Carbohydrate-based spiro-1,3-oxazolidine-2-thiones: stereoselective approaches using aziridines and epoxides

Article abstract of DOI:10.1055/s-2008-1067266

D-glucose and D-fructose have been used as starting materials to prepare spiro-1,3-oxazolidine-2-thiones anchored on the third position of both carbohydrates. Following different approaches and depending on the carbohydrate template explored, stereoselect

Full text of DOI:10.1055/s-2008-1067266

3108
PAPER
Carbohydrate-Based Spiro-1,3-oxazolidine-2-thiones: Stereoselective
Approaches Using Aziridines and Epoxides
C
arbohydrate-
é
Based Spiro
b
-1,3-oxazol
a
idine-2-thio
s
nes tien Tardy,a Joana Lobo Vicente,a Arnaud Tatibouët,*a Gilles Dujardin,b Patrick Rollina
a
ICOA UMR 6005 CNRS, Université d’Orléans, 45067 Orléans, France
E-mail: arnaud.tatibouet@univ-orleans.fr
b
UCO2M UMR 6011 CNRS, Université du Maine, 72085 Le Mans, France
Received 30 April 2008; revised 19 June 2008
hydrate template might improve the chiral induction po-
tential through geometric control of the rigid sugar
backbone.
Abstract: D-glucose and D-fructose have been used as starting ma-
terials to prepare spiro-1,3-oxazolidine-2-thiones anchored on the
third position of both carbohydrates. Following different ap-
proaches and depending on the carbohydrate template explored, ste-
reoselective reactions have been developed via the formation of
epoxides or aziridines.
The purpose of this study was to explore the introduction
of an OZT moiety onto the specific C-3 site of both
1,2:5,6-di-O-isopropylidene-a-D-glucofuranose (1) and
1,2:4,5-di-O-isopropylidene-b-D-fructopyranose (2), tak-
ing advantage of the well-defined frame of both carbohy-
drate structures to generate all possible OZT-isomers.
These spiroheterocyclic structures could be constructed
according to a simplified sequence based on a key stereo-
selective approach from uloses II via epoxides III and
aziridines VI (Scheme 1).
Key words: azide, epoxide, spiro-compounds, chirality
Carbohydrate-derived chiral auxiliaries are useful tem-
plates in asymmetric reactions.1 Various sugar series have
been used for chiral induction: among the selected series,
D-glucose2 and D-fructose3 are the most used, not only be-
cause they are among the cheapest sugars, but also due to
the remarkable efficiency of their derivatives in chiral in-
duction processes. Chiral 1,3-oxazolidin-2-ones are also
recognised as major asymmetry inducers4 and, more re-
cently, 1,3-oxazolidine-2-thiones (OZTs) have emerged
as useful alternatives on account of their enhanced possi-
bilities. For example, depending on conditions, a stereose-
lective modulation of aldol reactions has been attained.5
Connecting a broadly functionalisable OZT with a carbo-
The exo spiro-OZTs could be produced through a standard
reaction sequence (Scheme 1): a ketone II, readily ob-
tained by oxidation6 of a protected sugar I, is transformed
into the epoxide III via the key step of the process, leading
to both possible epimers. Completion of the sequence in-
volves regioselective nitrogen introduction to afford the
amino-alcohol IV and subsequent cyclisation to the exo-
spiro-OZT V.
S
OH
O
O
O
NH2
IV
O
III
epoxides
NH
V
O
O
exo-OZT
O
HO
1
I
II
OH
O
O
O
O
OH
S
H
O
NH2
N
HN
O
aziridines
VI
OH
VII
O
VIII
2
endo-OZT
Scheme 1 Overview of endo and exo spiro-OZT formation
SYNTHESIS 2008, No. 19, pp 3108–3120
x
x.
x
x
.
2
0
0
8
Advanced online publication: 05.09.2008
DOI: 10.1055/s-2008-1067266; Art ID: T07108SS
© Georg Thieme Verlag Stuttgart · New York

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Carbohydrate-Based Spiro-1,3-oxazolidine-2-thiones
3109
1
2
ii
i
O
O
O
O
O
O
O
O
iv
O
O
O
iv
O
O
O
O
O
H2C
O
O
O
O
CH2
O
5
O
3
6, 77%
iii
4
iii
45%, S/R = 6:4
v
iii
v
57%, S/R = 5:95
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
(R)-8
(R)-7
(S)-7
two steps, 42%, S/R = 94:6
(S)-8
83%
Scheme 2 Formation of epoxides. Reagents and conditions: (i) PDC, Ac2O, CH2Cl2, 98%; (ii) RuCl3, NaIO4, K2CO3, PhCH2N(Et)3Cl,
CHCl3–H2O; (iii) Me3SOI, BuLi, THF; (iv) Ph3PCH2, THF; (v) MCPBA, NaHCO3, CH2Cl2.
At first, a direct approach with the dimethylsulfoxonium action conditions (n-BuLi in THF, 0 °C) with the aim of
methylide reagent was used to generate the epoxides favouring attack on the upper face, resulted in only a 45%
(Scheme 2). As previously reported for ketone 3 (t-BuOK yield of an epimeric mixture of epoxides (S/R = 6:4). For-
in t-BuOH, 50 °C),7 a thermodynamic reaction was ob- tunately, epimers (S)-7 and (R)-7 could be readily separat-
served: despite the facial differentiation in favour of an at- ed by chromatography. When reacted under the above
tack on the upper face of the furanose ring, the methylene thermodynamic conditions, and at variance with previous-
group was introduced on the lower face to selectively ly reported data, ketone 4 afforded a mixture of epimeric
(S/R = 93:7) afford the epimer (S)-7. Reconsidering the re- epoxides 8 (S/R = 2:1) in only 35% yield, which could not
O
O
O
O
O
O
O
O
O
HN
O
O
N3
OH
S
(R)-9 91%
(R)-11 95%
ii
i
7 (R or S)
O
O
O
O
O
O
O
O
O
HO
N3
O
O
S
N
H
(S)-9 83%
(S)-11 89%
O
O
O
O
O
O
O
NH
S
OH
N3
O
O
O
O
i
ii
(R)-10 96%
(R)-12 94%
8 (R or S)
O
O
O
O
O
O
O
S
O
O
N3
O
NH
O
OH
(S)-10 94%
(S)-12 95%
Scheme 3 Formations of exo-spiro-OZTs. Reagents and conditions: (i) NaN3, NH4Cl, DMF–H2O (10:1); (ii) CS2, Ph3P, dioxane.
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

3110
S. Tardy et al.
PAPER
be separated.7,8 Moving back to a kinetic approach to the Direct cyclization to the corresponding OZTs 11 and 12
reaction (n-BuLi in THF, –70 °C), we were pleased to ob- was effected following a one-pot protocol, which in-
serve a satisfactory 95:5 stereoselectivity in favour of ep- volved a modified Staudinger condensation and spontane-
oxide (R)-8, while the global yield was raised to 57%.
ous cyclisation of the transient hydroxylated
isothiocyanate.11 A different approach involving cyano-
hydrin formation from the ketone was also explored in the
D-fructo series (Scheme 4). A mixture of epimeric cyano-
hydrins 13 was quantitatively formed from ketone 4 – al-
beit without stereoselection. Chromatographic separation
of (R)-13 and (S)-13 was straightforward and the former
epimer was selected to exemplify the two-step transfor-
mation into OZT. Reduction of (R)-13 by lithium alumin-
ium hydride (LAH) led to the corresponding amino
alcohol, which was further condensed with thiophosgene
to afford OZT (R)-12 in nearly 30% overall yield. Despite
its shorter pathway, the cyanohydrin route to the OZTs
was not exploited further, mainly because of the disap-
pointing yields in the last two steps. The configuration of
all spiro-OZTs was assigned through dedicated NOESY
experiments, which showed the specific space relation-
ships of the OZT methylene group with other hydrogens
of the carbohydrate backbone.
However, considering the moderate yields obtained when
using the sulfonium ylide approach with ketones 3 and 4,
we also explored a two-step route to the spiro-epoxides:
(i) Wittig methylenation (ii) stereoselective meta-chloro-
peroxybenzoic acid (MCPBA) epoxidation (Scheme 2).
Following such a protocol, ketone 3 afforded epoxide (S)-
7 in 42% overall yield and excellent selectivity (S/R =
94:6).9 In comparison, the D-fructose-derived ketone 4
produced the corresponding epoxide (S)-8 with a much
better overall yield of 64%.8 The Wittig methylenation
step was optimised by using butyllithium in tetrahydrofu-
ran at –78 °C to give a 77% yield of alkene 6, whereas
MCPBA epoxidation proceeded in 83% yield. All four
isomers [(S)-7, (R)-7 and (S)-8, (R)-8] – mostly obtained
stereoselectively – were thus in our hands.
The above epoxides were then regioselectively cleaved by
sodium azide under protic conditions (Scheme 3) to afford
the corresponding azido-alcohols 910 and 10 in excellent
yields, ranging from 83% to 96%.
The endo spiro-OZTs could be prepared through a reac-
tion sequence similar to that applied for the exo-spiro-
OZTs, with spiro-aziridine intermediates replacing the
key spiro-epoxides (Scheme 1). Earlier approaches to the
stereoselective preparation of spiro-aziridines involving
cyanohydrin or azido-alcohol intermediates have already
been disclosed, especially for D-gluco derivatives.12 Test-
ing cyanohydrin formation from ketones 3 and 4 under ki-
netic or thermodynamic conditions showed that only the
D-gluco-related ketone 3 offered efficient stereoselectivi-
ty, in contrast to the D-fructo-related ketone 4, for which
no selectivity was observed; we therefore concentrated
our efforts on the D-gluco series (Scheme 5).
O
O
i
O
ii, iii
CN
4
(R)-12 28%
O
O
OH
13 (1:1) 100%
Scheme 4 Cyanohydrin approach to an OZT. Reagents and condi-
tions: (i) NaCN, MeOH; (ii) LAH, THF; CaCO3, CSCl2, acetone–
H2O.
3
i
O
O
O
O
O
O
O
O
RO
NC
O
O
CN
OR
(thermodynamic approach)
85%
ii, 66%
(cinetic approach)
97%
ii, 85%
(S)-14 R = H
(S)-15 R = Ts
(R)-14 R = H
(R)-15 R = Ts
iii
iii
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
HN
HO
O
O
O
N
TsHN
O
OH
H
18, 56%
TsHN
19, 33%
17, 4.7%
16, 89%
Scheme 5 Aziridine formation in the D-gluco series. Reagents and conditions: (i) KCN, NaHCO3, Et2O, H2O; (ii) TsCl, pyridine; (iii) LAH,
Et2O.
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Carbohydrate-Based Spiro-1,3-oxazolidine-2-thiones
3111
The cyanohydrins 14 were prepared according to the pro-
tocol described by Bourgeois.12c Under kinetic conditions
(NaHCO3, 0 °C, 10 min), (R)-1412d was obtained in nearly
quantitative yield; in parallel, a modified procedure ap-
plied to 3 afforded the thermodynamic epimer (S)-1412d in
85% yield. The a-hydroxynitriles were further activated
by O-tosylation to afford (R)-1512e in 85% yield and (S)-
15 in only 66% yield, respectively – a surprising result
considering the steric difference between the two hydroxy
groups.
O
O
O
O
i
ii
O
O
O
O
18
O
O
Cl
AcO
NHNs
NHNs
28 96%
27 68%
Scheme 7 Spontaneous aziridine 18 opening. Reagents and condi-
tions: (i) o-NsCl, Et3N, THF; (ii) AcONa, DMF, 100 °C.
many attempts at improvement, sodium naphthalenide N-
desulfonylation could only be performed in poor yield.
Tentative direct transformation of 24 into the OZT using
thiophosgene under basic conditions failed.
Lithium aluminium hydride reduction of the cyano group
in 15 caused spontaneous intramolecular cyclization. A
highly selective reaction occurred with (R)-15, furnishing
aziridine 16 in 90% yield, while by controlling the condi-
tions, the competing tosyl migration leading to 17 was
limited to 5% yield.
We then turned our attention to the N-nosylated epimers
26 and 28, which were quantitatively de-O-acylated to 30
and 32, then de-N-sulfonylated under standard thiolate
deprotection conditions.14 The resulting epimeric b-amino
alcohols 33 and 34 were finally condensed with thiophos-
gene under basic conditions to yield the desired (endo-
OZT) 1,3-oxazolidine-2-thiones 35 and 36 in 78 and 70%
yield, respectively (Scheme 8).
Applying the same reaction conditions to cyanohydrine
(S)-15 optimally afforded the corresponding aziridine 18
in 53% yield, together with its epimer 16 (3%) and sul-
fonamide 19 (32%). Formation of 16 suggested incom-
plete selectivity in the formation of (S)-15. Direct
acetolysis of the aziridine 16 failed, even after N-Boc ac-
tivation into carbamate 20. As indicated in the literature,
opening of a spiro-aziridine ring often requires stronger
activation through N-sulfonylation.13
The OZT formation was further explored by taking advan-
tage of the azido group in derivative 25. Applying the ear-
lier modified Staudinger conditions to 25,11 a transient
isothiocyanate was formed which spontaneously cyclized
to furnish the spiro-1,3-imidazolidine-2-thione 31 in 65%
yield (Scheme 8).
Testing both N-tosylation and N-nosylation showed the
moderate reactivity of the aziridine, and afforded sulfon-
amides 21 and 22 in 49% and 60% yield, respectively
(Scheme 6). In contrast, N-mesylation afforded sulfon-
amide 23 in 95% yield, thus suggesting a marked steric ef-
fect. The N-tosylated spiroaziridine 21 underwent both
acetolysis and azidolysis to afford 24 and 25 with excel-
lent yields, while the N-nosylated spiroaziridine 22 under-
went acetate cleavage in moderate yield (58%) to produce
26. The same reactions were applied to compound 18,
which showed a different behaviour: N-nosylation of this
aziridine was followed by chloride ion counter-attack to
provide the cleaved product 27 in 68% yield. Finally, nu-
cleophilic displacement by acetate was realised to give a
nearly quantitative yield of 28 (Scheme 7).
In conclusion, we have developed two general approaches
to 1,3-oxazolidine-2-thiones clipped on standard carbohy-
drate templates. The epoxide approach could be realised
in a stereoselective manner depending on the conditions
used. On both templates, the epoxides (S)-7 and (S)-8
were obtained with very good stereoselectivity, whereas
their epimeric counterparts proved more difficult to syn-
thesize. Only the D-fructo derivative (R)-8 could be ob-
tained in reasonable yield and good stereoselectivity. The
further sequences involving azide formation and modified
Staudinger-aza-Wittig reaction were quite efficient. In
contrast, spiro-aziridine formation only showed efficient
selectivity with D-glucofurano derivatives. The D-fructo-
pyrano cyanohydrins were formed without selectivity and
lacked reactivity in O-sulfonyl activation. Following a
three-step sequence, the furano spiro-aziridines 16 and 18
were prepared in 73% and 30% yield, respectively. Fur-
ther steps to provide endo-spiro-OZTs were more
The final sequences were dedicated to the elaboration of
the precursor b-amino alcohols to be converted into the
OZTs. Compound 24 was efficiently de-O-acetylated us-
ing sodium methoxide to afford 29; however, despite
O
O
O
O
R2Na
O
O
O
O
16
R1N
R1HN
DMF, 100 °C
O
O
R2
i, 20: R1 = Boc 50%
ii, 21: R1 = Ts 49%
iii, 22: R1 = oNs 60%
iv, 23: R1 = Ms 95%
v, 24: R1 = Ts, R2 = OAc 91%
vi, 25: R1 = Ts, R2 = N3
92%
v, 26: R1 = oNs, R2 = OAc 58%
29: R1 = Ts, R2 = OH 97%
vii
vii
30: R1 = oNs, R2 = OH 92%
Scheme 6 Aziridine activations and opening. Reagents and conditions: (i) Boc2O, THF; (ii) TsCl, DIPEA, THF; (iii) o-NsCl, Et3N, THF;
(iv) MsCl, Et3N, THF; (v) AcONa, DMF, 100 °C; (vi) NaN3, DMF, 100 °C; (vii) MeONa, MeOH.
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3112
S. Tardy et al.
PAPER
26
28
i, 92% 30
ii, 80%
i, 95% 32
ii, 95%
O
O
O
O
O
O
O
O
H2N
HO
O
O
H2N
25
HO
33
34
iv
iii, 70%
iii, 78%
O
O
O
O
O
O
O
O
O
Ts
N
O
O
O
HN
O
O
O
NH
O
S
S
N
O
H
S
36
35
31 65%
Scheme 8 endo-OZT formation. Reagents and conditions: (i) MeONa, MeOH; (ii) PhSH, K2CO3, MeCN; (iii) Cl2CS, CaCO3; CS2, Ph3P,
dioxane.
3,7-Anhydro-3-C-hydroxymethyl-1,2:5,6-di-O-isopropylidene-
a-D-allofuranose [(R)-7] [136522-01-5]
The ulofuranose 3 (218 mg, 0.84 mmol) in THF (7 mL) reacted for
2.5 h at 0 °C with a THF solution (7 mL) of the sulfoxonium ylide.
Chromatography (PE–EtOAc, 4:1) afforded a 6:4 mixture of
epimeric epoxides (S)-7 and (R)-7 (103 mg, 45% global yield). Se-
lected analytical data for (R)-7:
[a]D +74 (c 1.5, CHCl3) [Lit.7b +85.6 (CH2Cl2)]; Rf = 0.24 (PE–
EtOAc, 8:2).
IR (film): 1164, 1073, 1021 (epoxide C–O) cm–1.
1H NMR: d = 1.32, 1.37, 1.40, 1.63 (4 × s, 12 H, 4 × CH3), 2.99 (d,
J7b–7a = 5.0 Hz, 1 H, H-7b), 3.39 (d, 1 H, H-7a), 3.86–4.10 (m, 3 H,
H-5, H-6b, H-6a), 4.25 (d, J4–5 = 6.9 Hz, 1 H, H-4), 4.43 (d,
J2–1 = 4.1 Hz, 1 H, H-2), 5.87 (d, 1 H, H-1).
13C NMR: d = 25.3, 26.7, 26.9, 27.1 (4 × CH3), 50.5 (C-7), 64.5 (C-
3), 67.2 (C-6), 75.3 (C-5), 75.8 (C-4), 80.6 (C-2), 103.9 (C-1),
110.1, 113.8 (2 × CIV).
straightforward using a N-ortho-nosyl activation/protec-
tion system and resulted in the formation of the corre-
sponding OZTs in overall 20% and 41%, respectively.
We have thus designed two approaches to the preparation
of spiro-1,3-oxazolidine-2-thiones from D-glucose and D-
fructose, either from epoxides or from aziridines, which
can be prepared with a stereoselectivity that depends on
the carbohydrate template used. All spiro-OZTs have
been submitted to a chirality transfer study, the results of
which will shortly be disclosed.
Solvents were dried and distilled by standard methods before use.
All reagents were of commercial quality (Acros, Aldrich or Lan-
caster) and used without purification. Compounds were visualised
with UV light and charring after a 10% H2SO4 ethanolic solution
spray. Column chromatography was performed on silica gel 60 M
(0.036–0.063 mm, Merck) using flash chromatographic elution
techniques and TLC analysis with silica gel plates (Kieselgel
MS (IS): m/z = 290.5 [M + NH4]+, 295.5 [M + Na]+, 327.5 [M +
MeOH + Na]+, 567.5 [2M + Na]+.
1
60F254, Merck). H and 13C NMR were recorded at 250 and 62.6
MHz, respectively, on a Bruker Avance DPX 250 spectrometer;
chemical shifts (d) are reported in ppm downfield from TMS or
from residual solvent peak (CDCl3); coupling constants (J) are re-
ported in Hz and refer to apparent peak multiplicity. Low-resolution
mass spectra were obtained using an Ionspray® (IS) method with an
API 300 Perkin–Elmer SCIEX spectrometer. Optical rotations were
measured at 20 °C with a Perkin–Elmer 341 polarimeter. IR spectra
were recorded on a Perkin–Elmer Paragon 1000 PC spectrometer.
HR-ESI-TOF-MS was performed on a Micromass LC TOF spec-
trometer. Microanalyses were performed on a Thermo Electron
FlashEA 1112 analyser.
3,7-Anhydro-3-C-hydroxymethyl-1,2:4,5-di-O-isopropylidene-
b-D-psicopyranose [(R)-8] [78136-24-0]
A solution of the ylide in THF (240 mL) was carefully added to a
cooled (–78 °C) solution of the ulopyranose 4 (4.0 g, 15.5 mmol) in
THF. The mixture was stirred and slowly allowed to come to r.t.
overnight. Column chromatography (PE–EtOAc, 4:1) afforded ep-
oxide (R)-8 as a colourless oil that crystallized on standing.
Yield: 2.4 g (57%); mp 42–44 °C; [a]D –120 (c 1.2, CHCl3) [Lit.7b
–120 (CH2Cl2)]; Rf = 0.36 (PE–EtOAc, 8:2).
IR (film): 1239, 1090, 1013 (epoxide C–O) cm–1.
1H NMR: d = 1.30, 1.31, 1.49, 1.51 (4 × s, 12 H, 4 × CH3), 2.66 (d,
J7b–7a = 5.7 Hz, 1 H, H-7b), 3.20 (d, 1 H, H-7a), 3.77 (d, J6b–
6a = 13.2 Hz, 1 H, H-6b), 3.84 (dd, J6a–5 = 1.6 Hz, 1 H, H-6a), 4.02
(d, J4–5 = 7.5 Hz, 1 H, H-4), 4.04 (d, J1b–1a = 9.2 Hz, 1 H, H-1b),
4.20 (d, 1 H, H-1a), 4.37 (d, J5–4 = 7.5 Hz, 1 H, H-5).
Me3SOI Epoxidation of Uloses; General Procedure
n-BuLi (1.1 equiv) was carefully added to a solution of trimethyl-
sulfoxonium iodide (1.2 equiv). When a clear solution was ob-
served, a solution of ulose (1 equiv) in THF was added. When the
reaction was complete, the resulting solution was hydrolysed
through the addition of brine (10 mL). The aqueous layer was ex-
tracted with EtOAc (4 × 30 mL) and the combined organic layers
were washed with brine (3 × 30 mL), dried over MgSO4, and evap-
orated. The crude residue was purified by silica gel column chroma-
tography.
13C NMR: d = 25.2, 26.1, 26.2, 26.3 (4 × CH3), 48.8 (C-7), 56.6 (C-
3), 64.0 (C-6), 73.7 (C-1), 75.2 (C-5), 76.0 (C-4), 103.5 (C-2),
110.5, 111.0 (2 × CIV).
MS (IS): m/z = 273.0 [M + H]+, 290.5 [M + NH4]+, 295.5 [M + Na]+.
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

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Carbohydrate-Based Spiro-1,3-oxazolidine-2-thiones
IR (film): 3543 (OH), 2108 (N3) cm–1.
3113
MCPBA Epoxidation; General Procedure
The exo-methylene (5 or 6) in 1,2-DCE was treated with MCPBA
(2.5 equiv) at 70 °C. After cooling, the mixture was diluted with
CH2Cl2 (40 mL). The organic layer was taken and successively
washed with a sat. aq Na2SO4 (10 mL), NaOH (0.2 M, 3 × 10 mL),
H2O (10 mL) then brine (10 mL). After drying the combined organ-
ic extracts over MgSO4 and concentration under vacuum, the resi-
due was purified by column chromatography on silica gel.
1H NMR: d = 1.37 (s, 6 H, 2 × CH3), 1.47, 1.60 (2 × s, 6 H, 2 × CH3),
2.96 (s, 1 H, OH), 3.07 (d, J7b–7a = 13.2 Hz, 1 H, H-7b), 3.80 (d,
J4–5 = 8.2 Hz, 1 H, H-4), 3.83 (d, 1 H, H-7a), 3.92 (m, 1 H, H-5),
4.09 (m, 2 H, H-6a, H-6b), 4.57 (d, J2–1 = 3.9 Hz, 1 H, H-2), 5.75 (d,
1 H, H-1).
13C NMR: d = 25.3, 26.6, 26.6, 26.8 (4 × CH3), 52.0 (C-7), 68.0 (C-
6), 73.1 (C-5), 80.3 (C-3), 80.4 (C-4), 81.6 (C-2), 103.7 (C-1),
110.1, 112.9 (2 × CIV).
3,7-Anhydro-3-C-hydroxymethyl-1,2:5,6-di-O-isopropylidene-
a-D-glucofuranose [(S)-7] [53270-27-2]
The exo-methylene 5 (121 mg, 0.47 mmol) was treated with
MCPBA in 1,2-DCE (4.5 mL). Column chromatography (PE–
EtOAc, 4:1) afforded a 93:7 ratio of epoxides (S)-7 (84 mg) and (R)-
7 (6 mg) with 70% global yield, as colourless oils.9d,10
MS (IS): m/z = 316.5 [M + H]+, 333.5 [M + NH4]+, 338.5 [M + Na]+,
370.5 [M + MeOH + Na]+.
HRMS-ES: m/z [M + Na]+ calcd for C13H21N3O6Na: 338.1328;
found: 338.1320.
[a]D +47 (c 1.2, CHCl3) [Lit.7b +55.5 (CH2Cl2)]; Rf = 0.59 (PE–
3-C-Azidomethyl-1,2:5,6-di-O-isopropylidene-a-D-glucofuran-
ose [(S)-9] [880486-64-6]10
The epoxide (S)-7 (210 mg, 0.77 mmol) was treated with NaN3 and
NH4Cl in DMF–H2O (6.5 mL) for 140 min. Chromatography (PE–
EtOAc, 4:1) afforded the azido-alcohol (S)-9.
EtOAc, 8:2).
IR (film): 1164, 1071, 1022 (C–O epoxide) cm–1.
1H NMR: d = 1.31, 1.33, 1.40, 1.56 (4 × s, 12 H, 4 × CH3), 3.09 (d,
J7a–7b = 4.8 Hz, 1 H, H-7a), 3.16 (d, J7b–7a = 4.8 Hz, 1 H, H-7b),
3.96–4.11 (m, 3 H, H-5, H-6a, H-6b), 4.28 (d, J2–1 = 3.9 Hz, 1 H, H-
2), 4.37 (d, J4–5 = 6.9 Hz, 1 H, H-4), 5.95 (d, J1–2 = 3.9 Hz, H-1).
Yield: 192 mg (83%); colourless oil.
HRMS-ES: m/z [M + Na]+ calcd for C13H21N3O6Na: 338.1328;
13C NMR: d = 25.4, 26.6, 26.9, 27.1 (4 × CH3), 46.4 (C-7), 65.2 (C-
3), 67.1 (C-6), 73.1 (C-5), 76.6 (C-4), 84.7 (C-2), 104.3 (C-1), 109.7
(CIV), 112.7 (CIV).
MS (IS): m/z = 273.0 [M + H]+, 290.5 [M + NH4]+, 295.5 [M + Na]+,
305.5 [M + MeOH + H]+, 327.5 [M + MeOH + Na]+, 567.5 [2M +
Na]+.
found: 338.1333.
3-C-Azidomethyl-1,2:4,5-di-O-isopropylidene-b-D-fructo-
pyranose [(S)-10]
The epoxide (S)-8 (279 mg, 1.02 mmol) was treated with NaN3 and
NH4Cl in DMF–H2O (7.5 mL) for 3 h. Chromatography (PE–
EtOAc, 4:1) afforded the azido-alcohol (S)-10.
Yield: 304 mg (94%); solid; mp 89–91 °C; [a]D –105 (c 1.1,
CHCl3); Rf = 0.45 (PE–EtOAc, 8:2).
IR (film): 3536 (OH), 2106 (N3) cm–1.
1H NMR: d = 1.31, 1.42, 1.43, 1.47 (4 × s, 12 H, 4 × CH3), 2.95 (s,
1 H, OH), 3.38 (d, J7a–7b = 12.8 Hz, 1 H, H-7b), 3.52 (d, 1 H, H-7a),
3.75 (d, J6a–6b = 12.6 Hz, 1 H, H-6b), 3.89 (d, J1a–1b = 10.1 Hz, 1 H,
H-1b), 4.15 (d, 1 H, H-1a), 4.18 (dd, J6a–5 = 2.4 Hz, 1 H, H-6a), 4.29
(dd, J5–4 = 7.6 Hz, 1 H, H-5), 4.44 (d, 1 H, H-4).
3,7-Anhydro-3-C-hydroxymethyl-1,2:4,5-di-O-isopropylidene-
b-D-fructopyranose [(S)-8] [78136-25-1]8
The exo-methylene 6 (661 mg, 2.58 mmol) was treated with
MCPBA in 1,2-DCE (26 mL). Column chromatography (PE–
EtOAc, 85:15) afforded epoxide (S)-8.
Yield: 583 mg (83%); solid; mp 93–95 °C; [a]D –105 (c 1.1, CHCl3)
[Lit.8 –119 (MeOH)]; Rf = 0.42 (PE–EtOAc, 8:2).
IR (film): 1187, 1093, 1067, 1022 (epoxide C–O) cm–1.
13C NMR: d = 24.7, 25.6, 26.1, 26.6 (4 × CH3), 54.5 (C-7), 63.3 (C-
6), 72.5 (C-1), 72.5 (C-5), 73.6 (C-3), 74.1 (C-4), 104.4 (C-2),
109.6, 110.4 (2 × CIV).
1H NMR: d = 1.33, 1.39, 1.49, 1.51 (4 × s, 12 H, 4 × CH3), 2.81 (d,
J7b–7a = 4.9 Hz, 1 H, H-7b), 2.88 (d, 1 H, H-7a), 3.88 (dd, J6b–6a
=
13.1 Hz, J6b–5 = 0.7 Hz, 1 H, H-6b), 3.97–4.13 (m, 4 H, H-6a, H-4,
H-1a, H-1b), 4.43 (dd, J5–4 = 7.4 Hz, 1 H, H-5).
MS (IS): m/z = 333.5 [M + NH4]+, 338.5 [M + Na]+.
13C NMR: d = 25.0, 25.8, 26.2, 26.4 (4 × CH3), 47.4 (C-7), 56.4 (C-
3), 63.3 (C-6), 74.1 (C-1), 74.5 (C-5), 75.0 (C-4), 103.0 (C-2),
110.6, 110.9 (2 × CIV).
HRMS-ES: m/z [M + Na]+ calcd for C13H21N3O6Na: 338.1328;
found: 338.1331.
MS (IS): m/z = 273.0 [M + H]+, 290.5 [M + NH4]+, 295.0 [M + Na]+.
3-C-Azidomethyl-1,2:4,5-di-O-isopropylidene-b-D-psicopyran-
ose [(R)-10]
The epoxide (R)-8 (1.1 g, 4.04 mmol) was treated with NaN3 and
NH4Cl in DMF–H2O (31 mL) for 3 h. Chromatography (PE–
EtOAc, 4:1) afforded the azido-alcohol (R)-10.
Azidolysis of Epoxides; General Procedure
The epoxides in a DMF–H2O (10:1 v/v) solution were reacted with
NaN3 (furano series: 4 equiv, pyrano series: 3 equiv) and NH4Cl
(furano series: 5 equiv, pyrano series: 8 equiv) at 80 °C. When the
reaction was complete, the reaction medium was diluted with H2O
(20 mL) and extracted with EtOAc (5 × 40 mL). The combined or-
ganic phases were washed with brine (3 × 20 mL), dried over
MgSO4, and evaporated. The crude residue was purified by silica
gel column chromatography.
Yield: 1.22 g (96%); white solid; mp 68–69 °C; [a]D –99 (c 1.2,
CHCl3); Rf = 0.52 (PE–EtOAc, 8:2).
IR (film): 3496 (OH), 2106 (N3) cm–1.
1H NMR: d = 1.40, 1.41, 1.47, 1.61 (4 × s, 12 H, 4 × CH3), 2.89 (s,
1 H, OH), 3.36 (s, 2 H, H-7a, H-7b), 3.98 (d, J1a–1b = 9.6 Hz, 1 H, H-
1b), 4.09–4.28 (m, 4 H, H-4, H-5, H-6a, H-6b), 4.51 (d, 1 H, H-1a).
3-C-Azidomethyl-1,2:5,6-di-O-isopropylidene-a-D-allofuran-
ose [(R)-9]
The epoxide (R)-7 (178 mg, 0.65 mmol) was treated with NaN3 and
NH4Cl in DMF–H2O (6.5 mL) for 140 min. Chromatography (PE–
EtOAc, 4:1) afforded the azido-alcohol (R)-9.
13C NMR: d = 25.3, 25.6, 26.1, 26.4 (4 × CH3), 54.9 (C-7), 59.8 (C-
6), 71.4 (C-5), 72.0 (C-3), 72.5 (C-1), 73.7 (C-4), 105.6 (C-2),
109.4, 112.6 (2 × CIV).
MS (IS): m/z = 333.5 [M + NH4]+, 338.5 [M + Na]+.
HRMS-ES: m/z [M + Na]+ calcd for C13H21N3O6Na: 338.1328;
Yield: 187 mg (91%); solid; mp 128–129 °C; [a]D –28 (c 1.0,
CHCl3); Rf = 0.47 (PE–EtOAc, 8:2).
found: 338.1324.
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

3114
S. Tardy et al.
PAPER
Conversion of Azido-Alcohols into Spiro-oxazolidinethiones;
General Procedure
The azido-alcohol in anhydrous 1,4-dioxane was treated with CS2
(19 equiv) and Ph3P (1.1 equiv), overnight at 70 °C. After evapora-
tion of the solvent, the residue was purified by column chromatog-
raphy on silica gel.
1H NMR: d = 1.32, 1.42 (2 × s, 6 H, 2 × CH3), 1.47 (br s, 6 H, 2 ×
CH3), 3.61 (d, J7a–7b = 10.5 Hz, 1 H, H-7b), 3.87 (d, J6a–6b = 13.1 Hz,
1 H, H-6b), 3.91 (d, J7b–7a = 10.5 Hz, 1 H, H-7a), 3.96 (d, J1a–1b = 9.9
Hz, 1 H, H-1b), 4.05 (d, 1 H, H-1a), 4.22 (dd, J6a–5 = 2.7 Hz, 1 H, H-
6a), 4.42 (dd, J5–4 = 7.3 Hz, J5–6a = 2.7 Hz, 1 H, H-5), 4.58 (d, 1 H,
H-4), 8.22 (s, 1 H, NH).
13C NMR: d = 24.6, 25.6, 25.9, 26.2 (4 × CH3), 48.1 (C-7), 62.5 (C-
6), 72.1 (C-1), 72.9 (C-5), 74.5 (C-4), 87.8 (C-3), 104.0 (C-2),
110.1, 112.1 (2 × CIV), 188.5 (CS).
1,2:5,6-Di-O-isopropylidene-3,5¢-spiro(1¢,3¢-oxazolidine-2¢-
thione)-a-D-allofuranose [(R)-11] [908848-39-5]
The azido-alcohol (R)-9 (1.163 g, 3.7 mmol) in dioxane (71 mL)
was treated with CS2 and Ph3P. Chromatography (PE–EtOAc, 2:3)
afforded the OZT (R)-11.
MS (IS): m/z = 332.5 [M + H]+, 349.0 [M + NH4]+, 354.0 [M + Na]+,
370.0 [M + K]+.
Anal. Calcd for C14H21NO6S: C, 50.74; H, 6.39; N, 4.23; S, 9.68.
Found: C, 50.47; H, 6,33; N, 4.26; S, 9.35.
Yield: 1.16 g (95%); solid; mp 197–199 °C; [a]D +94 (c 1.0,
CHCl3); Rf = 0.10 (PE–EtOAc, 8:2).
IR (film): 3314 (NH), 1533, 1184 (O–CS–N) cm–1.
1,2:4,5-Di-O-isopropylidene-3,5¢-spiro(1¢,3¢-oxazolidine-2¢-
thione)-b-D-psicopyranose [(R)-12]
The azido-alcohol (R)-10 (192 mg, 0.61 mmol) in dioxane (12 mL)
was treated with CS2 and Ph3P. Chromatography (PE–EtOAc, 1:1)
afforded the OZT (R)-12.
1H NMR: d = 1.33, 1.38, 1.48, 1.63 (4 × s, 12 H, 4 × CH3), 3.56 (d,
J7a–7b = 10.4 Hz, 1 H, H-7b), 4.02 (dd, J6a–6b = 11.8 Hz, J6b–5 = 6.0
Hz, 1 H, H-6b), 4.10 (d, 1 H, H-7a), 4.10–4.20 (m, 2 H, H-6a, H-5),
4.23 (d, J4–5 = 8.2 Hz, 1 H, H-4), 4.59 (d, J2–1 = 3.3 Hz, 1 H, H-2),
5.75 (d, 1 H, H-1).
13C NMR: d = 25.3, 26.6, 26.8, 26.9 (4 × CH3), 47.9 (C-7), 68.2 (C-
6), 73.8 (C-5), 77.3 (C-4), 84.0 (C-2), 91.4 (C-3), 103.1 (C-1),
110.5, 114.7 (2 × CIV), 188.7 (CS).
Yield: 190 mg (94%); solid; mp 203–205 C; [a]D –52 (c 1.0,
CHCl3); Rf = 0.13 (PE–EtOAc, 8:2).
IR (film): 3296 (NH), 1544, 1164 (O–CS–N) cm–1.
1H NMR (500 MHz): d = 1.36, 1.41, 1.48, 1.66 (4 × s, 12 H, 4 ×
CH3), 3.65 (d, J7b–7a = 10.5 Hz, 1 H, H-7b), 3.78 (d, 1 H, H-7a), 4.12
(d, J1a–1b = 10.0 Hz, 1 H, H-1b), 4.16 (d, 1 H, H-1a), 4.20 (dd,
J6a–6b = 13.0 Hz, J6b–5 = 3.0 Hz, 1 H, H-6b), 4.26 (m, 2 H, H-4, H-
5), 4.30 (d, 1 H, H-6a), 8.09 (s, 1 H, NH).
MS (IS): m/z = 332.5 [M + H]+, 349.5 [M + NH4]+, 354.5 [M + Na]+,
386.5 [M + MeOH + Na]+, 663.5 [2M + H]+, 685.5 [2M + Na]+.
HRMS-ES: m/z [M + Na]+ calcd for C14H21NO6SNa: 354.0987;
found: 354.1004.
Anal. Calcd for C14H21NO6S: C, 50.74; H, 6.39; N, 4.23; S, 9.68.
Found: C, 50.94; H, 6,39; N, 4.24; S, 9.28.
13C NMR: d = 25.2, 25.8, 26.0, 26.5 (4 × CH3), 49.6 (C-7), 60.6 (C-
6), 71.0 (C-5), 72.1 (C-1), 75.2 (C-4), 85.9 (C-3), 104.8 (C-2),
110.9, 113.0 (2 × CIV), 188.7 (CS).
1,2:5,6-Di-O-isopropylidene-3,5¢-spiro(1¢,3¢-oxazolidine-2¢-
thione)-a-D-glucofuranose [(S)-11] [908848-40-8]
The azido-alcohol (S)-9 (95 mg, 0.3 mmol) in dioxane (7.5 mL) was
treated with CS2 and Ph3P. Chromatography (PE–EtOAc, 7:3) af-
forded the OZT (S)-11.
MS (IS): m/z = 332.5 [M + H]+, 349.0 [M + NH4]+, 354.0 [M + Na]+,
370.0 [M + K]+.
Anal. Calcd for C14H21NO6S: C, 50.74; H, 6.39; N, 4.23; S, 9.68.
Found: C, 50.59; H, 6.37; N, 4.22; S, 9.31.
Yield: 89 mg (89%); solid; mp 136–138 °C; [a]D +39 (c 1.2,
CHCl3); Rf = 0.52 (PE–EtOAc, 8:2).
IR (film): 3222 (NH), 1534, 1162 (O–CS–N) cm–1.
3-C-Cyano-1,2:5,6-di-O-isopropylidene-a-D-allofuranose [(S)-
14] [43179-08-4]
Ulose 3 (5.07 g, 19.6 mmol) in an ice-cold solution of Et2O (50 mL)
and H2O (10 mL), was treated with NaHCO3 (3.3 g, 39.2 mmol) for
10 min with stirring at 0 °C. The solution was added dropwise to aq
KCN (5 mL, 1.34 g, 20.6 mmol). The mixture was stirred 20 min
then diluted with sat. aq NaHCO3 (20 mL). The aqueous layer was
extracted with Et2O (3 × 30 mL) and the combined organic phases
were washed with brine (1 × 20 mL), dried over MgSO4, and con-
centrated in vacuo to give the cyanohydrin (S)-14.
1H NMR: d = 1.31 (s, 6 H, 2 × CH3), 1.43, 1.51 (2 × s, 6 H, 2 × CH3),
3.94 (d, J7a–7b = 10.4 Hz, 1 H, H-7b), 3.96 (d, J4–5 = 8.2 Hz, 1 H, H-
4), 4.00 (d, 1 H, H-7a), 4.03 (dd, J6a–6b = 8.7 Hz, J6b–5 = 5.0 Hz, 1 H,
H-6b), 4.15 (dd, J6a–5 = 6.2 Hz, 1 H, H-6a), 4.38 (m, 1 H, H-5), 4.63
(d, J2–1 = 3.7 Hz, 1 H, H-2), 5.96 (d, 1 H, H-1), 8.30 (s, 1 H, NH).
13C NMR: d = 25.1, 26.4 (2 × CH3), 26.8 (2 × CH3), 46.0 (C-7), 67.5
(C-6), 72.5 (C-5), 81.1 (C-4), 83.5 (C-2), 94.3 (C-3), 104.8 (C-1),
110.0, 113.2 (2 × CIV), 188.1 (CS).
Yield: 5.42 g (97%); gum; [a]D +16 (c 0.85, CHCl3); Rf = 0.67 (PE–
EtOAc, 7:3).
IR (film): 3381 (OH), 1633 (CN) cm–1.
1H NMR: d = 1.40 (s, 6 H, 2 × CH3), 1.48, 1.61 (2 × s, 6 H, 2 × CH3),
3.66 (s, 1 H, OH), 3.85 (d, J4–5 = 8.8 Hz, 1 H, H-4), 4.03 (dd, J6a–6b
9.1 Hz, J6b–5 = 4.2 Hz, 1 H, H-6b), 4.20 (dd, J6a–5 = 6.1 Hz, 1 H, H-
6a), 4.42 (m, 1 H, H-5), 4.80 (d, J2–1 = 3.5 Hz, 1 H, H-2), 5.92 (d,
1 H, H-1).
MS (IS): m/z = 332.5 [M + H]+, 349.5 [M + NH4]+, 354.5 [M + Na]+,
386.5 [M + MeOH + Na]+, 663.5 [2M + H]+, 685.5 [2M + Na]+.
HRMS-ES: m/z [M + H]+ calcd for C14H21NO6SH: 332.1167;
found: 332.1167.
=
Anal. Calcd for C14H21NO6S: C, 50.74; H, 6.39; N, 4.23; S, 9.68.
Found: C, 50.61; H, 6.39; N, 4.20; S, 9.15.
13C NMR: d = 24.9, 26.5, 26.7, 26.8 (4 × CH3), 67.5 (C-6), 75.1 (C-
5), 77.2 (C-3), 79.7 (C-4), 82.2 (C-2), 104.1 (C-1), 110.6, 114.8 (2
× CIV), 117.3 (CN).
1,2:4,5-Di-O-isopropylidene-3,5¢-spiro(1¢,3¢-oxazolidine-2¢-
thione)-b-D-fructopyranose [(S)-12]
The azido-alcohol (S)-10 (1.3 g, 4.12 mmol) in dioxane (90 mL)
was treated with CS2 and Ph3P. Chromatography (PE–EtOAc, 7:3)
afforded the OZT (S)-12.
MS (IS): m/z = 259.5 [M – CN]+, 308.5 [M + Na]+.
3-C-Cyano-1,2:5,6-di-O-isopropylidene-a-D-glucofuranose
[(R)-14] [52290-80-9]
A solution of KCN (1.35 g, 20.7 mmol) in H2O (12 mL) was added
dropwise to a solution of ulose 3 (5.1 g, 19.7 mmol) in Et2O (60
Yield: 1.29 g (95%); solid; mp 134–136 °C; [a]D –127 (c 1.0,
CHCl3); Rf = 0.33 (PE–EtOAc, 8:2).
IR (film): 3198 (NH), 1549, 1182 (O–CS–N) cm–1.
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

PAPER
Carbohydrate-Based Spiro-1,3-oxazolidine-2-thiones
3115
mL). After 7 h at r.t., the mixture was diluted with sat. aq NaHCO3
(20 mL). The aqueous layer was extracted with Et2O (3 × 30 mL)
and the combined organic layers were washed with brine (1 × 20
mL), dried over MgSO4, and concentrated in vacuo to give the crude
cyanohydrin (R)-14.
J4–5 = 7.9 Hz, 1 H, H-4), 5.24 (d, J2–1 = 3.6 Hz, 1 H, H-2), 6.01 (d,
1 H, H-1), 7.37 (d, Jvic = 8.2 Hz, 2 H, ArH), 7.90 (d, 2 H, ArH).
13C NMR: d = 21.9 (CH3-Ar), 25.1, 26.1 (2 × CH3), 26.7 (2 × CH3),
66.9 (C-6), 71.8 (C-5), 81.4 (C-3), 83.8 (C-4), 84.0 (C-2), 105.4 (C-
1), 110.2, 114.4 (2 ×CIV), 111.9 (CN), 128.6 (2 × C-Ar), 129.8 (2 ×
C-Ar), 133.0 (CIV-Me), 146.1 (CIV-SO2).
Yield: 4.82 g (85%); solid; mp 91–93 °C; [a]D +46 (c 1.14, CHCl3);
Rf = 0.64 (PE–EtOAc, 7:3).
IR (film): 3374 (OH), 1633 (CN) cm–1.
MS (IS): m/z = 440.5 [M + H]+, 457.5 [M + NH4]+, 462.5 [M + Na]+,
494.5 [M + MeOH + Na]+.
1H NMR: d = 1.37, 1.39, 1.55, 1.58 (4 × s, 12 H, 4 × CH3), 4.09 (dd,
J6a–6b = 9.1 Hz, J6b–5 = 4.4 Hz, 1 H, H-6b), 4.20 (dd, J6a–5 = 6.0 Hz,
1 H, H-6a), 4.20 (d, J4–5 = 6.9 Hz, 1 H, H-4), 4.33 (m, 2 H, H-5,
OH), 4.58 (d, J2–1 = 3.5 Hz, 1 H, H-2), 5.95 (d, 1 H, H-1).
Formation of Spiro-Aziridines; General Procedure
To a cooled (–15 °C) and vigorously stirred suspension of LAH (4.3
equiv) in Et2O, a solution of the sulfonylated cyanohydrine (1
equiv) in Et2O was added dropwise. The reaction was maintained at
low temperature for 30 min, then allowed to reach r.t. and the reac-
tion mixture was cooled again in an ice-bath and quenched with ice.
EtOAc (30 mL) was added and the resulting emulsion was filtered
over a Celite® pad and the cake was washed with EtOAc (4 × 60
mL). The aqueous layer was further extracted with EtOAc and the
combined organic phase was washed with brine, dried over MgSO4
then evaporated. The crude product was purified by column chro-
matography on silica gel.
13C NMR: d = 25.1, 26.6, 26.7, 26.9 (4 × CH3), 67.1 (C-6), 73.2 (C-
5), 75.3 (C-3), 82.5 (C-4), 85.7 (C-2), 105.2 (C-1), 110.9, 113.8 (2
× CIV), 116.9 (CN).
MS (IS): m/z = 286.5 [M + H]+, 303.5 [M + NH4]+, 308.5 [M + Na]+,
340.5 [M + MeOH + Na]+.
3-C-Cyano-1,2:5,6-di-O-isopropylidene-3-O-(p-toluene-4-sulfo-
nyl)-a-D-allofuranose [(R)-15] [55052-95-4]
TsCl (8.73 g, 45.8 mmol) was added to a solution of (R)-14 (5.46 g,
19.1 mmol) in pyridine (30 mL) cooled to –50 °C. The mixture was
allowed to warm up slowly (80 h) to r.t., then the reaction was
quenched through the addition of ice (50 g). The resulting aqueous
layer was extracted with CHCl3 (5 × 50 mL) and the combined or-
ganic phase was washed with HCl (1M, 2 × 100 mL), then with sat.
aq NaHCO3 (2 × 100 mL) and with brine (100 mL). The organic
layer was dried over MgSO4 and concentrated in vacuo to give the
crude tosylate (R)-15.
3-C-Aminomethyl-3,7-anhydro-1,2:4,5-di-O-isopropylidene-a-
D-glucofuranose (16)
The tosylated cyanohydrin (R)-15 (2.0 g, 4.55 mmol) dissolved in
Et2O (25 mL) was treated with LAH (0.75 g, 19.56 mmol) suspend-
ed in Et2O (25 mL) at –30 °C. The reaction was quenched with ice
(100 g) and EtOAc (30 mL) and the organic layer was taken. Chro-
matography (PE–EtOAc, 2:3) afforded the spiro-aziridine 16. The
faster moving side-product 17 was also isolated.
Yield: 1.10 g (89%); colourless oil; [a]D +44 (c 0.72, CHCl3);
Rf = 0.22 (PE–EtOAc, 45:55).
IR (film): 3382 (NH), 1644 (C–N) cm–1.
Yield: 7.13 g (85%); solid; mp 82–85 °C; [a]D +42 (c 1.39, CHCl3);
Rf = 0.77 (PE–EtOAc, 7:3).
IR (film): 1598 (CN), 1455 cm–1.
1H NMR: d = 1.24, 1.26, 1.31, 1.49 (4 × s, 12 H, 4 × CH3), 1.97 (s,
1 H, H-7b), 2.02 (s, 2 H, H-7a, NH), 3.87 (m, 1 H, H-5), 3.93 (dd,
J6a–6b = 8.8 Hz, J6b–5 = 4.7 Hz, 1 H, H-6b), 4.05 (dd, J6a–5 = 6.4 Hz,
1 H, H-6a), 4.18 (d, J2–1 = 3.8 Hz, 1 H, H-2), 4.25 (d, J4–5 = 8.2 Hz,
1 H, H-4), 5.84 (d, 1 H, H-1).
1H NMR: d = 1.25, 1.31, 1.41, 1.57 (4 × s, 12 H, 4 × CH3), 2.47 (s,
3 H, CH3-Ar), 3.98 (dd, J6a–6b = 8.8 Hz, J6b–5 = 4.1 Hz, 1 H, H-6b),
4.07 (d, J4–5 = 7.8 Hz, 1 H, H-4), 4.10 (dd, J6a–5 = 5.7 Hz, 1 H, H-
6a), 4.23 (m, 1 H, H-5), 5.13 (d, J2–1 = 3.8 Hz, 1 H, H-2), 5.93 (d,
1 H, H-1), 7.36 (d, Jvic = 8.2 Hz, 2 H, ArH), 7.90 (d, 2 H, ArH).
13C NMR: d = 24.8, 26.3, 26.4, 26.7 (4 × CH3), 29.3 (C-7), 46.0 (C-
3), 67.3 (C-6), 74.1 (C-5), 77.2 (C-4), 86.9 (C-2), 104.0 (C-1),
109.3, 111.6 (2 × CIV).
13C NMR: d = 21.6 (CH3-Ar), 25.0, 26.3, 26.5, 26.9 (4 × CH3), 66.9
(C-6), 74.2 (C-5), 79.6 (C-4), 79.8 (C-3), 82.5 (C-2), 104.1 (C-1),
110.0, 114.6 (2 × CIV), 113.7 (CN), 128.2 (2 × C-Ar), 129.5 (2 × C-
Ar), 133.6 (CIV-Me), 145.5 (CIV-SO2).
MS (IS): m/z = 272.5 [M + H]+, 304.5 [M + MeOH + H]+.
MS (IS): m/z = 440.5 [M + H]+, 457.5 [M + NH4]+, 462.5 [M + Na]+,
HRMS-ES: m/z calcd for C13H21NO5H: 272.1498; found: 272.1484.
494.5 [M + MeOH + Na]+.
3-C-p-Toluenesulfonamidomethyl-1,2:4,5-di-O-isopropylidene-
a-D-allofuranose (17)
Yield: 95 mg (4.7%); white solid; mp 177–179 °C; [a]D +44 (c 1.23,
CHCl3); Rf = 0.60 (PE–EtOAc, 45:55).
3-C-Cyano-1,2:5,6-di-O-isopropylidene-3-O-(p-toluene-4-sulfo-
nyl)-a-D-glucofuranose [(S)-15]
TsCl (12.43 g, 65.2 mmol) and a catalytic amount of DMAP were
added to a solution of (S)-14 (4.65 g, 16.3 mmol) in pyridine (30
mL) at 0 °C. The mixture was then heated at 70 °C for 16 h. After
cooling to r.t., the reaction was quenched with ice. After separation,
the aqueous layer was extracted with CHCl3 (5 × 50 mL) and the
combined organic phase was washed with aq HCl (1M, 2 × 100
mL), then with sat. aq NaHCO3 (2 × 100 mL) and brine (100 mL).
The organic layer was dried over MgSO4 and concentrated in vacuo.
Silica gel column chromatography (PE–EtOAc, 4:1) afforded (S)-
15.
IR (film): 3443 (NH), 3290 (OH), 1336, 1161 (SO2) cm–1.
1H NMR: d = 1.28, 1.33, 1.35, 1.57 (4 × s, 12 H, 4 × CH3), 2.43 (s,
3 H, CH3-Ar), 3.04 (br s, 1 H, OH), 3.07 (dd, J7a–7b = 13.0 Hz,
J7b–NH = 9.4 Hz, 1 H, H-7b), 3.23 (dd, J7a–NH = 3.8 Hz, 1 H, H-7a),
3.75 (d, J4–5 = 7.2 Hz, 1 H, H-4), 3.89 (dd, J6a–6b = 11.3 Hz, J6b–5
8.8 Hz, 1 H, H-6b), 3.98–4.07 (m, 2 H, H-5, H-6a), 4.59 (d, J2–1
=
=
3.8 Hz, 1 H, H-2), 5.15 (dd, 1 H, NH), 5.75 (d, 1 H, H-1), 7.32 (d,
Jvic = 8.2 Hz, 2 H, ArH), 7.74 (d, 2 H, ArH).
Yield: 4.72 g (66%); colourless syrup; [a]D –34 (c 2.58, CHCl3);
Rf = 0.66 (PE–EtOAc, 8:2).
IR (film): 1598 (CN), 1455 cm–1.
1H NMR: d = 1.19, 1.33, 1.38, 1.57 (4 × s, 12 H, 4 × CH3), 2.46 (s,
3 H, CH3-Ar), 3.94 (dd, J6a–6b = 9.1 Hz, J6b–5 = 4.1 Hz, 1 H, H-6b),
4.03 (dd, J6a–5 = 5.7 Hz, 1 H, H-6a), 4.17 (m, 1 H, H-5), 4.24 (d,
13C NMR: d = 21.6 (CH3-Ar), 25.1, 26.5, 26.7 (4 × CH3), 44.1 (C-
7), 67.5 (C-6), 72.9 (C-5), 78.9 (C-4), 80.3 (C-3), 80.8 (C-2), 103.5
(C-1), 110.0, 112.7 (2 × CIV), 127.1 (2 × C-Ar), 129.9 (2 × C-Ar),
136.8 (CIV-Me), 143.7 (CIV-SO2).
MS (IS): m/z = 444.5 [M + H]+, 461.5 [M + NH4]+, 466.5 [M + Na]+,
909.5 [2M + Na]+.
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

3116
S. Tardy et al.
PAPER
3-C-Aminomethyl-3,7-anhydro-1,2:4,5-di-O-isopropylidene-a-
D-allofuranose (18)
MS (IS): m/z = 372.5 [M + H]+, 389.5 [M + NH4]+, 761.0 [2M +
NH4]+, 765.5 [2M + Na]+.
Tosylated cyanohydrin (S)-15 (362 mg, 0.82 mmol) dissolved in
Et2O (5 mL) was treated with LAH (134 mg, 3.53 mmol) in Et2O (5
mL) at –15 °C. The reaction was quenched with ice (50 g) and
EtOAc (20 mL) and the organic layer was taken. Chromatography
(PE–EtOAc, 1:1) afforded the spiro-aziridine 18, the spiro-aziridine
16 (8 mg, 3.6% yield) and the tosylamide 19.
HRMS-ES: m/z [M + Na]+ calcd for C18H29NO7Na: 394.1842;
found: 394.1846.
3,7-Anhydro-3-C-p-toluenesulfonamidomethyl-1,2:4,5-di-O-
isopropylidene-a-D-glucofuranose (21)
A solution of 16 (105 mg, 0.39 mmol) in THF (4 mL) was treated
with TsCl (184 mg, 0.97 mmol, 2.5 equiv) and DIPEA (202 mL,
1.16 mmol, 3 equiv) at r.t. overnight, then heated at 80 °C for 2 h.
The product was hydrolysed with H2O (50 mL), extracted with
CH2Cl2 (4 × 20 mL), and the organic phase was washed successive-
ly with HCl (1 M, 2 × 50 mL), sat. aq NaHCO3 (3 × 20 mL) and
brine (2 × 20 mL), then dried over MgSO4 and concentrated in vac-
uo. Chromatography (PE–EtOAc, 85:15) afforded 21.
Yield: 125 mg (56%); colourless oil; [a]D +71 (c 1.72, CHCl3);
Rf = 0.19 (PE–EtOAc, 45:55).
IR (film): 3300 (NH), 1643 (C–N) cm–1.
1H NMR: d = 1.30, 1.34, 1.38, 1.60 (4 × s, 12 H, 4 × CH3), 1.81 (s,
1 H, H-7b), 2.10 (s, 1 H, NH), 2.37 (s, 1 H, H-7a), 3.91 (m, 1 H, H-
5), 3.94 (dd, J6a–6b = 8.8 Hz, J6b–5 = 4.7 Hz, 1 H, H-6b), 4.10 (dd,
J6a–5 = 6.0 Hz, 1 H, H-6a), 4.17 (d, J4–5 = 8.2 Hz, 1 H, H-4), 4.26 (d,
J2–1 = 3.8 Hz, 1 H, H-2), 5.84 (d, 1 H, H-1).
13C NMR: d = 25.3 (CH3), 26.4 (C-7), 26.8 (CH3), 27.0 (2 × CH3),
46.9 (C-3), 68.4 (C-6), 75.5 (C-5), 82.6 (C-4), 84.1 (C-2), 104.3 (C-
1), 110.0, 112.9 (2 × CIV).
Yield: 80 mg (49%); white solid; mp 94–95 °C; [a]D –6 (c 0.73,
CHCl3); Rf = 0.56 (PE–EtOAc, 8:2).
IR (film): 1455 (Ar), 1328 (SO2) cm–1.
1H NMR: d = 1.25 (s, 3 H, CH3), 1.37 (s, 6 H, 2 × CH3), 1.57 (s, 3 H,
CH3), 2.45 (s, 3 H, CH3-Ar), 2.61 (s, 1 H, H-7b), 3.11 (s, 1 H, H-7a),
3.95–4.13 (m, 3 H, H-5, H-6a, H-6b), 4.32 (d, J4–5 = 6.0 Hz, 1 H, H-
4), 5.28 (d, J2–1 = 3.8 Hz, 1 H, H-2), 5.98 (d, 1 H, H-1), 7.34 (d,
Jvic = 8.0 Hz, 2 H, ArH), 7.82 (d, 2 H, ArH).
13C NMR: d = 21.8 (CH3-Ar), 25.3, 26.6, 26.8, 27.0 (4 × CH3), 33.8
(C-7), 56.1 (C-3), 66.6 (C-6), 73.7 (C-5), 77.2 (C-4), 80.6 (C-2),
104.8 (C-1), 109.5, 112.8 (CIV), 127.7 (2 × C-Ar), 129.9 (2 × C-Ar),
136.6 (CIV-Me), 144.9 (CIV-SO2).
MS (IS): m/z = 272.5 [M + H]+, 304.5 [M + MeOH + H]+, 543.5
[2M + H]+.
HRMS-ES: m/z [M + H]+ calcd for C13H21NO5H: 272.1498; found:
272.1497.
3-C-p-Toluenesulfonamidomethyl-1,2:4,5-di-O-isopropylidene-
a-D-glucofuranose (19)
Yield: 122 mg (33%); solid; [a]D +33 (c 1.19, CHCl3); mp 153–
155 °C; Rf = 0.62 (PE–EtOAc, 45:55).
MS (IS): m/z = 426.5 [M + H]+, 443.5 [M + NH4]+, 448.5 [M + Na]+,
475.5 [M + MeOH + NH4]+, 868.5 [2M + NH4]+.
IR (film): 3443 (NH), 3238 (OH), 1324, 1162 (SO2) cm–1.
HRMS-ES: m/z [M + Na]+ calcd for C20H27NO7SNa: 448.1406;
found: 448.1395.
1H NMR: d = 1.26, 1.33, 1.35, 1.42 (4 × s, 12 H, 4 × CH3), 2.43 (s,
3 H, CH3-Ar), 3.24 (dd, J7a–7b = 13.8 Hz, J7b–NH = 5.8 Hz, 1 H, H-
7b), 3.32 (dd, J7a–NH = 7.5 Hz, 1 H, H-7a), 3.47 (br s, 1 H, OH), 3.67
(d, J4–5 = 8.8 Hz, 1 H, H-4), 3.96 (dd, J6a–6b = 8.8 Hz, J6b–5 = 5.0 Hz,
1 H, H-6b), 4.11 (dd, J6a–5 = 6.3 Hz, 1 H, H-6a), 4.23–4.33 (m, 1 H,
H-5), 4.38 (d, J2–1 = 3.5 Hz, 1 H, H-2), 5.71 (dd, 1 H, NH), 5.84 (d,
1 H, H-1), 7.32 (d, Jvic = 8.2 Hz, 2 H, ArH), 7.76 (d, 2 H, ArH).
13C NMR: d = 21.6 (CH3-Ar), 25.2, 26.4, 26.8, 27.1 (4 × CH3), 45.5
(C-7), 67.8 (C-6), 72.0 (C-5), 80.3 (C-4), 82.6 (C-3), 86.4 (C-2),
104.6 (C-1), 109.7, 112.7 (2 × CIV), 127.2 (2 × C-Ar), 129.9 (2 × C-
Ar), 136.5 (CIV-Me), 143.9 (CIV-SO2).
3,7-Anhydro-3-C-o-nitrobenzenesulfonamidomethyl-1,2:4,5-
di-O-isopropylidene-a-D-glucofuranose (22)
Et3N (737 mL, 5.30 mmol) and o-nosyl chloride (878 mg, 3.96
mmol) were successively added to a cooled (ice-bath) THF solution
(13 mL) of 16 (359 mg, 1.32 mmol). After stirring at r.t. for 36 h,
the mixture was diluted with H2O (120 mL) and extracted with
CH2Cl2 (4 × 30 mL). The combined organic phase was washed with
H2O (3 × 20 mL), brine (2 × 20 mL), then dried over MgSO4 and
concentrated in vacuo. Chromatography (PE–EtOAc, 75:25) af-
forded 22.
MS (IS): m/z = 444.5 [M + H]+, 461.5 [M + NH4]+, 466.5 [M + Na]+,
909.5 [2M + Na]+.
Yield: 362 mg (60%); pale-yellow solid; mp 67–70 °C; [a]D –77 (c
0.96, CHCl3); Rf = 0.74 (PE–EtOAc, 6:4).
3,7-Anhydro-3-C-t-butoxycarboxamidomethyl-1,2:4,5-di-O-
isopropylidene-a-D-glucofuranose (20)
(Boc)2O (280 mL, 1.3 mmol, 3.5 equiv) was added to a solution of
the spiro-aziridine 16 (101 mg, 0.37 mmol) in THF (3 mL). After 24
h at r.t., the solvent was removed in vacuo and the crude product
was purified by chromatography (PE–EtOAc, 4:1) to afford the car-
bamate 20.
IR (film): 1546 (NO2), 1342 (SO2).
1H NMR: d = 1.24, 1.36, 1.38, 1.57 (4 × s, 12 H, 4 × CH3), 2.96 (s,
1 H, H-7b), 3.33 (s, 1 H, H-7a), 3.95–4.10 (m, 3 H, H-5, H-6a, H-
6b), 4.32 (d, J4–5 = 6.3 Hz, 1 H, H-4), 5.15 (d, J2–1 = 3.8 Hz, 1 H, H-
2), 6.05 (d, 1 H, H-1), 7.70–7.85 (m, 3 H, ArH), 8.15–8.20 (m, 1 H,
ArH).
Yield: 69 mg (50%); solid; mp 120–122 °C; [a]D +1 (c 1.06,
CHCl3); Rf = 0.42 (PE–EtOAc, 9:1).
IR (film): 1718 (C=O) cm–1.
1H NMR: d = 1.31, 1.33, 1.40 (3 × s, 9 H, 3 × CH3), 1.47 (s, 9 H,
tBu), 1.57 (s, 3 H, CH3), 2.48 (s, 1 H, H-7b), 2.66 (s, 1 H, H-7a),
4.01–4.12 (m, 3 H, H-5, H-6a, H-6b), 4.23 (d, J2–1 = 3.8 Hz, 1 H, H-
2), 4.28 (d, J4–5 = 6.0 Hz, 1 H, H-4), 5.93 (d, 1 H, H-1).
13C NMR: d = 26.4, 26.7 (2 × CH3), 26.8 (2 × CH3), 36.5 (C-7), 58.1
(C-3), 66.5 (C-6), 73.5 (C-5), 77.4 (C-4), 81.4 (C-2), 104.6 (C-1),
109.5 (CIV), 112.9 (CIV), 124.8 (ArC-3), 130.7 (ArC-6), 132.6 (ArC-
4), 134.7 (ArC-5), 141.6 (ArC-1), 148.2 (ArC-2).
MS (IS): m/z = 457.5 [M + H]+, 474.5 [M + NH4]+, 479.5 [M + Na]+.
HRMS-ES: m/z [M + Na]+ calcd for C19H24N2O9SNa: 479.1100;
found: 479.1078.
13C NMR: d = 25.2, 26.6, 26.9, 27.1 (4 × CH3), 28.1 (3 × CH3-tBu),
29.8 (C-7), 50.9 (C-3), 66.5 (C-6), 74.1 (C-5), 77.4 (C-4), 82.2
(CIV-tBu), 83.0 (C-2), 104.5 (C-1), 109.5, 112.7 (2 × CIV), 159.7
(CO).
3,7-Anhydro-3-C-methanesulfonamidomethyl-1,2:4,5-di-O-iso-
propylidene-a-D-glucofuranose (23)
Et3N (271 mL, 1.95 mmol) and MsCl (110 mL, 1.42 mmol) were suc-
cessively added dropwise to a cooled (–30 °C) solution of 16 (151
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

PAPER
Carbohydrate-Based Spiro-1,3-oxazolidine-2-thiones
3117
mg, 0.56 mmol) in THF (5 mL). The mixture was stirred overnight
while slowly reaching r.t., then diluted with H2O (100 mL) and ex-
tracted with CH2Cl2 (4 × 30 mL). The combined organic phase was
washed with brine, dried over MgSO4 and concentrated in vacuo.
Chromatography (PE–EtOAc, 7:3) afforded 23.
1H NMR: d = 1.28, 1.31, 1.39, 1.50 (4 × s, 12 H, 4 × CH3), 2.43 (s,
3 H, CH3-Ar), 3.59 (d, J7a–7b = 12.9 Hz, 1 H, H-7b), 3.70 (d, 1 H, H-
7a), 3.77 (d, J4–5 = 8.2 Hz, 1 H, H-4), 3.92 (dd, J6a–6b = 8.5 Hz,
J6b–5 = 4.7 Hz, 1 H, H-6b), 4.05 (dd, J6a–5 = 6.3 Hz, 1 H, H-6a), 4.15
(m, 1 H, H-5), 5.02 (d, J2–1 = 3.8 Hz, 1 H, H-2), 5.34 (s, 1 H, NH),
5.76 (d, 1 H, H-1), 7.32 (d, Jvic = 8.2 Hz, 2 H, ArH), 7.83 (d, 2 H,
ArH).
13C NMR: d = 21.6 (CH3-Ar), 24.9, 26.2 (2 × CH3), 26.6 (2 × CH3),
53.5 (C-7), 67.8 (C-6), 71.2 (C-3), 73.1 (C-5), 82.1 (C-4), 82.7 (C-
2), 105.0 (C-1), 110.1, 112.5 (2 × CIV), 127.0 (2 × C-Ar), 129.8 (2
× C-Ar), 139.3 (CIV-Me), 143.8 (CIV-SO2).
Yield: 186 mg (95%); white solid; mp 123–125 °C; [a]D –14 (c
1.13, CHCl3); Rf = 0.74 (PE–EtOAc, 6:4).
IR (film): 1325, 1153 (SO2) cm–1.
1H NMR: d = 1.31, 1.34, 1.39, 1.55 (4 × s, 12 H, 4 × CH3), 2.76 (s,
1 H, H-7b), 3.05 (s, 1 H, H-7a), 3.15 (s, 3 H, CH3SO2), 4.02–4.14
(m, 3 H, H-5, H-6a, H-6b), 4.23 (d, J4–5 = 7.2 Hz, 1 H, H-4), 5.10 (d,
J2–1 = 3.8 Hz, 1 H, H-2), 5.95 (d, 1 H, H-1).
MS (IS): m/z = 469.5 [M + H]+, 486.5 [M + NH4]+, 491.5 [M + Na]+.
HRMS-ES: m/z [M + Na]+ calcd for C20H28N4O7SNa: 491.1576;
13C NMR: d = 25.2, 26.4 (2 × CH3), 26.8 (2 × CH3), 34.2 (C-7), 41.9
(CH3SO2), 55.5 (C-3), 66.8 (C-6), 73.5 (C-5), 77.3 (C-4), 80.6 (C-
2), 104.8 (C-1), 109.5, 112.7 (2 × CIV).
found: 491.1568.
3-C-Acetoxymethyl-3-deoxy-1,2:5,6-di-O-isopropylidene-3-N-
o-nitrobenzenesulfonamido-a-D-glucofuranose (26)
The N-sulfonylated aziridine 23 (356 mg, 0.78 mmol) was treated
with AcONa in DMF (10 mL) for 80 min. Chromatography (PE–
EtOAc, 75:25) afforded the acetylated derivative 26.
MS (IS): m/z = 350.0 [M + H]+, 367.5 [M + NH4]+, 372.5 [M + Na]+,
716.5 [2M + NH4]+, 721.5 [2M + Na]+.
HRMS-ES: m/z [M + Na] calcd for C14H23NO7SNa: 372.1093;
found: 372.1095.
Yield: 235 mg (58%); pale-yellow oil; [a]D +22 (c 0.65, CHCl3);
Rf = 0.40 (PE–EtOAc, 6:4).
IR (film): 3356 (NH), 1743 (COO), 1542 (NO2), 1359 (SO2) cm–1.
Ring-Opening of Aziridines; General Procedure
AcONa (10 equiv) or NaN3 (6 equiv) was added to a DMF solution
of N-sulfonylated spiro-aziridine. The mixture was stirred at r.t.
(NaN3) or heated at 100 °C (AcONa). After complete conversion,
the mixture was diluted with H2O (150 mL) then extracted with
EtOAc (4 × 40 mL). The combined organic phase was washed with
brine (3 × 60 mL), dried over MgSO4 and evaporated in vacuo. The
crude product was purified by silica gel column chromatography.
1H NMR: d = 1.29, 1.35, 1.38, 1.51 (4 × s, 12 H, 4 × CH3), 1.76 (s,
3 H, CH3COO), 3.83 (d, J4–5 = 8.5 Hz, 1 H, H-4), 3.86 (dd, J6a–6b
=
8.5 Hz, J6b–5 = 5.3 Hz, 1 H, H-6b), 3.95 (dd, J6a–5 = 6.3 Hz, 1 H, H-
6a), 4.05 (m, 1 H, H-5), 4.31 (d, J7a–7b = 12.2 Hz, 1 H, H-7b), 4.52
(d, 1 H, H-7a), 5.23 (d, J2–1 = 3.8 Hz, 1 H, H-2), 5.98 (d, 1 H, H-1),
6.08 (s, 1 H, NH), 7.74–7.80 (m, 2 H, ArH), 7.90–7.95 (m, 1 H,
ArH), 8.10–8.20 (m, 1 H, ArH).
13C NMR: d = 20.5 (CH3CO2), 25.1, 26.4, 26.5, 26.8 (4 × CH3), 63.7
(C-7), 67.9 (C-6), 71.4 (C-3), 72.6 (C-5), 82.8 (C-4), 83.7 (C-2),
105.0 (C-1), 110.3, 112.9 (2 × CIV), 125.5 (ArC-3), 130.4 (ArC-6),
133.2 (ArC-4), 133.7 (ArC-5), 136.2 (ArC-1), 147.8 (ArC-2), 170.0
(COO).
3-C-Acetoxymethyl-3-deoxy-1,2:5,6-di-O-isopropylidene-3-N-
p-toluenesulfonamido-a-D-glucofuranose (24)
The N-sulfonylated aziridine 21 (306 mg, 0.72 mmol) was treated
with AcONa in DMF (13 mL) for 2.5 h. Chromatography (PE–
EtOAc, 75:25) afforded the acetylated derivative 24.
Yield: 317 mg (91%); gum; [a]D +14 (c 0.73, CHCl3); Rf = 0.32
(PE–EtOAc, 7:3).
MS (IS): m/z = 534.5 [M + NH4]+, 549.5 [M + MeOH + H]+.
IR (film): 3265 (NH), 1739 (COO), 1496, 1455 (Ar), 1335, 1162
(SO2) cm–1.
1H NMR: d = 1.29, 1.30, 1.38, 1.47 (4 × s, 12 H, 4 × CH3), 1.87 (s,
3 H, CH3CO2), 2.43 (s, 3 H, CH3-Ar), 3.75 (d, J4–5 = 8.2 Hz, 1 H, H-
4), 3.90 (dd, J6a–6b = 8.5 Hz, J6b-5 = 4.7 Hz, 1 H, H-6b), 4.04 (dd,
HRMS-ES: m/z [M + Na]+ calcd for C21H28N2O11SNa: 539.1312;
found: 539.1308.
De-O-acetylation; General Procedure
A solution of MeONa (0.8 equiv) in MeOH was added to a cooled
solution of the acetylated compound in MeOH. After the transfor-
mation, Amberlite® IR120 was added to neutrality, the solution was
filtered and concentrated in vacuo. The crude product was purified
by silica gel column chromatography.
J6a-5 = 6.3 Hz, 1 H, H-6a), 4.05–4.15 (m, 1 H, H-5), 4.17 (d, J7a–7b
=
11.9 Hz, 1 H, H-7b), 4.51 (d, 1 H, H-7a), 5.11 (d, J2–1 = 3.5 Hz, 1 H,
H-2), 5.22 (s, 1 H, NH), 5.74 (d, 1 H, H-1), 7.31 (d, Jvic = 8.3 Hz,
2 H, ArH), 7.79 (d, 2 H, ArH).
13C NMR: d = 20.8 (CH3COO), 21.6 (CH3-Ar), 25.0, 26.4, 26.6,
26.8 (4 × CH3), 63.8 (C-7), 67.9 (C-6), 70.8 (C-3), 73.0 (C-5), 82.4
(C-4), 82.8 (C-2), 105.1 (C-1), 110.1, 112.5 (2 × CIV), 127.1 (2 × C-
Ar), 129.7 (2 × C-Ar), 139.5 (CIV-Me), 143.7 (CIV-SO2), 170.7 (COO).
MS (IS): m/z = 486.5 [M + H]+, 503.5 [M + NH4]+.
HRMS-ES: m/z [M + Na]+ calcd for C22H31NO9SNa: 508.1617;
3-Deoxy-3-C-hydroxymethyl-1,2:5,6-di-O-isopropylidene-3-N-
p-toluenesulfonamido-a-D-glucofuranose (29)
Compound 24 (316 mg, 0.65 mmol) was methanolated in MeOH
(10 mL) for 1.5 h. Chromatography (PE–EtOAc, 3:2) afforded the
alcohol 29.
Yield: 280 mg (97%); solid; mp 57–60 °C; [a]D +10 (c 0.20,
CHCl3); Rf = 0.51 (PE–EtOAc, 6:4).
found: 508.1616.
IR (film): 3455 (NH, OH), 1455 (Ar), 1331, 1161 (SO2) cm–1.
3-C-Azidomethyl-3-deoxy-1,2:5,6-di-O-isopropylidene-3-N-p-
toluenesulfonamido-a-D-glucofuranose (25)
Compound 21 (0.3 g, 0.70 mmol) was treated with NaN3 in DMF
(13 mL) for 3.5 h. Chromatography (PE–EtOAc, 4:1) afforded the
azide 25.
1H NMR: d = 1.25, 1.29, 1.40, 1.46 (4 × s, 12 H, 4 × CH3), 2.43 (s,
3 H, CH3-Ar), 3.34 (dd, JOH–7b = 11.6 Hz, JOH–7a = 2.8 Hz, 1 H,
OH), 3.70 (dd, J7a–7b = 12.2 Hz, 1 H, H-7b), 3.76–3.83 (m, 2 H, H-
4, H-7a), 3.93–4.02 (m, 3 H, H-5, H-6a, H-6b), 5.06 (d, J2–1 = 3.5
Hz, H-2), 5.66 (s, 1 H, NH), 5.82 (d, 1 H, H-1), 7.32 (d, Jvic = 8.2
Hz, 2 H, ArH), 7.79 (d, 2 H, ArH).
Yield: 305 mg (93%); colourless oil; [a]D +29 (c 0.96, CHCl3);
Rf = 0.63 (PE–EtOAc, 7:3).
13C NMR: d = 21.5 (CH3-Ar), 24.9, 26.0 (2 × CH3), 26.4 (2 × CH3),
62.3 (C-7), 67.8 (C-6), 70.2 (C-3), 71.6 (C-5), 83.8 (C-4, C-2),
IR (film): 3264 (NH), 2107 (N3), 1496, 1455 (Ar), 1335, 1161 (SO2)
cm–1.
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3118
S. Tardy et al.
PAPER
104.6 (C-1), 110.2, 112.3 (2 × CIV), 127.0 (2 × C-Ar), 129.6 (2 × C-
IR (film): 3347 (NH), 1542 (NO2), 1357 (SO2) cm–1.
Ar), 139.3 (CIV-Me), 143.7 (CIV-SO2).
1H NMR: d = 1.07, 1.19, 1.40, 1.57 (4 × s, 12 H, 4 × CH3), 3.80 (d,
J4–5 = 9.7 Hz, 1 H, H-4), 3.87 (dd, J6a–6b = 8.8 Hz, J6b–5 = 5.6 Hz,
1 H, H-6b), 3.89 (d, J7a–7b = 12.2 Hz, 1 H, H-7b), 4.05 (d, 1 H, H-
7a), 4.20 (dd, J6a-5 = 6.3 Hz, 1 H, H-6a), 4.28–4.39 (m, 1 H, H-5),
4.91 (d, J2–1 = 3.5 Hz, 1 H, H-2), 5.80 (d, 1 H, H-1), 6.30 (s, 1 H,
NH), 7.67–7.73 (m, 2 H, ArH), 7.87–7.93 (m, 1 H, ArH), 8.13–8.17
(m, 1 H, ArH).
13C NMR: d = 25.0, 26.3 (2 × CH3), 26.4 (2 × CH3), 43.6 (C-7), 68.3
(C-3), 68.4 (C-6), 72.6 (C-5), 82.9 (C-4), 83.4 (C-2), 105.3 (C-1),
110.8, 112.7 (2 × CIV), 125.1 (ArC-3), 130.7 (ArC-6), 132.2 (ArC-
4), 132.9 (ArC-5), 137.0 (ArC-1), 147.3 (ArC-2).
MS (IS): m/z = 444.5 [M + H]+, 461.5 [M + NH4]+, 466.5 [M + Na]+.
HRMS-ES: m/z [M + Na]+ calcd for C20H29NO8SNa: 466.1512;
found: 466.1498.
3-Deoxy-3-C-hydroxymethyl-1,2:5,6-di-O-isopropylidene-3-N-
o-nitrobenzenesulfonamido-a-D-glucofuranose (30)
Compound 26 (404 mg, 0.78 mmol) in MeOH (9 mL) was meth-
anolated for 3 h. Chromatography (PE–EtOAc, 1:1) afforded the al-
cohol 30.
Yield: 342 mg (92%); pale-yellow amorphous solid; [a]D +14 (c
0.70, CHCl3); Rf = 0.35 (PE–EtOAc, 6:4).
MS (IS): m/z = 494.0 [M + H]+, 510.5 [M + NH4]+.
IR (film): 3436 (NH), 3322 (OH), 1539 (NO2), 1360 (SO2) cm–1.
HRMS-ES: m/z [M + Na]+ calcd for C19H25ClN2O9SNa: 515.0867;
found: 515.0853.
1H NMR: d = 1.26, 1.33, 1.38, 1.50 (4 × s, 12 H, 4 × CH3), 3.34 (dd,
JOH–7b = 11.6 Hz, JOH–7a = 2.8 Hz, 1 H, OH), 3.81–4.00 (m, 6 H, H-
4, H-6a, H-6b, H-5, H-7a, H-7b), 5.19 (d, J2–1 = 3.8 Hz, 1 H, H-2),
6.01 (d, 1 H, H-1), 6.24 (s, 1 H, NH), 7.72–7.77 (m, 2 H, ArH),
7.87–7.92 (m, 1 H, ArH), 8.12–8.18 (m, 1 H, ArH).
13C NMR: d = 25.0, 26.1 (2 × CH3), 26.6 (2 × CH3), 61.9 (C-7), 68.1
(C-6), 71.3 (C-5), 71.8 (C-3), 83.9 (C-4), 85.2 (C-2), 104.8 (C-1),
110.6, 112.7 (2 × CIV), 125.3 (ArC-3), 130.7 (ArC-6), 132.9 (ArC-
4), 133.6 (ArC-5), 136.1 (ArC-1), 147.7 (ArC-2).
3-C-Acetoxymethyl-3-deoxy-1,2:5,6-di-O-isopropylidene-3-N-
o-nitrobenzenesulfonamido-a-D-allofuranose (28)
Compound 27 (1.42 g, 2.88 mmol) in DMF (40 mL) was treated
with anhydrous AcONa (2.03 g, 24.7 mmol) at r.t. for 105 min. Af-
ter hydrolysis with H2O (350 mL), the resulting solution was ex-
tracted with EtOAc (4 × 80 mL). The combined organic phases
were washed with brine (3 × 100 mL), dried over MgSO4 then con-
centrated in vacuo. Chromatography (PE–EtOAc, 1:1) afforded
acetate 28.
MS (IS): m/z = 475.5 [M + H]+, 492.5 [M + NH4]+, 524.5 [M +
MeOH + NH4]+.
Yield: 1.426 g (96%); solid; mp 138–140 °C; [a]D +80 (c 0.81,
CHCl3); Rf = 0.42 (PE–EtOAc, 1:1).
IR (film): 3348 (NH), 1746 (COO), 1542 (NO2), 1360 (SO2) cm–1.
HRMS-ES: m/z [M + Na]+ calcd for C19H26N2O10SNa: 497.1206;
found: 497.1202.
1H NMR: d = 1.14, 1.18, 1.35, 1.54 (4 × s, 12 H, 4 × CH3), 1.97 (s,
3-Deoxy-3-C-hydroxymethyl-1,2:5,6-di-O-isopropylidene-3-N-
o-nitrobenzenesulfonamido-a-D-allofuranose (32)
Compound 28 (1.4 g, 2.71 mmol) was methanolated in MeOH (30
mL) for 4.5 h. Chromatography (PE–EtOAc, 1:1) afforded the alco-
hol 32.
3 H, CH3COO), 3.76 (d, J4–5 = 9.1 Hz, 1 H, H-4), 3.79 (dd, J6a–6b
=
8.2 Hz, J6b–5 = 5.3 Hz, 1 H, H-6b), 4.00–4.10 (m, 1 H, H-5), 4.14
(dd, J6a–5 = 6.3 Hz, 1 H, H-6a), 4.28 (d, J7a–7b = 11.9 Hz, 1 H, H-7b),
4.41 (d, 1 H, H-7a), 4.81 (d, J2–1 = 3.5 Hz, 1 H, H-2), 5.68 (d, 1 H,
H-1), 6.32 (s, 1 H, NH), 7.64–7.70 (m, 2 H, ArH), 7.84–7.90 (m,
1 H, ArH), 8.10–8.17 (m, 1 H, ArH).
13C NMR: d = 20.6 (CH3COO), 25.1 (CH3), 26.3 (3 × CH3), 63.0 (C-
7), 67.3 (C-6), 68.7 (C-3), 72.8 (C-5), 82.0 (C-4), 82.3 (C-2), 104.7
(C-1), 110.6, 112.5 (2 × CIV), 125.0 (ArC-3), 130.5 (ArC-6), 132.3
(ArC-4), 132.8 (ArC-5), 137.1 (ArC-1), 147.3 (ArC-2), 170.1
(COO).
Yield: 1.22 g (95%); white solid; [a]D +18 (c 0.22, CHCl3); mp 117–
119 °C; Rf = 0.36 (PE–EtOAc, 1:1).
IR (film): 3353 (NH, OH), 1542 (NO2), 1359 (SO2) cm–1.
1H NMR: d = 1.10, 1.12, 1.38, 1.56 (4 × s, 12 H, 4 × CH3), 2.73 (br
s, 1 H, OH), 3.76 (d, J4–5 = 9.4 Hz, 1 H, H-4), 3.82–4.01 (m, 3 H, H-
6b, H-7a, H-7b), 4.13–4.28 (m, 2 H, H-6a, H-5), 4.85 (d, J2–1 = 3.5
Hz, 1 H, H-2), 5.71 (d, 1 H, H-1), 6.29 (s, 1 H, NH), 7.67–7.73 (m,
2 H, ArH), 7.88–7.94 (m, 1 H, ArH), 8.15–8.20 (m, 1 H, ArH).
13C NMR: d = 25.1 (CH3), 26.3 (2 × CH3), 26.4 (CH3), 63.5 (C-7),
68.5 (C-6), 69.0 (C-3), 72.8 (C-5), 81.5 (C-4), 82.2 (C-2), 104.7 (C-
1), 110.7, 112.2 (2 × CIV), 125.1 (ArC-3), 130.8 (ArC-6), 132.2
(ArC-4), 132.9 (ArC-5), 136.8 (ArC-1), 147.4 (ArC-2).
MS (IS): m/z = 517.5 [M + H]+, 534.5 [M + NH4]+.
HRMS-ES: m/z [M + Na]+ calcd for C21H28N2O11SNa: 539.1312;
found: 539.1316.
3-Deoxy-1,2:5,6-di-O-isopropylidene-3,5¢-spiro(1¢-N-p-toluene-
sulfonyl-1¢,3¢-imidazolidine-2¢-thione)-a-D-glucofuranose (31)
An anhydrous 1,4-dioxane (5 mL) solution containing CS2 (280 mL,
4.7 mmol), azide 25 (115 mg, 0.25 mmol) and Ph3N (71 mg, 0.27
mmol) was heated for 2 h at 85 °C. After removal of the solvent, the
crude product was purified by chromatography (PE–EtOAc, 7:3) to
afford the imidazolidinethione 31.
MS (IS): m/z = 475.5 [M + H]+, 492.5 [M + NH4]+, 524.5 [M +
MeOH + NH4]+.
HRMS-ES: m/z [M + Na]+ calcd for C19H26N2O10SNa: 497.1206;
found: 497.1218.
Yield: 79 mg (65%); solid; mp 102–105 °C; [a]D –43 (c 1.1,
CHCl3); Rf = 0.56 (PE–EtOAc, 6:4).
3-C-Chloromethyl-3-deoxy-1,2:5,6-di-O-isopropylidene-3-N-o-
nitrobenzenesulfonamido-a-D-allofuranose (27)
A cooled solution (–78 °C) of spiro-aziridine 18 (745 mg, 2.74
mmol) in CH2Cl2 (40 mL), was treated with Et3N (1.3 mL, 9.35
mmol) and o-nitrobenzenesulfonyl chloride (1.03 g, 4.65 mmol)
and allowed to slowly come to r.t. overnight. After dilution with
CH2Cl2 (50 mL), the organic phase was washed with H2O (2 × 100
mL), then brine (1 × 50 mL), dried over MgSO4 and concentrated in
vacuo. Chromatography (PE–EtOAc, 75:25) afforded 27.
IR (film): 3374 (NH), 1534, 1259 (N–CS–N), 1494, 1455 (Ar),
1322, 1165 (SO2) cm–1.
1H NMR: d = 1.22, 1.37, 1.38, 1.51 (4 × s, 12 H, 4 × CH3), 2.44 (s,
3 H, CH3-Ar), 3.53 (d, J7a–7b = 11.3 Hz, 1 H, H-7b), 3.90 (d, J4–5
=
8.8 Hz, 1 H, H-4), 3.94 (dd, J6a–6b = 8.5 Hz, J6b–5 = 6.0 Hz, 1 H, H-
6b), 4.04 (dd, J6a–5 = 6.0 Hz, 1 H, H-6a), 4.07 (d, J7b–7a = 11.3 Hz,
1 H, H-7a), 4.18 (dt, 1 H, H-5), 5.33 (d, J2–1 = 3.8 Hz, 1 H, H-2),
6.21 (d, 1 H, H-1), 6.99 (s, 1 H, NH), 7.30 (d, Jvic = 8.2 Hz, 2 H,
ArH), 8.02 (d, 2 H, ArH).
Yield: 921 mg (68%); pale-yellow solid; mp 66–68 °C; [a]D +111
(c 0.85, CHCl3); Rf = 0.56 (PE–EtOAc, 6:4).
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

PAPER
Carbohydrate-Based Spiro-1,3-oxazolidine-2-thiones
3119
13C NMR: d = 21.8 (CH3-Ar), 25.1, 26.2, 26.6, 26.9 (4 × CH3), 47.9
(C-7), 68.0 (C-6), 72.9 (C-5), 81.3 (C-4), 85.4 (C-3), 86.8 (C-2),
106.3 (C-1), 110.0, 111.8 (2 × CIV), 129.1 (2 × ArC), 129.8 (2 ×
ArC), 136.3 (CIV-Me), 145.1 (CIV-SO2), 180.9 (CS).
MS (IS): m/z = 485.5 [M + H]+, 502.5 [M + NH4]+.
HRMS-ES: m/z [M + H]+ calcd for C21H28N2O7S2: 485.1416; found:
Conversion of Amino Alcohols into Spiro-oxazolidinethiones;
General Procedure
The b-amino alcohol, CaCO3 and thiophosgene were dissolved in
H2O–acetone (1:1), and stirred at r.t. overnight. The mixture was fil-
tered over a Celite® pad, which was then washed with acetone. After
evaporation of the solvent, the residue was purified by chromatog-
raphy on silica gel.
485.1424.
3-Deoxy-1,2:5,6-di-O-isopropylidene-3,4¢-spiro(1¢,3¢-oxazoli-
dine-2¢-thione)-a-D-glucofuranose (35)
The amino alcohol 33 (142 mg, 0.49 mmol) was treated with thio-
phosgene (94 mL, 1.23 mmol) and CaCO3 (428 mg, 4.27 mmol) in
H2O–acetone (1:1, 10 mL). Chromatography (PE–EtOAc, 65:35)
afforded the endo-spiro-OZT 35.
N-Deprotection of o-Nitrobenzenesulfonamides; General Pro-
cedure
A solution of the sulfonamide with thiophenol (3 equiv) and anhy-
drous K2CO3 (4 equiv) in MeCN was heated at 60 °C overnight. Af-
ter cooling to r.t., the mixture was filtered on a silica gel pad, which
was then rinsed with MeOH. The combined organic phase was con-
centrated in vacuo and the crude product was purified by column
chromatography on silica gel.
Yield: 127 mg (78%); solid; mp 71–74 °C; [a]D +13 (c 1.16,
CHCl3); Rf = 0.48 (PE–EtOAc, 65:35).
IR (film): 3148 (NH), 1520, 1164 (O-CS-N) cm–1.
3-Amino-3-deoxy-3-C-hydroxymethyl-1,2:5,6-di-O-isopropy-
lidene-a-D-glucofuranose (33)
The sulfonamide 30 (138 mg, 0.29 mmol) in MeCN (5 mL) was
treated with thiophenol (90 mL, 0.88 mmol) and K2CO3 (161 mg,
1.16 mmol). Chromatography (CH2Cl2–MeOH, 19:1) afforded the
amino-alcohol 33.
1H NMR: d = 1.29, 1.31, 1.40, 1.47 (4 × s, 12 H, 4 × CH3), 3.79 (d,
J4–5 = 8.8 Hz, 1 H, H-4), 3.95 (dd, J6a–6b = 8.5 Hz, J6b–5 = 4.7 Hz,
1 H, H-6b), 4.12 (dd, J6a–5 = 6.3 Hz, 1 H, H-6a), 4.15–4.25 (m, 1 H,
H-5), 4.53 (d, J2–1 = 3.5 Hz, 1 H, H-2), 4.74 (d, J7a–7b = 9.6 Hz, 1 H,
H-7b), 4.86 (d, 1 H, H-7a), 5.85 (d, 1 H, H-1), 9.48 (s, 1 H, NH).
13C NMR: d = 25.0, 26.3, 26.6, 26.8 (4 × CH3), 67.8 (C-6), 72.3 (C-
7), 72.4 (C-3), 73.0 (C-5), 80.0 (C-4), 84.7 (C-2), 104.2 (C-1),
110.1, 113.1 (2 × CIV), 190.1 (CS).
Yield: 67 mg (80%); solid; mp 106–107 °C; [a]D +26 (c 0.42,
CHCl3).
IR (film): 3456 (NH2, OH), 1599 (NH2) cm–1.
1H NMR: d = 1.31, 1.36, 1.43, 1.52 (4 × s, 12 H, 4 × CH3), 1.99 (br
s, 3 H, OH, NH2), 3.70–3.85 (m, 2 H, H-7a, H-7b), 3.81 (d, J4–5
8.8 Hz, 1 H, H-4), 4.00–4.09 (m, 1 H, H-5), 4.10–4.22 (m, 2 H, H-
6a, H-6b), 4.28 (d, J2–1 = 3.8 Hz, 1 H, H-2), 5.84 (d, 1 H, H-1).
13C NMR: d = 25.2, 26.4, 26.7, 27.0 (4 × CH3), 64.4 (C-7), 65.2 (C-
3), 68.3 (C-6), 72.4 (C-5), 82.9 (C-4), 87.9 (C-2), 104.5 (C-1),
109.9, 112.6 (2 × CIV).
MS (IS): m/z = 290.5 [M + H]+, 322.5 [M + MeOH + H]+.
HRMS-ES: m/z [M + H]+ calcd for C13H24NO6: 290.1604; found:
MS (IS): m/z = 332.5 [M + H]+, 349.0 [M + NH4]+.
Anal. Calcd for C14H21NO6S: C, 50.74; H, 6.39; N, 4.23; S, 9.68.
Found: C, 51.01; H, 6.44; N, 4.10; S, 9.25.
HRMS-ES: m/z [M + H]+ calcd for C14H22NO6S: 332.1168; found:
=
332.1177.
3-Deoxy-1,2:5,6-di-O-isopropylidene-3,4¢-spiro(1¢,3¢-oxazoli-
dine-2¢-thione)-a-D-allofuranose (36)
The amino alcohol 34 (53 mg, 0.183 mmol) was treated with thio-
phosgene (38 mL, 0.5 mmol) and CaCO3 (165 mg, 1.65 mmol) in
H2O–acetone (1:1, 3.5 mL). Chromatography (PE–EtOAc, 3:2) af-
forded the the endo-spiro-OZT 36.
290.1604.
3-Amino-3-deoxy-3-C-hydroxymethyl-1,2:5,6-di-O-isopropy-
lidene-a-D-allofuranose (34)
Yield: 43 mg (70%); solid; mp 242–244 °C; [a]D +116 (c 1.04,
CHCl3); Rf = 0.38 (PE–EtOAc, 6:4).
The sulfonamide 32 (1.206 g, 2.54 mmol) in MeCN (42 mL) was
treated with thiophenol (835 mL, 8.13 mmol) and K2CO3 (1.58 g,
11.43 mmol). Chromatography (CH2Cl2–MeOH, 96:4) afforded the
amino-alcohol 34.
IR (film): 3266 (NH), 1504, 1163 (O–CS–N) cm–1.
1H NMR: d = 1.33, 1.35, 1.46, 1.58 (4 × s, 12 H, 4 × CH3), 3.85 (d,
J4–5 = 7.9 Hz, 1 H, H-4), 3.97 (dd, J6a–6b = 11.6 Hz, J6b–5 = 6.9 Hz,
1 H, H-6b), 4.13–4.21 (m, 2 H, H-6a, H-5), 4.36 (d, J7a–7b = 9.7 Hz,
1 H, H-7b), 4.50 (d, J2–1 = 3.8 Hz, 1 H, H-2), 4.87 (d, 1 H, H-7a),
5.74 (d, 1 H, H-1), 7.68 (s, 1 H, NH).
Yield: 695 mg (95%); colourless oil; [a]D +18 (c 0.22, CHCl3).
IR (film): 3372 (NH2, OH), 1586 (NH2) cm–1.
1H NMR: d = 1.34 (s, 6 H, 2 × CH3), 1.44, 1.56 (2 × s, 6 H, 2 × CH3),
13C NMR: d = 25.0, 26.4, 26.6, 26.8 (4 × CH3), 68.4 (C-6), 70.8 (C-
3), 73.0 (C-7), 73.4 (C-5), 78.1 (C-4), 84.6 (C-2), 103.1 (C-1),
110.5, 113.9 (2 × CIV), 189.4 (CS).
2.20 (br s, 3 H, OH, NH2), 3.39 (d, J7a–7b = 11.0 Hz, 1 H, H-7b), 3.72
(d, J4–5 = 9.1 Hz, 1 H, H-4), 3.73 (d, 1 H, H-7a), 3.89 (dd, J6a–6b
=
8.5 Hz, J6b–5 = 5.0 Hz, 1 H, H-6b), 3.98–4.06 (m, 1 H, H-5), 4.12
(dd, J6a–5 = 6.0 Hz, 1 H, H-6a), 4.58 (d, J2–1 = 3.8 Hz, 1 H, H-2),
5.76 (d, 1 H, H-1).
MS (IS): m/z = 332.5 [M + H]+, 349.0 [M + NH4]+.
Anal. Calcd for C14H21NO6S: C, 50.74; H, 6.39; N, 4.23; S, 9.68.
Found: C, 50.64; H, 6.34; N, 4.16; S, 9.32.
HRMS-ES: m/z [M + Na]+ calcd for C14H21NO6SNa: 354.0987;
13C NMR: d = 25.2, 26.3, 26.8, 26.9 (4 × CH3), 61.9 (C-7), 64.4 (C-
3), 68.8 (C-6), 73.5 (C-5), 81.9 (C-4), 82.9 (C-2), 104.0 (C-1),
109.8, 112.2 (2 × CIV).
found: 354.0976.
MS (IS): m/z = 290.5 [M + H]+, 322.5 [M + MeOH + H]+.
HRMS-ES: m/z [M + Na]+ calcd for C13H23NO6Na: 312.1423;
found: 312.1426.
Acknowledgment
The authors would like to thank the CNRS, the Université d’Orléans
and the ANR for financial support.
Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York

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S. Tardy et al.
PAPER
(5) (a) Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chaudhary,
K. J. Org. Chem. 2001, 66, 894. (b) Crimmins, M. T.;
McDougall, P. J. Org. Lett. 2003, 5, 591. (c) Crimmins, M.
T.; Katz, J. D.; Washburn, D. G.; Allwein, S. P.; McAtee, L.
F. J. Am. Chem. Soc. 2002, 124, 5661.
(6) For examples, see: (a) Saito, Y.; Zevaco, T. A.; Agrofoglio,
L. A. Tetrahedron 2002, 58, 9593. (b) Mio, S.; Kumagawa,
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Synthesis 2008, No. 19, 3108–3120 © Thieme Stuttgart · New York