New synthesis of 2,6-anhydro-β-D-fructofuranoses, pivotal [2.2.1] bicyclic acetals for the conversion of D-fructose into 2,2,5-trisubstituted tetrahydrofurans

Article abstract of DOI:10.1016/S0040-4020(02)00233-8

2,6-Anhydro-β-D-fructofuranose derivatives were prepared by a novel tin-promoted 2,5-cyclisation of phenyl 2-thio-β-D-fructopyranosides. They were regioselectively opened by allyltrimethylsilane in the presence of catalytic Sc(OTf)₃ to give 2,2,5-trisubstituted tetrahydrofurans in high yields and major α-stereoselectivity.

Full text of DOI:10.1016/S0040-4020(02)00233-8

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 3629±3637
New synthesis of 2,6-anhydro-b-d-fructofuranoses, pivotal [2.2.1]
bicyclic acetals for the conversion of d-fructose into
2,2,5-trisubstituted tetrahydrofurans
p
 Â
Á
Fabrice Goursaud, Frederic Peyrane and Alain Veyrieres
Á Â Â
Laboratoire de Syntheses et Activations de Biomolecules, CNRS UMR 6052, Ecole Nationale Superieure de Chimie de Rennes,
Campus de Beaulieu, 35700 Rennes, France
Received 31 October 2001; revised 31 January 2002; accepted 26 February 2002
AbstractÐ2,6-Anhydro-b-d-fructofuranose derivatives were prepared by a novel tin-promoted 2,5-cyclisation of phenyl 2-thio-b-d-fructo-
pyranosides. They were regioselectively opened by allyltrimethylsilane in the presence of catalytic Sc(OTf)3 to give 2,2,5-trisubstituted
tetrahydrofurans in high yields and major a-stereoselectivity. q 2002 Elsevier Science Ltd. All rights reserved.
The synthesis of functionalized tetrahydrofuran rings has
received considerable attention because of their presence
in many biologically active compounds.1 Polyether anti-
biotics, such as lonomycin C, ionomycin or monensin,
contain 2,5-di and 2,2,5-trisubstituted tetrahydrofuran
units2 which can be obtained by C-glycosylation techniques.
Nucleophilic substitution at the anomeric centre of a carbo-
hydrate derivative can be to this respect an excellent
strategy, provided that the required furanosides are readily
attainable. We have recently shown3 that iodocyclisation of
6-O-protected d-galactal, followed by radical reduction,
affords [2.2.1] bicyclic acetals which are then regio-
selectively opened by various nucleophiles in the presence
of an acid promoter to give exclusively furanosyl
compounds. A 2,5-di-substituted tetrahydrofuran fragment
of annonaceous acetogenins was thus prepared from
d-galactal in a limited number of steps.4 Extension of
these reactions to ketose derivatives should lead to 2,2,5-
trisubstituted tetrahydrofurans which have been only
scarcely obtained5,6 by C-glycosylation of furanose
precursors.
In 1960 Goldschmid and Perlin7 reported the isolation of
crystalline 2,6-anhydro-b-d-fructofuranose (or 2,5-
anhydro-a-d-fructopyranose)
1 in 9% yield among
the products obtained by thermolysis of sucrose at
1808C. Acidic ethanolysis of 1 gave rapidly ethyl a-d-
fructofuranoside 2 which slowly anomerized to the
b-isomer (Scheme 1). Later on, 1 could be prepared8,9 in
better yields under modi®ed conditions of sucrose
thermolysis; chromatography techniques were however
required for its isolation. Vacuum pyrolysis of free ketoses
gives the corresponding 2,6-anhydrofuranoses in very low
yields.10
Scheme 1.
Keywords: allylation; bicyclic heterocyclic compounds; thioglycosides; tin and compounds.
Corresponding author. Tel.: 133-22-323-8075; fax: 133-22-323-8046
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00233-8

3630
F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
Scheme 2. Reagents and conditions: (i) PhSH (1.4 equiv.), BF3´OEt2 (2.9 equiv.), CH2Cl2, 08C!rt, 4 h; (ii) PhSH (1.5 equiv.), BF3´OEt2 (5.4 equiv.), CH2Cl2,
08C!rt, 8 h.
Scheme 3. Reagents and conditions: (i) PhSH (3.1 equiv.), BF3´OEt2 (9.1 equiv.), CH2Cl2, rt, 14 h; (ii) 5:1:1 MeOH±NEt3±H2O, 408C.
We now report a new access to various [2.2.1] bicyclic
acetal derivatives of d-fructose based on the chemistry of
2-thio-b-d-fructopyranosides.
apparent on t.l.c. (,14 h); prolonged treatment usually
brought extensive decomposition. Deacetylation of the
crude mixture of 4 and 5 gave crystalline thioglycosides 6
and 7 which were readily separated by extraction of 6 (41%)
in hot water and crystallization of residual 7 (51%) from
ethanol (Scheme 3).
Benzyl 2-thio-b-d-fructopyranoside is the only reported11
2-thio-d-fructopyranoside; it was isolated in 10% yield
among a mixture of thermodynamically equilibrated glyco-
sides obtained by addition of a-toluenethiol to d-fructose in
DMSO at 608C. We envisaged that crystalline 20-chloro-
ethyl b-d-fructopyranoside, readily prepared12,13 from
d-fructose in high yield, could be a convenient precursor
of 2-thio-d-fructopyranosides, since glycosides of ketoses
exhibit a high acid lability due to the easy formation of a
tertiary oxycarbenium ion.12 The standard Ferrier condi-
tions14 (thiophenol, BF3´OEt2 as a promoter in CH2Cl2 at
room temperature) allowed indeed the conversion of the
acetylated derivative 3 of 20-chloroethyl b-d-fructopyrano-
side into the 2-thio-b-d-fructopyranoside 4 in 74% yield.
But further treatment of 4 with BF3´OEt2 and thiophenol
gave the 1,2-dithio compound 5 in 54% yield together
with unreacted 4 (Scheme 2). Migrations of anomeric sulfur
atoms have been often reported15 among 1-thio-aldoglyco-
sides, but only once for an heptulopyranose derivative.16 In
the case of 4, the addition of a second molecule of thiol
occurs exclusively from the b-face delivering compound 5
stabilized by the anomeric effect of the sulfur atom, which
implies that a 1,2-episulfonium intermediate A must be in
equilibrium with an oxycarbenium ion B.17
Treatment of polyols with (Bu3Sn)2O is known18 to give an
equilibrium of partially O-stannylated products, which then
reacts regioselectively with an electrophile in an inter- or
intramolecular reaction. When thioglycosides 6 and 7 were
reacted with (Bu3Sn)2O (1 mol equiv.) in boiling propio-
nitrile, smooth 2,5-cyclisation occurred to give the bicyclic
acetals 1 (94%) and 8 (85%), respectively (Scheme 4).
Remarkably, no electrophilic activation of the anomeric
sulfur was found to be necessary. The driving force of
these unprecedented cyclisations must be the formation of
the thermodynamically stable Sn±S bond19 (Bu3SnSPh was
indeed isolated from reaction mixtures); but the 2,5-trans
diaxial con®guration of reacting oxygen and sulfur atoms
and the higher lability of anomeric groups in ketosides are
also crucial. A 6-O-protected phenyl 1-thio-a-d-galacto-
pyranoside20 did not undergo cyclisation under the above
conditions.
2C5 (d) Chair conformations of thioglycosides 4 and 5 were
ascertained by the respective values of coupling constant
J3,4 10.2 and 9.7 Hz and their b-con®guration by the values
of [a]d 2200 and 2113. For preparative purposes it was
found more advantageous to perform the addition of thio-
phenol (3.1 equiv.) to compound 3 in the presence of a large
excess of BF3´OEt2 (9.1 equiv.) and to let the reaction go
until a ,1:1 mixture of 4 and 5 with only traces of 3 became
Scheme 4. Reagents and conditions: (i) (Bu3Sn)2O (1 mol equiv.), EtCN,
Ê
4 A mol. sieves, re¯ux; (ii) BnBr, NaH, DMF, rt; (iii) Raney Ni, THF, rt.

F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
3631
Ê
Scheme 5. Reagents and conditions: (i) Bu2SnO (1.2 equiv.), CH3CN, 4 A mol. sieves, re¯ux, then BzCl (1.5 equiv.), rt; (ii) (Bu3Sn)2O (1 mol equiv.), EtCN,
Ê
4 A mol. sieves, re¯ux; (iii) Bu2SnO (1.3 equiv.), MeOH, re¯ux, then concentration, BnBr (1.5 equiv.), CsF (1.3 equiv.), DMF, rt; (iv) Ac2O, pyridine, rt.
Acetals 1 and 8 were O-benzylated to give 9 (67%) and 10
(85%) respectively. Desulfurization of 10 with Raney nickel
in THF gave acetal 11 with an angular methyl groupin 62%
yield (Scheme 4).
observed22 in carbohydrates, but does not apply to more
¯exible systems (phenylethylene glycol).23
4-O-Benzyl derivatives 19 (57%) and 21 (42%) were also
obtained by reaction of the stannylene derivatives of 6 and 7
with benzyl bromide in re¯uxing acetonitrile (Scheme 5);
the moderate yields can be attributed to side reactions of the
anomeric thiophenyl group leading to sulfonium salts. The
yield of 21 could be slightly improved (58%) by performing
benzylation of 7 in DMF at room temperature under CsF
activation.24 Conversion of triol 19 into the acetylated
derivative 20 allowed to ascertain the location of benzyl
groupat O-4 (H-4 at d 3.94), H-3 and H-5 being respec-
tively deshielded at d 5.66 and 5.41 by acetyl groups.
Treatment of thioglycosides 6 and 7 with Bu2SnO induced
no cyclisation; mixtures of dibutylstannanediyl acetals
(`stannylene') thus obtained18 reacted rather with benzoyl
chloride preferentially at equatorial O-4 to give respectively
13 (69%) and crystalline 15 (70%), where signals of H-4 at
d 5.24 and 5.42 were largely deshielded by the benzoyl
group(Scheme 5). In the case of 6, a 1,4-di-O-benzoyl
derivative 14 (26%) was also isolated. The postulated tin
derivative 12 obtained by opening of the 4,5-stannylene ring
did not undergo cyclisation even after prolonged heating,
most probably because the electron-attracting in¯uence of
the chlorine atom reduced too much the nucleophilicity of
O-5.
Thioglycoside 21 underwent cyclisation by treatment with
(Bu3Sn)2O to give the bicyclic acetal 22 in 85% yield.
Raney nickel desulfurization of 22 gave the deoxy
compound 23 in modest yield (40%); a side radical elimina-
tion led to a tetrahydrofuran intermediate with an exo
methylene group, which was reduced into 2,5-anhydro-1-
deoxy-d-mannitol 24 (Scheme 6).
Treatment of the 4-O-benzoyl compounds 13 and 15 with
(Bu3Sn)2O induced no cyclisation either, but gave orthoester
intermediates 16 which were hydrolyzed regioselectively21
during work-upto give the 5- O-benzoyl isomers 17 (70%)
and 18 (70%) respectively, where signals of H-5 at d 5.31
and 5.49 con®rmed the 4!5 migration of the benzoyl group
(Scheme 5). The absence of migration (and cyclisation as
well) in intermediates such as 12 has already been
Its methyl group appeared as a doublet (Jˆ6.6 Hz) at d 1.30
1
in H NMR spectrum and gave a 13C signal at d 18.63. A
minor product, C-2 epimer of 24 (a±b,9:1), gave corre-
sponding signals at dH 1.29 (Jˆ6.4 Hz) and dC 13.34. The
Ê
Scheme 6. Reagents and conditions: (i) (Bu3Sn)2O (1 equiv.), EtCN, 4 A mol. sieves, re¯ux; (ii) Raney Ni, THF, rt.

3632
F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
Scheme 7. Reagents and conditions: (i) Me3SiCH2CHvCH2 (5 equiv.), Sc(OTf)3 (0.1 equiv.), CH2Cl2, 230!08C, then MeOH±AcOH.
d-manno con®guration (a-methyl) of major 24 could be
deduced by the higher value of the 13C signal of its methyl
group( Dd 15.29 ppm), since the 13C chemical shift of the
carbon atom attached to the `anomeric position' of C-glyco-
sides and C-nucleosides is at higher ®eld when this atom has
any chelation at the opposite of carbohydrate bicyclic
acetals; coordination of O-1 and O-3 to Sc in intermediate
C might contribute to the increase of diastereoisomeric
excess when going from TMS tri¯ate to Sc(OTf)3 (de 46
vs 64%).
5,25,26
a cis-relationshipwith the OR-groupattached at C-3.
Acetal 11 reacted with allyltrimethylsilane in the presence
of catalytic Sc(OTf)3 to give the tetrahydrofuran compound
26 (79%, a±b 67:33). Diastereoisomers 26a and 26b were
separated by chromatography and showed optical rotation
values [a]d149 and136 respectively. Their ®ve-membered
ring structure was ascertained as follows: addition of
trichloroacetyl isocyanate (Cl3CCONCO) to 1H NMR
samples induced Dd 10.7 and 10.5±0.6 ppm shifts of
H-6a and H-6b signals due to the formation of a carbamate
function at O-6; H-5 underwent only a 0.1 ppm shift,
whereas the presence of a carbamate group at O-5 of a
six-membered ring isomer would have shifted it more
The reaction of [2.2.1] bicyclic acetals 9, 11 and 23 with
allyltrimethylsilane in the presence of a Lewis acid revealed
a total regioselectivity leading exclusively to 2,2,5-tri-
substituted tetrahydrofuran derivatives 25, 26 and 27
respectively (Scheme 7).
When conducted with TMS tri¯ate as a promoter, allylation
of 9 in acetonitrile or CH2Cl2 gave 25 in 63% yield (a±b
73:27). Con®guration at the `anomeric center' was
ascertained as above for compound 24; 13C NMR signal
of allylic CH2 appeared at lower ®eld (d 39.76) in the
major a-C-allyl glycoside than in the b-isomer (d 37.61).
Yield and stereoselectivity were both increased when
catalytic Sc(OTf)3 was used (83%, a±b 82:18). Lanthanide
tri¯ates are known to catalyze allylation reactions of car-
bonyl compounds27,28 and aldehyde acetals, but not ketone
dimethyl acetals.29 Coordination of the small Sc(III) cation
at the more nucleophilic O-6 atom induces formation of the
®ve-membered cyclic oxycarbenium ion C which is
preferentially attacked by the nucleophile on its less
hindered a-face with concomitant formation of TMS
tri¯ate. The Sc alkoxide then reacts with TMS tri¯ate to
regenerate Sc(OTf)3 and deliver the 6-O-trimethylsilyl
derivative 25a which can be visualized by tlc and is
converted to 25 by acid treatment (Scheme 8).
than 1 ppm. 13C NMR signals of the methyl groupat
d
21.27 and 23.31 and allylic CH2 at d 43.19 and 41.22 in
a- and b-products respectively con®rmed the attribution of
con®guration.
Finally, acetal 23 with a free OH-3 groupgave under
Sc(OTf)3-promoted allylation a 70:30 mixture of a- and
b-C-allyl furanosides 27 in 85% yield.
In conclusion, the opening reaction of now easily accessible
2,6-anhydro-b-d-fructofuranoses by allyltrimethylsilane in
the presence of catalytic Sc(OTf)3 occurs with a total regio-
selectivity and an acceptable a-stereoselectivity, leading to
2,2,5-trisubstituted tetrahydrofurans in high yield. Other
C-nucleophiles, such as 2-(trimethylsilyloxy)furan and
various silyl enolates, might lead to highly functionalized
fragments of natural products. The 2!1 migration of
anomeric phenylthio group in d-fructopyranosides can
probably be extended to other thiols and PhSeH, offering
better opportunities for radical reduction and coupling
reactions at C-1.
Yamamoto30 has reported stereoselective reductions of
bicyclic acetals by DIBAH or Et3SiH±TiCl4 in CH2Cl2;
the total lack of regioselectivity in the case of a [2.2.1]
bicyclic acetal is striking and can be probably attributed
to the bigger size of Al and Ti Lewis acids when compared
to Sc cation. The absence of oxygen substituents precludes
Scheme 8.

F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
3633
1. Experimental
1.1. General methods
(0.86 mL, 6.8 mmol) was added dropwise under stirring to
a solution of 4 (1 g, 2.3 mmol) and thiophenol (0.36 mL,
3.5 mmol) in dry CH2Cl2 (10 mL) at 08C under nitrogen.
The mixture was stirred at room temperature for 8 h, further
additions of boron tri¯uoride etherate (2£0.35 mL,
2£2.8 mmol) being made after 2 and 5 h. The solution
was worked up as described for the preparation of 4. The
residue was puri®ed by chromatography (CH2Cl2±Et2O,
97:3) to give 5 (0.6 g, 54%) as an amorphous solid; Rf
Melting points were determined using a Ko¯er hot stage
apparatus under a Reichert microscope and are uncorrected.
Optical rotations were measured at room temperature on a
Perkin±Elmer 341 automatic polarimeter (concentration in
g/100 mL). NMR spectra were recorded on a Bruker
ARX-400 instrument. 1H NMR were obtained at
1
0.52 (CH2Cl2±Et2O, 95:5); [a]d 2113 (c 1, CHCl3); H
NMR (CDCl3): d 7.40±7.06 (m, 10H, 2Ph), 6.01 (d, 1H,
J3,4ˆ9.7 Hz, H-3), 5.35±5.32 (m, 2H, H-4,5), 4.42 (d, 1H,
J6a,6bˆ13 Hz, H-6a), 3.79 (dd, 1H, J5,6bˆ1.5 Hz, H-6b), 3.32
(d, 1H, J1a,1bˆ13.7 Hz, H-1a), 3.07 (d, 1H, H-1b), 2.10, 2.03
and 1.95 (3 s, 9H, 3 OAc); 13C NMR (CDCl3): d 170.52,
170.15 and 169.45 (3CvO), 136.78 and 135.98 (2C quat.
arom.), 130.15, 129.12, 129.09, 129.05, 129.01, 128.62,
128.26, 126.27 and 125.34 (10C arom.), 93.54 (C-2),
69.48, 68.85 and 68.29 (C-3,4,5), 63.02 (C-6), 42.77
(C-1), 21.07, 20.91 and 20.75 (3 CH3CO). Anal. Calcd for
C24H26O7S2: C, 58.76; H, 5.34. Found: C, 58.68; H, 5.35.
400.13 MHz
(sˆ
singlet,
dˆdoublet,
tˆtriplet,
mˆmultiplet, bdˆbroad). Assignments were con®rmed by
homonuclear 2D COSY correlated experiments. 13C NMR
were obtained at 100.62 MHz in the proton-decoupled
mode. Heteronuclear 2D correlated spectra were recorded
in order to assist in carbon resonance assignments.
Chemical shifts are given in ppm relative to internal TMS
(d scale) and coupling constants (J) in Hz. Thin layer
chromatography (TLC) was performed on Merck DC-
Alufolien Kieselgel 60 F254 Art. 5554 with detection by
UV light and charring with 1:10 H2SO4±EtOH. Flash
chromatography was performed on Merck Kieselgel 60
(40±63 mm). All solvents were dried and distilled according
to standard laboratory procedures. Elemental analyses were
performed by the Service de Microanalyse du Centre
National de la Recherche Scienti®que (Gif-sur-Yvette,
France). High resolution mass spectra (HRMS) were obtained
by electrospray ionization (ESI) in a positive mode on a MS/
MS ZABSpec TOF spectrometer (Micromass) at the Centre
1.1.3. Phenyl 2-thio-b-d-fructopyranoside (6) and phenyl
1-deoxy-1-phenylthio-2-thio-b-d-fructopyranoside (7).
Boron tri¯uoride etherate (5.6 mL, 44.6 mmol) was added
dropwise under stirring to a solution of 3 (2 g, 4.9 mmol)
and thiophenol (1.55 mL, 15.2 mmol) in dry CH2Cl2
(20 mL). The mixture was stirred for 14 h at room tempera-
ture, then worked up as described for the preparation of 4. A
solution of the residue in MeOH±NEt3±H2O (5:1:1, 35 mL)
was heated for 16 h at 408C, then concentrated. The result-
ing solid was extracted several times with hot water, then
crystallized from ethanol to give 7 (0.9 g, 51%); Rf 0.50
(CH2Cl2-MeOH, 9:1); mp165±166 8C; [a]d 2122 (c 1,
Â
Regional de Mesures Physiques de l'Ouest.
1.1.1. Phenyl 1,3,4,5-tetra-O-acetyl-2-thio-b-d-fructo-
pyranoside (4). Boron tri¯uoride etherate (1.78 mL,
14.2 mmol) was added dropwise under stirring to a solution
of 20-chloroethyl 1,3,4,5-tetra-O-acetyl-b-d-fructopyrano-
side 3 (Ref. 12, 2 g, 4.9 mmol) and thiophenol (0.73 mL,
7.1 mmol) in dry CH2Cl2 (11 mL) at 08C under nitrogen.
The mixture was stirred at room temperature for 4 h, then
diluted with CH2Cl2 (20 mL) and washed with saturated
aqueous NaHCO3 (25 mL) until neutral. The aqueous
phase was extracted with CH2Cl2 (30 mL) and the combined
organic extracts were dried (MgSO4), then concentrated.
The residue was crystallized from ethanol to give 4
(1.09 g, 51%); Rf 0.69 (CH2Cl2-Et2O, 9:1); mp130±
1318C; [a]d 2200 (c 1, CHCl3); 1H NMR (CDCl3): d
7.46±7.30 (m, 5H, Ph), 5.77 (d, 1H, J3,4ˆ10.2 Hz, H-3),
5.43 (m, 1H, H-5), 5.41 (dd, 1H, J4,5ˆ3.3 Hz, H-4), 4.58
(dd, 1H, J5,6aˆ1 Hz, J6a,6bˆ13 Hz, H-6a), 4.35 (d, 1H,
J1a,1bˆ12.2 Hz, H-1a), 3.96 (dd, 1H, J5,6bˆ1.8 Hz, H-6b),
3.89 (d, 1H, H-1b), 2.16, 2.10, 2.07 and 2.01 (4 s, 12H, 4
OAc); 13C NMR (CDCl3): d 170.40, 170.27, 170.07 and
169.48 (4CvO), 135.82 (C quat. arom.), 129.32, 129.18
and 128.07 (5C arom.), 91.31 (C-2), 69.03, 68.89, 66.44,
65.40 and 63.22 (C-1,3,4,5,6), 20.99, 20.81, 20.75 and 20.73
(4 CH3CO). Anal. Calcd for C20H24O9S: C, 54.54; H, 5.49.
Found: C, 54.55; H, 5.48.
1
MeOH); H NMR (CD3OD): d 7.51±7.08 (m, 10H, 2Ph),
4.48 (d, 1H, J3,4ˆ9.9 Hz, H-3), 4.42 (dd, 1H, J5,6aˆ1.3 Hz,
J6a,6bˆ12.5 Hz, H-6a), 3.98 (m, 1H, H-5), 3.88 (dd, 1H,
J4,5ˆ3.3 Hz, H-4), 3.78 (dd, 1H, J5,6bˆ1.8 Hz, H-6b), 3.58
(d, 1H, J1a,1bˆ13.5 Hz, H-1a), 3.24 (d, 1H, H-1b); 13C NMR
(CD3OD): d 137.26 (2C quat. arom.), 131.88, 130.31,
129.87, 129.65, 129.60 and 126.71 (10C arom.), 97.34
(C-2), 72.06 (C-4), 70.87 (C-5), 70.45 (C-3), 66.91 (C-6),
42.96 (C-1). Anal. Calcd for C18H20O4S2: C, 59.32; H, 5.53.
Found: C, 59.23; H, 5.54.
The cooled aqueous ®ltrate was extracted with EtOAc, then
concentrated. The residue was crystallized from ethanol to
give 6 (0.54 g, 41%); Rf 0.22 (CH2Cl2±MeOH, 9:1); mp
1
205±2078C; [a]d 2277 (c 1, MeOH); H NMR (CD3OD):
d 7.49±7.30 (m, 5H, Ph), 4.47 (dd, 1H, J5,6aˆ1.4 Hz,
J6a,6bˆ12.4 Hz, H-6a), 4.28 (d, 1H, J3,4ˆ10 Hz, H-3), 3.95
(m, 1H, H-5), 3.88 (dd, 1H, J4,5ˆ3.5 Hz, H-4), 3.86 (d, 1H,
J1a,1bˆ11.7 Hz, H-1a), 3.80 (dd, 1H, J5,6bˆ1.9 Hz, H-6b),
3.43 (d, 1H, H-1b); 13C NMR (CD3OD): d 137.01 (C
quat. arom.), 131.67, 129.68 and 129.39 (5C arom.), 96.25
(C-2), 72.02 (C-4), 71.04 (C-5), 69.23 (C-3), 66.60 (C-6),
66.03 (C-1). Anal. Calcd for C12H16O5S: C, 52.93; H, 5.92.
Found: C, 52.86; H, 5.94.
The mother liquors were chromatographed on silica gel
(CH2Cl2±Et2O, 95:5) to give a further amount of 4
(0.49 g, 23%).
1.1.4. 2,6-Anhydro-b-d-fructofuranose (1). A mixture of
thioglycoside 6 (0.5 g, 1.8 mmol), (Bu3Sn)2O (0.94 mL,
Ê
1.8 mmol) and activated 4 A powdered molecular sieves
(2 g) in dry propionitrile (25 mL) was heated at re¯ux for
1.1.2. Phenyl 3,4,5-tri-O-acetyl-1-deoxy-1-phenylthio-2-
thio-b-d-fructopyranoside (5). Boron tri¯uoride etherate

3634
F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
20 h under vigorous stirring. The suspension was cooled,
then ®ltered. The ®ltrate was concentrated and the residue
was vigorously stirred for 1 h at room temperature in
petroleum ether±H2O (1:1, 30 mL). The aqueous phase
was evaporated under reduced pressure to give 1 (0.28 g,
94%) as an oil; Rf 0.38 (CH2Cl2±MeOH, 4:1); [a]d 2110 (c
0.5, MeOH); lit.7 mp118±119 8C, [a]d 2107 (c 1, H2O); 1H
to a solution of diol 8 (575 mg, 2.26 mmol) and benzyl
bromide (0.65 mL, 5.43 mmol) in dry DMF (3 mL) at
08C. The mixture was stirred at room temperature for 1 h,
then worked up as described for the preparation of 9. The
residue was puri®ed by chromatography (CH2Cl2±Et2O,
95:5) to give 10 (837 mg, 85%) as an oil; Rf 0.72 (petroleum
1
ether±EtOAc, 1:1); [a]d 243 (c 0.99, CHCl3); H NMR
NMR (CD3OD):
d
4.50 (dd, 1H, J3,5ˆ1.6 Hz,
(CDCl3): d 7.43±7.15 (m, 15H, 3Ph), 4.69 (dd, 1H,
J3,5ˆ1.6 Hz, J5,6exoˆ4.2 Hz, H-5), 4.51 and 4.42 (2d, 2H,
Jˆ12 Hz, CH2Ph), 4.49 and 4.45 (2d, 2H, Jˆ12.8 Hz,
CH2Ph), 3.96 (dd, 1H, J3,4ˆ1.2 Hz, H-3), 3.75 (dd, 1H,
J6endo,6exoˆ7.1 Hz, H-6exo), 3.65 (d, 1H, H-6endo), 3.61
(d, 1H, H-4), 3.48 (d, 1H, J1a,1bˆ14.4 Hz, H-1a), 3.38 (d,
1H, H-1b); 13C NMR (CDCl3): d 137.53 and 136.63 (3C
quat. arom.), 129.49, 128.94, 128.59, 128.53, 128.12,
128.05, 127.90 and 126.28 (15C arom.), 107.23 (C-2),
88.31 (C-3), 83.89 (C-5), 79.97 (C-4), 72.92 and 71.31 (2
CH2Ph), 66.96 (C-6), 33.82 (C-1). Anal. Calcd for
C26H26O4S: C, 71.86; H, 6.03. Found: C, 71.91; H, 6.12.
J5,6exoˆ3.9 Hz, H-5), 3.84 (dd, 1H, J3,4ˆ1.3 Hz, H-3),
3.82 (s, 2H, H-1a,1b), 3.69 (d, 1H, H-4), 3.67 (d, 1H,
J6endo,6exoˆ7.1 Hz, H-6endo), 3.61 (dd, 1H, H-6exo); 13C
NMR (CD3OD): d 109.23 (C-2), 84.38 (C-3), 82.96 (C-5),
80.11 (C-4), 67.50 (C-6), 59.19 (C-1). Anal. Calcd for
C6H10O5: C, 44.55; H, 6.22. Found: C, 44.20; H, 6.25.
1.1.5. 2,6-Anhydro-1,3,4-tri-O-benzyl-b-d-fructofura-
nose (9). Sodium hydride (60% suspension in oil, 266 mg,
6.65 mmol) was added portionwise to a solution of triol 1
(300 mg, 1.85 mmol) and benzyl bromide (0.8 mL,
6.74 mmol) in dry DMF (3 mL) at 08C. The mixture was
stirred at room temperature for 5 h, then quenched at 08C
with MeOH (2 mL), diluted with ether (35 mL), washed
with saturated aqueous NaCl, dried (MgSO4) and concen-
trated. The residue was puri®ed by chromatography
(CH2Cl2) to give 9 (534 mg, 67%) as a yellow oil; Rf 0.62
1.1.8. 2,6-Anhydro-3,4-di-O-benzyl-1-deoxy-b-d-fructo-
furanose (11). Raney nickel (Acros, washed with water,
then THF, 550 mg) was added portionwise within 3 h at
room temperature to a solution of thioether 10 (150 mg,
0.35 mmol) in dry THF (5 mL). The mixture was ®ltered
and the solid was washed with THF (3£10 mL). The
combined ®ltrates were concentrated and the residue was
puri®ed by chromatography (CH2Cl2±Et2O, 95:5) to give 11
(67 mg, 62%) as an oil; Rf 0.54 (petroleum ether±EtOAc,
3:2); [a]d 235 (c 0.94, CHCl3); 1H NMR (CDCl3): d 7.39±
7.29 (m, 10H, 2Ph), 4.63 (dd, 1H, J3,5ˆ1.5 Hz,
J5,6exoˆ4.3 Hz, H-5), 4.62 and 4.58 (2d, 2H, Jˆ12.2 Hz,
CH2Ph), 4.53 and 4.45 (2d, 2H, Jˆ12 Hz, CH2Ph), 3.70
(dd, 1H, J6endo,6exoˆ7.1 Hz, H-6exo), 3.66 (dd, 1H,
J3,4ˆ1.1 Hz, H-3), 3.59 (d, 1H, H-4), 3.58 (d, 1H,
H-6endo), 1.59 (s, 3H, CH3); 13C NMR (CDCl3): d 137.58
(2C quat. arom.), 128.61, 128.55, 128.14, 128.05 and 127.92
(10C arom.), 106.56 (C-2), 90.01, 84.16 and 79.67
(C-3,4,5), 72.85 and 71.33 (2 CH2Ph), 66.50 (C-6), 16.47
(C-1). Anal. Calcd for C20H22O4: C, 73.60; H, 6.79. Found:
C, 73.57; H, 6.79.
1
(CH2Cl2±Et2O, 95:5); [a]d 228 (c 1.14, CHCl3); H NMR
(CDCl3): d 7.33±7.22 (m, 15H, 3Ph), 4.67 (dd, 1H,
J3,5ˆ1.6 Hz, J5,6exoˆ4.2 Hz, H-5), 4.64 and 4.53 (2d, 2H,
Jˆ12.1 Hz, CH2Ph), 4.54 and 4.49 (2d, 2H, Jˆ12.1 Hz,
CH2Ph), 4.43 and 4.36 (2d, 2H, Jˆ12 Hz, CH2Ph),
3.98 (dd, 1H, J3,4ˆ1.3 Hz, H-3), 3.83 (d, 1H,
J1a,1bˆ11.7 Hz, H-1a), 3.79 (d, 1H, H-1b), 3.66 (dd, 1H,
J6endo,
ˆ7.1 Hz, H-6exo), 3.59 (d, 1H, H-6endo), 3.57
6exo
(d, 1H, H-4); 13C NMR (CDCl3): d 137.84, 137.83 and
137.68 (3C quat. arom.), 128.63, 128.55, 128.53, 128.31,
128.10, 128.05, 127.98 and 127.88 (15C arom.), 107.35
(C-2), 86.54, 83.97 and 80.36 (C-3,4,5), 73.79, 72.91 and
71.15 (3 CH2Ph), 66.42 and 66.23 (C-1,6). HRMS m/z
473.1932 [C27H28O5´H2O Na (M1H2O1Na1) requires
473.19401].
1.1.6. 2,6-Anhydro-1-deoxy-1-phenylthio-b-d-fructo-
furanose (8). A mixture of thioglycoside 7 (0.21 g,
0.58 mmol), (Bu3Sn)2O (0.29 mL, 0.58 mmol) and activated
1.1.9. Phenyl 4-O-benzoyl-2-thio-b-d-fructopyranoside
(13) and phenyl 1,4-di-O-benzoyl-2-thio-b-d-fructo-
pyranoside (14). A mixture of thioglycoside 6 (200 mg,
0.73 mmol), Bu2SnO (220 mg, 0.88 mmol) and activated
Ê
4 A powdered molecular sieves (0.5 g) in dry propionitrile
(10 mL) was heated at re¯ux for 5 h under vigorous stirring.
The mixture was worked up as described for the preparation
of 1 to give 8 (0.124 g, 85%) as an oil; Rf 0.46 (Et2O±
acetone, 4:1); [a]d 258 (c 0.83, MeOH); 1H NMR
(CD3OD): d 7.46±7.15 (m, 5H, Ph), 4.50 (dd, 1H,
J3,5ˆ1.5 Hz, J5,6exoˆ4.1 Hz, H-5), 3.91 (dd, 1H, J3,4ˆ
Ê
4 A powdered molecular sieves (500 mg) in dry acetonitrile
(10 mL) was heated at re¯ux for 5 h under vigorous stirring,
then cooled to room temperature under a stream of nitrogen.
Benzoyl chloride (128 mL, 1.1 mmol) was added and the
mixture was stirred for 2.5 h at room temperature. The solu-
tion was ®ltered, then concentrated and the residue was
puri®ed by chromatography (petroleum ether±EtOAc, 1:1)
to give ®rst dibenzoate 14 (90 mg, 26%) which crystallized
from ethanol; Rf 0.85 (CH2Cl2-MeOH, 4:1); mp180 8C; [a]d
2128 (c 1.07, CHCl3); 1H NMR (CD3OD): d 8.06 and 7.97
(2d, 4H, Jˆ7.2 Hz, C6H3H±oH±o0CO), 7.51±7.28 (m, 11H,
Ph), 5.35 (dd, 1H, J3,4ˆ10.5 Hz, J4,5ˆ3.1 Hz, H-4), 4.73 (d,
1H, H-3), 4.59 (d, 1H, J1a,1bˆ11.6 Hz, H-1a), 4.50 (dd, 1H,
J5,6aˆ1 Hz, J6a,6bˆ12.5 Hz, H-6a), 4.31 (d, 1H, H-1b), 4.24
(m, 1H, H-5), 3.78 (dd, 1H, J5,6bˆ1.9 Hz, H-6b); 13C NMR
(CDCl3): d 166.86 and 166.47 (2CvO), 135.93, 133.61 and
133.44 (3C quat. arom.), 129.97, 129.95, 129.54, 129.44,
1.3 Hz, H-3), 3.72 (d, 1H, H-4), 3.69 (d, 1H, J6endo,6exo
ˆ
7.1 Hz, H-6endo), 3.64 (dd, 1H, H-6exo), 3.45 (d, 1H,
J1a,1bˆ14.4 Hz, H-1a), 3.38 (d, 1H, H-1b); 13C NMR
(CD3OD): d 138.39 (C quat. arom.), 130.17, 129.87 and
127.06 (5C arom.), 108.99 (C-2), 84.97 (C-3), 84.42 (C-
5), 80.18 (C-4), 67.92 (C-6), 34.09 (C-1). Anal. Calcd for
C12H14O4S´0.25H2O: C, 55.69; H, 5.65. Found: C, 55.69; H,
5.72.
1.1.7. 2,6-Anhydro-3,4-di-O-benzyl-1-deoxy-1-phenyl-
thio-b-d-fructofuranose (10). Sodium hydride (60%
suspension in oil, 200 mg, 5 mmol) was added portionwise

F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
3635
129.23, 129.17, 128.58, 128.56 and 128.52 (15C arom.),
94.09 (C-2), 73.97, 68.23, 67.33, 66.30 and 65.28
(C-1,3,4,5,6). Anal. Calcd for C26H24O7S´0.5H2O: C,
63.79; H, 5.15. Found: C, 63.97; H, 5.01.
compound 15 (50 mg, 0.11 mmol), (Bu3Sn)2O (54 mL,
Ê
0.11 mmol) and activated 4 A powdered molecular sieves
(200 mg) in dry propionitrile (5 mL) was heated at re¯ux for
35 min under vigorous stirring, then cooled, ®ltered and
concentrated. The residue was puri®ed by chromatography
(petroleum ether±EtOAc, 3:2) to give 18 (35 mg, 70%) as
Then was eluted monobenzoate 13 (192 mg, 69%) as an oil;
1
1
Rf 0.74 (CH2Cl2±MeOH, 4:1); H NMR (CD3OD): d 8.02
an oil; Rf 0.34 (petroleum ether±EtOAc, 3:2); H NMR
(d, 2H, Jˆ7.2 Hz, C6H3H±oH±o0CO), 7.51±7.18 (m, 8H,
Ph), 5.24 (dd, 1H, J3,4ˆ10.6 Hz, J4,5ˆ3.2 Hz, H-4), 4.60 (d,
1H, H-3), 4.47 (dd, 1H, J5,6aˆ1 Hz, J6a,6bˆ12.4 Hz, H-6a),
4.16 (m, 1H, H-5), 3.81 (d, 1H, J1a,1bˆ11.8 Hz, H-1a), 3.72
(dd, 1H, J5,6bˆ1.9 Hz, H-6b), 3.38 (d, 1H, H-1b). HRMS m/z
399.0879 [C19H20O6NaS (M1Na1) requires 399.08783].
(CDCl3): d 8.15 (d, 2H, Jˆ7.2 Hz, C6H3H±oH±o0CO),
7.58±7.04 (m, 13H, Ph), 5.49 (m, 1H, H-5), 4.73 (d, 1H,
J3,4ˆ9.9 Hz, H-3), 4.52 (d, 1H, J6a,6bˆ12.9 Hz, H-6a), 4.22
(dd, 1H, J4,5ˆ2.9 Hz, H-4), 4.02 (dd, 1H, J5,6bˆ1 Hz, H-6b),
3.62 (d, 1H, J1a,1bˆ13.9 Hz, H-1a), 3.34 (d, 1H, H-1b), 3.00
(m, 2H, 2 OH); 13C NMR (CDCl3): d 166.53 (CvO),
136.86, 135.95 and 133.47 (3C quat. arom.), 130.08,
129.71, 129.36, 129.27, 129.08, 128.95, 128.87, 128.52
and 126.16 (15C arom.), 95.12 (C-2), 71.85, 70.48, 70.19
and 63.41 (C-3,4,5,6), 42.00 (C-1).
1.1.10. Phenyl 4-O-benzoyl-1-deoxy-1-phenylthio-2-thio-
b-d-fructopyranoside (15). A mixture of thioglycoside 7
(500 mg, 1.37 mmol), Bu2SnO (376 mg, 1.51 mmol) and
Ê
activated 4 A powdered molecular sieves (2 g) in dry aceto-
nitrile (25 mL) was heated at re¯ux for 5 h under vigorous
stirring, then cooled in an ice-bath under a stream of nitro-
gen. Benzoyl chloride (160 mL, 1.37 mmol) was added and
the mixture was stirred for 16 h at room temperature under
nitrogen. The solution was ®ltered, then concentrated and
the residue was puri®ed by chromatography (petroleum
ether±EtOAc, 7:3) to give 15 (450 mg, 70%) which crystal-
lized from ethanol; Rf 0.80 (EtOAc±petroleum ether, 3:2);
mp170.5 8C; [a]d 287 (c 0.82, CHCl3); 1H NMR (CDCl3): d
8.10 (d, 2H, Jˆ7.1 Hz, C6H3H±oH±o0CO), 7.61±7.12 (m,
13H, Ph), 5.42 (dd, 1H, J3,4ˆ10.4 Hz, J4,5ˆ3.1 Hz, H-4),
4.90 (dd, 1H, J3,OHˆ5 Hz, H-3), 4.59 (dd, 1H, J5,6aˆ1 Hz,
J6a,6bˆ12.4 Hz, H-6a), 4.31 (m, 1H, H-5), 3.94 (dd, 1H,
J5,6bˆ2.1 Hz, H-6b), 3.60 (d, 1H, J1a,1bˆ13.9 Hz, H-1a),
3.37 (d, 1H, H-1b), 2.57 (d, 1H, OH-3), 2.34 (bd, 1H,
OH-5); 13C NMR (CDCl3): d 166.70 (CvO), 136.79,
136.13 and 133.64 (3C quat. arom.), 130.00, 129.49,
129.42, 129.15, 129.10, 128.96, 128.91, 128.59 and
126.25 (15C arom.), 95.91 (C-2), 74.70, 68.28, 68.27 and
65.36 (C-3,4,5,6), 42.25 (C-1). Anal. Calcd for
C25H24O5S2´0.25H2O: C, 63.47; H, 5.22. Found: C, 63.51;
H, 5.21.
1.1.13. Phenyl 1,3,5-tri-O-acetyl-4-O-benzyl-2-thio-b-d-
fructopyranoside (20). A mixture of thioglycoside 6
(200 mg, 0.73 mmol), Bu2SnO (220 mg, 0.88 mmol) and
Ê
activated 4 A powdered molecular sieves (500 mg) in dry
acetonitrile (10 mL) was heated at re¯ux for 5 h under
vigorous stirring, then cooled to room temperature under a
stream of nitrogen. Benzyl bromide (105 mL, 0.88 mmol)
and tetrabutylammonium iodide (271 mg, 0.73 mmol) were
added and the mixture was again heated at re¯ux for 17 h
under stirring, then cooled, ®ltered and concentrated. The
residue was puri®ed by chromatography (petroleum ether,
then EtOAc±petroleum ether, 3:2) to give 19 (153 mg,
57%) as an oil; Rf 0.54 (EtOAc).
Acetic anhydride (1 mL) was added to a solution of
compound 19 (153 mg, 0.42 mmol) in dry pyridine
(3 mL). The solution was left for 16 h at room temperature,
then quenched at 08C with MeOH (0.5 mL) and concen-
trated. The residue was puri®ed by chromatography
(petroleum ether±EtOAc, 4:1) to give 20 (186 mg, 90%)
1
as an oil; [a]d 2109 (c 1.1, CHCl3); H NMR (CDCl3): d
7.39±7.19 (m, 10H, 2Ph), 5.66 (d, 1H, J3,4ˆ10.3 Hz, H-3),
5.41 (ddd, 1H, H-5), 4.63 and 4.43 (2d, 2H, Jˆ12 Hz,
CH2Ph), 4.42 (dd, 1H, J5,6aˆ1.3 Hz, J6a,6bˆ 13 Hz, H-6a),
4.28 (d, 1H, J1a,1bˆ12.1 Hz, H-1a), 3.94 (dd, 1H,
J4,5ˆ3.5 Hz, H-4), 3.92 (dd, 1H, J5,6bˆ2.1 Hz, H-6b), 3.77
(d, 1H, H-1b), 2.09, 2.01 and 1.99 (3 s, 9H, 3 OAc); 13C
NMR (CDCl3): d 170.32, 170.30 and 169.29 (3CvO),
137.32 and 135.47 (2C quat. arom.), 128.95, 128.89,
128.27, 128.15, 127.69 and 127.39 (10C arom.), 91.25
(C-2), 74.23 (C-4), 71.47 (CH2Ph), 67.71 and 67.61
(C-3,5), 65.26 and 63.26 (C-1,6), 20.91, 20.68 and 20.54
(3 CH3CO). HRMS m/z: 511.1407 [C25H28O8NaS
(M1Na1) requires 511.14026].
1.1.11. Phenyl 5-O-benzoyl-2-thio-b-d-fructopyranoside
(17). A mixture of the 4-O-benzoyl compound 13 (50 mg,
0.13 mmol), (Bu3Sn)2O (71 mL, 0.13 mmol) and activated
Ê
4 A powdered molecular sieves (200 mg) in dry propio-
nitrile (4 mL) was heated at re¯ux for 2.5 h under vigorous
stirring, then cooled, ®ltered and concentrated. The residue
was puri®ed by chromatography (EtOAc±petroleum ether,
7:3) to give 17 (35 mg, 70%) as an oil; Rf 0.48 (EtOAc±
1
petroleum ether, 7:3); H NMR (CD3OD): d 7.97 (d, 2H,
Jˆ7.2 Hz, C6H3H±oH±o0CO), 7.48±7.15 (m, 8H, Ph), 5.31
(m, 1H, H-5), 4.44 (dd, 1H, J5,6aˆ1 Hz, J6a,6bˆ12.5 Hz,
H-6a), 4.42 (d, 1H, J3,4ˆ10.1 Hz, H-3), 4.05 (dd, 1H,
J4,5ˆ3.4 Hz, H-4), 3.83 (dd, 1H, J5,6bˆ1.9 Hz, H-6b), 3.80
(d, 1H, J1a,1bˆ11.9 Hz, H-1a), 3.35 (d, 1H, H-1b); 13C NMR
(CD3OD): d 167.65 (CvO), 137.14 and 134.23 (2C quat.
arom.), 131.62, 131.53, 130.89, 130.69, 129.72, 129.46,
129.43 and 129.36 (10C arom.), 96.33 (C-2), 74.15, 70.52,
69.37, 65.57 and 64.24 (C-1,3,4,5,6). HRMS m/z 399.0877
[C19H20O6NaS (M1Na1) requires 399.08783].
1.1.14. Phenyl 4-O-benzyl-1-deoxy-1-phenylthio-2-thio-
b-d-fructopyranoside (21). A mixture of thioglycoside 7
(4 g, 11 mmol) and Bu2SnO (3.55 g, 14.3 mmol) in
methanol (80 mL) was heated at re¯ux for 4 h under
vigorous stirring, then cooled and concentrated. The residue
was dried under good vacuum to eliminate traces of
methanol, then dissolved in DMF (30 mL). Benzyl bromide
(2 mL, 16.7 mmol) and CsF (2.17 g, 14.3 mmol) were
added and the mixture was stirred at room temperature for
17 h, then diluted with CH2Cl2 (80 mL). The solution was
1.1.12. Phenyl 5-O-benzoyl-1-deoxy-1-phenylthio-2-thio-
b-d-fructopyranoside (18). A mixture of the 4-O-benzoyl

3636
F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
washed with 1 M aqueous KF (100 mL), then water
(100 mL), dried (MgSO4) and concentrated. The residue
was puri®ed by chromatography (CH2Cl2-MeOH,
99.5:0.5) to give 21 (2.88 g, 58%) which crystallized from
ethanol; Rf 0.80 (EtOAc±petroleum ether, 3:2); mp 1728C;
d 138.27, 138.11, 138.09, 138.07 and 137.91 (3C quat.
arom.), 134.56 and 133.11 (CHv), 128.69±127.76 (15C
arom.), 118.98 and 118.46 (CH2v), 86.42 and 86.29
(C-4), 84.62 and 84.29 (C-2), 83.38 and 83.02 (C-5),
81.49 and 80.86 (C-3), 73.71, 73.62, 72.90, 72.73, 72.65,
72.63, 72.54 and 72.13 (C-1, CH2Ph), 65.44 and 62.89
(C-6), 39.76 and 37.61 (CH2CHv). Anal. Calcd for
C30H34O5´H2O: C, 73.15; H, 7.37. Found: C, 73.25; H, 7.16.
1
[a]d 252 (c 1.01, CHCl3); H NMR (CDCl3): d 7.49±7.10
(m, 15H, 3Ph), 4.76 and 4.68 (2d, 2H, Jˆ11.5 Hz, CH2 Ph),
4.64 (dd, 1H, J3,4ˆ9.8 Hz, J3,OHˆ3.1 Hz, H-3), 4.40 (dd, 1H,
J5,6aˆ1.1 Hz, J6a,6bˆ12.6 Hz, H-6a), 4.13 (m, 1H, H-5), 3.97
(dd, 1H, J5,6bˆ1.8 Hz, H-6b), 3.84 (dd, 1H, J4,5ˆ3.2 Hz,
H-4), 3.58 (d, 1H, J1a,1bˆ13.8 Hz, H-1a), 3.32 (d, 1H,
H-1b), 2.58 (d, 1H, OH-3), 2.47 (bd, 1H, OH-5); 13C
NMR (CDCl3): d 137.63, 137.07 and 135.94 (3C quat.
arom.), 129.67, 129.60, 129.14, 128.92, 128.90, 128.46,
128.14 and 126.19 (15C arom.), 95.09 (C-2), 78.97 (C-4),
72.10, 69.02, 66.71 and 64.99 (C-3,5,6, CH2Ph), 42.39
(C-1). Anal. Calcd for C25H26O4S2: C, 66.05; H, 5.76.
Found: C, 66.15; H, 5.77.
1.1.17. 1-(3,4-Di-O-benzyl-1-deoxy-a-d-fructofuranosyl)-
prop-2-ene (26a) and 1-(3,4-di-O-benzyl-1-deoxy-b-d-
fructofuranosyl)-prop-2-ene (26b). Sc(OTf)3 (23 mg,
47 mmol) was added to a solution of acetal 11 (175 mg,
0.54 mg) and allyltrimethylsilane (0.44 mL, 2.7 mmol) in
dry CH2Cl2 (4 mL) at 2308C under nitrogen. The mixture
was allowed to warm to 08C, then stirred for 3 h 40 at 08C,
diluted with CH2Cl2, washed with water, dried (MgSO4) and
concentrated. The residue was dissolved in 4:1 MeOH±
AcOH (5 mL) and the solution was left at room temperature
for 4 h, then concentrated. The residue was puri®ed by chro-
matography (CH2Cl2-Et2O, 95:5) to give a 67:33 mixture of
26a and 26b (156 mg, 79%). Further chromatography gave
®rst 26b (25 mg, 13%) as an oil; Rf 0.69 (CH2Cl2±Et2O,
1.1.15. 2,6-Anhydro-4-O-benzyl-1-deoxy-1-phenylthio-
b-d-fructofuranose (22). A mixture of thioglycoside 21
(455 mg, 1 mmol), (Bu3Sn)2O (0.5 mL, 1 mmol) and
Ê
activated 4 A powdered molecular sieves (1 g) in dry
1
propionitrile (20 mL) was heated at re¯ux for 5 h under
vigorous stirring, then cooled, ®ltered and concentrated.
The residue was puri®ed by chromatography (petroleum
ether, then petroleum ether±EtOAc, 7:3) to give 22
7:3); [a]d136 (c 1, CHCl3); H NMR (CDCl3): d 7.39±
7.29 (m, 10H, 2Ph), 5.85 (m, 1H, CHv), 5.11 and 5.10
(2m, 2H, CH2v), 4.62 and 4.56 (2d, 2H, Jˆ11.7 Hz,
CH2Ph), 4.61 and 4.48 (2d, 2H, Jˆ11.5 Hz, CH2Ph), 4.08
(m, 2H, H-4,5), 3.78 (m, 2H, H-3,6a), 3.68 (m, 1H, H-6b),
2.45 (m, 2H, CH2CHv), 1.98 (bd, 1H, OH-6), 1.33 (s, 3H,
1
(293 mg, 85%) as an oil; Rf 0.40 (CH2Cl2±Et2O, 95:5); H
NMR (CDCl3): d 7.44±7.16 (m, 10H, 2Ph), 4.68 (dd, 1H,
J3,5ˆ1.4 Hz, J5,6exoˆ4 Hz, H-5), 4.63 and 4.52 (2d, 2H,
Jˆ12 Hz, CH2Ph), 4.06 (ddd, 1H, H-3), 3.72 (dd, 1H,
J6endo,6exoˆ7.3 Hz, H-6exo), 3.62 (d, 1H, H-6endo), 3.52
(d, 1H, J3,4ˆ1 Hz, H-4), 3.49 (d, 1H, J1a,1bˆ14.4 Hz,
H-1a), 3.42 (d, 1H, H-1b), 2.35 (d, 1H, J3,OHˆ10 Hz,
OH-3); 13C NMR (CDCl3): d 137.40 and 136.27 (2C quat.
arom.), 129.85, 129.12, 128.69, 128.12 and 126.67 (10C
arom.), 107.70 (C-2), 85.87, 82.04 and 80.90 (C-3,4,5),
70.82 (CH2Ph), 67.36 (C-6), 33.74 (C-1). HRMS m/z
367.0981 [C19H20O4NaS (M1Na1) requires 367.09800].
1
CH3); H NMR (CDCl31Cl3CCONCO): d 8.45 (s, 1H,
NH), 7.37±7.30 (m, 10H, 2Ph), 5.80 (m, 1H, CHv), 5.09
2
3
and 5.08 (2m, 2H, Jˆ2.2 Hz, Jˆ9.7 and 17 Hz, CH2v),
4.61 and 4.55 (2d, 2H, Jˆ11.8 Hz, CH2Ph), 4.57 and 4.51
(2d, 2H, Jˆ11.6 Hz, CH2Ph), 4.46 (m, 1H, H-6a), 4.20 (m,
1H, H-5), 4.18 (dd, 1H, J5,6bˆ6.7 Hz, J6a,6bˆ11.4 Hz, H-6b),
3.91 (dd, 1H, J3,4ˆ2.7 Hz, J4,5ˆ4.5 Hz, H-4), 3.77 (d, 1H,
H-3), 2.43 (m, 2H, CH2CHv), 1.31 (s, 3H, CH3); 13C NMR
(CDCl3): d 137.88 and 137.73 (2C quat. arom.), 134.60
(CHv), 128.59, 128.52, 127.97, 127.90, 127.78, 127.72
and 127.65 (10C arom.), 118.07 (CH2v), 88.14 (C-3),
84.24 (C-2), 83.88 and 81.92 (C-4,5), 72.38 and 71.88 (2
CH2Ph), 63.19 (C-6), 41.22 (CH2CHv), 23.31 (CH3).
HRMS m/z 391.1891 [C23H28O4Na (M1Na1) requires
391.18853].
1.1.16. 1-(1,3,4-Tri-O-benzyl-d-fructofuranosyl)-prop-2-
ene (25). TMSOTf (135 mL, 0.75 mmol) was added to a
solution of acetal 9 (300 mg, 0.69 mmol) and allyltrimethyl-
silane (0.57 mL, 3.57 mmol) in dry acetonitrile (5 mL) at
2308C under nitrogen. The mixture was allowed to warm to
08C, then stirred for 1.5 h at 08C, diluted with CH2Cl2 and
washed with saturated aqueous NaHCO3 until neutral. The
organic phase was dried (MgSO4) and concentrated. The
residue was puri®ed by chromatography (petroleum
ether±EtOAc, 4:1) to give a non separable 73:27 mixture
of 25a and 25b (209 mg, 63%) as an oil; Rf 0.42 (CH2Cl2±
Et2O, 95:5); 1H NMR (CDCl3): d 7.38±7.26 (m, 15H, 3Ph),
5.93 (m, 0.27H, CHv), 5.79 (m, 0.73H, CHv), 5.14±5.06
(m, 0.54H, CH2v), 5.10 (dd, 0.73H, 2Jˆ2.2 Hz,
3Jˆ10.2 Hz, CHaHbv), 5.03 (dd, 0.73H, 3Jˆ17.1 Hz,
CHaHbv), 4.70±4.53 (m, 6H, 3CH2Ph), 4.39 (dd, 0.73H,
J3,4ˆ5.5 Hz, J4,5ˆ6.7 Hz, H-4), 4.19 (d, 0.27H, J3,4ˆ4.8 Hz,
H-3), 4.12 (dd, 0.27H, J4,5ˆ6.6 Hz, H-4), 4.07 (d, 0.73H,
H-3), 4.00±3.94 (m, 1H, H-5), 3.86±3.78 (m, 1H, H-6a),
3.65±3.58 (m, 1H, H-6b), 3.57 (d, 0.73H, J1a,1bˆ9.7 Hz,
H-1a), 3.48 (d, 0.73H, H-1b), 3.46 (s, 0.54H, H-1a,1b),
2.88 (m, 0.73H, OH-6), 2.57±2.32 (m, 2H, CH2CHv),
2.05 (m, 0.27H, OH-6); 13C NMR (CDCl3, bold for 25a):
Then were eluted a mixture of 26a and 26b (68 mg, 34%)
and ®nally pure 26a (62 mg, 31%) as an oil; Rf 0.62
(CH2Cl2-Et2O, 7:3); [a]d 149 (c 1.08, CHCl3); H NMR
1
(CDCl3): d 7.38±7.29 (m, 10H, 2Ph), 5.82 (m, 1H,
CHv), 5.12 and 5.07 (2m, 2H, 2Jˆ2, 3Jˆ10.2 and
17.2 Hz, CH2v), 4.61±4.51 (m, 4H, 2CH2Ph), 4.09 (dd,
1H, J3,4ˆ3.4 Hz, J4,5ˆ5.7 Hz, H-4), 3.99 (ddd, 1H, H-5),
3.85 (d, 1H, H-3), 3.78 (dd, 1H, J5,6aˆ3 Hz, J6a,6b
ˆ
11.8 Hz, H-6a), 3.61 (dd, 1H, J5,6bˆ4.1 Hz, H-6b), 2.45
and 2.38 (2 dd, 2H, 2Jˆ13.9, 3Jˆ6.9 and 7.6 Hz,
1
CH2CHv), 1.95 (bd, 1H, OH-6), 1.29 (s, 3H, CH3); H
NMR (CDCl31Cl3CCONCO): d 8.45 (s, 1H, NH), 7.38±
7.28 (m, 10H, 2Ph), 5.79 (m, 1H, CHv), 5.11 and 5.05 (2m,
2H, 2Jˆ2.1, 3Jˆ10.2 and 17 Hz, CH2v), 4.60 and 4.53 (2d,
2H, Jˆ11.7 Hz, CH2Ph), 4.57 and 4.53 (2d, 2H, Jˆ12.2 Hz,
CH2Ph), 4.46 (dd, 1H, J5,6aˆ3.1 Hz, J6a,6bˆ11.3 Hz, H-6a),
4.18 (dd, 1H, J5,6bˆ6.4 Hz, H-6b), 4.11 (ddd, 1H,
J4,5ˆ5.7 Hz, H-5), 3.94 (dd, 1H, H-4), 3.87 (d, 1H, H-3),

F. Goursaud et al. / Tetrahedron 58 (2002) 3629±3637
3637
2.40 (m, 2H, CH2CHv), 1.28 (s, 3H, CH3); 13C NMR
(CDCl3): d 138.00 and 137.92 (2C quat. arom.), 133.69
(CHv), 128.57, 128.50, 127.95, 127.85, 127.72 and
127.66 (10C arom.), 118.54 (CH2v), 86.68 (C-3), 84.32
(C-4), 84.31 (C-2), 81.15 (C-5), 72.51 and 72.02 (2
CH2Ph), 63.02 (C-6), 43.19 (CH2CHv), 21.27 (CH3).
HRMS m/z 391.1886 [C23H28O4Na (M1Na1) requires
391.18853].
5. Nicotra, F.; Panza, L.; Russo, G. J. Org. Chem. 1987, 52,
5627±5630.
6. Bennek, J. A.; Gray, G. R. J. Org. Chem. 1987, 52, 892±897.
7. Goldschmid, H. R.; Perlin, A. S. Can J. Chem. 1960, 38,
2178±2186.
È
8. Taba, K. M.; Koster, R.; Dahloff, W. V. Synthesis 1983,
1036±1037.
9. Poncini, L. Indian J. Chem. 1991, 30B, 442.
È
10. Koll, P.; Deyhim, S.; Heyns, K. Chem. Ber. 1978, 111, 2909±
2912.
1.1.18. 1-(4-O-Benzyl-1-deoxy-d-fructofuranosyl)-prop-
2-ene (27). Raney nickel (4.8 g) was added portionwise
within 6 h at room temperature to a solution of thioether
22 (1.65 g, 4.8 mmol) in dry THF (25 mL). The mixture
was ®ltered and the solid washed with THF. The combined
®ltrates were concentrated and the residue was puri®ed by
chromatography (petroleum ether±EtOAc, 1:1) to give 23
(452 mg, 40%) as an oil; Rf 0.64 (EtOAc±petroleum ether,
4:1). Further elution with 7:3 EtOAc±petroleum ether gave
24b (Rf 0.42) and 24a (Rf 0.32).
11. Moody, W.; Richards, G. N. Carbohydr. Res. 1983, 124, 201±
213.
12. Chan, J. Y. C.; Cheong, P. P. L.; Hough, L.; Richardson, A. C.
J. Chem. Soc., Perkin Trans. 1 1985, 1447±1455.
13. Raaijmakers, H. W. C.; Eveleens, S. M.; Arnouts, E. G.;
Zwanenburg, B.; Chittenden, G. J. F. Recl. Trav. Chim. Pays
Bas 1993, 112, 511±514.
14. Ferrier, R. J.; Furneaux, R. H. Carbohydr. Res. 1976, 52, 63±
68.
15. Nicolaou, K. C.; Ladduwahetty, T.; Randall, J. L.;
Chucholowski, A. J. Am. Chem. Soc. 1986, 108, 2466±2467.
16. Heskamp, B. M.; Noort, D.; van der Marel, G. A.; van Boom,
J. H. Synlett 1992, 713±715.
Sc(OTf)3 (31 mg, 63 mmol) was added to a solution of 23
(100 mg, 0.42 mmol) and allyltrimethylsilane (0.35 mL,
2.2 mmol) in dry CH2Cl2 (4 mL) at 2308C under nitrogen.
The mixture was allowed to warm to 08C within 2.5 h, then
worked up as described for the preparation of 26. The
residue was puri®ed by chromatography (CH2Cl2-Et2O,
4:1) to give a 70:30 mixture (100 mg, 85%) of 27a (Rf
17. Jones, D. K.; Liotta, D. C. Tetrahedron Lett. 1993, 34, 7209±
7212.
18. Grindley, T. B. Adv. Carbohydr. Chem. Biochem. 1998, 53,
17±142.
1
0.28) and 27b (Rf 0.40); H NMR (CDCl3): d 7.39±7.28
19. Baldwin, J. C.; Lappert, M. F.; Pedley, J. B.; Poland, J. S.
J. Chem. Soc., Dalton Trans. 1972, 1943±1947.
20. Craig, D.; Munasinghe, V. R. N.; Tierney, J. P.; White, A. J. P.;
Williams, D. J.; Williamson, C. Tetrahedron 1999, 55,
15025±15044.
(m, 5H, Ph), 5.94±5.76 (m, 1H, CHv), 5.18±5.06 (m,
2H, CH2v), 4.75±4.54 (m, 2H, CH2Ph), 4.09±3.94 (m,
3H, H-3,4,5), 3.84±3.79 (m, 1H, H-6a), 3.63±3.59 (m,
1H, H-6b), 2.70±2.32 (m, 4H, CH2CHv, 2 OH), 1.32 (s,
2.1H, CH3), 1.24 (s, 0.9H, CH3); 13C NMR (CDCl3, bold for
27a): d 137.90 (C quat. arom.), 134.55 and 133.85 (CHv),
128.59, 128.58, 127.96, 127.94, 127.69 and 127.67 (5C
arom.), 118.42 and 118.18 (CH2v), 87.86, 87.31, 85.68,
85.51, 82.27, 81.64, 79.44 and 78.74 (C-2,3,4,5), 72.46
and 72.29 (CH2Ph), 42.43 and 41.24 (CH2CHv), 22.19
and 20.50 (CH3).
21. Deslongchamps, P. Stereoelectronic Effects in Organic
Chemistry; Pergamon: Oxford, 1983.
22. Bredenkamp, M. W.; Spies, H. S. C. Tetrahedron Lett. 2000,
41, 543±546.
23. Roelens, S. J. Org. Chem. 1996, 61, 5257±5263.
24. Nagashima, N.; Ohno, M. Chem. Pharm. Bull. 1991, 39,
1972±1982.
Â
25. De las Heras, F. G.; Fernandez-Resa, P. J. Chem. Soc., Perkin
Trans. 1 1982, 903±907.
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