Regio- and stereoselective synthesis of 3- and 5-(C-glycosyl)-4- nitroisoxazolidines by nitrone-nitroalkene [3+2] cycloaddition reactions

Article abstract of DOI:10.1016/S0957-4166(98)00488-1

Cycloaddition reactions of nitrones, including sugar nitrones, with nitroalkenes, including sugar nitroolefins, led with complete regioselectivity and stereospecificity to 4,5-trans-4-nitroisoxazolidines in 51-78% global yields. The endo/exo stereoselectivity depends on the type of sugar derivative used. As expected, the best π-diastereofacial selectivity was observed when both partners were sugar derivatives. Isomerisation of the first formed diastereomers by the action of silica gel was observed in some cases. Absolute configurations for two crystalline products were assigned by X-ray diffraction methods.

Full text of DOI:10.1016/S0957-4166(98)00488-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 10 (1999) 77–98
Regio- and stereoselective synthesis of 3- and 5-(C-glycosyl)-
4-nitroisoxazolidines by nitrone–nitroalkene [3+2] cycloaddition
reactions
Pastora Borrachero,a Francisca Cabrera,a Mp Jesús Diánez,b Mp Dolores Estrada,b
Manuel Gómez-Guillén,a,∗ Amparo López-Castro,b José Mp Moreno,a José L. de Paz a and
Simeón Pérez-Garrido b
aDepartamento de Química Orgánica ‘Profesor García González’, Facultad de Química, Universidad de Sevilla,
Apartado de Correos No. 553, E-41071 Sevilla, Spain
bInstituto de Ciencias de Materiales de Sevilla and Departamento de Física de la Materia Condensada,
C.S.I.C.-Universidad de Sevilla, Apartado de Correos No. 1065, E-41080 Sevilla, Spain
Received 19 October 1998; accepted 7 December 1998
Abstract
Cycloaddition reactions of nitrones, including sugar nitrones, with nitroalkenes, including sugar nitroolefins,
led with complete regioselectivity and stereospecificity to 4,5-trans-4-nitroisoxazolidines in 51–78% global yields.
The endo/exo stereoselectivity depends on the type of sugar derivative used. As expected, the best π-diastereofacial
selectivity was observed when both partners were sugar derivatives. Isomerisation of the first formed diastereomers
by the action of silica gel was observed in some cases. Absolute configurations for two crystalline products were
assigned by X-ray diffraction methods. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
1,3-Dipolar cycloaddition reactions1 have been widely used in the last two decades as the first step
in strategies for the synthesis of diverse natural products and analogues. Nitrones, easily available
from aldehydes or ketones and N-monosubstituted hydroxylamines, are one kind of 1,3-dipoles that
undergo [3+2] cycloaddition reactions with alkenes to afford isoxazolidine derivatives having a masked
1,3-aminoalcohol functionality.2 Three new stereogenic centres are generated in the reaction. Sugar
derivatives have been considered as suitable target molecules since cycloaddition reactions of nitrones
with certain dipolarophiles show, besides stereospecificity, good regio- and stereoselectivities.3 Thus,
the regio- and stereochemistry of reactions between N- or C-glycosyl nitrones and olefins leading to
∗
Corresponding author. Tel: +34 95 4557151; fax: +34 95 4624960; e-mail: mguillen@cica.es
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00488-1

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diversely substituted glycosyl isoxazolidines have been studied,4–6 and applications to the synthesis
of aminohexoses starting from C-glycosyl nitrones are known.7,8 The intramolecular version of the
nitrone–alkene cycloaddition reaction has been applied to sugar nitrones and the stereochemical course
has been studied, for instance in the case9 of nitrones of 3-O-allyl-D-hexoses. Reactions of alkenes having
heterotopic faces with sugar nitrones, like other chiral nitrones,10 are expected to proceed showing not
only endo/exo stereoselectivity, but also π-diastereofacial selectivity (asymmetric induction). This possi-
bility also arises when the chiral component is the dipolarophile11 instead of the nitrone. Moreover, when
both partners are enantiomerically pure, the diastereofacial selectivity will reach a much higher value if
they constitute a matched pair. Stereochemical control of the reaction is then necessary for obtaining one
of the eight possible diastereomers as the predominant product. We now report on the stereochemical
course of cycloaddition reactions of three C-glycosylnitrones with β-nitrostyrene and p-methoxy-β-
nitrostyrene, two sugar nitroolefins with N-benzyl-C-phenylnitrone, and two C-glycosylnitrones with
nitroolefins derived from the same sugars, respectively.
2. Results and discussion
The (Z)-N-benzyl-C-glycosylnitrones 1–3 (Scheme 1), easily obtained by reaction of N-
benzyl-hydroxylamine
with
1,2:3,4-di-O-isopropylidene-α-D-galacto-hexodialdo-1,5-pyranose,
1,2-O-isopropylidene-α-D-xylo-, and -α-D-ribo-pentodialdo-1,4-furanose, respectively, underwent
regioselective [3+2] cycloaddition reaction with excess β-nitrostyrene 5 in toluene at 50–110°C,
to afford diastereomeric mixtures of 2-benzyl-3-(glycopyranos-5-yl or glycofuranos-4-yl)-4-nitro-5-
phenylisoxazolidines 9, 11, and 12 in 54%, 48%, and 73% global yields, respectively. The presence of
an electron-donor group, such as the p-methoxy group, on the aromatic ring of β-nitrostyrene seems
to raise the reactivity of the dipolarophile, since the nitrone 1 reacted with p-methoxy-β-nitrostyrene 6
under similar conditions to afford a diastereomeric mixture of the corresponding isoxazolidine derivative
10 in a higher yield (72%). Starting from N-benzyl-C-phenylnitrone 4 and the sugar nitroolefins 7
and 8, derived from nitromethane and the two dialdo-sugars cited first and second above, resulted
in diastereomeric mixtures of the isoxazolidines 13 (global yield, 78%) and 14 (66%), respectively.
Reaction of equimolar amounts of the nitrone 1 and the nitroolefin 7, both derived from D-galactose,
afforded 52% of a mixture of cycloadducts 15, whereas the D-xylose derivatives 2 and 8 gave rise to one
predominant diastereomer (>90:10) of 16 in 51% yield.
1
The regioselectivity of these reactions, as deduced from the H and 13C NMR spectra of 9–16
(Tables 1 and 2, respectively), was that expected from antecedents for reactions of nitroalkenes, such
as β-nitrostyrene itself12 or nitroethylene13,14 with other nitrones, that is, the nitro group is oriented to
position 4 of the isoxazolidine ring. COSY and HETCOR experiments confirmed the assignments given
in Tables 1 and 2.
More problematic is the assignment of absolute configuration to the new stereogenic centres. It
is known15 that the coupling constant values measured on the signals of H-3, H-4, and H-5 of the
isoxazolidine ring are not clearly correlated with their cis or trans relative disposition, since different
ring conformations are possible. NOE experiments are normally needed for ascertaining the spatial
relationships in isoxazolidine derivatives.16 Some stereochemical features may be predicted; thus, star-
ting from a trans-1,2-disubstituted alkene, the formation of a trans-3,4-disubstituted isoxazolidine is
expected, due to the stereospecificity of the cycloaddition reactions. If it is assumed that this rule is
followed, the number of possible diastereomeric products will be limited to four (a, b, c, d, Scheme 2).
The stereoselective formation of a and c through endo transition states, over b and d, coming from

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
79
Scheme 1.
exo approaches, should be expected. However, this second rule is not always obeyed. It is known that
certain aldonitrones undergo Z–E isomerisation under the reaction conditions,17 and the presence of both
isomers of C-glycosyl nitrones in the reaction mixtures could not be ruled out5,11 in spite of the high
energy differences calculated by semiempirical methods.5 In the cases discussed here, we have not found
any evidence for the presence of E-isomers of 1–4, in agreement with other authors,18,19 but we cannot
completely exclude their formation in the course of the reactions.
In the reactions of 1 with 5 and 6, the formation of two diastereomers was observed (65:35 by
1H NMR), which underwent a partial isomerisation when in contact with the silica gel used in the
subsequent chromatographic separation, to give a new diastereomer 9b as the main component of the new
mixture of products (72:18:10; global yield, 54%); a similar isomerisation by silica gel had earlier13 been
observed for an isoxazolidine obtained in the reaction of nitroethylene with N-methyl-C-phenylnitrone,
and had been described as a 3,4-cis-to-trans isomerisation. In our case, the major isolated diastereomer 9b
could be crystallised and its absolute configuration was unambiguously determined by X-ray diffraction
analysis as 2S,3S,4S,5R, that is, its structure corresponds to one of the two possible invertomers at the
1
isoxazolidine nitrogen (2S)-9b (Fig. 1, Table 3). The two minor products were identical (by H NMR)
to the components of the original reaction mixture, respectively; the more abundant among these two
crystallised from the mother liquors of (2S)-9b, and was characterised as 9d from the following evidence:
(i) 1D NOESY experiments, carried out on a sample in DMSO-d6 at 40°C, clearly showed the 3,4-cis
and 4,5-trans configurations (H-3/H-4 contacts, absence of H-3/H-5 contact); (ii) it slowly isomerises to
9b in the same solvent, to give, after 5 days at room temperature, a ∼89:11 mixture of 9b and 9d. Apart
from that, compound 9d showed in solution the behaviour of a system in relatively slow equilibrium, as
suggested by the 1H NMR spectra in CDCl3 at room temperature or in DMSO-d6, where H-3, H-5 and
the benzylic methylene protons appeared as broadened signals. However, lowering the temperature of
the solution in CDCl3 down to −25°C resulted in the separation in the spectra of two isomers (86% and
14%), although neither was superimposable to that of 9b; hence, the equilibrating system is a mixture of
invertomers (2R)- and (2S)-9d. For the minor component of the diastereomer mixture, the endo structure
9a (or 9c) is tentatively assigned. Thus, an explanation for the foregoing results may be that the products
9d and 9a of the kinetic mixture isomerise over the course of chromatography to give the thermodynamic
mixture, from which the main product 9b crystallises; the isomerisation might occur through a silica gel
catalysed equilibration by cycloreversion of the former products and a new cycloaddition by attack of the
nitroalkene on the opposite face of the nitrone.

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Table 1
Selected 1H NMR data for compounds 9–16 at 500 MHza

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
81
The reaction of 1 with 6 proceeded in a similar manner, 1H NMR of the mixture showing the presence
of only two diastereomers of 10 (67:33); isomerisation of these products took place during column
chromatography, and the new diastereomer could be isolated pure as an oil, to which the absolute

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P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
Table 2
Selected 13C NMR data for compounds 9–16 in CDCl3
1
configuration 3S,4S,5R (10b) was assigned on the basis of the similarity found between its H and 13C
NMR spectra and those of 9b (Tables 1 and 2). For the main primitive diastereomer, the structure 10d is
assigned by analogy with the respective diastereomer of 9.
The reactions of the nitrones 2 and 3 with 5 led to 65:35 and 61:39 mixtures of diastereomers of
11 and 12, respectively. No isomerisation provoked by silica gel was observed in the chromatographic
purification. The absolute configuration of the major diastereomer of 11 was tentatively assigned by 1D
NOESY, which evidenced the 3,4-cis and 4,5-trans configurations (H-4/H-3 contact; absence of contacts
H-4/H-5 and H-3/H-5) and the cis disposition between the N-benzyl group and the sugar moiety (H-
5/NCHHPh and H-5/H-10 contacts), in agreement with the expected H-4/H-40 contact also observed.

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
83
Scheme 2.
These facts are compatible with 11b or 11d. Molecular models seem to indicate that 11d is sterically
more hindered than 11b due to the presence of the 30-O-benzyl group in the same configured sugar
moiety for both diastereomers; the 11b structure is thus tentatively assigned for the major isomer, to
which the 3S,4S,5R configuration should correspond. Moreover, in this case, the more stable invertomer
in solution seems to be the 2R configured one, as deduced from the NOE contact between H-5 and
one of the benzylic methylene protons mentioned above. For the minor diastereomer, the alternative
11d structure is assigned on the assumption that the exo attack, as for its isomer, is predominant. With
respect to the configuration of the major isomer of the ribose derivative 12, it was also determined on
the basis of 1D NOESY experiments, from which the 3,4-cis and 4,5-trans relationships were deduced
(H-4/H-3 contact; absence of contact between H-4 and H-5). By comparison of models of 12b and 12d,
it appears that the H-4/H-40 and H-4/H-30 contacts observed are more compatible for the former than
for the latter. The contact between H-5 and one of the methylene hydrogen atoms of N-benzyl again
agrees here with the assignment of the (2R)-12b structure for the major isomer. The 12d configurational
structure is tentatively assigned for the minor isomer.
Products 13 and 14, formed in the reactions of the nitrone 4 with the sugar nitroolefins 7 and 8,

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P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
Figure 1. A PLATON view of (2S)-9b showing the atomic labelling. Thermal ellipsoids enclose 30% probability. C–H bonds
are omitted for clarity
Table 3
Selected bond distances (Å) and torsion angles (°) for (2S)-9b
respectively, were also separated into pure diastereomers by chromatography on silica gel. For 13, three
diastereomers were detected in the reaction mixture (55:36:9 by 1H NMR). After column chromatogra-
phy, the two major products were isolated as pure diastereomers (44% and 25%, respectively); the second
one was crystalline and could be unambiguously characterized by X-ray diffraction methods as the
(2S,3R,4R,5R) diastereomer [(2S)-13a, Fig. 2, Table 4], formation of which is explained as coming from
the endo attack of the sugar nitroalkene to the si,si face of the nitrone (Scheme 2). The configurational
assignment for the major diastereomer is based only on NMR data and mechanistic considerations; thus,
the higher values of J3,4 and J4,5 (8.0 and 4.6 Hz) as compared, respectively, with those for 13a (6.9 and
0
2.7 Hz), and particularly the much lower value of J5,5 for the former (1.5 Hz) than for the latter (8.4
Hz) are in fair agreement with those expected for the structure 13c (3S,4S,5S, probably 2R as the more

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
85
Figure 2. A PLATON view of (2S)-13a showing the atomic labelling. Thermal ellipsoids enclose 30% probability. C–H bonds
are omitted for clarity
stable invertomer). In a first approach, molecular models show that the sugar moiety in 13a would adopt
in solution a preferred conformation around the C-5–C-50 bond having a dihedral H–C–C–H angle of
∼180°, similar to that adopted in the crystalline state (172.04°, see Table 4 and Fig. 2), but in 13c this
0
value would be incompatible with the J5,5 value (1.5 Hz) cited above, a rotation down at ∼110° (or ∼70°)
being in better agreement; the models reveal that a value of ∼180° in 13c (but not in 13a) would cause an
unfavourable dipolar interaction between the nitro group and the C-40–O bond of the sugar moiety. The
major diastereomer 13c would come from the endo attack of the sugar nitroalkene to the re,re face of the
nitrone, the π-diastereofacial selectivity being 55:36 (60:40). A mixed fraction from the chromatography
contained a small amount of 13a (2.4%) and the minor diastereomer (6%), a configurational assignment
for which could not be ascertained from the 1H NMR of this mixture, the remaining possibilities being
13b or 13d. With respect to the xylose derivative 14, the major isomer shows the 3,4-cis and the 4,5-trans
relationships as deduced from its 1D NOESY spectrum (H-4/H-3 contact, low intensity H-5/H-4 contact,
absence of H-5/H-3 contact), compatible with the structures 14b or 14d; the second main diastereomer
is tentatively formulated as the 14a or 14c isomer, since NOE experiments (1D NOESY) revealed the
trans relationship for both H-3/H-4 and H-4/H-5 proton pairs on the isoxazolidine ring (low intensity
contacts between them in each pair and also between H-3 and H-5). Two minor diastereomers (12% and
2%) were also isolated, although the experimental data obtained for them were insufficient to assign any
configuration.
The reaction of 1 with 7 led to 15 as a ∼70:30 mixture of two isomers (by 13C NMR), among which
1
only the major one (41% after column chromatography) could be studied as a pure substance. Its H
NMR spectrum, recorded in DMSO-d6 at 50°C, showed broadened H-3 and H-5 signals (Table 1), which
suggested a slowly equilibrating system similar to that found for 9d (see above). When the spectrum
was recorded in CDCl3 at −25°C, signals for two invertomers (77:23) were again observed here; for
the major invertomer under these last conditions, the cis-relationship between H-3 and H-4 and the
trans-disposition between H-4 and H-5 were deduced from 1D NOESY experiments (H-3/H-4 contact;
absence of H-4/H-5 and H-3/H-5 contacts). From these facts and by analogy with 9b (particularly the
chemical shift of H-4) the structure 15b is assigned for the isolated diastereomer; the major invertomer
has probably the (2S) configuration as deduced from the NOE contact also observed between H-3 and

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Table 4
Selected bond distances (Å) and torsion angles (°) for (2S)-13a
one of the benzylic methylene protons. A mixed fraction from the chromatography contained the minor
isomer (11% yield by 1H NMR), to which the structure 15d is tentatively assigned.
Finally, in the reaction of 2 with 8 a main product was formed accompanied by <10% of a diastereomer
(by 1H NMR). Only the major product was isolated after column chromatography (16, 51%), for which
the configurational structures 16b (3S,4S,5S) or 16d (3R,4R,5R) might be assigned on the basis of some
similarities of its NMR spectra with those of 11b and 11d, and mechanistic considerations, but the
available data are not conclusive.
2.1. X-Ray structure analysis of (2S)-9b
A PLATON view20 of the molecule along the c axis together with the atomic labelling is shown
in Fig. 1. Selected bond lengths and torsion angles are shown in Table 3. The pyranose endocyclic
bond lengths are O15–C1=1.417(11) and O15–C5=1.441(11) Å showing some anomeric effect. The
two phenyl groups are planar (max. s.d. 0.015 Å). The geometry observed for the pyranose ring shows
a heavily distorted conformation21 between twist-boat (skew-boat) OT2 and screw-boat OS5 deviated
towards B2,5. In terms of ring-puckering coordinates,22 amplitudes and phase magnitudes are Q=0.66(1)
Å, ϕ=−36(1)°, and θ=82(1)° for the sequence O15–C1–C2–C3–C4–C5, and the asymmetry parameters23
are ∆C2[C1]=0.059 and ∆C2[O15–C5]=0.042. The two dioxolane rings have different conformations.
The geometry observed for one dioxolane ring with sequence O1–C12–O2–C2–C1 is intermediate
between T and E with puckering coordinates Q=0.32(1) Å, ϕ=−99(2)°. The asymmetry parameters are
∆C2[O11]=0.031 and ∆Cs[O2]=0.040. The other dioxolane group, sequence O3–C34–O4–C4–C3 shows
a slightly distorted E conformation, Q=0.29(1) Å and ϕ=5(1)°, asymmetry parameters ∆C2[C4]=0.0038
and ∆Cs[O3]=0.023. The isoxazolidine ring conformation is slightly distorted E, of which puckering
and asymmetry parameters are Q=0.467(7) Å, ϕ=34(1)°, ∆Cs[N6]=0.017, and ∆C2[C7]=0.074 for
the sequence O8–N6–C6–C7–C8. The isoxazolidine substituents C61 and C81 are on one side at
−0.407(10) and −0.828(9) Å and N7 and C5 are on the other side of the least-squares best plane
at 1.448(10) and 0.877(10) Å. The dihedral angles formed by least-squares planes are: isopropyli-
dene–pyranose 78.3(3) and 86.1(3)° and isoxazolidine–pyranose 79.3(4)°. The packing of molecules is

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
87
governed by van der Waals forces. There are three intramolecular short contacts: C63· · ·O8=3.215(13),
C61· · ·O15=3.016(12), and C7· · ·O4=3.076(13) Å.
2.2. X-Ray structure analysis of (2S)-13a
A PLATON view20 of the molecule along the c axis together with the atomic labelling is shown
in Fig. 2. Selected bond lengths and torsion angles are shown in Table 4. The typical asymmetry
of endocyclic bonds for the pyranose ring O15–C1 and O15–C5 [1.405(6) and 1.431(7) Å, respec-
tively] caused by the anomeric effect, is observed. The two phenyl groups are planar and the C9
(benzyl methylene) is slightly distorted (0.066 Å) from the least-squares phenyl plane. The pyranose
geometry observed for this compound agrees with a heavily distorted conformation between twist-
boat (skew-boat) OT2 and screw-boat OS5 deviated towards B2,5, in agreement with the foregoing
compound and other 1,2:3,4-di-O-isopropylidene-D-galactopyranose derivatives.21 The ring-puckering
coordinates22 and asymmetry parameters are Q=0.65(1) Å, ϕ=−35(1)°, and θ=79(1)° for the sequence
O15–C1–C2–C3–C4–C5, and ∆C2[C1]=0.070 and ∆C2[O15–C5]=0.033. The geometries observed for
the two dioxolane rings are also different, in agreement with (2S)-9b. The conformation for one of
them with sequence O3–C34–O4–C4–C3 is intermediate between T and E, with puckering coordinates
and asymmetry parameters Q=0.27(1) Å, ϕ=−12(1)°, ∆C2[C4]=0.015 and ∆Cs[O3]=0.048. The other
dioxolane group sequence O1–C12–O2–C2–C1 shows a slightly distorted E conformation, Q=0.31(1)
Å, ϕ=−114(1)°, and ∆Cs[O2]=0.027 and ∆C2[C1]=0.038. The isoxazolidine ring shows a geometry
different to (2S)-9b, the conformation for the sequence O6–N8–C8–C7–C6 being intermediate between
T and E with parameters Q=0.49(1) Å, ϕ=−28(1)°, and ∆Cs[N8]=0.059, ∆C2[C7]=0.049. The isoxazo-
lidine substituents C81 and C5 are on one side at 0.310(8) and 1.663(5) Å and the C9 and N7 on the
other side of the least-squares best plane at −0.283(6) and −1.125(5) Å. The dihedral angles between the
least-squares planes of the pyranose and isopropylidene groups are 103.5(2) and 98.9(2)°, and between
those of isoxazolidine and pyranose 69.6(3)°. Crystal cohesion by van der Waals interactions: there is
one intramolecular short contact C5· · ·O2=3.101(7) Å.
3. Conclusion
The reactions studied here proceeded with complete regioselectivity to give isoxazolidines with the
nitro group at position 4. All the products 9–16 exhibited the 4,5-trans relationship, in agreement with
the stereospecificity rule of cycloaddition reactions. Table 5 summarizes the formed diastereomeric ratios
in the reaction mixtures and the global and isolated diastereomer yields after chromatography. Only
two diastereomers were formed when the glycosyl substituent is at position 3 9–12; for the D-galactose
derivatives 9 and 10, these isomers are exo/endo diastereomers, the exo one (d) undergoing isomerisation
in contact with silica gel to its more stable π-facial diastereomer b; for the pentose derivatives 11 and
12, the initially formed exo adducts suffered no isomerisation by silica gel and seem to be the isomers
b and d, the π-diastereofacial selectivity (expressed as formed diastereomeric ratio) rising to ∼3:2.
Starting from the sugar nitroalkenes 7 and 8 and the C-phenyl nitrone 4, the stereoselectivity is low,
as three isomers of 13 and four of 14 were formed (Table 5). Therefore, the exo/endo and/or the π-facial
stereoselectivities seem to be generally better for reactions of C-glycosyl nitrones than for those of sugar
nitroalkenes. The reactions between reagents both containing a sugar moiety gave the cycloadducts 15
and 16 with complete exo stereoselectivity, leading to b and d with better π-diastereofacial selectivity
values (∼7:3 for 15 and ∼9:1 for 16), as a consequence of the double asymmetric induction exerted by

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P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
Table 5
1
Diastereomeric ratios in the reaction mixtures (by H NMR) and globala and isolated diastereomer
yieldsa
both sugar derivatives used as the reagents, which form a matched pair. With respect to isolated products,
the major one agrees with the major formed product, except for 9 and 10, where a partial isomerisation
of the adducts d and c (or a) to b occurs during the chromatographic separation; this fact is explained
assuming a silica gel catalysed cycloreversion of the kinetic adduct followed by a new cycloaddition to
the thermodynamically more stable one.
4. Experimental
4.1. General
TLC was performed on silica gel 60 plates (DC-Alufolien F254, E. Merck, or Alugram Sil G/UV254
,
Macherey–Nagel), with detection by UV light (254 nm) or by charring with H2SO4. Silica gel 60 (E.
Merck) was used for column chromatography. Solutions were concentrated under reduced pressure.
Optical rotations were measured in CHCl3 with a Perkin–Elmer 241 MC polarimeter. IR spectra (films
on KBr discs) were recorded with an FTIR Bomem Michelson MB-120 spectrometer. UV spectra
1
were obtained on a Philips PU 8710 spectrophotometer. H NMR spectra (500 MHz) and 13C NMR
spectra (125.8 or 75.5 MHz) were recorded from solutions in CDCl3 or DMSO-d6 with a Bruker
AMX-500 or a Bruker AMX-300 spectrometer. Assignments were confirmed by decoupling and/or
homonuclear 2D COSY, 1D NOESY, and heteronuclear 2D correlated (HETCOR) experiments. HR-
EI mass spectra (70 eV) were measured with a Kratos MS-80RFA instrument, with an ionising current
of 100 µA, an accelerating voltage of 4 kV, and a resolution of 10 000 (10% valley definition). Fast-
atom bombardment mass spectrometry (FABMS) was performed on the same instrument; ions were
produced by a beam of xenon atoms (6–7 keV) using a matrix consisting of m-nitrobenzyl alcohol
or thioglycerol and NaI as salt. FAB-HRMS was performed on a VG Autospec spectrometer (Fisons
Instruments) (30 keV). Crystalline compounds were studied by X-ray diffraction; intensity data were

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
89
collected from a single crystal on an Enraf-CAD4 diffractometer with an ω–2θ scan technique at 295
K using a Mo-Kα radiation graphite monochromator, with scattering angles in the range 4<2θ<50°.
Three standard reflections measured every hour during the entire collection period showed no significant
trend. The raw step–scan data were converted into intensities and corrected for Lorentz and polarisation
factors, extinction factors were ignored. The structures were solved by direct methods using SIR9224 and
refinement based on F of the non-H atoms by full matrix least-squares methods. The function minimised
P
was w(|FO|−|FC|)2 with w=1/σ2(FO). All heavy atoms were refined with anisotropic parameters and
all hydrogen atoms were placed in geometrically calculated positions with C–H=1.00 Å and included
as fixed contributors in the structure factor calculations with isotropic thermal parameters as the atom
to which they were bonded but not refined. Atomic scattering factors were taken from International
Tables for X-Ray Crystallography25 and all calculations were carried out with the X-ray system of
crystallographic programs.26 The geometrical analysis was performed using PARST.27
4.2. (Z)-N-Benzyl-(1,2:3,4-di-O-isopropylidene-α-D-galactopyranos-6-ylidene)amine N-oxide 1
A solution of 1,2:3,4-di-O-isopropylidene-α-D-galacto-hexodialdo-1,5-pyranose28 (1.29 g, 5 mmol)
in dichloromethane (20 mL) was added, with stirring, to a suspension of sodium hydrogencarbonate
(0.48 g), magnesium sulphate (0.80 g), 4 Å molecular sieve, and N-benzyl-hydroxylamine hydrochloride
(0.85 g, 5.3 mmol) in dichloromethane (35 mL) at room temperature, and the stirring was maintained
for 5 h (monitoring by TLC). The mixture was then filtered and the filtrate was concentrated to give an
1
amorphous product (1.74 g, 96% of conversion by H NMR), column chromatography of which (2:3
hexane:EtOAc) afforded pure 1 (1.16 g, 60%); after recrystallisation (EtOH), 1 showed mp 105–107°C;
[α]D24 −111 (c 1); (lit.18 mp 106°C; [α]D20 −120.5); UV (96% EtOH) λmax 240 nm (εmM 4.60); IR (KBr)
νmax 1616 (C_N) and 862 cm−1 (NO); 1H NMR (300 MHz, CDCl3) δ 7.44–7.37 (m, 5H, Ph), 6.72 (d,
1H, J5,6=5.1, H-6), 5.50 (d, 1H, J1,2=5.0, H-1), 5.01 (dd, 1H, J4,5=2.0, H-5), 4.91 (s, 2H, CH2Ph), 4.74
(dd, 1H, J3,4=7.9, H-4), 4.61 (dd, 1H, J2,3=2.4, H-3), 4.31 (dd, 1H, H-2), 1.56, 1.42, 1.33, 1.32 (each
s, each 3H, 4Me); 13C NMR (75.5 MHz, CDCl3) δ 136.6 (C-6), 132.1 (ipso-C of Ph), 129.3, 128.8,
128.7 (the other 5C of Ph), 109.2, 108.9 (2CMe2), 95.9 (C-1), 70.2, 70.1 (C-2 and C-3), 69.6 (C-4),
69.1 (CH2Ph), 65.4 (C-5), 25.9, 25.8, 24.7, 24.1 (4Me); HRMS m/z 363.1686 (calcd for C19H25NO6:
363.1682). Anal. calcd for C19H25NO6: C, 62.80; H, 6.93; N, 3.85. Found: C, 62.70; H, 7.00; N, 3.89.
4.3. (Z)-N-Benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylofuranos-5-ylidene)amine N-oxide 2
A solution of 3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-pentodialdo-1,4-furanose29 (1.90 g, 6.82
mmol) in dichloromethane (29 mL) was added, with stirring, to a suspension of sodium hydrogen-
carbonate (0.65 g), magnesium sulphate (1.14 g), 4 Å molecular sieve, and N-benzyl-hydroxylamine
hydrochloride (1.15 g, 7.2 mmol) in dichloromethane (48 mL) at room temperature, and the stirring was
maintained for 3 h (monitoring by TLC). The solids were filtered off and the filtrate was concentrated
at reduced pressure to give a solid residue that, after recrystallisation from 96% EtOH afforded pure
25
20
2 (1.83 g, 70%); mp 98–100°C; [α]D −137 (c 1); (lit.18 mp 96°C; [α]D −135.7); IR (KBr) νmax
1613 (C_N) and 860 cm−1 (NO); H NMR (500 MHz, CDCl3) δ 7.36–7.18 (m, 10H, 2Ph), 6.86 (d,
1
1H, J4,5=4.4, H-5), 5.96 (d, 1H, J1,2=3.7, H-1), 5.28 (dd, 1H, J3,4=3.3, H-4), 4.91, 4.84 (each d, each
1H, Jgem=13.6, NCH2Ph), 4.60 (d, 1H, J2,3≈0, H-2), 4.56 (d, 1H, H-3), 4.51, 4.42 (each d, each 1H,
J
gem=11.7, OCH2Ph), 1.49, 1.30 (each s, each 3H, 2Me); 13C NMR (75.5 MHz, CDCl3) δ 136.0 (C-5),
137.5, 132.0 (2 ipso-C of 2Ph), 129.5, 129.1, 128.9, 128.4, 127.8, 127.4 (the other 10C of 2Ph), 112.2
(CMe2), 104.9 (C-1), 82.8 (C-2), 82.3 (C-3), 77.9 (C-4), 72.6 (OCH2Ph), 69.2 (NCH2Ph), 26.9, 26.3

90
P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
(2Me); HRMS m/z 383.1736 (calcd for C22H25NO5: 383.1733). Anal. calcd for C22H25NO5: C, 68.91;
H, 6.57; N, 3.65. Found: C, 68.91; H, 6.54; N, 3.69.
4.4. (Z)-N-Benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranos-5-ylidene)amine N-oxide 3
A solution of 3-O-benzyl-1,2-O-isopropylidene-α-D-ribo-pentodialdo-1,4-furanose30 (0.78 g, 2.81
mmol) in dichloromethane (11 mL) was added, with stirring, to a suspension of sodium hydrogen-
carbonate (0.26 g), magnesium sulphate (0.47 g), 4 Å molecular sieve, and N-benzyl-hydroxylamine
hydrochloride (0.475 g, 2.97 mmol) in dichloromethane (20 mL) at room temperature, and the stirring
was maintained for 5 h (monitoring by TLC). The solids were filtered off and the filtrate was concentrated
at reduced pressure to give a solid residue that, after column chromatography (4:1 ether:hexane) afforded
pure 3 (0.345 g, 32%); [α]D22 +14 (c 1); IR (KBr) νmax 1595 (C_N) and 866 cm−1 (NO); 1H NMR (500
MHz, CDCl3) δ 7.41–7.19 (m, 10H, 2Ph), 6.55 (d, 1H, J4,5=6.8, H-5), 5.72 (d, 1H, J1,2=3.5, H-1), 5.25
(dd, 1H, J3,4=8.7, H-4), 4.88, 4.85 (each d, each 1H, Jgem=13.6, NCH2Ph), 4.60 (dd, 1H, J2,3=4.4, H-2),
4.61, 4.51 (each d, each 1H, Jgem=12.4, OCH2Ph), 3.82 (dd, 1H, H-3), 1.62, 1.31 (each s, each 3H, 2Me);
13C NMR (125.8 MHz, CDCl3) δ 134.0 (C-5), 137.3, 132.1 (2 ipso-C of Ph), 129.3, 129.0, 128.8, 128.2
(the other 10C of Ph), 113.5 (CMe2), 103.8 (C-1), 79.6 (C-3), 78.4 (C-2), 72.8 (C-4), 71.9 (OCH2Ph),
70.3 (NCH2Ph), 26.7, 26.4 (2Me); HRMS m/z 383.17338 (calcd for C22H25NO5: 383.17327). Anal. calcd
for C22H25NO5: C, 68.91; H, 6.57; N, 3.65. Found: C, 68.98; H, 6.47; N, 3.55.
4.5. Reaction of (Z)-N-benzyl-(1,2:3,4-di-O-isopropylidene-α-D-galactopyranos-6-ylidene)amine N-
oxide 1 with β-nitrostyrene 5. Preparation of 2-benzyl-3-(1,2:3,4-di-O-isopropylidene-α-D-galacto-
pentopyranos-5-yl)-4-nitro-5-phenylisoxazolidines 9
A solution of 1 (0.235 g, 0.65 mmol) and 5 (0.385 g, 2.60 mmol) in toluene (0.5 mL) was stirred at
50°C. After 24 h, the conversion was complete, as indicated by 1H NMR, which showed the formation
of two diastereomers of 9 (65:35); for 0the major component 9d: (500 MHz, CDCl3) δ 7.49–7.26 (m,
0
0
10H, 2Ph), 5.60 (d, 1H, J1 ,2 =5.1, H-1 ), 5.35–5.25 (br, 1H, H-5), 5.25 (dd, 1H, J3,4=4.7, J4,5=6.6, H-
0
0
0
0
0
4), 4.78, 4.00 (each d, each 1H, Jgem=14.6, CH2Ph), 4.58 (dd, 1H, J2 ,3 =2.7, J3 ,4 =7.8, H-3 ), 4.38
(dd, 1H, J4 ,5 =1.5, J3,5 =8.5, H-5 ), 4.36 (dd, 1H, H-2 ), 4.05 (dd, 1H, H-4 ), 3.6–3.3 (br, 1H, H-3),
0
0
0
0
0
0
1
1.63, 1.45, 1.34, 1.28 (each s, each 3H, 4Me); for the minor component 9a or 9c: H NMR0(500 MHz,
0
0
CDCl3) δ 7.48–7.26 (m, aromatics), 5.78 (d, 1H, J4,5=6.6, H-5), 5.48 (d, 1H, J1 ,2 =5.1, H-1 ), 5.40 (dd,
0
0
0
0
0
1H, J3,4=2.3, H-4), 4.55 (dd, 1H, J2 ,3 =2.3, J3 ,4 =8.0, H-3 ), 4.45, 4.32 (each d, each 1H, Jgem=12.7,
CH2Ph), ∼4.35 (dd, overlapped signal, H-3), 4.27 (dd, 1H, H-20), ∼4.25 (overlapped signal, H-40), 3.76
0
0
0
0
(dd, 1H, J4 ,5 =1.7, J3,5 =10.1, H-5 ), 1.63 (overlapped with one Me signal of the major component),
1.38, 1.28 (overlapped with other Me signal of the major component) and 1.18 (each s, each 3H, 2Me).
Preparative TLC (12:1 hexane:EtOAc) of the reaction mixture allowed us to discard the excess of 5 and
afforded 0.181 g (54%) of a 72:18:10 (1H NMR) diastereomeric mixture; the major component was a
new diastereomer 9b, different (1H NMR) from any of the components in the original mixture before
chromatography, but the other two agreed with the former two. Treatment of this mixture with boiling
abs. EtOH gave a crystalline product (65 mg, 19.4%), mp 145–149°C, which proved (1H NMR) to be a
63:37 mixture of the new and the original major components. Further recrystallisation afforded pure the
new major diastereomer (mp 143–144°C), crystallographic analysis of which allowed the unequivocal
27
assignment of its (2S,3S,4S,5R) absolute configuration, corresponding to the structure (2S)-9b; [α]D
−112 (c 1); UV (CH2Cl2) λmax 229 nm (εmM 2.26); IR (KBr) νmax 1562 and 1383 cm−1 (NO2); 1H NMR
(500 MHz, CDCl3) δ 7.48–7.30 (m, 10H, 2Ph), 5.80 (dd, 1H, J3,4=3.5, J4,5=5.8, H-4), 5.53 (d, 1H, H-5),

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
91
0
0
0
0
0
0
0
0
0
0
0
5.50 (d, 1H, J1 ,2 =4.9, H-1 ), 4.60 (dd, 1H, J2 ,3 =2.3, J3 ,4 =8.0, H-3 ), 4.50 (dd, 1H, J4 ,5 =1.8, H-4 ),
4.48, 4.37 (each d, each 1H, Jgem=13.4, CH2Ph), 4.29 (dd, 1H, H-20), 4.19 (dd, 1H, J3,5 =7.0, H-3), 3.77
0
(dd, 1H, H-50), 1.52, 1.36, 1.35, 1.30 (each s, each 3H, 4Me); 13C NMR (125.8 MHz, CDCl3) δ 132.4,
129.3, 128.8, 128.4, 128.3, 127.7, 126.2 (2Ph), 109.4, 108.6 (2CMe2), 96.2 (C-10), 94.1 (C-4), 81.4 (C-
5), 71.3 (C-3), 70.7 (C-30), 70.7 (C-40), 70.5 (C-20), 66.4 (C-50), 62.5 (CH2Ph), 26.1, 25.8, 24.7, 24.1
(4Me); HRMS m/z 512.2172 (calcd for C27H32N2O8: 512.2159). Anal. calcd for C27H32N2O8: C, 63.27;
H, 6.29; N, 5.47. Found: C, 63.16; H, 6.37; N, 5.45.
From the mother liquors slowly crystallised the other component, mp 170–173°C, which proved to be
1
1
identical (by H NMR in CDCl3) to 9d; H NMR (500 MHz, DMSO-d6) δ 7.39–7.25 (m, 10H, 2Ph),
0
0
0
5.59 (d, 1H, J1 ,2 =5.1, H-1 ),05.40–5.30 (br, 1H, H-5), 5.29 (dd, 1H, J3,4=4.5, J4,5=6.4, H-4), 4.68 (dd,
1H, J2 ,3 =2.7, J3 ,4 =7.8, H-3 ), 4.67, 03.87 (each d, each 1H, Jgem=13.8, CH2Ph), 4.45 (dd, 1H, H-20),
0
0
0
0
0
0
0
0
4.26 (dd, 1H, J4 ,5 =1.6, J3,5 =8.5, H-5 ), 4.02 (dd, 1H, H-4 ), 3.60–3.40 (br, 1H, H-3), 1.53, 1.39, 1.31,
1.27 (each s, each 3H, 4Me); NOE contacts (1D NOESY, DMSO-d6, 40°C): H-3, H-4 (strong), NCH2Ph
(weak); H-4, H-3, H-40; H-50, H-40, Me; [after 5 days, the spectrum of this sample in DMSO-d6 showed
the presence of both diastereomers 9b and 9d, in a ∼89:11 ratio]; pure 9d was stable in CDCl3: 1H NMR
0
0
0
(500 MHz, CDCl3) δ 7.38–7.34 (m, 10H, 2Ph), 5.61 (d, 1H, J1 ,2 =5.0, H-1 ), 5.37–5.25 (br, 1H, H-5),
5.25 (dd, 1H, J3,4=4.7, J4,5=6.6, H-4), 4.80, 4.00 (each brd, each 1H, Jgem=14.0, CH2Ph), 4.58 (dd, 1H,
0
0
0
0
0
0
0
0
0
0
J2 ,3 =2.7, J3 ,4 =7.8, H-3 ), 4.37 (dd, 1H, J4 ,5 =1.5, J3,5 =8.5, H-5 ), 4.36 (dd, 1H, H-2 ), 4.05 (dd, 1H,
H-40), 3.65–3.20 (br, 1H, H-3), 1.63, 1.45, 1.34, 1.28 (each s, each 3H, 4Me); 13C NMR (75.5 MHz,
CDCl3) δ 136.9, 136.8 (2 ipso-C of Ph), 128.9, 128.7, 127.9, 127.0, 126.2 (the other 10C of Ph), 109.9,
109.4 (2CMe2), 96.3, 96.2 (C-10 and C-4), 83.7 (C-5), 71.0, 70.8 (C-3 and C-40), 69.8 (C-20), 67.5 (C-
30), 65.7 (C-50), 60.2 (CH2Ph), 25.8, 25.7, 25.0, 24.3 (4Me); 1H NMR (500 MHz, CDCl3, −25°C), major
0
0
0
invertomer (86%): δ 7.50–7.24 (m, 10H, 2Ph), 5.65 (d, 1H, J1 ,2 =5.1, H-1 ), 5.21 (overlapped d, 1H, H-
5), 5.21 (overlapped dd, 1H, J4,5=6.5, J3,4=not measured, H-4), 4.79, 4.07 (each d, each 1H, Jgem=14.5,
0
0
0
0
0
0
0
0
0
CH2Ph), 4.56 (dd, 1H, J2 ,3 =2.6, J3 ,4 =7.9, H-3 ), 4.38 (dd, 1H, H-2 ), 4.30 (dd, 1H, J4 ,5 =1.3, J3,5 =8.4,
H-50), 3.98 (dd, 1H, H-40), 3.37 (brdd, J3,4≈3.5, 1H, H-3), 1.63, 1.44, 1.34, 1.25 (each s, each 3H, 4Me);
0
0
0
minor invertomer (14%): δ 7.50–7.24 (m, 10H, 2Ph), 5.68 (d, 1H, J1 ,2 =5.1, H-1 ), 5.80 (d, 1H, J4,5=5.7,
0
0
H-5), 5.41 (dd, 1H, J3,4=7.5, H-4), 4.62 (overlapped dd, 1H, H-3), 4.61 (overlapped dd, 1H, J2 ,3 =2.6,
J3 ,4 =7.9, H-3 ), 4.49, 4.01 (each d, each 1H, Jgem=13.7, CH2Ph), 4.40 (dd, 1H, H-20), 4.37 (overlapped
0
0
0
dd, 1H, H-40), 4.15 (dd, 1H, J3,5 =10.1, J4 ,5 ≈0.5, H-5 ), 1.54, 1.49, 1.32, 1.30 (each s, each 3H, 4Me).
0
0
0
0
4.6. Reaction of (Z)-N-benzyl-(1,2:3,4-di-O-isopropylidene-α-D-galactopyranos-6-ylidene)amine N-
oxide 1 with p-methoxy-β-nitrostyrene 6. Preparation of 2-benzyl-3-(1,2:3,4-di-O-isopropylidene-α-D-
galacto-pentopyranos-5-yl)-4-nitro-5-p-methoxyphenylisoxazolidines 10
A solution of 1 (0.300 g, 0.83 mmol) and 6 (0.594 g, 3.32 mmol) in toluene (0.6 mL) was stirred at
70°C. After 24 h, the conversion was complete, as indicated by 1H NMR, which showed the formation of
10 as a 67:33 diastereomeric mixture; for the major diastereomer 10d: (500 MHz, CDCl3) δ 7.54–6.84
0
0
0
(m, 9H, Ph and –C6H4–, both isomers), 5.59 (d, 1H, J1 ,2 =5.1, H-1 ), 5.22 (brdd, 1H, J3,4=3.5, H-4),
∼5.2 (overlapped with the H-4 signal, 1H, H-5), 4.77, 3.98 (each d, each 1H, Jgem=14.0, CH2Ph), 4.57
0
0
0
0
0
0
0
(dd, 1H, J2 ,3 =2.6, J3 ,4 =7.8, H-3 ), 4.35 (dd, 1H, H-2 ), ∼4.3 (overlapped with the H-2 signal, H-3),
0
0
0
0
0
4.04 (dd, 1H, J4 ,5 =1.6, H-4 ), 3.83 (dd, 1H, J3,5 =2.3, H-5 ), 3.79 (s, 3H, OMe), 1.59, 1.45, 1.34, 1.28
(each s, each 3H, 2CMe2); for the minor component 10a or 10c: (500 MHz, CDCl3) δ 7.54–6.84 (m, 9H,
Ph and –C6H4–, both isomers), 5.72 (dd, 1H, J3,4≈J4,5≈6.8, H-4), 5.63 (d, 1H, J4,5≈7.0, H-5), 5.49 (d,
0
0
0
0
1H, J1 ,2 =5.0, H-1 ), 5.38 (dd, 1H, J3,4≈6.7, J3,5 ≈2.4, H-3), ∼4.35 (overlapped with the other isomer)
0
0
0
0
0
and 4.11 (each d, each 1H, Jgem≈14.5, CH2Ph), 4.55 (dd, 1H, J2 ,3 =2.4, J3 ,4 =7.9, H-3 ), 4.27 (dd, 1H,

92
P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
0
H-20), 3.80 (s, 3H, OMe), 4.34 (partially overlapped with the other isomer) (dd, 1H, J4 ,5 =1.5, H-4 ),
3.78 (dd, 1H, H-50), 1.59, 1.44, 1.30, 1.27 (each s, each 3H, 2CMe2). Column chromatography (12:1
to 3:1 gradient of hexane:EtOAc containing 2% of Et3N) of the reaction mixture afforded 0.512 g of
pure recovered 6, and three fractions containing isoxazolidine derivatives (global yield: 0.325 g, 72.1%),
two of which being mixed fractions (overall yield, 0.167 g) of the minor component (15%) with a new
diastereomer (22%), and the third consisting only of this last (10b, 0.158 g, 35%; overall yield for this:
0
0
1
57%); oil; H NMR (300 MHz, CDCl3) δ 7.50–7.30 (m, 5H, Ph), 7.19 (d, 2H, Jo,m=8.7, H-2 and H-6
of 4-MeO-C6H4-), 6.84 (d,02H, H-3 and H-5 of 4-MeO-C6H4-), 5.73 (dd, 1H, J3,4=3.6, J4,5=5.9, H-4),
0
0
0
0
0
0
0
5.50 (d, 1H, J1 ,2 =4.9, H-1 ), 5.46 (d, 1H, H-5), 4.59 (dd, 1H, J2 ,3 =2.3, J3 ,4 =8.0, H-3 ), 4.48 (dd, 1H,
0
J4 ,5 =1.8, H-4 ), 4.45, 4.36 (each d, each 1H, Jgem=13.4, CH2Ph), 4.28 (dd, 1H, H-20), 4.17 (dd, 1H,
0
0
0
0
J3,5 =7.1, H-3), 3.77 (s, 3H, OMe), 3.76 (dd, 1H, H-5 ), 1.50, 1.36, 1.34, 1.30 (each s, each 3H, 2CMe2);
13C NMR (75.5 MHz, CDCl3) δ 159.9, 136.4, 129.2, 128.4, 127.6, 127.5, 124.2, 113.7 (Ph and C6H4),
109.4, 108.6 (2CMe2), 96.1 (C-10), 94.1 (C-4), 81.2 (C-5), 71.2 (C-3), 70.7 (C-40), 70.6 (C-30), 70.4
(C-20), 66.4 (C-50), 62.5 (CH2Ph), 55.0 (OMe), 26.1, 25.7, 24.6, 24.0 (2CMe2); HRMS m/z 542.2264
(calcd for C28H34N2O9: 522.2264). Anal. calcd for C28H34N2O9: C, 61.98; H, 6.32; N, 5.16. Found: C,
61.94; H, 6.30; N, 5.55.
4.7. Reaction of (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylofuranos-5-ylidene)amine N-
oxide 2 with β-nitrostyrene 5. Preparation of 2-benzyl-3-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-
tetrofuranos-4-yl)-4-nitro-5-phenylisoxazolidines 11
Nitrone 2 (0.287 g, 0.75 mmol) was added to a solution of 5 (0.447 g, 3.00 mmol) in toluene (2
1
1
mL) and the mixture was heated to reflux until the reaction was complete (20 h, H NMR). The H
NMR spectrum showed the presence of two diastereomeric adducts (65:35). Evaporation of the solvent
at reduced pressure and subsequent column chromatography (1:6 ether:hexane) led to separate the excess
25
of 5 and to isolate pure the major component 11b as an oil (0.191 g, 48%); [α]D +2 (c 1); IR (KBr)
ν
max 1555 and01373 cm−1 (NO2); 1H NMR (500 MHz, CDCl3) δ 7.42–7.17 (m, 15H, 3Ph), 5.87 (d, 1H,
0
0
0
0
0
J1 ,2 =3.7, H-1 ), 5.75 (d, 1H, J4,5=6.3, H-5), 5.52 (dd, 1H, J3,4=2.3, H-4), 4.54 (d, 1H, J2 ,3 ≈0, H-2 ),
0
0
0
0
4.52 (dd, 1H, J3,4 =8.7, H-3), 4.35 (dd, 1H, J3 ,4 =3.2, H-4 ), 4.48, 4.26 (each d, each 1H, Jgem=11.8,
OCH2Ph), 4.43, 4.09 (each d, each 1H, Jgem=13.5, NCH2Ph), 4.05 (d, 1H, H-30), 1.45, 1.29 (each s, each
3H, 2Me); NOE contacts (1D NOESY): H-5, H-10, NCH2Ph; H-4, H-3, H-40; 13C NMR (75.5 MHz,
CDCl3) δ 136.8, 136.4, 135.4 (3 ipso-C of Ph), 128.9, 128.8, 128.7, 128.5, 128.4, 128.2, 128.0, 127.9,
127.7, 127.6, 126.7, 126.2 (the other 15C of Ph), 112.0 (CMe2), 105.0 (C-10), 97.2 (C-4), 83.9 (C-5), 81.9
(C-20), 81.2 (C-30), 80.0 (C-40), 71.7 (OCH2Ph), 68.0 (C-3), 60.3 (NCH2Ph), 26.9, 26.1 (2Me); HRMS
m/z 532.22131 (calcd for C30H32N2O7: 532.22095). Anal. calcd for C30H32N2O7: C, 67.65; H, 6.06; N,
5.26. Found: C, 67.73; H, 6.15; N, 5.06. The minor diastereomer 11d had (from the re0action mixture)
1H NMR (500 MHz, CDCl3) δ 7.56–7.17 (m, aromatics), 5.97 (d, 1H, J1 ,2 =4.0, H-1 ), 5.59 (d, 1H,
0
0
0
0
0
0
J
J
4,5=6.0, H-5), 5.13 (dd, 1H, J3,4≈5.0, H-4), 4.62 (dd, 1H, J2 ,3 ≈0.8, H-2 ), 4.22 (dd, 1H, J3,4 =7.6,
3,4=4.9, H-3), 4.35 (overlapped with the major isomer, H-40), 4.71, 3.92 (each d, each 1H, Jgem=14.8,
NCH2Ph), 4.51 (d, 1H, Jgem=11.4) and ∼4.0 (overlapped with the major isomer, 1H, both: OCH2Ph),
0
4.02 (dd, 1H, J3 ,4 =4.4, H-3 ), 1.47, 1.31 (each s, each 3H, 2Me); 13C NMR (75.5 MHz, CDCl3) δ
136.8–126.2 (18 aromatic C, overlapped with signals of the major isomer), 112.0 (CMe2), 105.3 (C-10),
96.8 (C-4), 82.9 (C-5), 82.6 (C-20), 82.4 (C-30), 80.7 (C-40), 70.3 (OCH2Ph), 68.0 (C-3), 61.2 (NCH2Ph),
26.9, 26.1 (2Me).
0
0

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
93
4.8. Reaction of (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranos-5-ylidene)amine N-
oxide 3 with β-nitrostyrene (5). Preparation of 2-benzyl-3-(3-O-benzyl-1,2-O-isopropylidene-α-D-ribo-
tetrofuranos-4-yl)-4-nitro-5-phenylisoxazolidines 12
Compound 5 (0.233 g, 1.56 mmol) was added to a solution of nitrone 3 (0.150 g, 0.39 mmol) in
1
toluene (3.8 mL) and the mixture was heated to reflux for 24 h. H NMR of the mixture showed the
presence of two diastereomers (61:39). Evaporation of the solvent at reduced pressure and subsequent
column chromatography (1:8 ether:hexane) led to the separation of the excess 5 and to the isolation of the
20
two new products. The major component (12b) was an oil (0.096 g, 46%); [α]D +116 (c 1); IR (KBr)
ν
max 1553 and 1375 cm−1 (NO2); 1H NMR (500 MHz, CDCl3) δ 7.41–7.17 (m, 15H, 3Ph), 5.74 (d, 1H,
0 0
0 0 0 0
4,5=5.6, H-5), 5.66 (d, 1H, J1 ,2 =3.6, H-1 ), 5.49 (dd, 1H, J3,4=4.9, H-4), 4.45 (dd, 1H, J2 ,3 =4.4, H-2 ),
J
0
0
0
0
4.45, 4.21 (each d, each 1H, Jgem=11.6, OCH2Ph), 4.39 (dd, 1H, J3 ,4 =8.8, J3,4 =3.0, H-4 ), 4.32 (s, 2H,
NCH2Ph), 4.13 (dd, 1H, H-3), 3.85 (dd, 1H, H-30), 1.57, 1.31 (each s, each 3H, 2Me); NOE contacts (1D
NOESY): H-4, H-3, H-30, H-40; H-5, NCH2Ph; 13C NMR (125.8 MHz, CDCl3) δ 137.1, 136.3, 136.2
(3 ipso-C of Ph), 129.3, 128.7, 128.4, 128.3, 127.9, 127.8, 127.7, 126.5 (the other 15C of Ph), 113.4
(CMe2), 103.9 (C-10), 94.7 (C-4), 82.1 (C-5), 78.5 (C-40), 78.3 (C-30), 77.3 (C-20), 71.8 (OCH2Ph), 69.9
(C-3), 61.7 (NCH2Ph), 26.8, 26.6 (2Me); HRMS m/z 532.22126 (calcd for C30H32N2O7: 532.22095).
Anal. calcd for C30H32N2O7: C, 67.65; H, 6.06; N, 5.26. Found: C, 67.57; H, 5.84; N, 5.04. The minor
18
isomer 12d was an oil (0.056 g, 27%); [α]D +3 (c 1); IR (KBr) νmax 1553 and 1373 cm−1 (NO2);
1H NMR (500 MHz, CDCl3) δ 7.46–7.17 (m, 15H, 3Ph), 5.88 (d, 1H, J1 ,2 =3.8, H-1 ), 5.71 (d, 1H,
0
0
0
0
0 0
4,5=6.4, H-5), 5.48 (dd, 1H, J3,4=3.8, H-4), 4.54 (dd, 1H, J2 ,3 =4.6, H-2 ), 4.35, 4.02 (each d, each
J
0
0
1H, Jgem=11.0, OCH2Ph), 4.33, 4.31 (each d, each 1H0, Jgem=12.6, NCH2Ph), 4.15 (dd, 1H, J3 ,4 =8.5,
J3,4 =4.2, H-4 ), 4.10 (dd, 1H, H-3), 3.69 (dd, 1H, H-3 ), 1.54, 1.34 (each s, each 3H, 2Me); 13C NMR
(125.8 MHz, CDCl3) δ 137.0, 135.8, 135.5 (3 ipso-C of Ph), 129.8, 129.0, 128.7, 128.5 128.2, 128.0,
127.9, 127.8, 127.0, 126.4 (the other 15C of Ph), 113.0 (CMe2), 104.4 (C-10), 96.9 (C-4), 83.7 (C-5),
79.5 (C-40), 78.9 (C-30), 77.2 (C-20), 71.7 (OCH2Ph), 69.3 (C-3), 61.2 (NCH2Ph), 26.6, 26.5 (2Me);
HRMS m/z 532.22369 (calcd for C30H32N2O7: 532.22095). Anal. calcd for C30H32N2O7: C, 67.65; H,
6.06; N, 5.26. Found: C, 67.66; H, 6.03; N, 5.03.
0
0
4.9. Reaction of (E)-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-7-nitro-α-D-galacto-hept-6-eno-1,5-
pyranose 7 with (Z)-N-benzyl-benzylideneamine N-oxide 4. Preparation of 2-benzyl-5-(1,2:3,4-di-O-
isopropylidene-α-D-galacto-pentopyranos-5-yl)-4-nitro-3-phenylisoxazolidines 13
Nitrone 4 (0.143 g, 0.68 mmol), prepared following a procedure similar to that used for the N-methyl
analogue,31 was added to a solution of 7 (0.205 g, 0.68 mmol) in toluene (3.4 mL) and the mixture
1
was heated to reflux for 24 h. H NMR of the mixture showed the presence of three diastereomers
(55:36:9). Evaporation of the solvent at reduced pressure and subsequent column chromatography (14:1
hexane:EtOAc) led to three fractions (global yield: 0.273 g, 78%). First eluted was a pure compound
(0.088 g, 25%), but the second fraction contained an additional amount of the same compound (total:
0.097 g, 28%); it crystallised from EtOH, mp 145–147°C, and was unambiguously characterised by X-ray
21
diffraction analysis as the (2S,3R,4R,5R) diastereomer (2S)-13a; [α]D −10 (c 1); IR (KBr) νmax 1561
and 1383 cm−1 (NO2); 1H NMR (300 MHz, CDCl3) δ 7.54–7.27 (m, 10H, 2Ph), 5.57 (d, 1H, J1 ,2 =5.1,
0
0
H-10), 5.39 (dd, 1H, J3,4=6.9, J4,5=2.7, H-4), 4.93 (dd, 1H, J5,5 =8.4, H-5), 4.59 (dd, 1H, J2 ,3 =2.4,
0
0
0
0
0
0
0
0
0
J3 ,4 =7.7, H-3 ), 4.35 (dd, 1H, H-2 ), 4.28 (d, 1H, H-3), 4.19–4.14 (m, 2H, H-4 and H-5 ), 4.00, 3.84
(each d, each 1H, Jgem=14.6, CH2Ph), 1.60, 1.40, 1.36, 1.29 (each s, each 3H, 4Me); 13C NMR (75.5
MHz, CDCl3) δ 136.7, 135.1, 129.0, 128.1, 128.0, 127.9, 127.1 (2Ph), 109.5, 108.6 (2CMe2), 96.5 (C-

94
P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
4), 96.3 (C-10), 78.2 (C-5), 76.1 (C-3), 70.5 (C-30), 70.5 (C-20), 70.3 (C-40), 66.5 (C-50), 58.7 (CH2Ph),
25.9, 25.7, 24.8, 24.2 (4Me); HRMS m/z 512.2168 (calcd for C27H32N2O8: 512.2159). Anal. calcd for
C27H32N2O8: C, 63.27; H, 6.29; N, 5.47. Found: C, 63.21; H, 6.35; N, 5.46. The second fraction was an
oil (0.030 g), a mixture of a small amount of 13a and the minor component of the reaction mixture (13b0or
13d, 6% yield); 1H NMR (300 MHz, CDCl3) δ 7.51–7.30 (m, 10H, 2Ph), 5.58 (d, 1H, J1 ,2 =4.9, H-1 ),
0
0
0
0
0
0
0
5.34 (dd, 1H, J3,4=7.0, J4,5=3.8, H-4), 4.93 (dd, 1H, J5,5 =8.2, H-5), 4.63 (dd, 1H, J2 ,3 =2.05, J3 ,4 =7.8,
H-30), 4.34 (dd, 1H, H-20), 4.33 (dd, J4 ,5 =1.8, H-4 ), 4.29 (d, 1H, H-3), 4.23 (dd, 2H, H-5 ), 4.06, 3.93
(each d, each 1H, Jgem=15.1, CH2Ph), 1.57, 1.40, 1.36, 1.31 (each s, each 3H, 4Me); 13C NMR (75.5
MHz, CDCl3) δ 136.6, 135.1, 129.1, 128.1, 128.0, 127.6, 127.1, 127.0 (2Ph), 109.9, 108.8 (2CMe2),
96.3 (C-10), 95.4 (C-4), 80.1 (C-5), 76.1 (C-3), 70.8 (C-20), 70.3 (C-30), 70.2 (C-40), 66.9 (C-50), 58.4
(CH2Ph), 26.0, 25.7, 24.9, 24.3 (4Me). Last eluted was the pure major compound (13c, 0.155 g, 44%);
oil; IR (KBr) νmax 1579 and 1377 cm−1 (NO2); 1H NMR (300 MHz, CDCl3) δ 7.48–7.33 (m, 10H, 2Ph),
0
0
0
0
0
0
0
5.63 (dd, 1H, J3,4=8.0, J4,5=4.6, H-4), 5.58 (d, 1H, J1 ,2 =4.9, H-1 ), 5.10 (dd, 1H, J5,5 =1.5, H-5), 4.60
0
0
0
0
0
0
0
0
0
(dd, 1H, J2 ,3 =2.5, J3 ,4 =8.0, H-3 ), 4.33 (dd, 1H, H-2 ), 4.19 (dd, 1H, J4 ,5 =1.9, H-4 ), 4.08 (d, 1H,
H-3), 4.05 (dd, 1H, H-50), 4.00, 3.69 (each d, each 1H, Jgem=14.6, CH2Ph), 1.61, 1.42, 1.42, 1.30 (each
s, each 3H, 4Me); 13C NMR (75.5 MHz, CDCl3) δ 136.8, 132.6, 129.1, 128.8, 128.1, 127.2 (2Ph), 109.6,
108.9 (2CMe2), 96.2 (C-10), 92.6 (C-4), 80.1 (C-5), 74.3 (C-3), 71.2 (C-40), 70.4 (C-30), 70.1 (C-20),
65.5 (C-50), 59.0 (CH2Ph), 26.0, 25.1, 24.8, 23.7 (4Me); HRMS m/z 512.2168 (calcd for C27H32N2O8:
512.2159). Anal. calcd for C27H32N2O8: C, 63.27; H, 6.29; N, 5.47. Found: C, 62.99; H, 6.42; N, 5.25.
4.10. Reaction of (E)-3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-α-D-xylo-hex-5-eno-1,4-
furanose 8 with (Z)-N-benzyl-benzylideneamine N-oxide 4. Preparation of 2-benzyl-5-(3-O-benzyl-1,
2-O-isopropylidene-α-D-xylo-tetrofuranos-4-yl)-4-nitro-3-phenylisoxazolidines 14
Nitrone 4 (0.101 g, 0.477 mmol) was added to a solution of the nitroalkene 8 (0.153 g, 0.477 mmol)
1
in toluene (2.5 mL), and the mixture was heated to reflux for 18 h. H NMR of the mixture showed
the presence of four diastereomers (45:34:14:7). Column chromatography (1:8 ether:hexane) afforded
separately the isomers (global yield: 0.168 g, 66%) as oils. The major isomer (14b or 14d, 0.069 g,
19
1
27%) had [α]D +60 (c 1); IR (KBr) νmax 1557 and 1377 cm−1 (NO2); H NMR (500 MHz, CDCl3)
0
0
0
δ 7.45–7.10 (m, 15H, 3Ph), 6.00 (d, 1H, J1 ,2 =3.8,0H-1 ), 5.60 (dd, 1H, J3,4=8.0, J4,5=4.6, H-4), 5.08
0
0
0
0
0
0
(dd, 1H, J4 ,5=1.5, H-5), 4.55 (d, 1H, J2 ,3 ≈0, H-2 ), 4.47 (dd, 1H, J3 ,4 =3.8, H-4 ), 4.45, 4.33 (each
d, each 1H, Jgem=12.0, OCH2Ph), 4.13 (d, 1H, J3,4=8.0, H-3), 3.97, 3.66 (each d, each 1H, Jgem=14.6,
NCH2Ph), 3.91 (d, 1H, H-30), 1.47, 1.32 (each s, each 3H, 2Me); NOE contacts (1D NOESY): H-5, H-40,
H-30, (H-4: low intensity); H-4, H-3; 13C NMR (125.8 MHz, CDCl3) δ 137.1, 135.8, 132.5 (3 ipso-C of
Ph), 129.2, 128.8, 128.7, 128.5, 128.4, 128.3, 128.2, 128.0, 127.2 (the other 15C of Ph), 112.1 (CMe2),
105.3 (C-10), 93.0 (C-4), 81.3 (C-20), 80.7 (C-30), 79.3 (C-5), 78.3 (C-40), 74.9 (C-3), 71.6 (OCH2Ph),
59.3 (NCH2Ph), 26.8, 26.2 (2Me); HRMS m/z 532.22240 (calcd for C30H32N2O7: 532.22095). Anal.
calcd for C30H32N2O7: C, 67.65; H, 6.06; N, 5.26. Found: C, 67.53; H, 5.85; N, 4.88. The second
19
main isomer (14a or 14c, 0.064 g, 25%) had [α]D −71 (c 1); IR (KBr) νmax 1555 and01373 cm−1
(NO2); 1H NMR (500 MHz, CDCl3) δ 7.47–7.19 (m, 15H, 3Ph), 5.93 (d, 1H, J1 ,2 =3.6, H-1 ), 5.45 (dd,
0
0
0
0
0
0
1H, J3,4=6.4,0J4,5=2.8, H-4), 5.01 (dd, 1H, J4 ,5=7.0, H-5), 4.58 (dd, 1H, J3 ,4 =3.3, H-4 ), 4.52 (d, 1H,
0
0
J2 ,3 ≈0, H-2 ), 4.45, 4.39 (each d, each 1H, Jgem=11.8, OCH2Ph), 4.29 (d, 1H, H-3), 4.03, 3.84 (each d,
each 1H, Jgem=14.4, NCH2Ph), 3.88 (d, 1H, H-30), 1.52, 1.32 (each s, each 3H, 2Me); NOE contacts (1D
NOESY): H-5, (H-4: low intensity); H-4, H-40, (H-5 and H-3: low intensity); H-3, NCH2Ph, (H-4: low
intensity); 13C NMR (125.8 MHz, CDCl3) δ 136.8, 136.7, 135.5 (3 ipso-C of Ph), 130.0, 129.9, 128.5,
128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 127.7, 127.3, 127.2 (the other 15C of Ph), 112.0 (CMe2), 105.3

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
95
(C-10), 96.6 (C-4), 82.4 (C-20), 81.0 (C-30), 79.8 (C-40), 77.7 (C-5), 76.1 (C-3), 72.3 (OCH2Ph), 59.0
(NCH2Ph), 26.9, 26.3 (2Me); HRMS m/z 532.21744 (calcd for C30H32N2O7: 532.22095). Anal. calcd
for C30H32N2O7: C, 67.65; H, 6.06; N, 5.26. Found: C, 67.85; H, 6.08; N, 5.05. The third diastereomer in
order of decreasing yield (14c or 14a, 0.030 g, 12%) had 1H NMR (500 MHz, CDCl3) δ 7.39–7.18 (m,
0
0
0
0
15H, 3Ph), 5.90 (d, 1H, J1 ,2 =4.0, H-1 ), 5.05 (dd, 1H, J3,4=7.1, J4,5=4.6, H-4), 4.92 (dd, 1H, J4 ,5=6.6,
0
0
0
H-5), 4.67 (dd, 1H, J3 ,4 =4.6, H-4 ), 4.54, 4.42 (each d, each 1H, Jgem=11.4, OCH2Ph), 4.44 (d, 1H,
J2 ,3 ≈0, H-2 ), 4.31 (d, 1H, H-3), 4.08, 3.90 (each d, each 1H, Jgem=14.2, NCH2Ph), 4.07 (d, 1H, H-30),
1.52, 1.31 (each s, each 3H, 2Me); 13C NMR (75.5 MHz, CDCl3) δ 136.6, 135.8, 135.0 (3 ipso-C of
Ph), 129.2, 128.9, 128.4, 128.1, 128.0, 127.8, 127.7, 127.6, 127.4 (the other 15C of Ph), 112.6 (CMe2),
105.4 (C-10), 96.0 (C-4), 82.6 (C-20), 82.5 (C-30), 80.1 (C-40), 79.7 (C-5), 74.6 (C-3), 71.6 (OCH2Ph),
58.5 (NCH2Ph), 27.2, 26.7 (2Me). The minor diastereomer (14d or 14b, 0.005 g, 2%) had 1H NMR (300
0
0
0
0
0
0
MHz, CDCl3) δ 7.42–7.04 (m, 15H, 3Ph), 5.96 (d, 1H, J1 ,2 =3.6, H-1 ), 5.55 (dd, 1H, J3,4=7.8, J4,5=5.1,
0
0
0
0
0
0
0
H-4), 5.25 (dd, 1H, J4 ,5=6.4, H-5), 4.62 (d, 1H, J2 ,3 ≈0, H-2 ), 4.47 (dd, 1H, J3 ,4 =3.6, H-4 ), 4.43,
4.32 (each d, each 1H, Jgem=11.8, OCH2Ph), 3.97, 3.66 (each d, each 1H, Jgem=14.0, NCH2Ph), 4.12 (d,
1H, H-3), 4.06 (d, 1H, H-30), 1.50, 1.33 (each s, each 3H, 2Me); 13C NMR (75.5 MHz, CDCl3) δ 137.0,
135.5, 131.9 (3 ipso-C of Ph), 129.1, 128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 127.9, 127.8 (the other
15C of Ph), 112.1 (CMe2), 105.1 (C-10), 93.5 (C-4), 82.8 (C-30), 81.4 (C-20), 78.2 (C-40), 78.4 (C-5),
74.9 (C-3), 71.9 (OCH2Ph), 58.4 (NCH2Ph), 29.6 (double intensity, 2Me).
4.11. Reaction of (Z)-N-benzyl-(1,2:3,4-di-O-isopropylidene-α-D-galactopyranos-6-ylidene)amine N-
oxide 1 with (E)-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-7-nitro-α-D-galacto-hept-6-eno-1,5-pyranose
7. Preparation of 2-benzyl-3,5-bis-(1,2:3,4-di-O-isopropylidene-α-D-galacto-pentopyranos-5-yl)-4-
nitroisoxazolidines 15
Nitroalkene 7 (0.186 g, 0.615 mmol) was added to a solution of 1 (0.223 g, 0.615 mmol) in toluene (4.4
mL), and the mixture was heated to reflux for 18 h. After elimination of the solvent at reduced pressure,
the residue was subjected to column chromatography (1:6 ether:hexane). A portion of 7 was recovered
26
unreacted (38.5 mg, 21%). The major product (15b, 0.169 g, 41%) had mp 185–187°C; [α]D −104 (c
1
1); IR (KBr) νmax 1555 and 1377 cm−1 (NO2); H NMR (500 MHz, DMSO-d6, at 50°C) (protons of
the sugar moiety on 3-position of the isoxazolidine ring are noted H-n0; those of the sugar moiety on
5-position are noted H-n00) δ 7.40–7.20 (m, 5H, Ph), 5.80 (dd, 1H, J3,4=6.5, J4,5=4.4, H-4), 5.56 (d, 1H,
0
00
0
0
0
00 00
0
0
0
0
J1 ,2 =5.0, H-1 ), 5.47 (d, 1H, J1 ,2 =4.9, H-1 ), 4.65 (dd, 1H, J2 ,3 =2.5, J3 ,4 =7.7, H-3 ), 4.57, 3.85
00
00 00
00 00
(each d, each 1H, Jgem=14.6, CH2Ph), 4.56 (dd, 1H, J2 ,3 =2.2, J3 ,4 =8.0, H-3 ), 4.53–4.47 (brm, 1H,
H-5), 4.40 (dd, 1H, H-20), 4.32 (dd, 01H, H-200), 4.30 (dd, 1H, J4 ,5 =1.5, H-4 ), 4.05 (dd, 1H, J4 ,5 =1.3,
00
00 00
0
0
H-40), 3.98 (dd, 1H, J3,5 =9.0, H-5 ), 3.93 (dd, 1H, J5,5 =6.8, H-5 ), 3.61–3.53 (brm, 1H, H-3), 1.45,
00
0
00
1
1.42, 1.40, 1.36, 1.31, 1.29, 1.27, 1.20 (each s, each 3H, 8Me); H NMR (500 MHz, CDCl3, −25°C),
major invertomer (77%): δ 7.45–7.26 (m, 5H, Ph), 5.75 (dd, 1H, J3,4=6.0, J4,5=3.2, H-4), 5.64 (d, 1H,
0
00
0
0
00 00
0
0
0
00 0
J1 ,2 =5.0, H-1 ), 5.48 (d, 1H, J1 ,2 =4.8, H-1 ), ∼4.59 (dd, 1H, H-5), 4.55 (dd, 1H, J2 ,3 =2.6, J3 ,4 =7.8,
H-30), 4.61, 4.28 (each d, each 1H, Jgem=15.2, CH2Ph), 4.39 (dd, 1H, J2
=2.1, J3 ,4 =8.1, H-3 ), 4.34
00 00
00,300
(dd, 1H, H-20), 4.22 (dd, 1H, H-200), 4.11 (dd, 1H, J4 ,5 ≈0.5, H-4 ), 3.96 (dd, 1H, J4 ,5 ≈0.5, H-4 ),
00
0
00 00
0
0
0
00
0
00
3.90 (dd, 1H, J3,5 =9.4, H-5 ), 3.89 (dd, 1H, J5,5 =5.6, H-5 ), 3.62 (dd, 1H, H-3), 1.51, 1.49, 1.45, 1.31,
1.29, 1.28, 1.24, 1.17 (each s, each 3H, 8Me); minor invertomer (23%): δ 7.40–7.20 (m, 5H, Ph), 6.08 (dd,
1H, J3,4=7.1, J4,5=4.4, H-4), ∼5.64 (d, 1H, overlapped, H-10), 5.53 (d, 1H, J1 ,2 =5.0, H-1 ), 4.48 (dd,
00
00 00
1H, overlapped, H-30), ∼4.59, 4.16 (each d, each 1H, Jgem=13.6, CH2Ph), ∼4.35 (dd, 1H, J3 ,4 =8.3,
00 00
H-300), 5.27 (dd 1H, H-5), ∼4.26 (dd, 1H, H-20), ∼4.22 (dd, 1H, H-200), ∼4.10 (dd, 1H, overlapped,
H-400), ∼4.00 (dd, 1H, overlapped, H-40), ∼4.10 (dd, 1H, J3,5 =10.9, H-5 ), ∼3.90 (dd, 1H, J5,5 =5.9,
0
0
00

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P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
H-500), 4.66 (dd, 1H, H-3), 1.51, 1.49, 1.45, 1.31, 1.29, 1.28, 1.24, 1.17 (each s, each 3H, 8Me); NOE
contacts (1D NOESY, at −25°C; for the major invertomer): H-3, H-4, CH2Ph (one of the protons), H-
500; 13C NMR (125.8 MHz, CDCl3) δ ∼136.3br, 130.3, 128.7, 127.7, 127.0 (Ph), 109.6, 109.4, 109.2,
108.7 (4CMe2), 96.3 (C-10), 96.2 (C-100), 91.2 (C-4), 80.5br (C-5), 71.1 (C-40), 70.8 (C-30), 70.8 (C-200),
70.5 (C-300), 70.0 (C-400), 69.8 (C-20), 66.2 (C-500), 64.9 (CH2Ph), 64.6 (C-50), ∼60.1br (C-3), 26.1,
26.0, 25.7, 25.4, 25.0, 24.7, 24.4, 24.0 (8Me); HRMS m/z 664.2842 (calcd for C32H44N2O13: 664.2843).
Anal. calcd for C32H44N2O13: C, 57.82; H, 6.67 N, 4.21. Found: C, 57.78; H, 6.66; N, 4.15. For the
minor component, present in a mixed fraction (44.7 mg, 11% yield, by 1H NMR), the structure 15d was
tentatively assigned; it had (only distinct signals) 1H NMR (500 MHz, CDCl3) δ 5.53 (d, 1H, J1 ,2 =5.0,
0
0
00
H-10), 5.51 (d, 1H, J1 ,2 =5.0, H-1 ), 5.31 (dd, 1H, J3,4=6.0, J4,5=2.8, H-4), ∼4.50 (overlapped dd, 1H,
00 00
00 0 0
0 0 0 0 0
=2.2, H-3 ), 4.39 (dd, 1H, J4 ,3 =7.9, J4 ,5 =1.3, H-4 ), 3.90 (dd, 1H, J3,5 =7.8, H-5 ), 3.85 (dd,
00,300
J2
00
00
1H, J5,5 =8.0, H-5 ), 3.42–3.40 (brm, 1H, H-3), 1.55, 1.52, 1.43, 1.39, 1.36, 1.32, 1.29, 1.25 (each s,
each 3H, 8Me); 13C NMR (125.8 MHz, CDCl3) δ 109.9, 109.5, 108.9, 108.6 (4CMe2), 96.4 (C-10), 96.3
(C-100), 91.3 (C-4), 79.7 (C-5), 71.5 (C-3), 70.7, 70.6, 70.4, 70.2, 70.2, 68.7 (C-40, C-30, C-20, C-400,
C-300, C-200), 66.4br (C-500), 64.6 (C-50), 60.8 (CH2Ph), 26.2, 26.0, 25.7, 25.6, 24.9, 24.9, 24.2, 24.1
(8Me).
4.12. Reaction of (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylopyranos-5-ylidene)amine
N-oxide
2
with (E)-3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-α-D-xylo-hex-5-eno-1,
4-furanose 8. Preparation of (3S,4S,5S)- 16b or (3R,4R,5R)-2-benzyl-3,5-di-(3-O-benzyl-1,2-O-
isopropylidene-α-D-xylo-tetrofuranos-4-yl)-4-nitroisoxazolidine 16d
Nitrone 2 (0.205 g, 0.536 mmol) was added to a solution of 8 (0.172 g, 0.536 mmol) in toluene (3.7
mL) and the mixture was heated to reflux for 18 h. 1H NMR of the reaction mixture showed resonances
for a main product accompanied by small signals of an isomer (<10%). After evaporation of the solvent,
the residue was subjected to column chromatography (1:2 ether:hexane) to give a major compound (16b
25
or 16d, 0.192 g, 51%); oil; [α]D −90 (c 1); IR (KBr) νmax 1559 and 1379 cm−1 (NO2); 1H NMR (500
MHz, CDCl3) (protons of the sugar moiety on 3-position of the isoxazolidine ring are noted H-n0; those
of the sugar moiety on 5-position ar0e noted H-n00) δ 7.40–7.17 (m, 15H, 3Ph), 5.92 (d, 1H, J1 ,2 =3.8,
00 00
H-100), 5.89 (d, 1H, J1 ,2 =3.8, H-1 ), 5.28 (dd, 1H, J3,4=5.00, J4,5=3.4, H-4), 4.83 (dd, 1H, J4 ,5=7.0,
0
0
00
00
00 00
0
0
H-5), 4.60 (d, 1H, J2 ,3 ≈0, H-2 ), 4.50 (d, 1H, J2 ,3 ≈0, H-2 ), 4.52, 4.49 (each d, each 1H, Jgem=11.7,
OCH2Ph), 4.41, 4.37 (each d, each 1H, Jgem=11.4, OCH2Ph), 4.50, 4.13 (each d, each 1H,0Jgem=14.5,
0
00
0
0
00 00
NCH2Ph), 4.43 (dd, 1H, J3 ,4 =3.4, H-4 ), 4.39 (dd, 1H, J3 ,4 =3.4, H-4 ), 4.14 (d, 1H, H-3 ), 4.01 (dd,
00
1H, J3,4 =9.2, H-3), 3.81 (d, 1H, H-3 ), 1.50, 1.46, 1.32, 1.29 (each s, each 3H, 4Me); 13C NMR (125.8
MHz, CDCl3) δ 137.4, 136.7, 136.7 (3 ipso-C of Ph), 129.1, 128.6, 128.5, 128.4, 128.3, 128.1, 128.0,
127.9, 127.8, 126.9, 126.8 (the other 15C of Ph), 112.0, 111.9 (2CMe2), 105.4 (C-100), 105.2 (C-10), 92.5
(C-4), 82.9 (C-30), 82.6 (C-20), 81.3 (C-200), 80.7 (C-40), 80.6 (C-300), 78.9 (C-400), 78.9 (C-5), 72.2, 71.5
(2OCH2Ph), 70.4 (C-3), 60.8 (NCH2Ph), 26.8, 26.7, 26.2, 26.1 (4Me); HRMS m/z 704.29118 (calcd for
C38H44N2O11: 704.29451). Anal. calcd for C38H44N2O11: C, 64.76H, H, 6.29; N, 3.98. Found: C, 64.81;
H, 6.40; N, 3.70.
0
4.13. Crystallographic analysis for (2S)-9b†
The compound crystallised as colourless rectangular parallelpipeds. A crystal of dimensions
0.20×0.36×0.45 mm was used for X-ray investigations; it belonged to the orthorhombic system with
†
Lists of the atomic coordinates, hydrogen coordinates, and thermal parameters have been deposited at the Cambridge
Crystallographic Data Centre.

P. Borrachero et al. / Tetrahedron: Asymmetry 10 (1999) 77–98
97
systematic absences consistent with the space group P212121. Accurate cell dimensions and crystal
orientation matrix, determined on an Enraf-CAD4 diffractometer by least-squares treatment of the
setting angles of 25 reflections in the range 2<θ<25°, were a=11.086(10), b=24.755(4), and c=9.577(2)
Å, α=β=γ=90°, V=2626(2) Å3, dcalc=1.30 g cm−3 for Z=4, F(000)=1088 and the absorption coefficient
µ=0.096 mm−1. A total of 2670 independent reflections were collected, 1825 intensities greater than
2σ(I0) were used as observed for the structure determination. The final discrepancy factors were
R=0.060 and Rw=0.071 for 334 variables, average shift/e.s.d. was 0.002, maximum and minimum
electron densities were 0.29 and −0.30 e Å−3, respectively.
4.14. Crystallographic analysis for (2S)-13a‡
The compound crystallised as colourless prisms. A crystal of dimensions 0.40×0.48×0.52 mm was
used for X-ray study; it belonged to the monoclinic space group P21. Accurate cell dimensions and
crystal orientation matrix, determined on an Enraf-CAD4 diffractometer by least-squares treatment of the
setting angles of 25 reflections in the range 2<θ<25°, were a=11.331(8), b=12.841(1), and c=9.709(8) Å,
α=90, β=102.54(1), γ=90°, V=1379(2) Å3, dcalc=1.23 g cm−3 for Z=2, F(000)=544 and the absorption
coefficient µ=0.091 mm−1. A total of 3156 independent reflections were collected, 2110 observed for
I greater than 2σ(I0). The final discrepancy factors were R=0.050 and Rw=0.046 for 333 variables (y
coordinate for O1 was held fixed), maximum and minimum electron densities were 0.41 and −0.21 e
Å−3, respectively.
Acknowledgements
The authors thank the Dirección General de Enseñanza Superior, Ministerio de Educación y Cultura
of Spain (Grant No. PB96-1326) and the Dirección General de Universidades e Investigación, Consejería
de Educación y Ciencia of Andalusia for financial support.
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