only one diastereoisomer at C-19 allowed us to
speculate that the result could be due to an intramolecular
hydrogen bond formation between the hemiacetal and the
oxygen of the trioxolane ring, which is suitably oriented,
thus stabilizing preferentially one of the epimers (Scheme
5).
O
OCH3
O
O
O
OCH3
CHO
O
O
O
a, b
H5C6
O
H
H5C6
O
H
AcO
OCH3
12
11
Scheme 4. Reagents and conditions: (a) O3, MeOH/CH2Cl2, NaHCO3,
ꢀ78 °C; (b) (CH3CO)2O, Et3N, CH2Cl2, rt.
3. Conclusion
A 1,2,4-trioxolane system was synthesized in a regio- and
stereocontrolled tandem reaction process. This nonsym-
metric ozonolysis is most likely controlled by the effect of
remote substituents.9 As proposed by Wu,15 in this case,
the aldehyde group in the norbornene system has a favor-
able spatial arrangement to induce the regioselective ozon-
ide fragmentation through space. Furthermore, its
proximity to the reacting double bond is made evident by
the formation of the cross-ozonide in 54% yield as the only
detectable reaction product. The material was stable to
flash column chromatography and other normal labora-
tory manipulations; furthermore, after storage at ꢀ20 °C
for several months it showed no evidence of
decomposition.
The analysis of the reaction product obtained and the pos-
sible alternative pathway that the ozonolysis reaction could
undergo showed a high degree of regio- and stereocontrol.
The reaction of cycloadduct 11 with ozone yielded the pri-
mary ozonide 13, which upon regioselective fragmentation
afforded only one of the two possible transient carbonyl
oxide intermediates. Carbonyl oxide 14 was trapped by
one of the two aldehyde groups present in the molecule
at this stage and formed the 1,2,4-trioxolane intermediate
15. It was not possible to detect any by-products derived
from the other two possible competing processes: reaction
of the carbonyl oxide with methanol and concomitant for-
mation of the methoxy hydroperoxide 18, nor its recombi-
O
OCH3
O
OCH3
CHO
O
O
OCH3
CHO
CHO
O
O
-
a
H5C6
O
x
x
H5C6
O
H5C6
O
H
CHO
H
H
O
O
O
+
O
O
11
13
17
O
OCH3
O
O
OCH3
CHO
-
O
OCH3
CHO
O
CHO
O
O
OH
O
+
O
x
H5C6
O
H5C6
O
H5C6
O
H
H
H
O
OCH3
CHO
O
CHO
O
14
19
18
O
OCH3
O
OCH3
O
O
OCH3
O
b
O
O
O
O
O
O
O
H5C6
O
H5C6
O
H5C6
O
H
CH3O
16
O
H
O
H
O
CHO
OH
CH3O
OAc
15
12
Scheme 5. Reagents and conditions: (a) O3, MeOH/CH2Cl2, NaHCO3, ꢀ78 °C; (b) (CH3CO)2O, Et3N, CH2Cl2, rt.

1784
M. I. Mangione et al. / Tetrahedron: Asymmetry 17 (2006) 1780–1785
4. Experimental
128.9 (1C, aromatic, Cpara), 132.3 (C-14), 137.3 (1C,
aromatic, Cipso), 139.2 (C-13), 199.6 (CHO); HRMS (EI)
observed mass: 341.139010 (for [MꢀH]+ calculated mass:
341.138899).
4.1. General
Melting points were taken on a Leitz Wetzlar Microscope
Heating Stage, Model 350 apparatus, and are uncorrected.
Optical rotations were recorded with a Jasco DIP 1000
polarimeter. IR spectra were recorded on a Nicolet Impact
Model 410 instrument. Room temperature 1H and 13C
NMR spectra using homo- and heteronuclear 2D NMR
techniques and NOE experiments (including heteronuclear
multiple bond correlation (HMBC) and NOESY) were re-
corded on Bruker AC 200 and DMX 500 spectrometers
with Me4Si as internal standard and chloroform-d as sol-
vent. High resolution mass spectrometry measurements
were performed using a Waters AutoSpect equipment or
Applied Biosystems MS. The reactions were monitored
by TLC on 0.25 mm E. Merck silica gel plates (60F254),
using UV light and anisaldehyde–H2SO4–AcOH as detect-
ing agent. Flash column chromatography, using Merck sil-
ica gel 60H, was performed by gradient elution created by
mixtures of hexanes and increasing amounts of EtOAc.
The reactions were performed under argon atmosphere
with dry, freshly distilled solvents under anhydrous condi-
tions, unless otherwise noted. Yields refer to chromato-
graphically and spectroscopically (1H NMR) homo-
geneous materials, unless otherwise stated.
4.3. Preparation of 12-acetoxymethoxy methyl-3-methoxy-
8-phenyl-4,7,9,16,17,18-hexoxapentacyclo-
[13.2.1.02,11.02,14.05,10]octadecane 12
Aldehyde 11 (121.3 mg, 0.4 mmol) was dissolved in a 5:1
mixture of CH2Cl2–CH3OH (6 mL) and solid NaHCO3
(120 mg, 1.4 mmol) was added. The suspension was cooled
down to ꢀ78 °C and an ozone stream was bubbled through
the stirred suspension. Ozone addition was stopped when
complete consumption of 11 was observed by TLC analy-
sis. The mixture was then flushed with argon, and NaHCO3
was removed by filtration. The filtrate was concentrated
under vacuum to give the crude as colorless oil, which
was taken up in CH2Cl2 (6 mL). The mixture was cooled
down to 0 °C, and acetic anhydride (170 lL, 1.8 mmol)
and triethylamine (75 lL, 0.4 mmol) were added. The mix-
ture was stirred at room temperature overnight and then
partitioned between ethyl acetate and, sequentially, 0.5 M
aqueous HCl, 0.625 M aqueous KOH, and brine. The com-
bined organic extract was dried (Na2SO4) and concentrated
under vacuum. Chromatography of the crude product
afforded pure 12 (87.3 mg, 54%) as a colorless oil. Com-
25
pound 12: ½aꢁD ¼ þ21:5 (c 0.44, CHCl3); IR (NaCl) mmax
:
4.2. Preparation of 3-methoxy-8-phenyl-4,7,9-trioxatetra-
cyclo[10.2.1.02,11.05,10]-pentadec-13-ene-2-carbaldehyde 11
700, 755, 941, 978, 1018, 1053, 1076, 1122, 1161, 1229,
1376, 1456, 1733 (COOC), 1761 (COOC), 2854,
1
2931 cmꢀ1; H NMR (500 MHz, CDCl3): d 2.08 (dd, 1H,
Methyl
4,6-O-benzylidene-2,3-dideoxy-2-C-formyl-a-D-
Jgem 14.9, Jvic 6.6 Hz, H-13b), 2.11 (s, 3H, CH3CO), 2.31
(dm, 1H, Jgem 14.9 Hz, H-13a), 2.55 (d, 1H, J10,11
10.1 Hz, H-11), 2.71 (d, 1H, J11,12 7.9 Hz, H-12), 2.77
(dd, 1H, J14,13b 11.8, J14,13a 3.2 Hz, H-14), 3.25 (dd, 1H,
J10,11 = J10,5 10.0 Hz, H-10), 3.43 (s, 3H, OCH3 anomeric),
3.51 (s, 3H, OCH3 acetalic), 3.71 (dd, 1H, Jgem = J5,6ax
10.4 Hz, H-6ax), 3.92 (m, 1H, H-5), 4.33 (dd, 1H, Jgem
10,3, J5,6eq 5,0 Hz, H-6eq), 4.63 (s, 1H, H-3), 4.92 (s, 1H,
H-19), 5.55 (s, 1H, H-8), 5.94 (s, 1H, H-1), 6.50 (s, 1H,
H-15), 7.38–7.44 (m, 3H aromatics), 7.49–7.53 (m, 2H aro-
matics); 13C NMR (125 MHz, CDCl3): d 21.3 (CH3CO),
26.6 (C-13), 43.6 (C-11), 46.7 (C-12), 50.9 (C-14), 55.2
(OCH3 anomeric), 57.5 (OCH3 acetalic), 60.8 (C-5), 62.4
(C-2), 69.2 (C-6), 78.2 (C-10), 97.3 (C-3), 102.4 (C-8),
106.6 (C-15), 107.8 (C-19), 111.4 (C-1), 126.2 (2C aromat-
ics, Cortho), 128.4 (2C aromatics, Cmeta), 129.3 (1C aro-
matic, Cpara), 137.2 (1C aromatic, Cipso), 169.7 (CH3CO);
HRMS (CI) observed mass: 482.2032 (for [M+NH4]+
calculated mass: 482.2026).
erythro-hex-2-enopyranoside 10 (583 mg, 2.1 mmol) was
azeotropically dried with dry benzene under vacuum and
dissolved in anhydrous petroleum ether (35 mL) at room
temperature under an argon atmosphere. Anhydrous lith-
ium perchlorate (18.6 g, 0.2 mol) and freshly cracked cyclo-
pentadiene (1.4 mL, 21.2 mmol) were added sequentially
under an inert atmosphere at room temperature to the
magnetically stirred solution. Stirring was continued for
7 days at rt. At this time, fresh amounts of anhydrous
petroleum ether and cyclopentadiene were added and the
reaction mixture was stirred for seven more days. The mix-
ture was diluted with ethyl acetate, washed with distilled
water, dried (Na2SO4), and concentrated. The crude prod-
uct was purified by flash chromatography to yield pure 11
23
(189 mg, 26%) as a colorless oil. Compound 11: ½aꢁD
¼
þ35:8 (c 8.24, CHCl3); IR (NaCl) mmax: 699, 755, 850,
974, 1086, 1212, 1374, 1454, 1721 (C@O), 2854,
2972 cmꢀ1; H NMR (200 MHz, CDCl3): d 1.63 (m, 2H,
1
H-15, H-150), 2.36 (dd, 1H, J10,11 9.2, J11,12 1.8 Hz, H-
11), 2.96 (bs, 1H, H-12), 3.14 (bs, 1H, H-1), 3.42 (s, 3H,
OCH3), 3.49 (dd, 1H, J10,11 = J5,10 9.5 Hz, H-10), 3.65
(dd, 1H, Jgem = J5,6ax 10.0, H-6ax), 3.81 (m, 1H, H-5),
4.33 (dd, 1H, Jgem 10.0, J5,6eq 4.6 Hz, H-6eq), 4.84 (s, 1H,
H-3), 5.53 (s, 1H, H-8), 6.08 (dd, 1H, J13,14 5.6, J12,13
3.2 Hz, H-13), 6.19 (dd, 1H, J13,14 5.6, J1,14 2.8 Hz, H-
14), 7.30–7.55 (m, 5H, aromatics), 9.53 (s, 1H, CHO);
13C NMR (50 MHz, CDCl3): d44.3 (C-15), 45.0 (C-12),
45.2 (C-11), 47.7 (C-1), 56.3 (OCH3), 62.4 (C-2), 65.5 (C-
5), 69.6 (C-6), 79.7 (C-10), 101.6 (C-8), 104.7 (C-3), 126.1
(2C, aromatics, Cortho), 128.1 (2C, aromatics, Cmeta),
Acknowledgements
This research was supported by the International Founda-
tion for Science, Stockholm, Sweden, the Organization for
the Prohibition of Chemical Weapons, The Hague, The
Netherlands, CONICET and Agencia Nacional de Pro-
´
´
´
mocion Cientıfica y Tecnologica, Argentina through the
Grants to R.A.S. and A.G.S., and a bilateral CNRS-CON-
ICET agreement (Res. 325/2003). M.I.M. and S.A.T.
thank CONICET for the award of their fellowships.

M. I. Mangione et al. / Tetrahedron: Asymmetry 17 (2006) 1780–1785
1785
8. Schreiber, S. L.; Claus, R. E.; Reagan, J. Tetrahedron Lett.
1982, 23, 3867–3870.
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