Intramolecular 1,3-dipolar nitrone and nitrile oxide cycloaddition of 2- and 4-O-allyl and propargyl glucose derivatives: A versatile approach to chiral cyclic ether fused isoxazolidines, isoxazolines and isoxazoles

Article abstract of DOI:10.1016/j.tet.2005.01.119

2-O- and 4-O-Allyl and -propargyl glucose and the corresponding oxime derivatives were prepared from readily available glucose dithioacetals. Intramolecular 1,3-dipolar cycloaddition of the N-benzyl and N-methyl nitrones of the above acyclic 2-O-allyl glucose derivatives led to the diastereoselective formation of chiral isoxazolidines incorporating the tetrahydrofuran ring. The EI mass spectra revealed a characteristic cleavage of the C-alkyl group adjacent to the furan oxygen atom. An enantiopure trisubstituted tetrahydrofuran was obtained by the reductive cleavage of the isoxazolidine ring of one of the cycloadducts. In contrast, the nitrile oxide cycloaddition of the 2-O-allyl derivatives afforded diastereomeric mixtures of the corresponding dihydroisoxazolines, the stereochemistry of which was tentatively assigned on the basis of the principle of optical superposition. The exclusive formation of a tetrahydrofuran ring from pentaallyl nitrone or nitrile oxide demonstrated the preferred formation of a five-membered ring to that of six or seven-membered rings. The nitrile oxide generated from a 3,4,5,6,7-pentaallyloxy-1-nitroheptane derivative obtained from pentaallylglucose underwent diastereoselective cycloaddition to give an isoxazoline fused to a pyran ring. Enantiopure isoxazoles containing tetrahydrofuran and oxepane rings were also prepared in good yields by the nitrile oxide cycloaddition of the 2-O- and 4-O-propargyl derivatives.

Full text of DOI:10.1016/j.tet.2005.01.119

Tetrahedron 61 (2005) 2999–3012
Intramolecular 1,3-dipolar nitrone and nitrile oxide cycloaddition
of 2- and 4-O-allyl and propargyl glucose derivatives:
a versatile approach to chiral cyclic ether fused isoxazolidines,
isoxazolines and isoxazoles
*
Subir Ghorai, Ranjan Mukhopadhyay, Asish P. Kundu and Anup Bhattacharjya
Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India
Received 28 October 2004; revised 13 January 2005; accepted 28 January 2005
Abstract—2-O- and 4-O-Allyl and -propargyl glucose and the corresponding oxime derivatives were prepared from readily available
glucose dithioacetals. Intramolecular 1,3-dipolar cycloaddition of the N-benzyl and N-methyl nitrones of the above acyclic 2-O-allyl glucose
derivatives led to the diastereoselective formation of chiral isoxazolidines incorporating the tetrahydrofuran ring. The EI mass spectra
revealed a characteristic cleavage of the C-alkyl group adjacent to the furan oxygen atom. An enantiopure trisubstituted tetrahydrofuran
was obtained by the reductive cleavage of the isoxazolidine ring of one of the cycloadducts. In contrast, the nitrile oxide cycloaddition of
the 2-O-allyl derivatives afforded diastereomeric mixtures of the corresponding dihydroisoxazolines, the stereochemistry of which was
tentatively assigned on the basis of the principle of optical superposition. The exclusive formation of a tetrahydrofuran ring from pentaallyl
nitrone or nitrile oxide demonstrated the preferred formation of a five-membered ring to that of six or seven-membered rings. The nitrile
oxide generated from a 3,4,5,6,7-pentaallyloxy-1-nitroheptane derivative obtained from pentaallylglucose underwent diastereoselective
cycloaddition to give an isoxazoline fused to a pyran ring. Enantiopure isoxazoles containing tetrahydrofuran and oxepane rings were also
prepared in good yields by the nitrile oxide cycloaddition of the 2-O- and 4-O-propargyl derivatives.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
4-O-allyl and propargyl glucose derivatives leading to
enantiopure isoxazolidine, dihydroisoxazoline and isoxa-
zole ring fused tetrahydrofuran, pyran and oxepane
derivatives.
One of the frequently used strategies employed for the
synthesis of heterocyclic compounds is the 1,3-dipolar
cycloaddition reactions involving a nitrone or nitrile oxide
and an alkene or alkyne.1–4 Recently, these two cyclo-
addition reactions have been successfully applied to O- and
N-alkenylcarbohydrate derivatives leading to the synthesis
of enantiomerically pure cyclic ethers and amines fused
to isoxazolidine and dihydroisoxazoline rings.5–7 Most of
these cycloadditions have been applied to 3-O-allyl
carbohydrate derivatives giving rise to pyran and oxepane
rings.8 Examples of the synthesis of tetrahydrofuran rings
from carbohydrate derivatives by employing these cyclo-
additions have remained scarce.9–11 Earlier, we reported the
formation of tetrahydrofuran rings via the nitrone cyclo-
addition of acyclic 2-O-allyl glucose derivatives.9 Herein,
we describe in detail the earlier work9 and hitherto
unreported nitrile oxide cycloaddition of acyclic 2-O- and
The general strategy for the above cycloaddition reactions
is depicted in Scheme 1. A nitrone or nitrile oxide
Keywords: Nitrone; Nitrile oxide; Cycloaddition; Glucose; Isoxazolidine;
Isoxazoline; Isoxazole.
* Corresponding author. Tel.: C91 33 2472 8697; fax: C91 33 2472 3967;
e-mail: anupbh@hotmail.com
Scheme 1. O-Allyl and -propargylcarbohydrate nitrone and nitrile oxide
cycloaddition strategy.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.119

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S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
functionality is generated at the 1-C of an acyclic glucose
derivative having a 2-O- or 4-O-allyl or propargyl moiety
corresponding to the values of nZ1 and 3. The nitrone 1 or
the nitrile oxides 2 and 3 formed in this manner undergo
cycloaddition to afford an isoxazolidine 4, a dihydroisoxa-
zoline 5 and an isoxazole 6, respectively. A noteworthy
feature of this strategy is the availability of different sizes of
cyclic ethers fused to diverse types of heterocyclic rings.
acetylation followed by reduction with NaBH4 without
isolation of the intermediates (Scheme 2).
Another set of acyclic intermediates were prepared from the
1,2-isopropylidene glucose derivative 15,19 which was
converted to the methyl glycoside 16 as an anomeric
mixture, alkylation of which with allyl bromide, propargyl
bromide and benzyl bromide separately afforded the
anomeric mixtures of the 2-O-allyl, 2-O-propargyl and
2-O-benzyl derivatives 17, 18 and 19, respectively (Scheme
3). Although, the respective a and b anomers in the mixtures
could be separated by column chromatography, in this study
the mixtures were used without separation for the next steps
viz. deglycosylation to 20, 21 and 22 and dithioacetylation
to 23, 25 and 27 followed by alkylation of the 4-OH with
either benzyl or allyl or propargyl bromide giving rise to the
dithioacetal derivatives 24, 26, 28 and 29.
2. Results and discussion
2.1. Preparation of the nitrone and nitrile oxide
precursors
The nitrones used in this work were prepared from the
reaction of the corresponding aldehydes and N-benzyl-
hydroxylamine or N-methylhydroxylamine, whereas nitrile
oxides were generated from the corresponding aldoximes
using chloramine-T,12 and in one case from a primary nitro
compound using 4-chlorophenyl isocyanate.13 The starting
acyclic aldehydes were prepared by the cleavage of the
corresponding dithioacetals, which were obtained from
readily available glucose derivatives according to Scheme
2. The glucose dithioacetal 714 was converted to the
pentaallyl and pentapropargyl derivatives 8 and 9 by
alkylation with allyl bromide and propargyl bromide using
sodium hydride in DMF. The dithioacetal 8 was converted
to the aldehyde 10 by treatment with HgCl2 and CaCO3 in
aqueous acetonitrile.15 The aldehyde 10 and other aldehyde
intermediates in this study were used directly for the next
steps, because they were found to be sensitive to chromato-
graphic purification. The penta-O-propargyl glucose
dithioacetal 9 was converted to the aldehyde 13 by a two-
step procedure involving oxidation with NaIO4 followed by
treatment of the crude sulfoxide intermediate with H2SO4
and THF,16,17 because the direct HgCl2 mediated cleavage
of 9 failed to afford 13. The aldehydes 10 and 13 were
converted to the respective oximes 11 and 14 by treatment
with NH2OH.HCl in pyridine–methanol. The primary nitro
derivative 12 was prepared from 10 by following a known
protocol18 involving treatment with nitromethane and
Scheme 3. Synthesis of 2-O- and 4-O-allyl and -propargyl glucose
dithioacetals. Reagents and conditions: (a) p-TsOH, MeOH, reflux, 6 h;
(b) allylbromide, Bu4NBr, CH2Cl2, 50% aq NaOH, 25 8C, 12 h;
(c) propargylbromide, Bu4NBr, CH2Cl2, 50% aq NaOH, 25 8C, 12 h;
(d) benzylbromide, Bu4NBr, CH2Cl2, 50% aq NaOH, 25 8C, 12 h; (e) 50%
aq TFA, 25 8C, 24 h, 20 (96%), 21 (94%), 22 (89%); (f) EtSH, conc H2SO4,
0 8C, 20 h, 23 (81%), 25 (76%), 27 (73%); (g) NaH, benzylbromide, THF,
25 8C, 12 h; (h) NaH, allylbromide, THF, 25 8C, 12 h; (i) NaH,
propargylbromide, THF, 25 8C, 12 h.
Scheme 2. Synthesis of penta-O-allyl and penta-O-propargyl glucose, their
respective oximes and the nitro derivative 12. Reagents and conditions:
(a) NaH, allylbromide, DMF, 25 8C, 12 h; (b) NaH, propargylbromide,
DMF, 25 8C, 12 h; (c) HgCl2, CaCO3, CH3CN–H2O (4:1), 25 8C, 6 h;
(d) NH2OH.HCl, pyridine, MeOH, reflux, 8 h; (e) (i) CH3NO2, KF,
2-propanol, 25 8C, 15 h, (ii) Ac2O, DMAP, CH2Cl2, 25 8C, 12 h,
(iii) NaBH4, EtOH, 0–25 8C, 6 h; (f) (i) NaIO4, EtOH, 25 8C, 10 h,
(ii) THF, conc H2SO4, 25 8C, 12 h.
Scheme 4. Synthesis of 2-O- and 4-O-allyl and -propargyl glucose oximes
from their dithioacetals. Reagents and conditions: (a) HgCl2, CaCO3,
CH3CN:H2O (4:1), 25 8C, 6 h; (b) NH2OH.HCl, pyridine, MeOH, reflux,
8 h; (c) (i) NaIO4, EtOH, 25 8C, 10 h, (ii) THF, conc H2SO4, 25 8C, 12 h.

S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
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The O-allylcarbohydrate aldehydes 30 and 34 were obtained
from the corresponding dithioacetal derivatives 24 and 28
by treatment with HgCl2 and CaCO3 in aqueous acetonitrile
(Scheme 4). The O-propargyl aldehydes 32 and 36 were
obtained in good yields from the O-propargyl dithioacetals
26 and 29 via the earlier mentioned oxidative method using
NaIO4 followed by treatment with an acid. The aldehydes
30, 32, 34 and 36 were converted to the corresponding
oximes 31, 33, 35 and 37, respectively, as described before
(Scheme 4).
juncture 3a-C and 6a-C at d 48.4 (CH) and 71.9 (CH),
respectively.
However, it was more difficult to ascertain whether 42 was a
tetrahydrofuran derivative arising out of the cycloaddition
to the 2-O-allyl group or a tetrahydropyran derivative due to
the cycloaddition to the 3-O-allyl group of 39. The problem
was resolved by the analysis of the EI mass spectrum
2.2. 2-O-Allyl carbohydrate nitrone cycloaddition
As reported earlier the N-benzyl nitrones 38 and 39 prepared
from 3,5,6-tri-O-benzylglucofuranose 20 and 10 by treat-
ment with N-benzylhydroxylamine in refluxing ethanol
afforded via in situ cycloaddition the fused isoxazolidines
41 (70%) and 42 (75%), respectively, as exclusive products
(Table 1).9 The presence of a one-proton multiplet at d 3.36
(3a-H) in the 1H NMR spectrum and a peak at d 47.5 (3a-C)
in the 13C NMR spectrum clearly indicated 41 to be a fused
isoxazolidine.20 The mass spectrum of 41 exhibited besides
the molecular ion at m/z 595 a strong peak at m/z 204 due to
the fragment 44, which is indicative of the presence of the
furoisoxazolidine skeleton. The presence of multiple allyl
groups in 42 caused extensive overlapping of signals in its
1H NMR spectrum. However, the occurrence of cyclo-
addition was evident from the appearance of peaks in the
spectrum due to the phenyl group as well as the ratio (5:4) of
the relative integrations of the aromatic protons and the
vinylic methine protons. The 13C NMR spectrum, however,
appeared to be more helpful, and clearly indicated the ring
of 42, in which the fragment 44 at m/z 204 appeared besides
the molecular ion at m/z 485 indicating the presence of the
tetrahydrofuran skeleton. The absence of any peak corre-
sponding to the mass spectral fragment 46 (m/z 274) in the
mass spectrum ruled out the alternative pyran structure. The
occurrence of the furoisoxazolidine fragment appeared to be
a characteristic of the EI mass spectra of furoisoxazolidines,
because the mass spectrum of 43, formed in 75% yield
by the cycloaddition of the N-methyl nitrone 40, also
exhibited a strong peak at m/z 128 corresponding to the
furoisoxazolidine fragment 45.
The assignment of the ring-junction stereochemistry in 41,
42 and 43 proved difficult by NMR spectral analysis due to
the presence of a number of allyl and benzyl moieties.
Hassner et al. reported a number of tetrahydropyrroloisoxa-
zolidine derivatives of the type 49 by the oxime-olefin
cycloaddition of 47 (Scheme 5).21,22 It is generally believed
that oxime-olefin cycloaddition proceeds via the formation
of the NH nitrone such as 48. The cis–trans stereochemistry
of the sequence 3a–6a–6 in 49 was established on the basis
of NMR spectral analysis.22 This stereochemical assign-
ment was also corroborated by MM2 calculations, which
revealed a 3.8 kcal difference in energy between the cis–cis
and the cis–trans isomers in favor of the latter.22 Due to
close structural resemblance, the transition state geometries
of the nitrones 38–40 are not expected to be much different
from that of 48, and the sequence 3a–6a–6 in 41–43 was
accordingly assigned the cis–trans stereochemistry.
Table 1. 2-O-Allyl carbohydrate nitrone cycloadditiona
Nitrone
precursor
Nitrone
Product
Yieldb
20
10
10
70%
41
38
39
40
75%
42
75%
Scheme 5. Reported examples of isoxazolidines prepared by oxime-olefin
cycloaddition.
43
An interesting feature of the cycloaddition of the pentaallyl
nitrones 39 and 40 is that although they contain three
potentially reactive alkenes viz. 2-, 3- and 4-O-allyl residues
available for cycloaddition to the dipole, the tetrahydrofuran
ring was formed exclusively. The result reflected the great
a Conditions: for N-benzyl nitrones–N-benzyl hydroxylamine, benzene,
reflux; for N-methyl nitrone 40–N-methyl hydroxylamine hydrochloride,
NaHCO3, 80% aq EtOH, reflux.
b Yields refer to chromatographically isolated products.

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S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
propensity of the formation of five-membered rings
compared to six- and seven-membered rings.
Table 2. In contrast to the diastereoselective nitrone
cycloaddition of the 2-O-allyl carbohydrate derivatives,
the corresponding nitrile oxide cycloaddition appeared to
furnish mixtures of diastereomers. The nitrile oxide 51,
generated from the pentaallyl carbohydrate oxime 11 by
treatment with chloramine-T in ethanol under reflux,
underwent in situ cycloaddition giving rise to a separable
mixture of the diastereomeric dihydrofuro[3,4-c]isoxazoles
55 and 56. The presence of the isoxazoline rings in these
compounds was evident from the appearance of 3a-C
signals at d 44.7 and d 50.4 as well as quaternary carbon
signals due to C]N at d 156.1 and d 157.7 in their 13C NMR
spectra. The furoisoxazole nature of the rings in 55 and 56
was evident from the appearance of strong peaks at m/z 112
corresponding to the ion 62 in their mass spectra.
The cleavage of the isoxazolidine ring is frequently a
necessary step in any synthetic exercise involving the
application of the cycloaddition strategy. Although
attempted reaction of 43 with LiAlH4 led to intractable
products, Zn and aqueous acetic acid successfully cleaved
43 to the trisubstituted tetrahydrofuran derivative 50 in 75%
yield (Scheme 6).
Scheme 6. Cleavage of the isoxazolidine ring of 43.
2.3. O-Allyl and -propargyl nitrile oxide cycloaddition
The results of the hitherto unreported application of the
intramolecular nitrile oxide cycloaddition to acyclic 2-O-
allyl and 4-O-allyl carbohydrate derivatives are presented in
The formation of epimeric pairs of racemic dihydroisoxa-
zolines fused to tetrahydrofuran rings has also been
observed in the cycloaddition of nitrile oxides generated
from 2-allyloxynitroethanes.23 The configurations at the
newly formed chiral center 3a-C could not be established by
NMR spectral analysis, for example, NOESY due to
Table 2. O-Allyl carbohydrate nitrile oxide cycloadditiona
Nitrile oxide
precursor
Nitrile oxide
Productb
Yield
(%)c
1
extensive overlapping of relevant signals in the H NMR
spectrum. However, a tentative assignment was made on the
basis of an empirical correlation of optical rotation with
configuration, which will be described later in this study.
The cycloaddition of the tetra-O-benzyl-2-O-allyl nitrile
oxide 52 prepared from the oxime 31 afforded an
inseparable mixture of the diastereomers 57 and 58. The
1H and 13C NMR spectra of the enriched chromatographic
fractions of the mixture had closely similar features, which
indicated that they were indeed 3a-epimers. In contrast, the
pentaallyl nitrile oxide 53, the homolog of the nitrile oxide
51 and generated from the nitro derivative 12 by treatment
with 4-chlorophenyl isocyanate, underwent cycloaddition to
give exclusively the pyran-fused isoxazoline 59 in 68%
yield. The pyranoisoxazoline ring in 59 was characterized
by the facile cleavage of the substituent at 6-C in the EI
mass spectrum, which exhibited a strong peak at m/z 126
corresponding to the ion 63. The 500 MHz 1H NMR
spectrum exhibited the 3a-H as a multiplet centered around
d 3.42. The gross structure of 59 was established by
DQFCOSY and HMQC spectra. The NOESY spectrum of
59 revealed cross peaks between 3a-H and 11-CH2, and
hence the stereochemistry of 3a-C was assigned as shown.
The cycloaddition of the 4-O-allyl carbohydrate nitrile
oxide 54 prepared from the oxime 35 by treatment with
chloramine-T led to the formation of a diastereomeric
mixture of the oxepanoisoxazolines 60 and 61, which were
separated by column chromatography and characterized.
The appearance of 3a-C signals at d 52.7 and 50.2 as well as
quaternary C]N carbon signals at d 159.7 and 157.7 in the
13C NMR spectra indicated the presence of the isoxazoline
ring in the above compounds.
11
31
61
51
55/56
57/58
54
52
53
12
68
59
35
64
60/61
54
a Conditions: nitrile oxides from (a) oximes–chloramine-T, ethanol, reflux;
(b) the nitro derivative 12–4-chlorophenyl isocyanate, triethylamine,
benzene, 25 8C.
b Except for 59, all the cycloadducts were isolated as mixtures of
diastereomers.
c Yields refer to chromatographically isolated mixtures.

S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
3003
The general yields of the abovementioned nitrile oxide
2.4. Empirical assignment of stereochemistry of the
3a-epimeric pairs of isoxazolines 55/56 and 60/61
cycloadditions were found to be rather poor compared to the
results observed for the corresponding nitrone cyclo-
addition. Although nitrile oxides are known to be suscep-
tible to dimerization, no dimeric products were detected in
the reactions. Intractable polymeric products were observed,
and the reasons for the inefficiency of the reaction in these
cases are not known to us.
As mentioned earlier that although individual components
of the epimeric pairs of the isoxazolines 55/56 and 60/61
were available, the stereochemistry of the newly formed
chiral centres in these compounds could not be established
by NOE due to overlapping of signals. The application of
X-ray diffraction analysis was precluded by their liquid
nature. In the past several attempts were made to
empirically assign stereochemistry on the basis of the
comparison of optical rotation values.25,26 With recourse to
such an assignment a survey of literature revealed that a
number of epimeric pairs of enantiomerically pure isoxa-
zolines with known optical rotation values exist, and are
listed in Table 4.27–32 It is apparent if the isoxazolines are
represented by 70 and 71, the former with the R
The approach described above for the synthesis of chiral
isoxazolines from 2-O- and 4-O-allyl nitrile oxides was also
suitable for preparing chiral isoxazole derivatives by the
nitrile oxide cycloaddition of the corresponding O-propar-
gyl derivatives. Although the synthesis of chiral isoxazolo-
pyrans and isoxazolooxepanes from 3-O-propargyl
carbohydrate derivatives has been reported,24 to our
knowledge synthesis of similar systems from the acyclic
counterparts is not yet known. In Table 3 are presented the
results of the cycloaddition of the nitrile oxides 64, 65 and
66. The 2-O-propargyl nitrile oxides generated from the
corresponding oximes 14 and 33 by treatment with
chloramine-T smoothly underwent cycloaddition giving
rise to the isoxazoles 67 and 68 in yields of 72 and 77%,
respectively. The cycloaddition of 4-O-propargyl nitrile
oxide 66 obtained from the oxime 37 led to the formation of
the oxepinoisoxazole derivative 69 in 80% yield. The
presence of the isoxazole ring in 67–69 was clearly evident
from the appearance of singlets at d 8.05, 7.96 and 8.18 in
Table 4. Examples of epimeric dihydroisoxazolines and their [a]D values
reported in the literature
Entry
3a R-isoxazoline [a]D
3a S-isoxazoline [a]D
Reference
27
1
K23.7
K160.0
2
3
27
28
their 1H NMR spectra due to the isoxazole protons. The 13
C
K206.0
K19.2
NMR spectra also exhibited peaks due to C]N and
quaternary C]C at d 170.5/123.6, 171.1/124.0 and 160.3/
118.5, respectively. The yields encountered in the alkyne-
nitrile oxide cycloadditions in the present study were found
to be considerably higher than those of the corresponding
alkene-nitrile oxide reactions, and reflected the high
efficiency of the reaction leading to the formation of a
stabilized heterocyclic ring.
C133.0
K54.0
4
5
6
29
30
31
C34.7
C94.0
C49.0
K20.4
K14.0
Table 3. O-Propargyl carbohydrate nitrile oxide cycloaddtiona
Nitrile oxide
precursor
Nitrile oxide
Product
Yield
(%)b
14
72
64
67
68
K12.5
33
37
77
80
7
8
31
32
65
66
C2.4
K67.4
C26.7
69
a Conditions: chloramine-T, ethanol, reflux.
b Yields refer to chromatographically isolated products.
C264.9

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S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
configuration of the newly formed center 3a-C (with the
arbitrarily assigned sequence priority as shown) has the
higher positive rotation. An interesting feature of the optical
rotation values is that the difference in the specific rotation
values of epimers is appreciable and ranges from C55.1 to
C238.2, although the magnitude of the differences does
not conform to any correlation with the structural
ether refers to a fraction boiling between 60 and 80 8C.
Room temperature refers to 25 8C.
3.1.1. Penta-O-allylglucose diethyl dithioacetal 8. The
glucose dithioacetal 714 (4.00 g, 14.00 mmol) was added in
portions to a stirred suspension of NaH (2.00 g,
83.00 mmol) in DMF (60 mL) at 0 8C. After the addition
was over, the mixture was stirred at 25 8C for 1 h. A solution
of allyl bromide (7.5 mL, 87.00 mmol) in DMF (20 mL)
was added dropwise to the mixture at 0 8C and the stirring
was continued for 30 min. The mixture was then stirred for
another 12 h at 25 8C. The whole reaction mixture was
poured into water (500 mL) and extracted with CH2Cl2. The
combined organic layers were washed with water, dried and
concentrated in vacuo affording a yellowish liquid, which
on chromatography (EtOAc–petroleum ether, 1:24) gave 8
(6.50 g, 96%) as a light yellow liquid, [a]2D5C13.2 (c 0.97,
CHCl3); IR (Neat): 3080, 3013, 1645, 1455 cmK1; MS
pattern. Following this trend, the isoxazolines 55, 56, 60 and
61 were empirically assigned the stereochemistry shown in
Figure 1.
1
(FAB): m/z 487 (MCH); H NMR: d 6.03–5.85 (m, 5H),
5.37–5.09 (m, 10H), 4.34–3.97 (m, 12H), 3.88–3.80 (m,
2H), 3.73–3.56 (m, 3H), 2.82–2.61 (m, 4H), 1.25 (t, 6H, JZ
7.6 Hz); 13C NMR: d 135.1 (CH), 134.9 (CH), 134.7 (2!
CH), 134.5 (CH), 116.5 (CH2), 116.4 (CH2), 116.0 (2!
CH2), 115.8 (CH2), 82.7 (CH), 80.4 (CH), 78.8 (CH), 78.1
(CH), 74.2 (CH2), 73.7 (CH2), 72.5 (CH2), 71.9 (CH2), 70.6
(CH2), 69.2 (CH2), 52.9 (CH), 24.7 (CH2), 24.6 (CH2), 14.2
(2!CH3). Anal. Calcd for C25H42O5S2: C, 61.69; H, 8.70.
Found: C, 61.61; H, 8.39.
3.1.2. Penta-O-propargylglucose diethyl dithioacetal 9.
The above procedure using 7 (1.50 g, 5.24 mmol) and
propargyl bromide (4.84 mL, 32.50 mmol) as the alkylating
agent yielded after chromatography of the crude product
(EtOAc–petroleum ether, 1:19) 9 (2.20 g, 88%) as a pale
yellow liquid, [a]2D5K12.0 (c 0.76, CHCl3); IR (Neat): 3291,
2117, 1449 cmK1; MS (EI): m/z 476 (M), 415 (MKSEt); 1H
NMR: d 4.51 (t, 2H, JZ2.4 Hz), 4.49 (d, 2H, JZ2.1 Hz),
4.41 (d, 2H, JZ2.2 Hz), 4.36 (t, 2H, JZ2.4 Hz), 4.22–4.21
(m, 2H), 4.11 (t, 2H, JZ4.5 Hz), 4.00–3.96 (m, 3H), 3.88 (t,
1H, JZ4.3 Hz), 3.73 (dd, 1H, JZ11.3, 6.1 Hz), 2.81–2.68
(m, 4H), 2.47–2.45 (m, 5H), 1.28 (t, 6H, JZ7.4 Hz); 13C
NMR: d 81.9 (CH), 80.0 (CH), 79.7 (CH), 79.6 (2!CH),
79.3 (CH), 79.2 (CH), 78.2 (CH), 77.4 (CH), 74.8 (q), 74.6
(q), 74.5 (2!q), 74.4 (q), 68.5 (CH2), 60.0 (CH2), 59.8
(CH2), 58.8 (CH2), 58.1 (CH2), 57.2 (CH2), 52.5 (CH), 25.1
(CH2), 24.8 (CH2), 14.2 (CH3), 14.1 (CH3). Anal. Calcd for
C25H32O5S2: C, 63.00; H, 6.77. Found: C, 63.24; H, 6.68.
Figure 1. Empirically assigned stereochemistry of isoxazolines.
In conclusion, the work described here demonstrated that
intramolecular nitrone and nitrile oxide cycloaddition of
readily available acyclic 2- and 4-O-allyl and -propargyl
carbohydrate derivatives can furnish diverse types of chiral
cyclic ether fused isoxazolidine, isoxazoline and isoxazole
rings.
3. Experimental
3.2. General procedure for the cleavage of diethyl
dithioacetals by HgCl2
3.1. General
Melting points are uncorrected. Unless otherwise mentioned
1H and 13C NMR spectra were recorded in CDCl3 at 300 and
75 MHz, respectively. Assignment of CH3, CH2, CH and
quaternary (q) carbon atoms in 13C NMR spectra was based
on DEPT analysis. Elemental analyses were performed at
the Indian Association for the Cultivation of Science,
Kolkata. Reactions were monitored by thin layer chroma-
tography using Merck 60 F254 precoated silica gel plate
(No. 1.05554). Organic extracts were dried over anhydrous
sodium sulfate. Unless otherwise mentioned 60–120 mesh
silica gel was used for column chromatography. Solvents
were distilled and dried immediately prior to use. Petroleum
Preparation of the aldehydes 10, 30 and 34. The general
procedure for the cleavage of the dithioacetals by HgCl2 is
illustrated by the preparation of 10.
A mixture of 8 (1.00 g, 2.00 mmol) in 80% aq CH3CN
(30 mL), HgCl2 (1.20 g, 4.40 mmol) and CaCO3 (0.45 g,
4.40 mmol) were added and stirred at 25 8C for 6 h. After
completion of the reaction as revealed by TLC, the resulting
precipitate was filtered and washed with CH3CN. The
combined filtrate and washings were evaporated under
reduced pressure. The residue obtained was extracted with
CH2Cl2 and the combined organic extracts were washed

S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
3005
with water and dried. Removal of solvent yielded 10
(0.76 g, 96%) as a light yellow liquid, which was used
without purification for the next step.
3.4.1. Aldoxime 14. Pale yellow syrup; yield: 66%; mixture
of syn and anti isomers; IR (Neat): 3362, 3293, 2119,
1445 cmK1; MS (FAB): m/z 386 (MCH), 330 (MK
1
OCH2CCH); H NMR: d 7.97 (br s, 1H), 7.54 (d, 0.8H,
The aldehydes 30 and 34 prepared by this method were also
used without purification.
JZ7.6 Hz), 6.99 (d, 0.2H, JZ6.5 Hz), 5.09 (dd, 0.2H, JZ
6.4, 3.7 Hz), 4.46–4.12 (m, 10.8H), 4.01–3.86 (m, 4H),
3.77–3.73 (m, 1H), 2.49–2.44 (m, 5H); 13C NMR: d 149.8
(CH), 148.6 (CH), 79.8 (CH), 79.7 (CH), 79.6 (2!CH),
79.5 (CH), 79.3 (CH), 79.2 (CH), 79.0 (CH), 78.9 (CH),
78.3 (CH), 77.9 (CH), 77.7 (CH), 77.3 (CH), 75.8 (CH),
75.4 (q), 75.3 (q), 75.0 (q), 74.9 (q), 74.8 (q), 74.7 (q), 74.6
(q), 74.4 (q), 70.6 (CH), 67.8 (CH2), 67.7 (CH2), 59.8 (CH2),
59.7 (CH2), 59.6 (CH2), 59.5 (CH2), 58.2 (CH2), 57.4 (CH2),
57.2 (CH2), 56.3 (CH2). Anal. Calcd for C21H23NO6: C,
65.44; H, 6.02; N, 3.63. Found: C, 65.57; H, 6.23; N, 3.53.
3.3. General procedure for the cleavage of diethyl
dithioacetals by NaIO4–H2SO4
Preparation of the aldehydes 13, 32 and 36. The general
procedure for the cleavage of the dithioacetals is illustrated
by the preparation of 13.
To a solution of 9 (1.00 g, 2.10 mmol) in EtOH (40 mL) was
added with stirring a solution of NaIO4 (1.12 g, 5.23 mmol)
in water (10 mL) and the mixture was stirred at 25 8C for
10 h. It was then filtered and the filtrate was concentrated
under reduced pressure. The residue was extracted with
CH2Cl2 and the combined organic extracts were washed
with water, dried and removal of solvent afforded a syrupy
material. A solution of the above material in THF (20 mL)
containing a catalytic amount of conc H2SO4 was stirred at
25 8C for 12 h. The reaction mixture was neutralised with
saturated NaHCO3 solution and solvent was removed until a
syrupy residue was obtained. The residue was extracted with
CH2Cl2 and the combined organic layers were washed with
water, dried and concentrated to give 13 (0.56 g, 72%) as a
colorless liquid, which was immediately used without
purification for the next step.
3.4.2. Aldoxime 31. Colorless syrup; yield: 59%; mixture of
syn and anti isomers; IR (Neat): 3354, 3062, 3031, 1644,
1
1603, 1494, 1454 cmK1; MS (FAB): m/z 596 (MCH); H
NMR: d 7.41 (d, 0.75H, JZ7.6 Hz), 7.31–7.26 (m, 20H),
6.89 (d, 0.25H, JZ6.2 Hz), 5.89–5.76 (m, 1H), 5.24 (dd,
1H, JZ17.2, 1.4 Hz), 5.14 (dd, 1H, JZ10.3, 1.4 Hz), 4.88
(dd, 0.25H, JZ6.2, 4.5 Hz), 4.74–4.43 (m, 7.75H), 4.24 (dd,
1H, JZ7.4, 6.3 Hz), 4.11–4.05 (m, 1H), 4.00–3.96 (m, 1H),
3.91–3.82 (m, 4H), 3.70–3.66 (m, 1H); 13C NMR: d 151.3
(CH), 149.6 (CH), 138.4 (q), 138.36 (q), 138.2 (q), 138.0
(q), 134.0 (CH), 133.9 (CH), 128.3 (CH), 128.2 (CH),
128.16 (CH), 128.1 (CH), 128.0 (CH), 127.9 (CH), 127.7
(CH), 127.6 (CH), 127.5 (CH), 127.4 (CH), 127.36 (CH),
117.7 (CH2), 117.5 (CH2), 79.8 (CH), 78.4 (CH), 78.3 (CH),
76.9 (CH), 75.0 (CH2), 74.6 (CH2), 74.1 (CH2), 73.2 (CH2),
71.9 (CH2), 71.7 (CH2), 71.1 (CH2), 70.3 (CH2), 69.3 (CH2),
68.8 (CH2). Anal. Calcd for C37H41NO6: C, 74.60; H, 6.94;
N, 2.35. Found: C, 74.82; H, 6.97; N, 2.21.
The aldehydes 32 and 36 prepared by the above method was
also used without purification.
3.4. General procedure for the preparation of aldoximes
11, 14, 31, 33, 35 and 37
3.4.3. Aldoxime 33. Colorless syrup; yield: 64%; mixture of
syn and anti isomers; IR (Neat): 3362, 3292, 3062, 3031,
2117, 1604, 1495, 1453 cmK1; MS (FAB): m/z 616 (MC
Na), 594 (MCH), 576 (MKOH), 538 (MKOCH2CCH),
The general procedure is illustrated by the preparation of 11.
1
486 (MKOBn); H NMR: d 7.40 (d, 0.8H, JZ7.4 Hz),
A mixture of 10 (0.80 g, 2.10 mmol), pyridine (0.4 mL,
5.00 mmol), NH2OH.HCl (0.22 g, 3.15 mmol) and MeOH
(20 mL) was heated under reflux for 8 h. After removal of
solvent, the residue was extracted with CH2Cl2. The organic
extract was washed with water, dried and evaporated under
reduced pressure. The residue was repeatedly co-evaporated
with dry toluene, and then chromatographed (EtOAc–
petroleum ether, 1:16–1:12) to give the oxime 11 (0.60 g,
72%, mixture of syn and anti isomers) as a pale yellow
7.31–7.25 (m, 20H), 6.91 (d, 0.2H, JZ6.0 Hz), 5.07 (dd,
0.2H, JZ5.9, 3.8 Hz), 4.76–4.59 (m, 5H), 4.57–4.41 (m,
3.8H), 4.26–3.99 (m, 3H), 3.92–3.83 (m, 3H), 3.75 (dd,
0.2H, JZ10.3, 5.8 Hz), 3.69 (dd, 0.8H, JZ10.1, 4.6 Hz),
2.36 (t, 1H, JZ2.2 Hz); 13C NMR: d 149.0 (CH), 138.5 (q),
138.3 (q), 138.1 (q), 128.3 (CH), 128.24 (CH), 128.22 (CH),
128.19 (CH), 128.16 (CH), 127.9 (CH), 127.7 (CH), 127.6
(CH), 127.44 (CH), 127.39 (CH), 79.7 (CH), 79.5 (CH),
79.2 (CH), 78.7 (CH), 78.3 (CH), 76.1 (CH), 75.1 (q), 74.8
(CH2), 74.3 (CH2), 73.2 (CH2), 71.9 (CH2), 68.9 (CH2), 56.3
(CH2). Anal. Calcd for C37H39NO6: C, 74.85; H, 6.62; N,
2.36. Found: C, 74.77; H, 6.87; N, 2.16.
syrup, IR (Neat): 3363, 3081, 3014, 1646, 1457, 1424 cmK1
;
1
MS (FAB): m/z 396 (MCH); H NMR: d 7.48 (d, 0.75H,
JZ7.5 Hz), 6.95 (d, 0.25H, JZ6.5 Hz), 5.96–5.83 (m, 5H),
5.30–5.10 (m, 10H), 4.88 (dd, 0.25H, JZ6.4, 4.6 Hz), 4.33–
3.54 (m, 15.75H); 13C NMR: d 150.9 (CH), 149.4 (CH),
135.2 (CH), 134.9 (2!CH), 134.8 (CH), 134.7 (CH), 134.6
(CH), 134.5 (CH), 134.3 (CH), 134.0 (CH), 133.9 (CH),
117.4 (CH2), 117.2 (CH2), 117.0 (CH2), 116.9 (CH2), 116.8
(CH2), 116.7 (CH2), 116.5 (CH2), 116.4 (CH2), 116.3
(CH2), 116.2 (CH2), 80.3 (CH), 79.5 (CH), 79.1 (CH), 78.5
(CH), 78.2 (CH), 77.8 (2!CH), 76.8 (CH), 74.2 (CH2), 73.9
(CH2), 73.6 (CH2), 73.2 (CH2), 72.1 (CH2), 71.4 (CH2), 71.0
(CH2), 70.7 (CH2), 70.1 (CH2), 68.8 (CH2), 68.4 (CH2), 68.3
(CH2). Anal. Calcd for C21H33NO6: C, 63.78; H, 8.41; N,
3.54. Found: C, 63.59; H, 8.47; N, 3.42.
3.4.4. Aldoxime 35. Colorless syrup; yield: 82%; mixture of
syn and anti isomers; IR (Neat): 3354, 3063, 3031, 1644,
1604, 1495, 1454 cmK1; MS (FAB): m/z 634 (MCK), 618
1
(MCNa), 596 (MCH); H NMR: d 7.49 (d, 0.75H, JZ
7.6 Hz), 7.31–7.25 (m, 20H), 6.93 (d, 0.25H, JZ6.6 Hz),
5.94–5.81 (m, 1H), 5.18 (dd, 1H, JZ17.2, 1.4 Hz), 5.08 (dd,
1H, JZ10.2, 1.4 Hz), 4.98 (dd, 0.25H, JZ6.2, 4.0 Hz), 4.72
(d, 1H, JZ11.5 Hz), 4.65–4.46 (m, 4.75H), 4.43–4.27 (m,
3H), 4.19–4.11 (m, 2H), 3.91–3.76 (m, 4H), 3.67–3.60 (m,
1H); 13C NMR: d 150.8 (CH), 149.4 (CH), 138.4 (q), 138.3

3006
S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
(q), 138.2 (q), 138.1 (q), 138.0 (q), 137.5 (q), 137.4 (q),
135.1 (CH), 134.8 (CH), 128.2 (CH), 128.1 (CH), 128.0
(CH), 127.9 (CH), 127.6 (CH), 127.5 (CH), 127.4 (CH),
127.3 (CH), 116.5 (CH2), 116.3 (CH2), 79.3 (CH), 79.1
(CH), 78.7 (CH), 78.5 (CH), 78.0 (CH), 77.9 (CH), 76.8
(CH), 74.8 (CH2), 74.3 (CH2), 73.5 (CH2), 73.2 (CH2), 73.1
(CH2), 72.0 (CH2), 71.7 (CH2), 71.6 (CH2), 71.2 (CH2), 69.0
(CH2), 68.4 (CH2). Anal. Calcd for C37H41NO6: C, 74.60;
H, 6.94; N, 2.35. Found: C, 74.46; H, 7.12; N, 2.16.
CH2Cl2 and the combined organic layers were washed with
water, dried and concentrated to give 16 (4.2 g, 98%) as a
light yellow viscous oil, which was a mixture of the a and b
anomers and used as such for the next steps. The mixture
was separated by chromatography (100–200 mesh; EtOAc–
petroleum ether, 1:9) to give the a-16 as a colorless syrup,
[a]2D8C28.9 (c 0.32, CHCl3); IR (Neat): 3517, 3062, 3031,
1604 cmK1; MS (FAB): m/z 487 (MCNa), 465 (MCH),
447 (MKOH), 433 (MKOCH3); 1H NMR: d 7.33–7.25 (m,
15H), 5.02 (d, 1H, JZ4.5 Hz), 4.78 (d, 1H, JZ11.5 Hz),
4.69 (d, 1H, JZ11.7 Hz), 4.61–4.57 (m, 2H), 4.54 (d, 1H,
JZ11.5 Hz), 4.51 (d, 1H, JZ11.7 Hz), 4.30 (dd, 1H, JZ
8.2, 4.4 Hz), 4.24 (dd, 1H, JZ4.1, 1.4 Hz), 4.06–4.00 (m,
2H), 3.86 (dd, 1H, JZ10.5, 1.9 Hz), 3.69 (dd, 1H, JZ10.6,
5.8 Hz), 3.46 (s, 3H).
3.4.5. Aldoxime 37. Colorless syrup; yield: 67%; mixture of
syn and anti isomers; IR (Neat): 3363, 3292, 3061, 3032,
2119, 1604, 1495, 1453 cmK1; MS (FAB): m/z 594 (MC
1
H), 576 (MKOH), 486 (MKOBn); H NMR: d 7.54 (d,
0.7H, JZ7.6 Hz), 7.31–7.26 (m, 20H), 6.98 (d, 0.3H, JZ
6.2 Hz), 4.95 (dd, 0.3H, JZ6.4, 4.4 Hz), 4.71–4.46 (m, 6H),
4.43–4.27 (m, 4.7H), 4.03 (dd, 0.3H, JZ5.6, 4.3 Hz), 3.96–
3.81 (m, 2.7H), 3.77–3.72 (m, 1H), 3.67–3.62 (m, 1H), 2.39
(t, 1H, JZ2.3 Hz). Anal. Calcd for C37H39NO6: C, 74.85; H,
6.62; N, 2.36. Found: C, 74.69; H, 6.59; N, 2.32.
Further elution with EtOAc–petroleum ether (1:7) afforded
the b-16 as a colorless syrup, [a]2D8K54.9 (c 0.25, CHCl3);
IR (Neat): 3431, 3062, 3031, 1604 cmK1; MS (FAB): m/z
487 (MCNa), 465 (MCH), 447 (MKOH), 433 (MK
OCH3); 1H NMR: d 7.36–7.25 (m, 15H), 4.79 (s, 1H), 4.75
(d, 1H, JZ11.4 Hz), 4.62–4.58 (m, 3H), 4.53 (d, 1H, JZ
11.9 Hz), 4.50 (d, 1H, JZ11.4 Hz), 4.39 (dd, 1H, JZ8.9,
4.9 Hz), 4.18 (s, 1H), 4.06 (ddd, 1H, JZ8.7, 5.1, 1.9 Hz),
3.96 (dd, 1H, JZ4.8, 1.1 Hz), 3.89 (dd, 1H, JZ10.7,
1.9 Hz), 3.72 (dd, 1H, JZ10.7, 5.2 Hz), 3.36 (s, 3H).
3.4.6. (3S,4R,5R,6R)-3,4,5,6,7-Pentaallyloxy-1-nitrohep-
tane (12). A mixture of the aldehyde 10 (1.76 g, 4.63 mmol)
prepared as described above, nitromethane (5.1 mL,
92.60 mmol), anhydrous KF (0.40 g, 6.90 mmol) and
isopropanol (20 mL) was stirred at 25 8C for 15 h. The
mixture was then filtered and the filtrate was concentrated to
afford a syrupy liquid. To a solution of this material in
CH2Cl2 (20 mL) at 0 8C, Ac2O (1 mL) and 4-dimethyl-
aminopyridine (DMAP) (50 mg) were added, and the
mixture was kept at 25 8C for 12 h. After addition of
water (25 mL), the mixture was extracted with CH2Cl2, and
the combined organic layers were washed with 10% HCl
(5 mL), water, dried and concentrated to yield an oil. The
latter was dissolved in ethanol (10 mL) and added dropwise
to a stirred suspension of NaBH4 (1.00 g) in EtOH (30 mL)
at 0 8C and the resulting mixture was stirred for 6 h at 25 8C.
Excess NaBH4 was destroyed by the addition of 10%
aqueous AcOH, and the residue obtained after removal of
solvent was extracted with CH2Cl2. The combined organic
layers were washed with water, dried and concentrated
under reduced pressure to give a syrupy residue, which was
chromatographed (EtOAc–petroleum ether, 1:12) to give 12
(1.40 g, 71%) as a light yellow syrupy liquid, [a]2D5K16.7 (c
0.86, CHCl3); IR (Neat): 3081, 1646, 1553 cmK1; MS
3.5. General procedure for the alkylation of 16
The procedure is illustrated by the preparation of methyl-2-
O-allyl-3,5,6-tri-O-benzylglucofuranoside (17).
3.5.1. Methyl-2-O-allyl-3,5,6-tri-O-benzylglucofurano-
side (17). A mixture of 16 (3.3 g, 7.11 mmol) in CH2Cl2
(50 mL), 50% aq NaOH solution (40 mL), tetrabutylammo-
niumbromide (15 mol%) and allyl bromide (0.92 mL,
10.66 mmol) was vigorously stirred for 12 h at 25 8C.
Water (50 mL) was added and the mixture was extracted
with CH2Cl2. The combined organic layer was washed with
water, dried and the solvent was removed under reduced
pressure to afford 17 (3.26 g, 91%) as a colorless syrup,
which was a mixture of the a and b anomers and used as
such for the next steps. The mixture was separated by
chromatography (EtOAc–petroleum ether, 1:19) to give the
b-17 as a colorless syrup, [a]2D5K39.1 (c 2.15, CHCl3); IR
(Neat): 3063, 3031, 1644, 1603 cmK1; MS (FAB): m/z 527
(MCNa), 505 (MCH), 473 (MKOCH3); 1H NMR: d 7.37–
7.24 (m, 15H), 5.87–5.76 (m, 1H), 5.26–5.14 (m, 2H), 4.85
(s, 1H), 4.78 (d, 1H, JZ11.4 Hz), 4.59–4.57 (m, 4H), 4.51
(d, 1H, JZ11.4 Hz), 4.31 (dd, 1H, JZ9.0, 4.6 Hz), 4.08
(ddd, 1H, JZ9.0, 5.3, 2.0 Hz), 4.02 (dd, 1H, JZ4.5,
0.7 Hz), 3.92–3.87 (m, 4H), 3.72 (dd, 1H, JZ10.7, 5.3 Hz),
3.38 (s, 3H); 13C NMR: d 138.8 (q), 138.5 (q), 137.8 (q),
133.9 (CH), 128.2 (2!CH), 128.16 (2!CH), 128.1 (2!
CH), 127.8 (2!CH), 127.6 (CH), 127.5 (2!CH), 127.4
(2!CH), 127.3 (CH), 127.2 (CH), 117.3 (CH2), 108.5
(CH), 85.4 (CH), 80.4 (CH), 80.1 (CH), 76.5 (CH), 73.2
(CH2), 72.2 (CH2), 72.1 (CH2), 70.7 (CH2), 70.5 (CH2), 55.8
(CH3). Anal. Calcd for C31H36O6: C, 73.79; H, 7.19. Found:
C, 73.56; H, 7.28.
1
(FAB): m/z 426 (MCH); H NMR: d 5.98–5.82 (m, 5H),
5.30–5.13 (m, 10H), 4.55 (dd, 1H, JZ13.3, 7.4 Hz), 4.46
(dd, 1H, JZ13.3, 6.4 Hz), 4.23–3.96 (m, 10H), 3.78–3.53
(m, 6H), 2.47–2.39 (m, 1H), 2.17–2.09 (m, 1H); 13C NMR:
d 134.7 (CH), 134.64 (CH), 134.62 (CH), 134.4 (CH), 134.2
(CH), 117.0 (CH2), 116.7 (2!CH2), 116.5 (CH2), 116.2
(CH2), 79.5 (CH), 77.8 (CH), 77.5 (CH), 75.4 (CH), 73.5
(CH2), 72.8 (CH2), 72.2 (CH2), 72.0 (CH2), 71.9 (CH2), 70.5
(CH2), 68.0 (CH2), 28.6 (CH2). Anal. Calcd for C22H35NO7:
C, 62.10; H, 8.29; N, 3.29. Found: C, 62.02; H, 8.14;
N, 3.35.
3.4.7. (a,b)-Methyl-3,5,6-tri-O-benzylglucofuranoside
(16). A solution of 15 (4.5 g, 9.18 mmol) in dry MeOH
(75 mL) containing TsOH (0.22 g, 1.41 mmol) was heated
at reflux for 6 h. The reaction mixture was neutralised with
saturated NaHCO3 solution and solvent was removed until a
syrupy residue was obtained. The residue was extracted with
Further elution with EtOAc–petroleum ether (1:16) afforded
the a-17 as a colorless syrup, [a]2D5C43.2 (c 1.20, CHCl3);

S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
3007
IR (Neat): 3063, 3031, 1644, 1602 cmK1; MS (FAB): m/z
505 (MCH); H NMR: d 7.33–7.27 (m, 15H), 5.97–5.84
(m, 20H), 4.90 (s, 1H), 4.77 (d, 1H, JZ11.4 Hz), 4.59 (s,
2H), 4.52 (s, 2H), 4.51 (d, 1H, JZ11.2 Hz), 4.43 (s, 2H),
4.35 (dd, 1H, JZ9.0, 4.6 Hz), 4.11–4.06 (m, 2H), 3.92 (s,
1H), 3.88 (d, 1H, JZ1.7 Hz), 3.72 (dd, 1H, JZ10.7,
5.3 Hz), 3.37 (s, 3H); 13C NMR: d 138.8 (q), 138.6 (q),
137.8 (q), 137.4 (q), 128.4 (2!CH), 128.3 (2!CH), 128.2
(2!CH), 128.1 (2!CH), 127.9 (2!CH), 127.8 (CH),
127.6 (CH), 127.5 (6!CH), 127.3 (CH), 127.2 (CH), 108.6
(CH), 85.6 (CH), 80.5 (CH), 80.1 (CH), 76.5 (CH), 73.3
(CH2), 72.3 (CH2), 72.1 (CH2), 71.7 (CH2), 70.7 (CH2), 55.8
(CH3). Anal. Calcd for C35H38O6: C, 75.79; H, 6.91. Found:
C, 75.91; H, 6.83.
1
(m, 1H), 5.27 (d, 1H, JZ17.3 Hz), 5.20 (d, 1H, JZ
10.3 Hz), 4.95 (d, 1H, JZ4.2 Hz), 4.79 (d, 1H, JZ11.6 Hz),
4.63 (d, 1H, JZ11.8 Hz), 4.56 (s, 2H), 4.55 (d, 1H, JZ
11.5 Hz), 4.54 (d, 1H, JZ11.3 Hz), 4.33 (t, 1H, JZ6.4 Hz),
4.21 (dd, 1H, JZ5.7, 4.0 Hz), 4.12–3.98 (m, 3H), 3.94 (t,
1H, JZ4.0 Hz), 3.86 (dd, 1H, JZ10.6, 1.7 Hz), 3.71 (dd,
1H, JZ10.5, 6.1 Hz), 3.41 (s, 3H); 13C NMR: d 138.8 (q),
138.5 (q), 138.0 (q), 134.4 (CH), 129.7 (CH), 128.9 (CH),
126.8 (CH), 117.7 (CH2), 101.4 (CH), 83.6 (CH), 81.9 (CH),
76.8 (CH), 76.7 (CH), 73.3 (CH2), 72.5 (CH2), 72.2 (CH2),
71.7 (CH2), 71.2 (CH2), 55.4 (CH3). Anal. Calcd for
C31H36O6: C, 73.79; H, 7.19. Found: C, 73.68; H, 7.36.
Further elution with EtOAc–petroleum ether (1:14) afforded
the a-19 as a colorless syrup, [a]2D5C40.6 (c 1.19, CHCl3);
IR (Neat): 3062, 3031, 1603 cmK1; MS (EI): m/z 554 (M);
1H NMR: d 7.34–7.19 (m, 20H), 4.87 (d, 1H, JZ4.2 Hz),
4.77 (d, 1H, JZ11.6 Hz), 4.63 (d, 1H, JZ12.0 Hz), 4.55–
4.45 (m, 6H), 4.35 (t, 1H, JZ6.2 Hz), 4.23 (dd, 1H, JZ5.7,
3.9 Hz), 4.02–3.95 (m, 2H), 3.85 (dd, 1H, JZ10.5, 2.0 Hz),
3.69 (dd, 1H, JZ10.5, 6.1 Hz), 3.39 (s, 3H); 13C NMR: d
138.8 (q), 138.5 (q), 137.9 (q), 137.5 (q), 128.3 (2!CH),
128.2 (2!CH), 128.1 (2!CH), 128.0 (2!CH), 127.9 (2!
CH), 127.8 (CH), 127.5 (3!CH), 127.4 (2!CH), 127.3
(2!CH), 127.2 (CH), 127.1 (CH), 101.3 (CH), 83.5 (CH),
81.9 (CH), 76.7 (CH), 76.5 (CH), 73.2 (CH2), 72.5 (CH2),
72.4 (CH2), 72.0 (CH2), 71.1 (CH2), 55.3 (CH3). Anal.
Calcd for C35H38O6: C, 75.79; H, 6.91. Found: C, 75.72; H,
6.74.
3.5.2. Methyl-2-O-propargyl-3,5,6-tri-O-benzylgluco-
furanoside (18). The above procedure using propargyl
bromide as the alkylating agent gave 18 (88%) as a mixture
of anomers, which was used without separation for the next
step. The mixture was separated by chromatography
(EtOAc–petroleum ether, 1:19) to give the b-18 as a
colorless syrup, [a]2D5K54.0 (c 1.49, CHCl3); IR (Neat):
3285, 3062, 3031, 2117, 1602 cmK1; MS (FAB): m/z 525
(MCNa), 503 (MCH), 471 (MKOCH3); 1H NMR: d 7.37–
7.25 (m, 15H), 4.87 (s, 1H), 4.77 (d, 1H, JZ11.4 Hz), 4.64
(d, 1H, JZ12.0 Hz), 4.59 (s, 2H), 4.57 (d, 1H, JZ12.0 Hz),
4.51 (d, 1H, JZ11.4 Hz), 4.29 (dd, 1H, JZ9.0, 4.7 Hz),
4.15–4.01 (m, 5H), 3.89 (dd, 1H, JZ10.7, 2.0 Hz), 3.71 (dd,
1H, JZ10.7, 5.3 Hz), 3.39 (s, 3H), 2.44 (t, 1H, JZ2.5 Hz);
13C NMR: d 138.8 (q), 138.5 (q), 137.7 (q), 128.3 (2!CH),
128.2 (2!CH), 128.1 (2!CH), 127.8 (2!CH), 127.6
(CH), 127.5 (4!CH), 127.3 (CH), 127.2 (CH), 108.3 (CH),
84.9 (CH), 80.0 (CH), 79.9 (CH), 79.0 (CH), 76.4 (CH),
75.1 (q), 73.3 (CH2), 72.3 (CH2), 72.0 (CH2), 70.6 (CH2),
57.0 (CH2), 55.9 (CH3). Anal. Calcd for C31H34O6: C,
74.08; H, 6.82. Found: C, 73.84; H, 6.73.
3.6. General procedure for the deglycosylation of the
methylfuranosides 20, 21, 22
The general deglycosylation procedure is illustrated by the
preparation of 20.
3.6.1. 2-O-Allyl-3,5,6-tri-O-benzylglucofuranose (20). A
solution of the a/b mixture 17 (2.60 g) in 50% aq TFA
(30 mL) was stirred at 25 8C for 24 h. The reaction mixture
was neutralized with solid NaHCO3. The resulting mixture
was extracted with CH2Cl2 and the combined organic
extract was washed with water, dried and concentrated to
give a syrupy liquid, which on chromatography (EtOAc–
petroleum ether, 1:9) gave an anomeric mixture of 20
(2.42 g, 96%) as a colorless syrup, IR (Neat): 3508, 3062,
3031, 1644, 1603 cmK1; MS (FAB): m/z 513 (MCNa), 491
Further elution with EtOAc–petroleum ether (1:16) afforded
the a-18 as a colorless syrup, [a]2D5C39.5 (c 1.04, CHCl3);
IR (Neat): 3285, 3063, 3032, 2119, 1602 cmK1; MS (FAB):
m/z 525 (MCNa), 503 (MCH), 471 (MKOCH3); 1H NMR:
d 7.35–7.21 (m, 15H), 5.02 (d, 1H, JZ3.9 Hz), 4.79 (d, 1H,
JZ11.6 Hz), 4.68 (d, 1H, JZ11.7 Hz), 4.56 (s, 2H), 4.55 (d,
1H, JZ11.6 Hz), 4.53 (d, 1H, JZ11.7 Hz), 4.35–4.16 (m,
5H), 4.03 (ddd, 1H, JZ8.2, 6.1, 2.2 Hz), 3.86 (dd, 1H, JZ
10.6, 2.2 Hz), 3.70 (dd, 1H, JZ10.6, 6.1 Hz), 3.41 (s, 3H),
2.46 (t, 1H, JZ2.5 Hz); 13C NMR: d 138.8 (q), 138.5 (q),
137.9 (q), 128.4 (CH), 128.3 (2!CH), 128.2 (2!CH),
128.1 (2!CH), 127.6 (2!CH), 127.5 (2!CH), 127.4 (2!
CH), 127.3 (CH), 127.2 (CH), 101.3 (CH), 82.7 (CH), 81.6
(CH), 79.2 (CH), 76.8 (CH), 76.5 (CH), 75.3 (q), 73.3
(CH2), 72.5 (CH2), 72.0 (CH2), 71.1 (CH2), 57.6 (CH2), 55.4
(CH3). Anal. Calcd for C31H34O6: C, 74.08; H, 6.82. Found:
C, 74.26; H, 6.68.
1
(MCH), 473 (MKOH); H NMR: d 7.36–7.21 (m, 15H),
5.88–5.77 (m, 1H), 5.48 (d, 0.4H, JZ3.3 Hz), 5.28–5.17 (m,
2.6H), 4.84 (d, 0.6H, JZ11.4 Hz), 4.83 (d, 0.4H, JZ
11.4 Hz), 4.63–4.47 (m, 5H), 4.31 (dd, 0.6H, JZ9.4,
3.7 Hz), 4.23 (dd, 0.4H, JZ9.1, 3.3 Hz), 4.12–3.89 (m,
5.6H), 3.78 (d, 0.4H, JZ3.7 Hz), 3.72 (dd, 0.6H, JZ10.6,
5.5 Hz), 3.70 (dd, 0.4H, JZ10.6, 5.8 Hz).
3.6.2. 2-O-Propargyl-3,5,6-tri-O-benzylglucofuranose
(21). The same procedure starting from the a/b mixture of
18 (2.95 g) yielded an anomeric mixture of 21 (2.70 g, 94%)
as a colorless syrup, IR (Neat): 3435, 3287, 3062, 3031,
2117, 1603 cmK1; MS (FAB): m/z 511 (MCNa), 471 (MK
3.5.3. Methyl-2,3,5,6-tetra-O-benzylglucofuranoside
(19). The above procedure using benzyl bromide as the
alkylating agent gave 19 (90%) as a mixture of anomers,
which was used without separation for the next step. The
mixture was separated by chromatography (EtOAc–petro-
leum ether, 1:16) to give the b-19 as a colorless syrup,
[a]2D5K30.4 (c 1.35, CHCl3); IR (Neat): 3062, 3031,
1
OH), 411 (MKPh); H NMR: d 7.35–7.25 (m, 15H), 5.50
(d, 0.35H, JZ3.4 Hz), 5.22 (s, 0.65H), 4.82 (d, 0.65H, JZ
11.5 Hz), 4.81 (d, 0.35H, JZ11.4 Hz), 4.64–4.47 (m, 6H),
4.30–4.22 (m, 1H), 4.18–4.12 (m, 3H), 4.07–3.99 (m, 1H),
1
1603 cmK1; MS (EI): m/z 554 (M); H NMR: d 7.36–7.26

3008
S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
3.94–3.88 (m, 1H), 3.72 (dd, 0.65H, JZ10.7, 5.4 Hz), 3.69
(dd, 0.35H, JZ10.7, 5.9 Hz), 2.45 (t, 1H, JZ2.5 Hz).
135.0 (CH), 128.1 (CH), 128.08 (CH), 128.03 (CH), 128.0
(CH), 127.9 (CH), 127.5 (CH), 127.44 (CH), 127.4 (CH),
127.36 (CH), 127.2 (CH), 116.1 (CH2), 82.9 (CH), 80.7
(CH), 79.4 (CH), 78.6 (CH), 75.2 (CH2), 73.8 (CH2), 73.4
(CH2), 73.1 (CH2), 71.8 (CH2), 70.0 (CH2), 53.3 (CH), 24.9
(CH2), 24.7 (CH2), 14.3 (CH3), 14.2 (CH3). Anal. Calcd for
C41H50O5S2: C, 71.68; H, 7.34. Found: C, 71.57; H, 7.17.
3.6.3. 2,3,5,6-Tetra-O-benzylglucofuranose (22). The
same procedure starting from the a/b mixture of 19
(2.00 g) yielded an anomeric mixture of 22 (1.73 g, 89%)
asacolorlesssyrup, IR(Neat):3508, 3062, 3031, 1603 cmK1
;
1
MS (FAB): m/z 563 (MCNa), 523 (MKOH); H NMR: d
7.36–7.17 (m, 20H), 5.48 (br s, 0.4H), 5.25 (br s, 0.6H), 4.83
(d, 0.6H, JZ11.4 Hz), 4.81 (d, 0.4H, JZ11.3 Hz), 4.63–
4.41 (m, 7H), 4.34 (dd, 0.6H, JZ9.4, 3.7 Hz), 4.26 (dd,
0.4H, JZ9.1, 3.3 Hz), 4.12–3.83 (m, 4H), 3.73 (dd, 0.6H,
JZ10.5, 5.4 Hz), 3.69 (dd, 0.4H, JZ10.5, 5.5 Hz).
3.7.1. Dithioacetal 26. The same procedure starting from
21 (2.69 g) yielded after chromatography (EtOAc–petro-
leum ether, 1:10) 25 (2.48 g, 76%) as a light yellow syrup,
[a]2D5K33.2 (c 0.64, CHCl3); IR (Neat): 3536, 3288, 3062,
3031, 2120, 1603, 1496, 1452 cmK1; MS (FAB): m/z 633
1
(MCK), 617 (MCNa), 595 (MCH), 533 (MKSEt); H
NMR: d 7.34–7.26 (m, 15H), 4.86 (d, 1H, JZ11.1 Hz), 4.73
(d, 1H, JZ11.7 Hz), 4.57 (s, 2H), 4.48 (d, 2H, JZ1.7 Hz),
4.43 (d, 1H, JZ11.1 Hz), 4.34 (d, 1H, JZ11.7 Hz), 4.22–
4.20 (m, 1H), 4.09 (dd, 1H, JZ7.4, 2.9 Hz), 3.97 (d, 1H, JZ
2.9 Hz), 3.89 (dd, 1H, JZ10.4, 2.4 Hz), 3.75–3.70 (m, 2H),
3.66–3.62 (m, 1H), 2.72 (q, 2H, JZ7.3 Hz), 2.70 (q, 2H, JZ
7.3 Hz), 2.40 (t, 1H, JZ2.4 Hz), 1.26 (t, 3H, JZ7.3 Hz),
1.23 (t, 3H, JZ7.3 Hz); 13C NMR: d 138.2 (q), 138.1 (q),
138.0 (q), 128.2 (CH), 128.15 (CH), 128.11 (CH), 128.0
(CH), 127.5 (CH), 127.4 (CH), 127.3 (CH), 83.0 (CH), 79.8
(CH), 78.0 (CH), 77.8 (CH), 74.6 (q), 74.6 (CH2), 73.3
(CH2), 71.4 (CH2), 70.6 (CH), 69.8 (CH2), 60.1 (CH2), 52.7
(CH), 25.6 (CH2), 25.5 (CH2), 14.3 (2!CH3).
3.7. General procedure for the preparation of the diethyl
dithioacetal derivatives 24, 26, 28 and 29
The general procedure for the preparation of the above
compounds is illustrated by the preparation of 24.
A solution of 20 (2.40 g) in conc HCl (18 mL) was cooled to
0 8C with stirring for 15 min. To the mixture was added
EtSH (9 mL) dropwise and the resulting solution was stirred
for another 4 h at 0 8C. The solution was kept in a freezer for
16 h. The reaction mixture was neutralised with solid
NaHCO3 and then extracted with CH2Cl2. The combined
organic layers were washed with water, dried and
evaporated under reduced pressure yielding a light yellow
syrup, which was chromatographed (EtOAc–petroleum
ether, 1:11) to give 23 (2.37 g, 81%) as a colorless syrup,
[a]2D5K46.7 (c 0.14, CHCl3); IR (Neat): 3539, 3063, 3030,
1604, 1496, 1453 cmK1; MS (FAB): m/z 619 (MCNa), 597
Alkylation of 25 (1.07 g, 1.80 mmol) with benzyl bromide
(0.32 mL, 2.70 mmol) using the procedure described for the
convertion of 23 to 24 gave after chromatography (EtOAc–
petroleum ether, 1:16) 26 (0.93 g, 76%) as a colorless syrup,
[a]2D5C1.0 (c 0.20, CHCl3); IR (Neat): 3289, 3062, 3031,
2120, 1603, 1495, 1452 cmK1; MS (FAB): m/z 685 (MC
1
(MCH), 535 (MKSEt); H NMR: d 7.34–7.26 (m, 15H),
6.01–5.88 (m, 1H), 5.25 (dd, 1H, JZ17.2, 1.6 Hz), 5.12 (dd,
1H, JZ10.5, 1.4 Hz), 4.83 (d, 1H, JZ11.2 Hz), 4.72 (d, 1H,
JZ11.6 Hz), 4.57 (s, 2H), 4.43 (d, 1H, JZ11.2 Hz), 4.34–
4.28 (m, 3H), 4.19 (d, 1H, JZ7.5 Hz), 3.98–3.87 (m, 3H),
3.75–3.62 (m, 3H), 2.76–2.61 (m, 4H), 1.25 (t, 3H, JZ
7.4 Hz), 1.23 (t, 3H, JZ7.4 Hz).
1
H), 623 (MKSEt), 577 (MKOBn); H NMR: d 7.36–7.23
(m, 20H), 4.81 (d, 1H, JZ11.2 Hz), 4.76 (d, 1H, JZ
11.3 Hz), 4.72 (d, 1H, JZ11.2 Hz), 4.68 (d, 1H, JZ
11.2 Hz), 4.66 (d, 1H, JZ11.4 Hz), 4.55–4.51 (m, 3H),
4.47–4.45 (m, 2H), 4.20–4.17 (m, 1H), 3.96–3.87 (m, 5H),
3.76–3.70 (m, 1H), 2.64 (q, 2H, JZ7.4 Hz), 2.59–2.50 (m,
2H), 2.37 (t, 1H, JZ2.2 Hz), 1.20 (t, 3H, JZ7.4 Hz), 1.15
(t, 3H, JZ7.4 Hz); 13C NMR: d 138.5 (2!q), 138.2 (q),
138.1 (q), 128.2 (3!CH), 128.1 (3!CH), 128.0 (4!CH),
127.9 (2!CH), 127.5 (2!CH), 127.4 (3!CH), 127.3
(CH), 127.27 (CH), 127.2 (CH), 82.0 (CH), 80.2 (CH), 80.0
(CH), 79.2 (CH), 78.8 (CH), 75.1 (CH2), 74.5 (q), 73.6
(CH2), 73.1 (CH2), 71.8 (CH2), 69.8 (CH2), 59.5 (CH2), 52.8
(CH), 25.1 (CH2), 24.7 (CH2), 14.3 (CH3), 14.1 (CH3).
Anal. Calcd for C41H48O5S2: C, 71.89; H, 7.06. Found: C,
71.82; H, 7.24.
A solution of 23 (2.30 g, 3.86 mmol) in THF (20 mL) was
added dropwise to a stirred suspension of NaH (60%
suspension in mineral oil; 0.232 g, 5.79 mmol) in THF
(20 mL) at 0 8C. After the addition was over, the mixture
was stirred at 25 8C for 1 h. To this mixture was added
dropwise with stirring a solution of benzyl bromide
(0.70 mL, 5.79 mmol) in THF (20 mL) at 0 8C and stirring
was continued for 30 min. The mixture was heated at 25 8C
for 12 h. It was then cooled to 0 8C and few drops of water
were added to destroy excess NaH. After concentration of
the mixture, the residue was extracted with CH2Cl2. The
combined organic layers were washed with water, dried,
concentrated and the residue was chromatographed
(EtOAc–petroleum ether, 1:10) to give 24 (1.72 g, 65%)
as a colorless syrup, [a]D25K2.4 (c 0.11, CHCl3); IR (Neat):
3062, 3030, 1644, 1604, 1495, 1453 cmK1; MS (FAB): m/z
3.7.2. Dithioacetal 28. Dithioacetylation of 22 (1.54 g)
afforded after chromatography (EtOAc–petroleum ether,
1:11) 27 (1.34 g, 73%) as a colorless syrup, [a]2D8K18.9 (c
0.23, CHCl3); IR (Neat): 3538, 3062, 3031, 1604, 1496,
1452 cmK1; MS (FAB): m/z 669 (MCNa), 585 (MKSEt);
1H NMR: d 7.37–7.18 (m, 20H), 4.86 (d, 1H, JZ11.1 Hz),
4.80 (d, 1H, JZ11.2 Hz), 4.78 (d, 1H, JZ11.1 Hz), 4.71 (d,
1H, JZ11.6 Hz), 4.57 (s, 2H), 4.42 (d, 1H, JZ11.1 Hz),
4.30 (d, 1H, JZ11.6 Hz), 4.22 (d, 1H, JZ7.7 Hz), 4.09
(dd, 1H, JZ7.7, 2.7 Hz), 3.96 (d, 1H, JZ2.7 Hz), 3.90 (dd,
1H, JZ10.7, 2.8 Hz), 3.76–3.71 (m, 2H), 3.66–3.61 (m,
1H), 2.74–2.59 (m, 4H), 1.24 (t, 3H, JZ7.4 Hz), 1.20 (t, 3H,
1
709 (MCNa), 625 (MKSEt), 579 (MKOBn); H NMR: d
7.33–7.25 (m, 20H), 5.99–5.87 (m, 1H), 5.22 (d, 1H, JZ
17.2 Hz), 5.08 (d, 1H, JZ10.3 Hz), 4.82–4.61 (m, 5H),
4.51–4.48 (m, 3H), 4.29–4.26 (m, 2H), 4.17–4.14 (m, 1H),
3.95–3.83 (m, 5H), 3.76–3.73 (m, 1H), 2.66 (q, 2H, JZ
7.4 Hz), 2.56–2.48 (m, 2H), 1.20 (t, 3H, JZ7.4 Hz), 1.14 (t,
3H, JZ7.4 Hz); 13C NMR: d 138.6 (q), 138.5 (q), 138.2 (q),

S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
3009
JZ7.4 Hz); 13C NMR: d 138.2 (3!q), 138.0 (q), 128.1
(CH), 128.03 (CH), 127.99 (CH), 127.9 (CH), 127.7 (CH),
127.6 (CH), 127.4 (CH), 127.3 (CH), 127.2 (CH), 83.3
(CH), 78.1 (CH), 77.9 (CH), 75.1 (CH2), 74.4 (CH2), 73.2
(CH2), 71.3 (CH2), 70.5 (CH), 69.8 (CH2), 53.3 (CH), 25.6
(CH2), 25.2 (CH2), 14.2 (2!CH3).
(0.21 g) for 8 h. It was then filtered and washed with
benzene. The combined filtrate and the washings were
evaporated to afford a syrupy residue, which on chroma-
tography (EtOAc–petroleum ether, 1:7) gave 42 (0.36 g,
75%) as a colorless syrup, [a]2D5C21.8 (c 1.42, CHCl3); IR
(Neat): 3079, 3013, 1645 cmK1; MS (EI): m/z 485 (M), 204;
1H NMR: d 7.39–7.24 (m, 5H), 6.00–5.83 (m, 3H), 5.77–
5.64 (m, 1H), 5.33–5.00 (m, 8H), 4.30–4.24 (m, 1H), 4.18–
4.00 (m, 9H), 3.82–3.48 (m, 9H), 3.38–3.28 (m, 3H); 13C
NMR: d 136.6 (q), 135.3 (CH), 135.0 (CH), 134.8 (CH),
134.7 (CH), 129.0 (2!CH), 128.3 (2!CH), 127.4 (CH),
116.4 (CH2), 116.3 (CH2), 116.0 (CH2), 115.9 (CH2), 83.2
(CH), 80.5 (CH), 78.5 (CH), 78.2 (CH), 73.9 (CH2), 73.4
(CH2), 73.2 (CH2), 72.0 (CH2), 71.9 (CH), 70.6 (CH2), 69.7
(CH2), 69.2 (CH2), 59.9 (CH2), 48.4 (CH). Anal. Calcd for
C28H39NO6: C, 69.25; H, 8.09; N, 2.88. Found: C, 68.95; H,
7.99; N, 2.72.
Alkylation of 27 (1.70 g, 2.63 mmol) with allyl bromide
(0.34 mL, 3.95 mmol) gave after chromatography (EtOAc–
Petroleum ether, 1:16) 28 (1.10 g, 61%) as a colorless syrup,
[a]2D5C3.8 (c 0.39, CHCl3); IR (Neat): 3063, 3030, 1644,
1604, 1496, 1453 cmK1; MS (FAB): m/z 685 (MKH), 625
(MKSEt), 579 (MKOBn); 1H NMR: d 7.44–7.26 (m, 20H),
5.95–5.82 (m, 1H), 5.20 (d, 1H, JZ17.2 Hz), 5.12 (d, 1H,
JZ10.3 Hz), 4.86 (d, 1H, JZ11.0 Hz), 4.80 (d, 1H, JZ
11.2 Hz), 4.79 (d, 1H, JZ10.8 Hz), 4.66 (d, 1H, JZ
11.1 Hz), 4.62 (d, 1H, JZ11.6 Hz), 4.51 (s, 2H), 4.37 (d,
1H, JZ11.8 Hz), 4.24–4.20 (m, 2H), 4.13–4.04 (m, 3H),
3.91–3.83 (m, 2H), 3.77 (t, 1H, JZ4.4 Hz), 3.67 (dd, 1H,
JZ9.9, 4.7 Hz), 2.77–2.59 (m, 4H), 1.22 (t, 3H, JZ7.3 Hz),
1.20 (t, 3H, JZ7.3 Hz); 13C NMR: d 138.6 (q), 138.5 (q),
138.4 (q), 138.2 (q), 134.8 (CH), 128.3 (CH), 128.1 (CH),
128.0 (CH), 127.9 (CH), 127.8 (CH), 127.6 (CH), 127.4
(CH), 127.3 (CH), 127.2 (CH), 127.1 (CH), 116.8 (CH2),
82.7 (CH), 80.5 (CH), 78.9 (CH), 78.7 (CH), 75.1 (CH2),
74.5 (CH2), 73.1 (CH2), 72.8 (CH2), 71.6 (CH2), 69.5 (CH2),
53.4 (CH), 24.8 (2!CH2), 14.3 (2!CH3). Anal. Calcd for
C41H50O5S2: C, 71.68; H, 7.34. Found: C, 71.52; H, 7.32.
Compound 41. The same procedure starting from 20 (0.42 g,
0.86 mmol) with BnNHOH (0.16 g, 1.30 mmol) yielded
after chromatography (EtOAc–petroleum ether, 1:5) 41
(0.36 g, 70%) as a white solid, mp 98–99 8C, [a]2D5K16.4 (c
1.40, CHCl3); IR (KBr): 3508, 3061, 3031, 1604 cmK1; MS
1
(EI): m/z 595 (M), 204; H NMR (100 MHz): d 7.36–7.28
(m, 20H), 4.74 (d, 1H, JZ12.0 Hz), 4.58 (s, 2H), 4.42 (s,
2H), 4.32–4.08 (m, 2H), 3.96–3.52 (m, 12H), 3.36 (m, 1H),
1.64 (br s, 1H); 13C NMR (25 MHz): d 138.6 (2!q), 138.4
(q), 136.2 (q), 129.2 (CH), 128.4 (CH), 128.2 (CH), 128.1
(CH), 127.6 (CH), 127.5 (CH), 127.3 (CH), 85.4 (CH), 77.7
(CH), 77.4 (CH), 73.7 (CH2), 73.6 (CH2), 73.3 (CH2), 72.7
(CH), 71.7 (CH2), 71.3 (CH), 70.0 (2!CH2), 59.8 (CH2),
47.5 (CH). Anal. Calcd for C37H41NO6: C, 74.60; H, 6.94;
N, 2.35. Found: C, 74.48; H, 7.23; N, 2.18.
3.7.3. Dithioacetal 29. Alkylation of 27 (1.30 g,
2.01 mmol) with propargyl bromide (0.45 mL, 3.02 mmol)
yielded after chromatography (EtOAc–Petroleum ether,
1:16) 29 (1.00 g, 73%) as a colorless syrup, [a]2D8K11.2 (c
0.27, CHCl3); IR (Neat): 3289, 3062, 3031, 2120, 1604,
1496, 1452 cmK1; MS (FAB): m/z 707 (MCNa), 684 (M),
3.8.1. Preparation of the N-methyl nitrone 40 and its
cycloaddition to (10R,20R,30R,3aR,6S,6aS)-1-methyl-6-
(10,20,30,40-tetraallyloxy)butyltetrahydrofuro[3,4-c]-
isoxazole (43). A solution of 10 (1.16 g, 3.05 mmol),
MeNHOH.HCl (0.33 g, 3.95 mmol) and NaHCO3 (0.39 g,
4.64 mmol) in 80% aqueous EtOH (40 mL) was heated
under reflux for 12 h. After it was cooled to 25 8C, the
mixture was concentrated under reduced pressure to give a
residue, which was extracted with CH2Cl2. The organic
layer was washed with water, dried and concentrated to give
a reddish yellow syrupy residue, which on chromatography
(EtOAc–petroleum ether, 1:6) gave 43 (0.94 g, 75%) as a
pale yellow syrup. [a]D25C19.8 (c 0.65, CHCl3); IR (Neat):
1
623 (MKSEt), 577 (MKOBn); H NMR: d 7.38–7.22 (m,
20H), 4.89 (d, 1H, JZ11.0 Hz), 4.80 (d, 1H, JZ11.1 Hz),
4.79 (d, 1H, JZ11.4 Hz), 4.66 (d, 1H, JZ11.3 Hz), 4.61 (d,
1H, JZ11.8 Hz), 4.50 (s, 2H), 4.42–4.37 (m, 3H), 4.21–4.08
(m, 3H), 3.97–3.90 (m, 2H), 3.84–3.79 (m, 1H), 3.65 (dd,
1H, JZ10.5, 5.4 Hz), 2.77–2.63 (m, 4H), 2.44 (t, 1H, JZ
2.3 Hz), 1.23 (t, 3H, JZ7.4 Hz), 1.22 (t, 3H, JZ7.4 Hz);
13C NMR: d 138.3 (q), 138.2 (q), 138.1 (q), 137.9 (q), 127.9
(CH), 127.8 (CH), 127.4 (CH), 127.2 (CH), 127.0 (CH),
82.5 (CH), 80.3 (CH), 79.9 (CH), 79.0 (CH), 77.8 (CH),
75.0 (CH2), 74.7 (q), 74.5 (CH2), 72.9 (CH2), 71.5 (CH2),
69.3 (CH2), 58.5 (CH2), 53.2 (CH), 24.7 (CH2), 24.5 (CH2),
14.2 (2!CH3). Anal. Calcd for C41H48O5S2: C, 71.89; H,
7.06. Found: C, 71.97; H, 7.12.
1
3079, 1645 cmK1; MS (FAB): m/z 410 (MCH), 128; H
NMR: d 6.00–5.85 (m, 4H), 5.30–5.09 (m, 8H), 4.35–3.99
(m, 10H), 3.84–3.81 (m, 2H), 3.72–3.51 (m, 7H), 3.34–3.29
(m, 1H), 2.63 (s, 3H); 13C NMR: d 135.0 (CH), 134.7 (CH),
134.6 (CH), 134.4 (CH), 116.3 (CH2), 116.1 (CH2), 116.0
(CH2), 115.5 (CH2), 82.6 (CH), 79.7 (CH), 78.7 (CH), 77.9
(CH), 75.1 (CH), 73.5 (CH2), 73.0 (2!CH2), 71.7 (CH2),
70.4 (CH2), 69.1 (CH2), 68.8 (CH2), 48.4 (CH), 43.4 (CH3).
Anal. Calcd for C22H35NO6: C, 64.52; H, 8.61; N, 3.42.
Found: C, 64.53; H, 8.77; N, 3.22.
3.8. General procedure for the preparation of the
N-benzyl nitrones 38 and 39 and their cycloaddition to
(10R,20R,30R,3aR,6S,6aS)-6-(20-hydroxy-10,30,40-tri-
benzyloxy)butyltetrahydrofuro[3,4-c]isoxazole (41) and
(10R,20R,30R,3aR,6S,6aS)-1-benzyl-6-(10,20,30,40-tetra-
allyloxy)butyltetrahydrofuro[3,4-c]isoxazole (42)
The general procedure is illustrated by the preparation of 39
and its cycloaddition to 42.
3.8.2. (10R,20R,30R,2S,3S,4S)-3-Methylamino-4-hydroxy-
methyl-2-(10,20,30,40-tetraallyloxy)butyltetrahydrofuran
(50). A mixture of the isoxazolidine 43 (2.06 g, 5.01 mmol)
and Zn dust (1.31 g, 20.04 mmol) in 60% aqueous AcOH
(35 mL) was heated under reflux for 7 h. After completion
A solution of the aldehyde 10 (0.38 g, 1.00 mmol) and
BnNHOH (0.19 g, 1.54 mmol) in benzene (10 mL) was
˚
heated under reflux in the presence of 3 A molecular sieves

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S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
of the reaction as revealed by TLC, the mixture was
concentrated under reduced pressure. The residue was
extracted with CH2Cl2 and the combined organic extracts
were washed with NaHCO3, water, dried and concentrated
under reduced pressure to give a syrupy residue, which was
chromatographed (MeOH–CH2Cl2, 1:49) to give 50 (1.40 g,
75%) as a colorless syrup, [a]2D8C2.1 (c 0.81, CHCl3); IR
(Neat): 3331, 3080, 3012, 1645 cmK1; MS (EI): m/z 412
(MCH), 130; 1H NMR: d 6.01–5.84 (m, 4H), 5.30–5.11 (m,
8H), 4.34–4.25 (m, 2H), 4.18–4.05 (m, 4H), 4.01–3.96 (m,
3H), 3.85–3.66 (m, 8H), 3.58–3.51 (m, 2H), 3.29 (t, 1H, JZ
7.3 Hz), 2.85 (br s, 2H, exchangeable with D2O), 2.49 (s,
3H); 13C NMR: d 135.1 (CH), 134.9 (CH), 134.6 (CH),
134.4 (CH), 116.7 (CH2), 116.4 (2!CH2), 115.8 (CH2),
82.6 (CH), 79.9 (CH), 79.2 (CH), 77.7 (CH), 74.0 (CH2),
72.5 (CH2), 71.9 (CH2), 70.7 (CH2), 69.5 (CH2), 69.1 (CH2),
64.0 (CH), 61.4 (CH2), 42.0 (CH), 35.7 (CH3). Anal. Calcd
for C22H37NO6: C, 64.21; H, 9.06; N, 3.40. Found: C, 63.96;
H, 8.78; N, 3.13.
5.32–5.14 (m, 8H), 4.75 (d, 1H, JZ4.7 Hz), 4.59 (dd, 1H,
JZ10.7, 8.1 Hz), 4.28–4.20 (m, 2H), 4.11–3.82 (m, 10H),
3.76–3.59 (m, 5H); 13C NMR: d 157.7 (q), 135.0 (CH),
134.9 (CH), 134.6 (CH), 133.7 (CH), 117.6 (CH2), 117.5
(CH2), 116.8 (CH2), 116.6 (CH2), 80.5 (CH), 76.3 (CH),
75.4 (CH), 73.6 (CH2), 72.3 (CH2), 72.2 (CH), 71.4 (CH2),
71.2 (CH2), 70.8 (CH2), 69.8 (CH2), 68.3 (CH2), 50.4 (CH).
Anal. Calcd for C21H31NO6: C, 64.10; H, 7.94; N, 3.56.
Found: C, 63.87; H, 7.88; N, 3.63.
3.9.3. (10R,20R,30R,3aR,6S)-6-(10,20,30,40-Tetrabenzy-
loxy)-butyl-3a,4-dihydro-3H,6H-furo[3,4-c]isoxazole
(57) and (10R,20R,30R,3aS,6S)-6-(10,20,30,40-tetrabenzyl-
oxy)butyl-3a,4-dihydro-3H,6H-furo[3,4-c]isoxazole (58).
NMR and mass spectra of the preparative TLC fractions
enriched in either 57 or 58 were obtained. Data for the
fraction enriched in the faster moving compound 57 in TLC
(EtOAc–petroleum ether, 1:3): MS (FAB): m/z 594 (MC
H); 1H NMR (peaks assignable to 57 are presented): d 7.32–
7.29 (m), 4.83 (d, JZ3.3 Hz), 4.76 (s), 4.67 (d, JZ11.9 Hz),
4.62 (d, JZ10.7 Hz), 4.56 (d, JZ12.2 Hz), 4.52 (s), 4.27
(t, JZ7.9 Hz), 4.08 (dd, JZ6.1, 4.2 Hz), 3.67 (dd, JZ9.6,
4.7 Hz), 3.59 (t, JZ9.0 Hz); 13C NMR (peaks assignable to
57 are presented): d 170.3 (q), 138.7 (q), 138.4 (q), 138.2
(q), 138.1 (q), 128.4–127.4 (aromatic CH), 80.6 (CH), 79.8
(CH), 78.6 (CH), 75.3 (CH2), 74.6 (CH2), 73.43 (CH2),
73.36 (CH2), 73.1 (CH), 72.0 (CH2), 69.8 (CH2), 69.3
(CH2), 56.0 (CH). Anal. Calcd for C37H39NO6: C, 74.85; H,
6.62; N, 2.36. Found: C, 74.73; H, 6.69; N, 2.25. Data for the
fraction enriched in the slower moving compound 58 in
TLC (EtOAc–petroleum ether, 1:3): MS (FAB): m/z 594
(MCH); 1H NMR (peaks assignable to 58 are presented): d
7.32–7.28 (m), 4.86 (d, JZ3.1 Hz), 4.76–4.68 (m), 4.58 (d,
JZ11.8 Hz), 4.52 (s), 4.23 (dd, JZ5.9, 4.5 Hz), 4.15 (dd,
JZ5.9, 3.8 Hz), 3.70 (dd, JZ9.9, 5.1 Hz); 13C NMR (peaks
assignable to 58 are presented): d 170.4 (q), 138.8 (q), 138.6
(q), 138.5 (q), 138.3 (q), 128.4–127.4 (aromatic CH), 81.3
(CH), 79.6 (CH), 79.1 (CH), 75.5 (CH2), 74.5 (CH2), 73.4
(CH2), 72.4 (CH), 72.0 (CH2), 69.7 (CH2), 56.6 (CH). Anal.
Calcd for C37H39NO6: C, 74.85; H, 6.62; N, 2.36. Found: C,
74.95; H, 6.53; N, 2.23.
3.9. General procedure for the generation of O-allyl and
O-propargyl nitrile oxides from oximes and their
cycloaddition
A mixture of chloramine-T hydrate (0.64 mmol) and the
oxime (0.25 mmol) in EtOH (10 mL) was heated under
reflux for 9 h. After completion of the reaction as revealed
by TLC, the resulting precipitate was filtered and the filtrate
was evaporated under reduced pressure. The residue was
extracted with CH2Cl2 and the combined organic layer was
washed successively with water, 1 M aq NaOH solution and
water. The organic extract was then dried, and removal of
solvent afforded a syrupy residue, which on chromatog-
raphy over silicagel (100–200 mesh; EtOAc–petroleum
ether) gave the dihydroisoxazoline as a mixture of
3a-epimers or the isoxazole. The yields of the mixture of
3a-epimeric dihydroisoxazolines are presented in Table 2.
The individual epimers 55, 56, 60 and 61 could be isolated
by column chromatography. The mixture of 57 and 58 on
preparative TLC gave enriched fractions of the two
compounds.
3.9.1. (10R,20R,30R,3aR,6S)-6-(10,20,30,40-Tetraallyloxy)-
butyl-3a,4-dihydro-3H,6H-furo[3,4-c]isoxazole (55).
[a]2D5K39.7 (c 0.21, CHCl3); IR (Neat): 3080, 1645 cm-1;
MS (EI): m/z 393 (M), 112; 1H NMR: d 6.02–5.81 (m, 4H),
5.34–5.11 (m, 8H), 4.51 (dd, 1H, JZ10.2, 8.3 Hz), 4.41 (s,
1H), 4.38 (dd, 1H, JZ10.6, 6.7 Hz), 4.29 (dd, 1H, JZ12.5,
5.8 Hz), 4.21 (dd, 1H, JZ12.5, 5.8 Hz), 4.10–3.97 (m, 6H),
3.89–3.81 (m, 2H), 3.74–3.64 (m, 3H), 3.59–3.55 (m, 1H),
3.50 (dd, 1H, JZ7.8, 1.3 Hz), 3.34 (t, 1H, JZ10.8 Hz); 13C
NMR: d 156.1 (q), 135.6 (CH), 134.8 (CH), 134.5 (CH),
133.3 (CH), 118.4 (CH2), 116.8 (CH2), 116.6 (CH2), 116.4
(CH2), 82.5 (CH), 78.7 (CH), 77.4 (CH), 74.3 (CH2), 72.2
(CH2), 71.9 (CH2), 70.7 (CH2), 70.0 (CH2), 69.9 (CH2), 69.9
(CH), 68.9 (CH2), 44.7 (CH). Anal. Calcd for C21H31NO6:
C, 64.10; H, 7.94; N, 3.56. Found: C, 63.87; H, 7.93; N,
3.43.
3.9.4. (10R,3aR,6R,7R,8R)-6-(10,20-Dibenzyloxy)ethyl-
7,8-dibenzyloxy-3a,4,7,8-tetrahydro-3H,6H-2,5-dioxa-1-
azaazulene (60). [a]2D5C75.2 (c 0.37, CHCl3); IR (Neat):
1
3061, 3031, 1602 cmK1; MS (FAB): m/z 594 (MCH); H
NMR: d 7.31–7.20 (m, 18H), 7.09–7.07 (m, 2H), 4.79 (d,
1H, JZ12.3 Hz), 4.70 (d, 1H, JZ11.6 Hz), 4.63–4.42 (m,
6H), 4.25 (d, 1H, JZ12.0 Hz), 4.21 (d, 1H, JZ12.0 Hz),
4.10–4.04 (m, 2H), 3.93–3.79 (m, 3H), 3.73–3.65 (m, 3H),
3.52 (t, 1H, JZ10.7 Hz); 13C NMR: d 159.7 (q), 138.5 (2!
q), 137.5 (q), 137.4 (q), 128.4 (4!CH), 128.3 (2!CH),
128.2 (2!CH), 128.1 (2!CH), 128.0 (2!CH), 127.9
(CH), 127.8 (CH), 127.6 (2!CH), 127.5 (2!CH), 127.4
(2!CH), 77.7 (CH), 77.0 (CH), 75.5 (CH), 73.4 (CH2), 72.5
(CH2), 71.7 (CH2), 71.1 (CH2), 70.9 (CH), 70.4 (CH2), 69.3
(CH2), 69.0 (CH2), 52.7 (CH). Anal. Calcd for C37H39NO6:
C, 74.85; H, 6.62; N, 2.36. Found: C, 74.62; H, 6.86; N,
1.99.
3.9.2. (10R,20R,30R,3aS,6S)-6-(10,20,30,40-Tetraallyloxy)-
butyl-3a,4-dihydro-3H,6H-furo[3,4-c]isoxazole (56).
3.9.5. (10R,3aS,6R,7R,8R)-6-(10,20-Dibenzyloxy)ethyl-7,8-
dibenzyloxy-3a,4,7,8-tetrahydro-3H,6H-2,5-dioxa-1-
azaazulene (61). [a]2D5K57.9 (c 0.52, CHCl3); IR (Neat):
[a]2D5K69.4 (c 0.46, CHCl3); IR (Neat): 3081, 1646 cmK1
;
MS (EI): m/z 393 (M), 112; 1H NMR: d 6.01–5.81 (m, 4H),

S. Ghorai et al. / Tetrahedron 61 (2005) 2999–3012
3011
3061, 3031, 1607 cmK1; MS (FAB): m/z 616 (MCNa), 594
(MCH); 1H NMR: d 7.33–7.22 (m, 20H), 4.81 (d, 1H, JZ
4.5 Hz), 4.68–4.46 (m, 7H), 4.31 (d, 1H, JZ3.3 Hz), 4.27
(d, 1H, JZ3.6 Hz), 4.09–4.03 (m, 3H), 3.82–3.75 (m, 4H),
3.68–3.58 (m, 2H); 13C NMR: d 157.7 (q), 138.4 (q), 138.3
(q), 137.4 (q), 137.0 (q), 128.4 (2!CH), 128.3 (2!CH),
128.2 (6!CH), 127.9 (CH), 127.6 (5!CH), 127.4 (2!
CH), 127.4 (CH), 127.3 (CH), 80.3 (CH), 76.4 (CH), 75.2
(CH), 73.6 (CH2), 73.2 (CH2), 72.0 (CH), 71.8 (CH2), 71.7
(2!CH2), 69.6 (CH2), 68.2 (CH2), 50.2 (CH). Anal. Calcd
for C37H39NO6: C, 74.85; H, 6.62; N, 2.36. Found: C, 74.54;
H, 6.87; N, 2.14.
3.9.9. Preparation of the nitrile oxide 53 and its
cycloaddition to (10R,20R,30R,3aR,6S)-6-(10,20,30,40-tetra-
allyloxy)butyl-3a,4,6,7-tetrahydro-3H-pyrano[4,3-c]-
isoxazole (59). To a solution of 12 (0.19 g, 0.45 mmol) in
benzene (10 mL) was added 4-chlorophenyl isocyanate
(0.69 g, 4.50 mmol) and Et3N (0.6 mL, 4.50 mmol), and the
mixture was stirred at 25 8C for 50 h under N2 atmosphere.
Water (5 mL) was added and the mixture was stirred for
24 h. It was then filtered and the residue was washed
repeatedly with benzene. The organic layer of the filtrate
was separated and the aqueous layer was extracted with
benzene. The combined organic extracts were washed with
water and dried. Removal of solvent yielded a residue,
which was chromatographed over silicagel (100–200 mesh;
EtOAc–petroleum ether, 1:10) to afford 59 (0.12 g, 68%) as
a colorless syrup, [a]D25C49.1 (c 2.33, CHCl3); IR (Neat):
3.9.6. (10R,20R,30R,6S)-6-(10,20,30,40-Tetrapropargyloxy)-
butyl-4H,6H-furo[3,4-c]isoxazole (67). 72%; [a]2D8C10.4
(c 0.25, CHCl3); IR (Neat): 3289, 2120 cmK1; MS (EI): m/z
383 (M); 1H NMR: d 8.05 (s, 1H), 5.42 (d, 1H, JZ6.1 Hz),
4.96 (d, 1H, JZ11.7 Hz), 4.86 (d, 1H, JZ11.7 Hz), 4.51–
4.38 (m, 4H), 4.33–4.31 (m, 2H), 4.26–4.23 (m, 2H), 4.05
(dd, 1H, JZ6.2, 3.7 Hz), 3.99–3.96 (m, 3H), 3.79 (dd, 1H,
JZ11.4, 4.9 Hz), 2.48–2.43 (m, 4H); 13C NMR: d 170.5 (q),
148.0 (CH), 123.6 (q), 79.9 (CH), 79.7 (2!CH), 79.4 (CH),
78.8 (CH), 77.9 (CH), 77.3 (CH), 76.7 (CH), 74.8 (q), 74.7
(q), 74.6 (q), 74.4 (q), 67.8 (CH2), 64.1 (CH2), 60.1 (CH2),
59.7 (CH2), 58.4 (CH2), 57.3 (CH2). Anal. Calcd for
C21H21NO6: C, 65.79; H, 5.52; N, 3.65. Found: C, 65.58; H,
5.87; N, 3.38.
1
3079, 1645 cmK1; MS (EI): m/z 407 (M), 126; H NMR
(500 MHz): d 6.01–5.83 (m, 4H), 5.28–5.12 (m, 8H), 4.47
(dd, 1H, JZ10.3, 8.3 Hz), 4.36 (dd, 1H, JZ10.6, 6.8 Hz),
4.30 (ddt, 1H, JZ12.2, 5.7, 1.3 Hz), 4.24 (ddt, 1H, JZ12.6,
5.5, 1.3 Hz), 4.20–4.14 (m, 2H), 4.13 (ddt, 1H, JZ12.9, 5.5,
1.3 Hz), 4.05 (ddt, 1H, JZ12.9, 5.5, 1.4 Hz), 4.00–3.99 (m,
2H), 3.88 (dd, 1H, JZ6.2, 4.0 Hz), 3.74–3.69 (m, 3H), 3.63
(dd, 1H, JZ8.9, 4.8 Hz), 3.57–3.52 (m, 2H), 3.45–3.38 (m,
1H), 3.26 (t, 1H, JZ10.7 Hz), 2.68–2.59 (m, 2H); 13C NMR
(125 MHz): d 157.3 (q), 135.2 (CH), 134.9 (2!CH), 134.5
(CH), 117.5 (CH2), 116.9 (CH2), 116.8 (CH2), 116.5 (CH2),
80.4 (CH), 79.5 (CH), 78.03 (CH), 78.0 (CH), 74.7 (CH2),
73.5 (CH2), 72.2 (CH2), 71.6 (CH2), 70.8 (CH2), 69.3 (CH2),
68.8 (CH2), 47.3 (CH), 28.0 (CH2). Anal. Calcd for
C22H33NO6: C, 64.84; H, 8.16; N, 3.44. Found: C, 64.61;
H, 8.36; N, 3.32.
3.9.7. (10R,20R,30R,6S)-6-(10,20,30,40-Tetrabenzyloxy)-
butyl-4H,6H-furo[3,4-c]isoxazole (68). 77%; [a]2D8C13.5
(c 0.40, CHCl3); IR (Neat): 3062, 3031, 1602 cmK1; MS
(FAB): m/z 592 (MCH), 500 (MKBn), 484 (MKOBn); 1H
NMR: d 7.96 (s, 1H), 7.34–7.21 (m, 18H), 7.09–7.07 (m,
2H), 5.39 (d, 1H, JZ3.8 Hz), 4.92 (d, 1H, JZ11.5 Hz),
4.81–4.77 (m, 3H), 4.70–4.53 (m, 6H), 4.21 (t, 1H, JZ
4.9 Hz), 4.01–3.87 (m, 3H), 3.71 (dd, 1H, JZ10.0, 5.0 Hz);
13C NMR: d 171.1 (q), 147.6 (CH), 138.7 (q), 138.5 (q),
138.4 (q), 138.2 (q), 128.3 (2!CH), 128.25 (2!CH), 128.2
(2!CH), 128.1 (2!CH), 127.8 (2!CH), 127.74 (2!CH),
127.7 (2!CH), 127.6 (2!CH), 127.5 (CH), 127.4 (CH),
127.3 (2!CH), 124.0 (q), 81.2 (CH), 79.5 (CH), 78.7 (CH),
76.2 (CH), 75.1 (CH2), 74.5 (CH2), 73.3 (CH2), 72.0 (CH2),
69.4 (CH2), 64.3 (CH2). Anal. Calcd for C37H37NO6: C,
75.11; H, 6.30; N, 2.37. Found: C, 74.97; H, 6.38; N, 2.26.
Acknowledgements
S. G. is grateful to Council of Scientific and Industrial
Research, India for the award of a Senior Research
Fellowship. Thanks are due to Dr. V. S. Giri, Mr. A.
Banerjee and Mr. S. Chowdhury for spectral analyses.
References and notes
3.9.8. (10R,6R,7R,8R)-6-(10,20-Dibenzyloxy)ethyl-7,8-
dibenzyloxy-7,8-dihydro-4H,6H-2,5-dioxa-1-aza-azu-
lene (69). 80%; [a]2D8C6.7 (c 0.24, CHCl3); IR (Neat):
3061, 3031, 1603 cmK1; MS (FAB): m/z 592 (MCH), 500
1. Padwa, A. In Comprehensive Organic Synthesis; Trost, B.,
Ed.; Pergamon: New York, 1992; pp 1069–1109.
2. Wade, P. A. In Comprehensive Organic Synthesis; Trost, B.,
Ed.; Pergamon: New York, 1992; pp 1111–1168.
3. Torsell, K. B. G. In Nitrile Oxides, Nitrones and Nitronates in
Organic Synthesis; New York: VCH, 1988.
1
(MKBn), 484 (MKOBn); H NMR: d 8.18 (s, 1H), 7.34–
7.05 (m, 20H), 4.87 (d, 1H, JZ5.4 Hz), 4.72 (d, 1H, JZ
13.8 Hz), 4.69 (d, 1H, JZ11.6 Hz), 4.64 (d, 1H, JZ
12.3 Hz), 4.54–4.18 (m, 9H), 3.86 (dd, 1H, JZ12.4,
4.1 Hz), 3.75–3.70 (m, 2H); 13C NMR: d 160.3 (q), 154.1
(CH), 138.5 (2!q), 137.3 (q), 137.2 (q), 128.5 (2!CH),
128.4 (3!CH), 128.37 (3!CH), 128.2 (2!CH), 127.9
(CH), 127.8 (2!CH), 127.74 (CH), 127.68 (2!CH), 127.6
(2!CH), 127.5 (CH), 127.4 (CH), 118.5 (q), 79.2 (CH),
77.0 (CH), 73.9 (CH), 73.3 (CH2), 72.2 (CH2), 71.8 (CH2),
70.8 (CH2), 69.8 (CH), 69.1 (CH2), 62.5 (CH2). Anal. Calcd
for C37H37NO6: C, 75.11; H, 6.30; N, 2.37. Found: C, 75.27;
H, 6.47; N, 2.23.
4. Adams, J. P.; Paterson, J. R. J. Chem. Soc., Perkin Trans. 1
2000, 3695.
5. Osborn, H. M. I.; Gemmell, N.; Harwood, L. M. J. Chem. Soc.,
Perkin Trans. 1 2002, 2419.
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Kundu, A. P.; Pal, A.; Mukhopadhyay, R.; Chowdhury, S.;
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