Synthesis, high-resolution NMR spectroscopic analysis, and single-crystal X-ray diffraction of isoxazoline tetracycles

Article abstract of DOI:10.1016/S0008-6215(02)00258-6

Three isoxazoline tetracycles were obtained enantiomerically pure by intramolecular 1,3-dipolar cycloaddition. The characterization of the new compounds was performed by high-resolution ¹H and ¹³C NMR spectroscopy. The relative configuration of the new chiral centers was determined by NOESY experiments and confirmed by single-crystal X-ray structural analysis.

Full text of DOI:10.1016/S0008-6215(02)00258-6

Carbohydrate Research 337 (2002) 2419–2425
www.elsevier.com/locate/carres
Synthesis, high-resolution NMR spectroscopic analysis, and
single-crystal X-ray diffraction of isoxazoline tetracycles
Mirta L. Fascio,a Angel Alvarez-Larena,b Norma B. D’Accorsoa,*
aCentro de In6estigaciones de Hidratos de Carbono (CIHIDECAR), Departamento de Qu´ımica Orga´nica,
Facultad de Ciencias Exactas y Naturales, Uni6ersidad de Buenos Aires, Ciudad Uni6ersitaria, Pabello´n II, 3o Piso, C.P. 1428,
Buenos Aires, Argentina
bUnitat de Cristal.lograf´ıa, Uni6ersitat Auto`noma de Barcelona, 08193 Bellaterra, Barcelona, Spain
Received 24 May 2002; accepted 30 July 2002
Abstract
Three isoxazoline tetracycles were obtained enantiomerically pure by intramolecular 1,3-dipolar cycloaddition. The characteri-
1
zation of the new compounds was performed by high-resolution H and 13C NMR spectroscopy. The relative configuration of the
new chiral centers was determined by NOESY experiments and confirmed by single-crystal X-ray structural analysis. © 2002
Elsevier Science Ltd. All rights reserved.
Keywords: Isoxazolines; Intramolecular 1,3-dipolar cycloaddition; Stereocontrol, NMR spectroscopy; X-Ray crystallography
1. Introduction
tion, we synthesized three tetracyclic isoxazolines 4–6,
by the technique described in literature7 for similar
compounds. Thus, the hydroxyl group on C-3 of the
1,3-Dipolar cycloadditions are among the most pow-
erful methods for construction of a variety of five-mem-
bered heterocycles in a one-step route.1 Particularly,
intramolecular cycloadditions with regio- and stere-
ocontrol are important tools for efficient assembly of
complex molecular structures.2
1,2:5,6-di-O-isopropylidene-a-
D
-glucofuranose8
was
functionalized with the (E)-2-butenyl (a), the (E)-3-
phenyl-2-propenyl (b) or the 3-methyl-2-butenyl (c)
group to yield the compounds (1a–1c). The deprotec-
tion of the hydroxyl groups on C-5 and C-6 gave the
1,2-O-isopropylidene derivatives (2a–2c). The dialdose
derivatives were obtained by oxidation of the vicinal
diols. As these compounds were very unstable, they
were directly used for the next step and were character-
ized only by 13C NMR spectroscopy. The treatment of
the dialdose derivatives with hydroxylamine produced
the corresponding mono-oxime derivatives (3a–3c).
Nitrogen–oxygen heterocycles constitute the largest
class of biologically active compounds,3 and several of
these compounds have
system.4,5
a chiral isoxazoline ring
Carbohydrate compounds are a primary source of
chirality in organic synthesis and are used as starting
material to prepare other chiral compounds. In this
field Bhattacharjya and co-workers6 have reported sev-
eral isoxazoline syntheses as precursors of natural prod-
ucts with biologycal interest, where the key steps are
the synthesis and cleavage of heterocyclic ring.
2. Results and discussion
Synthesis.—In order to study the stereocontrol in-
duced by 1,3-intramolecular dipolar cycloaddition reac-
* Corresponding author. Tel./fax: +54-11-4576-3346
E-mail address: norma@qo.fcen.uba.ar (N.B. D’Accorso).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00258-6

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M.L. Fascio et al. / Carbohydrate Research 337 (2002) 2419–2425

M.L. Fascio et al. / Carbohydrate Research 337 (2002) 2419–2425
2421
Although during the cyclization two new stereogenic
centers (compounds 4 and 5) or one new chiral center
(compound 6) were generated, the spectroscopical anal-
ysis showed the presence of only one diasteromer in
Compounds 1–3 were characterized by their NMR
spectra (1D and 2D homonuclear experiments). The
chemical shifts and coupling constants are listed in
Tables 1 and 2, respectively. The assignment of the 13C
NMR spectra was performed using 2D heteronuclear
experiment (HETCOR), see Table 3.
The cycloaddition reaction from compounds 3a–3c
using Chloramine-T yielded the tetracyclic isoxazolines
4–6. We characterized these new compounds spectro-
scopically using 2D NMR techniques for unequivocal
assignation.
1
each case. The chemical shifts for H NMR, coupling
constants and 13C NMR assigments are shown in Ta-
bles 4–6, respectively. The stereochemistry at C-3a and
C-3 were determined by the combined analysis of the
NOESY spectrum and molecular modeling (AM1) of
all the epimers.
In the NOESY spectrum of compound 4 the correla-
tion observed for the pairs H-4/H-5a let us to discard
the 3S, 3aR and the 3R, 3aS stereoisomers, because
these diasteromers do not present this correlation. So
both, the 3S, 3aS or the 3R, 3aR stereoisomers, are
possible. The single-crystal X-ray crystallographic data
concluded that the configuration of new chiral centers
of compound 4 are 3R, 3aR (Fig. 1).
Table 2
1H NMR coupling constants (Hz) for compounds 1–3
Compound
J1,2
J2,3
J3,4
J4,5
J5,6a
J5,6b
J6a,6b
J1%a,2%
J1%b,2%
6.4
J1%a,1%b
J2%,3%
J3%,4%
1a
1b
1c
2a
2b
2c
3a (syn)
(anti )
3b (syn)
(anti )
3c (syn)
(anti )
3.6
3.7
3.6
3.9
3.8
3.8
3.7
3.7
3.6
4.0
3.6
3.7
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
2.9
3.1
2.9
3.4
3.1
3.2
3.2
3.4
3.3
3.4
3.2
3.2
7.5
7.9
5.8
5.5
5.9
5.7
5.0
5.5
–
6.2
6.2
6.2
3.6
3.3
3.3
–
8.5
8.6
8.5
11.5
11.4
11.5
–
12.3
12.9
15.3
16.0
–
15.3
15.9
–
15.2
15.2
15.9
15.9
–
6.5
–
–
6.4
–
–
6.8
6.8
–
6.0
6.8
6.6
6.2
7.3
6.4
6.4
6.1
6.1
6.1
6.2
5.9
6.8
6.2
5.8
6.8
6.1
6.1
6.4
6.4
7.1
7.1
7.4
7.8
8.0
7.5
4.1
7.4
4.4
7.5
4.1
11.8
12.7
11.7
12.0
12.0
12.9
12.8
11.5
11.5
–
–
–
–
–
–
–
–
Table 3
13C NMR chemical shifts (l, ppm) for compounds 1–3, performed in CDCl3
Compound C-1
C-2 C-3 C-4 C-5
C-6 C-1% C-2%
C-3%
C-4%
C6
(CH3)2
Aromatic
carbons
1aa
105.2 82.9 81.0 81.2
72.5 67.2 71.1 127.0 129.7 17.6
72.5 67.4 70.9 125.4 132.6
72.5 67.3 67.0 120.6 133.6 17.9; 25.7
69.1 64.2 70.8 126.5 130.5 17.6
108.8; 111.6
109.0; 111.8
108.8; 111.6
111.6
111.7
111.6
111.9
112.0
112.0
112.1
–
1ba
105.3 82.9 81.2 81.2
105.2 83.0 80.9 81.3
104.9 82.2 81.4 79.7
105.0 82.3 81.9 79.9
105.0 82.3 81.7 79.8
105.3 83.2 83.0 77.8 147.7
104.8 82.8 81.8 75.5 149.4
104.8 83.1 83.5 77.9 147.8
105.3 82.8 82.1 75.6 149.6
105.3 83.3 83.2 77.9 148.1
104.8 82.9 82.0 75.5 149.7
–
126.5–136.6
–
–
126.5–136.3
–
–
1ca
2aa
2bb
69.1 64.2 70.8 124.8 133.2
–
2ca
69.4 64.3 66.5 120.0 138.3 18.0; 25.6
3aa (syn)
(anti )
3bb (syn)
(anti )
3ca (syn)
(anti )
–
–
–
71.2 126.7 130.3 17.6
71.3 126.4 130.5
71.0 124.6 133.0
71.1 125.0 133.2
–
126.5; 136.5
67.2 120.0 138.3 18.0; 25.7
67.0 120.2 138.0 18.1; 25.7
112.0
111.9
–
a Performed at 125 MHz.
b Performed at 50 MHz.

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M.L. Fascio et al. / Carbohydrate Research 337 (2002) 2419–2425
Table 4
1H NMR chemical shifts (l, ppm) for compounds 4–6 performed at 500 MHz in CDCl3
Compound H-3
H-3a H-4
H-4%
H-5a H-5b H-8a H-9a H-10
CH3
Aromatic protons
4
5
6
4.29
5.11
–
3.17
3.57
3.16
3.31
3.47
3.40
4.15
4.27
4.05
3.97
4.05
3.94
4.57
4.59
4.57
5.97
5.95
5.97
4.93
5.01
4.94
1.45
–
1.25; 1.45
1.33; 1.53
1.34; 1.55
1.33; 1.53
–
7.31–7.41
–
Table 5
1H NMR coupling constants (Hz) for compounds 4–6
Compound
J3,3a
J3,10
J3a,4
J3a,4%
J4,4%
J5a,9a
J5a,5b
J5b,8a
4
5
6
8.6
9.1
–
6.2
–
–
11.3
11.2
11.7
5.5
6.2
5.9
9.9
10.3
10.5
2.2
1.8
2.0
ꢀ0
ꢀ0
ꢀ0
3.7
3.5
3.6
Table 6
13C NMR chemical shifts (l, ppm) for compounds 4–6 performed at 125 MHz in CDCl3
Compound C-3 C-3a C-4 C-5a C-5b C-7
C-8a C-9a C-9b C-10
C(CH3)2
Aromatic carbons
4
5
6
79.1 50.0 70.2 82.4 83.3 112.4 106.1 71.5 154.5 19.7
84.6 51.0 70.6 82.4 83.3 112.6 106.1 71.6 154.3
85.0 51.3 67.5 82.2 83.4 112.4 106.1 72.2 154.0 21.7; 28.4
26.2; 26.7
26.3; 26.8
26.2; 26.8
–
–
126.1–138.8
–
In the NOESY spectrum of compound 5 the correla-
with isotropic displacement parameters 1.5 (methyl H)
or 1.2 (the rest) times the Ueq values of corresponding
carbons. The weighting scheme was w=[|2(F02)+
(0.0743P)2+0.0565P]−1 where P=[max(F02, 0)+2F2c]/
3.
tion observed between H-4/H-5a showed that the
3S,3aS or 3R,3aR configurations are the only possibles.
As there was a correlation for the pairs H-4/H-aromatic
(only possible for 3R,3aR stereoisomer) and no correla-
tion between H-3a/H-9a, which should be present in the
3S,3aS stereoisomer, we could discard the latter one.
Thus the new chiral centers are of the R configuration
(Fig. 2). It should be noted that the configurations at
C-3 and C-3a are coincident with that of compound 4.
The NOESY spectrum of compound 6 showed a
correlation for the pair H-4/H-5a that is only possible if
C-3a has the R configuration.
In conclusion, we obtained three compounds enan-
tiomerically pure by intramolecular 1,3-dipolar cycload-
dition reaction. In our cases, the steroechemistry of the
reaccion happened to be independently of the
sustituents on the dipolarophile moiety.
X-Ray crystallographic data.—Suitable crystals of 4
were obtained by cristalization from hexane. Data were
collected on an Enraf–Nonius CAD4 diffractometer
using Mo Ka radiation. Crystal data and structure
determination details are shown in Table 7. The struc-
ture was solved by direct methods (SHELXS-86)9 and
refined by least-squares on F2 for all reflections
(
SHELXL-97).10 Atomic coordinates are included in
Table 8. Non-hydrogen atoms were refined anisotropi-
cally. Hydrogen were placed in calculated positions
Fig. 1. (a) NOESY correlations for compound 4. (b) ORTEP
structure for compound 4.

M.L. Fascio et al. / Carbohydrate Research 337 (2002) 2419–2425
2423
points are uncorrected. AM1 calculations were per-
formed with HyperChem™. Elemental analyses were
performed at the UMYMFOR, Facultad de Ciencias
Exactas y Naturales, University of Buenos Aires,
Buenos Aires, Argentina.
General procedure I. Synthesis of 3-O-alkenyl-1,2:5,6-
di-O-isopropylidene-h-D-glucofuranose (1).—1,2:5,6-Di-
O-isopropylidene-a- -glucofuranose (3.00 g, 11.5
D
Fig. 2. NOESY correlations for compound 5.
mmol)8 was dissolved in dry N,N-dimethylformamide
(DMF 10 mL), and 0.3 g of solid NaH was added. The
mixture was maintained under a nitrogen atmosphere
at 0 °C. When the bubbling stopped, 12 mmol of the
appropriate alkenyl clhoride was added. The reaction
mixture was stirred for 1 h at room temperature, and
then MeOH was added to destroy the excess NaH. The
mixture was concentrated at diminished pressure, and
the product was extracted with CH2Cl2, dried with
anhyd Na2SO4, and the solvent was evaporated under
reduced pressure. The colourless syrup was purified by
column chromatography on aluminium oxide (90 ac-
tive, neutral, 70–230 mesh ASTM) using 9:1 cyclohex-
ane–EtOAc as the eluent. The products were
characterized as follows:
Table 7
Crystal data and structure refinement for compound 4
Empirical formula
Formula weight
Temperature (K)
C12H17NO5
255.27
293(2)
,
Wavelength (A)
Crystal system
Space group
0.71069
Orthorhombic
P212121
Unit cell dimensions
,
a (A)
b (A)
5.261(3)
10.491(2)
23.566(4)
90
,
,
c (A)
h (°)
i (°)
90
(2%E)-3-O-(2%-Butenyl)-1,2;5,6-di-O-isopropylidene-h-
k (°)
90
1300.7(8)
4
3
D
-glucofuranose (1a). Yield: 3.10 g (86%); [h]2D0 −25.2°
,
V (A )
1
(c 0.8, CHCl3); H NMR see Tables 1 and 2; 13C NMR
see Table 3; EIMS m/z (relative intensity) 299 (M−
CH3, 4), 101 (33), 55 (100). Anal. Calcd for C16H26O6:
C, 61.15; H, 8.28. Found: C, 60.79; H, 8.10.
Z
Density (calculated) (Mg
1.304
m−3
)
Absorption coefficient
(mm−1
F(000)
0.102
)
544
Crystal size (mm3)
Theta range for data
collection (°)
0.72×0.50×0.36
1.73–24.95
Table 8
Atomic coordinates (×104) and equivalent isotropic displace-
2
3
,
ment parameters (A ×10 ) for compound 4
Index ranges
05h56, 05k512,
05l527
x
y
z
Ueq
Independent reflections
Refinement method
1141
C(1)
C(2)
O(3)
N(4)
C(5)
C(6)
C(7)
O(8)
C(9)
C(10)
O(11)
C(12)
C(13)
O(14)
C(15)
O(16)
C(17)
C(18)
−777(13)
1391(10)
3016(8)
3417(7)
2082(7)
647(9)
1491(11)
1084(6)
2636(7)
2242(7)
−183(5)
−326(6)
1609(6)
3519(4)
2403(6)
449(4)
−2208(5)
−2277(5)
−1131(4)
−523(3)
−1095(3)
−2239(4)
−3336(4)
−3018(2)
−2015(3)
−804(3)
−349(3)
−592(3)
−1633(3)
−1000(2)
117(3)
6644(2)
7062(2)
6987(1)
7503(2)
7882(1)
7688(2)
8057(2)
8641(1)
8839(1)
8497(1)
8689(1)
9272(1)
9410(1)
9726(1)
9967(1)
9589(1)
9976(2)
131(2)
102(1)
129(1)
102(1)
74(1)
84(1)
99(1)
89(1)
61(1)
64(1)
78(1)
67(1)
64(1)
67(1)
62(1)
68(1)
90(1)
94(1)
Full-matrix least-squares on
F2
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I\2s (I)]
1141/0/163
1.040
R(F)=0.0388,
Rw(F2)=0.1070
R(F)=0.0506,
Rw(F2)=0.1109
0.140 and −0.122
R indices (all data)
Largest diff. peak and hole
−3
,
(e A
)
3. Experimental
General methods.—1H and 13C NMR spectra were
recorded at 200 or 500 MHz and 50 or 125 MHz,
respectively, in CDCl3 with Me4Si as internal standard.
Mass spectra were performed with a Shimadzu QP-
5000 instrument by electron impact ionization. Optical
rotations were recorded at 20 °C, and the melting
471(2)
1157(4)
−161(4)
4362(6)
1302(8)
10548(2)
Ueq is defined as one third of the trace of the orthogonalized
Uij tensor.

2424
M.L. Fascio et al. / Carbohydrate Research 337 (2002) 2419–2425
(2%E)-3-O-(3%-Phenyl-2%-propenyl)-1,2;5,6-di-O-iso-
dissolved in MeOH (10 mL), and a solution of 0.48 g
propylidene-h-
D
-glucofuranose (1b). Yield: 3.40 g (78%);
(6.3 mmol) of hydroxylamine hydrochloride in water (2
mL) and 0.14 g (6.0 mmol) of Na in MeOH (5 mL) was
added. The mixture was allowed to stand at room
temperature until the starting material disappeared as
determined by TLC. The syrup was purified by column
chromatography on aluminium oxide (90 active, neu-
tral, 70–230 mesh ASTM) using 9:1 toluene–EtOAc as
the eluent.
[h]2D5 −34.9° (c 1.3, CHCl3); H NMR see Tables 1 and
2; 13C NMR see Table 3; EIMS m/z (relative intensity)
376 (M, 1), 361 (M−CH3, 2), 117 (100), 101 (39), 43
(99). Anal. Calcd for C21H28O6: C, 67.00; H, 7.50.
Found: C, 67.04; H, 7.37.
1
3-O-(3%-Methyl-2%-butenyl)-1,2;5,6-di-O-isopropyli-
dene-h-
D
-glucofuranose (1c). Yield: 2.65 g (70%); [h]D25
1
−19.4° (c 0.8, CHCl3); H NMR see Tables 1 and 2;
13C NMR see Table 3; EIMS m/z (relative intensity)
328 (M, 1), 313 (M−CH3, 1), 101 (44), 69 (100), 43
(90). Anal. Calcd for C17H28O6: C, 62.20; H, 8.54.
Found: C, 61.85; H, 8.33.
General procedure II. Synthesis of 3-O-alkenyl-1,2-O-
isopropylidene-h-
1,2:5,6-di-O-isopropylidene-a-
mmol) was dissolved in MeOH (10 mL), and 0.8%
sulfuric acid (10 mL) was added. The reaction mixture
was allowed to stand at room temperature until the
starting material disappeared, checked by TLC. The
solution was neutralized with barium carbonate, boiled,
and filtered. The filtrate was evaporated under reduced
pressure. The colourless syrup was purified by chro-
matography on aluminium oxide (90 active, neutral
70–230 mesh ASTM) using 3:2 toluene–EtOAc as the
eluent. The products were characterized as follows:
(2%E)-3-O-(2%-Butenyl)-1,2-O-isopropylidene-h-D-
xylo-pentodialdo-1,4-furanose oxime (3a). Yield: 1.12 g,
4.37 mmol (80%); [h]2D5 −92.0° (c 0.9, CHCl3); 1H
NMR see Tables 1 and 2; 13C NMR see Table 3; EIMS
m/z (relative intensity) 258 (M+1, 3), 242 (M−CH3,
2), 129 (27), 59 (28), 55 (100). Anal. Calcd for
C12H19NO5: C, 56.02; H, 7.44; N, 5.44. Found: C,
56.10; H, 7.59; N, 5.14.
D-glucofuranose
(2).—3-Alkenyl-
D-glucofuranose (1) (7.96
(2%E)-3-O-(3%-Phenyl-2%-propenyl)-1,2-O-isopropyli-
dene-h- -xylo-pentodialdo-1,4-furanose oxime (3b).
D
Yield: 1.47 g, 4.60 mmol (84%); [h]2D5 −98.6° (c 1.3,
1
CHCl3); H NMR see Tables 1 and 2; 13C NMR see
Table 3; EIMS m/z (relative intensity) 319 (M, 1), 304
(M−CH3, 2), 129 (28), 117 (100), 91 (25), 59 (23), 55
(45), 43 (70). Anal. Calcd for C17H21NO5: C, 63.95; H,
6.58; N, 4.39. Found: C, 63.93; H, 6.87; N, 4.17.
3-O-(3%-Methyl-2%-butenyl)-1,2-O-isopropylidene-h-
D
-xylo-pentodialdo-1,4-furanose oxime (3c). Yield: 1.04
1
(2%E) - 3 - O - (2% - Butenyl) - 1,2 - O - isopropylidene-h-
D-
g, 3.83 mmol (70%); [h]2D5 −94.6° (c 1.7, CHCl3); H
NMR see Tables 1 and 2; 13C NMR see Table 3; EIMS
m/z (relative intensity) 272 (M+1, 2), 256 (M−CH3,
2), 143 (19), 69 (100). Anal. Calcd for C13H21NO5: C,
57.55; H, 7.80; N, 5.16. Found: C, 58.04; H, 8.13; N,
4.84.
glucofuranose (2a). Yield: 1.60 g, 5.85 mmol (74%); [h]D25
1
−43.6° (c 1.0, CHCl3); H NMR see Tables 1 and 2;
13C NMR see Table 3; EIMS m/z (relative intensity)
275 (M+1, 5), 259 (M−CH3, 1), 61 (33), 55 (100).
Anal. Calcd for C13H22O6: C, 56.93; H, 8.03. Found: C,
57.20; H, 8.30.
General procedure IV. Synthesis of isoxazoline tetra-
(2%E)-3-O-(3%-Phenyl-2%-propenyl)-1,2-O-isopropyli-
cyclic.—3-O-Alkenyl-1,2-O-isopropylidene-a-D-xylo-
dene-h-
D
-glucofuranose (2b). Yield: 2.15 g, 6.39 mmol
pentodialdo-1,4-furanose oxime (3, 3.89 mmol) was dis-
solved in 4:1 MeOH–water (10 mL), and Chloramine-T
(1.32 g, 4.67 mmol) was added. The reaction was stirred
at room temperature until the starting material disap-
peared as determined by TLC. The reaction product
was purified by flash chromatography on Silica Gel G,
using 95:5 cyclohexane–EtOAc as the eluent. The prod-
ucts were characterized as follows:
(80%); [h]2D5 −34.4° (c 2.5, CHCl3); 1H NMR see
Tables 1 and 2; 13C NMR see Table 3; EIMS m/z
(relative intensity) 335 (M−1, 7), 321 (M−CH3, 1),
131 (87), 117 (100). Anal. Calcd for C18H24O6: C, 64.29;
H, 7.14. Found: C, 64.41; H, 7.34
3-O-(3%-Methyl-2%-butenyl) -1,2-O-isopropylidene-h-
D
-glucofuranose (2c). Yield: 1.72 g, 5.99 mmol (75%);
1
[h]2D5 −22.5° (c 1.0, CHCl3); H NMR see Tables 1 and
2; 13C NMR see Table 3; EIMS m/z (relative intensity)
289 (M+1, 1), 273 (M−CH3, 1), 221 (9), 69 (100), 41
(45). Anal. Calcd for C14H24O6: C, 58.32; H, 8.39.
Found: C, 58.25; H, 8.51.
(3R,3aR,5aS,5bR,8aR,9aR) - 3,7,7 - Trimethyl - 3a,4,
5a,5b,8a,9a - hexahydro - 3H - [1,3]dioxolo[4%%,5%%:4%,5%]-
oxolo[2%,3%:5,6]oxino[4,3-c]isoxazole (4). Yield: 0.77 g,
3.04 mmol (78%); mp 115–117 °C; [h]2D5 +182.5° (c 1.0,
1
CHCl3); H NMR see Tables 4 and 5; 13C NMR see
General procedure III. Synthesis of 3-O-alkenyl-1,2-
Table 6; EIMS m/z (relative intensity) 255 (M, 2), 240
(M−CH3, 24), 55 (27), 43 (100). Anal. Calcd for
C12H17NO5: C, 56.47; H, 6.67; N, 5.49. Found: C,
56.74; H, 6.95; N, 5.46.
(3R,3aR,5aS,5bR,8aR,9aR)-7,7-Dimethyl-3-phenyl-
3a,4,5a,5b,8a,9a-hexahydro-3H-[1,3]dioxolo[4%%,5%%:4%,5%]-
oxolo[2%,3%:5,6]oxino[4,3-c]isoxazole (5). Yield: 0.88 g,
2.77 mmol (71%); mp 119–121 °C; [h]2D5 +252.8° (c 1.0,
O-isopropylidene-h-D-xylo-pentodialdo-1,4-furanose ox-
ime (3).—3-O-Alkenyl-1,2-O-isopropylidene-a-
D
-
glucofuranose (2) (5.48 mmol) was treated according to
the technique described in literature,11 and 3-O-alkenyl-
1,2-O-isopropylidene-a-D-xylo-pentodialdo-1,4-fura-
nose was obtained as an unstable syrup, which was
identified by its 13C NMR spectrum. The syrup was

M.L. Fascio et al. / Carbohydrate Research 337 (2002) 2419–2425
2425
1
CHCl3); H NMR see Tables 4 and 5; 13C NMR see
de Buenos Aires for financial support. Dr. N. B. D’Ac-
corso is research member of CONICET. They are also
very grateful to UMYMFOR (CONICET-FCEyN
Table 6; EIMS m/z (relative intensity) 317 (M, 8), 302
(M−CH3, 14), 105(14), 91 (23), 59 (28), 55 (20), 43
(100). Anal. Calcd for C17H19NO5: C, 64.34; H, 6.03.
Found: C, 64.02; H, 6.44.
1
UBA) for the recording of the H and 13C NMR, as
well as for the microanalyses and mass spectra.
(3aR,5aS,5bR,8aR,9aR) - 3,3,7,7 - Tetramethyl - 3a,4,
5a,5b,8a,9a - hexahydro - [1,3]dioxolo[4%%,5%%:4%,5%]oxolo-
[2%,3%:5,6]oxino[4,3-c]isoxazole (6). Yield: 0.80 g, 2.98
mmol (77%); mp 129–131 °C; [h]2D5 +122.6° (c 1.0,
References
1
CHCl3); H NMR see Tables 4 and 5; 13C NMR see
1. Padwa, A. 1,3-Dipolar Cycloaddition Chemistry; John
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Re6. 1995, 95, 1677–1716.
Table 6; EIMS m/z (relative intensity) 269 (M, 2), 254
(M−CH3, 25), 43 (100). Anal. Calcd for C12H17NO5:
C, 57.99; H, 7.06; N, 5.20. Found: C, 58.29; H, 7.34; N,
5.14.
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4. Supplementary material
Full crystallographic details, excluding structure fac-
tors, have been deposited with the Cambridge Crystal-
lographic Data Centre. These data (CCDC 189789)
may be obtained, on request, from the CCDC, 12
Union Road, Cambridge CB2 1EZ, UK. Tel. + 44
1223 336408, Fax
+
44 1223 336033, E-mail
deposit@ccdc.cam.ac.uk
9. Sheldrick, G. M. In Crystallographic Computing 3;
Sheldrick, G. M.; Kruger, C.; Goddard, R., Eds.; Oxford
University Press: Oxford, 1985; pp 175–189.
10. Sheldrick, G. M. SHELX97. Program for Crystal Struc-
ture Analysis (Release 97-2). University of Go¨ttingen,
Germany, 1997.
Acknowledgements
The authors thank the Consejo Nacional de Inves-
tigaciones Cient´ıficas y Te´cnicas and the Universidad
11. Sowden, J. C. J. Am. Chem. Soc. 1951, 73, 5496–5497.