Carbocyclic ring closure of hex-5-enopyranosides and pent-4-enofuranosides: A nitrile oxide approach

Article abstract of DOI:10.1039/b007654f

A nitrile oxide approach on the carbocyclic ring closure of hex-5-enopyranosides and pent-4-enofuranosides was studied. The densely functionalised cyclopentane and cyclohexane derivatives were found suitable for the synthetic transformations. The N-O bond

Full text of DOI:10.1039/b007654f

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Carbocyclic ring closure of hex-5-enopyranosides and pent-4-
enofuranosides: a nitrile oxide approach
John K. Gallos* and Theocharis V. Koftis
1
Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 540 06, Greece.
E-mail: igallos@chem.auth.gr
Received (in Cambridge, UK) 18th September 2000, Accepted 3rd January 2001
First published as an Advance Article on the web 31st January 2001
Nitrile oxide cycloadditions to protected enopyrano(furano)sides derived from -glucose and -ribose afford spiro-
isoxazolines in good yield and high diastereoselectivity, which upon Raney Nickel hydrogenation in MeOH–AcOH
(6:1) undergo N–O bond cleavage followed by spontaneous aldol-like condensation to give good yields of
hydroxylated six- and five-membered cyclic enaminones as the main products.
unsuitable to convert pent-4-enofuranosides into the respective
Introduction
cyclopentanoids.17
The development of new synthetic methods for the construc-
tion of chiral polyoxygenated cyclopentanes and cyclohexanes
is of considerable importance in organic synthesis,1 since these
units constitute substructures in many bioactive compounds,
such as glycosidase inhibitors,2 aminoglycoside antibiotics,3
carbocyclic nucleosides4 and prostaglandins.5 Carbohydrates,
increasingly used as a chiral pool in natural-products synthesis,6
are excellent starting materials and the transfer of their chiral-
ity to the products is today the most common method for the
preparation of chiral polyoxygenated carbocycles. Carbanion
cyclisations,7 1,3-dipolar cycloadditions,8 free-radical cyclis-
ations,9 cyclisations via organometallic intermediates10 and,
most recently, ring-closing olefin metathesis11 are among the
methods developed over the last twenty years for carbocyclic
ring closure in sugar templates.
We wished to examined whether the N–O bond cleavage of
the isoxazoline ring generated by cycloaddition of nitrile oxides
to both hex-5-enopyranosides and pent-4-enofuranosides could
lead to the formation of six- and five-membered carbocycles
(Scheme 1).18 It was expected that, depending upon the relative
rates of competitive reactions, the N–O bond cleavage by
Raney Ni hydrogenation could give either an enamine-aldehyde
or a tricarbonyl compound, both suitable for intramolecular
aldol-like condensations.
Results and discussion
We initially added the stable 2,6-dichlorobenzonitrile oxide to
the double bond of pent-4-enofuranoside19 5, by refluxing their
solution in methylene dichloride for 4 h. The spiro-isoxazoline
6a (Scheme 2) was isolated chromatographically as a single
diastereoisomer in good yield. The absolute configuration of
the newly formed stereocenter in 6a was determined by NOE
experiments: the mutual signal enhancement between one
proton of the isoxazoline ring and one methyl of the acetonide
group, as well as the enhancement of 1-H (sugar numbering)
upon irradiation of both methylene protons of the isoxazoline
ring, leave no doubt as to the assigned structure. As expected,
the obtained diastereoisomer 6a was generated by the addition
of the nitrile oxide to the less hindered face of the double bond.
The N–O bond cleavage of isoxazolines derived from nitrile
oxide cycloadditions to olefins, usually by Raney Ni hydrogen-
ation, gives β-hydroxy ketones, being thus an important altern-
ative route to aldol condensation.20,21 In the special case of
cycloadducts to enol ethers, enaminones and further 1,3-diones
are produced by the hydrogenation.21 When Raney Ni or Pd/C
in MeOH or tetrahydrofuran (THF) were used as catalysts for
the hydrogenation (1 atm) of 6a, a very complex mixture of
products was obtained, but when boric acid (2.2 equiv.) was
used as additive in the Raney Ni hydrogenation (1 atm) of 6a in
MeOH–water (9:1), the cyclisation products 7 and 8 were
isolated, each one in 5% yield, together with the open-structure
enaminone 9 (18%). The same results were obtained by varying
the concentration of the additive (1.5 to 10 equiv.), with
increased yields of the open-chain product 9 at higher concen-
trations of boric acid, with compound 9 being the only isolated
product when 20 equiv. of boric acid were added.
Since the discovery, by Ferrier,12 that easily available hex-5-
enopyranosides such as 1 (Fig. 1) are converted into highly
functionalised cyclohexane derivatives 2 in the presence of
HgII salts, this remarkable rearrangement (or Ferrier II reac-
tion) has become a popular route to many biologically interest-
ing compounds, such as aminocyclitols, carba-sugars and
inositols.13 The HgCl2 initially used was replaced by the more
effective Hg(OAc)2, HgO, HgSO4 and Hg(O2CCF3)2, either
stoichiometric or catalytic.14 Furthermore, the problem of
toxicity of mercury salts was overcome by using catalytic PdCl2
or Pd(OAc)2.15 Alternatively, the cyclohexane derivatives 3 and
4 were formed from 2 in carbacyclisation reactions, promoted
by AliBu3 and Ti(OiPr)Cl3, respectively, in which the glycosidic
bond survives.16 However, despite its effectiveness for the con-
struction of six-membered carbocycles, the Ferrier II reaction is
At this point, it was evident that the acidic medium was
necessary, but it also assisted the reduction of the aldehyde
Fig. 1
DOI: 10.1039/b007654f
J. Chem. Soc., Perkin Trans. 1, 2001, 415–423
This journal is © The Royal Society of Chemistry 2001
415

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Scheme 1
Scheme 2 Reagents and conditions: i, 2,6-Cl2C6H3CNO, (1.1 equiv.), CH2Cl2, reflux, 4 h; ii, Raney Ni, H2 (1 atm), MeOH–CH3CO2H (6:1), 20 ЊC,
90 min (for yields see text).
intermediately produced before cyclisation. Furthermore, the
low yields of the products should rather be attributed to
undesirable hydrolysis caused by the presence of water before
cyclisation. Indeed, the yields of 7 (23%) and 8 (18%) were
improved and no 9 was formed when MeOH, 2.2 equiv. of boric
acid, and MgSO4 were used for the hydrogenolysis of 6a.
Finally, the most satisfactory results were obtained when a mix-
ture of methanol and glacial acetic acid was used as solvent,
which in the ratio 6:1 in the presence of MgSO4 gave yields of
64% for 7 and 17% for 8, while 9 was not detected. The absolute
configuration of the C-1 (ribose numbering) stereocenter, bear-
ing the MeO or OH group, in 7 and 8 was assigned on the basis
of the lack of any NOE enhancement between 1-H and 2-H as
well as from the coupling constant J1,2 = 0, which indicates a
trans arrangement between the C-1 and C-2 substituents.22
Having established the best conditions for the reductive
cyclisation of the spiro-isoxazoline 6a, a number of spiro-
cycloadducts were prepared by using in situ prepared nitrile
oxides and also by performing the cycloadditions with the
hex-5-enopyranoside 1 (Scheme 3). Both general methods,
namely oxidation of aldoximes23 (R = Me, Et) and dehydration
of primary nitroparaffins24 (R = phenyl, p-tolyl), were used for
the in situ generation of the unstable nitrile oxides. Excellent
yields were obtained from the stable nitrile oxides and those
generated in situ from primary nitroparaffins, while the method
of oxidation of aromatic aldoximes afforded moderate yields
of cycloadducts. In all reactions, the respective symmetrically
3,4-disubstituted furoxans (1,2,5-oxadiazole N-oxides) were
formed in low yields (<15%), resulting from the dimerisation
of nitrile oxides, which were characterised by comparison of
their physical data and NMR spectra with those of authentic
samples.25
irradiating the methyl group, clearly corroborates the stereo-
chemistry assigned.
The less diastereoselective cycloadditions to hex-5-eno-
pyranoside 1 compared with those of pent-4-enofuranoside 5
can be attributed to the strong hindrance of the one face of the
double bond of 5, induced by the acetonide group. In 1, the
benzyloxy groups adopting pseudo-equatorial positions affect
the double bond less selectively, because it is more strongly
hindered from one face by the methoxy group. The overall effect
is that the less hindered face of 5 is more available than that of 1
and this fact is reflected to the reaction time required for the
completion of cycloadditions to 1 and 5. The diastereo-
selectivity, however, of the cycloadditions is of no importance,
since the spiro carbon loses its chirality in the next step. Indeed,
when compounds 13a–d were further used as diastereomeric
mixtures, both diastereomers gave the same products.
The isoxazoline ring of cycloadducts 6b–e and 13a–e was
further cleaved by applying the conditions established for 6a
[Raney Ni, MgSO4, H2 (1 atm), MeOH–CH3CO2H 6:1, 90 min]
to give compounds 10b–e and 14a–e, respectively, which were
isolated as the main cyclisation products. Compared with com-
pounds 7 and 8 prepared by reductive cyclisation of 6a under
the same conditions, the methoxy or hydroxy group is now miss-
ing. Furthermore, when R = alkyl, the respective 1,3-diones
were formed as by-products, whereas in one instance the
bicyclic product 12d was isolated. All cyclisation products,
which are new compounds, were isolated by column chrom-
atography and characterised by their spectral and analytical
data. Despite their dense functionalisation, they were found to
be stable enough at room temperature, while they can be stored
in the refrigerator for several months without appreciable
decomposition.
All cycloaddition products of pent-4-enofuranoside 5 were
isolated as single diastereoisomers, evidently with the configur-
ation established for 6a. The cycloadditions to hex-5-eno-
pyranoside 1 were somewhat less selective: products 13a, 13b
and 13c were found to be mixtures of diastereoisomers in the
ratio 9:1, cycloadduct 13d was a 17:1 mixture of diastereo-
isomers (always the major isomer is depicted in Scheme 3),
while 13e was isolated as a single diastereoisomer. NOE
experiments confirmed again the assigned structure for the
major isomer of 13a: the signal enhancement of both methyl-
ene protons of the isoxazoline ring (18.1 and 6.8%), when
With the exception of 14a, the proton shifts (in CDCl3 at
20 ЊC) of the amino group in all enaminones prepared (7–10,
14) appeared at δ ≈ 5.5 and ≈ 10.0 as two broad singlets, which
reveal the intramolecular hydrogen bond, demonstrating the
geometry of the double bond.26 These signals were missing in
compound 14a (in CDCl3 at 20 ЊC), but appeared at δ 8.0 and
10.05 in DMSO-d6 at 20 ЊC and coalesced at 50 ЊC in the same
solvent. The diones 11b and 15b,c exist exclusively as enols, the
enolic proton appearing at δ ≈ 15.5 for 15b,c.
Scheme 4 could account for the hydrogenation–ring-closure
reaction as well as for the formation of by-products. The N–O
416
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Scheme 3 Reagents and conditions: i, 2,6-Cl2C6H3CNO, CH2Cl2, reflux, 24 h; ii, RCH2NO2, PhNCO, Et3N, C6H6, 20 ЊC, 5 days for 5 or reflux, 7 days
for 1; iii, RCH᎐NOH, NCS, pyridine, Et3N, CHCl3, reflux, 90 min for 5 or 24 h for 1; iv, Raney Ni, H2 (1 atm), MeOH–CH3CO2H (6:1), 20 ЊC,
᎐
90 min.
Scheme 4
bond scission triggered a sequence of reactions with intermedi-
ate formation of imine 17 and enaminones 18 or 19, which
easily underwent aldol-like condensation to 20 via 19 or 22 with
subsequent hydrogenation of the double bond formed to give
the final products 21. It is apparent that the reaction conditions,
the nature of substituents and the ring size expected to be
formed can affect the reaction pathway. Thus in the case of
hydrogenation of adduct 6a (Scheme 2), the condensation stops
J. Chem. Soc., Perkin Trans. 1, 2001, 415–423
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Scheme 5 Reagents and conditions: i, NCS, pyridine, 5, Et3N, CHCl3, reflux, 90 min, 48%; ii, Raney Ni, H2 (1 atm), MeOH–CH3CO2H (6:1), 20 ЊC,
90 min.
after the first step and it is not followed by elimination, possibly
due to steric reasons. In acidic media also, the aldehyde 22 is
further reduced to alcohol 23. When R = alkyl the imine 17,
being less stable, is partially hydrolysed to ketone 24, before its
isomerisation to 18. Elimination of MeOH from 24 gives the
tricarbonyl compound 25, which after a typical Knoevenagel
condensation and hydrogenation of the double bond formed in
the intermediate enedione 26 gives the cyclic diketone 27.
Finally, the bicyclic hemiacetal 30 isolated in one case is evi-
dently formed from the amino derivative 29, which in turn can
be generated either by hydrogenation of imine 17 or by hydro-
sulfuric acid. Column chromatography was performed with
Merck silica gel 60 (0.063–0.200 mm). Optical rotations were
determined at room temperature on an A. Krüss P3000 Auto-
matic Digital Polarimeter. [α]D-Values are given in units of 10Ϫ1
deg cm2 gϪ1. The 1H and 13C NMR spectra were recorded at 300
and 75 MHz, respectively, on a Bruker 300 AM spectrometer,
with tetramethylsilane (TMS) as internal standard. J-Values are
given in Hz. Mass spectra were recorded under electron-impact
(EI) conditions at 70 eV on a VG TS-250 spectrometer and
microanalyses were performed on a Perkin-Elmer 2400-II
Element analyser. High-resolution mass spectra (HRMS) were
obtained on a VG ZAB-ZSE mass spectrometer under fast-
atom bombardment (FAB) conditions with nitrobenzyl alcohol
(NBA) as the matrix or on an IONSPEC FTMS spectrometer
(matrix-assisted laser-desorption ionisation, MALDI) with
2,5-dihydroxybenzoic acid (DHB) as matrix.
genation of the C᎐N bond in 16 at first, followed by N–O bond
᎐
cleavage in intermediate 28.
The densely functionalised cyclic enaminones 7, 8, 10 and 14
are suitable for a number of further synthetic transformations,
namely hydrolysis to diones,27 reduction28 and condensation to
fused heterocycles.29 When the nitrile oxide is derived from a
sugar, the cyclisation product would be a modified C-disacchar-
ide. To demonstrate this possibility, the spiro-isoxazoline 32 was
prepared in 48% yield from 5 by adding the nitrile oxide gener-
ated in situ by oxidation of oxime 3130 (Scheme 5), together with
the nitrile oxide dimer 33. Further reductive cleavage of the
N–O bond of 32 led to the formation of a mixture of enamin-
ones 34, 35 and 36, in 24, 11 and 14% yield, respectively. Com-
pound 34 resulted from 32 by analogy to enaminones 10 and 14
(Scheme 3), while 35 and 36 were formed, like enaminones 7
and 8 (Scheme 2), by failure of the intramolecular condensation
to go to completion, evidently because of the bulkiness of the
substituents.
In short, we have outlined a new approach for converting
carbohydrates in carbocycles, which complements the Ferrier
method since it can be applied to the synthesis of five-
membered rings as well as six-membered ones. The densely
functionalised cyclopentane and cyclohexane derivatives are
suitable for further transformations and we have demonstrated
the possibility of preparing modified C-disaccharides by the
present method.
(5R,7R,8R,9S)-3-(2,6-Dichlorophenyl)-8,9-isopropylidenedioxy-
7-methoxy-1,6-dioxa-2-azaspiro[4.4]non-2-ene 6a
A solution of 5 (186 mg, 1 mmol) and 2,6-dichlorobenzonitrile
oxide (207 mg, 1.1 mmol) in methylene dichloride (5 ml) was
refluxed for 4 h. The mixture was then evaporated on a
rotavapor and the residue was chromatographed on silica gel
with hexane–ethyl acetate 30:1 to give 6a (247 mg, 66%) as a
colorless solid, mp 62–64 ЊC (from diethyl ether–hexane), [α]D
ϩ77.2 (c 0.17, MeOH) (Found: C, 51.29; H, 4.53; N, 3.62. Calc.
for C16H17Cl2NO5: C, 51.35; H, 4.58; N, 3.74%); δH (CDCl3)
1.36 (3H, s, CMe2), 1.45 (3H, s, CMe2), 3.20 (1H, d, J 18.7,
4-Ha), 3.44 (3H, s, MeO), 3.78 (1H, d, J 18.7, 4-Hb), 4.78
(1H, d, J 5.5, 8-H), 4.87 (1H, d, J 5.5, 9-H), 4.95 (1H, s, 7-H)
and 7.36 (3H, m, ArH); δC (CDCl3) 24.8 and 26.2 (CMe2),
43.5 (C-4), 54.7 (MeO), 83.2 and 84.2 (C-8, -9), 108.0 (C-7),
112.9 (CMe2), 118.8 (C-5), 127.9, 128.2, 131.0 and 134.9
(ArC), and 154.6 (C-3); m/z 373/375/377 (Mϩ/Mϩ ϩ 2/Mϩ ϩ
4), 359/361/363, 315/317/319, 289/291/293, 255/257/259 and
230/232/234.
(5R,7S,8R,9R,10S)-8,9,10-Tris(benzyloxy)-3-(2,6-dichloro-
phenyl)-7-methoxy-1,6-dioxa-2-azaspiro[4.5]dec-2-ene 13a
Experimental
Mps were determined on a Kofler hot-stage microscope and are
uncorrected. All commercially available reagents were used
without further purification. Raney Ni suspension in water was
purchased from Fluka. Solvents were dried by standard
methods. The progress of the reactions was checked by TLC on
Merck silica gel 60F254 glass plates (0.25 mm). The spots were
visualised by heat staining with p-anisaldehyde in ethanol–
A solution of 1 (446 mg, 1 mmol) and 2,6-dichlorobenzonitrile
oxide (207 mg, 1.1 mmol) in methylene dichloride (5 ml) was
refluxed for 24 h. The mixture was then evaporated on a
rotavapor and the residue was chromatographed on silica gel
with hexane–ethyl acetate 15:1 to give a mixture of 13a and its
epimer (582 mg, 92%) in the ratio 9:1 (by H NMR spectro-
scopy). The major isomer 13a was crystallised from diethyl
1
418
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ether–hexane as a white solid, mp 75–76.5 ЊC; [α]D Ϫ95.0
(c 0.82, CHCl3) (Found: C, 66.14; H, 5.17; N, 2.12. Calc. for
C35H33Cl2NO6: C, 66.25; H, 5.24; N, 2.21%); δH (CDCl3) 3.30
(1H, d, J 18.4, 4-Ha), 3.50 (3H, s, MeO), 3.69 (1H, dd, J 5.3
and 4.3, 8-H), 3.88 (2H, m, 9-, 10-H) 3.93 (1H, d, J 18.4, 4-
Hb), 4.65 (1H, d, J 12.0, PhCH2), 4.67 (1H, d, J 4.3, 7-H),
4.85 (5H, m, PhCH2), 7.35 (18H, m, ArH); δC (CDCl3) 42.8
(C-4), 57.1 (MeO), 73.9, 75.4 and 75.9 (C-8, -9, -10), 78.7,
78.8 and 80.3 (3 × PhCH2), 100.0 (C-7), 111.6 (C-5), 127.65,
127.70, 127.9, 128.0, 128.1, 128.2 (two peaks), 128.3, 128.4,
128.47, 128.50, 131.2, 135.0, 137.8, 137.9, 138.4 (ArC), and
156.1 (C-7).
major isomer 13b was crystallised from diethyl ether–hexane as
a white solid, mp 109–110.5 ЊC; [α]D Ϫ28.2 (c 0.57, CHCl3)
(Found: C, 71.39; H, 6.53; N, 2.70. Calc. for C30H33NO6: C,
71.55; H, 6.60; N, 2.78%); δH (CDCl3) 2.02 (3H, s, 3-Me), 2.96
(1H, d, J 18.2, 4-Ha), 3.43 (3H, s, MeO), 3.46 (1H, d, J 18.2,
4-Hb), 3.64 (1H, dd, J 9.6, 4.0, 8-H), 3.76 (1H, dd as t, J 9.6,
9-H), 3.84 (1H, d, J 9.6, 10-H), 4.60 (1H, d, J 4.3, 7-H), 4.63
(1H, d, J 12.5, PhCH2), 4.71 (1H, d, J 10.8, PhCH2), 4.78 (1H,
d, J 12.5, PhCH2), 4.80 (2H, m, PhCH2), 4.88 (1H, d, J 10.8,
PhCH2), 7.31 (15H, m, ArH); δC (CDCl3) 13.3 (3-Me), 43.8
(C-4), 56.6 (MeO), 73.7, 75.2 and 75.8 (C-8, -9, -10), 78.7, 78.8
and 80.2 (3 × PhCH2), 99.6 (C-7), 110.7 (C-5), 127.6, 127.65,
127.85, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 137.7, 137.9,
138.4 (ArC), and 157.5 (C-3).
General procedure for the nitrile oxide generation from nitro-
alkanes and their addition to enopyrano(furano)sides 1 and 5
(5R,7S,8R,9R,10S)-8,9,10-Tris(benzyloxy)-3-ethyl-7-
methoxy-1,6-dioxa-2-azaspiro[4.5]dec-2-ene 13c. Compound
13c (as a mixture with its minor epimer in a 9:1 ratio) was
prepared from 1 and nitropropane according to the general
procedure above and was isolated by subsequent column
chromatography (CH2Cl2–hexane 3:1) as a colorless oil (458
mg, 87%). The major isomer 13c was crystallised from diethyl
ether–hexane as a white solid, mp 99–95 ЊC; [α]D Ϫ32.6 (c 1.32,
CHCl3) (Found: C, 71.82; H, 6.68; N, 2.76. Calc. for C31H35-
NO6: C, 71.93; H, 6.82; N, 2.71%); δH (CDCl3) 1.17 (3H, t, J 7.4,
3-CH2CH3), 2.39 (2H, q, J 7.4, 3-CH2CH3), 2.99 (1H, d, J 18.2,
4-Ha), 3.43 (3H, s, MeO), 3.45 (1H, d, J 18.2, 4-Hb), 3.64 (1H,
dd, J 9.3, 4.0, 8-H), 3.77 (1H, dd as t, J 9.3, 9-H), 3.84 (1H,
d, J 9.3, 10-H), 4.60 (1H, d, J 4.0, 7-H), 4.63 (1H, d, J 12.6,
PhCH2), 4.72 (1H, d, J 11.5, PhCH2), 4.78 (1H, d, J 12.6,
PhCH2), 4.82 (1H, d, J 11.5, PhCH2), 4.84 (1H, d, J 10.5,
PhCH2), 4.89 (1H, d, J 10.5, PhCH2) and 7.32 (15H, m, ArH);
δC (CDCl3) 10.9 (3-CH2CH3), 21.4 (3-CH2CH3), 42.1 (C-4), 56.6
(MeO), 73.8, 75.2 and 75.8 (C-8, -9, -10), 78.8, 78.9 and 80.3
(3 × PhCH2), 99.7 (C-7), 110.6 (C-5), 127.6, 127.7, 127.9, 128.0,
128.05, 128.1, 128.2, 128.3, 128.5, 137.8, 138.0, 138.5 (ArC), and
162.1 (C-3).
To a solution of compound 1 or 5 (1 mmol) in benzene (5 ml)
were added nitroethane or nitropropane (1.1 mmol), triethyl-
amine (0.1 mmol) and phenyl isocyanate (3.6 mmol) and the
mixture was stirred at 20 ЊC for 5 days (for the reactions of 5) or
refluxed for 7 days (for the reactions of 1). During this time
additional amounts of nitroalkane (3 equiv.) and phenyl
isocyanate (9 equiv.) were added in small portions until the dis-
appearance of the enopyrano(furano)side (TLC monitoring).
The mixture was subsequently stirred with water (5 ml) for 1 h
at 20 ЊC and extracted with cyclohexane (2 × 10 ml). The
organic layer was dried over Na2SO4, filtered and the solvent
was then removed under reduced pressure. Purification of the
products was accomplished by column chromatography. The
furoxans resulting from the dimerisation of nitrile oxides were
eluted first in low yields (<15%), followed by the cycloaddition
products.
(5R,7R,8R,9S)-8,9-Isopropylidenedioxy-7-methoxy-3-methyl-
1,6-dioxa-2-azaspiro[4.4]non-2-ene 6b. Compound 6b was
prepared from 5 and nitroethane according to the general
procedure above and was isolated by subsequent column
chromatography (CH2Cl2–ethyl acetate 50:1) as a colorless oil
(229 mg, 94%), [α]D ϩ63.4 (c 0.88, CHCl3) (Found: C, 54.28; H,
7.01; N, 5.49. Calc. for C11H17NO5: C, 54.31; H, 7.04; N,
5.76%); δH (CDCl3) 1.33 (3H, s, CMe2), 1.44 (3H, s, CMe2), 2.04
(3H, s, 3-Me), 2.87 (1H, d, J 18.8, 4-Ha), 3.38 (3H, s, MeO), 3.41
(1H, d, J 18.8, 4-Hb), 4.72 (1H, d, J 5.5, 8-H), 4.79 (1H, d, J 5.5,
9-H) and 5.01 (1H, s, 7-H); δC (CDCl3) 12.9 (3-Me), 24.8 and
26.2 (CMe2), 45.0 (C-4), 54.7 (MeO), 83.2 and 84.3 (C-8, -9),
107.9 (C-7), 112.7 (CMe2), 118.1 (C-5) and 156.2 (C-3); m/z 243
(Mϩ), 228 and 212.
General procedure for the nitrile oxide generation from aldoximes
and their addition to enopyrano(furano)sides 1 and 5
To a solution of benzaldoxime or p-methylbenzaldoxime or
the oxime 3130 (1.2 mmol) in dry CHCl3 (10 ml) were added
N-chlorosuccinimide (NCS) (155 mg, 1.3 mmol) and dry
pyridine (2 drops) and the stirred mixture was refluxed for 20
min. The solution was cooled to room temperature a solution
of compound 1 or 5 (1 mmol) and Et3N (111 mg, 1.1 mmol) in
CHCl3 (5 ml) were added, and the mixture was refluxed again
for 90 min (for the reactions of 5) or 24 h (for the reactions of
1). The solvent was then removed under reduced pressure and
purification of the products was accomplished by column
chromatography. The furoxans resulting from the dimerisation
of nitrile oxides were eluted first in low yields (<15%), followed
by the cycloaddition products.
(5R,7R,8R,9S)-3-Ethyl-8,9-isopropylidenedioxy-7-methoxy-
1,6-dioxa-2-azaspiro[4.4]non-2-ene 6c. Compound 6c was
prepared from 5 and nitropropane according to the general
procedure above and was isolated by subsequent column
chromatography (CH2Cl2–ethyl acetate 50:1) as a colorless oil
(231 mg, 90%), [α]D ϩ53.6 (c 1.11, CHCl3) (Found: C, 55.83; H,
7.36; N, 5.37. Calc. for C12H19NO5: C, 56.02; H, 7.44; N,
5.44%); δH (CDCl3) 1.19 (3H, t, J 7.5, 3-CH2CH3), 1.33 (3H, s,
CMe2), 1.45 (3H, s, CMe2), 2.41 (2H, q, J 7.5, 3-CH2CH3), 2.87
(1H, d, J 18.5, 4-Ha), 3.38 (3H, s, MeO), 3.40 (1H, d, J 18.5,
4-Hb), 4.72 (1H, d, J 5.9, 8-H), 4.80 (1H, d, J 5.9, 9-H) and 5.01
(1H, s, 7-H); δC (CDCl3) 10.7 (3-CH2CH3), 21.2 (3-CH2CH3),
24.9 and 26.2 (CMe2), 43.5 (C-4), 54.7 (MeO), 83.3 and 84.4
(C-8, -9), 107.9 (C-7), 112.8 (CMe2), 118.0 (C-5) and 160.8
(C-3); m/z 257 (Mϩ), 242, 226 and 200.
(5R,7R,8R,9S)-8,9-Isopropylidenedioxy-7-methoxy-3-phenyl-
1,6-dioxa-2-azaspiro[4.4]non-2-ene 6d. Compound 6d was
prepared from 5 and benzaldoxime according to the general
procedure above and was isolated by subsequent column
chromatography (hexane–ethyl acetate 20:1) as a colorless oil
(89 mg, 29%), [α]D ϩ54.5 (c 2.98, CHCl3) (Found: C, 62.99; H,
6.21; N, 4.50. Calc. for C16H19NO5: C, 62.94; H, 6.27; N,
4.59%); δH (CDCl3) 1.35 (3H, s, CMe2), 1.50 (3H, s, CMe2), 3.31
(1H, d, J 18.4, 4-Ha), 3.41 (3H, s, MeO), 3.78 (1H, d, J 18.4,
4-Hb), 4.77 (1H, d, J 5.6, 8-H), 4.88 (1H, d, J 5.6, 9-H), 5.06
(1H, s, 7-H), 7.40 (3H, m, m- and p-ArH), 7.69 (2H, m, o-ArH);
δC (CDCl3) 24.8 and 26.3 (CMe2), 41.5 (C-4), 54.8 (MeO), 83.3
and 84.4 (C-8, -9), 108.1 (C-7), 112.9 (CMe2), 118.7 (C-5),
126.6, 128.6, 129.0, 130.2 (ArC), and 157.1 (C-3); m/z 305 (Mϩ),
290, 274 and 248.
(5R,7S,8R,9R,10S)-8,9,10-Tris(benzyloxy)-7-methoxy-3-
methyl-1,6-dioxa-2-azaspiro[4.5]dec-2-ene 13b. Compound 13b
(as a mixture with its minor epimer in a 9:1 ratio) was prepared
from 1 and nitroethane according to the general procedure
above and was isolated by subsequent column chromatography
(CH2Cl2–hexane 3:1) as a colorless oil (458 mg, 91%). The
J. Chem. Soc., Perkin Trans. 1, 2001, 415–423
419

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(5R,7R,8R,9S)-8,9-Isopropylidenedioxy-7-methoxy-3-
(4-methylphenyl)-1,6-dioxa-2-azaspiro[4.4]non-2-ene 6e. Com-
pound 6e was prepared from 5 and p-methylbenzaldoxime
according to the general procedure above and was isolated by
subsequent column chromatography (hexane–ethyl acetate
15:1) as a colorless oil (176 mg, 55%), [α]D ϩ59.4 (c 0.21,
CHCl3) (Found: C, 63.96; H, 6.62; N, 4.44. Calc. for
C17H21NO5: C, 63.94; H, 6.63; N, 4.39%); δH (CDCl3) 1.35 (3H,
s, CMe2), 1.49 (3H, s, CMe2), 2.36 (3H, s, ArCH3), 3.29 (1H, d,
J 18.4, 4-Ha), 3.40 (3H, s, MeO), 3.75 (1H, d, J 18.4, 4-Hb), 4.76
(1H, d, J 5.7, 8-H), 4.87 (1H, d, J 5.7, 9-H), 5.05 (1H, s, 7-H),
7.19 (2H, d, J 8.1, m-ArH), 7.57 (2H, d, J 8.1, o-ArH);
δC (CDCl3) 21.3 (ArCH3), 24.8 and 26.3 (CMe2), 41.6 (C-4),
54.8 (MeO), 83.3 and 84.4 (C-8, -9), 108.1 (C-7), 112.8 (CMe2),
118.6 (C-5), 126.2, 126.6, 129.3, 140.4 (ArC), and 157.0 (C-3);
m/z 319 (Mϩ), 304 and 290.
(from diethyl ether–hexane); [α]D ϩ39.4 (c 1.24, CHCl3)
(Found: C, 53.92; H, 6.77; N, 3.53. Calc. for C18H27NO9: C,
53.86; H, 6.78; N, 3.49%); δH (CDCl3) 1.32 (6H, s, CMe2), 1.44
(3H, s, CMe2), 1.50 (3H, s, CMe2), 2.96 (1H, d, J 18.8, 4-Ha),
3.37 (3H, s, MeO), 3.38 (3H, s, MeO), 3.48 (1H, d, J 18.8, 4-Hb),
4.63 (1H, d, J 5.9, 4Ј-H), 4.71 (1H, d, J 5.7, 8-H), 4.77 (1H, d,
J 5.7, 9-H), 4.95 (1H, s, 2Ј-H), 5.01 (1H, s, 5Ј-H), 5.02 (1H, s,
7-H), 5.27 (1H, d, J 5.9, 3Ј-H); δC (CDCl3) 24.9, 25.0, 26.28 and
26.34 (2 × CMe2), 41.7 (C-4), 54.8 (MeO), 55.8 (MeO), 81.3,
81.7, 83.2, 84.3 and 85.1 (C-8, -9, -2Ј, -3Ј, -4Ј), 108.1 (C-7), 110.5
(C-5Ј), 112.6 and 112.9 (2 × CMe2), 118.8 (C-5), 158.7 (C-3);
m/z 401 (Mϩ), 386, 371, 370, 354, 338, 312 and 284.
For furoxan 33: δH (CDCl3) 1.35 (3H, s, CMe2), 1.38 (3H, s,
CMe2), 1.50 (3H, s, CMe2), 1.53 (3H, s, CMe2), 3.13 (3H, s,
MeO), 3.19 (3H, s, MeO), 4.73 (1H, d, J 5.9, 4Ј-H), 4.77 (1H, d,
J 5.7, 4Љ-H), 5.03 (1H, s, 5Ј-H), 5.09 (1H, s, 5Љ-H), 5.35 (1H, s,
2Ј-H), 5.47 (1H, s, 2Љ-H), 5.63 (1H, d, J 5.7, 3Љ-H), 5.67 (1H, d,
J 5.9, 3Ј-H); δC (CDCl3) 24.8, 24.9 and 26.3 (two peaks)
(2 × CMe2), 55.2 (MeO), 55.7 (MeO), 76.0, 78.7, 79.1, 80.0,
85.0 and 85.3 (C-2Ј, C-2Љ, C3Ј, C-3Љ, C-4Ј, C-4Љ), 110.3 and
110.6 (C-5Ј, -5Љ), 112.4 and 112.9 (2 × CMe2), 113.0 (C-5), 156.3
(C-4).
(5R,7S,8R,9R,10S)-8,9,10-Tris(benzyloxy)-7-methoxy-3-
phenyl-1,6-dioxa-2-azaspiro[4.5]dec-2-ene 13d. Compound 13d
(as a mixture with its minor epimer in a 17:1 ratio) was
prepared from 1 and benzaldoxime according to the general
procedure above and was isolated by subsequent column
chromatography (hexane–ethyl acetate 10:1) as a colorless oil
(226 mg, 40%). The major isomer 13d was crystallised from
diethyl ether–hexane as a white solid, mp 99–101 ЊC; [α]D Ϫ30.5
(c 2.54, CHCl3) (Found: C, 74.53; H, 6.18; N, 2.47. Calc. for
C35H35NO6: C, 74.32; H, 6.24; N, 2.48%); δH (CDCl3) 3.42 (3H,
s, MeO), 3.45 (1H, d, J 18.3, 4-Ha), 3.69 (1H, dd, J 9.0, 4.1,
8-H), 3.89 (1H, d, J 18.3, 4-Hb), 3.90 (2H, m, 9-, 10-H), 4.65
(1H, d, J 4.1, 7-H), 4.66 (1H, d, J 11.9, PhCH2), 4.74 (1H, d,
J 11.0, PhCH2), 4.88 (3H, m, PhCH2), 4.92 (1H, d, J 11.0,
PhCH2), 7.49 (18H, m, 3 × PhCH2 and m- and p-H of 3-Ph),
7.69 (2H, m, o-H of 3-Ph); δC (CDCl3) 40.8 (C-4), 57.0 (MeO),
73.8, 75.3 and 75.7 (C-8, -9, -10), 78.5 (two peaks) and 80.2
(3 × PhCH2), 99.8 (C-7), 111.8 (C-5), 126.7, 127.65, 127.66,
127.9, 128.1, 128.15, 128.25, 128.3, 128.5, 128.6, 128.7, 130.5,
137.8, 137.9, 138.5, 141.7 (ArC), and 159.2 (C-3); m/z 565 (Mϩ)
and 534.
General procedure for the catalytic hydrogenation of spiro-
isoxazolines 6, 13 and 32
To a solution of 6, a spiro-compound 13 or 32 (0.5 mmol) in
MeOH–AcOH 6:1 (20 ml) were added MgSO4 (200 mg) and a
catalytic amount of Raney Ni and the mixture was stirred at
room temperature for 90 min under H2. The solids were then
filtered off, the solvent was removed under reduced pressure,
and purification of the products was accomplished by column
chromatography.
(3R,4S,5S)-2-[(Z)-Amino(2,6-dichlorophenyl)methylene]-4,5-
isopropylidenedioxy-3-methoxycyclopentanone 7 and (3R,4S,-
5S)-2-[(Z)-amino(2,6-dichlorophenyl)methylene]-3-hydroxy-4,5-
(isopropylidenedioxy)cyclopentanone 8. Hydrogenation of spiro-
isoxazoline 6a according to the general procedure above and
subsequent column chromatography (hexane–ethyl acetate 4:1)
gave compound 7 (115 mg, 64%) as colorless crystals, mp
202 ЊC (decomp.) (from diethyl ether–hexane), followed by
compound 8 (29 mg, 17%) as colorless crystals, mp 88 ЊC
(decomp.) (from diethyl ether–hexane). For (3R,4S,5S)-2-[(Z)-
amino(2,6-dichlorophenyl)methylene]-4,5-isopropylidenedioxy-
3-methoxycyclopentanone 7: [α]D ϩ148.3 (c 0.29, CHCl3)
(Found: C, 53.81; H, 4.68; N, 3.70. C16H17Cl2NO4 requires C,
53.65; H, 4.78; N, 3.91%); δH (CDCl3) 1.36 (3H, s, CMe2), 1.38
(3H, s, CMe2), 2.95 (3H, s, MeO), 3.90 (1H, s, 3-H), 4.43 (1H, d,
J 5.9, 5-H), 4.71 (1H, d, J 5.9, 4-H), 5.76 (1H, s br, NH), 7.36
(3H, m, ArH), 9.90 (1H, s br, NH); δC (CDCl3) 25.8 and 27.4
(CMe2), 55.9 (MeO), 79.2 (C-3), 81.3 and 82.9 (C-4, -5), 103.2
(C-2), 111.9 (CMe2), 127.9, 128.0, 131.0, 132.4, 132.7, 134.4
(ArC), 159.3 (᎐CNH ), 198.5 (C-1); m/z 357/359/361 (Mϩ/
(5R,7S,8R,9R,10S)-8,9,10-Tris(benzyloxy)-7-methoxy-3-(4-
methylphenyl)-1,6-dioxa-2-azaspiro[4.5]dec-2-ene 13e. Com-
pound 13e was prepared as a single diastereoisomer from 1 and
p-methylbenzaldoxime according to the general procedure
above and was isolated by subsequent column chromatography
(hexane–ethyl acetate 10:1) as colorless crystals (255 mg, 44%),
mp 178–180 ЊC (from diethyl ether–hexane); [α]D Ϫ47.8 (c 0.5,
CHCl3) (Found: C, 74.63; H, 6.43; N, 2.35. Calc. for C36H37-
NO6: C, 74.59; H, 6.43; N, 2.42%); δH (CDCl3) 2.39 (3H, s,
ArCH3), 3.41 (3H, s, MeO), 3.44 (1H, d, J 18.0, 4-Ha), 3.69 (1H,
dd, J 9.0, 3.8, 8-H), 3.85 (1H, d, J 18.0, 4-Hb), 3.88 (2H, m, 9-,
10-H), 4.65 (1H, d, J 3.8, 7-H), 4.66 (1H, d, J 11.2, PhCH2),
4.73 (1H, d, J 10.8, PhCH2), 4.82 (1H, d, J 11.2, PhCH2), 4.83
(1H, d, J 12.0, PhCH2), 4.86 (1H, d, J 12.0, PhCH2), 4.91 (1H,
d, J 10.8, PhCH2), 7.26 (17H, m, 3 × PhCH2 and 2 × m-H of
3-tolyl), 7.57 (2H, d, J 7.5, o-H of 3-tolyl); δC (CDCl3) 21.4
(ArCH3), 40.3 (C-4), 56.7 (MeO), 73.8, 75.3 and 75.8 (C-8, -9,
-10), 78.85, 78.88 and 80.2 (3 × PhCH2), 99.8 (C-7), 111.3
(C-4), 126.3, 126.7, 127.63, 127.66, 127.9, 128.02, 128.08,
128.12, 128.23, 128.32, 128.5, 129.5, 137.8, 137.9, 138.5, 140.8
(ArC), and 158.5 (C-3); m/z 579 (Mϩ).
᎐
2
Mϩ ϩ 2/Mϩ ϩ 4), 322/324 and 269/271/273.
For (3R,4S,5S)-2-[(Z)-amino(2,6-dichlorophenyl)methylene]-
3-hydroxy-4,5-(isopropylidenedioxy)cyclopentanone 8: [α]D
ϩ93.3 (c 0.15, CHCl3) (Found: C, 52.28; H, 4.35; N, 3.94.
C15H15Cl2NO4 requires C, 52.34; H, 4.39; N, 4.07%); δH (CDCl3)
1.34 (3H, s, CMe2), 1.36 (3H, s, CMe2), 4.32 (1H, s, 3-H), 4.42
(1H, d, J 5.3, 5-H), 4.73 (1H, d, J 5.3, 4-H), 5.75 (1H, s br, NH),
7.40 (3H, m, ArH), 9.79 (1H, s br, NH); δC (CDCl3) 26.0
and 27.6 (CMe2), 73.0 (C-3), 81.0 and 82.0 (C-4, -5), 105.8
(C-2), 112.0 (CMe2), 128.3, 128.5, 131.5, 132.5, 133.1, 133.6
(ArC), 158.2 (᎐CNH ), 200.1 (C-1); m/z 343/345/347 (Mϩ/Mϩ ϩ
(5R,7R,8R,9S)-8,9-Isopropylidenedioxy-3-[(2ЈR,3ЈR,4ЈR,
5ЈR)-3Ј,4Ј-isopropylidenedioxy-5Ј-methoxytetrahydrofuran-2Ј-
yl]-7-methoxy-1,6-dioxa-2-azaspiro[4.4]non-2-ene 32. Com-
pound 32 was prepared from 5 and oxime 3130 according to the
general procedure above. Subsequent column chromatography
(hexane–ethyl acetate 15:1) gave, first, the dimer 33 (78 mg,
15%) as a colorless oil (Found: C, 50.11; H, 6.19; N, 6.44. Calc.
for C18H26N2O10: C, 50.23; H, 6.09; N, 6.51%), followed by
compound 32 as colorless crystals (193 mg, 48%), mp 70–72 ЊC
᎐
2
2/Mϩ ϩ 4), 308/310 and 232/234.
(Z,4S,5S)-1-Amino-1-(2,6-dichlorophenyl)-6-hydroxy-4,5-
(isopropylidenedioxy)hex-1-en-3-one 9. Hydrogenation of
spiro-isoxazoline 6a according to the general procedure above
420
J. Chem. Soc., Perkin Trans. 1, 2001, 415–423

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using MeOH–water (9:1) as solvent in the presence of H3BO3
(2.2 equiv.) and subsequent column chromatography (hexane–
ethyl acetate 4:1) gave further to compounds 7 (5%) and 8 (5%),
compound 9 as an oil (62 mg, 18%) (Found: C, 52.24; H, 5.06;
N, 4.25. Calc. for C15H17Cl2NO4: C, 52.04; H, 4.95; N, 4.05%);
δH (CDCl3) 1.26 (3H, s, CMe2), 1.54 (3H, s, CMe2), 3.09 (1H, s
br, OH), 3.65 (1H, dd, J 11.5, 7.0, 6-Ha), 3.73 (1H, dd, J 11.5,
6.0, 6-Hb), 4.54 (1H, m, 5-H), 4.66 (1H, d, J 8.1, 4-H), 5.35 (1H,
s br, NH), 5.63 (1H, s, 2-H), 7.35 (3H, m, ArH), 10.13 (1H, s br,
NH); δC (CDCl3) 25.0 and 27.0 (CMe2), 62.0 (C-6), 78.5 and
80.7 (C-4, -5), 94.3 (C-2), 109.8 (CMe2), 128.3, 130.8, 133.6,
134.9 (ArC), 159.0 (C-1) and 198.0 (C-3); m/z 345/347/349 (Mϩ/
Mϩ ϩ 2/Mϩ ϩ 4).
(C-1), 101.5 (C-5), 113.1 (CMe2), 126.3, 127.9, 128.8 and 140.9
(ArC) [MALDI-FTMS Found: (M ϩ Hϩ Ϫ H2O), 260.1279.
C15H18NO3 (M ϩ Hϩ Ϫ H2O) requires m/z, 260.1287.
For (2S,3S)-5-[(Z)-amino(phenyl)methyene]-2,3-(isopropyl-
idenedioxy)cyclopentanone 10d: [α]D Ϫ110.0 (c 0.3, CHCl3);
δH (CDCl3) 1.38 (3H, s, CMe2), 1.44 (3H, s, CMe2), 2.62 (1H, d,
J 15.5, 4-Ha), 2.88 (1H, dd, J 15.5, 5.0, 4-Hb), 4.56 (1H, d, J 5.0,
2-H), 4.68 (1H, dd as t, J 5.0, 3-H), 5.31 (1H, s br, NH), 7.22
(5H, m, ArH), 9.98 (1H, s br, NH); δC (CDCl3) 25.6 and 27.5
(CMe2), 31.4 (C-4), 74.9 (C-3), 82.3 (C-2), 99.2 (C-5), 111.1
(CMe ), 127.2, 128.8, 130.2, 136.4 (ArC), 160.2 (᎐CNH ) and
᎐
2
2
199.3 (C-1); m/z 259 (Mϩ) and 201 [MALDI-FTMS Found:
M ϩ Naϩ, 282.1100. C15H17NNaO3 (M ϩ Naϩ) requires m/z,
282.1106.
(2S,3S)-5-[(Z)-1-Aminoethylidene]-2,3-(isopropylidenedioxy)-
cyclopentanone 10b and (2S,3S)-5-[(Z)-1-hydroxyethylidene]-
2,3-(isopropylidenedioxy)cyclopentanone 11b. Hydrogenation of
spiro-isoxazoline 6b according to the general procedure above
and subsequent column chromatography (hexane–ethyl acetate
3:1) gave compound 11b (19 mg, 23%) as an oil (Found: C,
60.74; H, 7.28. C10H14O4 requires C, 60.59; H, 7.12%), followed
by compound 10b (60 mg, 64%) as colorless crystals, mp 165 ЊC
(decomp.) (from diethyl ether–hexane). For (2S,3S)-5-[(Z)-1-
aminoethylidene]-2,3-(isopropylidenedioxy)cyclopentanone
10b: [α]D Ϫ4.4 (c 0.5, CHCl3); δH (CDCl3) 1.37 (3H, s, CMe2),
(2S,3S)-5-[(Z)-Amino(4-methylphenyl)methylene]-2,3-(iso-
propylidenedioxy)cyclopentanone 10e. Hydrogenation of spiro-
isoxazoline 6e according to the general procedure above and
subsequent column chromatography (hexane–ethyl acetate 3:1)
gave compound 10e as colorless crystals (72 mg, 53%), mp 195–
198 ЊC (from diethyl ether–hexane); [α]D Ϫ58.9 (c 0.17, CHCl3);
δH (CDCl3) 1.36 (3H, s, CMe2), 1.42 (3H, s, CMe2), 2.40 (3H, s,
ArMe), 2.67 (1H, d, J 15.9, 4-Ha), 2.87 (1H, dd, J 15.9, 5.0,
4-Hb), 4.55 (1H, d, J 5.7, 2-H), 4.65 (1H, dd, J 5.7, 5.0, 3-H),
5.24 (1H, br s, NH), 7.25 (2H, d, J 8.2, m-ArH), 7.36 (2H, d,
J 8.2, o-ArH), 9.98 (1H, br s, NH); δC (CDCl3) 21.4 (Ar-Me),
25.7 and 27.5 (CMe2), 31.5 (C-4), 74.9 (C-3), 82.3 (C-2), 99.1
(C-5), 111.1 (CMe2), 127.2, 128.8, 130.2, 140.5 (ArC), 160.4
(᎐CNH ) and 199.1 (C-1); m/z 273 (Mϩ), 258 and 215 [MALDI-
1.41 (3H, s, CMe ), 1.97 (3H, s, ᎐CMe), 2.65 (1H, d, J 15.3,
᎐
2
4-Ha), 2.75 (1H, dd, J 15.3, 5.2, 4-Hb), 4.49 (1H, d, J 5.5, 2-H),
4.69 (1H, dd, J 5.5, 5.2, 3-H), 5.55 (1H, s br, NH), 9.70 (1H, s
br, NH); δ (CDCl ) 20.6 (᎐CMe), 25.6 and 27.4 (CMe ), 30.6
᎐
᎐
C
3
2
2
(C-4), 74.7 (C-3), 82.2 (C-2), 99.1 (C-5), 110.9 (CMe2), 160.5
(᎐CNH ), 196.7 (C-1) [MALDI-FTMS Found: M ϩ Hϩ,
FTMS Found: M ϩ Hϩ, 274.1433. C16H20NO3 (M ϩ Hϩ)
requires m/z, 274.1443].
᎐
2
198.1123. C10H16NO3 (M ϩ Hϩ) require m/z 198.1130.
For (2S,3S)-5-[(Z)-1-hydroxyethylidene]-2,3-(isopropylidene-
dioxy)cyclopentanone 11b: δH (CDCl3) 1.38 (3H, s, CMe2), 1.42
(3H, s, CMe ), 2.11 (3H, s, ᎐CMe), 2.71 (1H, d, J 14.5, 4-Ha),
(2S,3R,4S)-6-[(Z)-Amino(2,6-dichlorophenyl)methylene]-
2,3,4-tris(benzyloxy)cyclohexanone 14a. Hydrogenation of
spiro-isoxazoline 13a according to the general procedure above
and subsequent column chromatography (hexane–ethyl acetate
7:1) gave compound 14a as colorless crystals (235 mg, 80%),
mp 104–105 ЊC (from diethyl ether–hexane); [α]D Ϫ9.9 (c 0.93,
CHCl3) (Found: C, 69.68; H, 5.39; N, 2.41. Calc. for C34H31-
Cl2NO4: C, 69.39; H, 5.31; N, 2.38%); δH (CDCl3) 2.18 (1H, dd,
J 14.6, 5.0, 5-Heq), 2.22 (1H, dd, J 14.6, 8.4, 5-Hax), 3.68 (1H,
ddd, J 8.4, 7.3, 5.0, 4-H), 3.83 (1H, dd as t, J 7.3, 3-H), 4.03
(1H, d, J 7.3, 2-H), 4.48 (1H, d, J 12.0, PhCH2), 4.53 (1H, d,
J 12.0, PhCH2), 4.73 (1H, d, J 11.0, PhCH2), 4.76 (1H, d, J 11.0,
PhCH2), 4.78 (1H, d, J 11.5, PhCH2), 5.10 (1H, d, J 11.5,
PhCH2), 7.30 (18H, m, ArH); δC (CDCl3) 28.2 (C-5), 71.7, 73.8,
74.2, 78.5 and 84.1 (two peaks) (C-2, -3, -4 and 3 × PhCH2),
99.0 (C-6), 127.4, 127.5, 127.6, 127.9, 128.1, 128.2, 128.3, 128.5,
130.8, 133.4, 134.1, 138.47, 138.52, 138.55 (ArC), 155.3
(᎐CNH ) and 196.0 (C-1); m/z 587/589/591 (Mϩ/Mϩ ϩ 2/
᎐
2
2.80 (1H, dd, J 14.5, 5.5, 4-Hb), 4.72 (1H, dd, J 5.5, 5.0, 3-H),
4.80 (1H, d, J 5.0, 2-H); δ (CDCl ) 22.6 (᎐CMe), 25.4 and 27.3
᎐
C
3
(CMe2), 31.0 (C-4), 75.0 (C-3), 81.2 (C-2), 107.4 (C-5), 111.5
(CMe ), 186.1 (᎐COH), 190.5 (C-1).
᎐
2
(2S,3S)-5-[(Z)-1-Aminopropylidene]-2,3-(isopropylidene-
dioxy)cyclopentanone 10c. Hydrogenation of spiro-isoxazoline
6c according to the general procedure above and subsequent
column chromatography (hexane–ethyl acetate 3:1) gave com-
pound 10c as colorless crystals (91 mg, 43%), mp 117 ЊC
(decomp.) (from diethyl ether–hexane); [α]D ≈ 0 (c 0.4, CHCl3)
(Found: C, 62.34; H, 8.01; N, 6.52. Calc. for C11H17NO3: C,
62.54; H, 8.11; N, 6.63%); δH (CDCl3) 1.18 (3H, t, J 7.5,
CH2CH3), 1.37 (3H, s, CMe2), 1.40 (3H, s, CMe2), 2.25 (2H, q,
J 7.5, CH2CH3), 2.65 (1H, d, J 15.4, 4-Ha), 2.75 (1H, dd, J 15.4,
5.5, 4-Hb), 4.49 (1H, d, J 5.9, 2-H), 4.70 (1H, dd, J 5.9, 5.5,
3-H), 5.63 (1H, br s, NH), 9.86 (1H, br s, NH); δC (CDCl3) 10.5
(CH2CH3), 25.5, 27.1 and 27.4 (CMe2, CH2CH3), 30.2 (C-4),
᎐
2
Mϩ ϩ 4) and 495/497/499.
(2S,3R,4S)-6-[(Z)-1-Aminoethylidene]-2,3,4-tris(benzyloxy)-
cyclohexanone 14b and (2S,3R,4S)-2,3,4-tris(benzyloxy)-6-[(Z)-
1-hydroxyethylidene]cyclohexanone 15b. Hydrogenation of
spiro-isoxazoline 13b according to the general procedure above
and subsequent column chromatography (hexane–ethyl acetate
5:1) gave compound 15b (34 mg, 15%) as a syrup, followed by
compound 14b (80 mg, 35%), also as a syrup.
74.7 (C-3), 82.2 (C-2), 98.1 (C-5), 110.8 (CMe ), 165.3 (᎐CNH )
᎐
2
2
and 196.9 (C-1); m/z 211 (Mϩ), 196, 170 and 153.
(2S,3S)-5-[(Z)-Amino(phenyl)methylene]-2,3-(isopropylidene-
dioxy)cyclopentanone 10d and (1R,5R,6S,7R)-6,7-isopropyl-
idenedioxy-3-phenyl-8-oxa-2-azabicyclo[3.2.1]octan-5-ol
12d.
Hydrogenation of spiro-isoxazoline 6d according to the general
procedure above and subsequent column chromatography
(hexane–ethyl acetate 3:1) gave compound 12d (16 mg, 11%) as
an oil, followed by compound 10d (62 mg, 48%), mp 165 ЊC
(decomp.) (from diethyl ether–hexane). For (1R,5R,6S,7R)-6,7-
isopropylidenedioxy-3-phenyl-8-oxa-2-azabicyclo[3.2.1]octan-
5-ol 12d: δH (CDCl3) 1.42 (3H, s, CMe2), 1.56 (3H, s, CMe2),
2.08 (2H, m, 4-H2), 3.22 (2H, br s, NH, OH), 3.87 (1H, dd,
J 11.8, 4.9, 3-H), 4.44 (1H, d, J 5.6, 6-H), 4.82 (1H, d, J 5.6,
7-H), 4.91 (1H, s, 1-H), 7.35 (5H, m, ArH); δC (CDCl3) 25.2 and
26.0 (CMe2), 39.4 (C-4), 52.9 (C-3), 80.0 and 83.0 (C-6, -7), 88.3
For (2S,3R,4S)-2,3,4-tris(benzyloxy)-6-[(Z)-1-hydroxyethyl-
idene]cyclohexanone 15b: [α]D ≈ 0 (c 0.1, CHCl3); δH (CDCl3)
2.13 (3H, s, Me), 2.40 (1H, dd, J 14.8, 8.8, 5-Hax), 2.69 (1H, dd,
J 14.8, 5.0, 5-Heq), 3.67 (1H, ddd, J 8.8, 8.5, 5.0, 4-H), 3.78 (1H,
dd as t, J 8.5, 7.3, 3-H), 4.17 (1H, d, J 7.3, 2-H), 4.66 (1H, d,
J 12.0, PhCH2), 4.72 (1H, d, J 12.5, PhCH2), 4.76 (1H, d, J 12.5,
PhCH2), 4.79 (1H, d, J 11.0, PhCH2), 4.83 (1H, d, J 12.0,
PhCH2), 5.04 (1H, d, J 11.0, PhCH2), 7.35 (15H, m, ArH), 15.5
(1H, br s, OH); δC (CDCl3) 22.6 (Me), 28.7 (C-5), 72.6, 74.7,
75.2, 76.5, 80.2 and 82.5 (C-2, -3, -4 and 3 × PhCH2), 103.9
(C-6), 127.68, 127.71, 127.77, 127.95, 128.1, 128.2, 128.3,
J. Chem. Soc., Perkin Trans. 1, 2001, 415–423
421

View Article Online
128.35, 128.41, 138.0, 138.3, 138.34 (ArC), 178.6 (᎐COH) and
3 × PhCH2), 97.4 (C-6), 127.4, 127.5, 127.7, 127.9, 128.2, 128.6,
᎐
198.4 (C-1) [MALDI-FTMS Found: M ϩ Naϩ, 481.1983.
129.6, 136.9, 138.4, 138.5, 138.6 (ArC), 161.2 (᎐CNH ) and
᎐
2
C29H30NaO5 (M ϩ Naϩ) requires: 481.1991.
195.1 (C-1) [MALDI-FTMS Found: M ϩ Naϩ, 542.2308.
C34H33NNaO4 (M ϩ Naϩ) requires m/z, 542.2307].
For (2S,3R,4S)-6-[(Z)-1-aminoethylidene]-2,3,4-tris(benzyl-
oxy)cyclohexanone 14b: [α]D ϩ77.2 (c 0.1, CHCl3); δH (CDCl3)
2.16 (3H, s, Me), 2.45 (1H, dd, J 14.5, 8.2, 5-Hax), 2.61 (1H, dd,
J 14.5, 4.9, 5-Heq), 3.73 (1H, ddd, J 8.2, 7.0, 4.9, 4-H), 3.79 (1H,
dd as t, J 7.5, 7.0, 3-H), 3.97 (1H, d, J 7.5, 2-H), 4.63 (1H, d,
J 11.8, PhCH2), 4.69 (1H, d, J 11.8, PhCH2), 4.71 (1H, d, J 11.5,
PhCH2), 4.75 (1H, d, J 13.0, PhCH2), 4.79 (1H, d, J 13.0,
PhCH2), 5.09 (1H, d, J 11.5, PhCH2), 5.23 (1H, br s, NH), 7.30
(15H, m, ArH), 10.66 (1H, br s, NH); δC (CDCl3) 21.4 (Me),
28.6 (C-5), 71.9, 74.0, 74.3, 78.5, 83.8 and 83.85 (C-2, -3, -4
and 3 × PhCH2), 97.0 (C-6), 120.0, 124.3, 127.4, 127.5, 127.6,
127.7, 128.0, 128.24, 128.31, 128.36, 129.0, 138.66, 138.71
(2S,3R,4S)-6-[(Z)-Amino(4-methylphenyl)methylene]-2,3,4-
tris(benzyloxy)cyclohexanone 14e. Hydrogenation of spiro-
isoxazoline 13e according to the general procedure above and
subsequent column chromatography (hexane–ethyl acetate 5:1)
gave compound 14e as a syrup (136 mg, 51%), [α]D Ϫ1.3 (c 0.3,
CHCl3); δH (CDCl3) 2.40 (3H, s, Me), 2.46 (1H, dd, J 15.2, 4.0,
5-Heq), 2.53 (1H, dd, J 15.2, 7.2, 5-Hax), 3.67 (1H, m, 4-H), 3.81
(1H, dd, J 7.3, 7.2, 3-H), 4.08 (1H, d, J 7.3, 2-H), 4.38 (2H, s,
PhCH2), 4.67 (1H, d, J 11.2, PhCH2), 4.74 (1H, d, J 11.9,
PhCH2), 4.75 (1H, d, J 11.2, PhCH2), 5.03 (1H, br s, NH), 5.08
(1H, d, J 11.9, PhCH2), 7.28 (17H, m, ArH), 7.46 (2H, d, J 7.4,
o-H of C6H4Me), 10.35 (1H, br s, NH); δC (CDCl3) 21.3 (Me),
28.2 (C-5), 70.7, 73.3, 73.6, 78.9, 84.1 and 84.2 (C-2, -3, -4 and
3 × PhCH2), 97.8 (C-6), 127.4, 127.5, 127.7, 128.0, 128.3, 129.3,
(ArC), 161.2 (᎐CNH ) and 192.9 (C-1) [MALDI-FTMS
᎐
2
Found: M ϩ Hϩ, 458.2331. C29H32NO4 (M ϩ Hϩ) requires m/z
458.2331.
(2S,3R,4S)-6-[(Z)-1-Aminopropylidene]-2,3,4-tris(benzyl-
oxy)cyclohexanone 14c and (2S,3R,4S)-2,3,4-tris(benzyloxy)-6-
[(Z)-1-hydroxypropylidene]cyclohexanone 15c. Hydrogenation
of spiro-isoxazoline 13c according to the general procedure
above and subsequent column chromatography (hexane–ethyl
acetate 5:1) gave compound 15c (36 mg, 15%) as a syrup,
followed by compound 14c (68 mg, 29%), also as a syrup.
138.5, 138.6, 138.77, 139.8 (ArC), 161.5 (᎐CNH ), 195.0 (C-1)
᎐
2
[MALDI-FTMS Found: M ϩ Naϩ, 556.2457. C35H35NNaO4
(M ϩ Naϩ) requires m/z, 556.2464.
(2S,3S)-5-{(Z)-Amino[(2ЈR,3ЈR,4ЈR,5ЈR)-3Ј,4Ј-isopropyl-
idenedioxy-5Ј-methoxytetrahydrofuran-2Ј-yl]methylene}-2,3-
(isopropylidenedioxy)cyclopentanone 34, (3R,4S,5S)-2-{(Z)-
amino[(2ЈR,3ЈR,4ЈR,5ЈR)-3Ј,4Ј-isopropylidenedioxy-5Ј-methoxy-
tetrahydrofuranЈ2Ј-yl]methylene}-4,5-isopropylidenedioxy-3-
methoxycyclopentanone 35 and (3R,4S,5S)-2-{(Z)-amino-
[(2ЈR,3ЈR,4ЈR,5ЈR)-3Ј,4Ј-isopropylidenedioxy-5Ј-methoxy-
tetrahydrofuran-2Ј-yl]methylene}-3-hydroxy-4,5-(isopropyl-
idenedioxy)cyclopentanone 36. Hydrogenation of spiro-
isoxazoline 32 according to the general procedure above and
subsequent column chromatography (hexane–ethyl acetate 3:1)
gave compound 35 (21 mg, 11%) as a syrup, followed by
compound 34 (43 mg, 24%), also as a syrup and compound 36
(26 mg, 14%) again as a syrup.
For
(2S,3R,4S)-2,3,4-tris(benzyloxy)-6-[(Z)-1-hydroxy-
propylidene]cyclohexanone 15c: [α]D ≈ 0 (c 0.1, CHCl3);
δH (CDCl3) 1.11 (3H, t, J 7.3, CH2CH3), 2.34–2.48 (3H, m,
CH2CH3 and 5-Hax), 2.70 (1H, dd, J 14.8, 5.2, 5-Heq), 3.67 (1H,
ddd, J 9.0, 8.9, 5.2, 4-H), 3.78 (1H, dd, J 8.9, 7.3, 3-H), 4.19
(1H, d, J 7.3, 2-H), 4.67 (1H, d, J 11.7, PhCH2), 4.74 (1H, d,
J 12.9, PhCH2), 4.77 (1H, d, J 11.7, PhCH2), 4.78 (1H, d, J 11.0,
PhCH2), 4.81 (1H, d, J 12.9, PhCH2), 5.05 (1H, d, J 11.0,
PhCH2), 7.35 (15H, m, ArH), 15.5 (1H, br s, OH); δC (CDCl3)
8.1 (CH2CH3), 28.1 and 29.7 (C-5 and CH2CH3), 72.6, 74.7,
75.75, 75.8, 80.2 and 82.6 (C-2, -3, -4 and 3 × PhCH2), 103.4
(C-6), 127.7, 127.9, 128.1, 128.2, 128.35, 128.4, 138.1, 138.3,
For (2S,3S)-5-{(Z)-amino[(2ЈR,3ЈR,4ЈR,5ЈR)-3Ј,4Ј-isoprop-
ylidenedioxy-5Ј-methoxytetrahydrofuran-2Ј-yl]methylene}-
2,3-(isopropylidenedioxy)cyclopentanone 34: [α]D ϩ53.1 (c
0.35, CHCl3); δH (CDCl3) 1.33 (3H, s, CMe2), 1.37 (3H, s,
CMe2), 1.38 (3H, s, CMe2), 1.40 (3H, s, CMe2), 2.56 (1H, d,
J 15.3, 4-Ha), 2.72 (1H, dd, J 15.3, 4.7, 4-Hb), 3.52 (3H, s,
MeO), 4.49 (1H, d, J 5.7, 4Ј-H), 4.59 (1H, d, J 5.7, 3Ј-H), 4.66
(1H, d, J 4.5, 2-H), 4.72 (1H, dd as t, J 4.5, 3-H), 4.84 (1H, s,
2Ј-H), 5.15 (1H, s, 5Ј-H), 6.40 (1H, br s, NH), 9.54 (1H, br s,
NH); δC (CDCl3) 25.1, 25.6, 26.6 and 27.4 (2 × CMe2), 29.6
(C-4), 56.5 (MeO), 75.0, 81.9, 84.7, 84.9 and 86.0 (C-2, -3, -2Ј,
-3Ј, -4Ј), 96.5 (C-5), 111.0, 111.9 and 113.5 (C-5Ј and 2 ×
138.4, 176.5 (᎐COH) and 198.1 (C-1) [MALDI-FTMS Found:
᎐
M ϩ Naϩ, 495.2138. C30H32NaO5 (M ϩ Naϩ) requires m/z,
495.2147.
For
(2S,3R,4S)-6-[(Z)-1-aminopropylidene]-2,3,4-tris-
(benzyloxy)cyclohexanone 14c: [α]D ϩ8.4 (c 0.5, CHCl3);
δH (CDCl3) 1.13 (3H, t, J 7.4, CH2CH3), 2.23 (2H, q, J 7.4,
CH2CH3), 2.47 (1H, dd, J 14.5, 8.4, 5-Hax), 2.61 (1H, dd, J 14.5,
5.0, 5-Heq), 3.72 (1H, ddd, J 8.4, 7.3, 5.0, 4-H), 3.79 (1H, dd as t,
J 7.3, 3-H), 3.97 (1H, d, J 7.3, 2-H), 4.62 (1H, d, J 11.4,
PhCH2), 4.69 (1H, d, J 11.4, PhCH2), 4.70 (1H, d, J 12.0,
PhCH2), 4.74 (1H, d, J 12.0, PhCH2), 4.79 (1H, d, J 11.0,
PhCH2), 5.09 (1H, d, J 11.0, PhCH2), 5.25 (1H, br s, NH), 7.30
(15H, m, ArH), 10.81 (1H, br s, NH); δC (CDCl3) 11.2
(CH2CH3), 27.3 and 27.9 (C-5 and CH2CH3), 71.8, 73.8, 74.2,
78.7, 83.8, 83.9 (C-2, -3, -4 and 3 × PhCH2), 96.2 (C-6), 127.4,
127.5, 127.6, 128.0, 128.2, 128.24, 128.31, 138.6, 138.7 (ArC),
CMe ), 159.9 (᎐CNH ), 198.4 (C-1); m/z 355 (Mϩ) and 340
᎐
2
2
[MALDI-FTMS Found: M ϩ Naϩ, 378.1526. C17H25NNaO7
(M ϩ Naϩ) requires m/z 378.1528].
For (3R,4S,5S)-2-{(Z)-amino[(2ЈR,3ЈR,4ЈR,5ЈR)-3Ј,4Ј-iso-
propylidenedioxy-5Ј-methoxytetrahydrofuran-2Ј-yl]methylene}-
4,5-isopropylidenedioxy-3-methoxycyclopentanone 35: [α]D
ϩ63.8 (c 0.45, CHCl3); δH (CDCl3) 1.31 (3H, s, CMe2), 1.38
(3H, s, CMe2), 1.52 (3H, s, CMe2), 1.53 (3H, s, CMe2), 3.44 (3H,
s, MeO), 3.53 (3H, s, MeO), 4.34 (1H, s, 3-H), 4.48 (1H, d, J 5.9,
5-H), 4.53 (1H, d, J 5.9, 4-H), 4.58 (1H, d, J 6.0, 4Ј-H), 4.85
(1H, d, J 6.0, 3Ј-H), 4.91 (1H, s, 2Ј-H), 5.15 (1H, s, 5Ј-H), 7.04
(1H, br s, NH), 9.93 (1H, br s, NH); δC (CDCl3) 24.9, 25.5, 26.5
and 27.2 (2 × CMe2), 55.9 (MeO), 56.5 (MeO), 78.4, 81.0, 82.3,
84.7, 85.6 and 86.5 (C-5, -4, -3, -2Ј, -3Ј, -4Ј), 100.4 (C-2), 111.1,
165.9 (᎐CNH ), 193.1 (C-1) [MALDI-FTMS Found:
᎐
2
M ϩ Naϩ, 494.2311. C30H33NNaO4 (M ϩ Naϩ) requires m/z,
494.2307.
(2S,3R,4S)-6-[(Z)-Amino(phenyl)methylene]-2,3,4-tris-
(benzyloxy)cyclohexanone 14d. Hydrogenation of spiro-
isoxazoline 13d according to the general procedure above and
subsequent column chromatography (hexane–ethyl acetate 8:1)
gave compound 14d as a syrup (135 mg, 52%), [α]D ϩ3.0 (c 0.3,
CHCl3); δH (CDCl3) 2.43 (1H, dd, J 15.0, 4.6, 5-Heq), 2.50 (1H,
dd, J 15.0, 7.1, 5-Hax), 3.67 (1H, m, 4-H), 3.81 (1H, dd, J 7.3,
7.0, 3-H), 4.09 (1H, d, J 7.3, 2-H), 4.38 (2H, s, PhCH2), 4.67
(1H, d, J 11.0, PhCH2), 4.74 (1H, d, J 11.5, PhCH2), 4.76 (1H,
d, J 11.0, PhCH2), 5.08 (1H, br s, NH), 5.09 (1H, d, J 11.5,
PhCH2), 7.30 (20H, m, ArH), 10.34 (1H, br s, NH); δC (CDCl3)
28.1 (C-5), 70.6, 73.3, 73.6, 78.8, 84.1 and 84.2 (C-2, -3, -4 and
112.0 and 112.7 (C-5Ј and 2 × CMe ), 164.6 (᎐CNH ), 197.1
᎐
2
2
(C-1); m/z 385 (Mϩ), 369, 355 [MALDI-FTMS Found: M ϩ
Hϩ, 386.1813. C18H28NO8 (M ϩ Hϩ) requires m/z, 386.1815].
For (3R,4S,5S)-2-{(Z)-amino[(2ЈR,3ЈR,4ЈR,5ЈR)-3Ј,4Ј-iso-
propylidenedioxy-5Ј-methoxytetrahydrofuran-2Ј-yl]methyl-
ene}-3-hydroxy-4,5-(isopropylidenedioxy)cyclopentanone 36:
[α]D ϩ74.5 (c 0.38, CHCl3); δH (CDCl3) 1.34 (3H, s, CMe2),
422
J. Chem. Soc., Perkin Trans. 1, 2001, 415–423

View Article Online
9 (a) A. Martínez-Grau and J. Marco-Contelles, Chem. Soc. Rev.,
1998, 27, 155; (b) J. Marco-Contelles, C. Alhabra and A. Martínez-
Grau, Synlett, 1998, 693.
1.37 (6H, s, CMe2), 1.57 (3H, s, CMe2), 3.55 (3H, s, OMe), 4.53
(1H, d, J 5.4, 4Ј-H), 4.62 (1H, d, J 5.8, 5-H), 4.72 (1H, d, J 5.4,
3Ј-H), 4.76 (1H, dd, J 5.8, 2.7, 4-H), 4.88 (1H, d, J 2.7, 3-H),
4.89 (1H, s, 2Ј-H), 5.18 (1H, s, 5Ј-H), 6.69 (1H, br s, NH),
9.83 (1H, br s, NH); δC (CDCl3) 25.2, 25.7, 26.8 and 27.4
(2 × CMe2), 56.7 (MeO), 71.8 (C-3), 80.8, 82.4, 84.5, 84.7 and
85.3 (C-5, -4, -2Ј, -3Ј, -4Ј), 102.9 (C-2), 110.5, 111.8 and 114.1
10 (a) H. Ito, Y. Motoki, T. Taguchi and Y. Hanzawa, J. Am. Chem.
Soc., 1993, 115, 8835; (b) H. Redlich, Angew. Chem., Int. Ed. Engl.,
1994, 33, 1345.
11 (a) R. Roy and S. K. Das, Chem. Commun., 2000, 519; (b) M.
Jørgensen, P. Hadwiger, R. Madsen, A. E. Stütz and T. M.
Wrodnigg, Curr. Org. Chem., 2000, 4, 565.
12 R. J. Ferrier, J. Chem. Soc., Perkin Trans. 1, 1979, 1455.
13 R. J. Ferrier and S. Middleton, Chem. Rev. 1993, 93, 2779.
14 (a) R. Blatther, R. J. Ferrier and S. R. Haines, J. Chem. Soc., Perkin
Trans. 1, 1985, 2413; (b) A. S. Machado, A. Olesker and G. Lukacs,
Carbohydr. Res., 1985, 135, 231; (c) N. Chida, M. Ohtsuka,
K. Ogura and S. Ogawa, Bull. Chem. Soc. Jpn., 1991, 64, 218.
15 (a) S. Adam, Tetrahedron Lett., 1988, 29, 6589; (b) D. H. R. Barton,
S. Augy-Dorey, J. Camara, P. Dalko, J. M. Delaumeny, S. D. Gero,
B. Quicccler-Sire and P. Stutz, Tetrahedron, 1990, 46, 215; (c) T.
Iimori, H. Takahashi and S. Ikegami, Tetrahedron Lett., 1996, 37,
649; (d) H. Takahashi, T. Iimori and S. Ikegami, Tetrahedron Lett.,
1998, 39, 6939; (e) H. Takahashi, H. Kittaka and S. Ikegami,
Tetrahedron Lett., 1998, 39, 9303, 9307.
(C-5Ј and 2 × CMe ), 163.4 (᎐CNH ) and 204.9 (C-1); m/z 371
᎐
2
2
(Mϩ), 355, 340 [MALDI-FTMS Found: M ϩ Naϩ, 394.1482.
C17H25NNaO8 (M ϩ Naϩ) requires m/z, 394.1478.
Acknowledgements
We are grateful to Dr E. Coutouli-Argyropoulou for the NOE
experiments, and to the ‘Leonidas Zervas’ Foundation for a
fellowship to T. V. Koftis.
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423