Efficient synthesis of α,β-unsaturated γ-lactones linked to sugars

Article abstract of DOI:10.1016/S0957-4166(01)00197-5

A series of structurally diverse unsaturated sugar-derived lactones has been prepared. α,β-Butenolides were introduced to the sugar moiety starting from epoxides, while α-methylene-γ-lactones were constructed from a carbonyl precursor, either an aldehyde, a ketone or a lactone. In the last case, an unprecedented Reformatsky-type reaction has been developed.

Full text of DOI:10.1016/S0957-4166(01)00197-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1131–1146
Efficient synthesis of a,b-unsaturated g-lactones linked to sugars†
Ame´lia P. Rauter,a,* Jose´ Figueiredo,b Maria Ismael,b Tana Canda,a,c Josep Fontd and
Marta Figueredod
aDepartamento de Qu´ımica e Bioqu´ımica, Faculdade de Cieˆncias, Universidade de Lisboa, Ed. C8, 6° Piso,
Campo Grande 1749-016 Lisbon, Portugal
b
`
Departamento de Qu´ımica, Universidade da Beira Interior, Av. Marqueˆs de Avila e Bolama, 6201-001 Covilha˜, Portugal
cDepartamento de Qu´ımica, Faculdade de Cieˆncias, Universidade Agostinho Neto, Luanda, Angola
dDepartamento de Qu´ımica, Universitat Auto`noma de Barcelona, 08193 Bellaterra, Spain
Received 24 February 2001; accepted 1 May 2001
Abstract—A series of structurally diverse unsaturated sugar-derived lactones has been prepared. a,b-Butenolides were introduced
to the sugar moiety starting from epoxides, while a-methylene-g-lactones were constructed from a carbonyl precursor, either an
aldehyde, a ketone or a lactone. In the last case, an unprecedented Reformatsky-type reaction has been developed. © 2001
Published by Elsevier Science Ltd.
1. Introduction
moted by titanium tetrachloride,9 and various trans-
formations of C3 synthons, glycidaldehyde among oth-
ers.10 Distinct approaches have also been used, as in
two recently reported examples dealing with the synthe-
sis of some insect anti-feedant a,b-butenolide
derivatives11 and the preparation of g-alkylidene-a,b-
butenolides.12 A general synthetic approach to the exo-
cyclic class, a-methylene-g-butyrolactones, through an
indium promoted reaction of 2-(bromomethyl)acrylic
acid with carbonyl compounds has been described,
giving the products in 7–96% yields, depending on their
structure.13
a,b-Unsaturated g-lactones occur widely in nature and
appear throughout the plant kingdom from the simple
metabolites of lichens and fungi1 to the sesquiterpenes2
and the steroidal glycosides.3 They have also been
described in animal species such as sponges,4
butterflies5 and insects,6 playing an important role as
chemical defence weapons. Many of these compounds
exhibit a variety of properties such as antifungal, insec-
ticidal, antibacterial, phytotoxic, or anti-inflammatory
activities, and some are antibiotics, potential anti-can-
cer agents and cyclooxygenase or phospholipase A2
inhibitors.7
We have already reported the introduction of a,b-
unsaturated g-lactones in sugar derivatives by two dif-
ferent methodologies outlined in Scheme 1.14,15 In one
of them (path A), the sugar butenolide 2 was prepared
through condensation of the sugar epoxide 1 with the
dianion of phenylselenoacetic acid, followed by hydro-
lysis and subsequent oxidation of the intermediate
phenylselenolactone.16,17 Since the nucleophilic opening
of the oxirane is stereospecific, the configuration of the
stereogenic centre in the final lactone is determined by
that of the starting epoxide. The second approach (path
B) makes use of a Reformatsky-type reaction of a
ketosugar or a dialdofuranose derivative with ethyl
bromomethylacrylate and zinc in THF under reflux.
Ethyl bromomethylacrylate and zinc–silver/graphite at
−78°C have been successfully applied to the synthesis of
hydroxyesters from cyclic ketones,18 ketosugars and a
Due to their biological importance, many synthetic
methods have been developed for the preparation
of both exocyclic and endocyclic a,b-unsaturated g-
lactones. For the endocyclic class (a,b-butenolides),
well established synthetic approaches described in the
literature include the mercuration–carbonylation of
propargylic alcohols,8 condensation of 2,5-bis(tri-
methylsiloxy)furans with carbonyl compounds pro-
* Corresponding author. Tel.: +351 21 7500952; fax: +351 21
7500088; e-mail: aprauter@fc.ul.pt
This article is dedicated to Professor Pierre Sinay¨ on the occasion of
†
his 62nd birthday.
0957-4166/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0957-4166(01)00197-5

1132
A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
Scheme 1. (a) PhSeCH2CO2H/LDA; (b) H+, D; (c) H2O2, H+; (d) BrCH2C(ꢀCH2)CO2Et, Zn, THF, D.
2,3-O-isopropylidene-
D
-erythronolactone,19 and to the
factors on the bioactivity. The results of the synthetic
work are reported herein.
synthesis of a,b-unsaturated g-lactones from some keto-
sugars.18 Synthesis of 3-ulosonic acids via a samarium
iodide Reformatsky reaction on aldonolactones has
also been reported.20
2. Results and discussion
The fungicidal efficacy of some of the compounds
previously synthesised14,15 encouraged us to prepare
new related derivatives. We also undertook the devel-
opment of new synthetic methodologies to broaden the
structural diversity of these a,b-unsaturated lactone
sugars. Derivatives which differ only in hydroxyl pro-
tective groups or stereochemistry have been synthesised
in order to investigate the influence of these structural
2.1. Synthesis of the a,b-butenolide sugar derivatives
The epoxides 1,15 621 and 7 (Scheme 2) were prepared
through a Mitsunobu reaction from the corresponding
diol precursors in 72, 73 and 76% yield, respectively.
Deoxygenation at position 3 for the synthesis of 7 was
accomplished via iodination of 1,2;5,6-di-O-isopropyl-
idene-a-D-glucofuranose with the system Ph3P/I2/imida-
Scheme 2. (a) PhXCHR%COOH, LDA, THF, 0°C; (b) MCPBA for 8 and 9; NaIO4 for 10; toluene, D; (c) H2O2, H+ for 11–15.

A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1133
zole,22 followed by reduction with LiAlH4. Treatment
of the epoxides 1, 6 and 7 with the dianion of phenyl-
thioacetic acid, gave, after cyclisation under acidic con-
ditions, the corresponding phenylthiolactones 8 in 53%
yield, 9 in 55% yield and 10 in 64% yield, as an
inseparable diastereomeric mixture in 3:2, 5:3 and 2:1
ratios, respectively. These ratios were determined by the
integration curves of the corresponding 1H NMR
C(1)H signals. Oxidation of these lactones with m-
chloroperbenzoic acid23 in the case of 8 and 9, or with
sodium metaperiodate in the case of 10, afforded the
corresponding sulfoxides, which were directly subjected
to pyrolysis in refluxing toluene, giving the butenolides
diastereomeric ratio of 3:1. This reaction type was
previously described using a 3-C-epoxyethyl sugar
derivative as the starting material.25 Acid catalysed
oxidation of the lactones 24a and 24b with H2O2
1
yielded the butenolide 25 (36%). The H NMR spec-
trum of 25 contained signals at l 7.30 and l 1.96, as
expected for the olefinic proton and the methyl group,
respectively, and at l 3.71 and l 3.61 with a coupling
constant of 3 Hz, indicative of the epoxide.
2.2. Synthesis of the a-methylenebutyrolactone sugar
derivatives
1
2.2.1. From aldehydes. Preparation of the dialdofura-
nose 27 (Scheme 4) was accomplished by partial hydro-
lysis of 3-deoxy-1,2;5,6-di-O-isopropylidene-a-D-ribo-
16–18 in 43, 30 and 14% yields, respectively. In the H
NMR spectra of the new compounds 17 and 18, the
signals of the a and b olefinic protons appear respec-
tively at l 6.08 and l 7.42 for 17 and at l 6.19 and
l 7.59 for 18, as expected for the conjugated double
bond. When the epoxides 1 and 6 were condensed with
the dianion of phenylselenoacetic acid (instead of
phenylthioacetic acid), the phenylselenolactones 11
(51%) and 12 (80%) were isolated, both with a
diastereomeric ratio of 1:1, as determined by the inte-
hexofuranose 26a26 with acetic acid,27 followed by
sodium periodate oxidation in 52% overall yield,
according to the procedure previously described for
related compounds.28 Reformatsky-type reaction of 27
with ethyl bromomethylacrylate and activated zinc14,15
gave a diastereoisomeric mixture of 28 and 29 (ratio
7:3), determined by the ratio of the integration of the
1H NMR C(1)H signals of the lactones 28 and 29,
isolated in 86% total yield. The related derivatives 4, 30
and 31 (Scheme 5) have been previously shown to have
fungicidal efficacy against Puccinia recondita, Plasmopara
1
gration curve of the corresponding H NMR signal of
C(1)H; their acid catalysed oxidation with H2O2 then
afforded the butenolides 16 and 17 in 75 and 91% yield,
respectively. Therefore, with this last procedure the
yield of the overall transformation is improved (32
versus 23% from 1 to 16, and 73 versus 25% from 6 to
17).
The epoxides 1, 6 and 7 were also treated with the
dianion of a-phenylselenopropionic acid to produce the
lactones 13 (79%), 14 (47%) and 15 (58%), as insepar-
able mixtures of two diastereomers in the ratios 1:2,
3:2, and 7:3, respectively, calculated from the integra-
1
tion curve of the corresponding C(1)H signals in H
NMR. After oxidation–pyrolysis, compounds 13–15
gave the corresponding a-methyl-a,b-butenolides 19
(64%), 20 (73%) and 21 (93%). Diagnostic signals for
the structural assignment of these molecules are the
b-carbonyl olefinic proton at l ꢀ7.2 and the singlet of
the allylic methyl group at l ꢀ1.9.
Reduction of methyl 2,5-di-O-tosyl-b-D-glucofura-
nosidurono-6,3-lactone24 with lithium borohydride gave
22, which was treated with potassium hydroxide,
affording the bisepoxide 23 in 97% overall yield
(Scheme 3). Condensation of 23 with a-phenylse-
lenopropionic acid was regioselective furnishing a mix-
ture of the lactones 24a and 24b (32%), with a
Scheme 4. (a) 80% AcOH, D, 1 h; (b) NaIO4, H2O/EtOH; (c)
BrCH2C(ꢀCH2)CO2Et, Zn, THF, D.
Scheme 3. (a) KOH/H2O, rt; (b) PhSeCHMeCOOH, LDA, THF, 0°C; H3O+, D; (c) H2O2, H+.

1134
A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
Scheme 5. (a) Me2BBr, ClCH2CH2Cl, −78°C, 24 h.
viticola and Botrytis cinerea.15 In order to determine
the contribution of the protective groups to the bio-
logical activity, selective deprotection was attempted.
Treatment of the (5S) diastereoisomers 4 and 30
with dimethylboron bromide in 1,2-dichloroethane at
−78°C29 gave the O-benzyl derivatives 32 (30%) and
34 (31%), along with the fully deprotected compounds
33 (50%) and 35 (52%), in the respective product mix-
tures. When the (5R) diastereoisomers 5 and 31 were
subjected to the same treatment, only the fully depro-
tected compounds 36 and 37 were isolated in 50%
yields.
2.2.2. Spirolactones from ketosugars. Spirolactones at
positions 2 and 3 of a furanoside ring have been
reported previously14,15 and it was shown that one of
the diastereoisomers of the a,b-unsaturated spirolac-
tone in position 3 was biologically active.15 In order to
introduce this unit into position 3 of a 2-deoxyfurano-
sidic system by a Reformatsky-type reaction, the pre-
cursor ketosugar 41 was prepared (Scheme 6), starting
from 2-deoxy- -glucose 38 in three steps. Reaction of
D
38 with MeOH/AcCl at room temperature over 3 h
gave the a- and b-methyl glycosides 39a and 39b in 65
and 33% yield, respectively. Treatment of a mixture of
+
,
Scheme 6. (a) Me2CO, H , ZnCl2, rt, 40 h; 40a p=65%, 40b p=20%; (b) PCC/3 A molecular sieves powder, CH2Cl2, 40°C, 2 h,
p=85%; (c) BrCH2C(ꢀCH2)CO2Et, Zn, THF, D.

A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1135
39a and 39b with acetone/H+ in the presence of zinc
A second, more complex ketosugar substrate 50 was
prepared as indicated in Scheme 7. Treatment
,
chloride and powdered 3 A molecular sieves afforded
the isopropylidene furanosidic anomers a 40a and b 40b
in 65 and 20% yield, respectively. Oxidation of 40a with
PCC/powdered molecular sieves in CH2Cl2 at 40°C
over 2 h gave the ketosugar 41 in 85% yield. The
reaction of 41 with ethyl bromomethylacrylate and zinc
in THF under reflux afforded a mixture of four com-
pounds, the expected diastereoisomeric spirolactones 42
(49%) and 43 (17%) and the corresponding deprotected
diols 44 (5%) and 45 (8%), presumably formed by
hydrolysis of the 5,6-O-isopropylidene group during the
of 1,2;5,6-di-O-isopropylidene-a-D-ribo-hexofuranosid-
3-ulose 4614 with 75% formic acid at 50°C gave 47 in
60% yield. Reaction of 47 with methanol/acetyl chloride
at room temperature afforded the a/b methyl glycosides
48a and 48b which could be separated by column
chromatography and isolated in 80 and 20% yield,
respectively. Treatment of the glycoside mixture 48a
and 48b with acetone/H+ in the presence of ZnCl2 led to
the synthesis of the a-anomer 49a in 65% yield and the
b-anomer 49b in 20% yield. Oxidation of 49a with the
1
acidic work up of the reaction mixture. The H NMR
,
PCC/powdered 4 A molecular sieves system at 40°C
spectra of compounds 42–45 contain two signals for the
olefinic protons (at around l 6.2 and l 5.6) and two
signals for the allylic protons (at around l 3.4 and
l 2.9). The configuration of the new stereogenic centre
was assigned by NOESY experiments, in which a corre-
lation was detected between the allylic methylene group
and C(4)H for compounds 43 and 45, the isopropyl-
idene group for C(6a)H in 42 and C(6b)H for com-
pound 44.
afforded 50 in 90% yield. The Reformatsky-type reac-
tion of 50 furnished the spirolactone 51 in 73% yield as
a single diastereoisomer. The (R) configuration of the
new stereogenic centre was elucidated by an NOESY
NMR experiment, which showed a correlation of the
allylic methylene group (l 3.14 and l 2.97) with C(1)H
and C(2)H. The highest diastereofacial selectivity in the
addition of the zinc reagent observed for the ketosugar
Scheme 7. (a) HCOOH (75%), 50°C, 1 h, p=60% (a/b 2:1); (b) MeOH, AcCl, rt, 4 h; (c) Me2CO, H+, ZnCl2, rt, 38 h; (d) PCC/
,
4 A molecular sieves powder, CH2Cl2, 40°C, 2 h, p=90%; (e) BrCH2C(ꢀCH2)CO2Et, Zn, THF, D, p=73%.

1136
A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
50 compared to 41 is probably due to the high steric
hindrance impeding the approach of the Reformatsky-
type reagent to the endo face of the carbonyl group of
50.
nose ring, the high diastereoselectivity may be due to a
favourable interaction between the zinc reagent and an
oxygen of the isopropylidene group in the transition
state. In the case of 56, most probably steric effects are
again decisive.
2.2.3. Spirolactones from sugar lactones. Although it is
known from the literature that allylzinc bromide does
not react with lactones,30 during the course of these
investigations, we realised that the Reformatsky-type
reagent prepared from ethyl bromomethylacrylate and
activated zinc was also reactive towards the carbonyl
group of a lactone functionality. This new reaction
brought about the possibility of synthesising new spiro-
lactone sugar derivatives, broadening their structural
diversity. Commercially available 2,3-O-isopropylidene-
In summary, a series of structurally diverse unsaturated
lactone sugar derivatives have been prepared. a,b-
Butenolides have been introduced to the sugar residue
starting from epoxides, while a-methylene-g-lactones
have been constructed from a carbonyl group precur-
sor, either of an aldehyde, a ketone or a lactone. In the
last case, a novel Reformatsky-type reaction of lactones
has been developed. The biological activity of these new
sugar lactones is under study.
D
-ribonic-g-lactone 52 and 1,2-O-isopropylidene-a-D-
glucofuranurono-6,3-lactone 56 were used as substrates
for this reaction, along with the sugar lactone 5431
(Scheme 8), which was prepared from 2,3;5,6-di-O-iso-
3. Experimental
propylidene-a-D-mannofuranose in 85% yield by PCC/
molecular sieves oxidation. Starting from these
substrates, the spirolactones 53, 55 and 57 were
obtained in 65, 75 and 78% yield, respectively, each as
a single diastereoisomer. The configuration of these
compounds was established by NOESY NMR as
above, considering the interaction between the allylic
methylene group of the new lactone ring and the iso-
propylidene group for 53, the protons at C-(6) for 55
and the anomeric proton for 57. For substrates 52 and
54, in which the reacting lactone belongs to the fura-
3.1. General methods
Melting points were determined with a melting point
apparatus (Tottoli) and are uncorrected. Optical rota-
tions were measured with an Atago Polax-D polarime-
ter and IR spectra were recorded with a Biorad FTS 25
1
PC spectrophotometer. H NMR spectra were carried
out using a Varian Unity 300 MHz spectrometer (com-
pounds 1–25) or a Bruker ACC-250 P spectrometer
(compounds 26–58) and the NOE experiments were
Scheme 8. (a) BrCH2C(ꢀCH2)CO2Et, Zn, THF, D; (b) BrCH2C(ꢀCH2)CO2Et, Zn, dioxane, D.

A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1137
with a Bruker AM-400 WB spectrometer. Chemical
shifts are expressed in parts per million downfield from
TMS. Homonuclear 1H{1H} experiments were per-
formed at 400 MHz in acetone-d6 or chloroform-d,
using a low decoupler setting (typically 40 L, 5 mW
approximately) with a total presaturation time of 6 s.
The FiDs were acquired using 16 K points and a sweep
width of 5000 Hz in alternate groups of eight, irradia-
tion on/off resonance. A 90° pulse was used during
acquisition. The 13C NMR spectra were recorded with a
Bruker AC-250 P spectrometer at 62.90 MHz. The
progress of all reactions was monitored by thin-layer
chromatography (TLC) using aluminium sheets pre-
coated with silica gel 60F254 to a thickness of 0.2 mm
(Merck). Preparative TLC was performed with alu-
minium plates coated with silica gel 60F254 to a thick-
ness of 0.5 mm (Merck). Compounds were detected
with UV light (254 nm) and/or by spraying the sheets
with a 3% vanillin–sulfuric acid solution. Column chro-
matography (CC) was conducted under low pressure by
elution of columns with silica gel (0.040–0.063 mm,
Merck).
(t, 1H, H-2, J2,3a=4.4 Hz), 4.05–4.12 (m, 1H, H-4), 3.04
(m, 1H, H-5), 2.70 (t, 1H, H-6a, J6a,6b=5.1 Hz, J5,6a
=
4.47 Hz), 2.49 (dd, 1H, H-6b, J5,6b=3.0 Hz), 1.95 (dd,
1H, H-3b, J4,3b=4.4 Hz, J3a,3b=13.75 Hz), 1.61 (ddd,
1H, H-3a, J2,3a=4.4 Hz, J3a,4=4.7 Hz), 1.50 (s, 3H,
Me), 1.32 (s, 3H, Me); 13C NMR (CDCl3): l 110.2 (Cq,
isop.), 105.2 (C-1), 79.9 (C-2), 77.4 (C-4), 51.2 (C-5),
44.5 (C-6), 33.8 (C-3), 25.7 (Me), 26.3 (Me). Anal. calcd
for C9H14O4 (186.19): C, 58.05; H, 7.58. Found: C,
57.73; H, 7.34%.
3.3. General procedure for the preparation of the
lactones 8–15
A solution of n-butyllithium (1.6 M in n-hexane, 2.75
mL, 4.4 mmol) was added dropwise to a solution of
diisopropylamine (0.62 mL, 4.4 mmol) in anhydrous
THF (8 mL) under argon at 0°C, and the mixture was
stirred at 0°C for 25 min. A solution of either phenylse-
lenoacetic, a-phenylselenopropionic or phenylthioacetic
acid (2 mmol) in anhydrous THF (2 mL) was added
dropwise at 0°C and the reaction mixture was stirred
for 1 h at 0°C. A solution of the epoxide (2 mmol) in
anhydrous THF (3 mL/g epoxide) was then added
dropwise and, after stirring for 1 h at 0°C, the reaction
mixture was stirred for 16 h at rt. The reaction mixture
was treated with 50% acetic acid (5 mL) under reflux
for 6 h, and cooled to rt. After neutralisation with a
saturated NaHCO3 solution, the mixture was extracted
with diethyl ether (3×10 mL) and the organic phases
were washed with water and dried over sodium sulfate.
The lactones were isolated after solvent evaporation
and purification by CC.
3.2. General procedure for the synthesis of the epoxides 6
and 7
Triphenylphosphine (2.6 equiv.) was added to a solu-
tion of the diol (1 mmol) in benzene (17.5 mL) and the
mixture was stirred at rt for 15 min. After addition of
,
activated powdered molecular sieves (3 A, 800 mg),
DEAD (2.6 equiv.) was added dropwise to the mixture,
which was stirred at 80°C for 48 h. After filtration and
solvent evaporation under reduced pressure, the residue
was subjected to CC.
3.3.1. (7R)- and (7S)-3-O-Benzyl-6,7-dideoxy-1,2-O-
3.2.1. 5,6-Anhydro-3-O-benzyl-1,2-O-isopropylidene-a-
isopropylidene-7-phenylsulfanyl-a-D-gluco-octofuranuro-
D
-allofuranose 6. 3-O-Benzyl-1,2-O-isopropylidene-a-
D
-
no-8,5-lactone 8a and 8b. Starting from 1 (350 mg, 1.20
mmol), this procedure gave 8a and 8b (280 mg, p=
53%, ratio 8a/8b=3:2); CC eluent: EtOAc/n-hexane
(1:6); Rf=0.45 (EtOAc/n-hexane 1:3); IR (neat): 1782
(CꢀO), 1382 (CꢁO, isop.) cm−1; 1H NMR (CDCl3):
l 7.57–7.54 (m, 4H, Ph), 7.38–7.29 (m, 16H, Ph), 5.91
(d, 1H, H-1a, J1,2=3.6 Hz), 5.88 (d, 1H, H-1b, J1,2=3.6
Hz), 4.73–4.55 (m, 6H, H-2, OCH2Ph), 4.23 (d, 1H,
H-3a, J2,3=3.6 Hz), 4.20 (d, 1H, H-3b, J2,3=3.3 Hz),
4.14–3.95 (m, 6H, H-5, H-4, H-7), 2.86–2.76 (m, 2H,
H-6a), 2.43–2.33 (m, 2H, H-6b), 1.48 (s, 6H, Me), 1.31
(s, 6H, Me); 13C NMR (CDCl3): l 174.5 (CꢀO), 137.1,
137.0 (Cq, Ph), 133.4, 133.3, 129.2, 128.6, 128.5, 128.1,
128.0, 127.7 (Ph), 112.2, 112.1 (Cq, isop.), 105.2, 105.0
(C-1), 82.3, 82.2, 81.6, 81.3, 81.0 (C-2, C-3, C-4), 75.2,
73.8 (C-5), 72.5, 72.3 (OCH2Ph), 45.2, 44.5 (C-7), 33.0,
32.4 (C-6), 26.8, 26.7, 26.2, 26.1 (Me). Anal. calcd for
C24H26O6S (442.50): C, 65.14; H, 5.92; S, 7.24. Found:
C, 64.90; H, 5.92; S, 7.07%.
allofuranose28 (2.40 g, 8.2 mmol) gave 6 (1.75 g,
p=73%) as a syrup after purification by CC with
EtOAc/n-hexane (1:3); Rf=0.41 (EtOAc/n-hexane 1:3);
[h]2D0=+62 (c 1.0, CHCl3); IR (neat): 1262 (CꢁO, epox-
ide), 1380 (CꢁO, isop.) cm−1; 1H NMR (CDCl3):
l 7.39–7.29 (m, 5H, Ph), 5.74 (d, 1H, H-1, J1,2=3.6
Hz), 4.76, 4.72 (part A of AB system, OCH2Ph, JAB
=
11.7 Hz), 4.59–4.55 (m, 2H, H-2, OCH2Ph, part B of
AB system), 3.66 (dd, 1H, H-3, J2,3=4.2 Hz, J3,4=8.7
Hz), 3.19–3.16 (m, 1H, H-5), 4.20 (dd, 1H, H-4, J4,5
=
3.0 Hz), 2.79–2.73 (m, 2H, H-6a, H-6b), 1.53 (s, 3H,
Me), 1.37 (s, 3H, Me); 13C NMR (CDCl3): l 137.1 (Cq,
Ph), 128.5, 128.3, 127.9 (Ph), 112.8 (Cq, isop.), 103.8
(C-1), 71.8 (OCH2Ph), 77.5 (C-2), 77.0 (C-3), 76.5
(C-4), 50.4 (C-5), 44.2 (C-6), 26.6 (Me), 26.4 (Me).
Anal. calcd for C16H20O5 (292.3): C, 65.74; H, 6.88.
Found: C, 65.40; H, 6.88%.
3.2.2.
ribo-hexofuranose 7. Starting from 3-deoxy-1,2-O-iso-
propylidene-a- -ribo-hexofuranose 26b (730 mg, 3.57
mmol), this procedure gave 7 (500 mg, p=76%) after
CC purification with EtOAc/n-hexane (1:3); Rf=0.34
(EtOAc/n-hexane 1:3); [h]2D0=−18 (c 1.0, CHCl3); IR
(neat): 1380 (CꢁO, isop.), 1262 (CꢁO, epoxide) cm−1; 1H
NMR (CDCl3): l 5.73 (d, 1H, H-1, J1,2=3.8 Hz), 4.76
5,6-Anhydro-3-deoxy-1,2-O-isopropylidene-a-
D-
3.3.2. (7R)- and (7S)-3-O-Benzyl-6,7-dideoxy-1,2-O-
D
isopropylidene-7-phenylsulfanyl-a-D-allo-octofuranurono-
8,5-lactone 9a and 9b. Starting from 6 (280 mg, 0.96
mmol), this experiment gave 9 (232.6 mg, p=55%, ratio
9a/9b=5:3); CC eluent: EtOAc/n-hexane (1:3); Rf=
0.21 (EtOAc/n-hexane 1:3); IR (neat): 1786 (CꢀO), 1384
1
(CꢁO, isop.) cm−1; H NMR (CDCl3): l 7.53–7.30 (m,

1138
A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
20H, Ph), 5.73 (d, 1H, H-1a, J1,2=3.6 Hz), 5.69 (d, 1H,
H-1b, J1,2=3.6 Hz), 4.81–4.45 (m, 8H, OCH2Ph, H-2,
H-5), 4.26–4.22 (m, 2H, H-4), 3.95 (dd, 1H, H-7b), 3.82
(dd, 1H, H-7a), 3.70 (dd, 1H, H-3b, J2,3=4.2 Hz,
1774 (CꢀO), 1384 (CꢁO, isop.) cm−1; 1H NMR
(CDCl3): l 7.65–7.27 (m, 20H, Ph), 5.71–5.67 (m, 2H,
H-1), 4.74–4.43 (m, 8H, H-2, OCH2Ph, H-5), 4.21–4.17
(m, 2H, H-4), 4.00 (t, 1H, H-7b, J6a,7=J6b,7=9.6 Hz),
3.83 (dd, 1H, H-7a, J6a,7=9.3 Hz, J6b,7=4.5 Hz), 3.72–
3.67 (m, 2H, H-3), 2.61 (ddd, 1H, H-6aa, J5,6a=8.4
Hz), 2.42–2.35 (m, 2H, H-6ab, H-6bb), 2.04 (ddd, 1H,
H-6ba, J6a,6b=14.1 Hz, J5,6b=7.2 Hz), 1.57 (s, 6H, Me),
1.33 (s, 6H, Me); 13C NMR (CDCl3): l 175.1 (CꢀO),
136.8 (Cq, Ph), 135.7, 135.2, 129.4, 129.3, 129.1, 128.5,
128.3, 128.1 (Ph), 113.3 (Cq, isop.), 103.9 (C-1), 77.9,
77.8 (C-4), 77.4 (C-2), 77.3, 77.1 (C-5), 77.0, 76.0 (C-3),
72.0 (OCH2Ph), 37.0, 36.0 (C-7), 30.8, 30.3 (C-6), 26.7
(Me), 26.5 (Me). Anal. calcd for C24H26O6Se (489.37):
C, 58.90; H, 5.35. Found: C, 59.17; H, 5.41%.
J3,4=8.7 Hz), 3.63 (dd, 1H, H-3a, J2,3=4.5 Hz, J3,4=
9.3 Hz), 2.54 (ddd, 1H, H-6aa, J5,6a=6.6 Hz, J6a,7=9.0
Hz), 2.42–2.32 (m, 2H, H-6ab, H-6bb, J6a,7=11.1 Hz,
J
J
6b,7=9.3 Hz), 2.04 (ddd, 1H, H-6ba, J6b,7=5.4 Hz,
6a,6b=13.2 Hz, J5,6b=7.8 Hz), 1.59 (s, 6H, Me), 1.37
(s, 6H, Me); 13C NMR (CDCl3): l 174.2 (CꢀO), 173.8
(CꢀO), 136.8 (Cq, Ph), 133.4, 133.1, 129.2, 128.7, 128.4,
128.2 (Ph), 113.4 (Cq, isop.), 104.0 (C-1), 78.2 (C-4),
77.7, 76.7 (C-2, C-5), 76.6 (C-3), 72.1 (OCH2Ph), 45.8
(C-7b), 44.3 (C-7a), 30.4 (C-6b), 29.6 (C-6a), 26.8 (Me),
26.5 (Me). Anal. calcd for C24H26O6S (442.50): C,
65.14; H, 5.92; S, 7.24. Found: C, 65.15; H, 6.01; S,
7.06%.
3.3.6. (7R)- and (7S)-3-O-Benzyl-6,7-dideoxy-1,2-O-
isopropylidene-7-methyl-7-phenylselenyl-a- -gluco-octo-
D
3.3.3. (7R)- and (7S)-3,6,7-Trideoxy-1,2-O-isopropyl-
furanurono-8,5-lactone 13a and 13b. Starting from 1
(430 mg, 1.47 mmol), the same experiment gave 13a
and 13b (590 mg, p=79%, ratio 13a/13b=1:2); CC
eluent: EtOAc/n-hexane (1:6); Rf=0.49 (EtOAc/n-hex-
ane 1:6); IR (neat): 1773 (CꢀO), 1382 (CꢁO, isop.) cm−1;
1H NMR (CDCl3): l 7.67–7.63 (m, 4H, Ph), 7.41–7.26
(m, 16H, Ph), 5.95 (d, 1H, H-1a, J1,2=3.6 Hz), 5.90 (d,
1H, H-1b, J1,2=3.6 Hz), 4.83–4.17 (m, 7H, OCH2Ph,
H-2, H-5a), 4.18 (dd, 1H, H-4a, J3,4=10.2 Hz, J4,5=3.3
Hz), 4.09–4.05 (m, 2H, H-3), 3.78–3.75 (dd, 1H, H-4b,
idene-7-phenylsulfanyl-a- -ribo-octofuranurono-8,5-lact-
D
one 10a and 10b. Starting from 7 (250 mg, 1.34 mmol),
this experiment gave 10a and 10b (290 mg, p=64%,
ratio 10a/10b=2:1); CC eluent: EtOAc/n-hexane (1:3);
Rf=0.22 (EtOAc/n-hexane 1:3); IR (KBr): 1774 (CꢀO),
1384 (CꢁO, isop.) cm−1; 1H NMR (CDCl3) of 10a:
l 7.72–7.69 (m, 2H, Ph), 7.57–7.53 (m, 3H, Ph), 5.80 (d,
1H, H-1, J1,2=3.3 Hz), 4.76–4.73 (m, 1H, H-5 or H-7),
4.74 (t, 1H, H-2, J2,3b=4.5 Hz), 4.40–4.36 (m, 1H, H-7
or H-5), 3.95 (dd, 1H, H-4, J4,3b=9 Hz, J4,3a=5.4 Hz),
2.55–2.49 (m, 1H, H-6b), 2.35–2.33 (m, 1H, H-6a), 2.17
(m, 1H, H-3a), 1.67 (m, 1H, H-3b), 1.49 (s, 3H, Me),
1.31 (s, 3H, Me); 13C NMR (CDCl3) of 10a: l 174.2
(CꢀO), 133.5 (Cq, Ph), 131.6, 129.2, 128.7 (Ph), 111.6
(Cq, isop.), 105.6 (C-1), 80.3, 78.4, 78.4 (C-5, C-4, C-2),
44.5 (C-7), 34.9 (C-6), 31.5 (C-3), 26.7 (Me), 26.0 (Me).
Anal. calcd for C17H20O5S (336.38): C, 60.70; H, 5.98;
S, 9.53. Found: C, 60.80; H, 6.13; S, 9.46%.
J3,4=7.2 Hz, J4,5=3.3 Hz), 3.16 (d, 1H, H-5b, J5,6=3.9
Hz), 2.94 (dd, 1H, H-6ab, J5,6a=3.9 Hz, J6a,6b=5.1 Hz),
2.79 (dd, 1H, H-6bb, J5,6b=2.4 Hz), 2.59 (dd, 1H,
H-6aa, J5,6a=5.7 Hz, J6a,6b=14.4 Hz), 2.38 (dd, 1H,
H-6ba, J5,6b=9.9 Hz), 1.63 (s, 6H, Me-7), 1.51 (s, 6H,
Me, isop.), 1.31 (s, 6H, Me, isop.); 13C NMR (CDCl3):
l 176.7 (CꢀO), 137.6 (CqPh), 129.8, 129.0, 128.5, 128.1,
127.8, 127.6 (Ph), 112.1 (Cq, isop.), 105.2 (C-1), 82.6
(C-2), 82.5, 82.0 (C-3), 81.7, 81.5 (C-4), 73.1 (C-5a),
72.6 (OCH2Ph), 48.2 (C-5b), 46.9 (CH2-6a), 45.0, 44.2
(C-7), 41.3 (CH2-6b), 26.8 (Me, isop.), 26.2 (Me, isop.),
24.0 (Me-7). Anal. calcd for C25H28O6Se (503.42): C,
59.65; H, 5.60. Found: C, 60.00; H, 5.93%.
3.3.4. (7R) - and (7S) - 3 - O - Benzyl - 6,7 - dideoxy - 1,2 -
O-isopropylidene-7-phenylselenyl-a- -gluco-octofura-
D
nurono-8,5-lactone 11a and 11b. Starting with the epox-
ide 1 (170 mg, 0.58 mmol), this procedure gave 11 (145
mg, p=51%, ratio 11a/11b=1:1). CC eluent: EtOAc/
toluene (1:5); Rf=0.58 (EOAc/toluene 1:5); IR (neat):
3.3.7. (7R)- and (7S)-3-O-Benzyl-6,7-dideoxy-1,2-O-
isopropylidene-7-methyl-7-phenylselenyl-a- -allo-octofur-
D
1
1772 (CꢀO), 1376 (CꢁO, isop.) cm−1; H NMR (CDCl3)
anurono-8,5-lactone 14a and 14b. Starting from 6 (360
mg, 1.23 mmol), this procedure gave 14a and 14b (290
mg, p=47%, ratio 14a/14b=3:2); CC eluent: EtOAc/n-
hexane (1:3); Rf=0.40 (EtOAc/n-hexane 1:3); IR (neat):
of 11a: l 7.62–7.59 (m, 2H, Ph), 7.24–7.19 (m, 8H, Ph),
5.79 (s, 1H, H-1), 4.68–4.52 (m, 4H, H-3, H-5,
OCH2Ph), 4.06–3.95 (m, 3H, H-2, H-3, H-7), 2.75 (dd,
1H, H-6a, J6a,6b=13.4 Hz), 2.30 (dd, 1H, H-6b), 1.40 (s,
3H, Me), 1.24 (s, 3H, Me); 13C NMR (CDCl3) of 11a:
l 175.4 (CꢀO), 135.5 (Cq, Ph), 129.3, 128.8, 128.0,
127.6 (Ph), 112.2 (Cq, isop.), 105.2 (C-1), 82.6 (C-2),
81.5 (C-3), 81.5 (C-4), 74.5 (C-5), 72.7 (OCH2Ph), 53.3
(C-7), 36.3 (C-6), 27.0 (Me), 26.4 (Me). Anal. calcd for
C24H26O6Se (489.37): C, 58.90; H, 5.35. Found: C,
59.00; H, 5.38%.
1
1774 (CꢀO), 1380 (CꢁO, isop.) cm−1; H NMR (CDCl3)
of 14a and 14b: l 7.67–7.62 (m, 4H, Ph), 7.42–7.26 (m,
16H, Ph), 5.72 (d, 1H, H-1a, J1,2=3.6 Hz), 5.65 (d, 1H,
H-1b, J1,2=3.6 Hz), 4.78–4.72 (part A of AB system,
2H, OCH2Ph, JAB=12 Hz), 4.65–4.47 (m, 6H, part B of
AB system, OCH2Ph, H-2, H-5), 4.28 (dd, 1H, H-4b,
J
2,3=3.3 Hz, J3,4=9.3 Hz), 4.22 (dd, 1H, H-4a, J2,3=
2.7 Hz, J3,4=7.5 Hz), 3.75–3.67 (m, 2H, H-3), 2.61 (dd,
1H, H-6ab, J5,6a=8.4 Hz, J6a,6b=13.5 Hz), 2.35 (dd,
1H, H-6aa, J5,6a=10.5 Hz, J6a,6b=14 Hz), 2.13–1.99 (m,
2H, H-6b), 1.59 (s, 6H, Me), 1.54 (s, 6H, Me), 1.36 (s,
6H, Me); 13C NMR (CDCl3) of 14a and 14b: l 176.21
(CꢀO), 137.7, 137.6 (Cq, Ph), 129.9, 129.4, 129.1, 129.0,
128.6, 128.5, 128.3, 128.2, 128.1 (Ph), 113.3 (Cq, isop.),
103.9 (C-1), 77.8, 77.6 (C-3, C-4), 75.9 (C-5), 75.2 (C-2),
3.3.5. (7R)- and (7S)-3-O-Benzyl-6,7-dideoxy-1,2-O-iso-
propylidene-7-phenylselenyl-a- -allo-octofuranurono-8,5-
D
lactone 12a and 12b. Starting from 6 (300 mg, 1.03
mmol), this procedure gave 12a and 12b (240 mg,
p=80%, ratio 12a/12b=1:1); CC eluent: EtOAc/n-hex-
ane (1:3); Rf=0.34 (EtOAc/n-hexane 1:3); IR (neat):

A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1139
72.1, 71.9 (OCH2Ph), 44.7, 44.0 (C-7), 37.5, 37.3 (C-6),
26.8, 26.7, 26.6, 26.5 (Me), 23.9, 23.6 (Me-7). Anal.
calcd for C25H28O6Se (503.42): C, 59.65; H, 5.60.
Found: C, 59.84; H, 5.80%.
17 (20 mg, p=30%). Method B: Starting from 12 (130
mg, 0.3 mmol), this experiment gave 17 (100 mg, p=
91%); Rf=0.60 (EtOAc/n-hexane 1:1); [h]2D0=+47 (c
0.5, CH2Cl2); IR (KBr): 1774 (CꢀO), 1382 (CꢁO, isop.),
1
1662 (CꢀC) cm−1; H NMR (CDCl3): l 7.42 (d, H-6,
3.3.8. (7R)- and (7S)-3,6,7-Trideoxy-1,2-O-isopropyl-
J6,7=6 Hz), 7.36–7.29 (m, 5H, Ph), 6.08 (dd, H-7,
5,7=2.1 Hz), 5.7 (d, H-1, J1,2=3.6 Hz), 5.28 (br s,
idene-7-methyl-7-phenylselenyl-a- -ribo-octofuranurono-
D
J
8,5-lactone 15a and 15b. Starting from 7 (380 mg, 2.04
mmol), this experiment gave 15a and 15b (470 mg,
p=58%, ratio 15a/15b=7:3); CC eluent: EtOAc/n-hex-
ane (1:3); Rf=0.27 (EtOAc/n-hexane 1:3); IR (KBr):
H-5), 4.65, 4.61, 4.47 and 4.43 (AB system OCH2Ph,
AB=12 Hz), 4.51 (dd, H-2, J2,3=4.2 Hz), 4.33 (dd,
J
H-4, J4,5=3.3 Hz, J3,4=9 Hz), 3.62 (dd, H-3), 1.59 (s,
3H, Me, isop.), 1.35 (s, 3H, Me, isop.); 13C NMR
(CDCl3): l 173.8 (CꢀO), 152.9 (C-6), 136.4 (Cq, Ph),
128.6, 128.3 (Ph), 121.9 (C-7), 112.0 (Cq, isop.), 104.3
(C-1), 86.8 (C-5), 81.5 (C-4), 78.5 (C-2), 72.2
(OCH2Ph), 68.0 (C-3), 26.5 (Me, isop.), 26.3 (Me,
isop.). Anal. calcd for C18H20O6 (332.33): C, 65.06; H,
6.06. Found: C, 65.05; H, 6.29%.
1
1754 (CꢀO), 1378 (CꢁO, isop.) cm−1; H NMR (CDCl3)
of 15a: l 7.74–7.67 (m, 2H, Ph), 7.49–7.29 (m, 3H, Ph),
5.84 (d, 1H, H-1, J1,2=3.3 Hz), 4.78 (t, 1H, H-2,
J
J
2,3b=3.9 Hz), 4.48–4.41 (ddd, 1H, H-5, J4,5=5.1 Hz,
5,6b=10.1 Hz), 4.31–4.24 (ddd, 1H, H-4), 2.52 (dd, 1H,
H-6a, J5,6a=5.5 Hz, J6a,6b=14.1 Hz), 2.27–2.14 (m, 2H,
H-6b, H-3a), 1.73–1.66 (m, 4H, H-3b, Me), 1.53 (s, 3H,
Me), 1.35 (s, 3H, Me); 13C NMR (CDCl3) of 15a:
l 176.4 (CꢀO), 137.8 (Cq, Ph), 129.9, 129.1 (Ph), 111.6
(Cq, isop.), 105.6 (C-1), 80.2 (C-2), 78.6 (C-4), 76.9
(C-5), 44.7 (C-7), 40.5 (C-6), 35.1 (C-3), 26.7 (Me), 26.1
(Me), 24.0 (Me). Anal. calcd for C18H22O5Se (397.30):
C, 54.41; H, 5.57. Found: C, 54.79; H, 5.72%.
3.5.2. 3-O-Benzyl-6,7-dideoxy-1,2-O-isopropylidene-7-
methyl-a-
D
-gluco-oct-6-enofuranurono-8,5-lactone
19.
Method B: Starting from 13 (130 mg, 0.26 mmol), this
procedure gave 19 (45 mg, p=64%); unreacted 13 was
recovered (26 mg, p=20%); Rf=0.40 (EtOAc/n-hexane
1:4); [h]2D0=−22 (c 1.0, CHCl3); IR (neat): 1770 (CꢀO),
1378 (CꢁO, isop.), 1662 (CꢀC) cm−1; 1H NMR (CDCl3):
3.4. General procedure for the preparation of the
butenolides 16 and 17 (method A)
l 7.35–7.30 (m, 6H, H-6, Ph), 5.93 (d, 1H, H-1, J1,2=
3.6 Hz), 5.17 (dd, 1H, H-5, J4,5=8.6 Hz, J5,6=1.5 Hz),
4.69 (s, 2H, OCH2Ph), 4.63 (d, 1H, H-2), 4.14 (d, 1H,
H-3, J3,4=3.0 Hz), 3.91 (dd, 1H, H-4), 1.93 (s, 3H,
Me-7), 1.48 (s, 3H, Me, isop.), 1.25 (s, 3H, Me, isop.);
13C NMR (CDCl3): l 174.0 (CꢀO), 148.7 (C-6), 137.1
(Cq, Ph), 130.2 (C-7), 128.5, 128.1, 127.8 (Ph), 112.3
(Cq, isop.), 105.3 (C-1), 82.3 (C-2), 81.8 (C-3), 81.5
(C-4), 76.8 (C-5), 72.8 (OCH2Ph), 10.7 (Me-7), 26.73
(Me, isop.), 26.11 (Me, isop.). Anal. calcd for C19H22O6
(346.35): C, 65.89; H, 6.39. Found: C, 65.57; H, 6.45%.
A solution of m-CPBA (43 mg, 0.25 mmol) in CH2Cl2
(0.5 mL) was added under an argon atmosphere to a
solution of the phenylsulfanyllactone (0.2 mmol) in
CH2Cl2 (0.8 mL), previously cooled to 0°C. The reac-
tion mixture was stirred at 0°C for 1 h, washed with
aqueous NaHCO3 solution (10%) and extracted with
CH2Cl2 (3×5 mL). The organic phase was dried with
sodium sulfate and evaporated. The residue was solved
in toluene (10 mL/mmol) and heated for 3 h under
reflux. Solvent evaporation in vacuo gave a residue
which was purified by CC with EtOAc/n-hexane (1:4).
3.5.3. 3-O-Benzyl-6,7-dideoxy-1,2-O-isopropylidene-7-
methyl-a-
D
-allo-oct-6-enofuranurono-8,5-lactone
20.
Method B: Starting from 14 (100 mg, 0.2 mmol), this
method gave 20 (40 mg, p=73%, based upon reacted
starting material), recovered 14 (20 mg, p=20%); Rf=
0.23 (EtOAc/n-hexane 1:3); [h]2D0=+122 (c 1.0, CHCl3);
IR (neat): 1786 (CꢀO), 1384 (CꢁO, isop.), 1662 (CꢀC)
3.4.1. 3-O-Benzyl-6,7-dideoxy-1,2-O-isopropylidene-a-D-
gluco-oct-6-enofuranurono-8,5-lactone 16. Method A:
Starting from 8 (146 mg, 0.33 mmol), this method gave
16 (33 mg, p=43%). The physical and spectroscopic
data were in full agreement with those given in the
literature.15
1
cm−1; H NMR (CDCl3): l 7.41–7.30 (m, 5H, Ph), 7.25
(s, 1H, H-6), 5.77 (d, 1H, H-1, J1,2=3.6 Hz), 5.16 (br s,
1H, H-5), 4.68, 4.64 (part A of AB system, OCH2Ph,
3.5. General procedure for the synthesis of the
butenolides 17, 19–21 and 25, starting from the
corresponding phenylselenyllactones (method B)
JAB=12 Hz), 4.56 (t, 1H, H-2, J2,3=4.4 Hz), 4.49, 4.45
(part B of AB system), 4.32 (dd, 1H, H-4, J3,4=8.7 Hz,
J
4,5=3.0 Hz), 3.65 (dd, 1H, H-3), 1.93 (s, 3H, Me-7),
1.55 (s, 3H, Me, isop.), 1.39 (s, 3H, Me, isop.); 13C
NMR (CDCl3): l 173.8 (CꢀO), 145.3 (C-6), 136.9 (Cq,
Ph), 130.4 (C-7), 128.5, 128.2, 128.0 (Ph), 113.3 (Cq,
isop.), 104.1 (C-1), 79.3 (C-5), 78.6 (C-4), 72.1
(OCH2Ph), 76.6 (C-2), 75.5 (C-3), 26.8 (Me, isop.), 26.5
(Me, isop.), 10.7 (Me-7). Anal. calcd for C19H22O6
(346.35): C, 65.89; H, 6.39. Found: C, 65.63; H, 6.48%.
Glacial acetic acid (1–2 drops) was added to a solution
of the phenylselenyllactone (1 mmol) in THF (1 mL) at
0°C. H2O2 (6.7 equiv.) was added dropwise and the
mixture was stirred at 0°C for 45 min. Treatment with
saturated NaHCO3 solution was followed by extraction
with CH2Cl2 (3×5 mL). The organic phase was dried
with sodium sulfate and evaporated in vacuo. The
residue was purified by CC to give the butenolides.
3.5.4. 3,6,7-Trideoxy-1,2-O-isopropylidene-7-methyl-a-
D
-ribo-oct-6-enofuranurono-8,5-lactone 21. Method B:
3.5.1. 3-O-Benzyl-6,7-dideoxy-1,2-O-isopropylidene-a-
allo-oct-6-enofuranurono-8,5-lactone 17. Method A:
Starting from 9 (90 mg, 0.2 mmol), this procedure gave
D
-
Starting from 15 (100 mg, 0.25 mmol), this method
gave 21 (50 mg, p=93%, based upon reacted starting
material), recovered 15 (10 mg, p=10%); Rf=0.27

1140
A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
(EtOAc/n-hexane 1:3); [h]2D0=+40 (c 1.0, CH2Cl2); IR
(neat): 1766 (CꢀO), 1380 (CꢁO, isop.), 1662 (CꢀC) cm−1;
1H NMR (CDCl3): l 7.18 (br s, 1H, H-6), 5.84 (d, 1H,
H-1, J1,2=3.6 Hz), 4.87 (br d, 1H, H-5, J4,5=4.5 Hz),
4.77 (t, 1H, H-2, J2,3b=3.9 Hz), 4.19 (ddd, 1H, H-4,
gave 24a and 24b (460 mg, p=32%, ratio 24a/24b=3:1);
Rf=0.23 (EtOAc/n-hexane 1:1); IR (neat): 1784 (CꢀO),
1
1286 (CꢁO, epoxide) cm−1; H NMR (CDCl3) of 24a:
l 7.68–7.65 (m, 2H, Ph), 7.48–7.36 (m, 3H, Ph), 5.08 (s,
1H, H-1), 4.77 (ddd, 1H, H-5, J4,5=6.9 Hz, J5,6a=5.7 Hz,
J5,6b=10.5 Hz), 4.02 (d, 1H, H-4, J3,4=6.6 Hz), 3.74 (d,
J
J
3a,4=4.5 Hz, J3b,4=10.5 Hz), 2.19 (dd, 1H, H-3a,
3a,3b=13.5 Hz), 1.74 (ddd, 1H, H-3b), 1.94 (s, 3H,
1H, H-3, J2,3=2.7 Hz), 3.68 (d, 1H, H-2), 3.55 (s, 3H,
OCH3), 2.52 (dd, 1H, H-6a, J6a,6b=14.1 Hz), 2.32 (dd,
1H, H-6b), 1.66 (s, 3H, Me); 13C NMR (CDCl3) of 24a:
l 176.0 (C-8), 137.7 (Cq, Ph), 129.7, 128.9 (Ph), 102.2
(C-1), 77.0 (C-4), 75.7 (C-5), 56.8 (OMe), 54.7 (C-2), 53.4
(C-3), 44.5 (C-7), 39.0 (C-6), 23.9 (Me). Anal. calcd for
C16H18O5Se (369.25): C, 52.04; H, 4.90. Found: C, 51.78;
H, 4.95%.
Me-7), 1.49 (s, 3H, Me, isop.), 1.32 (s, 3H, Me, isop.);
13C NMR (CDCl3): l 173.7 (CꢀO), 146.4 (C-6), 130.9
(C-7), 111.7 (Cq, isop.), 105.6 (C-1), 81.2 (C-5), 80.2
(C-2), 78.3 (C-4), 35.2 (C-3), 26.8 (Me, isop.), 26.7 (Me,
isop.), 10.7 (Me-7). Anal. calcd for C12H16O5 (240.24): C,
60.00; H, 6.71. Found: C, 59.83; H, 6.80%.
3.5.5. Methyl 2,3-anhydro-6,7-dideoxy-7-methyl-b-D-
manno-oct-6-enofuranurono-8,5-lactone 25. Method B:
Starting from 24a and 24b (145 mg, 0.25 mmol), this
experiment gave 25 (30 mg, p=36%); Rf=0.13 (EtOAc/
n-hexane 1:1); [h]D20=−116 (c 1.5, CH2Cl2); IR (KBr):
1762 (CꢀO), 1662 (CꢀC) cm−1; 1H NMR (CDCl3): l 7.30
(d, 1H, H-6), 5.10 (d, 1H, H-5, J4,5=3.9 Hz, J5,6=3.3
Hz), 5.07 (s, 1H, H-1), 4.12 (dd, 1H, H-4, J3,4=5.7 Hz),
3.71 (d, 1H, H-2, J2,3=3 Hz), 3.61 (d, 1H, H-3), 3.55 (s,
3H, OMe), 1.96 (s, 3H, Me); 13C NMR (CDCl3): l 174.0
(CꢀO), 146.2 (C-6), 130.0 (C-7), 102.5 (C-1), 79.5 (C-5),
77.9 (C-4), 57.2 (OMe), 55.2 (C-2), 53.3 (C-3), 10.8 (Me).
Anal. calcd for C10H12O5 (212.2): C, 56.60; H, 5.69.
Found: C, 56.17; H, 5.94%.
3.8. Methyl 2,5-di-O-tosyl-b-
D
-glucofuranoside 22
-glucofura-
A solution of methyl 2,5-di-O-tosyl-b-
D
nurono-6,3-lactone24 (500 mg, 1 mmol) in THF (10 mL)
was added dropwise over 1 h to a suspension of LiBH4
(42 mg, 1.93 mmol) in THF (5 mL), previously cooled
to −10°C. The suspension was then stirred at +14°C for
16 h. Neutralisation with acetic acid (50% in H2O),
filtration and concentration under reduced pressure gave
a syrup which was treated with MeOH (3×5 mL) and
concentrated in vacuo. The residue was solved in EtOAc
and extracted with H2O. The organic phase was dried
with sodium sulfate and evaporated under reduced
pressure. The residue was purified by CC with EtOAc/
toluene (1:3) to give 22 (472 mg, p=94%); Rf=0.25
(EtOAc/toluene 1:3); [h]2D0=+44 (c 1, CHCl3); IR (KBr):
3500 (OH) cm−1; 1H NMR (CDCl3): l 7.85–7.82 (m, 4H,
Ph), 7.41–7.37 (m, 4H, Ph), 4.92–4.88 (m, 2H, H-1, H-5),
4.70 (s, 1H, H-2), 4.35 (t, 1H, H-3, J3,OH=8.1 Hz), 4.32
(dd, 1H, H-4, J4,5=3.9 Hz, J3,4=8.4 Hz), 3.90–3.82 (m,
2H, H-6a, H-6b), 3.31 (s, 3H, OCH3), 2.46 (s, 3H,
CH2Ph), 2.45 (s, 3H, CH2Ph); 13C NMR (CDCl3):
l 145.0, 145.1 (Cq, Ph), 130.0, 129.8, 128.8, 127.9 (CH,
Ph), 100.8 (C-1), 83.3 (C-2), 79.2 (C-5), 76.7 (C-4), 73.5
(C-3), 61.7 (C-6), 56.0 (OMe), 21.7 (CH3, Ts). Anal. calcd
for C21H26O10S2 (502.54): C, 50.21; H, 5.21; S, 12.76.
Found: C, 50.23; H, 5.30; S, 12.65%.
3.6. 3,6,7-Trideoxy-1,2-O-isopropylidene-a- -ribo-oct-
D
6-enofuranurono-8,5-lactone 18
A solution of NaIO4 (143 mg, 0.67 mmol) in H2O (1.7
mL) was added dropwise to a solution of 10 (190 mg, 0.56
mmol) in MeOH (1.7 mL), previously cooled to 0°C.
After 1 h at 0°C, the reaction mixture was stirred at rt
for 17 h. The solids were separated by filtration and the
filtrate was extracted with CH2Cl2 (3×5 mL). The organic
phase was washed with water, and dried with sodium
sulfate; solvent evaporation in vacuo afforded a residue
which was purified by CC with EtOAc/n-hexane (1:1)
giving the intermediate sulfoxide (60 mg, 0.17 mmol),
which was dissolved in toluene (2 mL) and heated under
reflux for 3 h to give, after evaporation, 18 (17 mg,
p=14%); Rf=0.35 (EtOAc/n-hexane 1:1); [h]2D0=+6 (c
1.0, CH2Cl2); IR (neat): 1792 (CꢀO), 1382 (CꢁO, isop.)
3.9. Methyl 2,3;5,6-dianhydro-b-D-mannofuranoside 23
1
cm−1; H NMR (CDCl3): l 7.59 (d, 1H, H-6), 6.19 (dd,
1H, H-7, J5,7=1.5 Hz, J6,7=6.0 Hz), 5.85 (d, 1H, H-1,
A solution of KOH (56 mg, 1.0 mmol) in water (1 mL)
J
1,2=3.0 Hz), 5.00 (dd, 1H, H-5, J4,5=6.0 Hz), 4.78 (t,
1H, H-2, J2,3a=3 Hz), 4.22 (ddd, 1H, H-4, J3a,4=9.0 Hz,
3b,4=3.0 Hz), 2.22 (dd, 1H, H-3b, J3a,3b=12.0 Hz), 1.77
was cooled to 10°C and added to a solution of methyl
2,5-ditosyl-b- -glucofuranoside 22 (202 mg, 0.4 mmol) in
D
J
water (4.0 mL) and THF (1.0 mL), previously cooled to
10°C. The reaction mixture was stirred at rt and followed
by TLC until the reaction was complete. After extraction
with CHCl3 (10×10 mL), the organic phases were dried
over sodium sulfate and concentrated under reduced
pressure. The residue was purified by CC with EtOAc/
toluene (1:3) to give 23 (61 mg, p=97%); Rf=0.5
(ddd, 1H, H-3a), 1.50 (s, 3H, Me, isop.), 1.33 (s, 3H, Me,
isop.); 13C NMR (CDCl3): l 172.5 (CꢀO), 154.1 (C-6),
122.5 (C-7), 111.9 (Cq, isop.), 105.7 (C-1), 83.6 (C-5),
80.82 (C-2), 78.0 (C-4), 35.4 (C-3), 27.1 (Me, isop.), 26.8
(Me, isop.). Anal. calcd for C11H14O5 (226.21): C, 58.40;
H, 6.23. Found: C, 57.92; H, 6.44%.
1
(EtOAc/n-hexane 1:1); [h]2D0=+66 (c 0.5, CH2Cl2); H
3.7. Methyl (7R)- and (7S)-2,3-anhydro-6,7-dideoxy-7-
NMR (CDCl3): l 5.01 (s, 1H, H-1), 3.78 (d, 1H, H-4,
methyl-7-phenylselenyl-b-
D
-manno-octofuranurono-8,5-
J
4,5=6.0 Hz), 3.68–3.65 (m, 2H, H-2, H-3), 3.43 (s, 3H,
OCH3), 3.19 (ddd, 1H, H-5), 2.87 (dd, 1H, H-6a,
5,6a=4.2 Hz), 2.75 (dd, 1H, H-6b, J5,6b=3 Hz, J6a,6b=6
Hz); 13C NMR (CDCl3): l 102.4 (C-1), 76.7 (C-4), 55.7
lactone 24a and 24b
J
Starting from 23 (624 mg, 3.95 mmol), this procedure

A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1141
(OMe), 55.6 (C-2), 53.7 (C-3), 50.4 (C-5), 44.0 (C-6).
Anal. calcd for C7H10O4 (158.14): C, 53.16; H, 6.36.
Found: C, 53.13; H, 6.35%.
3.11.1. 3,6,7-Trideoxy-1,2-O-isopropylidene-7-C-methyl-
ene-b- -lyxo-octofuranurono-8,5-lactone 28 and 3,6,7-
trideoxy-1,2-O-isopropylidene-7-C-methylene-a- -ribo-
L
D
octofuranurono-8,5-lactone 29. Starting from 27 (0.5 g,
2.9 mmol), this method gave a mixture of 28 and 29
(0.60 g, p=86%, ratio 28/29=7:3); IR (neat): 1767
(CꢀO), 1668 (CꢀC), 1370 (CꢁO, isop.) cm−1. Physical
3.10. 3-Deoxy-1,2-O-isopropylidene-a- -erythro-pento-
D
dialdo-1,4-furanose 27
and spectroscopic data for 28: Rf=0.59 (EtOAc/toluene
A mixture of 3-deoxy-1,2;5,6-di-O-isopropylidene-a-D-
1
2:1); H NMR (CDCl3): l 6.15 (t, 1H, H-7%a, J7%a,6a
=
ribo-hexofuranose 26a26 (1.0 g, 4.1 mmol) and 80%
acetic acid (29 mL) was stirred at 60°C for 1 h. After
cooling to rt, the reaction mixture was concentrated in
vacuo and toluene (3×21 mL) was added and evapo-
rated under reduced pressure. The residue was purified
by CC with the eluent EtOAc/toluene 1:4 to give
J
7%a,6b=2.9 Hz), 5.70 (d, 1H, H-1, J1,2=3.5 Hz), 5.56 (t,
1H, H-7%b, J7%b,6a=J7%b,6b=2.5 Hz), 4.68 (dd, 1H, H-2,
2,3a=7.5 Hz, J2,3b%=5.5 Hz), 4.53–4.47 (m, 1H, H-5),
J
4.29–4.25 (m, 1H, H-4), 2.99–2.95 (m, 2H, H-6a, H-6b),
2.03–1.87 (m, 2H, H-3a, H-3b), 1.44 (s, 3H, Me, isop.),
1.25 (s, 3H, Me, isop.); 13C NMR (CDCl3): l 170.0
(C-8), 133.7 (C-7), 121.9 (C-7%), 111.5 (Cq, isop.), 105.5
(C-1), 80.4 (C-2), 78.9 (C-4), 75.4 (C-5), 33.8 (C-3), 30.0
(C-6), 26.8 (Me, isop.), 26.0 (Me, isop.). Anal. calcd for
C12H16O5: C, 59.99; H, 6.71. Found: C, 60.22; H,
6.67%.
3-deoxy-1,2-O-isopropylidene-a- -ribo-hexofuranose 26b
D
as a syrup (0.67 g, p=80%); Rf=0.39 (EtOAc/toluene
2:1); [h]2D2=+20 (c 1.4, CHCl3); IR (neat): 3580 (OH),
1
1385 (CꢁO, isop.) cm−1; H NMR (CDCl3): l 5.79 (d,
1H, H-1, J1,2=3.1 Hz), 4.74 (t, 1H, H-2, J2,3=3.6 Hz),
4.35 (br s, 1H, OH-6), 4.20–4.13 (m, 1H, H-4), 3.81–
3.80 (m, 1H, H-5), 3.72–3.64 (m, 1H, H-6a), 3.53–3.50
(m, 1H, H-6b), 2.05 (dd, 1H, H-3a, J3,4=3.5, J3a,3b
=
3.11.2. (3S) - 2,3 - Dideoxy - 5,6 - O - isopropylidene - 1-
13.3), 1.87–1.78 (m, 1H, H-3b), 1.49 (s, 3H, Me, isop.),
1.31 (s, 3H, Me, isop.); 13C NMR (CDCl3): l 111.0
(Cq, isop.), 105.0 (C-1), 80.3 (C-2), 78.2 (C-4), 72.2
(C-5), 63.4 (C-6), 33.5 (C-3), 26.5 (Me), 25.9 (Me). A
solution of sodium metaperiodate (1.7 g, 8 mmol) in
water (30 mL) was added to the solution of 26b (0.67 g,
3.3 mmol) in ethanol (7 mL). After 20 min stirring at rt
in the dark, ethanol (250 mL) was added and the
mixture was filtered and concentrated. The residue was
extracted with dichloromethane (3×20 mL), and the
dichloromethane solution was dried with sodium sulfate
and concentrated to give 27 as a syrup (0.67 g, p=
65%); Rf=0.59 (EtOAc/toluene 2:1); [h]2D2=+32 (c 1.4,
CHCl3); IR (neat): 1775 (CꢀO), 1380 (CꢁO, isop.) cm−1;
1H NMR (CDCl3): l 9.60 (s, 1H, H-5), 5.77 (d, 1H,
H-1, J1,2=2.9 Hz), 4.69 (t, 1H, H-2, J2,3=3.5 Hz),
4.18–4.15 (m, 1H, H-4), 3.82–3.72 (m, 2H, H-5, H-6a),
3.48–3.43 (m, 1H, H-6b), 2.09–2.01 (m, 1H, H-3a),
1.87–1.78 (m, 1H, H-3b), 1.42 (s, 3H, Me, isop.), 1.24
(s, 3H, Me, isop.); 13C NMR (CDCl3): l 199.8 (C-5),
111.1 (Cq, isop.), 105.5 (C-1), 95.9 (C-2), 80.3 (C-4),
34.1 (C-3), 26.5 (Me), 25.9 (Me).
O-methyl-3%-methylene-2%-oxospiro[a- -erythro-hexofura-
D
nose-3,5%-tetrahydrofuran] 42. Starting from 41 (1 g, 4.63
mmol), this method gave 42 (0.64 g, p=49%); Rf=0.78
(EtOAc/toluene 10:1); [h]2D2=+18 (c 1.9, CHCl3); IR
(CHCl3): 1775 (CꢀO), 1669 (CꢀC), 1375 (CO, isop.)
1
cm−1; H NMR (CDCl3): l 6.18 (t, 1H, H-3¦a, J3¦a,4%a
=
J
3¦a,4%b=2.8 Hz), 5.61 (t, 1H, H-3¦b, J3¦b,4%a=J3¦b,4%b=2.5
Hz), 5.13 (dd, 1H, H-1, J1,2a=3.4 Hz, J1,2b=5.6 Hz),
4.23–4.19 (m, 1H, H-5), 4.12 (dd, 1H, H-6a, J5,6a=4.9
Hz, J6a,6%b=8.4 Hz), 3.96 (dd, 1H, H-6b, J5,6b=6.2 Hz),
3.82 (d, 1H, H-4, J4,5=8.1 Hz), 3.36 (s, 3H, OMe), 3.27
(dt, 1H, H-4%a, J4%a,4%b=17.5 Hz), 3.02 (dt, 1H, H-4%b),
2.65 (dd, 1H, H-2), 2.12 (dd, 1H, H-2b, J2a,2b=14.7
Hz), 1.37 (s, 3H, Me, isop.), 1.27 (s, 3H, Me, isop.); 13C
NMR (CDCl3): l 168.9 (CꢀO), 134.3 (H2CꢀC
6 ), 121.0
(H2Cꢀ), 109.1 (Cq, isop.), 103.5 (C-1), 87.8 (C-3), 83.1
6
(C-4), 72.7 (C-5), 67.2 (C-6), 55.0 (OMe), 47.7 (C-2),
35.2 (C-4%), 26.2 (Me, isop.), 24.7 (Me, isop.). Anal.
calcd for C14H20O6: C, 59.14; H, 7.09. Found: C, 59.11;
H, 7.14%.
3.11.3. (3R) - 2,3 - Dideoxy - 5,6 - O - isopropylidene - 1-
O-methyl-3%-methylene-2%-oxospiro[a- -erythro-hexofura-
D
3.11. General procedure for the synthesis of compounds
28, 29, 42–45, 51, 53, 55 and 57 by Reformatsky-type
reaction
nose-3,5%-tetrahydrofuran] 43. Starting from 41 (1 g, 4.63
mmol), this method gave 43 (0.22 g, p=17%); Rf=0.76
(EtOAc/toluene 10:1); [h]2D2=+8.3 (c 2.4, CHCl3); IR
(CHCl3): 1767 (CꢀO), 1660 (CꢀC), 1375 (CO, isop.)
A solution of ethyl bromomethylacrylate32 (5 mmol) in
anhydrous THF (2.5 mL) was added at rt under nitro-
gen to the mixture of activated33 granulated zinc 20
mesh and a solution of the carbonyl compound (3
mmol) in anhydrous THF (1.2 mL). The reaction mix-
ture was heated at 45°C for 1 h under nitrogen. After
cooling to rt, a 10% hydrochloric acid solution (25 mL),
previously cooled to 0°C, was added. After extraction
with dichloromethane (3×15 mL), the organic phase
was neutralised with aqueous sodium hydrogen carbon-
ate solution (2.5% 25 mL) and then dried with sodium
sulfate. Evaporation of the solvent afforded a residue
which was purified by CC.
cm−1; H NMR (CDCl3): l 6.19 (t, 1H, H-3¦a, J3¦a,4%a
=
1
J
3¦a,4%b=2.8 Hz), 5.61 (t, 1H, H-3¦b, J3¦b,4%a=J3¦b,4%b=2.5
Hz), 5.01 (dd, 1H, H-1, J1,2a=5.5 Hz, J1,2b=2.2 Hz),
4.16–3.93 (m, 4H, H-4, H-5, H-6a, H-6b), 3.37 (s, 3H,
OMe), 3.53 (dt, 1H, H-4%a, J4%a,4%b=17.2 Hz), 2.75 (dt,
1H, H-4%b), 2.45 (dd, 1H, H-2b, J2a,2b=14.3 Hz), 2.25
(dd, 1H, H-2a), 1.34 (s, 3H, Me, isop.), 1.28 (s, 3H, Me,
isop.); 13C NMR (CDCl3): l 168.9 (CꢀO), 134.8
(H2CꢀC6 ), 120.9 (H2C6 ꢀ), 110.1 (Cq, isop.), 103.1 (C-1),
87.6 (C-3), 82.7 (C-4), 74.2 (C-5), 68.1 (C-6), 55.2
(OMe), 46.8 (C-2), 34.9 (C-4%), 26.5 (Me, isop.), 25.5
(Me, isop.). Anal. calcd for C14H20O6: C, 59.14; H,
7.09. Found: C, 59.23; H, 7.14%.

1142
A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1
3.11.4. (3S)-2,3-Dideoxy-1-O-methyl-3%-methylene-2%-
oxospiro[a- -erythro-hexofuranose-3,5%-tetrahydrofuran]
1383 (CO, isop.) cm−1; H NMR (CDCl3): l 6.28 (t,
D
1H, H-3¦a, J3¦a,4%a=J3¦a,4%b=2.9 Hz), 5.73 (t, 1H, H-3¦b,
J3%b,4%a=J3¦b,4%b=2.5 Hz), 4.89 (d, 1H, H-3, J2,3=5.8
Hz), 4.72 (d, 1H, H-2), 4.38 (t, 1H, H-4, J4,5a=5.2 Hz,
4,5b=4.9 Hz), 4.14–3.72 (m, 2H, H-5a, H-5b), 3.44 (dt,
44. Starting from 41 (1 g, 4.63 mmol), this method gave
44 (0.04 g, p=5%); Rf=0.21 (EtOAc/toluene 10:1);
[h]2D2=+45.0 (c 1.0, CHCl3); IR (CHCl3): 3447 (OH),
1759 (CꢀO), 1636 (CꢀC) cm−1; 1H NMR (CDCl3):
l 6.19 (t, 1H, H-3¦a, J3¦a,4%a=J3¦a,4%b=2.8 Hz), 5.61 (t,
1H, H-3¦b, J3¦b,4%a=J3¦b,4%b=2.5 Hz), 5.13 (dd, 1H, H-1,
J
1H, H-4%a, J4%a,4%b=18.2 Hz), 2.95 (dt, 1H, H-4%b), 1.50
(s, 3H, Me, isop.), 1.35 (s, 3H, Me, isop.); 13C NMR
(CDCl3): l 167.8 (CꢀO), 133.1 (H2CꢀC6 ), 123.2 (H2C6 ꢀ),
J1,2a=5.5 Hz, J1,2b=3.2 Hz), 4.19–3.65 (m, 4H, H-4,
114.1 (Cq, isop.), 112.1 (C-1), 87.9 (C-4), 85.1 (C-2),
81.5 (C-3), 63.1 (C-5), 34.2 (C-4%), 26.2 (Me, isop.), 24.9
(Me, isop.). Anal. calcd for C12H16O6: C, 56.25; H,
6.29. Found: C, 56.22; H, 6.33%.
H-5, H-6a, H-6b), 3.37 (s, 3H, OMe), 3.40 (dt, 1H,
H-4%a, J4%a,4%b=17.2 Hz), 3.01 (dt, 1H, H-4%b), 2.64 (dd,
1H, H-2a, J2a,2b=14.6 Hz), 2.12 (dd, 1H, H-2b); 13C
NMR (CDCl3): l 170.0 (CꢀO), 134.6 (H2CꢀC
6 ), 121.8
(H2C
6
ꢀ), 103.6 (C-1), 88.7 (C-3), 74.3 (C-4),), 69.8 (C-5),
3.11.8. (1R) - 1 - Deoxy - 2,3;5,6 - di - O - isopropylidene-
62.3 (C-6), 55.4 (OMe), 48.0 (C-2), 35.9 (C-4%). Anal.
calcd for C11H16O6: C, 54.09; H, 6.60. Found: C, 53.98;
H, 6.65%.
3%-methylene-2%-oxospiro[D-mannofuranose-1,5%-tetrahy-
drofuran] 55. Starting from 54 (0.5 g, 1.94 mmol), this
method gave 55 (0.47 g, p=75%); Rf=0.65 (EtOAc/tol-
uene 1:2); [h]2D2=+120 (c 2.0, CHCl3); IR (neat): 1768
1
3.11.5. (3R)-2,3-Dideoxy-1-O-methyl-3%-methylene-2%-
(CꢀO), 1665 (CꢀC), 1385 (C-O, isop.) cm−1; H NMR
oxospiro[a-
D
-erythro-hexofuranose-3,5%-tetrahydrofuran]
(CDCl3): l 6.28 (t, 1H, H-3¦a, J3¦a,4%a=J3¦a,4%b=2.2 Hz),
5.73 (t, 1H, H-3¦b, J3¦b,4%a=J3¦b,4%b=2.5 Hz), 4.93 (dd,
1H, H-3, J3,4=3.6 Hz), 4.70 (d, 1H, H-2, J2,3=5.7 Hz),
4.40–4.33 (m, 1H, H-5), 4.10–3.95 (m, 3H, H-4, H-6a,
H-6b), 3.33 (dt, 1H, H-4%a, J4%a,4%b=18.3 Hz), 2.89 (dt,
1H, H-4%b), 1.48 (s, 3H, Me, isop.), 1.44 (s, 3H, Me,
isop.), 1.37 (s, 3H, Me, isop.), 1.34 (s, 3H, Me, isop.);
45. Starting from 41 (1 g, 4.63 mmol), this method gave
45 (0.08 g, p=8%); Rf=0.13 (EtOAc/toluene 10:1);
[h]2D2=−5.3 (c 1.9, CHCl3); IR (CHCl3): 3448 (OH),
1763 (CꢀO), 1645 (CꢀC) cm−1; 1H NMR (CDCl3):
l 6.21 (t, 1H, H-3¦a, J3¦a,4%a=J3¦a,4%b=2.8 Hz), 5.65 (t,
1H, H-3¦b, J3¦b,4%a=J3¦b,4%b=2.5 Hz), 4.47 (dd, 1H, H-1,
J1,2a=5.4 Hz, J1,2b=2.1 Hz), 3.92–3.55 (m, 4H, H-4,
13C NMR (CDCl3): l 167.8 (CꢀO), 132.8 (H2CꢀC
6
),
H-5, H-6a, H-6b), 3.50 (s, 3H, OMe), 3.33 (dt, 1H,
H-4%a, J4%a,4%b=17.2 Hz), 2.93 (dt, 1H, H-4%b), 2.14 (dd,
1H, H-2a, J2a,2b=14.1 Hz), 1.79 (dd, 1H, H-2b); 13C
123.0 (H2C6 ꢀ), 113.1 (Cq, isop.), 111.9 (C-1), 109.2 (Cq,
isop.), 84.3 (C-2), 80.8 (C-4),), 79.4 (C-3), 72.4 (C-5),
66.5 (C-6), 32.9 (C-4%), 26.7 (Me, isop.), 25.7 (Me,
isop.), 25.0 (Me, isop.), 24.5 (Me, isop.). Anal. calcd for
C16H22O7: C, 58.89; H, 6.79. Found: C, 58.85; H,
6.69%.
NMR (CDCl3): l 170.0 (CꢀO), 134.4 (H2CꢀC
6 ), 122.2
(H2C
6
ꢀ), 99.5 (C-1), 88.1 (C-3), 74.0 (C-4), 70.6 (C-5),
62.3 (C-6), 55.1 (OMe), 42.4 (C-2), 36.3 (C-4%). Anal.
calcd for C11H16O6: C, 54.09; H, 6.60. Found: C, 54.06;
H, 6.64%.
3.11.9. (6S)-3,6-Anhydro-1,2-O-isopropylidene-3%-meth-
ylene-2%-oxospiro[a-D-glucofuranose-6,5%-tetrahydrofuran]
3.11.6. (5R)-3,6-Anhydro-2,3-O-isopropylidene-1-O-
57. Starting from 56 (0.5 mg, 2.50 mmol), this method
gave 57 (0.55 g, p=78%); mp=145–146°C; Rf=0.65
(EtOAc/toluene 1:5); [h]2D2=+86 (c 1.0, CHCl3); IR
methyl-3%-methylene-2%-oxospiro[a- -ribo-hexofuran-3-
D
uloside-5,5%-tetrahydrofuran] 51. Starting from 50 (1 g,
4.35 mmol), this method gave 51 (0.95 g, p=73%);
mp=155.0–155.5°C; Rf=0.5 (EtOAc/toluene 1:2);
[h]2D2=+88 (c 1.6, CHCl3); IR (CHCl3): 1783 (CꢀO),
(CHCl3): 1786 (CꢀO), 1626 (CꢀC), 1380 (C-O, isop.)
1
cm−1; H NMR (CDCl3): l 6.22 (t, 1H, H-3¦a, J3¦a,4%a
=
J
3¦a,4%b=2.7 Hz), 6.14 (d, 1H, H-1, J1,2=3.4 Hz), 5.63 (t,
1H, H-3¦b, J3¦b,4%a=J3¦b,4%b=2.4 Hz), 4.84 (t, 1H, H-4,
J3,4=J4,5=4.9 Hz), 4.70 (d, 1H, H-3), 4.64 (d, 1H,
1
1628 (CꢀC), 1385 (CO, isop.) cm−1; H NMR (CDCl3):
l 6.26 (t, 1H, H-3¦a, J3¦a,4%a=J3¦a,4%b=2.7 Hz), 5.98 (d,
1H, H-1, J1,2=2.5 Hz), 5.71 (t, 1H, H-3¦b, J3¦b,4%a
=
H-2), 4.18 (br d, 1H, H-5), 3.86 (br s, 1H, OH-5), 3.14
(td, 1H, H-4%a, J4%a,4%b=17.6 Hz), 2.90 (td, 1H, H-4%b),
2.42 (s, 3H, Me, isop.), 1.29 (s, 3H, Me, isop.); 13C
J3¦b,4%b=2.4 Hz), 4.55 (d, 1H, H-2), 4.26 (s, 1H, H-4),
4.22 (part A of AB system, 1H, H-6a, JAB=10.0 Hz),
3.99 (part B of AB system, 1H, H-6b), 3.42 (s, 3H,
OMe), 3.14 (td, 1H, H-4%a, J4%a,4%b=17.4 Hz), 2.97 (td,
1H, H-4%b), 1.55 (s, 3H, Me, isop.), 1.38 (s, 3H, Me,
isop.); 13C NMR (CDCl3): l 168.2 (CꢀO), 132.8
NMR (CDCl3): l 168.1 (CꢀO), 132.7 (H2CꢀC
6 ), 123.1
(H2Cꢀ), 113.4 (Cq, isop.), 109.2 (C-6), 107.3 (C-1), 86.0
6
(C-2), 85.0 (C-3), 79.4 (C-4), 76.5 (C-5), 35.3 (C-4%),
27.5 (Me, isop.), 27.0 (Me, isop.). Anal. calcd for
C13H16O7: C, 54.93; H, 5.67. Found: C, 54.91; H,
5.69%.
(H2CꢀC6 ), 128.8 (C-5), 123.2 (H2C6 ꢀ), 114.9 (C-3), 114.0
(Cq, isop.), 107.2 (C-1), 87.6 (C-4), 80.1 (C-2), 75.2
(C-6), 51.8 (OMe), 36.0 (C-4%), 27.4 (Me, isop.), 26.9
(Me, isop.). Anal. calcd for C14H18O7: C, 56.37; H,
6.08. Found: C, 56.25; H, 6.03%.
3.12. General procedure for the synthesis of compounds
32–37
3.11.7. (1S)-1-Deoxy-2,3-O-isopropylidene-3%-methylene-
A solution of dimethylboron bromide (7.5 mL, 10.8
equiv.) in 1,2-dichloroethane (25 mL) was added at
−78°C under argon to a solution of the protected
lactone (2.9 mmol) in dichloromethane (24 mL). After
stirring for 2 h at −78°C, the temperature was raised to
0°C and triethylamine (0.082 mL) was added. The
2%-oxospiro[
D
-ribofuranose-1,5%-tetrahydrofuran]
53.
Starting from 52 (0.5 g, 2.66 mmol), and using dioxane
(3 mL) as solvent, this method gave 53 (0.44 g, p=
65%); Rf=0.43 (EtOAc/toluene 1:1); [h]2D2=+81 (c 1.6,
CHCl3); IR (neat): 3488 (OH), 1783 (CꢀO), 1669 (CꢀC),

A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1143
mixture was stirred at 18°C for 1 h and cooled to 0°C.
Addition of THF (30 mL) was followed by addition of
a saturated solution of sodium hydrogen carbonate (12
mL), dichloromethane (14 mL) and finally diethyl ether
(14 mL). The organic phase was washed with a saturated
solution of sodium chloride (2×9 mL), dried with sodium
sulfate, and evaporated in vacuo.
CHCl3); IR (CHCl3): 3452 (OH), 1771 (CꢀO), 1660
1
(CꢀC) cm−1; H NMR (C3D6O): l 6.09–6.05 (m, 2H,
H-7%a, H-1), 5.70 (t, 1H, H-7%b, J7%b,6a=J7%b,6b=2.3 Hz),
4.93–4.86 (m, 2H, H-5, OH-3), 4.68 (d, 1H, H-2, J1,2=4.3
Hz), 4.25 (d, 1H, H-3, J3,4=2.7 Hz), 4.03 (dd, 1H, H-4,
J
4,5=5.9 Hz), 3.12–3.07 (m, 2H, H-6a, H-6b), 1.23 (br s,
1H, OH), 0.90 (br s, 1H, OH); 13C NMR (C3D6O):
), 121.6 (H2C
l 170.3 (CꢀO), 133.9 (H2CꢀC
6
6 ꢀ), 105.7 (C-1),
3.12.1. 3-O-Benzyl-6,7-dideoxy-7-C-methylene-
L
-talo-
87.4 (C-2), 81.0 (C-4), 75.2 (C-3), 74.4 (C-5), 29.8 (C-6).
Anal. calcd for C9H12O6: C, 50.00; H, 5.59. Found: C,
50.05; H, 5.56%.
octofuranurono-8,5-lactone 32. Starting from 4 (1 g, 2.89
mmol), this method gave 32 (0.27 g, p=30%); mp=139–
141°C; Rf=0.30 (EtOAc/toluene 1:1); [h]2D2=+86.5 (c 1.0,
CHCl3); IR (CHCl3): 3446 (OH), 1770 (CꢀO), 1665
(CꢀC) cm−1; 1H NMR (CDCl3): l 7.32–7.20 (m, 5H, Ph),
6.17 (t, 1H, H-7%a, J7%a,6a=J7%a,6b=2.6 Hz), 5.82 (d, 1H,
H-1, J1,2=4.3 Hz), 5.58 (t, 1H, H-7%b, J7%b,6a=J7%b,6b=2.5
Hz), 4.79, 4.75 (part A of AB system, 1H, OCH2Ph,
3.12.5. 6,7-Dideoxy-7-C-methylene- -allo-octofuran-
D
urono-8,5-lactone 36. Starting from 5 (1 g, 2.89 mmol),
this method gave 36 (0.31 g, p=50%); mp=145–146°C;
Rf=0.12 (EtOAc/toluene 1:1); [h]2D2=+88 (c 1.0, CHCl3);
IR (CHCl3): 3450 (OH), 1775 (CꢀO), 1669 (CꢀC) cm−1;
1H NMR (CDCl3): l 6.28 (t, 1H, H-7%a, J7%a,6a=J7%a,6b
=
J
AB=11.2 Hz), 4.67–4.64 (m, 2H, H-2, H-5), 4.56, 4.52
(part B of AB system), 4.03 (dd, 1H, H-3, J2,3=5.5 Hz,
3,4=8.8 Hz), 3.82 (d, 1H, H-4), 2.99–2.88 (m, 2H, H-6a,
H-6b); 13C NMR (CDCl3): l 169.6 (CꢀO), 136.9 (Cq, Ph),
), 127.9, 127.9, 127.8 (Ph), 121.7 (H2C6 ꢀ),
2.8 Hz), 5.81 (d, 1H, H-1, J1,2=4.1 Hz), 5.60 (t, 1H,
H-7%b, J7%b,6a=J7%b,6b=2.5 Hz), 4.81–4.78 (m, 1H, H-5),
4.66 (t, 1H, H-2, J2,3=4.1 Hz), 4.25 (dd, 1H, H-4,
J
133.3 (H2CꢀC
6
J
3,4=2.3 Hz, J4,5=8.6 Hz), 3.70 (dd, 1H, H-3), 3.11–3.05
(m, 1H, H-6a), 2.95–2.83 (m, 1H, H-6b); 13C NMR
), 121.5 (H2C6 ꢀ),
104.3 (C-1), 78.7 (C-4), 77.2 (C-2), 76.8 (C-3), 72.9 (C-5),
72.0 (OCH2Ph), 29.3 (C-6). Anal. calcd for C16H18O6: C,
62.74; H, 5.92. Found: C, 62.71; H, 5.89%.
(CDCl3): l 169.7 (CꢀO), 133.5 (H2CꢀC
6
104.9 (C-1), 84.0 (C-4), 79.5 (C-2), 75.4 (C-3), 73.5 (C-5),
30.8 (C-6). Anal. calcd for C9H12O6: C, 50.00; H, 5.59.
Found: C, 49.96; H, 5.63%.
3.12.2. 6,7-Dideoxy-7-C-methylene- -talo-octofuran-
L
urono-8,5-lactone 33. Starting from 4 (1 g, 2.89 mmol),
this method gave 33 (0.31 g, p=50%); mp=150–151°C;
Rf=0.15 (EtOAc/toluene 1:1); [h]2D2=+142 (c 1.1,
CHCl3); IR (CHCl3): 3452 (OH), 1771 (CꢀO), 1660
3.12.6. 6,7-Dideoxy-7-C-methylene- -gluco-octofuran-
D
urono-8,5-lactone 37. Starting from 31 (1 g, 2.89 mmol),
this method gave 37 (0.31 g, p=50%); mp=140–141°C;
Rf=0.12 (EtOAc/toluene 1:1); [h]2D2=+85 (c 1.0, CHCl3);
IR (CHCl3): 3451 (OH), 1776 (CꢀO), 1670 (CꢀC) cm−1;
1
(CꢀC) cm−1; H NMR (CDCl3): l 6.28 (t, 1H, H-7%a,
J
7%a,6a=J7%a,6b=2.7 Hz), 6.07 (d, 1H, H-1, J1,2=4.2 Hz),
5.72 (t, 1H, H-7%b, J7%b,6a=J7%b,6b=2.3 Hz), 4.87–4.82
(ddd, 1H, H-5), 4.69 (dd, 1H, H-2, J2,3=2.6 Hz),
4.38–4.36 (d, 1H, H-4, J3,4=2.3 Hz), 3.86 (dd, 1H, H-3,
1H NMR (CDCl3): l 6.18 (t, 1H, H-7%a, J7%a,6a=J7%a,6b
=
2.8 Hz), 5.99 (d, 1H, H-1, J1,2=3.6 Hz), 5.54 (t, 1H,
H-7%b, J7%b,6a=J7%b,6b=2.5 Hz), 4.78–4.74 (m, 1H, H-5),
4.60 (d, 1H, H-2), 4.24–4.21 (m, 1H, H-4), 3.99–3.96 (m,
1H, H-3), 2.90–2.84 (m, 1H, H-6a), 2.59–2.45 (m, 1H,
H-6b); 13C NMR (CDCl3): l 171.1 (CꢀO), 134.0
J
2,3=8.0 Hz), 3.15–3.06 (m, 2H, H-6a, H-6b); 13C NMR
(CDCl3): l 170.2 (CꢀO), 133.3 (H2CꢀC6 ), 123.7 (H2C6 ꢀ),
104.9 (C-1), 86.3 (C-4), 80.6 (C-2), 74.3 (C-3), 73.1 (C-5),
30.7 (C-6). Anal. calcd for C9H12O6: C, 50.00; H, 5.59.
Found: C, 50.04; H, 5.57%.
(H2CꢀC6 ), 122.5 (H2C6 ꢀ), 106.0 (C-1), 82.2 (C-4), 77.8
(C-2), 78.8 (C-3), 72.0 (C-5), 29.6 (C-6). Anal. calcd for
C9H12O6: C, 50.00; H, 5.59. Found: C, 49.96; H, 5.63%.
3.12.3. 3-O-Benzyl-6,7-dideoxy-7-C-methylene- -ido-
L
octofuranurono-8,5-lactone 34. Starting from 30 (1 g, 2.89
mmol), this method gave 34 (0.28 g, p=31%); mp=135–
136°C; Rf=0.30 (EtOAc/toluene 1:1); [h]2D2=+99.5 (c 2.0,
CHCl3); IR (CHCl3): 3509 (OH), 1769 (CꢀO), 1667
(CꢀC) cm−1; 1H NMR (CDCl3): l 7.38–7.33 (m, 5H, Ph),
6.27 (t, 1H, H-7%a, J7%a,6a=J7%a,6b=2.9 Hz), 6.04 (d, 1H,
H-1, J1,2=4.4 Hz), 5.69 (t, 1H, H-7%b, J7%b,6a=J7%b,6b=2.5
Hz), 4.88–4.67 (m, 4H, H-5, H-2, OCH2Ph), 4.09 (d, 1H,
H-3, J3,4=3.2 Hz), 3.94 (dd, 1H, H-4, J4,5=7.5 Hz),
3.08–3.05 (m, 2H, H-6a, H-6b), 1.93 (s, 1H, OH), 1.73
(s, 1H, OH); 13C NMR (CDCl3): l 169.8 (CꢀO), 136.9
3.13. Methyl 2-deoxy-a,-b-D-arabinopyranoside 39a
and 39b
2-Deoxyglucose (1.0 g, 6.1 mmol) was added to a solution
of acetyl chloride in methanol, previously dried over 3
,
A molecular sieves. After stirring for 3 h at rt, the
reaction mixture was neutralised with potassium carbon-
ate, filtered over Celite and concentrated, affording a
mixture of 39a, 39b (1.04 g, p=98%, ratio 39a/39b=2:1).
Spectroscopic data of 39a: 1H NMR (C3D6O): l 4.75 (br
d, 1H, H-1, J1,2b=2.9 Hz), 4.14 (br s, 3H, OH-3, OH-4,
OH-6), 3.87–3.67 (m, 3H, H-5, H-6a, H-6b), 3.45–3.23
(m, 5H, H-3, H-4, OMe), 2.07–1.98 (m, 1H, H-2b), 1.60
(td, 1H, H-2a, J2a,2b=J2a,3=9.4 Hz, J1,2a=1.3 Hz); 13C
NMR (C3D6O): l 97.4 (C-1), 71.5 (C-4), 71.3 (C-3), 67.7
(C-5), 60.8 (C-6), 52.9 (OMe), 36.5 (C-2). Spectroscopic
(Cq, Ph), 133.4 (H2CꢀC
6 ), 128.4, 128.0, 127.7 (Ph), 123.0
(H2C
6
ꢀ), 104.8 (C-1), 83.1 (C-2), 81.6 (C-3), 80.0 (C-4),
72.9 (C-5), 72.4 (OCH2Ph), 30.2 (C-6). Anal. calcd for
C16H18O6: C, 62.74; H, 5.92. Found: C, 62.77; H, 5.88%.
3.12.4. 6,7 - Dideoxy - 7 - C - methylene - - ido - octofuran-
L
1
urono-8,5-lactone 35. Starting from 30 (1 g, 2.89 mmol),
this method gave 35 (0.32 g, p=52%); mp=153–154°C;
Rf=0.16 (EtOAc/toluene 1:1); [h]2D2=+122 (c 1.5,
data of 39b: H NMR (C3D6O): l 4.45 (dd, 1H, H-1,
J
1,2a=7.5 Hz, J1,2b=1.8 Hz), 4.14 (br s, 3H, OH-3, OH-4,
OH-6), 3.87–3.67 (m, 3H, H-5, H-6a, H-6b), 3.45–3.23

1144
A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
(m, 5H, H-3, H-4, OMe), 2.07–1.98 (m, 1H, H-2b), 1.41
(q, 1H, H-2a, J1,2a=J1,2b=J2a,2b=9.4 Hz); 13C NMR
(C3D6O): l 99.9 (C-1), 79.5 (C-4), 75.5 (C-3), 70.2 (C-5),
61.0 (C-6), 54.7 (OMe), 38.0 (C-2).
(0.82 g, p=85%); Rf=0.7 (EtOAc/toluene 10:1); [h]2D0=
+65 (c 1.6, CHCl3); IR (CHCl3): 1775 (CꢀO), 1375 (CꢁO,
isop.) cm−1; 1H NMR (CDCl3): l 5.36 (d, 1H, H-1,
J1,2a=5.3 Hz), 4.40–3.98 (m, 4H, H-4, H-5, H-6a, H-6b),
3.44 (s, 3H, OMe), 2.64 (dd, 1H, H-2a, J2a,2b=14.3), 2.47
(d, 1H, H-2b), 1.47 (s, 3H, Me, isop.), 1.36 (s, 3H, Me,
isop.); 13C NMR (CDCl3): l 210.8 (C-3), 110.0 (Cq,
isop.), 101.1 (C-1), 78.8, 75.1 (C-4, C-5), 66.1 (C-6), 55.9
(OMe), 44.2 (C-2), 25.8 (Me, isop.), 25.3 (Me, isop.).
Anal. calcd for C10H16O5: C, 55.55; H, 7.46. Found: C,
55.25; H, 7.66%.
3.14. Methyl 2-deoxy-5,6-O-isopropylidene-a,-b-
D
-ara-
bino-hexofuranoside 40a and 40b
Methyl 2-deoxy-a,-b- -arabinopyranoside 39a and 39b
D
(1.0 g, 5.62 mmol) was added to acetone, previously dried
,
over 3 A molecular sieves, containing powdered anhy-
drous zinc chloride (0.13 g), orthophosphoric acid (0.03
,
mL) and powdered 3 A molecular sieves. The mixture
3.15.2. Methyl (3R)-3,6-anhydro-2,3-O-isopropylidene-a-
was stirred at rt for 40 h, filtered, neutralised with basic
ion-exchange resin and concentrated. After extraction of
the residue with chloroform (3×25 mL), the solution was
dried with sodium sulfate and evaporated. CC with
EtOAc/toluene 1:5 gave 40a (0.8 g, p=65%) and 40b
(0.25 g, p=20%).
D
-ribo-hexo-3,5-diulofuranoside 50. Starting from 49a
(1.15 g, 5 mmol), this method gave 50 (1.04 g, p=90%);
mp=139–141°C; Rf=0.7 (EtOAc/toluene 1:1); [h]2D2=
+60 (c 1.0, CHCl3); IR (CHCl3): 1765 (CꢀO), 1380 (CO,
isop.) cm−1; 1H NMR (CDCl3): l 5.99 (d, 1H, H-1,
J1,2=3.7 Hz), 4.63 (d, 1H, H-2), 4.37, 4.32 (part A of AB
system, 1H, H-6a, JAB=10.8 Hz), 4.30–4.21 (m, 2H, part
B of AB system, H-6b, H-4), 3.49 (s, 3H, OMe), 1.57 (s,
3H, Me, isop.), 1.39 (s, 3H, Me, isop.); 13C NMR
(CDCl3): l 206.2 (C-5), 114.4 (C-3), 113.6 (Cq, isop.),
108.1 (C-1), 79.8 (C-4), 79.7 (C-2), 70.0 (C-6), 51.7
(OMe), 27.3 (Me, isop.), 27.0 (Me, isop.). Anal. calcd for
C10H14O6: C, 52.17; H, 6.13. Found: C, 52.20; H, 6.29%.
Data for 40a: Rf=0.6 (EtOAc); [h]2D0=+48.6 (c 1.3,
CHCl3); IR (neat): 3441 (OH), 1370 (CꢁO isop.) cm−1;
1H NMR (CDCl3): l 5.08 (t, 1H, H-1, J1,2a=J1,2b=4.3
Hz), 4.43–4.38 (dd, 1H, H-4, J3,4=8.4 Hz, J4,5=3.5 Hz),
4.26–4.24 (m, 1H, H-3), 4.09 (t, 1H, H-6a, J5,6a=J6a,6b
=
8.5 Hz), 3.93–3.73 (m, 2H, H-5, H-6b), 3.27 (s, 3H, OMe),
2.11–2.07 (m, 2H, H-2a, H-2b), 1.36 (s, 3H, Me, isop.),
1.20 (s, 3H, Me, isop.); 13C NMR (CDCl3): l 109.7 (Cq,
isop.), 105.2 (C-1), 81.9 (C-4), 73.8 (C-3), 71.8 (C-5), 68.0
(C-6), 55.5 (OMe), 42.5 (C-2), 27.1 (Me, isop.), 25.6 (Me,
isop.). Anal. calcd for C10H18O5: C, 55.03; H, 8.31.
Found: C, 55.29; H, 8.10%.
3.15.3. 2,3;5,6-Di-O-isopropylidene-
D-mannono-1,4-lac-
tone 5431. Starting from 2,3;5,6-di-O-isopropylidene-
D
-
mannofuranose (1.0 g, 3.85 mmol), this method gave 54
(0.84 g, p=85%); Rf=0.56 (EtOAc/toluene 1:2); IR
1
(neat): 1797 (CꢀO), 1389 (CꢁO, isop.) cm−1; H NMR
(CDCl3): l 4.91–4.84 (m, 2H, H-2, H-3), 4.48–4.36 (m,
2H, H-4, H-5), 4.19–4.05 (m, 2H, H-6a, H-6b), 1.49 (s,
3H, Me, isop.), 1.47 (s, 3H, Me, isop.), 1.43 (s, 3H, Me,
isop.), 1.40 (s, 3H, Me, isop.); 13C NMR (CDCl3): l 173.5
(C-1), 114.4 (Cq, isop.), 109.9 (Cq, isop.), 78.0 (C-4), 75.8
(C-2), 75.8 (C-3), 72.5 (C-5), 66.4 (C-6), 26.9 (Me, isop.),
26.7 (Me, isop.), 25.9 (Me, isop.), 25.0 (Me, isop.). Anal.
calcd for C12H18O6: C, 55.81; H, 7.02. Found: C, 55.76;
H, 7.08%.
Data for 40b: Rf=0.5 (EtOAc); [h]2D0=+2.8 (c 1.0,
CHCl3); IR (neat): 3440 (OH), 1373 (CꢁO, isop.) cm−1;
1H NMR (CDCl3): l 5.05 (d, 1H, H-1, J1,2b=5.6 Hz),
4.42 (t, 1H, H-4, J3,4=J4,5=3.9 Hz), 4.13–4.07 (m, 1H,
H-3), 3.89 (dd, 1H, H-6a, J5,6a=2.5 Hz, J6a,6b=11.2 Hz),
3.79–3.66 (m, 2H, H-5, H-6b), 3.36 (s, 3H, OMe),
2.20–2.16 (m, 2H, H-2a, H-2b), 1.36 (s, 3H, Me, isop.),
1.27 (s, 3H, Me, isop.); 13C NMR (CDCl3): l 106.0 (Cq,
isop.), 101.0 (C-1), 79.4 (C-4), 74.6 (C-3), 70.4 (C-5), 63.5
(C-6), 55.2 (OMe), 39.2 (C-2), 29.4 (Me, isop.), 25.6 (Me,
isop.). Anal. calcd for C10H18O5: C, 55.03; H, 8.31.
Found: C, 55.37; H, 8.09%.
3.16. 3,6-Anhydro- -ribo-hex-3-ulofuranose 47
D
A solution of 4616 (1.0 g, 3.9 mmol) in 75% formic acid
(36 mL) was heated at 50°C for 1 h. The reaction mixture
was concentrated under vacuum and, after adding tolu-
ene (20 mL) to the residue, the solution was concentrated.
This procedure was repeated three times and the final
residue was purified by CC with EtOAc/toluene 1:1 to
give 47 (0.42 g, p=60%); IR (neat): 3580 (OH) cm−1; 1H
NMR (C3D6O): l 5.31 (d, 1H, H-1, J1,2=3.2 Hz),
4.36–4.29 (m, 2H, H-4, H-5), 3.98–3.94 (d, 1H, H-2),
3.70–3.65 (m, 2H, H-6a, H-6b); 13C NMR (C3D6O):
114.3 (C-3), 96.7 (C-1), 76.5 (C-4), 73.7 (C-2), 73.5 (C-6),
68.2 (C-5). Anal. calcd for C6H10O6: C, 40.45; H, 5.66.
Found: C, 40.55; H, 5.60%.
3.15. General procedure for the preparation of
compounds 41, 50 and 54 by oxidation with pyridinium
chlorochromate/powdered molecular sieves
The starting material (4.39 mmol) was added to a
,
suspension of molecular sieves powder (4 A, 4.39 g) and
pyridinium chlorochromate (3.8 g, 13.6 mmol) in anhy-
drous dichloromethane (22 mL). After stirring for 2 h at
40°C, the reaction mixture was cooled to rt and added
to diethyl ether (260 mL) under stirring. The suspension
was filtered and filtered again over florisil (21 g). The
colourless solution was evaporated to dryness.
3.17. Methyl 3,6-anhydro-a,-b- -ribo-hex-3-
D
3.15.1. Methyl 2-deoxy-5,6-O-isopropylidene-a-
thro-hexofuranosid-3-ulose 41. Starting from methyl 2-
deoxy-5,6-O-isopropylidene-a- -arabino-hexofuranoside
40a (1.0 g, 4.39 mmol), this method gave 41 as a syrup
D
-ery-
ulofuranoside 48a and 48b
D
Acetyl chloride (0.17 mL) was added to a solution of 47a
and 47b (1 g, 5.6 mmol, ratio 2:1) in dry methanol

A. P. Rauter et al. / Tetrahedron: Asymmetry 12 (2001) 1131–1146
1145
(17 mL). After stirring for 4 h at rt, the reaction
mixture was neutralised with potassium carbonate,
filtered over Celite (8.0 g) and evaporated to dryness.
The residue was purified by CC with EtOAc/toluene 1:5
and gave 48a (0.86 g, 80%) and 48b (0.22 g, 20%).
72.2 (C-5), 50.5 (OMe), 28.0 (Me, isop.), 26.8 (Me,
isop.). Anal. calcd for C10H16O6: C, 51.72; H, 6.94.
Found: C, 51.98; H, 6.57%.
Acknowledgements
Data for compound 48a: Rf=0.53 (EtOAc/toluene 1:2);
[h]2D0=+60 (c 1.0, CHCl3); IR (neat): 3589 (OH) cm−1;
1H NMR (C3D6O): l 5.31 (d, 1H, H-1, J1,2=3.2 Hz),
4.26–4.19 (m, 2H, H-4, H-5), 3.91–3.86 (m, 2H, H-2,
H-6a), 3.70–3.65 (m, 1H, H-6b), 3.31 (s, 3H, OMe); 13C
NMR (CDCl3): l 114.3 (C-3), 99.9 (C-1), 81.5 (C-4),
76.4 (C-2), 73.3 (C-6), 70.3 (C-5), 50.3 (OMe). Anal.
calcd for C7H12O6: C, 43.75; H, 6.29. Found: C, 43.70;
H, 6.20%.
The authors are grateful to the Junta Nacional de
Investigac¸a˜o Cient´ıfica e Tecnolo´gica for a research
grant and Eng. Fernando Matos for running some
NMR spectra.
References
Data for compound 48b: Rf=0.4 (EtOAc/toluene 1:2);
[h]2D0=+2.0 (c 1.4, CHCl3); IR (neat): 3600 (OH) cm−1;
1H NMR (C3D6O): l 5.30 (s, 1H, H-1), 4.37 (br s, 1H,
H-4), 4.26–4.20 (m, 1H, H-5), 4.01–3.90 (m, 3H, H-2,
H-6a, H-6b), 3.29 (s, 3H, OMe); 13C NMR (CDCl3):
l 115.7 (C-3), 106.1 (C-1), 85.7 (C-4), 75.00 (C-6), 71.4
(C-2), 71.0 (C-5), 50.5 (OMe). Anal. calcd for C7H12O6:
C, 43.75; H, 6.29. Found: C, 43.98; H, 6.01%.
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3.18. Methyl 3,6-anhydro-2,3-O-isopropylidene-a,-b-
ribo-hex-3-ulofuranoside 49a and 49b
D-
Methyl
3,6-anhydro-a,-b-D-ribo-hex-3-ulofuranoside
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,
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1
(CꢁO, isop.) cm−1; H NMR (CDCl3): l 5.91 (d, 1H,
H-1, J1,2=3.5 Hz), 4.55 (d, 1H, H-2), 4.46 (br s, 2H,
H-4, H-5), 4.16 (dd, 1H, H-6a, J5,6a=6.3 Hz, J6a,6b=9.3
Hz), 3.80 (dd, 1H, H-6b, J5,6b=4.5 Hz), 3.40 (s, 3H,
OMe), 2.90 (br s, 1H, OH-5), 1.60 (s, 3H, Me, isop.),
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(C-2), 74.5 (C-6), 71.4 (C-5), 51.5 (OMe), 27.5 (Me,
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51.72; H, 6.94. Found: C, 51.75; H, 6.90%.
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1
(CꢁO, isop.) cm−1; H NMR (CDCl3): l 5.40 (s, 1H,
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(dd, 1H, H-6a, J5,6a=6.4 Hz, J6a,6b=9.4 Hz), 3.82 (dd,
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.