Oxidatively induced glycosylation starting from hydroquinone glycosides

Article abstract of DOI:10.1016/j.tet.2008.03.056

As a new class of glycosyl donors, hydroquinone glycosides can be used for glycosylation reactions. Their activation can be performed either electrochemically or under homogeneous chemical conditions. Conventionally, several glucosides were produced with yields greater than 77% using DDQ in CH₂Cl₂ as oxidizing agent. For electrolyses, glycosides of trimethylhydroquinone are preferably used because their low oxidation potentials allow the utilization of an undivided cell. The synthesis of the glycosyl donors was achieved with high efficiency by direct coupling of the phenols with peracetylated monosaccharides employing boron trifluoride etherate as the catalyst. The oxidation of hydroquinone derivatives can also be applied to the generation of other stabilized cations.

Full text of DOI:10.1016/j.tet.2008.03.056

Tetrahedron 64 (2008) 5124–5131
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Oxidatively induced glycosylation starting from hydroquinone glycosides
,
Hans Gu¨nter Thomas a, Jean-Luc Mieusset b
*
a Institut fu¨r Organische Chemie, Rheinisch-Westfa¨lische Technische Hochschule Aachen, Professor-Pirlet-Straße 1, 52074 Aachen, Germany
b Institut fu¨r Organische Chemie, Universita¨t Wien, Wa¨hringer Straße 38, A-1090 Wien, Austria
a r t i c l e i n f o
a b s t r a c t
Article history:
As a new class of glycosyl donors, hydroquinone glycosides can be used for glycosylation reactions. Their
activation can be performed either electrochemically or under homogeneous chemical conditions.
Conventionally, several glucosides were produced with yields greater than 77% using DDQ in CH2Cl2 as
oxidizing agent. For electrolyses, glycosides of trimethylhydroquinone are preferably used because their
low oxidation potentials allow the utilization of an undivided cell. The synthesis of the glycosyl donors
was achieved with high efficiency by direct coupling of the phenols with peracetylated monosaccharides
employing boron trifluoride etherate as the catalyst. The oxidation of hydroquinone derivatives can also
be applied to the generation of other stabilized cations.
Received 13 February 2008
Received in revised form 12 March 2008
Accepted 17 March 2008
Available online 21 March 2008
Keywords:
Glycosylation
Oxidation
Electrochemistry
Carbohydrates
Hydroquinones
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
also achieved by electrochemical reduction of glycosyl halides8 and
electrooxidative N-glycosylations leading to the formation of
Carbohydrate derivatives play a central role in biological sys-
tems, especially in the modification of proteins and in molecular
recognition processes. Therefore, a wide range of methodologies
have been developed to perform glycosylations.1 The most com-
monly used glycosyl donors are glycosyl halides, thioglycosides,
and trichloroacetimidates. For this purpose, electrochemistry offers
some advantages; it enables the activation of stable glycosides,
which are resistant to a wide range of reaction conditions. The first
reported use was the oxidation of aryl glycosides by Noyori.2 During
the following years, this method was applied to glycosylations that
start from thio-,3–5 seleno-5,6 or telluroglycosides.6 The disadvan-
tage of this reaction path is that radical species are produced during
the reaction and therefore the prepared glycosides contain many
side products. The leaving group also is a cause of side reactions. For
phenyl compounds, a mixture of aryl ethers2 is formed. By the use
of thioglycosides, the thio radical dimerizes first to a disulfide,
which is further oxidized during the course of the electrolysis.3 In
the absence of a good nucleophile, the initially produced glycosyl
cations tend to react with the supporting electrolyte, generating
more or less stable glycosyl halides, perchlorates or triflates.7
Therefore, the choice of the conducting salt is of crucial importance
in order to minimize the amount of side products and to control the
stereoselectivity of the reaction. Alternatively, glycosylation was
nucleosides that have already been reported.9
Johnson10 showed that the oxidation of hydroquinone esters
permits to realize a transacylation. With this method, the only
byproduct is benzoquinone. Assuming that the glycosyl cation
could be formed as easily as an acyl cation, we will show in this
paper that hydroquinone glycosides can be used for glycosylations
(Scheme 1) and that the sole side product is the corresponding
quinone, a compound that can be removed very easily. In-
terestingly, hydroquinone bis-glucosides are found in traditional
medicinal plants.11 They are also used for the modification of the
properties of conducting polymers in order to enhance their solu-
bility or improve their binding properties.12 Moreover, 4-hydroxy-
phenyl-b-
D-glucopyranoside,
a
compound commonly called
arbutin, is a readily available and cheap natural product especially
found in bearberries. Since it has already been shown that un-
protected sugars can serve as glycosyl donors, this methodology
may be promising for glycosylation reactions in water.13
2. Results and discussion
2.1. Synthesis of the starting material
Aryl glycosides like 4, 5, and 25 can be easily prepared from
pentaacetyl-b-D
-glucose with BF3$OMe2 as activator (Scheme 2).14
The corresponding benzylated compounds 6 and 9 were prepared
by substitution of the protecting groups with benzyl chloride and
KOH.15
* Corresponding author. Tel.: þ43 1 4277 52112; fax: þ43 1 4277 52140.
E-mail address: jeanluc.mieusset@univie.ac.at (J.-L. Mieusset).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.056

H.G. Thomas, J.-L. Mieusset / Tetrahedron 64 (2008) 5124–5131
5125
OBn
OBn
O
O
O
O
BnO
BnO
BnO
BnO
+ ROH
- 2 e-, - 2 H+
+
OR
O
OH
OBn
OBn
2
1
Scheme 1.
OAc
OAc
OAc
1 eq BF3.OEt2
O
O
OAc
2
AcO
AcO
+
AcO
O
AcO
AcO
OAc
OH
HO
O
OAc
O
O
CH2Cl2, 24 h, RT
OAc
OAc
3
4: y = 81%
OBn
OAc
OBn
OBn
OAc
BnCl, KOH
5 h, 120 °C
O
O
BnO
BnO
BnO
AcO
AcO
AcO
OAc
O
O
O
O
O
OBn
OAc
OBn
OAc
6: y = 95%
5
Scheme 2. Representative synthesis of the glycosyl donors.
4-Hydroxyphenyl 2,3,4,6-tetra-O-benzyl-b-
D
-glucopyranoside
groups. Oxidation of the benzylic protecting groups occurs only
with potentials higher than 2 V.
(1) was prepared by the imidate method.16
The glycosyl donors were investigated by cyclic voltammetry
and their oxidation potentials are listed in Table 1. All oxidations are
irreversible, a sign that the generated radical cation decomposes
rapidly. In all cases, benzylated donors (armed sugars) have a lower
oxidation potential than their acetylated counterparts (disarmed
sugars). Hence, a quinone, which may activate a benzylated donor
may not be suitable for a glycoside bearing acetyl protecting
Initially, compound 1 (Eox¼1.3 V) was oxidized in an undivided
cell. The produced glucosyl cation reacted with cyclohexanol to
produce the corresponding glucoside17 11. To obtain the best yield
of 85%, 1 equiv BF3$OMe2 was used as an electrolyte in MeCN/THF
95:5. Acetonitrile was necessary to make the reaction mixture
conductive, but we needed tetrahydrofuran as an additional sol-
vent, because the donor 1 cannot be dissolved in pure acetonitrile.
This method favors the b-anomer with an anomeric ratio of 1:3, but
it is not stereospecific. Utilization of tetrabutylammonium tetra-
fluoroborate as conducting salt improves the stereoselectivity
(a/b¼1:9), but the crude product contains 30% of a-tetrabenzyl
glucosyl fluoride. Similarly, the use of tin tetrachloride leads to
contamination by the glucosyl chloride and utilization of lithium
perchlorate favors the formation of tetrabenzyl glucose. When
higher alcohols were used, there was a competitive reaction with
Table 1
Oxidation potentials of the glycosyl donors
OR1
R1O
R1O
O
R2
OR1
7
7a: R1=Ac; R2=SPh
7e: R1=Bn; R2=p-HOPhO
the free hydroxy group of
1 and bisglucosyloxybenzene 9
7b: R1=Ac; R2=p-MeOPhO
7c: R1=Bn; R2=p-MeOPhO
7d: R1=Ac; R2=p-HOPhO
7f: R1=Bn; R2=p-CF3CO2PhO
7g: R1=Bn; R2=p-Me3SiOPhO
7h: R1=Bn; R2=p-HOMe3PhO
(Eox¼1.6 V) became the most important product, because it could
not be oxidized under these conditions.
2.2. Indirect electroglycosylation
OR1
R2
R2
R1O
OR1
R1O
R1O
O
OR1
OR1
When the glycosyl donor 9 was oxidized in an undivided cell in
the presence of cyclohexanol, only traces of products could be
detected through TLC. The conversion was so low that no com-
pounds could be isolated. Probably, with this procedure, the re-
action begins and generates a small quantity of glucoside and
benzoquinone. The latter compound is directly reduced at the
cathode to hydroquinone. This compound prevents a further oxi-
dation of the reactant 9 and the reaction stops. Therefore, 9 must be
oxidized in a divided cell. In this device, the conductivity of the
solution is limited and a mediator has to be used in order to obtain
a better selectivity during the oxidation. CoCl2 and tris(2,4-dibro-
mophenyl)amine18 could be employed for this purpose. Indeed,
under these conditions, cyclohexyl glucoside 11 is produced in
a yield of 77% (Table 2, Scheme 3), the favored anomer being the
a-anomer. As a side product, 7–15% of 1,6-anhydro-2,3,4-tri-O-
O
O
O
OR1
R3
R3
8
8b: R1=Ac; R2=Cl; R3=Cl
8c: R1=Ac; R2=CN; R3=H
Hydroquinone glycoside
Eox1/2a (V)
7a
16
9
5
7b
6
7c
25
7d
7e
7f
7g
29
7h
8a
8b
1.80
1.75
1.60
1.60
1.55
1.50
1.45
1.40
1.35
1.30
1.20
1.20
1.10
benzyl-b-D
-glucopyranose19 20 is formed. These observations let us
assume that the reaction proceeds through the trialkyloxonium ion
19 as an intermediate (Scheme 4). A further reason for the pre-
dominance of the a-anomer is that the anodic compartment is
significantly more acidic than in the other experiments conducted
in this work and that isomerization to the more stable a-glycoside
takes place. In contrast, during the electrolyses in an undivided cell
1.05
>2.0
>2.0
a
Against Ag, AgCl/3 M KCl in acetonitrile.

5126
H.G. Thomas, J.-L. Mieusset / Tetrahedron 64 (2008) 5124–5131
Table 2
in tetrahydrofuran and in acetonitrile, the b-anomer predominates;
a possible explanation is that the glucosyl cation is stabilized by the
solvent. As a consequence of the reverse anomeric effect,20 the
a-anomer 18a is less stable and therefore more reactive than
the corresponding b-anomer. Overall, it leads to formation of a
b-glucoside.21
Hydroquinone bis-glucoside 9 reacts cleanly in a divided cell
with (ꢀ)-menthol 12 and tetrabenzyl glucose15 14 (a/b¼3:1). The
glucosides 13 and 15 were obtained in 62 and 34% yield,
Glycosylation of some alcohols by means of an indirect electrolysis of 1,4-bis(2,3,4,6-
tetra-O-benzyl-b- -glucopyranosyloxy)benzene (9) or 1,4-bis(methyl 2,3,4-tri-O-
-glucopyranosyloxyuronate)benzene (16)
D
acetyl-b-
D
Donor
Acceptor
Product
Solvent
Yield (%)
a/b
9
9
9
16
10
12
11
13
15
17
MeCN
MeCN
MeCN/CH2Cl2
MeCN
77
62
34
75
3:1
3:1
3:2 (aa/ab)
a
14 (a/b 3:1)
10
OBn
O
y = 77%
= 3/1
BnO
BnO
MeCN
MeCN
9 +
O
HO
BnO
11
10
OBn
y = 62%
= 3/1
O
BnO
BnO
9 +
HO
O
OBn
13
12
y = 34%
OBn
OBn
MeCN
= 3/2
CH2Cl2
O
O
BnO
BnO
BnO
BnO
OBn
OBn
9 +
16
BnO
OH
BnO
15
BnO
14
O
O
OBn
OMe
OMe
O
AcO
AcO
OMe
O
O
O
O
y = 75%
AcO
AcO
MeO
MeCN
OMe
O
O
O
OMe
AcO
17
OAc
O
16
Scheme 3. Glycosylation in a divided cell in presence of CoCl2.
OBn
OBn
O
BnO
O
BnO
BnO
OBn
OBn
O
O
OBn
9
-2 e-
-2 e-
[1e OA]*
OBn
O
BnO
BnO
OBn
OBn
OBn
Bn
O
O
O
O
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
X
O
O
BnO
BnO
OBn
OBn
X
20
18
19
18
X = MeCN, THF
c-C6H11OH
c-C6H11OH
OBn
OBn
O
O
BnO
BnO
BnO
BnO
O
BnO
OBn
11
O
11
Scheme 4. Proposed mechanism for the oxidative transglycosidation of hydroquinone glycosides.

H.G. Thomas, J.-L. Mieusset / Tetrahedron 64 (2008) 5124–5131
5127
Table 3
Glucoside formation by direct electrolysis of 1,4-bis(2,3,4,6-tetra-O-benzyl-b-
2.3. Direct electroglycosylation
D
-
glucopyranosyloxy)-2,3,5-trimethylbenzene (6) and its peracetylated analog 5 in the
presence of alcohols
Tris(4-bromophenyl)amine or LiCl$MnCl2 can be used as medi-
ator for donors with a low oxidation potential like 1,4-bis(2,3,4,
6-tetra-O-benzyl-b-D-glucopyranosyloxy)-2,3,5-trimethylbenzene
Donor
Acceptor
Product
Solvent
Yield (%)
a/b
6
6
5
5
10
12
12
21
11
13
27
28
MeCN/CH2Cl2
CH2Cl2
MeCN
88
82
61
43
3:2
1:1
b
(6) (Eox¼1.5 V). However, because of the low oxidation potential of
6, this compound can also be directly oxidized in an undivided cell.
Due to this fact, solvents with low polarity like CH2Cl2 could be
used. In this way, the glycosylation system becomes more efficient
and the yields improve (Table 3). The disadvantage of this method
is, however, that the anomeric selectivity is very low. For example,
with (ꢀ)-menthol 12 as acceptor, the corresponding glucoside 13 is
obtained in a yield of 82% with an anomeric ratio of 1:1.
MeCN
b
Table 4
Reaction between 1,4-bis(2,3,4,6-tetra-O-benzyl-b-
D-glucopyranosyloxy)-2,3,5-tri-
methylbenzene (6) and alcohols in the presence of DDQ
Acceptor
Product
Catalyst quantity
Reaction time (h)
Yield (%)
a/b
With acetylated donors, glucoside formation occurs only in the
presence of an acid. In the case of suitable reaction conditions, the
trans-glucoside will be exclusively formed due to the stabilization
of the intermediate compound through the ester group at C(2). We
compared the results obtained with the Lewis acids BF3$OMe2,
FeCl3, ZnCl2, SnCl4, and trimethylsilyl trifluoromethanesulfonate
(TMSOTf), which were already used in glycosylation reactions, es-
pecially for the activation of 1-O-acyl sugars.1b The best results
were obtained when tin(IV) chloride was used as the activator in
acetonitrile. In this solvent, SnCl4 dissociates and no other
electrolyte is necessary. Under these conditions, 1,4-bis(2,3,4,6-
10
12
14
21
23
11
13
15
22
24
0.3 equiv TfOH
0.3 equiv TfOH
0.3 equiv TfOH
0.45 equiv TfOH
1 equiv SnCl4
2.5
2.5
1.5
2
98
93
89
87
77
2:1
2:1
1:1a
2:1
2:1
1
a
aa/ab.
O
O
HO
O
O
HO
O
21
23
tetra-O-acetyl-b-D-glucopyranosyloxy)-2,3,5-trimethylbenzene (5)
O
produces only the b-glucosides 2723 and 28 during the glycosyla-
tion of (ꢀ)-menthol 12 and methyl 12-hydroxyoctadecanoate (21).
The yields are 61 and 43%, respectively.
respectively (Table 2). Also with these alcohols, merely a-anomer
was produced with the anomeric ratios a/b¼3:1 and aa/ab¼3:2,
respectively.
2.4. Oxidation under homogeneous chemical conditions
The behavior of 1,4-bis(methyl 2,3,4-tri-O-acetyl-b-D-glucopyr-
anosyloxyuronate)benzene (16) (Eox¼1.75 V) is not exactly the
same. This compound can be oxidized in a divided cell and it yields
specifically the a-glucuronoside 17 of cyclohexanol (yield¼75%).
The reason for this a-glycosylation is probably that the carbonyl
group at C(6) stabilizes the intermediate in a way that the alcohol
can attack the glycosyl cation only in the a-position.22
Alternatively the oxidation could be performed with oxidizing
agents instead of an anode. In our case, one-electron oxidizing
agents like cobalt(III) acetylacetonate and tris(2,4-dibromophenyl)-
ammoniumyl hexachloroantimonate18 could not be used, because
they provide tribenzyl anhydroglucose 20 as main product. In
contrast, when 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
OBn
O
0.3 equiv TfOH
10, rt, 2.5 h
BnO
BnO
O
y = 98%
: 2/1
OBn
11
OBn
0.3 equiv TfOH
12, rt, 2.5 h
O
BnO
BnO
O
y = 93%
: 2/1
OBn
13
OBn
OBn
OBn
OBn
OBn
0.3 equiv TfOH
14, rt, 1.5 h
OBn
OBn
BnO
O
O
BnO
O
BnO
BnO
O
y = 89%
: 1/1
O
O
BnO
BnO
OBn
OBn
OBn
O
OBn
15
6
0.45 equiv TfOH
O
BnO
BnO
O
21, rt, 2 h
O
y = 87%
: 2/1
OBn
22
O
O
OBn
O
O
BnO
BnO
1 equiv SnCl4
23, rt, 1 h
y = 77%
: 2/1
O
OBn
24
O
O
Scheme 5. Glycosylations with DDQ under homogeneous conditions.

5128
H.G. Thomas, J.-L. Mieusset / Tetrahedron 64 (2008) 5124–5131
Table 5
Glucosylation of some alcohols by oxidation of the diglucosylated naphthohydroquinone 25 with DDQ
Acceptor
Product
Reaction conditions
Turnover (%)
Yielda (%)
a/b
10
10
12
21
26
26
27
28
0.1 equiv BF3$OMe2, CH2Cl2
2 h, MeCN/SnCl4
2 days, MeCN/SnCl4
2 days, MeCN/SnCl4
100
37
52
64
63
81
78
1:2
1:9
b
52
b
a
Based on the turnover.
OAc
OAc
OAc
O
O
AcO
AcO
AcO
O
AcO
AcO
OAc
O
O
O
OAc
26
OAc
OAc
25
OAc
OAc
O
AcO
AcO
O
AcO
AcO
O
O
O
OAc
27
OAc
O
28
OAc
O
AcO
OAc
O
OH
OAc
29
is used, 20 is not observed. The difference between these two
methods is that the electron transfer occurs through a CT-complex
when DDQ is used and that two electrons are rapidly transferred.
Similarly, this oxidizing agent was already applied for glycosyla-
tions starting from methoxybenzyl-2-deoxyglucosides.24
the carbohydrate in presence of the prospective leaving group.
Nevertheless, these hydroquinone glycosides can be activated un-
der mild conditions at room temperature by oxidation with DDQ
and can even glycosylate poorly accessible hydroxy groups with
good yields.
With bisglucosyloxytrimethylbenzene 6, glucoside formation
succeeds only under specific conditions. Dichloromethane is the
solvent of choice because the reaction proceeds faster than in THF
or toluene. Of course, dry conditions are required but the usage of
molecular sieves is prohibited because it inhibits the reaction. With
benzylated compounds the reaction should last no longer than
a few hours, because benzaldehyde is very slowly produced
through cleavage of the protecting groups.25 Therefore, a catalytic
quantity of trifluoromethane sulfonic acid (TfOH), BF3$OMe2 or
SnCl4 is needed. In this way, the glucoside 11 of cyclohexanol was
formed quantitatively in less than 3 h in the presence of TfOH
(Table 4, Scheme 5). With the higher alcohols 12, 14, and 21, we
obtained the glucosides 13, 15, and 22 in yields greater than 87%.
Only dipalmitine26 23 did not react in the presence of TfOH or
BF3$OMe2 as catalyst and needs SnCl4 to give glucoside 24.
This methodology is especially convenient because DDQH2 is
insoluble in CH2Cl2 and can easily be removed by filtration. The
facile recovery of the side products and the inexpensive re-
generation of the reagents, for example, electrochemically,27 make
this procedure particularly attractive and sustainable. The acety-
lated glucoside 5 of trimethylhydroquinone could not be used in
combination with DDQ because its oxidation potential (Eox¼1.6 V)
is too high. Instead, we employed 1,4-bis(2,3,4,6-tetra-O-acetyl-b-
4. Experimental section
4.1. General methods and material
Melting points were determined on a Tottoli apparatus, Bu¨chi
510 and are uncorrected. IR spectra were recorded with a Perkin–
Elmer FTIR 1750 spectrophotometer. The locations of the absorp-
tion peaks are given in cmꢀ1. NMR spectra were recorded on
a Varian VXR 300. Tetramethylsilane (TMS) was used as an internal
standard. 1H spectra were recorded at 300 MHz and 13C spectra at
75 MHz in CDCl3. The chemical shifts (d) are listed in parts per
million against TMS. The coupling constants (J) are given in hertz
and the following abbreviations are used for the description of the
patterns: s¼singlet, d¼doublet, t¼triplet, q¼quartet, p¼pentet,
m¼multiplet. Mass spectra were obtained with a Varian MAT 212
spectrometer. The masses of the ions are characterized through
their m/z value. The peak intensity is expressed as a percentage of
the basis peak. Elemental analyses were performed with a Heraeus
CHN-O-Rapid analyzer. Reactions were monitored by TLC on pre-
coated Silica Gel 60 F254 plates (E. Merck). The spots were made
visible with phosphomolybdic acid (3% in EtOH). Cyclic voltam-
metry was performed in 30 ml of acetonitrile with 0.1 M tetrabu-
tylammonium tetrafluoroborate as electrolyte and a platinum
electrode as working electrode against Ag/AgCl/3 M KCl. Com-
pounds, which are insoluble in pure MeCN were first dissolved in
1 ml of CH2Cl2.
D
-glucopyranosyloxy)naphthalene (25) (Eox¼1.4 V). With BF3$OMe2
in CH2Cl2 in the presence of cyclohexanol, compound 25 reacts
faster quantitatively and the purification procedure is simple.
Unfortunately, a 1:2 mixture of a- and b-anomers of cyclohexyl
glucoside 26 is formed. Therefore, the use of the combination SnCl4/
MeCN is recommended because it provides trans-glucosides like 27
and 28 in good yields (Table 5).
4.1.1. 4-Hydroxyphenyl 2,3,4,6-tetra-O-benzyl-b-
pyranoside (1)
D-gluco-
Hydroquinone (32.5 g, 296 mmol, 4 mol equiv) was dissolved
with tetrabenzylglucosyl trichloracetimidate (50.7 g, 74 mmol) in
600 ml of ether/dichloromethane 1:1 and cooled to ꢀ30 ꢁC in the
presence of molecular sieves. Then, BF3$OMe2 (0.2 mol equiv) was
added and the solution was stirred for 2 h, while the temperature
was slowly raised up to 20 ꢁC. During the reaction, the product
3. Conclusion
We have developed an efficient glycosylation method starting
from a readily available glycoside donor that is stable under a wide
range of reaction conditions allowing a further transformation of

H.G. Thomas, J.-L. Mieusset / Tetrahedron 64 (2008) 5124–5131
5129
precipitated. Before the crude reaction mixture could be washed
with a potassium carbonate solution and water, the aryl glucoside
should be dissolved by addition of dichloromethane. Then, the or-
ganic phase was dried over magnesium sulfate, filtered, and the
solvent was removed by distillation. The obtained solid was
recrystallized from ethyl acetate and ethanol. Yield 32.5 g
(51 mmol, 69%); mp 156 ꢁC (EtOH); IR (KBr) 3305 (OH), 3088, 3064,
3027 (]C–H), 2939, 2905, 2878 (–C–H), 1602, 1512 (Ph), 1453
(CH2), 1086, 1066, 1048 (C–O–C), 736, 698 (Ph, mono-
69.13, 71.08, 71.87, 72.59 (C-2, C-3, C-4, C-5), 99.80 (C-1), 118.54
(arom CH), 152.79 (arom C–O), 166.90 (C-6), 169.22, 169.36, 170.08
(3MeCO); MS 742 (0.02) Mþ, 683 (0.01) MþꢀAcO, 623 (0.005)
Mþꢀ2AcOHþH, 317 (22) Mþꢀaglycon, 275 (0.20) 317ꢀH2C]C]O,
257 (41) 317ꢀAcOH, 215 (18) 317ꢀAcOHꢀH2C]C]O,197 (29) 317ꢀ
2AcOH, 155 (100) 317ꢀ2AcOHꢀH2C]C]O, 127 (60). Anal. Calcd for
C
52H58O20 (742.65): C, 51.75; H, 5.16. Found: C, 51.46; H, 5.48.
4.2.3. 1,4-Bis(2,3,4,6-tetra-O-acetyl-b-
naphthalene (25)
D-glucopyranosyloxy)-
substitution) cmꢀ1 1H NMR (CDCl3) d 3.55–3.80 (m, 5H, H-2, H-3,
;
H-4, H-5, H-6), 3.78 (dd, J¼10.7, 1.7 Hz, 1H, H-6), 4.87 (d, J¼7.4 Hz,
1H, H-1), 4.50–5.07 (8d, 8H, 4PhCH2), 6.65, 6.93 (2d, J¼8.73 Hz, 4H,
O–Ph–O), 7.15–7.35 (m, 20H, 4Ph); 13C NMR (CDCl3) d 68.85 (C-6),
74.93 (C-5), 73.48, 75.05, 75.05, 75.76 (PhCH2), 77.70 (C-4), 82.05
(C-2), 84.61 (C-3), 102.75 (C-1), 115.99, 118.52 (O–Ph–O), 127.66–
128.41 (arom CH, PhCH2), 137.94, 137.94, 138.18, 138.45 (arom C,
PhCH2), 151.29, 151.35 (arom C–O); MS 522 (0.53) Mþꢀaglycon, 415
(0.50) 522ꢀBnO, 307 (0.27) 522ꢀ2BnOꢀH, 181 (19.13), 179 (2.41),
110 (1.19) HOPhOHþ, 91 (100) Bnþ, 65 (2.20) C5Hþ5 . Anal. Calcd for
According to method A, naphthohydroquinone (5.0 g,
31.2 mmol, 0.4 mol equiv) was combined with pentaacetyl-b-
D
-
glucose (30.4 g, 78 mmol) and BF3$OMe2 (36 ml, 390 mmol,
5 mol equiv) in CH2Cl2/Et2O 200:100 ml. The crude reaction mix-
ture was filtered before it was extracted. Yield 9.8 g (11.94 mmol,
31%); mp 179 ꢁC (EtOH); IR (KBr) 3077 (]C–H), 2961, 2889 (–C–H),
1756 (C]O), 1229, 1038 (C–O–C), 769, 758 cmꢀ1 1H NMR (CDCl3)
;
d 2.05, 2.06, 2.07, 2.08 (4s, 24H, 8MeCO), 3.95 (ddd, J¼9.4, 4.7,
2.3 Hz, 2H, H-5), 4.22 (dd, J¼2.3, 12.1 Hz, 2H, H-6), 4.35 (dd, J¼12.1,
4.7 Hz, 2H, H-6), 5.18 (d, J¼7.7 Hz, 2H, H-1), 5.24, 5.37 (2t, J¼9.4 Hz,
4H, H-3, H-4), 5.47 (dd, J¼9.4, 7.7 Hz, 2H, H-2), 7.01 (s, 2H, O–Ph–O),
7.54, 8.03 (2dd, J¼6.4, 3.0 Hz, Ph); 13C NMR (CDCl3) d 20.54, 20.58,
20.64, 20.64 (8MeCO), 61.88 (C-6), 68.39, 71.14, 71.99, 72.59 (C-2, C-
3, C-4, C-5), 100.02 (C-1), 109.50 (O–Ph–O), 121.53, 126.76 (arom
CH), 126.58 (arom C), 148.68 (arom C–O), 169.44, 169.47, 170.11,
170.48 (4CO); MS 490 (0.01) Mþꢀ331þH, 331 (6.3) Mþꢀaglycon,
271 (2.8) 331ꢀAcOH, 229 (1.4) 331ꢀAcOHꢀH2C]C]O, 211 (2.5)
331ꢀ2AcOH, 187 (1.3) 331ꢀAcOHꢀ2H2C]C]O, 169 (100) 331ꢀ
2AcOHꢀH2C]C]O, 160 (5.0) aglyconþ, 127 (20) 331ꢀ2AcOHꢀ
2H2C]C]O, 109 (68) 331ꢀ3AcOHꢀH2C]C]O. Anal. Calcd for
C
40H40O7 (632.75): C, 75.93; H, 6.37. Found: C, 76.15; H, 6.60.
4.2. Method A
Hydroquinone was dissolved in ether and 2 g of pulverized
molecular sieves as well as the peracetylated sugar dissolved in
dichloromethane were added. After 30 min, 5 mol equiv of boron
trifluoride etherate was added and the reaction mixture was stirred
for 3 days. Then, this solution was extracted with water and with
a NaHCO3 solution, and dried over MgSO4. The crude product was
recrystallized from ethanol.
C38H44O20 (820.76): C, 55.61; H, 5.40. Found: C, 55.21; H, 5.42.
4.2.1. 1,4-Bis(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyloxy)-
2,3,5-trimethylbenzene (5)
4.3. Method B
Glucose-b-pentaacetate (3) (50 g, 129 mmol) dissolved in
500 ml of dichloromethane, 59 ml (641 mmol, 5 mol equiv) of bo-
ron trifluoride etherate, and 7.85 g (51.6 mmol, 0.4 mol equiv) of
trimethylhydroquinone dissolved in 200 ml of ether were com-
bined using method A. Yield 26.4 g (32.5 mmol, 50%); mp 213 ꢁC
(EtOH); IR (KBr) 2965, 2876 (–C–H), 1747 (C]O), 1226, 1041 (C–O–
The acetylated aryl glucoside was heated with 20 mol equiv
KOH, 15 mol equiv of benzyl chloride, and 0.1 mol equiv of water for
5 h at 100 ꢁC. After the mixture had cooled down, it was extracted
with dichloromethane and water, and dried over potassium car-
bonate. The volatile compounds were removed under reduced
pressure until 160 ꢁC was reached. The residue was recrystallized
from ethanol.
C) cmꢀ1 1H NMR (CDCl3) d 2.01–2.24 (11s, 33H, 11Me), 3.54 (ddd,
;
J¼9.4, 4.5, 3.0 Hz, 1H, H-50), 3.87 (ddd, J¼10.0, 5.5, 2.7 Hz, 1H, H-5),
4.07 (dd, J¼12.0, 2.7 Hz, 1H, H-6), 4.16–4.30 (m, 3H, H-6, H-60), 4.74
(d, J¼7.7 Hz, 1H, H-10), 4.98 (d, J¼7.7 Hz, 1H, H-1), 5.10–5.40 (m, 6H,
H-2, H-3, H-20, H-30, H-40), 6.69 (s, 1H, Ph); 13C NMR (CDCl3) d 12.06,
13.63, 17.23 (3Me), 20.62 (8MeCO), 61.62, 62.17 (C-6, C-60), 68.45,
68.50, 71.16, 71.60, 71.80, 71.96, 72.72, 72.98 (C-2, C-3, C-4, C-5, C-20,
C-30, C-40, C-50), 99.78, 101.79 (C-1, C-10), 115.31 (arom CH), 125.47,
129.22, 131.73 (arom C), 148.30, 151.78 (arom C–O), 169.25–170.50
(8C]O); MS 812 (0.05) Mþ, 482 (0.24) Mþꢀ333þH, 331 (18)
Mþꢀaglycon, 289 (0.11) 331ꢀH2C]C]O, 271 (7.9) 331ꢀAcOH, 229
(1.5) 331ꢀAcOHꢀH2C]C]O, 211 (5.4) 331ꢀ2AcOH, 169 (100)
331ꢀ2AcOHꢀH2C]C]O, 127 (17) 331ꢀ2AcOHꢀ2H2C]C]O, 109
(61) 331ꢀ3AcOHꢀH2C]C]O. Anal. Calcd for C37H48O20 (812.78):
C, 54.68; H, 5.95. Found: C, 54.64; H, 6.02.
4.3.1. 1,4-Bis(2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyloxy)-
2,3,5-trimethylbenzene (6)
1,4-Bis(2,3,4,6-tetra-O-acetyl-b-
D-glucopyranosyloxy)-2,3,5-tri-
methylbenzene (5) (15 g, 18.46 mmol) was treated according to
method B. Yield 21.1 g (17.6 mmol, 95%); mp 184 ꢁC (EtOH); IR (KBr)
3088, 3063, 3030 (]C–H), 2902, 2867 (–C–H), 1497 (Ph), 1453
(CH2), 1072 (C–O–C), 734, 696 (Ph, monosubstitution) cmꢀ1 1H
;
NMR (CDCl3) d 2.20, 2.27, 2.28 (3s, 9H, 3Me), 3.28 (ddd, 1H, J¼9.7,
5.5, 2.7 Hz, H-50), 3.50–3.80 (m, 11H, H-2, H-3, H-4, H-5, H-6, H-20,
H-30, H-40, H-60), 4.50–5.07 (9d, 18H, 8PhCH2, H-1, H-10), 6.81 (s, 1H,
O–Ph–O), 7.15–7.35 (m, 40H, 8Ph); 13C NMR (CDCl3) d 12.76, 14.09,
13.35 (3Me), 68.90 (C-6, C-60), 73.49, 73.54, 74.99, 74.99, 75.17,
75.38, 75.75, 75.75 (8PhCH2), 74.93, 75.06, 77.78, 77.83, 82.30,
82.94, 84.82, 84.87 (C-2, C-20, C-3, C-30, C-4, C-40, C-5, C-50), 102.41,
104.58 (C-1, C-10), 116.19 (arom CH, O–Ph–O), 125.43, 129.43, 131.80
(arom C, O–Ph–O), 127.54–128.38 (arom CH, PhCH2), 138.10–138.74
(arom C, PhCH2), 148.52, 151.91 (arom C–O). Anal. Calcd for
4.2.2. 1,4-Bis(methyl 2,3,4-tri-O-acetyl-b-
uronate)benzene (16)
D-glucopyranosyloxy-
Methyl tetraacetyl-b-glucuronate (19.7 g, 52.2 mmol), hydro-
quinone (2.3 g, 20.9 mmol, 0.4 mol equiv), and BF3$OMe2 (24 ml,
261 mmol, 5 mol equiv) were dissolved in 500 ml of dichloro-
methane/diethyl ether 2:1 using method A. Yield 8.1 g (10.9 mmol,
42%); mp 206 ꢁC (Et2O); IR (KBr) 2959 (–C–H), 1757 (C]O), 1219,
C77H80O12 (1197.48): C, 77.23; H, 6.73. Found: C, 77.03; H, 6.73.
4.3.2. 1,4-Bis(2,3,4,6-tetra-O-benzyl-b-
benzene (9)
D-glucopyranosyloxy)-
1043 (C–O–C) cmꢀ1 1H NMR (CDCl3) d 2.04, 2.04, 2.06 (2s, 18H,
;
6MeCO), 3.74 (s, 6H, 2OMe), 4.16 (d, J¼9.40 Hz, 2H, H-5), 5.05 (d,
J¼7.39 Hz, 2H, H-1), 5.21–5.36 (m, 6H, H-2, H-3, H-4), 6.94 (s, 4H,
Ph); 13C NMR (CDCl3) d 20.49, 20.60, 20.60 (6MeCO), 52.98 (2OMe),
1,4-Bis(2,3,4,6-tetra-O-acetyl-b-D
-glucopyranosyloxy)benzene14
(4) (1 g, 1.3 mmol) was treated according to method B. Yield 710 mg
(0.615 mmol, 47%); mp 123 ꢁC (EtOH); IR (KBr) 3062, 3030 (]C–H),

5130
H.G. Thomas, J.-L. Mieusset / Tetrahedron 64 (2008) 5124–5131
2912, 2860 (–C–H), 1505 (Ph), 1454 (CH2), 1070 (C–O–C), 735, 697
(Ph, monosubstitution) cmꢀ1 1H NMR (CDCl3) d 3.55–3.80 (m,
chloride as mediator. The electrolysis was performed at room
temperature at a constant current intensity of 20 mA, until the
reaction was complete. Then, the reaction mixture was first con-
centrated and taken in ether, washed with water, dried over mag-
nesium sulfate, filtered, and evaporated. The product was isolated
by column chromatography with hexane/ethyl acetate 1:1 as the
eluent. Yield 840 mg (2.01 mmol, 75%); mp 114 ꢁC (EtOH); IR (KBr)
;
12H, H-2, H-3, H-4, H-5, H-6), 4.93 (d, J¼7.72 Hz, 2H, H-1), 4.50–
5.07 (8d, 16H, 8PhCH2), 7.02 (s, 4H, O–Ph–O), 7.15–7.35 (m, 40H,
8PhCH2); 13C NMR (CDCl3) d 68.72 (C-6), 75.01 (C-5), 73.41, 75.01,
75.01, 75.71 (4PhCH2), 77.60 (C-4), 81.96 (C-2), 84.59 (C-3), 102.37
(C-1), 118.45 (O–Ph–O), 127.68–128.37 (arom CH, PhCH2), 137.96,
138.04, 138.17, 138.45 (arom C, PhCH2), 152.93 (arom C–O).
Anal. Calcd for C74H74O12 (1155.40): C, 76.93; H, 6.45. Found: C,
76.91; H, 6.45.
2940, 2860 (C–H), 1749 (C]O) 1220, 1044 (C–O–C) cmꢀ1 1H NMR
;
(CDCl3) d 1.2–1.9 (m, 10H, CH2), 2.03, 2.03, 2.05 (2s, 9H, 3MeCO),
3.59 (tt, J¼8.3, 4.1 Hz, 1H, HC–Oaglycon), 3.75 (s, 3H, OMe), 4.44 (d,
J¼10.2 Hz, 1H, H-5), 4.84 (dd, J¼10.2, 3.8 Hz, 1H, H-2), 5.15 (dd, J¼
10.2, 9.4 Hz, 1H, H-3 or H-4), 5.31 (d, J¼3.8 Hz, 1H, H-1), 5.54 (dd,
J¼10.2, 9.4 Hz, 1H, H-3 or H-4); 13C NMR (CDCl3) d 20.54, 20.63,
20.73 (3MeCO), 23.55, 23.88 (CH2CH2CH–O), 25.45 (CH2CH2CH2CH–
O), 31.28, 33.18 (CH2CH–O), 52.84 (OMe), 68.28, 69.43, 69.90, 70.82
(C-2, C-3, C-4, C-5), 94.15 (C-1), 168.42 (C-6), 169.64, 170.01, 170.15
(3C]O); MS 417 (0.09) MþþH, 405 (0.24), 357 (3.9) MþꢀAcO, 317
(4.6) Mþꢀaglycon, 296 (4.5) Mþꢀ2AcOH, 274 (17) 317ꢀAc, 228 (70)
317ꢀAcOHꢀ(C-1)ꢀOH, AcO3C4Hþ4 , 186 (65) 228ꢀH2C]C]O, 157
(100) (AcOCH)2CHþ. Anal. Calcd for C19H8O10 (416.42): C, 54.80; H,
6.78. Found: C, 54.79; H, 6.69.
4.4. Electrolysis in an undivided cell
4.4.1. (ꢀ)-Menthyl 2,3,4,6-tetra-O-benzyl-b-
D-glucopyranoside (13)
This electrolysis was performed in an undivided 100 ml cell. The
cell was fitted with a ground glass lid and was provided with
openings for a thermometer and a gas inlet. The electrodes were
two cylindrical platinum gauzes with a surface of 25 cm2 and
a space of 2 mm between them. 1,4-Bis(2,3,4,6-tetra-O-benzyl-b-D-
glucopyranosyloxy)-2,3,5-trimethylbenzene (6) (1 g, 0.834 mmol)
was mixed together with 261 mg (1.67 mmol) (ꢀ)-menthol in
CH2Cl2 and NEt4ClO4. The electrolyses were carried out at room
temperature at a constant current intensity of 50 mA and under
stirring. The oxidation was monitored by TLC until complete dis-
appearance of the glycosyl donor. The complete reaction requires
between 2 and 3 F/mol. Then, the solution was washed with water,
dried over magnesium sulfate, filtered, and evaporated. The prod-
uct was isolated as an anomer mixture by column chromatography
with hexane/CH2Cl2 1:9 as the eluent. The b-anomer could be
separated by repeated chromatographies. Yield 930 mg
(1.37 mmol, 82%) (ꢀ)-menthyl 2,3,4,6-tetrabenzylglucopyranoside
(a/b 1:1); mp 84 ꢁC (EtOH); IR (KBr) 3063, 3033 (]C–H), 2953,
2927, 2867 (C–H), 1454 (CH2), 1073 (C–O–C), 746, 698 (Ph, mono-
substitution) cmꢀ1; 1H NMR (CDCl3) d 0.83, 0.90, 0.92 (3d, J¼6.9 Hz,
9H, 3Me), 1.00, 1.27, 1.34, 1.64, 2.12 (5m, 8H, CH), 2.36 (hd, J¼6.9,
2.5 Hz, 1H, CHMe2), 3.41 (dd, J¼8.5, 2.7 Hz, 1H, H-6), 3.43 (dd, J¼8.5,
4.7 Hz, 1H, H-6), 3.50 (td, J¼10.4, 4.1 Hz, 1H, HC–Oaglycon), 3.55–3.72
(m, 4H, H-2, H-3, H-4, H-5), 4.47 (d, J¼7.9 Hz, 1H, H-1), 4.50–5.00
(8d, J¼10.0–12.4 Hz, 8H, 4CH2Ph), 7.15–7.40 (m, 20H, 4Ph); 13C NMR
(CDCl3) d 15.98, 21.09, 22.25 (3Me), 23.22, 34.47, 40.98 (CH2), 25.29,
31.47, 48.14 (CH), 69.34 (C-6), 74.83 (C-5), 73.68, 74.83, 75.00, 75.59
(CH2Ph), 77.76, 77.97 (C-4, HC–Oaglycon), 82.24, 84.99 (C-2, C-3),
100.80 (C-1), 127.49–128.40 (arom CH, PhCH2), 138.27, 138.42,
138.60, 138.87 (arom C, PhCH2); MS 678 (0.01) Mþ, 587 (0.25)
MþꢀBn, 522 (0.08) MþꢀaglyconꢀH, 495 (0.01) Mþꢀ2BnꢀH, 481
(0.10) MþꢀBnꢀBnOþH, 431 (2.0) 522ꢀBn, 325 (1.9) 522ꢀ
BnꢀBnOþH, 301 (2.0), 275 (6.8), 253 (21) (BnOCH)2CHþ, 240 (8.6)
(BnOCH)þ2 , 181 (14) Bnþ2 ꢀH, 139 (13) aglyconþꢀOH, 91 (100)
Bnþ. Anal. Calcd for C44H54O6 (678.91): C, 77.84; H, 8.02. Found: C,
77.72; H, 7.98.
4.6. Method C
1,4-Bis(2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyloxy)-2,3,5-
trimethylbenzene (6) (500 mg, 0.418 mmol), DDQ (95 mg,
0.42 mmol), and 0.84 mmol of alcohol were dissolved in 20 ml of
dry dichloromethane. TfOH (10 mg) was added and the solution
was stirred for 10 min. If no turbidity appeared, 10 mg of TfOH was
added again. The progress of the reaction was monitored by TLC.
The reaction mixture was filtered, washed with NaHCO3 and water,
dried over magnesium sulfate, and evaporated. The product was
isolated by column chromatography.
4.6.1. Methyl 12-(2,3,4,6-tetra-O-benzyl-D-glucopyranosyloxy)-
octadecanoate (22)
Methyl 12-hydroxyoctadecanoate (21) (264 mg, 0.84 mmol) was
treated according to method C with 30 mg of TfOH. The reaction
lasted 2 h and the product was isolated by column chromatography
with hexane/ethyl acetate 3:1 as eluent. Yield 610 mg (0.73 mmol,
87%) a/b 2:1; IR (capillar) 3088, 3063, 3030 (]C–H), 2927, 2855 (C–
H), 1739 (C]O), 1454 (CH2), 1072 (C–O–C), 736, 698 (Ph, mono-
substitution) cmꢀ1
;
1H NMR (CDCl3) a-anomer: d 0.87 (t, J¼6.0 Hz,
3H, Me), 1.26 (‘s’, 24H, CH2), 1.53, 1.59 (2 m, 4H, CH2CH–O), 2.26 (t,
J¼7.4 Hz, 2H, CH2C]O), 3.44 (br t, J¼7.7 Hz, 1H, HC–Oaglycon), 3.61
(s, 3H, OMe), 3.52–3.73 (m, 3H, HC–O), 3.74 (dd, J¼10.4, 3.4 Hz, 1H,
H-6), 3.90 (br d, J¼9.4 Hz, 1H, H-5), 4.00 (t, J¼9.4 Hz, 1H, H-3 or H-
4), 4.4–5.0 (9d, 9H, H-1, 4PhCH2), 7.10–7.40 (m, 20H, Ph); 13C NMR
(CDCl3) a-anomer:
d
14.12 (Me), 22.65 (MeCH2), 24.89
(CH2CH2C]O), 24.89, 25.67 (CH2CH2CH–O), 29.10, 29.23, 29.39,
29.56, 29.66, 29.81, 29.94 (CH2), 31.77 (MeCH2CH2), 33.17, 34.47
(CH2CH–O), 51.29 (OMe), 68.50 (C-6), 73.18, 73.41, 74.98, 75.51
(PhCH2), 70.41, 73.18, 77.94, 80.09, 82.09 (HC–O), 95.66 (C-1),
127.44–128.28 (arom CH, PhCH2), 137.97, 138.29, 138.33, 138.93
(arom C, PhCH2), 174.08 (C]O); characteristic peaks of the b-
anomer: d 25.13, 25.29 (CH2CH2CH–O), 31.75 (MeCH2CH2), 34.21,
34.90 (CH2CH–O), 69.17 (C-6), 73.52, 74.88, 74.98, 75.57 (PhCH2),
74.88, 78.02, 79.84, 82.40, 84.91 (HC–O), 102.63 (C-1), 138.22,
138.39, 138.59, 138.73 (arom C, PhCH2); MS 745 (0.0006) MþꢀBn,
698 (0.0008), 639 (0.0001) MþꢀBnOꢀBnþH, 607 (0.004), 539
(0.04) 522þOH, 522 (0.03) MþꢀaglyconꢀH, 431 (0.64) 522ꢀBn,
355 (1.1), 325 (1.1) 522ꢀBnꢀBnOþH, 297 (11) aglyconþꢀOH,
253 (10) (BnOCH)2CHþ, 240 (6.6) C17H3þ6, 181 (13) Bnþ2 ꢀH, 91 (100)
Bnþ. Anal. Calcd for C53H72O8 (837.15): C, 76.04; H, 8.67. Found: C,
76.27; H, 8.54.
4.5. Electrolysis in a divided cell
4.5.1. Methyl (cyclohexyl 2,3,4-tri-O-acetyl-a-
uronate (17)
D-glucopyranosid)-
This electrolysis was performed in a divided cell. A ‘H’-cell was
employed. Each of the two electrode compartments held approxi-
mately 100 ml of electrolyte. They were connected by a 4 cm di-
ameter glass frit (No. 4). The cell was hermetically closed and the
lids had an inlet and outlet for the passage of nitrogen gas. The
electrodes were suspended from the lids. The anode was a platinum
gauze and the cathode a carbon cylinder. Lithium perchlorate (3 g)
was placed into each compartment and dissolved in 90 ml aceto-
nitrile. 1,4-Bis(methyl 2,3,4-tri-O-acetyl-b-D-glucopyranosyloxy-
uronate)benzene (16) (1 g, 1.34 mmol) and 269 mg (2.68 mmol) of
cyclohexanol were added together with 50 mg of cobalt (II)

H.G. Thomas, J.-L. Mieusset / Tetrahedron 64 (2008) 5124–5131
5131
4.6.2. 1,3-Bis(hexadecanoyloxy)prop-2-yl 2,3,4,6-tetra-O-
benzyl- -glucopyranoside (24)
References and notes
D
1. (a) Fu¨gedi, P. Organic Chemistry of Sugars; Levy, D. E., Fu¨gedi, P., Eds.; CRC: Boca
Raton, FL, 2006; pp 89–179; (b) Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93,
1503–1531; (c) Boons, G. J. Tetrahedron 1996, 52, 1095–1121; (d) Davis, B. G.
J. Chem. Soc., Perkin Trans. 1 2000, 2137–2160; (e) Toshima, K. Carbohydr. Res.
2006, 341, 1282–1297.
Dipalmitine 23 (477 mg, 0.84 mmol) was treated according to
method C with SnCl4 (218 mg, 0.84 mmol). The reaction lasted 1 h
and the product was isolated by column chromatography with
hexane/ethyl acetate 6:1 as eluent. Yield 700 mg (0.64 mmol, 77%);
a/b 2:1; IR (KBr) 3087, 3063, 3030 (]C–H), 2918, 2852 (C–H), 1739
(C]O), 1457 (CH2), 1072 (C–O–C), 738, 699 (Ph, mono-
substitution) cmꢀ1; 1H NMR (CDCl3) a-anomer: d 0.88 (t, J¼6.5 Hz,
6H, Me), 1.26, 1.76 (2m, 48H and 4H, CH2), 2.26 (m, 4H, CH2C]O),
3.4–4.4 (m, 11H, HC–O), 4.4–5.0 (8d, 8H, 4PhCH2), 5.05 (d, J¼3.4 Hz,
1H, H-1), 7.10–7.40 (m, 20H, Ph); 13C NMR (CDCl3) a-anomer:
d 14.13 (Me), 22.70 (MeCH2), 24.85 (CH2CH2C]O), 29.38–29.71
(CH2), 31.94 (MeCH2CH2), 34.09, 34.13 (CH2C]O), 62.77, 63.67
(CH2O), 68.35 (C-6), 73.07, 73.53, 75.01, 75.68 (PhCH2), 70.71, 72.92,
77.53, 79.75, 81.80 (HC–O), 96.40 (C-1), 127.55–128.47 (arom CH,
PhCH2), 138.12, 138.12, 138.31, 138.82 (arom C, PhCH2), 173.32
2. Noyori, R.; Kurimoto, I. J. Org. Chem. 1986, 51, 4320–4322.
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Commun. 1990, 718–719; (b) Mallet, J.-M.; Meyer, G.; Yvelin, F.; Jutand, A.;
Amatore, C.; Sinay¨, P. Carbohydr. Res. 1993, 244, 237–246; (c) Amatore, C.;
Jutand, A.; Meyer, G.; Bourhis, P.; Machetto, F.; Mallet, J.-M.; Sinay¨, P.; Tabeur, C.;
Zhang, Y.-M. J. Appl. Electrochem. 1994, 24, 725–729.
4. (a) Balavoine, G.; Gref, A.; Fischer, J. C.; Lubineau, A. Tetrahedron Lett. 1990, 31,
5761–5764; (b) Vijayakumar, S.; Nagarajan, P.; Sulochana, N. Indian J. Chem.,
Sect. B 1993, 32, 599–600; (c) Hamann, C. H.; Polligkeit, H.; Wolf, P.; Smiatacz, Z.
Carbohydr. Res. 1994, 265, 1–7; (d) Patricia, J. F. R.; Jasintha, T.; Nagarajan, P.;
Subramanian, N. S.; Sulochana, N. Bull. Electrochem. 1995, 11, 324–325; (e)
Balavoine, G.; Berteina, S.; Gref, A.; Fischer, J. C.; Lubineau, A. J. Carbohydr. Chem.
1995, 14, 1217–1236; (f) Tanaka, N.; Ohnishi, F.; Uchihata, D.; Torii, S.; Nokami, J.
Tetrahedron Lett. 2007, 48, 7383–7387.
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Biomol. Chem. 2004, 2, 2188–2194; (b) France, R. R.; Compton, R. G.; Davis, B. G.;
Fairbanks, A. J.; Rees, N. V.; Wadhavan, J. D. Org. Biomol. Chem. 2004, 2, 2195–
2202; (c) Drouin, L.; Compton, R. G.; Fietkau, N.; Fairbanks, A. J. Synlett 2007,
2711–2717.
6. (a) Yamago, S.; Kokubo, K.; Yoshida, J. Chem. Lett. 1997, 26, 111–112; (b) Yamago,
S.; Kokubo, K.; Hara, O.; Masuda, S.; Yoshida, J. J. Org. Chem. 2002, 67, 8584–
8592.
(C]O); characteristic peaks of the b-anomer:
d
24.81
(CH2CH2C]O), 34.01, 34.28 (CH2C]O), 63.32, 63.50 (CH2O), 68.86
(C-6), 73.52, 74.69, 75.02, 75.68 (PhCH2), 75.01, 81.99, 84.63 (HC–O),
103.47 (C-1), 137.86, 137.86, 138.47, 138.59 (arom C, PhCH2), 173.47
(C]O); MS 1123 (<0.1) MþþCO2ꢀH, 595 (1.7) aglyconþþCO2ꢀOH,
551 (30) aglyconþꢀOH, 522 (<1) MþꢀaglyconꢀH, 431 (4.0)
522ꢀBn, 341 (7.0) 522ꢀ2BnþH, 325 (3.9) 522ꢀBnꢀBnOþH, 313
(21), 299 (8.9), 253 (12) (BnOCH)2CHþ, 239 (14) C15H31COþ, 181
(8.7) Bnþ2 ꢀH, 106 (92) BnOþꢀH, 91 (100) Bnþ. Anal. Calcd for
7. (a) Suzuki, S.; Matsumoto, K.; Kawamura, K.; Suga, S.; Yoshida, J. Org. Lett. 2004,
6, 3755; (b) Nokami, T.; Shibuya, A.; Tsuyama, H.; Suga, S.; Bowers, A. A.; Crich,
D.; Yoshida, J. J. Am. Chem. Soc. 2007, 129, 10922–10928.
8. (a) Rondinini, S.; Mussini, P. R.; Sello, G.; Vismara, E. J. Electrochem. Soc. 1998,
145, 1108–1112; (b) Benedetto, M.; Miglierini, G.; Mussini, P. R.; Pelizzoni, F.;
Rondinini, S.; Sello, G. Carbohydr. Lett. 1995, 1, 321–328; (c) Brevet, D.; Mugnier,
Y.; Samreth, S.; Dellis, P. Carbohydr. Res. 2003, 338, 1543–1552.
C
69H102O10 (1091.56): C, 75.92; H, 9.42. Found: C, 75.80; H, 9.24.
9. (a) Nokami, J.; Osafune, M.; Ito, Y.; Miyake, F.; Sumida, S.-I.; Torii, S. Chem. Lett.
1999, 28, 1053–1054; (b) Mitsudo, K.; Kawaguchi, T.; Miyahara, S.; Matsuda, W.;
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4.6.3. Methyl 12-(2,3,4,6-tetra-O-acetyl-b-
octadecanoate (28)
D-glucopyranosyloxy)-
1,4-Bis(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyloxy)naph-
thalene (25) (500 mg, 0.61 mmol), DDQ (138 mg, 0.61 mmol),
methyl 12-hydroxyoctadecanoate (337 mg, 1.22 mmol, 1 mol equiv)
dissolved in 2 ml of dry dichloromethane and SnCl4 (318 mg,
1.22 mmol) were stirred together in 20 ml of MeCN. After 2 days,
the reaction mixture was concentrated and the residue was dis-
solved in CH2Cl2, washed with NaHCO3 and water, and dried over
magnesium sulfate. The product was isolated by column chroma-
tography with hexane/ethyl acetate 3:1 as eluent. Yield 320 mg
(0.5 mmol, 41%); IR (KBr) 2929, 2856 (C–H), 1757 (C]O) 1225, 1040
(C–O–C) cmꢀ1; 1H NMR (CDCl3) d 0.88 (t, J¼6.8 Hz, 3H, Me),1.2–1.65
(m, 28H, CH2), 2.00, 2.02, 2.02, 2.07 (3s, 12H, 4MeCO), 2.30 (t,
J¼7.5 Hz, 2H, CH2C]O), 3.55 (p, J¼5.5 Hz, 1H, HC–Oaglycon), 3.66 (s,
3H, OMe), 3.68 (ddd, J¼9.5, 5.4, 2.3 Hz, 1H, H-5), 4.12 (dd, J¼12.1,
2.3 Hz, 1H, H-6), 4.23 (dd, J¼12.1, 5.4 Hz, 1H, H-6), 4.56 (d, J¼8.0 Hz,
1H, H-1), 4.96 (dd, J¼9.4, 8.0 Hz, 1H, H-2), 5.06, 5.20 (2t, J¼9.4 Hz,
2H, H-3, H-4); 13C NMR (CDCl3) d 14.08 (Me), 20.60, 20.60, 20.64,
20.68 (4MeCO), 22.65 (MeCH2), 24.96 (CH2CH2C]O), 25.02, 25.10
(CH2CH2CH-O), 29.15, 29.26, 29.46, 29.55, 29.59, 29.67 (CH2), 31.89
(MeCH2CH2), 34.08 (CH2C]O), 34.17, 34.81 (CH2CH–O), 51.38
(OMe), 62.30 (C-6), 68.74, 71.55, 71.73, 73.08 (C-2, C-3, C-4, C-5),
81.35 (HC–Oaglycon), 100.48 (C-1), 169.18, 169.43, 170.32, 170.55
(4MeCO); MS 645 (0.06) MþþH, 613 (0.16) MþꢀMeO, 585 (0.09)
MþꢀC2H3O2, 553 (0.66) MþꢀAcOHꢀMeO, 524 (0.05) Mþꢀ2AcOH,
493 (0.13) Mþꢀ2AcOHꢀMeO, 464 (0.55) Mþꢀ3AcOH, 422 (0.50)
Mþꢀ3AcOHꢀH2C]C]O, 331 (56) Mþꢀaglycon, 297 (59) agly-
conþꢀOH, 289 (20) 331ꢀH2C]C]O, 271 (16) 331ꢀAcOH, 242 (82)
331ꢀAcOHꢀ(C-1)ꢀOH, 229 (23) 331ꢀAcOꢀAc, 200 (46)
242ꢀH2C]C]O, 169 (100) 331ꢀ2AcOHꢀHC]C]O. Anal. Calcd for
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C
33H56O12 (644.80): C, 61.47; H, 8.75. Found: C, 61.17; H, 8.81.