Electrochemical reduction in an aprotic medium of new functionalized amphiphilic molecules derived from sugars: Stereoselective pinacolization and an example of a glycosidic carbon-oxygen bond cleavage

Article abstract of DOI:10.1002/(SICI)1099-0690(200003)2000:5<813::AID-EJOC813>3.0.CO;2-Q

Electroreducible amphiphilic aromatic ketones derived from D-glucose and D-glucofuranurono-6,3-lactone (D-glucurone) have been synthesized by Schmidt condensation and reaction of the unprotected lactone with the appropriate substrates, respectively. The m

Full text of DOI:10.1002/(SICI)1099-0690(200003)2000:5<813::AID-EJOC813>3.0.CO;2-Q

FULL PAPER
Electrochemical Reduction in an Aprotic Medium of New Functionalized
Amphiphilic Molecules Derived from Sugars: Stereoselective Pinacolization and
an Example of a Glycosidic Carbon-Oxygen Bond Cleavage
Catherine Maurice,[a] Bernd Schöllhorn,[a] Isabelle Canet,[a] Guy Mousset,[a]
[a]
[b]
[b]
´ ˆ
Christine Mousty,* Jerome Guilbot, and Daniel Plusquellec
Keywords: Amphiphiles / Ketone / Glycosides / Electron transfer / Enantiomeric resolution
Electroreducible amphiphilic aromatic ketones derived from
-glucose and -glucofuranurono-6,3-lactone ( -glucurone)
use of a redox mediator (couple anthracene–•/anthracene)
has demonstrated that a glucosidic bond can be reduced by
D
D
D
have been synthesized by Schmidt condensation and reac- a homogeneous electron transfer. In the presence of a proton
tion of the unprotected lactone with the appropriate sub- donor the expected -glucuronic pinacol is obtained. The
strates, respectively. The macroscale electrolyses of the glu- radical-radical coupling involves the formation of two chiral
cose derivatives, performed in an aprotic solvent (DMF), centers. The diastereo- and the enantioselectivity of the reac-
yield the pinacols possessing two glycosidic side chains. Un- tion have been studied by 1H- and 2H-NMR spectroscopy, re-
D
der the same conditions of electrolysis with the
D-glucurone
spectively.
derivative, the glyosidic carbon-oxygen bond is cleaved. The
Introduction
In previous work, we studied the electrochemical be-
havior of such surfactant molecules and their adsorption
mode at the mercury electrolyte interface.[9] In the present
article, we report the results of the macroscale electrolyses
of glycosidic amphiphilic molecules derived from -glucose
1 and 2 or from -glucurone 3 performed in an aprotic me-
dium. In the latter case, 3, the electrolyses were achieved in
the absence or in the presence of a proton donor. The influ-
ence of the sugar unit on the diastereo- and enantioselectiv-
Alkyl glycosides and alkyl polyglucosides have gained
wide interest during the past two decades. They have been
used for miscellaneous applications in biological pro-
cesses[1–3] for the isolation of membrane proteins or as non-
toxic detergents produced in industry.[4,6] The presence of
chiral centers in the sugar moiety coupled with their ability
to form ordered systems (visicules, micelles) has been used
for regioselective and enantioselective reduction of pro-
chiral carbonyl derivatives.[7,8] In the context of electro-
chemistry in a micellar medium, we have synthesized new
alkyl glycosides of the following general structure:
1
2
ity has been analyzed by H- and H-NMR spectroscopy,
respectively. A comparison with the nonglycosidic ketone 4
has also been made.
The main aim of this study was to convert the two ke-
tones into the corresponding bolaamphiphilic-type surfact-
ants by carbon-carbon bond formation. Such bolaamphi-
philes are of growing interest as models for lipids found in
membranes of thermophilic archaebaceria,[10] for the pre-
paration of monolayer stable vesicles[11] and the disruption
of biological membranes.[12]
Results and Discussion
[a]
´
Universite Blaise Pascal, "SEESIB" (UMR CNRS 6504),
`
24, Avenue des Landais, F-63177 Aubiere cedex, France
[b]
`
´
ENSCR,"Syntheses et Activations de Biomolecules" (ESA
CNRS 6052),
In a previous paper,[9] we described the syntheses of the
glucopyranosides 1 and 2 according to the Schmidt glycos-
ylation reaction.[13] The synthesis of the 1-O-[8-(4-acetyl-
phenoxy)octyl] β--glucofuranosidurono-6,3-lactone 3 was
performed in dry tetrahydrofuran in a single condensation
´ ´
Avenue du General Leclerc, F-37500 Rennes, France
Present address of C. Mousty:
Laboratoire d’Electrochimie Organique et de Photochimie
´
Redox, Universite Joseph Fourier Grenoble 1
301, rue de la Chimie, BP 53, F-38041 Grenoble Cedex 9, France
E-mail: Christine.Mousty@ujf-grenoble.fr
Eur. J. Org. Chem. 2000, 813Ϫ821
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0305Ϫ0813 $ 17.50ϩ.50/0
813

C. Maurice, B. Schöllhorn, I. Canet, G. Mousset, C. Mousty, J. Guilbot, D. Plusquellec
FULL PAPER
Scheme 1. Synthesis of glycosidic ketones 3 and 6
step involving the ketone 5, an excess of -glucurone (4 one electron transfer and leads to an anion-radical that
equiv.) and boron trifluoride (10 equiv.) as a promoter couples, resulting in the formation of the corresponding pi-
(Scheme 1).
nacol.[14]
In an aprotic solvent (DMF), the cyclic voltammograms
At the end of every electrolysis, the reduction products
of the three ketones 1, 2 and 3 present only one irreversible were purified by chromatography on a silica gel column and
peak located at –2.18 V/SCE (Figure 1). The nonglycosidic characterized by 1H, NMR spectroscopy and HRMS
aromatic ketone 4 exhibits a slightly reversible peak under (FABϩ) (see Experimental Section).
the same conditions at –2.23 V/SCE.
Electrolysis of the Model Compound 4
Electrolysis of 4 led to the formation of the pinacol 7.
Two chiral centers have been generated by the radical-radical
coupling reaction, implying that the molecule may exist in
two diastereomeric forms (d,l and meso). The 1H, NMR
spectrum of the crude electrolysis mixture shows, in the aro-
matic area, a set of doublets characteristic of two p-disubsti-
tuted benzene rings (Figure 2).
Figure 1. Voltammogram of 2 ϫ 10–3  2 in 0.1  Bu4NPF6/DMF,
v ϭ 0.05 V s–1
The macroscale electrolyses of the two ketones derived
These signals correspond to the presence of the racemic
from glucose (1 and 2), performed in dry DMF, consume 1 d,l and meso diastereoisomers. The assignment of each signal
Faraday/mol (Table 1). With 4, the electrolysis once more to the corresponding stereoisomer was based on a compar-
indicates an electricity consumption of one electron per mo- ison with similar spectra recorded under the same conditions
lecule. Indeed, it is generally known that the electroreduc- for authentic samples of the pinacols of the trifluoromethyl
tion of aromatic ketones in an aprotic medium involves a acetophenone and the methyl acetophenone. In these cases,
Table 1. Electrolysis in DMF
Substrate
Electrolysis
Remaining
Electricity
Reduction
product
d,l/meso
Electrolysis
yield[c] (%)
Conditions[a]
ketone[b] (%)
consumption (F. mol–1)
4
2
1
3
3
A
B
B
C
D
20
1.00
1.10
1.05
2.55
1.44
7
9.53
2.12
2.45
4.41
4.26
80
60
60
–
Ͻ10
Ͻ10
Ͻ10
Ͻ10
8 (n ϭ 8)
9 (n ϭ 3)
5 and 10
12
40
[a]
A: 0.1  Bu4NBF4, Eappl ϭ –2.20 V/SCE, 500 mg starting material; B: 0.1  Bu4NBF4, Eappl ϭ –2.10 V/SCE, 200–300 mg starting
material; C: 0.1  Bu4NPF6, Eappl ϭ –2.15 V/SCE, 200 mg starting material; D: 0.1  Bu4NPF6, 1.72 ϫ 10–2  Bu4NHSO4, Eappl ϭ –2.15
V/SCE, 160 mg starting material. –
isolated picacol/amount of initial ketone.
[b]
[c]
Remaining ketone: remaining amount of ketone/initial amount. –
Electrolysis yield: weight of
814
Eur. J. Org. Chem. 2000, 813Ϫ821

Stereoselective Pinacolization and an Example of a Glycosidic Carbon-Oxygen Bond Cleavage
FULL PAPER
icals by the hydroxyl groups of the carbohydrate that com-
petes with the ion pair formation by BuNϩ. The steric inter-
actions of the carbohydrate groups promote a head-to-tail
orientation of the two anion-radicals. Coupling from this
configuration favors, as postulated by Stocker et al.,[18,19] the
formation of the meso pinacol (Scheme 3).
1
Figure 2. H aromatic and hydroxyl NMR signals of pinacols 7 re-
sulting from the electroreduction of 4 in an aprotic medium
each diastereoisomer was characterized by gas chromato-
graphy on a chiral column (LIPODEX-E) and by 1H, NMR
spectroscopy (400 MHz, [D6]DMSO). In the case of meso
diastereoisomers, the set of doublets characteristic of p-dis-
ubstituted benzene rings is systematically situated at lower
field as compared with that corresponding to the d,l diastere-
isomers. This sequence is inverted for the protons of the alco-
hol function (Figure 2).[15] The d,l/meso ratio of 9.5 for the
two diastereomeric pinacols 7 is quite high. Bewick et
al.[16,17] and Stocker et al.[18,19] have postulated that this dias-
tereoselectivity can be explained by ion-pair formation be-
tween the anion-radical and BuNϩ from the supporting elec-
trolyte. Thereby the less hindered radical pair with the methyl
and phenyl groups facing each other (Scheme 2) leads to the
favoured d,l diatereiosomer.
Scheme 3. Steric interactions postulated in the case of carbohyd-
rate compounds
Electrolysis of the Ketone Derived from -Glucurone 3
The results of the macroscale electrolysis of compound 3
(200 mg) performed at E ϭ –2.15 V/SCE are different to
those observed with the three others ketones. Firstly, the elec-
tricity consumption corresponds to 2.55 Faraday per mol of
ketone and, secondly, the formation of three products is ob-
served by thin layer chromatography. Two of these products,
corresponding to the higher Rf values (0.77 and 0.65 in Ac-
1
OEt), have been identified by H, NMR spectroscopy and
HRMS as ketone 5 (20 mg) and pinacol 10 (80 mg), respect-
ively. These main reaction products (5 and 10) result from a
cleavage of the carbon-oxygen glycosidic bond, the pinacol
being formed by reduction of the ketone 5 at the fixed poten-
tial. The d,l/meso ratio for the pinacol 10 is 4.41, an interme-
diate value between those observed with 4 (d,l/meso ϭ 9.53)
and with the ketones 2 and 1 (d,l/meso ϭ 2.12 and 2.45,
respectively) (Table 1).
Scheme 2. Steric interactions involved in the case of ion pair forma-
tion[18,19]
Electrolysis of the Glycosidic Ketones 1 and 2
Electroreduction in DMF of the glycosidic ketones 2 and
1 leads to the formation of the expected pinacols 8 and 9:
The structure of the third product (Rf ϭ 0), or mixture of
products, cannot be elucidated but it probably corresponds
to the protonated form of the carbanion and/or the ammo-
nium salt of the ring opened carbohydrate (Scheme 4).
However, in these cases, the d,l/meso ratio decreases to 2,
close to the value reported for an aqueous medium.[18,19]
This shift can be explained by a solvation of the anion rad-
Eur. J. Org. Chem. 2000, 813Ϫ821
815

C. Maurice, B. Schöllhorn, I. Canet, G. Mousset, C. Mousty, J. Guilbot, D. Plusquellec
FULL PAPER
Scheme 4. Electrocatalytic process involved in the cleavage of the glycosidic bond of the lactonic ketone 3
Two hypotheses can be formulated to explain such a car-
bon-oxygen bond cleavage. The first explanation involves a
direct electron transfer to the glycosidic bond occurring at
the applied potential. A comparison with the alkyl glycoside
11 reveals that such a reduction process cannot take place at
the applied potential used for macroscale electrolyses of our
aromatic ketone. Indeed, the lactone 11 is reduced in an ill-
defined wave that appears very close to the electrolyte dis-
charge (E Х –2.8 V/SCE) (Figure 3).
Figure 4. Voltammograms of 2 ϫ 10–3  anthracene (A) in 0.1 
Bu4NPF6/DMF, v ϭ 0.02 V s–1, (a) alone, (b) with 4 ϫ 10–3  lac-
tone 11
formed by a well adapted mediator. We chose anthracene
(A), which gives a redox couple A–•/A at Eo ϭ –1.97 V/SCE.
In spite of the fact that the cyclic voltammogram of pure
anthracene is disturbed by interactions of A–• with the Hg
electrode, Figure 4 shows that, in the presence of 11, the
signal becomes irreversible and a catalytic effect is observed
on the cathodic response.
Figure 3. Voltammogram of 2 ϫ 10–3  lactone 11 in 0.1 
Bu4NPF6/DMF, v ϭ 0.05 V s–1
This result confirms the proposed electrocatalytic process
Secondly, the electricity consumption (2.55 F.mol–1) sug- involved in the cleavage of the glycosidic bond of the lactonic
gests an electrocatalytic process involving the anion-radical surfactant (Scheme 5).
of 3 –• playing the role of mediator in a homogeneous trans-
In a homogeneous electron transfer implying an anion-
fer to the glycosidic bond. This transfer can be either intra- radical, the presence of a proton donor can disturb the cata-
or intermolecular with, as a consequence, the formation of a lytic process by consumption of the mediator. In the presence
sugar radical R• further reduced at the electrode or in solu- of Bu4NHSO4, we noted that the intensity of the reduction
tion by the anion-radical 3–• (Scheme 4).
peak of 3 is decreased compared to that observed in the ab-
Taking into account the possibility of reducing the alkyl sence of a proton donor, and the electricity consumption
glycoside 11 at a more negative potential, we verified that measured for macroscale electrolyses falls to 1.44
the reductive cleavage of the glycosidic bond can be per- F mol–1. The major product isolated under these condi-
816
Eur. J. Org. Chem. 2000, 813Ϫ821

Stereoselective Pinacolization and an Example of a Glycosidic Carbon-Oxygen Bond Cleavage
FULL PAPER
tion with CD3I in the presence of NaH. A first experiment
was performed with the pinacol 7 of the nonglycosidic model
molecule. Two reaction products were isolated and identified
to be the monoether 13 and the diether 14 (Scheme 6).
Figure 5a and 5b show the spectra obtained for the deuter-
ium signal of the trideuteriomethyl monoether and of the
trideuteriomethyl diether. The spectrum of the first one con-
sists of two sets of doublets. The most important of these is
attributed to the ether of the d,l pinacol and the other to
that of pinacol meso. Each enantiomer of the racemic pinacol
is characterized by a doublet with quadrupolar splittings
1
2
∆νQ ϭ 65 Hz and ∆νQ ϭ 82 Hz. As expected for this ex-
ample, no asymmetric induction is observed. No quadrupo-
lar splitting was observed for the diether 14 (Figure 5b).
Scheme 5. Electrocatalytic process, performed with anthracene as
redox mediator, leading to the cleavage of the glycosidic bond of the
lactone 11
tions corresponds to the diastereomeric pinacols 12 still bear-
ing the saccharidic groups:
In this case, the ratio d,l/meso is 4.26, a value close to that
obtained for pinacols 10.
Study of the Enantioselectivity
As previously shown (vide supra), the electrochemical re-
duction of aromatic ketones in an aprotic medium leads
mainly to the pinacols possessing two chiral centers. In our
case, we wished to investigate whether the radical-radical
coupling induces chirality due to the presence of the sugar
moiety. Several methods, such as chromatography on a chiral
support or NMR in the presence of chiral shift reagents, are
commonly used to determine the enantiomeric excesses. Un-
fortunately these methods were unsuccessful for our prod-
ucts. Moreover, Mosher’s method[20] for the determination of
enantiomeric compositions was not applicable because of the
steric hindrance of the tertiary alcohols. During the past dec-
ade, a very convenient technique based on the 2H-NMR
spectroscopy in liquid crystals has been developed.[21] The
solvent used for the NMR experiments is a liquid crystal
obtained by dissolution of poly-γ-benzyl--glutamate
(PBLG) in dichloromethane. In such a chiral medium, the
two enantiomers of the studied substrate can be set out dif-
ferently and in this way give two quadrupolar splittings for
Figure 5. 2H-NMR spectra in a polypeptide liquid crystal of (a)
monoether 13, (b) diether 14
Application of the same method to the pinacol 8, derived
from glucose, required the selective protection of the hy-
droxyl groups of the sugar. Their esterification with benzoyl
chloride is possible but the reaction product 15 does not re-
act further with CD3I.
2
the H signal. The deuterium atoms were introduced in our
pinacols
by
mean
of
an
etherification
reac-
Scheme 6
Eur. J. Org. Chem. 2000, 813Ϫ821
817

C. Maurice, B. Schöllhorn, I. Canet, G. Mousset, C. Mousty, J. Guilbot, D. Plusquellec
an aqueous medium of these ketones, are in progress in our
FULL PAPER
The protection of pinacol 8 can be successfully achieved group.[22]
with benzyl bromide in the presence of NaH. However, the
reaction evolution must be carefully monitored by thin layer
Experimental Section
chromatography and stopped before the etherification of the
tertiary hydroxyl functions of the pinacol. With this pro-
tecting group the monotrideuteriomethyl ether (17) can be
obtained:
A Tacussel PRT 100-1X potentiostat coupled with a Tacussel IG5-N
integrator was used for controlled-potential electrolyses, which were
performed in a three compartment glass cell joined by two glass
sinters. The cathodic cell contained the ketone (200–500 mg) dis-
solved in 60 mL of DMF in the presence of 0.1  Bu4NBF4 or 0.1 
Bu4NPF6 as supporting electrolyte at 20 °C. The aqueous saturated
calomel electrode (SCE) with an extension (DMF saturated with
Bu4NBF4 or Bu4NPF6) was used as the reference electrode. The
cathode was a mercury pool of 16 cm2 and the anode a graphite
electrode. In the case of glycosidic compounds 1, 2 and 3, 10 drops
of water were also added to the cathodic solution after complete
electrolysis in order to protonate the anions. The DMF was further
distilled under reduced pressure at 50 °C. In the case of the nongly-
cosidic molecule 4, the organic solution was poured into 400 mL of
water and the products extracted with ether. The reduction products
were chromatographed on a silica gel column (Merck, 70–230 mesh)
and characterized by 1H, and 13C-NMR spectroscopy and mass
spectrometry. The electrolysis yields are given in Table 1.
The NMR analysis (Figure 6) shows that no significant
enantiomeric excess has been induced by the chiral
auxiliary.
The 1H- and 13C-NMR spectra were recorded on Bruker AC 400
and ARX 400 spectrometers. Infrared spectra were obtained with
2
Nicolet Impact 400 FT and Nicolet 205 FT spectrometers. The H,
NMR spectra were registered on Bruker AM 250 and MSL 300
spectrometers. The high resolution mass spectrometry (HRMS) was
performed at the Centre National de la Recherche Scientifique
(CNRS) at Vernaison (France). All the solvents were reagent grade
and purchased from Aldrich.
The general synthetic pathways to the ketones 1, 2, 4 and lactone 11
have been described in previous papers.[9][23][24]
1-O-[8-(4-Acetylphenoxy)octyl] β-D-Glucofuranosidurono-6,3-lactone
(3): To a suspension of -glucurone (3.06 g, 17.4 mmol, 4 equiv.) in
dry THF (30 mL) was added the electroreducible alcohol 5 (1.15 g,
4.35 mmol, 1 equiv.) and then BF3·Et2O (48% BF3, 5.35 mL,
43.5 mmol, 10 equiv.). The mixture was magnetically stirred and
heated under reflux for 1 h 45 min. The solvent was evaporated
under reduced pressure and the colored residue dissolved in ethyl
acetate (30 mL). The organic layer was washed twice with water,
dried over MgSO4 and concentrated under reduced pressure. Prod-
Figure 6. 2H-NMR spectrum in a polypeptide liquid crystal of mon-
oether 17
Conclusion
In summary, the electrochemical reduction in an aprotic uct 3 was purified by chromatography on a silica gel column [elu-
ent: ethyl acetate/petroleum ether (1:1 then 7:3 v/v), TLC: Rf (3) ϭ
0.55 in ethyl acetate]. Compound 3 was obtained as a white powder
in 55% yield (1 g), mp: 70–72 °C. – HRMS (FABϩ) calcd. for
[C22H30O8Li]ϩ: 429.2100; found 429.2094. – [α]2D0 ϭ –32.7 (c ϭ
medium of glycosidic amphiphilic molecules derived from -
glucose and -glucurone appears to be a convenient route to
obtain two-chain surfactants. The carbon-carbon bond
formation is performed with a high chemoselectivity. The
presence of the nonprotected sugar unit therefore involves a
decrease in the diastereoselectivity (d,l/meso ratio) compared
to that observed under the same conditions for the nonglyos-
idic aromatic ketone. The radical-radical coupling generates
1
1.01; CHCl3). – H NMR (400 MHz, [D6]DMSO): δ ϭ 7.95 (d, 2
H, J ϭ 8.9 Hz, aromatic), 7.06 (d, 2 H, J ϭ 8.9 Hz, aromatic), 5.86
(d, 1 H, J ϭ 6.4 Hz, OH), 5.71 (d, 1 H, J ϭ 3.9 Hz, OH), 4.94 (s,
1 H, H1), 4.79 (dd, 1 H, J ϭ 6.4, 4.4 Hz, H4), 4.73 (d, 1 H, J ϭ
4.4 Hz, H3), 4.47 (t, 1 H, J ϭ 5.9 Hz, H5), 4.09 (t, 2 H, J ϭ 6.9 Hz,
CH2OAr), 4.08 (d, 1 H, J ϭ 5.4 Hz, H2), 3.72 (m, 1 H, OCH2),
2
two new stereogenic centers. A recent method based on H-
NMR spectroscopy has been applied for the first time, to the 3.23 (mc, 1 H, OCH2), 2.54 (s, 3 H, CH3), 1.76 (quint, 2 H, J ϭ
7.0 Hz, CH2), 1.18–1.50 (m, 10 H, CH2). – 13C NMR (100 MHz,
CDCl3): δ ϭ 197.67, 174.55, 163.32, 130.72, 129.88, 114.26, 109.17,
83.20, 77.54, 77.10, 69.13, 69.11, 68.27, 25.79–29.18.
best of our knowledge, to the determination of enantiomeric
excesses of diastereomeric pinacols. In the particular case of
the glucurone derivative, an electrochemical cleavage of the
glycosidic bond is observed in the absence of a proton donor
while the expected pinacol is isolated in the presence of
Sodium 1-O-[8-(4-Acetylphenoxy)octyl]-β-
(6): To a solution of compound 3 (0.93 g, 2.2 mmol, 1 equiv.) in
D-glucofuranosiduronate
Bu4NHSO4. Further investigations, especially electrolyses in acetone (30 mL) was added very slowly (30 min), at –10 °C, 4.4 mL
818 Eur. J. Org. Chem. 2000, 813Ϫ821

Stereoselective Pinacolization and an Example of a Glycosidic Carbon-Oxygen Bond Cleavage
FULL PAPER
of a 0.5  solution of NaOH in H2O (2.2 mmol, 1 equiv.). The (400 MHz, [D6]DMSO): δ ϭ 6.99 (d, 4 H, J ϭ 8.4 Hz, aromatic),
mixture was stirred at 15 °C for 2 h and then diluted with diethyl 6.70 (d, 4 H, J ϭ 8.9 Hz, aromatic), 5.06 (d, 2 H, J ϭ 4.9 Hz, OH,
ether. The organic solution was extracted with water (2 ϫ 15 mL). sugar), 4.98 (d, 2 H, J ϭ 4.4 Hz, OH, sugar), 4.95 (d, 2 H, J ϭ
Ethyl acetate was added to the yellow aqueous phase and the solu-
tion concentrated under reduced pressure at 40–45 °C. The colored
residue was dried under reduced pressure and chromatographed on
a silica gel column [eluent: dichloromethane/methanol (4:1 then 3:2
v/v), TLC: Rf (6) ϭ 0–0.30 in 3:2 v/v]. Compound 6 was obtained
4.9 Hz, OH, sugar), 4.86 (s, 2 H, OH), 4.53 (t, 2 H, J ϭ 5.9 Hz,
OH, sugar), 4.17 (d, 2 H, J ϭ 7.9 Hz, H1), 4.03 (t, 4 H, J ϭ 6.6 Hz,
CH2OAr), 3.93 (m, 2 H), 3.70 (ddd, 2 H, J ϭ 11.3, 5.9, 1.5 Hz),
3.63 (m, 2 H), 3.47 (m, 2 H), 3.03–3.19 (m, 6 H), 2.98 (m, 2 H),
1.98 (quint, 4 H, J ϭ 6.6 Hz, CH2), 1.43 (s, 6 H, CH3). – meso
1
as a white powder in 55% yield (0.55 g), mp 130–135 °C. MS (ES); diastereoisomer: H NMR (400 MHz, [D6]DMSO): δ ϭ 7.34 (d, 4
C22H31O9Na (462.47): m/z 439.5 ([C22H31O9]1–), 879.4 (dimer). –
H, J ϭ 8.9 Hz, aromatic), 6.81 (d, 4 H, J ϭ 8.9 Hz, aromatic), 5.06
(d, 2 H, J ϭ 4.9 Hz, OH, sugar), 4.98 (d, 2 H, J ϭ 4.4 Hz, OH,
[α]2D0 ϭ –26.3 (c ϭ 1.028; CH3OH). – 1H NMR (400 MHz,
CD3OD): δ ϭ 7.92 (d, 2 H, aromatic), 6.95 (d, 2 H, aromatic), 4.87 sugar), 4.95 (d, 2 H, J ϭ 4.9 Hz, OH, sugar), 4.75 (s, 2 H, OH),
(s, 1 H, H1), 4.57 (dd, 1 H, J ϭ 5.8, 3.1 Hz, H4), 4.40 (d, 1 H, J ϭ 4.53 (t, 2 H, J ϭ 5.9 Hz, OH, sugar), 4.17 (d, 2 H, J ϭ 7.9 Hz,
3.1 Hz, H5), 4.21 (d, 1 H, J ϭ 3.7 Hz, H3), 4.12 (s, 1 H, H2), 4.03
H1), 4.07 (t, 4 H, J ϭ 6.4 Hz, CH2OAr), 3.93 (m, 2 H), 3.70 (ddd,
(t, 2 H, J ϭ 6.3 Hz, CH2OAr), 3.79 (td, 1 H, OCH2), 3.50 (td, 1 2 H, J ϭ 11.3, 5.9, 1.5 Hz), 3.63 (m, 2 H), 3.47 (m, 2 H), 3.03–3.19
H, OCH2), 2.51 (s, 3 H, CH3), 1.76–1.77 (m, 2 H, CH2), 1.60–1.62 (m, 6 H), 2.98 (m, 2 H), 1.98 (quint, 4 H, J ϭ 6.6 Hz, CH2), 1.27
(m, 1 H, CH2), 1.45–1.47 (m, 1 H, CH2), 1.35 (s, 8 H, CH2). – 13C
NMR (100 MHz, CD3OD): δ ϭ 199.37, 195.00, 164.90, 131.81,
131.38, 115.44, 109.72, 83.19, 82.06, 78.21, 74.45, 70.23, 69.50,
27.03–30.59, 26.28.
(s, 6 H, CH3).
Bis-8-[4-(1-hydroxyethyl)phenoxy]octan-1-ol (10): Chromatography:
eluent; dichloromethane/methanol (32:1 then 9:1 v/v), Rf ϭ 0.65. –
HRMS (FABϩ) calcd. for [C32H50O6Li]ϩ: 537.3767; found
1
Bis-1-[4-(1-hydroxyethyl)phenoxy]hexane (7): Chromatography: elu-
ent; dichloromethane/ethyl acetate (19:1 then 9:1 v/v), Rf ϭ 0.47. –
HRMS (FABϩ) calcd. for [C28H42O4Li]ϩ: 449.3243; found
537.3778. – d,l diastereoisomer: H NMR (400 MHz, [D6]DMSO):
δ ϭ 6.98 (d, 4 H, J ϭ 8.9 Hz, aromatic), 6.67 (d, 4 H, J ϭ 8.9 Hz,
aromatic), 4.84 (s, 2 H, OH), 4.37 (t, 2 H, J ϭ 5.1 Hz, OH), 3.91 (t,
4 H, J ϭ 6.4 Hz, CH2OAr), 3.34–3.46 (m, 4 H, CH2), 1.70 (quint, 4
1
449.3224. – d,l diastereoisomer: H NMR (400 MHz, [D6]DMSO):
δ ϭ 6.97 (d, 4 H, J ϭ 8.9 Hz, aromatic), 6.67 (d, 4 H, J ϭ 8.9 Hz, H, J ϭ 7.0 Hz, CH2), 1.23–1.53 (m, 26 H, CH2 ϩ CH3). – 13C
aromatic), 4.86 (s, 2 H, OH), 3.91 (t, 4 H, J ϭ 6.6 Hz, CH2OAr),
NMR (100 MHz, [D6]DMSO): δ ϭ 156.79, 137.82, 128.41, 112.05,
1.70 (quint, 4 H, J ϭ 7.0 Hz, CH2), 1.39–1.48 (m, 4 H, CH2), 1.43 77.26, 67.17, 60.76, 32.57, 28.98, 28.95, 28.82, 25.60, 25.52, 24.71. –
1
(s, 6 H, CH3), 1.30–1.38 (m, 8 H, CH2), 0.91 (t, 6 H, J ϭ 6.9 Hz, meso diastereoisomer: H NMR (400 MHz, [D6]DMSO): δ ϭ 7.31
CH3). – 13C NMR (100 MHz, CDCl3): δ ϭ 158.10, 135.53, 128.56,
(d, 4 H, J ϭ 8.4 Hz, aromatic), 6.78 (d, 4 H, J ϭ 8.9 Hz, aromatic),
112.98, 78.77, 67.97, 31.66, 29.53, 25.79, 22.66, 24.99, 14.10. – meso 4.73 (s, 2 H, OH), 4.37 (t, 2 H, J ϭ 5.1 Hz, OH), 3.95 (t, 4 H, J ϭ
1
diastereoisomer: H NMR (400 MHz, [D6]DMSO): δ ϭ 7.32 (d, 4
H, J ϭ 8.9 Hz, aromatic), 6.78 (d, 4 H, J ϭ 8.4 Hz, aromatic), 4.75 7.0 Hz, CH2), 1.23–1.53 (m, 26 H, CH2 ϩ CH3). – 13C NMR
(s, 2 H, OH), 3.95 (t, 4 H, J ϭ 6.4 Hz, CH2OAr), 1.70 (quint, 4 H, (100 MHz, [D6]DMSO): δ ϭ 156.79, 138.72, 128.59, 112.26, 76.84,
6.4 Hz, CH2OAr), 3.34–3.46 (m, 4 H, CH2), 1.70 (quint, 4 H, J ϭ
J ϭ 7.0 Hz, CH2), 1.39–1.48 (m, 4 H, CH2), 1.30–1.38 (m, 8 H, 67.17, 60.76, 32.57, 28.98, 28.95, 28.82, 25.60, 25.52, 25.15.
CH2), 1.28 (s, 6 H, CH3), 0.91 (t, 6 H, J ϭ 6.9 Hz, CH3). – 13C
NMR (100 MHz, CDCl3): δ ϭ 158.00, 135.87, 128.12, 113.16,
78.56, 67.97, 31.66, 29.53, 25.79, 22.66, 25.14, 14.10.
Bis-1-O-{8-[4-(1-hydroxyethyl)phenoxy]octyl} β-D-Glucofuranosid-
urono-6,3-lactone (12): Chromatography: eluent; dichloromethane/
methanol (19:1 then 4:1 v/v). – HRMS (FABϩ) calcd. for
[C44H62O16Li]ϩ: 853.4197; found 853.4229. – d,l diastereoisomer:
Bis-1-O-{8-[4-(1-hydroxyethyl)phenoxy]octyl} β-D-Glucopyranoside
(8): Chromatography: eluent; ethyl acetate/methanol (9:1 then 7:3 1H NMR (400 MHz, [D6]DMSO): δ ϭ 6.98 (d, 4 H, J ϭ 8.4 Hz,
v/v), Rf ϭ 0.34. – HRMS (FABϩ) calcd. for [C44H70O16Na]ϩ: aromatic), 6.68 (d, 4 H, J ϭ 8.4 Hz, aromatic), 5.86 (d, 2 H, J ϭ
877.4561; found 877.4575.
–
d,l diastereoisomer: 1H NMR
5.4 Hz, OH, sugar), 5.72 (s, 2 H, OH, sugar), 4.93 (s, 2 H, H1),
4.85 (s, 2 H, OH), 4.79 (t, 2 H, J ϭ 5.4 Hz, H4), 4.73 (d, 2 H, J ϭ
4.9 Hz, H3), 4.46 (t, 2 H, J ϭ 5.4 Hz, H5), 4.08 (s, 2 H, H2), 3.91
(400 MHz, [D6]DMSO): δ ϭ 6.98 (d, 4 H, J ϭ 7.9 Hz, aromatic),
6.67 (d, 4 H, J ϭ 7.9 Hz, aromatic), 5.00 (d, 2 H, J ϭ 5.4 Hz, OH,
sugar), 4.97 (d, 2 H, J ϭ 5.9 Hz, OH, sugar), 4.93 (d, 2 H, J ϭ (t, 4 H, J ϭ 6.4 Hz, CH2OAr), 3.71 (m, 2 H, OCH2), 3.23 (m, 2
4.4 Hz, OH, sugar), 4.85 (s, 2 H, OH), 4.52 (t, 2 H, J ϭ 5.9 Hz, H, OCH2), 1.70 (m, 4 H, CH2), 1.55–1.65 (m, 4 H, CH2), 1.20–
1
OH, sugar), 4.13 (d, 2 H, J ϭ 7.4 Hz, H1), 3.91 (t, 4 H, J ϭ 6.4 Hz,
1.50 (m, 22 H, CH2 ϩ CH3). – meso diastereoisomer: – H NMR
CH2OAr), 3.79 (m, 2 H), 3.69 (ddd, 2 H, J ϭ 11.3, 5.9, 1.5 Hz), (400 MHz, [D6]DMSO): δ ϭ 7.32 (d, 4 H, J ϭ 8.4 Hz, aromatic),
3.49 (m, 4 H), 3.01–3.19 (m, 6 H), 2.96 (m, 2 H), 1.65–1.78 (m, 4 6.78 (d, 4 H, J ϭ 8.9 Hz, aromatic), 5.86 (d, 2 H, J ϭ 5.4 Hz, OH,
H, CH2), 1.50–1.62 (m, 4 H, CH2), 1.21–1.49 (m, 22 H, CH2
ϩ
sugar), 5.72 (s, 2 H, OH, sugar), 4.93 (s, 2 H, H1), 4.79 (t, 2 H, J ϭ
5.4 Hz, H4), 4.73 (s, 2 H, OH), 4.73 (d, 2 H, J ϭ 4.9 Hz, H3), 4.46
CH3). – meso diastereoisomer: 1H NMR (400 MHz, [D6]DMSO):
δ ϭ 7.32 (d, 4 H, J ϭ 8.9 Hz, aromatic), 6.78 (d, 4 H, J ϭ 9.3 Hz, (t, 2 H, J ϭ 5.4 Hz, H5), 4.08 (s, 2 H, H2), 3.95 (t, 4 H, J ϭ 5.9 Hz,
aromatic), 5.00 (d, 2 H, J ϭ 5.4 Hz, OH, sugar), 4.97 (d, 2 H, J ϭ CH2OAr), 3.71 (m, 2 H, OCH2), 3.23 (m, 2 H, OCH2), 1.70 (m,
5.9 Hz, OH, sugar), 4.93 (d, 2 H, J ϭ 4.4 Hz, OH, sugar), 4.74 (s,
2 H, OH), 4.52 (t, 2 H, J ϭ 5.9 Hz, OH, sugar), 4.13 (d, 2 H, J ϭ
7.4 Hz, H1), 3.94 (t, 4 H, J ϭ 6.6 Hz, CH2OAr), 3.79 (m, 2 H),
3.69 (ddd, 2 H, J ϭ 11.3, 5.9, 1.5 Hz), 3.49 (m, 4 H), 3.01–3.19 (m,
6 H), 2.96 (m, 2 H), 1.65–1.78 (m, 4 H, CH2), 1.50–1.62 (m, 4 H,
CH2), 1.21–1.49 (m, 22 H, CH2 ϩ CH3).
4 H, CH2), 1.55–1.65 (m, 4 H, CH2), 1.20–1.50 (m, 22 H, CH2
ϩ CH3).
2-Hydroxy-2-(4-hexyloxyphenyl)-3-trideuteriomethoxy-3-(4’-
hexyloxyphenyl)butane (13) and 2,3-Ditrideuteriomethoxy-2,3-bis(4-
hexyloxyphenyl)butane (14): Dry tetrahydrofuran (15 mL) was
placed in a dry, deaerated round-bottomed flask (equipped with a
reflux condenser and a magnetic stirring bar). After deoxygenation
with argon the THF was heated to 38 °C with stirring. Sodium
Bis-1-O-{3-[4-(1-hydroxyethyl)phenoxy]propyl} β-D-Glucopyranoside
(9): Chromatography: eluent; dichloromethane/methanol (9:1 then
3:2 v/v), Rf ϭ 0.22. – HRMS (FABϩ) calcd. for [C34H50O16Li]ϩ: hydride (15.5 mg of 60% dispersion in oil, 0.39 mmol, 3.25 equiv.),
721.3258; found 721.3288.
–
d,l diastereoisomer: 1H NMR
methyl iodide-d3 (105 µL, 1.68 mmol, 14 equiv.) and then a solution
Eur. J. Org. Chem. 2000, 813Ϫ821
819

C. Maurice, B. Schöllhorn, I. Canet, G. Mousset, C. Mousty, J. Guilbot, D. Plusquellec
FULL PAPER
of pinacol 7 (54 mg, 0.12 mmol, 1 equiv.) in dry tetrahydrofuran
(1 mL) was added. After 2 h heating, sodium hydride (15.5 mg,
0.39 mmol, 3.25 equiv.) and methyl iodide-d3 (105 µL, 1.68 mmol,
14 equiv.) were added and then every hour (two or three times)
methyl iodide-d3 (105 µL). The successive formation of two prod-
ucts [TLC: eluent; cyclohexane/ethyl acetate (9:1 v/v); Rf ϭ 0.51
(first observed) and 0.75] was observed. After 6 h heating, the reac-
tion mixture was cooled and methanol was added dropwise until
the evolution of hydrogen had ceased. The solvents were evapor-
ated under reduced pressure and the residue treated with diethyl
ether (10 mL). Insoluble compounds were filtered off and the or-
ganic solution was extracted with 5 mL of a 0.1  aqueous solution
of NH4Cl, washed with water (2 ϫ 2 mL), dried over MgSO4, fil-
7.9 Hz, Ar-benzoyl), 7.46–7.73 (m, 20 H, Ar-benzoyl), 7.39–7.45
(m, 4 H, Ar-benzoyl), 6.98 (d, 4 H, J ϭ 8.4 Hz, aromatic), 6.65 (d,
4 H, J ϭ 8.9 Hz, aromatic), 6.02 (t, 2 H, J ϭ 9.6 Hz), 5.64 (t, 2 H,
J ϭ 9.3 Hz), 5.39 (t, 2 H, J ϭ 8.9 Hz), 5.20 (dd, 2 H, J ϭ 7.9,
2.5 Hz), 4.86 (s, 2 H, OH), 4.48–4.59 (m, 6 H), 3.82 (m, 6 H), 3.57
(m, 2 H), 1.55 (m, 4 H, CH2), 1.40–1.50 (m, 10 H), 0.92–1.32 (m,
1
16 H). – meso diastereoisomer: H NMR (400 MHz, [D6]DMSO):
δ ϭ 8.01 (d, 4 H, J ϭ 7.9 Hz, Ar-benzoyl), 7.89–7.94 (m, 4 H, Ar-
benzoyl), 7.86 (d, 4 H, J ϭ 7.4 Hz, Ar-benzoyl), 7.75 (d, 4 H, J ϭ
7.9 Hz, Ar-benzoyl), 7.46–7.73 (m, 20 H, Ar-benzoyl), 7.39–7.45
(m, 4 H, Ar-benzoyl), 7.31 (d, 4 H, J ϭ 8.9 Hz, aromatic), 6.77 (d,
4 H, J ϭ 8.9 Hz, aromatic), 6.02 (t, 2 H, J ϭ 9.6 Hz), 5.64 (t, 2 H,
J ϭ 9.3 Hz), 5.39 (t, 2 H, J ϭ 8.9 Hz), 5.20 (dd, 2 H, J ϭ 7.9,
tered then concentrated under reduced pressure. The yellow oil was 2.5 Hz), 4.76 (s, 2 H, OH), 4.48–4.59 (m, 6 H), 3.82 (m, 6 H), 3.57
purified by chromatography on a silica gel column [eluent; cyclo-
hexane/ethyl acetate (19:1 v/v)]. Compounds 13 [TLC: eluent;
cyclohexane/ethyl acetate (9:1 v/v); Rf ϭ 0.51] and 14 [TLC: Rf ϭ
0.75] were obtained as beige soaps in 42 and 53% yield, respectively
(23 and 30 mg).
(m, 2 H), 1.55 (m, 4 H, CH2), 1.40–1.50 (m, 10 H), 0.92–1.32 (m,
16 H).
Bis-1-O-{8-[4-(1-hydroxyethyl)phenoxy]octyl}-2,3,4,6-tetra-O-benzyl
β-D-Glucopyranoside (16): Sodium hydride (68.1 mg of 60% disper-
sion in oil, 1.70 mmol, 16 equiv.) was introduced into a dry, deaer-
ated round-bottomed flask (equipped with a magnetic stirring bar).
After washing the dispersion with dry cyclohexane, DMF (5 mL)
was added followed by a solution of pinacol 8 (97 mg, 0.11 mmol,
1 equiv.) in DMF (1 mL). After 30 min stirring at 20 °C, benzyl
bromide (108 µL, 0.91 mmol, 8 equiv.) was introduced. The reac-
tion was monitored by TLC [eluent; cyclohexane/ethyl acetate (7:3
v/v)]. Methanol was added dropwise when the reaction product
(Rf ϭ 0.40) was detected as the major component. The solution
was concentrated and the DMF was distilled off under reduced
pressure. The residue was dissolved in 10 mL of a diethyl ether/
water mixture (1:1 v/v). The aqueous phase was separated and ex-
tracted with ether. The combined organic phases were washed with
water, dried over MgSO4, filtered and concentrated under reduced
pressure. The residue was purified by chromatography on a silica
gel column [eluent; cyclohexane/ethyl acetate (4:1 v/v)]. Compound
16 [TLC: eluent; cyclohexane/ethyl acetate (7:3 v/v); Rf ϭ 0.40] was
obtained as a thick colorless oil in 30% yield (53 mg). – HRMS
(FABϩ) calcd. for [C100H118O16Li]ϩ: 1581.8579; found
1581.8694. – d,l diastereoisomer: 1H NMR (400 MHz, [D6]DMSO):
δ ϭ 7.26–7.41 (m, 36 H, Ar-benzyl), 7.18–7.23 (m, 4 H, Ar-benzyl),
6.97 (d, 4 H, J ϭ 8.4 Hz, aromatic), 6.65 (d, 4 H, J ϭ 8.8 Hz,
aromatic), 4.86–4.92 (m, 2 H, CH2-benzyl), 4.81–4.86 (m, 4 H,
CH2-benzyl ϩ OH), 4.72–4.78 (m, 4 H, CH2-benzyl), 4.66–4.71 (m,
2 H, CH2-benzyl), 4.48–4.60 (m, 8 H, CH2-benzyl ϩ H1), 3.80–
3.93 (m, 6 H), 3.60–3.74 (m, 6 H), 3.43–3.59 (m, 6 H), 3.29 (t, 2
H, J ϭ 8.4 Hz), 1.66 (m, 4 H, CH2), 1.59 (m, 4 H, CH2), 1.23–1.46
(m, 22 H, CH2 ϩ CH3). – meso diastereoisomer: 1H NMR
(400 MHz, [D6]DMSO): δ ϭ 7.26–7.41 (m, 40 H, Ar-benzyl ϩ aro-
matic), 7.18–7.23 (m, 4 H, Ar-benzyl), 6.75 (d, 4 H, J ϭ 8.9 Hz,
aromatic), 4.86–4.92 (m, 2 H, CH2-benzyl), 4.81–4.86 (m, 2 H,
CH2-benzyl), 4.72–4.78 (m, 6 H, CH2-benzyl ϩ OH), 4.66–4.71 (m,
2 H, CH2-benzyl), 4.48–4.60 (m, 8 H, CH2-benzyl ϩ H1), 3.80–
3.93 (m, 6 H), 3.60–3.74 (m, 6 H), 3.43–3.59 (m, 6 H), 3.29 (t, 2
H, J ϭ 8.4 Hz), 1.66 (m, 4 H, CH2), 1.59 (m, 4 H, CH2), 1.23–1.46
(m, 22 H, CH2 ϩ CH3).
13: HRMS (FABϩ) calcd. for [C29H41O4LiD3]ϩ: 466.3587; found
1
466.3573. – d,l diastereoisomer: H NMR (400 MHz, CDCl3): δ ϭ
6.90–7.01 (m, 4 H, aromatic), 6.78 (d, 2 H, J ϭ 8.9 Hz, aromatic),
6.72 (d, 2 H, J ϭ 8.9 Hz, aromatic), 3.90–3.99 (m, 4 H, CH2OAr),
1.72–1.84 (m, 4 H, CH2), 1.40–1.55 (m, 7 H, CH2 ϩ CH3), 1.30–
1.40 (m, 11 H, CH2 ϩ CH3), 0.92 (m, 6 H, CH3). – meso diastereo-
isomer: 1H NMR (400 MHz, CDCl3): δ ϭ 7.07 (d, 4 H, J ϭ 8.4 Hz,
aromatic), 6.76 (d, 2 H, J ϭ 8.4 Hz, aromatic), 6.70 (d, 2 H, J ϭ
8.4 Hz, aromatic), 3.90–3.99 (m, 4 H, CH2OAr), 1.72–1.84 (m, 4
H, CH2), 1.40–1.55 (m, 7 H, CH2 ϩ CH3), 1.30–1.40 (m, 11 H,
CH2 ϩ CH3), 0.92 (m, 6 H, CH3).
14: HRMS (FABϩ) calcd. for [C30H40O4LiD6]ϩ: 483.3932; found
1
483.3965. – d,l diastereoisomer: H NMR (400 MHz, CDCl3): δ ϭ
6.70–6.85 (m, 4 H, aromatic), 6.65 (d, 4 H, J ϭ 8.9 Hz, aromatic),
3.92 (t, 4 H, J ϭ 6.4 Hz, CH2OAr), 1.77 (m, 4 H, CH2), 1.58 (s, 6
H, CH3), 1.40–1.55 (m, 4 H, CH2), 1.30–1.40 (m, 8 H, CH2), 0.91
(t, 6 H, J ϭ 7.7 Hz, CH3).
Bis-1-O-{8-[4-(1-hydroxyethyl)phenoxy]octyl}-2,3,4,6-tetra-O-
benzoyl β-D-Glucopyranoside (15): Dry dichloromethane (5 mL)
and anhydrous pyridine (58 µL) (0.72 mmol, 8.8 equiv.) were intro-
duced into a dry, deaerated round-bottomed flask. The reaction
mixture was cooled to 5 °C. Benzoyl chloride (76 µL, 0.66 mmol,
8 equiv.) and pinacol 8 (70 mg, 0.082 mmol, 1 equiv.) were added
successively with stirring. The temperature was maintained at
around 5–10 °C and the reaction monitored by thin layer chroma-
tography [eluent; cyclohexane/ethyl acetate (3:2 v/v)]. Every 30 min
(five times) was added benzoyl chloride (19 µL, 0.16 mmol, 2
equiv.) and pyridine (15 µL, 0.18 mmol, 2.2 equiv.) and the reaction
mixture was then stirred for 12 h at room temperature. A major
component, characterized by Rf ϭ 0.45, was observed by TLC. The
organic phase was diluted with dichloromethane (10 mL), washed
with a 0.015  aqueous solution of H2SO4, water, a saturated aque-
ous solution of sodium hydrogencarbonate, and then water. The
organic phase was dried over MgSO4, filtered and then concen-
trated under reduced pressure. The crude product was purified by
chromatography on a silica gel column [eluent; dichloromethane
followed by dichloromethane/ethyl acetate (9:1 v/v)]. Product 15
[TLC: eluent; cyclohexane/ethyl acetate (3:2 v/v); Rf (15) ϭ 0.45]
was obtained as a sticky beige powder in 50% yield (70 mg). –
2-Hydroxy-2-[4-(1,8-octyldioxy)phenyl-1-O-2,3,4,6-tetra-O-benzyl-
β-
phenyl-1-O-2,3,4,6-tetra-O-benzyl-β-
Dry tetrahydrofuran (3 mL) was placed in a dry, deaerated round-
D
-glucopyranosyl]-3-trideuteriomethoxy-3-[4-(1,8-octyldioxy)-
D-glucopyranosyl]butane (17):
HRMS (FABϩ) calcd. for [C100H102O24Li]ϩ: 1693.6921; found bottomed flask (equipped with a reflux condenser and a magnetic
1693.7036. – d,l diastereoisomer: 1H NMR (400 MHz, [D6]DMSO): stirring bar). After deoxygenation with argon the THF was heated
δ ϭ 8.01 (d, 4 H, J ϭ 7.9 Hz, Ar-benzoyl), 7.89–7.94 (m, 4 H, Ar-
benzoyl), 7.86 (d, 4 H, J ϭ 7.4 Hz, Ar-benzoyl), 7.75 (d, 4 H, J ϭ
to 38 °C with stirring. Sodium hydride (1.2 mg of 60% dispersion
in oil, 0.03 mmol, 3 equiv.), methyl iodide-d3 (10 µL, 0.16 mmol,
820
Eur. J. Org. Chem. 2000, 813Ϫ821

Stereoselective Pinacolization and an Example of a Glycosidic Carbon-Oxygen Bond Cleavage
FULL PAPER
16 equiv.) and a solution of pinacol 16 (16 mg, 0.01 mmol, 1 equiv.)
in dry tetrahydrofuran (1 mL) were added. After 1, 2 and 3 h heat-
ing, sodium hydride (1.2 mg, 0.03 mmol, 3 equiv.) and methyl iod-
ide-d3 (10 µL, 0.16 mmol, 16 equiv.) were added followed by methyl
iodide-d3 (15 µL) every hour until compound 17 was the major
component [TLC: eluent; cyclohexane/ethyl acetate (4:1 v/v); Rf ϭ
0.37]. The reaction mixture was cooled and methanol was added
dropwise until hydrogen the evolution had ceased. The solvents
were evaporated under reduced pressure and the residue dissolved
in 10 mL of a mixture of diethyl ether/water (1:1 v/v). The aqueous
phase was separated and extracted with diethyl ether. The com-
bined organic phases were washed with water, dried over MgSO4,
filtered and concentrated under reduced pressure. The residue was
purified by chromatography on a silica gel column [eluent; cyclo-
hexane/ethyl acetate (4:1 v/v)]. Compound 17 was obtained as a
thick colorless oil in 65% yield (11 mg). – HRMS (FABϩ) calcd.
C. Mousty and C. Maurice are grateful to the ANVAR Auvergne
for financial support for this work (Convention n° J96070012C/JJ)
2
and to A. Meddour for performing some of the H-NMR spectro-
scopy.
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[9]
C. Maurice, C. Mousty, B. Schöllhorn, B. Aboab, G. Mousset,
for [C101H117O16LiD3]ϩ: 1598.8924; found 1598.8970.
– d,l
New J. Chem. 1998, 1469–1477.
[10]
diastereoisomer: 1H NMR (400 MHz, CDCl3): δ ϭ 7.23–7.40 (m,
36 H, Ar-benzyl), 7.14–7.19 (m, 4 H, Ar-benzyl), 6.91–7.02 (m, 4
H, aromatic), 6.77 (d, 2 H, J ϭ 9.4 Hz, aromatic), 6.71 (d, 2 H,
J ϭ 9.4 Hz, aromatic), 4.96 (d, 2 H, J ϭ 11.8 Hz, CH2-benzyl),
4.94 (d, 2 H, J ϭ 10.8 Hz, CH2-benzyl), 4.82 (d, 2 H, J ϭ 10.8 Hz,
CH2-benzyl), 4.79 (d, 2 H, J ϭ 10.8 Hz, CH2-benzyl), 4.73 (d, 2 H,
J ϭ 11.3 Hz, CH2-benzyl), 4.63 (d, 2 H, J ϭ 12.3 Hz, CH2-benzyl),
4.56 (d, 2 H, J ϭ 12.3 Hz, CH2-benzyl), 4.53 (d, 2 H, J ϭ 10.8 Hz,
CH2-benzyl), 4.40 (d, 2 H, J ϭ 7.9 Hz, H1), 3.86–4.02 (m, 6 H),
3.75 (dd, 2 H, J ϭ 10.6, 1.7 Hz), 3.50–3.71 (m, 6 H), 3.54 (m, 2
H), 3.42–3.50 (m, 4 H), 1.62–1.82 (m, 8 H, CH2), 1.31–1.50 (m,
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8.9 Hz, aromatic), 6.70 (d, 2 H, J ϭ 8.9 Hz, aromatic), 4.96 (d, 2
H, J ϭ 11.8 Hz, CH2-benzyl), 4.94 (d, 2 H, J ϭ 10.8 Hz, CH2-
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3.50–3.71 (m, 6 H), 3.54 (m, 2 H), 3.42–3.50 (m, 4 H), 1.62–1.82
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Received June 25, 1999
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Acknowledgments
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821