Formation of septanoses from hexopyranosides via 5,6-exo-glycals

Article abstract of DOI:10.1016/j.carres.2012.02.026

Methyl d-hexo-5-ulosides are obtained in high yield by dihydroxylation of 5,6-exo-glucal compounds. The bicyclic structure (1,6-anhydropyrano-5-ulose) of the products is adopted in solution and in solid state in a ⁴C ₁ conformation.

Full text of DOI:10.1016/j.carres.2012.02.026

Carbohydrate Research 356 (2012) 93–103
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Carbohydrate Research
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Formation of septanoses from hexopyranosides via 5,6-exo-glycals
Olivier Jackowski a, Françoise Chrétien a, Claude Didierjean b, Yves Chapleur a,
⇑
a UMR 7565 SRSMC, Nancy Université-CNRS, Groupe SUCRES, BP 70239, F-54506 Nancy Vandœuvre, France
b UMR 7036 CRM2, Nancy-Université-CNRS, BP 70239, F-54506 Nancy Vandoeuvre, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Methyl
The bicyclic structure (1,6-anhydropyrano-5-ulose) of the products is adopted in solution and in solid
state in a 4C1 conformation. This methodology has been used to prepare 1,6-anhydro-
-idopyrano-
5-uloses. Further manipulation of the 1,6-anhydro bridge allowed the preparation of the yet unknown
septano-5-uloses in moderate to high yields.
D-hexo-5-ulosides are obtained in high yield by dihydroxylation of 5,6-exo-glucal compounds.
Received 26 December 2011
Received in revised form 20 February 2012
Accepted 25 February 2012
Available online 14 March 2012
L
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
exo-Glycal
Dihydroxylation
Septanose
Radical deoxygenation
1,6-Anhydro bridge opening
1. Introduction
manipulation of the so-formed double bond by dihydroxylation
or epoxidation is then performed to complete the construction of
Hexoses exist mainly in two different forms, the pyranose and
furanose ring forms. In free sugars, these forms are in equilibrium
with each other and with the linear form. In contrast with pen-
toses, the primary hydroxyl group is rarely involved in a cycle
except in 1,6-anhydro derivatives. Simple glycosylation or proper
hydroxyl group protection of a hexose, for example, can drive this
equilibrium toward a favoured form furanose or pyranose or give a
mixture of both cyclic forms. As they are higher in energy com-
pared to furanose and pyranose forms, the formation of septanoses,
the seven-membered ring oxepane form of sugars, is by far less
frequent. Although there are no naturally-occurring septanosides,
the pioneering work of Stevens has shown that they can been
obtained, for example, in the classical protection of hexoses upon
reaction with acetone and methanol.1 Interestingly, tetra-
hydroxyoxepanes have also been obtained by simple dehydration
of alditols2 This type of seven-membered oxygenated ring is pres-
ent in many natural polyether compounds;3 thus, new accesses to
oxepane rings have been developed in the last decade.4
sugar analogues.11 Other useful approaches used the cyclo-isomer-
ization of an appropriate alkynol,12 or the homologation of a suit-
ably protected hexose at its reducing end.13 In addition to their
interest as carbohydrate mimics, septanoses offer the unique pos-
sibility of 5-OH group manipulation, which is rather difficult in
pyranose ring systems. This has been used to access
ured sugars from
-glucose.14 In this context, we decided to
explore new access to septanose and septanoside derivatives of
-glucose.
L-ido-config-
D
D
2. Results and discussion
2.1. Dihydroxylation of 5,6-exo-glycals
Some years ago, we investigated the olefin dihydroxylation of
5,6-exo-glycals using ruthenium(III) chloride and sodium perio-
date.15 Applied to a glucose derivative, this oxidation easily gave
a 1,6-anhydro derivative with a free hydroxyl group at C-5 by spon-
taneous or silica gel catalyzed trans-glycosylation. As shown later
by Murphy and co-workers, epoxidation of 5,6-exo-glycals also
led to this type of compound.16 In principle, displacement of the
equilibrium of the 1,6-anhydro pyranosidic form toward the 5-
ulo-septanose would allow easy manipulation of the 5-position.
Starting from the known 4,6-O-benzylidene derivative 1 the 4-O-
benzoyl derivative 3 was obtained by a classical route involving
our modified Hanessian–Hullar procedure17 and DBU catalyzed
dehydrobromination to give 2 and 3, respectively (Scheme 1). The
4-O-benzyl protected analogue 4 was obtained using a modification
Due to their growing importance as carbohydrate mimics,5 sep-
tanoses and septanosides have attracted interest and have been
introduced in biologically significant structures,6 or used as such.7
Thus, new elegant routes to heptoses in their septanose forms have
been opened by ring expansion of pyranoses8 mainly using cyclo-
propanation of glycals, or furanolactones9 or by de novo construc-
tion of the oxepane ring by ring closing metathesis.10 Further
⇑
Corresponding author. Fax: +33 383 68 47 80.
E-mail address: yves.chapleur@uhp-nancy.fr (Y. Chapleur).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.02.026

94
O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
NBS, CaCO3,
CCl4, reflux
DBU (2 eq.), DMF,
Ph
O
Br
BzO
MeO
μwave, 90°C., 4 h
O
O
O
O
BzO
MeO
MeO
MeO
90 %
45 %
MeO
MeO
OMe
OMe
OMe
1
2
3
1) MeONa, MeOH
2) BnBr, NaH, DMF
BH3-THF
Yb(OTf)3 94 %
CH2Cl2, rt
69%
NaH (3 eq.),
DMF, r.t., 6 h
HO
BnO
MeO
I
PPh3, I2
O
O
O
BnO
MeO
BnO
MeO
Tol, 70°C
90%
MeO
80 %
MeO
MeO
OMe
OMe
OMe
4
5
6
Scheme 1. Synthesis of 5,6-exo-glycals.
We were able to crystallize compound 8 and perform X-ray
crystal structure analysis. This confirmed the configuration at C-5
and showed a 4C1 conformation for the chair pyranose ring with
all substituents in equatorial orientation (Fig. 1).
Table 1
Dihydroxylation of 5,6-exo-glycals 3 and 6
OH
O
Dihydroxylation
O
RO
MeO
MeO
RO
MeO
MeO
OMe
O
2.2. Attempted deoxygenation at C-5
3 R = Bz
7 R = Bz
6
8
R = Bn
R = Bn
With these compounds in hands, it was attractive to open a
stereospecific route to L-idose derivatives, which would be avail-
Entry
Substrate
Conditionsa
Product
Reaction time (h)
Yield (%)
able by simple deoxygenation at C-5. We then focused on the
chemical manipulation of the OH-5 of compound 8. Different acyl-
ation and alkylation reactions were first tested and the results are
summarized on Table 2. All these reactions invariably led to the
easy transformation of the tertiary alcohol. Acetylation (entry 1),
methylation (entry 2), triflate formation (entry 3) proceeded well
in good to excellent yields. The reaction with thiocarbonyl diimi-
dazole needed microwave activation at 100 °C to proceed in 60%
yield (entry 4) giving the radical precursor 12. The structure of
these compounds was established on the basis of spectral data.
In particular 1H NMR spectra were very similar to those of 8 in
terms of coupling constants.
1
2
3
4
5
6
7
3
6
3
6
6
6
6
A
A
B
B
C
D
E
7
8
7
8
8
8
8
0.2
0.2
180
120
120
16
55
61
62
66
80
75
82
12
a
Reagents and conditions: (A) RuCl3 2 mol %, NaIO4 (1.5 equiv), EtOAc–acetoni-
trile–H2O, ꢀ5 °C; (B) K2OsO4 2.5 mol %, NMO (1.5 equiv), Acetone–water (4:1), rt;
(C) K2OsO4 2.5 mol %, NMO (1.5 equiv), t-BuOH–water (1:1), rt; (D) K2OsO4 8 mol %,
NMO (1.5 equiv), t-BuOH–water (1:1), rt. (E) K2OsO4 8 mol %, NMO (1.5 equiv),
THF–water (9:1), 45 °C.
In addition to compound 12, other esters suitable for radical
deoxygenation were prepared. However, the situation was more
complex upon treatment of 8 with phenylthionochloroformate in
of the method of Hung.18 Thus, treatment of 1 with borane–THF
complex in the presence of 9 mol % amount of Yb(OTf)3 in CH2Cl2
at room temperature gave 4 in 94% yield. To our knowledge, this
is the first example of the use of Yb(OTf)3 for this purpose. Upon
treatment of the crude material with the Garegg reagent, the iodide
5 was obtained in 90% over these two steps. Formation of the
exo-glycal 6 was cleanly achieved by the method of Chrétien.19
Alternatively, compound 6 can be obtained from 2 by the same
method in 69% yield over the two steps.
Oxidation of exo-glycal 3 was first carried out with a catalytic
amount of (2 mol %) ruthenium(III) chloride in the presence of
sodium periodate in a biphasic system at ꢀ5 °C for 12 min. The
1,6-anhydro derivative 7 was obtained after silica gel chromatog-
raphy in 55% yield (Table 1, entry 1). Similarly, dihydroxylation
of olefin 6 gave the 1,6-anhydro derivative 8 in 61% yield (Table
1, entry 2). These conditions proved critical and some over-oxida-
tion products were observed on prolonged reaction time or using
larger amounts of ruthenium chloride. Thus, classical dihydroxyla-
tion conditions were tested. Upon treatment with a catalytic
amount (2.5 mol %) of potassium osmate in the presence of
1.5 equiv of N-methyl morpholine oxide in a 4:1 acetone–water
mixture (Table 1, conditions B), the reaction was much slower
(entries 3 and 4) but provided the anhydro derivative as the sole
product in about 60% yield. Changing acetone for t-BuOH slightly
improved the yield of 8 to 80% (entry 5) whereas using 8 mol %
of potassium osmate gave useful reaction time and yield (entry
6). The reaction worked equally well in a THF–water 9:1 mixture
using 8 mol % of potassium osmate and in a reasonable reaction
time at 45 °C (entry 7).
Figure 1. ORTEP diagram of the X-ray molecular structure of compound 8.

O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
95
Table 2
wave activation (entry 5) gave a modest yield of the three com-
pounds in a ratio comparable to the conditions shown in entry 1.
One puzzling question was the mechanism involved in the
formation of the carbonate 13. In a series of papers reporting the
synthesis of thionocarbonates, Rist and co-workers discovered
the transformation of thionocarbonate into carbonate.20 Several
oxidants such as silver nitrate,21 lead tetraacetate,22a and chlo-
rine22b can be used to perform this transformation. This last reac-
tion is believed to proceed via addition of chlorine to the C@S
double bond followed by in situ hydrolysis of the unstable chloro-
sulfenyl species by residual water of the solvent. Such sulfur–oxy-
gen exchange has been also mentioned by Barton et al. in a radical
reaction but in the presence of tris-(4-bromophenyl)aminium
hexachloro antimonate is supposed to produce chloride ions.23
Pyridine could play an important role in this reaction as it is known
to react with phenylchlorothionoformate.24 When the pure thiono-
carbonate 14 was treated with phenyl chlorothionoformate in
dichloromethane in the presence of pyridine and DMAP, no reac-
tion occurred.
Chemical manipulation of OH-5 of 8
OH
OR
O
O
BnO
MeO
MeO
BnO
MeO
MeO
O
O
8
Entry
Conditionsa
R
Compound
Yield (%)
1
2
3
4
A
B
C
D
Ac
Me
Tf
Im(CS)
9
95
50
90
60
10
11
12
a
Reagents and conditions: (A) Ac2O (2 equiv), Pyr., cat. DMAP, CH2Cl2, 4 h; (B)
NaH (2.5 equiv), MeI (excess), DMF, rt 6 h; (C) Tf2O (3 equiv), Pyr., CH2Cl2, 3 h; (D)
Thiocarbonyl di-imidazole (4.4 equiv), DMAP cat., toluene, microwave activation
(50 W), 100 °C, 1 h 30 min.
With the two radical precursors 12 and 14 in hand, we explored
the radical deoxygenation reaction. The radical deoxygenation of
tertiary alcohols is a well documented process25 and thionocarbon-
ate,26 thionocarbamate27 at such a bridgehead position have been
successfully used. The thiono derivatives 12 and 14 were treated
under usual radical conditions (Bu3SnH, or tris(trimethylsilyl)silane,
AIBN, toluene, reflux). Whatever the conditions and the starting
thiono derivative, the only compound obtained was the starting
alcohol in yield ranging from 40% to 70%. Such reversal reactions
to the starting alcohol are known.28 This particular behavior is
attributed to the hemiketal nature of the alcohol. Deoxygenation
should proceed through the intermediate radical 17 produced by
homolytic C–O bond cleavage from the first radical 16 formed by
radical addition to the sulfur atom. As seen form a Newman projec-
tion of 17 along the C-5–O6 bond, the two alkoxy substituents,
(benzyloxy at C-4 and C-6–O-1 bond) do not efficiently stabilize
the radical by the b-alkoxy effect for geometrical reasons; the bonds
are not synclinal to the scissile C-5–O-5 bond.29 This radical, which
could assume a pyramidal geometry,30 is not stabilized by ring oxy-
gen lone pair also for geometrical reasons.31 Thus, the formation of
radical 17 from the intermediate carbon radical 16 would be slow
and 16 is faster trapped by tin hydride to form an orthoester, which
hydrolyzed to the starting alcohol. (Scheme 2)
pyridine at room temperature in the presence of DMAP. The O-5
acylated compound 14 was isolated in only 30% yield together with
two other compounds isolated in 45% and 25% yields, respectively.
The first one was the carbonate 13, which was also obtained in 80%
yield by reaction of 8 with phenylchloroformate (Table 3, entry 7).
The second compound was the 5-keto septanosyl chloride 15 (see
below).
Thus, from this reaction it was possible to obtain a radical pre-
cursor, that is, the thionocarbonate 14 albeit in low yield together
with the corresponding carbonate. The structure of this compound
was established inter alia by mass spectrometry (m/z = 439,
[M+Na]+) and 13C NMR spectroscopy, which did not show a thio-
carbonyl group signal (d 189.9 in 14) but instead a carbonyl group
signal at d 170 ppm. Also interesting was the formation of the sept-
anosyl chloride 15, a yet unknown compound suitable for further
transformation.
In an attempt to improve thionocarbonate formation we ex-
plored different reaction conditions, which are summarized in Table
3. The initial conditions were the use of dichloromethane as solvent
with pyridine as a base and DMAP as the acylating catalyst. Replac-
ing dichloromethane with THF was deleterious and no reaction oc-
curred. When using pyridine as solvent (Table 3, entry 3) the
expected thionocarbonate 14 and the septanosyl chloride 15 were
no longer formed and the carbonate 13 was formed in 90% yield
establishing a crucial role for pyridine in carbonate formation. Using
triethylamine as a base in dichloromethane, the reaction formed
only the expected thionocarbonate 14 in 60% yield (entry 4). Using
toluene as the solvent in the presence of pyridine and under micro-
We also attempted to use oxalates, which have been reported as
useful intermediates for alcohol deoxygenation.25e According to
Barton and Crich,25e alcohol 8 was treated with oxalyl chloride in
benzene for 20 h at room temperature followed by addition of
N-hydroxypyridine 2-thione and a catalytic amount of DMAP. Sub-
Table 3
Reaction of 8 with phenylthionoformates
S
O
O
PhO
BnO
+ MeO
MeO
PhO
BnO
MeO
MeO
OH
O
O
O
BnO
MeO
MeO
O
BnO
MeO
MeO
O
PhO(C=S)Cl
cat DMAP
O
+
Cl
O
O
O
8
13
14
15
Entry
Conditions
Products
Yield (product ratio)
1
2
3
4
5
6
7
Pyr. (10 equiv), CH2Cl2, 20 h
Pyr. (10 equiv), THF
Pyr., rt, 20 h
13 14 15
—
13
95 (1.3:1:1)
No reaction
90
Et3N (10 equiv), CH2Cl2, 24 h
14
60
Pyr. (10 equiv),
l
wave, toluene, 100 °C, 2 h.
13 14 15
13 14 15
13
30 (1.3:1:1)
93 (1.3:1:1)
80
Pyr. (10 equiv), hydroquinone (3 equiv), CH2Cl2, 20 h
PhO(CO)Cl (2 equiv), Pyr., DMAP cat., CH2Cl2, rt, 6 h

96
O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
SnBu3
SnBu3
H
S
X
S
HSnBu3
R
R
R
O
O
O
OH
O
Bu3SnH
H2O
O
O
O
BnO
MeO
MeO
BnO
MeO
MeO
BnO
MeO
MeO
BnO
MeO
MeO
O
O
O
O
12 R = ImS
14 R = PhO
16
8
O
BnO
4
Newman projection of 17
MeO
along the C5-O1 axis
OBn
O 1
MeO
2
17
O
Scheme 2. Possible mechanism of the radical reaction of thiono derivatives 12 and 14.
S
O
OH
O
O
O
Cl-
BnO
MeO
MeO
BnO
MeO
MeO
PhO
Cl
BnO
MeO
MeO
BnO
MeO
MeO
O
O
O
O
OH
1
OPh
Cl
O
8
18
15
S
NaH, DMF
ONa
O
O
O
O
BnO
MeO
MeO
BnO
MeO
MeO
BnO
MeO
BnO
MeO
MeO
Bu3SnH
SMe
CS2
O
O
ONa
O
O
MeO
O
19
20
S
Scheme 3. Septanose formation from 8.
R'O
OH
Et3SiH
O
O
BnO
MeO
MeO
BnO
MeO
BF3-Et2O
R
MeO
O
R
F
B
Et3SiH
21
22
23
24
R = H, R' = H
R = D, R' = H
R = H, R' = Ac
R = D, R' = Ac
F
8
F
Ac2O
Pyr.
HO
OH
O
OH
Et3SiH
O
BnO
MeO
MeO
HO
O
R
BnO
MeO
BnO
MeO
H
MeO
HO
H
MeO
R
25
26 R = H
27 R = D
28
Scheme 4. Lewis acid catalyzed ring opening using triethylsilane.
bon disulfide and methyl iodide to form the observed anomeric
xanthates 19 (Scheme 3). Radical deoxygenation of this mixture
using tri-n-butyltin hydride gave the expected deoxy compound
20 in 75% yield.
Figure 2. ORTEP diagram of the X-ray molecular structure of compound 15.
sequent addition of t-butyl thiol and heating for one hour at reflux
gave only the starting alcohol. As the formation of the mixed ester-
acylchloride was checked by 1H and 13C NMR spectroscopy, we
assumed that the thioester formation was successful and its
decomposition led to the starting alcohol as above.
The formation of xanthates, which are useful radical precursors,
was next examined. Treatment of 8 with 2 equiv of sodium hydride
in DMF for 10 min followed by addition of excess carbon disulfide
and then methyl iodide gave 19 as a mixture of anomers in 40%
yield together with the starting alcohol (23%). 1H and 13C NMR spec-
tra of the two compounds confirmed the presence of a carbonyl
group and a thionocarbonyl group and the septanose structure. This
contrasting result can be explained by initial formation of a tertiary
alcoholate in equilibrium with the secondary anomeric alcoholate
upon treatment of 8 with a strong base. The latter reacts with car-
The formation of the septanosyl chloride 15 could be explained
by a related mechanism. It might result from the reaction of phen-
ylthionochloroformate with the open form of 8, which rearranges
to produce a secondary hemiketal at C-1. The latter is then
transformed into a transient thionocarbonate 18, which is then
substituted with chlorine to afford 15 (Scheme 3). The structure of
15 was established from spectral data and the absolute configura-
tion at C-1 confirmed by single crystal X-ray analysis (Fig. 2).
To our knowledge, compound 15 is the first representative of
this class of compounds; thus, we attempted to find an efficient
way to produce it from 8. However, all attempts to drive the phen-
ythionocarbonylation reaction toward the septanosyl chloride 15
by modification of the stoichiometry were unsuccessful. On the
basis of the above mechanism involving anomeric hydroxyl activa-
tion, we investigated other alcohol activations. As in the case of

O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
97
triflate (Table 2, entry 3), mesylation led to the tertiary mesylate in
+ Ac2O
Yb(OTf)3
OR
O
"CH3CO+"
BnO
80% yield, but not unexpectedly, these activated compounds were
inert toward nucleophilic substitution. Finally, treatment of 8 with
triphenylphosphine and carbon tetrachloride gave no reaction and
complete recovery of the starting compound.
MeO
(TfO)3Yb
MeO
O
O
O
δ
8 R = H
9 R = Ac
O
δ
Reasoning that opening of the bicyclic system could occur under
acidic catalysis, the behavior of 8 in the presence of different
Brönsted and Lewis acids was investigated. Upon treatment with
Et3SiH in the presence of boron trifluoride etherate, 8 gave the
new compound 21 in 65% yield resulting from the deoxygenation
of the pyranose ring. From NMR data, it appeared that 21 no longer
had a bicyclic structure but rather a pyranose structure with two
methylenecarbons. It was thus an alditol derivativewith onealcohol
function. Due to overlapping signals for proton H-2, H-3, H-4 and
H-5 at 400 MHz, it was difficult to extract all coupling constants.
However, H-4 appeared as a pseudo triplet of 18 Hz width in agree-
ment with an axial orientation of H-5 (J4,5 = 9 Hz). Conventional
acetylation of 21 gave the corresponding acetate 23 showing a shift
of the two H-6 protons in the NMR spectra.
A tentative mechanism is given in Scheme 4. It is assumed that
the first reduction took place at the anomeric center of the bicyclic
system to provide stereoselectively the reduced compound 26 via
the intermediate oxonium 25. The lactol 26 is then subsequently re-
duced to 21 via the corresponding oxonium ion 28 (R = H). This
reductive sequence was carried out by using Et3SiD showing that
the resulting compound 22 isolated at the corresponding acetate
24 incorporated two deuterium atoms. Both deuteriums are axially
oriented at C-1 and C-5 in agreement with the generally observed
stereochemical course in the Lewis acid catalyzed reduction of gly-
cosides32 or lactols33 governed by the kinetic anomeric effect. Inter-
estingly, compound 26 was also obtained by careful reduction of 8
with sodium borohydride.
O
O
O
O
O
O
BnO
Ph
O
Ac
O
O Ac
MeO
MeO
MeO
MeO
31
O
30
O
O
Ac2O
Ph
O
O
Ac
MeO
MeO
32
O
AcO
MeO
+
PhCH2OAc +
"CH3CO+"
O
OAc
MeO
29
Scheme 5. Possible mechanism of the ytterbium(III) triflate catalyzed ring opening
by acetolysis.
OMe
O
OMe
O
Yb(OTf)3
Ac2O
BnO
MeO
BnO
MeO
OAc
OAc
MeO
MeO
O
10
33
OMe
O
OMe
O
BnO
MeO
BnO
MeO
2.3. Lewis acid catalyzed 1,6-anhydro ring opening
MeO
MeO
O
Ac
O
Ac
1,6-Anhydro sugars are widely used intermediates34 en route to
modified monosaccharides or more complex compounds. One of
the most important advantages of these compounds is the simulta-
neous protection at O-6 and O-1 and the facile ring opening to form
glycosides, glycosyl halides35 or thioglycosides.36 Thus, it was
interesting to investigate the ring opening of this new family of
1,6-anhydro compounds by examining the behavior of 8. Acid
34
35
Scheme 6. Ytterbium(III) triflate catalyzed acetolysis of 10.
the presence of 1 mol % of Yb(OTf)3 for 20 h, an anomeric mixture
of acetates 29 was obtained (entry 1, Table 4). It is interesting to
note that the benzyl group at C-4 also underwent solvolysis under
these conditions. In an attempt to control the whole reaction, ace-
tic anhydride was used in stoichiometric amount in dichlorometh-
ane as the solvent. The reaction was then very slow requiring one
week to achieve partial transformation of 8 into its acetate 9 and
the mixture of septanoses 29. Partial conversion of 8 into open
derivatives 29 and the acetate 9 using 4 equiv of acetic anhydride
required 16 h (entry 2).
catalysis is
a widely used method for 1,6-anhydro-bridge
opening.37
When submitted to methanolysis in the presence of HCl or
acidic resin, compound 8 led only to extensive decomposition.
Methanolysis in the presence of zinc bromide left 8 unchanged.
Acetolysis is a method of choice for 1,6-anhydro opening. This
reaction has been carried out inter alia using TMSOTf38 or other
Lewis acids such as metal triflates.39 After some experimentation,
we found that ytterbium triflate was an efficient catalyst for this
purpose. Upon treatment of 8 with Ac2O used as the solvent in
Increasing the catalyst amount significantly increased the reac-
tion rate. Thus, using 10 mol % of ytterbium catalyst shortened the
Table 4
Acetolysis of 1,6-anhydro derivatives 8 and 9
O
OR
Ac2O
Yb(OTf)3
AcO
O
BnO
MeO
MeO
O
OAc
MeO
MeO
O
8
9
29
R = H
R = Ac
Entry
Starting compound
Conditions
Products
Yield
1
2
3
4
8
8
8
9
Yb(OTf)3 (1 mol %), Ac2O 20 h
Yb(OTf)3 (1 mol %), Ac2O (4 equiv) CH2Cl2 16 h
Yb(OTf)3 (10 mol %), Ac2O 2 h
29–9
29–9
29
82–12
41–30
90
Yb(OTf)3 (10 mol %), Ac2O 8 h
29
80

98
O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
reaction time to 2 h (entry 3). In each case, a substantial amount of
acetate 9 was formed from 8 upon treatment with Ac2O and
Yb(OTf)3. This suggested that 9 could be an intermediate of the
reaction or at least that 9 could be opened as 8. This was indeed
the case as shown from entry 4, compound 9 giving 29 in 80% yield
within 8 h. Proton NMR analysis of compound 29 showed that it
Kieselgel 60 F254 plates (Merck). Compounds were visualized using
UV light (254 nm) and (or) 30% methanolic H2SO4 and heat as
developing agent. Column chromatography was performed on Sil-
ica Gel SI 60 (63–200 lm) (Merck) and high pressure column chro-
matography was performed on an axially compressed (8 bars)
20 mm id stainless steel column (Separex–Novasep) filled with
TLC Silica Gel 60H (Merck) using hexanes or EtOAc mixtures. FTIR
spectra were recorded on a Perkin–Elmer spectrum 1000 on NaCl
windows. Melting points were determined with a Tottoli apparatus
and are uncorrected. Optical rotations were measured on an Anton
Paar MC300 polarimeter. 1H and 13C NMR spectra were recorded
on a Bruker spectrometer DPX250 (250 MHz and 62.9 MHz, respec-
tively) and DRX400 (400 MHz and 100.6 MHz, respectively). For
complete assignment of 1H and 13C signals, two-dimensional
1H,1H COSY and 1H,13C correlation spectra were recorded. Chemical
shifts (d) are given in ppm relative to the solvent residual peak. The
following abbreviations are used for multiplicity of NMR signals:
s = singlet, d = doublet, t = triplet, q = quadruplet, m = multiplet,
br = broad signal. MS spectra were recorded on a Waters Platform
and HRMS on a Bruker MicroTOFQ apparatus. Microanalyses were
recorded on a Thermofinnigan Flash EA1112 apparatus. Microwave
syntheses were performed on a CEM Discover mono-mode oven
the temperature being controlled by standard external IR-sensor.
was a 1:4 a/b anomeric mixture.
A tentative mechanism of this unusual reaction is given in
Scheme 5. As usual, the lanthanide triflate activates acetic anhy-
dride to produce an acylating species that acetylates the tertiary
hydroxyl group of 8 to produce 9.39 The same acylating species
then activates the ring oxygen to give an intermediate oxonium
derivative 30, which should open releasing the ring strain and
giving the intermediate 31. Solvolysis of the benzyl group should
then occur intramolecularly to provide 29 via intermediate 32. This
1,6-anhydro opening mechanism proceeding via C-5–O-1 bond
cleavage is clearly different from the usual solvolysis reaction of
standard 1,6-anhydro sugars, which clearly involves the breaking
of the anomeric bond.
Although we have no definitive proof of this mechanism, it is
supported by different observations. Thus, we carried out the same
reaction on several substrates. The methyl glycoside 10 and the
triflate derivative 11 were treated according to the conditions of
entry 4, Table 4. Almost no reaction was observed with the latter
the starting compound being recovered. Compound 10 reacted
smoothly giving two compounds which were identified as the
anomeric acetates 33 in 82% yield. 1H NMR spectra confirmed the
4.2. Methyl 2,3-di-O-methyl-4-O-benzoyl-6-deoxy-a-D-xylo-hex-
5-enopyranoside (3)
formation of the b anomer as the major product (
a
/b ratio 1:2) b
Compound 3 was prepared by a modification of the method of
Sato.40 To a solution of the known bromide 241 (3.3 g, 8.5 mmol)
in dry DMF (10 mL) was added DBU (0.39 mL, 2.52 mmol) was
applied microwave activation at 90 °C (300 W monomode oven)
for 4 h. After cooling, the reaction medium was concentrated in
vacuo and the residue diluted with EtOAc (300 mL). The organic
layer was washed with saturated aqueous Na2SO3 (5 mL) and satu-
rated aqueous NaHCO3 (5 mL), dried over MgSO4 and concentrated.
Purification by column chromatography (hexanes–EtOAc 2:1) gave
3 (1 g, 42%) as white crystals, mp 70–72 °C (from CH2Cl2–hexane);
anomer: J1,2 = 6.6 Hz, d C-1 92.2; anomer: J1,2 = 3 Hz, d C-1 88.5).
a
From the above experiments, one may conclude that the nature
of the substituent at O-5 strongly influences the course of the reac-
tion. The presence of an attracting group like a triflate seems to deac-
tivate the 1,6-anhydro bridge opening. In contrast, the presence of
electron-donating group like a methyl favors the classical opening
via activation at O-1 to give 34 and a mixture of anomers 33 via
the oxenium 35 (Scheme 6). The presence of an acetate at O-5 should
favor activation of the oxygen ring pictured in 30 (Scheme 5). The
higher ratio of the b anomer in 29 also supports this hypothesis.
½
a 2D5
ꢁ
+75 (c 1.5, CHCl3), lit.40: mp 69–70 °C; +76 (c 1.5, CHCI3); Rf
0.59 (hexanes–EtOAc 2:1); IR (film), 1725, 1661 cmꢀ1 1H NMR
;
(CDCl3, 250 MHz): d 3.48 (dd, 1H, J1,2 3.6 J2,3 9.5 Hz, H-2), 3.49,
3.53, 3.58 (3s, 9H, H-Me), 3.79 (dd, 1H, J3,4 9.5 Hz, H-3), 4.55 (dd,
3. Conclusions
1H, J4,6 2.2, J6,6 2.2 Hz, H-6), 4.71 (dd, 1H, J4,6 2.2 Hz,H-60), 4.95
(d, 1H, H-1), 5.58 (ddd, 1H, H-4), 7.47, 7.61, 8.13 (m, 5H, H-Bz);
13C NMR (CDCl3 62.9 MHz): d 55.9, 59.5, 61.1 (C-Me), 71.8 (C-4),
80.7 (C-3), 81.5 (C-2), 96.4 (C-6), 98.4 (C-1), 128.7, 130.2, 133.6
(C-Bz), 151.4 (C-5), 165.2 (C-CO); MS 277 [MꢀOMe]+.
0
0
While developing the chemistry of exo-glycals, we found that
5,6-exo-glycals are readily transformed into 1,6-anhydro sugars
on simple dihydroxylation of the double bond. The reactivity of
these scarcely reported compounds has been explored. The chem-
ical manipulation of the tertiary anomeric alcohol was found easy
but attempted radical deoxygenation proved unfeasible. Under
certain conditions thionocarbonylation of this alcohol led invari-
ably to a septanose derivative albeit in low yield. Attempts to drive
this reaction toward this septanosyl chloride failed. The ring open-
ing of these peculiar 1,6-anhydro compounds having two anomeric
centers has been explored and found to depend on the substituent
at the anomeric O-5. Provided that an acetate is present, ytter-
bium(III)triflate catalyzed acetolysis of the C-5–O bond was ob-
served leading to a septanose ring. Concomitant benzyl ether
acetolysis probably via acetyl transfer was observed. This repre-
sents a unique way to obtain seven-membered ring ketohexoses,
species for which their chemistry is yet unknown.
4.3. Methyl 2,3-di-O-methyl-4-O-benzyl-6-deoxy-6-iodo-a-D-
glucopyranoside (5)
To a vigorously stirred solution of the known compound 442
(3.36 g, 10.6 mmol) in anhydrous toluene (100 mL) at 60 °C were
added triphenylphosphine (4.2 g, 16 mmol) and imidazole
(2.39 g, 36 mmol). After dissolution, iodine (2,95 g, 11.6 mmol)
was added and the heating was continued for 4 h. The solution
was cooled and diluted with EtOAc (200 mL). The organic layer
was washed with saturated solution of Na2SO3 (10 mL) then water
(2 x 20 mL), 1 N HCl (20 mL), water and finally satd NaHCO3
(20 mL) and water (20 mL). After drying over magnesium sulfate,
the solvent was removed under vacuum and the residue purified
4. Experimental
by column chromatography (hexanes–EtOAc 4:1) to yield
5
(4.02 g, 90%) as white crystals, mp 64–66 °C (from CH2Cl2–hex-
ane); ½a 2D5
ꢁ
+110.5 (c 1, CHCl3); Rf 0.37 (hexanes–EtOAc 4:1); 1H
4.1. General methods
NMR (CDCl3, 250 MHz): d 3.43–3.23 (m, 4H, H-4, H-2, H-5 et
H-60), 3.45 (s, 3H, H-Me), 3.52 (m, 1H, H-6), 3.55 (s, 3H, H-Me),
3.66 (m, 1H, H-3), 3.67 (s, 3H, H-Me), 4.70 (d, J 11 Hz, 1H, H-
All reactions were carried out in commercially available dry sol-
vents. TLC analyses were performed using standard procedures on

O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
99
CH2Ph), 4.86 (d, J 3.6 Hz, 1H, H-1), 4.93 (d, J 11 Hz, 1H, CH2Ph), 7.32
(m, 5H, H-arom Ph); 13C NMR (CDCl3 62.9 MHz): d 7.9 (C-6), 55.6,
59.2, 61.2 (C-Me), 69.3 (C-5), 75.4 (C-CH2Ph), 81.5 (C-4), 82.1 (C-
2), 83.4 (C-3), 97.6 (C-1), 128.1, 128.2, 128.6, 138.2 (C-arom Ph);
MS (EI) 422 [M]+, 391 [MꢀOMe]+. Anal. Calcd for C16H23IO5: C,
45.51; H, 5.49. Found: C, 45.44; H, 5.5.
on silica gel to give pure 8 (724 mg, 82%) as white crystals, mp
106–108 °C (from CH2Cl2–hexane); ½a D25
ꢁ
+71.8 (c 1, CHCl3); Rf
0.39 (hexanes–EtOAc 3:2); IR (KBr), 3338 cmꢀ1
;
1H NMR (CDCl3,
250 MHz): d 2.89 (bs, 1H,OH), 3.23 (dd, 1H, J1,2 1.5 Hz, J2,3 8.0 Hz,
0
H-2), 3.35 (dd, 1H, J4,6 2.2 J6,6 8.0 Hz, H-3), 3.46 (t, 1H, J3,4 8.0 Hz,
H-3), 3.50 (s, 3H, H-Me), 3.59 (dd, 1H, H-4), 3.61 (s, 3H, H-Me),
4.18 (d, 1H, H-60), 4.84 (AB, 2H, J 11.7 Hz, CH2Ph), 5.41 (d, 1H, J
1.5 Hz, H-1), 7.40–7.28 (m, 5H, H-arom. Ph); 13C NMR (CDCl3
62.9 MHz): d 58.6, 61.0 (C-Me), 68.5 (C-6), 74.7 (CH2Ph), 82.1 (C-
4), 83.7 (C-2), 84.6 (C-3), 97.9 (C-1), 103.6 (C-5), 127.8, 128.0,
128.6, 138.5 (C-arom Ph); MS (ESI) 319 [M+Na]+. Anal. Calcd for
4.4. Methyl 2,3-di-O-methyl-4-O-benzyl-6-deoxy-a-D-xylo-hex-
5-enopyranoside (6)
Sodium hydride 60% (98 mg, 4 mmol) was suspended in dry
THF (5 mL) and stirred for 5 min under an argon atmosphere. The
solvent was then removed and replaced with dry DMF (40 mL).
Compound 5 (430 mg, 1 mmol) was then added and the mixture
stirred at rt. After 6 h water (4 mL) was cautiously added then
EtOAc (100 mL). The organic layer was washed with saturated
NaHCO3 solution (5 mL), water (10 mL), dried over MgSO4. After fil-
tration and evaporation the residue was purified by column chro-
matography (hexane–EtOAc 2:1) to give pure 6 (240 mg, 80%) as a
C15H20O6: C, 60.80; H, 6.80. Found: C, 60.72; H, 6.83.
4.7. 1,6-Anhydro-5-C-O-acetyl-2,3-di-O-methyl-4-O-benzyl-b-L-
idopyranose (9)
To a solution of compound 8 (150 mg, 0.5 mmol) in CH2Cl2
(2 mL) was added pyridine (0.2 mL), acetic anhydride (0.2 mL,
1.5 mmol) and a catalytic amount of DMAP. After stirring at rt for
4 h, the mixture was concentrated under vacuum and the residue
was taken up in EtOAc (100 mL), washed with 3 M HCl (5 mL),
water (5 mL), 3 M NaOH (5 mL), water (5 mL) and dried over
Na2SO4. Filtration and evaporation of the solvent gave crude 9,
which was purified by column chromatography (hexanes–EtOAc
gum, ½a 2D5
ꢁ
+61.7 (c 1.5, CHCl3); lit.40
½
a 2D5
= +62.3 (c 0.154 CHCl3); Rf
ꢁ
0.48 (hexanes–EtOAc 2:1); IR (film), 1661 cmꢀ1; 1H NMR (acetone-
d6, 250 MHz): d 3.33 (dd, 1H, J1,2 3.2 Hz, J2,3 9.7 Hz, H-2), 3.41(s, 3H,
H-Me), 3.47 (s, 3H, H-Me), 3.60 (dd, 1H, J3,4 9.0 Hz, H-3), 3.58 (s, 3H,
0
H-Me), 3.84 (ddd, 1H, J4,6 J4,6 1.5 Hz, H-4), 4.67 (d, 1H, H-6), 4.79 (s,
2H, CH2Ph), 4.87 (m, 1H, H-60), 4.90 (d, 1H, H-1), 7.48–7.31 (m, 5H,
H-arom. Ph); 13C NMR (acetone-d6, 62.9 MHz): d 61.4, 59.0, 55.9 (C-
Me), 75.2 (CH2Ph), 80.6 (C-4), 82.6 (C-2), 84.0 (C-3), 96.9 (C-6), 99.7
(C-1), 128.8, 129.0, 129.6, 140.1 (C-arom Ph), 155.9 (C-5); MS 294
[M]+, 263 [MꢀOMe]+, 203 [MꢀPh]+.
2:1) to give pure 9 (160 mg, 95%) as an oil, ½a D25
ꢁ
+96.9 (c 1, CHCl3);
Rf 0.70 (hexanes–EtOAc 2:1); IR (film), 1765 cmꢀ1; 1H NMR (CDCl3,
250 MHz): d 1.98 (s, 3H, H-Ac), 3.27 (dd, 1H, J1,2 1.8, J2,3 8.0 Hz, H-
2), 3.41 (dd, 1H, J3,4 8.0 Hz, H-3), 3.47, 3.55 (2s, 6H, Me), 3.75 (dd,
1H, J4,6 1.4, J6,6 8.0 Hz, H-6), 4.17 (dd, 1H, H-4), 4.28 (d,1H, H-60),
0
4.70 (AB, 2H, J 11.6 Hz, CH2Ph), 5.45 (d, 1H, H-1), 7.42–7.17 (m,
5H, H-arom Ph); 13C NMR (CDCl3 62.9 MHz): d 21.5 (Ac), 60.7,
58.4 (Me), 67.9 (C-6), 74.6 (CH2Ph), 80.1 (C-4), 83.9 (C-2), 84.4
(C-3), 98.5 (C-1), 104.0 (C-5), 127.6, 127.8, 128.3, 137.9 (C-arom
Ph), 167.9 (CO); MS (ESI) 361 [M+Na]+. Anal. Calcd for C17H22O7:
C, 60.34; H, 6.55. Found: C, 60.49; H, 6.60.
4.5. 1,6-Anhydro-2,3-di-O-methyl-4-O-benzoyl-5-C-hydroxy-b-
L
-idopyranose (7)
Using RuCl3 (Method A of Table 1): To a solution of compound 3
(1.1 g, 3.56 mmol) in EtOAc–CH3CN 1:1 (30 mL) at 0 °C was added
under stirring a solution of RuCl3ꢂH2O (18 mg, 2 mol %) and NaIO4
(916 mg, 4.3 mmol) in water (15 mL). After 10 min, 5 mL of satu-
rated Na2S2O3 solution was added and the stirring continued for
30 min. The reaction medium was diluted with EtOAc (200 mL)
and the organic layer was washed with water (50 mL) and dried
over Na2SO4. After filtration and evaporation of the solvent under
vacuum, the residue was purified by chromatography on silica
gel to give pure 7 (0.6 g, 55%) as a white solid mp 120–123 °C (from
4.8. 1,6-Anhydro-2,3-di-O-methyl-5-C-methoxy-4-O-benzyl-b-L-
idopyranose (10)
To a solution of 8 (150 mg, 0.5 mmol) in DMF (5 mL) was added
NaH (50 mg, 1.25 mmol) at rt. After 15 min was added MeI (1 mL)
and the stirring was continued for 1 h. Water (2 mL) was cau-
tiously added, then EtOAc (100 mL). The organic phase was washed
with water, 3 M HCl (5 mL) and water. After drying on Na2SO4 fil-
tration and evaporation, the residue was purified by column chro-
matography (hexanes–EtOAc 4:1) to give pure 10 (80 mg, 50%) as
CH2Cl2–hexane), ½a D25
ꢁ
ꢀ2.3 (c 1, CHCl3); Rf 0.30 (hexanes–EtOAc–
Et2O 2:1:1); IR (KBr), 1723 cmꢀ1
;
1H NMR (CDCl3, 400 MHz): d
0
3.38 (dd, 1H, J1,2 1.8, J2,3 8.0 Hz, H-2), 3.52 (dd, 1H, J4,6 2.0, J6,6
8..2 Hz, H-6), 3.57, 3.60 (2s, 6H, H-Me), 3.75 (dd, 1H, J3,4 8.2 Hz,
H-3), 4.12 (d, 1H, H-60), 4.65 (s, 1H, H-OH), 5.23 (dd, 1H, H-4),
5.50 (d, 1H, H-1), 7.57, 7.66, 8.10 (3 m, 5H, H-Bz); 13C NMR (CDCl3
62.9 MHz): d 58.7, 60.8 (C-Me), 67.7 (C-6), 77.1 (C-4), 81.0 (C-3),
84.2 (C-2), 98.4 (C-1), 102.5 (C-5), 128.7, 129.9, 134.0 (C-Bz),
168.4 (C-CO); MS (EI) 311 [M+H]+, 293 [MꢀOH]+. Anal. Calcd for
an oil, ½a 2D5
ꢁ
+16.3 (c 0.3, CHCl3); Rf 0.78 (hexanes–EtOAc 1:1); 1H
NMR (CDCl3, 250 MHz): d 3.21 (dd, 1H, J1,2 1.9, J2,3 7.9 Hz, H-2),
3.40 (dd, 1H, J3,4 8.0 Hz, H-3), 3.44, 3.49, 3.58 (3s, 9H, OMe), 3.62
(m, 2H, H-4, H-6), 3.96 (d, 1H, H-4), 4.73 (d, 1H, J 11.5 Hz, CH2Ph),
4.88 (d, 1H, CH2Ph), 5.38 (d, 1H, H-1), 7.42–7.20 (m, 5H, H-arom
Ph); 13C NMR (CDCl3 62.9 MHz): d 50.8 (C-Me), 58.7, 61.0 (C-Me),
63.6 (C-6), 74.4 (CH2Ph), 81.2 (C-4), 83.9(C-2), 84.7 (C-3), 97.8
(C-1), 106.4 (C-5), 127.9, 127.9, 128.5, 138.7 (C-arom Ph); MS
(ESI) 333 [M+Na]+. Anal. Calcd for C16H22O6: C, 61.92; H, 7.14.
Found: C, 62.10; H, 7.18.
C15H18O7: C, 58.06; H, 5.84. Found: C, 58.22; H, 5.80.
4.6. 1,6-Anhydro-2,3-di-O-methyl-5-C-hydroxy-4-O-benzyl-b-L-
idopyranose (8)
Using K2OsO4 (Method E of Table 1): To a solution of compound
3 (882 mg, 3 mmol) in THF–water 9:1 (20 mL) was added under
stirring K2OsO4 (90 mg, 10 mol %) and NMO (486 mg, 3.6 mmol.).
The solution was stirred at the temperature and time indicated
in Table 1. After cooling, the reaction mixture was diluted with
CH2Cl2 (50 mL) the organic layer was washed with 1 N HCl
(5 mL), water (5 mL) and dried over Na2SO4. After filtration and sol-
vent evaporation under vacuum, the residue was chromatographed
4.9. 1,6-Anhydro-2,3-di-O-methyl-4-O-benzyl-5-C-
trifluoromethanesulfonyloxy-b-L-idopyranose (11)
To a solution of compound 8 (30 mg, 0.1 mmol) in CH2Cl2 (2 mL)
was added pyridine (0.1 mL), triflic anhydride (0.05 mL, 0.3 mmol)
and a catalytic amount of DMAP. After stirring at rt for 4 h the mix-
ture was concentrated under vacuum, the residue was taken up in
EtOAc (100 mL), washed with HCl 3 M (5 mL), water (5 mL), 3 M

100
O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
NaOH (5 mL), water (5 mL) and dried over Na2SO4. Filtration and
evaporation of the solvent, column chromatography (hexanes–
by high pressure chromatography (hexane–CH2Cl2 f1:2 ? 1:4) to
provide 14 (253 mg, 60%) as an oil, ½a D25
ꢁ
+91.5 (c 0.9, CHCl3); Rf
EtOAc 2:1) gave pure 11 (40 mg, 93%) as an oil, ½a D25
ꢁ
+56.8 (c 0.6,
0.76 (hexanes–EtOAc 2:1); 1H NMR (CDCl3, 250 MHz): d 3.37 (dd,
1H, J1,2 1.8, J2,3 8.0 Hz, H-2), 3.51 (t, 1H, J3,4 8.0 Hz, H-3), 3.54 (s,
CHCl3); Rf 0.63 (hexanes–EtOAc 2:1); 1H NMR (CDCl3, 250 MHz):
d 3.32 (dd, 1H, J1,2 1.8, J2,3 8.0, Hz, H-2), 3.42 (dd, 1H, J3,4 8.0 Hz,
H-3), 3.59, 3.93 (2s,.6H, Me), 4.00 (m, 2H, H-4, H-6), 4.35 (d, 1H,
0
3H, H-Me), 3.62 (s,.3H, H-Me), 4.08 (dd, 1H, J6,6 8.0, J4,6 1.8 Hz,
H-6), 4.41 (d, 1H, H-60), 4.69 (dd, 1H, H-4), 4.97–4.80 (AB, 2H, J
11.2 Hz, CH2Ph), 5.62 (d, 1H, H-1), 7.49–7.33 (m, 8H, H-arom Ph
and Ph), 7.02 (d, 2H, J 8 Hz, H-arom); 13C NMR (CDCl3 62.9 MHz):
d 58.5 (Me), 60.8 (Me), 68.1 (C-6), 74.7 (CH2Ph), 79.1 (C-4), 83.8
(C-3), 84.2 (C-2), 99.3 (C-1), 107.4 (C-5), 121.7, 126.8, 127.8,
128.3, 129.6 (C-arom), 138.7 (C-ipso), 150.7 (C-ipso), 189.9 (C-
CS); MS (ESI) 455 [M+Na]+. Anal. Calcd for C22H24O7S: C, 61.09;
H, 5.59. Found: C, 61.16; H, 5.74.
0
J6,6 8.0 Hz, H-6), 4.97–4.82 (AB, 2H, J 11.0 Hz, CH2Ph), 5.59 (d,
1H, H-1), 7.40–7.31 (m, 5H, H-arom); 13C NMR (CDCl3 62.9 MHz):
d 61.1, 58.8 (C-Me), 67.7 (C-6), 75.37 (CH2Ph), 81.4 (C-4), 83.9 (C-
3), 84.2 (C-2), 99.7 (C-1), 111.1 (C-5), 110.5, 120.8115.7, 125.9 (q,
J
322 Hz, CF3), 128.3, 128.6, 137.3 (C-arom Ph); NMR (
19F,
235 MHz CDCl3): d ꢀ79.91; .
4.10. 1,6-Anhydro-2,3-di-O-methyl-4-O-benzyl-5-C-
thiocarbonylimidazole-b-L-idopyranose (12)
4.13. (4S,5S,6R,7R)-4-Benzyloxy-7-chloro-5,6-
dimethoxyoxepan-3-one (15)
To a solution of 8 (150 mg, 0.5 mmol) in acetonitrile (3 mL) was
added thiocarbodiimidazole (400 mg, 4.4 equiv) and a catalytic
amount of DMAP. The flask was sealed and placed in a microwave
oven and irradiated at 300 W and 85 °C for 30 min. The solvents
were then removed and the residue chromatographed (hexanes–
To a stirred solution of compound 8 (300 mg, 1 mmol) in de-
gassed CH2Cl2 (5 mL) under argon was added pyridine (1 mL)
and phenylthiochloroformate (0.4 mL, 3 mmol) and a catalytic
amount of DMAP. After 20 h, CH2Cl2 (50 mL) was added. The or-
ganic layer was washed with 3 M HCl (5 mL), water NaHCO3 sat
(5 mL), and brine (5 mL). After drying over Na2SO4, filtration
and evaporation the residue was purified by high pressure chro-
matography (hexanes–EtOAc 95:5) to provide 13 (162 mg, 39%),
14 (130 mg, 29%) and 15(80 mg, 25%) as white crystals, mp 99–
EtOAc 2:1) to provide 12 (123 mg, 60%) as an oil, ½a D25
ꢁ
+25.9 (c
0.3, CHCl3); Rf 0.20 (hexanes–EtOAc 2:1); 1819 cmꢀ1
;
1H NMR
(CDCl3, 250 MHz): d 3.09 (s, 3H, H-Me), 3.58 (d, 1H, J 9.5 Hz, H-4)
3.37 (dd,1H, J 8.3 J 9.5 Hz, H-2), 3.68 (s, 3H, H-Me), 3.76 (t, 1H, J
9.5 Hz, H-3), 4.17 (AB, 2H, J 9.9 Hz, H-6), 4.87 (AB, 2H, J 12 Hz,
CH2Ph), 5.49 (d, 1H, J 8.3 Hz, H-1), 7.06, 7.13 (2s, 1H, H-Im),
7.48–7.32 (m, 5H, H-arom Ph), 7.70 (s, 1H, H-Im); 13C NMR (CDCl3
62.9 MHz): d 61.5, 60.7 (C-Me), 74.8 (C-6), 74.9 (CH2Ph), 76.0 (C-1),
82.1 (C-4), 83.2 (C-2), 83.7 (C-3), 108.6 (C-5), 116.8 (C-Im), 128.4,
128.6, 128.9, 136.8 (C-arom Ph), 136.7 130.5, 189.5 (C-CS); MS
(ESI) 391 [MꢀMe]+, 319 [M+H+Naꢀ(CS)Im]+.
101 °C (from CH2Cl2–hexane); ½a D25
ꢁ
+160.8 (c 0.87, CHCl3); Rf
0.78 (hexanes–EtOAc 2:1)); IR (KBr), 1739 cmꢀ1
;
1H NMR (CDCl3,
250 MHz): d 3.47 (s, 3H, H-Me), 3.46 (s, 3H, H-Me), 3.61 (dd, 1H,
J5,6 4.5, J6,7 2.9 Hz, H-6), 3.72 (dd, 1H, J4,53.7 Hz, H-5), 4.06 (d, 1H,
0
J2,2 17.7 Hz, H-2), 4.59 (d, 1H, J 11.2 Hz, CH2Ph), 4.60 (d,1H, H-4),
4.72 (d, 1H, H-20), 4.79 (d, 1H, CH2Ph), 6.18 (d, 1H, H-7), 7.35–
7.27 (m, 5H, H-arom Ph); 13C NMR (CDCl3 62.9 MHz): d 58.5
(C-Me), 60.7 (C-Me), 70.5 (C-2), 72.4 (CH2Ph), 82.7 (C-6), 83.2
(C-5), 85.2(C-4), 91.2 (C-7), 128.8–127.7, 137.2 (C-arom Ph),
203.6 (C-3); MS (ESI) 339 [M(37Cl)+Na]+, 337 [M+Na]+.
Anal. Calcd for C15H19ClO5: C, 57.23; H, 6.08. Found: C, 57.45;
H, 6.12.
4.11. 1,6-Anhydro-2,3-di-O-methyl-5-C-phenoxycarbonate-4-O-
benzyl-b-L-idopyranose (13)
To a stirred solution of compound 8 (130 mg, 0.44 mmol) in
CH2Cl2 (5 mL) at rt was added pyridine (1 mL), phenylchlorofor-
mate (0.11 mL, 0.88 mmol) and a catalytic amount of DMAP. After
stirring at rt for 6 h, the mixture was diluted with CH2Cl2 (100 mL),
washed with HCl 1 M (5 mL), water (5 mL), 3 M NaOH (5 mL),
water (5 mL) and dried over Na2SO4. Filtration and evaporation
of the solvent gave crude 9, which was purified by column chroma-
tography (hexanes–EtOAc 1:1) to give pure 13 (145 mg, 80%) as an
4.14. (3R,4R,5S)-5-Benzyloxy-3,4-dimethoxy-6-oxo-oxepan-2-yl
S-methyl carbonodithioate (19)
Sodium hydride 60% (85 mg, 2 mmol) was suspended in dry
THF (5 mL) and stirred for 5 min under argon atmosphere. The sol-
vent was then removed and replaced by dry DMF (10 mL). A solu-
tion of compound 8 (300 mg, 1 mmol) in DMF (1 mL) was added
and the mixture is stirred at rt for 15 min. Carbon disulfide
(1 mL) was added and after 15 min MeI (0.5 mL, 5 mmol) was
added. After 45 min, the mixture was quenched by the addition
of water (1 mL) and diluted with EtOAc (100 mL). The organic layer
was washed with water and dried over magnesium sulfate. Purifi-
cation on high pressure silica gel column (hexanes–EtOAc 9:1,
7 mL/min) gave 19, 3:1 anomeric mixture (160 mg, 40%) as a foam,
oil,
½
a 2D5
ꢁ
+75.9 (c 1, CHCl3); Rf 0.72 (hexanes–EtOAc 2:1);
;
1779 cmꢀ1
1H NMR (CDCl3, 400 MHz): d 3.35 (dd, 1H, J1,2 2.0, J2,3
8.0 Hz, H-2), 3.50 (dd, 1H, J3,4 8.0 Hz, H-3), 3.54, 3.62 (2s, 6H, H-
0
Me), 3.96 (dd,1H, J4,6 2, J6,6 8.0 Hz, H-6), 4.32 (dd,1H, H-4), 4.37
(d, 1H, H-60), 4.80 (d, 1H, J 11.2 Hz, CH2Ph), 4.86 (d, 1H, CH2Ph),
5.57 (d,1H, H-1), 7.09–7.43 (m, 10H, H-arom); 13C NMR (CDCl3
100 MHz): d 59.0, 61.2 (Me), 68.1 (C-6), 75.2 (CH2Ph), 80.4 (C-4),
84.3 (C-3), 84.8 (C-2), 99.5 (C-1), 105.9 (C-5), 121.2, 126.8, 128.1,
128.3, 128.8, 130.0, 138.3, 150.4, (C-arom), 151.0 (CO); MS (ESI)
439 [M+Na]+. Anal. Calcd for C22H24O8: C, 63.45; H, 5.80. Found:
C, 63.44; H, 5.87.
Rf 0.67 (hexanes–EtOAc 2:1); 1742, 1174, 1102, 1034 cmꢀ1 1H
;
NMR (CDCl3, 250 MHz): d 2.60 (s, 3H, SMe), 3.44*, 3.48*, 3.49,
3.59 (4s, 6H, Me), 3.74 (m, 1H, H-4), 3.93 (m, 1H, H-3), 4.40 (AB,
1H J 17.7 Hz, H-7), 4.70 (d, 1H, J4,5 3.9 Hz, H-5), 4.60* (AB, 1H, J
11.3 Hz, CH2Ph), 4.58 (AB, 1H, CH2Ph), 6.23 (s, H-2), 6.83* (d, J2,3
2.9 Hz, H-2), 7.42–7.30 (m, 5H, H-arom) *refer to major anomer
signals; 13C NMR (CDCl3 62.9 MHz): d 19.6, 19.4* (C-SMe), 58.7*,
59.9, 60.2*, 60.5 (C-Me), 72.6*, 74.7 (CH2Ph).72.9, 71.4* (C-7),
78.4, 79.3* (C-3), 81.7, 82.7* (C-4), 83.7, 86.2* (C-5), 98.0*, 101.7
(C-2), 127.9, 128.1, 128.4, 128.6, 137.5*, 137.8 (C-arom Ph),
204.2*, 207.0 (C-6), 214.8*, 215.1 (C-CS); MS (ESI) 409
[M+Na]+.
4.12. 1,6-Anhydro-2,3-di-O-methyl-4-O-benzyl-5-C-
phenyoxythiocarbonyloxy-b-L-idopyranose (14)
To a stirred solution of compound 8 (300 mg, 1 mmol) in de-
gassed CH2Cl2 (5 mL) under argon was added NEt3 (1.2 mL,
10 mmol) and phenylthiochloroformate (0.8 mL, 6 mmol) and a
catalytic amount of DMAP. After 30 h, EtOAc (150 mL) was added.
The organic layer was washed with 3 M HCl (5 mL), water satu-
rated solution of NaHCO3 (5 mL), and brine (5 mL). After drying
over Na2SO4, filtration and evaporation, the residue was purified

O. Jackowski et al. / Carbohydrate Research 356 (2012) 93–103
101
4.15. (4S,5R,6S)-4-Benzyloxy-5,6-dimethoxyoxepan-3-one (20)
4.19. (1R)-6-O-Acetyl-1,5-anhydro-1,5-dideutero-2,3-di-O-
methyl-4-O-benzyl- -glucitol (24)
D
To a solution of compounds 19 (40 mg, 0.1 mmol) in degassed
toluene (3 mL) and AIBN (2 mg, 10 mol %) under argon at 95 °C,
was slowly added by syringe a solution of n-Bu3SnH (0.15 mL,
3 mmol) in toluene (1 mL) within 1 h. The mixture was then con-
centrated in vacuo and purified by column chromatography (hex-
ane–EtOAc 4:1) to provide 20 (25 mg, 90%) as an oil, Rf 0.78
Crude compound 22 was treated by the procedure described for
the synthesis of 9 and gave 24 (107 mg, 82%) as an oil, ½a D25
ꢁ
+58.3
(c 0.5, CHCl3); Rf 0.5 (toluene–EtOAc 2:1); 1H NMR (CDCl3,
400 MHz): d 2.06 (s, 3H, COCH3), 3.26–3.40 (m, 3H, H-2, H-3, H-
4), 3.50 (s, 3H, OMe), 3.69 (s, 3H, OMe), 4.65 (d, 1H, J 1,2 4 Hz, H-
(hexanes–EtOAc 2:1); IR (film), 1736 cmꢀ1
;
1H NMR (CDCl3,
1), 4.20 (d, 1H, J6,6 12 Hz, H-6), 4.32 (d, 1H, H-60), 4.60 (d, 1H, J
0
250 MHz): d 3.55, 3.47 (2s, 6H, Me), 3.57 (t, 1H, J 4.0 Hz, H-7),
3.74 (m, 2H, H-6, H-5), 4.09 (m, 3H, H-70, H-2, H-20), 4.61 (AB,
2H, J 11.3 Hz, CH2Ph), 4.74 (d, 1H, J4,3 3.7 Hz, H-4), 7.41–7.28 (m,
5H, H-arom Ph); 13C NMR (CDCl3 62.9 MHz): d 58.7, 57.7 (C-Me),
68.7 (C-7), 72.4 (C-2), 75.3 (CH2Ph), 80.6 (C-4), 83.5(C-6), 86.7 (C-
5), 128.1, 128.4, 128.6, 137.8 (C-arom Ph), 206.7 (C-3). Anal. Calcd
for C15H20O5: C, 64.27; H, 7.19. Found: C, 64.39; H, 7.25.
12 Hz, CH2Ph), 4.88 (d, 1H, J 12 Hz, CH2Ph), 7.37 (m, 5H, Ph); 13C
NMR (CD3OD 100 MHz): d 19.5 (Ac), 57.8 (OMe), 60.0 (OMe),
63.4 (C-6), 66.8 (t, J 21 Hz, C-1), 74.6 (CH2Ph), 76.7 (C-2), 77.3 (t,
J 21 Hz, C-5), 80.3 (C-3), 88.1 (C-4), 127.7 (Ar), 127.9 (Ar), 127.9
(Ar), 128.0 (Ar), 128.2 (Ar), 138.4 (C ipso), 171.4 (CO); MS (HR-
ESI) calcd for C17H22D2NaO6 [M+Na]+ 349.1594. Found: 349.1628.
4.20. (4R,5R)-3-Benzyloxy-2-hydroxymethyl-4,5-dimethoxy-
tetrahydro-2H-pyran-2-ol (26)
4.16. 1,5-Anhydro-2,3-di-O-methyl-4-O-benzyl-D-glucitol (21)
To a solution of compound 8 (200 mg, 0.675 mmol) in ethanol
at room temperature was added NaBH4 (55 mg, 1.35 mmol). After
30 minutes, a few drops of 3 M HCl were added and the mixture
diluted with EtOAc (50 mL). The organic phase was washed with
saturated solution of NaHCO3 (5 mL) water (5 mL) and dried over
Na2SO4. After filtration and evaporation, the residue was chro-
To a stirred solution of compound 8 (30 mg, 0.1 mmol) in
CH2Cl2 (5 mL) under argon at ꢀ20 °C were added BF3ꢂOEt2
(0.1 mL, 0.4 mmol) then Et3SiH (0.3 mL, 1 mmol). The mixture
was allowed to cool to rt and stirred for 1 h. CH2Cl2 (60 mL) was
added then washed with satd NaHCO3 (1 mL) and water (2 mL).
After drying over MgSO4, filtration and evaporation provided 21
(28 mg, 100%) as an oil, Rf 0.14 (hexanes–EtOAc 2:1); 1H NMR
matographed to provide pure 26 (131 mg, 65%) as a gum, ½a D25
ꢁ
+13 (c 0.96, CHCl3); Rf 0.16 (hexanes–EtOAc 3:2); IR (film),
3417 cmꢀ1 1H NMR (CDCl3, 250 MHz): d 2.3 (bs, 2H, OH), 3.30–
;
0
(CDCl3, 400 MHz): d 3.16 (m, 1H, H-1), 3.25 (ddd, 1H, J5,6 4.7 Hz,
3.25 (m, 1H, H-2), 3.36 (d, 1H, J 9.5 Hz, H-4), 3.44 (AB, 2H, J
11 Hz, H-6, H-60), 3.48 (s, 3H, H-Me), 3.57 (t, 1H, J 9.5 Hz, H-3),
3.64 (t, 1H, J 11 Hz, H-10), 3.66 (s 3H, H-Me), 3.76 (dd, 1H, J 5.8, J
11 Hz, H-1), 4.76 (AB, 2H, J 11 Hz, H-CH2Ph), 7.36–7.28 (m, 5H,
H-arom Ph); 13C NMR (CDCl3 62.9 MHz): d 58.9 (C-Me)., 60.6 (C-
1), 61.1 (C-Me), 65.7 (C-6), 75.4 (CH2Ph), 78.5 (C-4), 80.3 (C-2),
84.5 (C-3), 97.4 (C-5), 126.6, 137.9 (C-arom Ph); MS (HR-ESI) calcd
for C15H22NaO6 [M+Na]+ 321.1314. Found: 321.1333.
J5,6 2.5 Hz, J4,5 9.0 Hz, H-5), 3.26 (m, 2H, H-2, H-3), 3.39 (m, 1H,
0
H-4), 3.51 (s, 3H, OMe), 3.66 (dd, 1H, J6,6 12 Hz, H-6), 3.69 (s, 3H,
OMe), 3.84 (dd, 1H, H-60) 4.08 (dd, 1H, J1,1 11 Hz, J1,2 4.5 Hz, H-
0
10), 4.66 (d, 1H, J 12 Hz, CH2Ph), 4.89 (d, 1H, J 12 Hz, CH2Ph), 7.37
(m, 5H, H-arom. Ph); 13C NMR (CDCl3 100 MHz): d 59.2 (C-Me),
61.4 (C-Me), 62.7 (C-6), 67.9 (C-1); 75.4 (CH2Ph), 77.8 (C-4), 79.9
(C-5), 81.8 (C-2), 88.4 (C-3), 128.3, 128.5, 128.9, 138.5 (C-arom
Ph); MS (ESI) 305 [M+Na]+, 283 [M+H]+. Anal. Calcd for C15H22O5:
C, 63.81; H, 7.85. Found: C, 63.74; H, 7.81.
4.21. (3R,4R,5S)-3,4-Dimethoxy-6-oxo-oxepane-2,5-diyl
diacetate (29)
4.17. 1,5-Anhydro-1,5-dideutero-2,3-di-O-methyl-4-O-benzyl-D-
glucitol (22)
Method A: To a solution of compound 8 (75 mg, 0.25 mmol) in
acetic anhydride (0.5 mL) was added Yb(OTf)3 (1.5 mg, 5 mol %).
The mixture was stirred for 24 h and 1 mL of methanol was added.
The solvent was evaporated and the residue was taken up in EtOAc
(60 mL). The organic phase was washed with a saturated solution
of NaHCO3 (5 mL), water (5 mL), brine (5 mL) and dried over so-
dium sulfate. The organic phase was concentrated under vacuum
and the residue was purified by column chromatography (hex-
anes–EtOAc 1:1) to give the anomeric mixture of products 29
(60 mg, 80%). Method B: To a solution of compound 9 (26 mg,
0.08 mmol) in acetic anhydride (0.5 mL) was added Yb(OTf)3
(1 mg 5% mol). The mixture was stirred for 24 h and 1 mL of meth-
anol was added. The solvent was evaporated in vacuo and the res-
idue was taken up in EtOAc (60 mL). The organic phase was
To a stirred solution of compound 8 (118 mg, 0.4 mmol) in
CH2Cl2 (5 mL) under argon at ꢀ20 °C were added BF3ꢂOEt2
(0.2 mL, 0.4 mmol) then Et3SiD (234 mg, 2 mmol). The mixture
was allowed to warm to rt and stirred for 1 h. CH2Cl2 (60 mL)
was added then washed with saturated solution of NaHCO3
(1 mL) and water (2 mL). After drying over MgSO4 and filtration,
evaporation provided crude 22 (118 mg, 100%) as an oil, Rf 0.14
(hexanes–EtOAc 2:1).
4.18. 6-O-Acetyl-1,5-anhydro-2,3-di-O-methyl-4-O-benzyl-D-
glucitol (23)
Crude compound 21 was treated by the procedure described for
washed with
a saturated solution of NaHCO3 (5 mL), water
the synthesis of 9 and gave 23 (28 mg, 85%) as a white solid, ½a D25
ꢁ
(5 mL), brine (5 mL) and dried over sodium sulfate. The organic
phase was concentrated under vacuum and the residue was puri-
fied by column chromatography (hexanes–EtOAc 1:1) to give the
anomeric mixture of products 29 (20 mg, 90%) as an oil, Rf 0.27
+51.0 (c 1, CHCl3); Rf 0.50 (toluene–EtOAc 2:1); 1H NMR (CDCl3,
400 MHz): d 2.07 (s, 3H, COCH3), 3.13 (m, 1H, H-1), 3.26 (m, 4H,
0
J5,6 4.7 Hz, J5,6 2.5 Hz, J4,5 9 Hz, H-5, H-2, H-3, H-4), 3.51 (s, 3H,
OMe), 3.70 (s, 3H, OMe), 4.10 (dd, 1H, J1,1 11 Hz, J1,2 4 Hz, H-10),
0
(hexanes–EtOAc 2:1); 1742 cmꢀ1 1H NMR (CDCl3, 250 MHz): d
;
0
0
4.20 (dd, 1H, J5,6 4 Hz, J6,6 12 Hz, H-6), 4.33 (dd, 1H, J5,6 2 Hz, H-
60), 4.60 (d, 1H, J 12 Hz, CH2Ph), 4.89 (d, 1H, J 12 Hz, CH2Ph), 7.37
(m, 5H, Ph); 13C NMR (CDCl3 62.9 MHz): d 21.1(Me), 59.0 (OMe),
61.2 (OMe), 63.7 (C-6), 67.8 (C-1), 75.2 (CH2Ph), 77.8 (C-4), 77.5
(C-5), 80.4 (C-2), 88.3 (C-3), 128.0 (2Ph), 128.3 (Ph), 128.5 (Ph),
128.9 (Ph), 138.1 (C ipso), 171.0 (CO); MS (HR-ESI) calcd for
2.16, 2.12 (2 s, 6H, OAc), 3.35 (s, 3H, OMeb), 3.38 (s, 3H, OMea),
3.42 (s, 3H, OMea), 3.45 (s, 3H, OMeb), 3.88 (s, 1H, H-2b), 3.94
(at, 1H, J 4.O Hz, H-2a), 4.03 (d, 1H, J 5.1 Hz, H-3b), 4.12 (dd, 1H,
J 4.0, J 6.0 Hz, H-3), 4.79 (d, 1H, J 17.5 Hz, H-6a), 4.79 (d, 1H, J
5.1 Hz, H-4b), 4.87 (d, 1H, J 18 Hz, H-6b), 4.99 (d, J 17.9 Hz, H-
60a), 5.06 (d, J 18 Hz, H-60b), 6.25 (s, H-1), 6.45 (d, 1H, J 4.3 Hz, H-
1); 13C NMR (CDCl3 62.9 MHz): d 20.7 (OAc), 20.8 (OAc), 21.2
C17H24NaO6 [M+Na]+ 347.1465. Found: 347.1482.

102
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(OAc), 21.4 (OAc), 58.1 (OMe), 58.8 (OMe), 58.8 (OMe), 59.3 (OMe),
67.9 (C-6), 68.3 (C-6), 83.5 (C-2), 84.4 (C-2), 84.5 (C-3), 84.5 (C-3),
85.4 (C-4), 87.8 (C-4), 95.8 (C-1), 100.8 (C-1), 169.8 (CO), 170.1
(CO), 170.2 (CO), 170.3 (CO), 200.4 (C-5), 201.5 (C-5); MS (ESI)
313 [M+Na]+, 231 [MꢀOAc]+.
4.22. 1,6-Di-O-acetyl-2,3-di-O-methyl-5-C-methoxy-4-O-benzyl-
L
-idopyranoses (33)
Method A was applied to compound 10 (80 mg, 0.25 mmol) to
give after purification by column chromatography 33b (42 mg,
56%) and 33a (20 mg, 26%).
4.22.1. 1,6-Di-O-acetyl-2,3-di-O-methyl-5-C-methoxy-4-O-
benzyl-b-L-idopyranose (33a)
Compound 33a foams, ½a D25
ꢀ15.1 (c 0.1, CHCl3); Rf 0.3 (toluene–
ꢁ
EtOAc 3:1); 1H NMR (CDCl3, 400 MHz): d 2.00 (s, 6H, OAc), 3.31 (s,
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H-2, H-3, H-4), 4.27 (d, 1H, J6,6 12 Hz, H-6), 4.38 (d, 1H, H-60),
0
4.69 (AB, 2H, CH2Ph), 6.27 (d, 1H, J1,2 2.5 Hz, H-1), 7.24–7.4 (m,
5H, Ar); 13C NMR (CDCl3 100 MHz): d 21.2 (Ac), 21.5 (Ac), 49.5
(C-6), 59.4 (C-Me), 60.1 (C-Me), 62.4 (C-Me), 73.5 (CH2Ph), 78.6
(C-4), 79.3 (C-2), 80.4 (C-3), 88.5 (C-1), 101.5 (C-5), 128.2, 128.3,
128.7 , 128.8 (C-arom Ph), 138.1 (C ipso), 170.3 (CO), 170.8 (CO);
MS (HR-ESI) calcd for C20H28NaO9 [M+Na]+ 435.1631. Found:
435.1622.
4.22.2. 1,6-Di-O-acetyl-2,3-di-O-methyl-5-C-methoxy-4-O-
benzyl-a-L-idopyranose (33b)
Compound 33b foam, ½a D25
ꢁ
+3.8 (c 0.7, CHCl3); Rf 0.46 (toluene–
EtOAc 3:1); IR (film), 1750 cmꢀ1; 1H NMR (CDCl3, 400 MHz): d 1.98
(s, 3H, OAc), 2.15 (s, 3H, OAc), 3.32 (s, 3H, OMe), 3.47 (dd, 1H, J2,3
7.4, J3,4 4.7 Hz, H-3), 3.54 (s, 3H, OMe), 3.58 (s, 3H, OMe), 3.64
0
(dd, 1H, J1,2 6.7 Hz, H-2), 3.67 (d, 1H, H-4), 4.20 (d, 1H, J6,6 12 Hz,
H-6), 4.40 (d, 1H, H-60), 4.66 (d, 1H, J 12 Hz, CH2Ph), 4.74 (d, 1H, J
12 Hz, CH2Ph), 5.94 (d, 1H, J 6.7 Hz, H-1), 7.27–7.39 (m, 5H, Ar);
13C NMR (CDCl3 100 MHz): d 20.1 (COCH3), 21.4 (COCH3), 49.3
(C-Me), 59.5 (C-Me), 59.9 (C-Me), 60.3 (C-6), 73.0 (CH2Ph), 79.4
(C-4), 83.1 (C-2), 83.5 (C-3), 92.2 (C-1), 101.5 (C-5), 128.0, 128.2,
128.5 (C-arom Ph), 169.6 (CO), 170.4 (CO); MS (HR-ESI) calcd for
11. (a) Fyvie, W. S.; Peczuh, M. W. J. Org. Chem. 2008, 73, 3626–3629; (b) Markad, S.
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references cited therein.
C
20H28NaO9 [M+Na]+ 435.1631. Found: 435.1625.
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Acknowledgment
We thank Sanofi–Aventis for a fellowship to O.J.
Supplementary data
Complete crystallographic data for the structural analysis of
compounds 8 and 15 have been deposited with the Cambridge Crys-
tallographic Data Centre, CCDC 857232 for 8 and CCDC 857233 for
15. Copies of these informations may be obtained free of charge from
the Director, Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge, CB2 1EZ, UK. (fax: +44-1223-336033, e-mail: de-
posit@ccdc.cam.ac.uk or via: www.ccdc.cam. ac.uk).
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2012.
02.026.
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