TEMPO-mediated anodic oxidation of methyl glycosides and 1-methyl and 1-azido disaccharides

Article abstract of DOI:10.1002/ejoc.200390041

Methyl glycosides of L-sorbopyranoside, D-fructopyranoside, D-glucosaminopyranoside, 2,3-dehydro-2,3-dideoxyglucopyranoside, cellobiose, lactose, and maltose and the 1-azido derivatives of glucose, cellobiose, lactose, and maltose have been converted into the corresponding uronic acids in moderate to excellent yields by TEMPO-mediated anodic oxidation. The anode proves to be an advantageous alternative to other cooxidants in TEMPO⁺ oxidations of carbohydrates and is compatible with N-acylamino and azido groups and with double bonds. The electrolyte, a carbonate buffer, can easily be removed with a cation-exchange resin, a facile scale-up by increasing the electrode area is possible. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200390041

FULL PAPER
TEMPO-Mediated Anodic Oxidation of Methyl Glycosides and 1-Methyl and
1-Azido Disaccharides
Matthias Schämann[a] and Hans J. Schäfer*[a]
Keywords: Azides / Carbohydrates / Glycosides / Oxidation / TEMPO / Uronic acids
Methyl glycosides of
L-sorbopyranoside,
D-fructopyranoside,
other cooxidants in TEMPO+ oxidations of carbohydrates and
D-glucosaminopyranoside, 2,3-dehydro-2,3-dideoxyglucopy- is compatible with N-acylamino and azido groups and with
ranoside, cellobiose, lactose, and maltose and the 1-azido de-
rivatives of glucose, cellobiose, lactose, and maltose have
double bonds. The electrolyte, a carbonate buffer, can easily
be removed with a cation-exchange resin, a facile scale-up
been converted into the corresponding uronic acids in mod- by increasing the electrode area is possible.
erate to excellent yields by TEMPO-mediated anodic oxida-
tion. The anode proves to be an advantageous alternative to
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
Results and Discussion
We have recently shown that the primary hydroxy groups
in the monosaccharides 1Ϫ8 can be oxidized selectively at
the anode with TEMPO as mediator to afford the corres-
ponding uronic acids in yields between 45 and 98%.[31] To
proceed in exploration of the scope of this TEMPO-medi-
ated oxidation the methyl glycosides 9؊15 were prepared
and oxidized.
The selective oxidation of carbohydrates has been intens-
ively studied over recent decades and continues to be an
area of current interest.[1Ϫ5] For oxidation to uronic acids,
stoichiometrically employed reagents such as nitric acid[6]
and nitrogen dioxide[6,7] have been developed, as well as
catalytic methods: oxygen with noble metal catalysts[3,5,8,9]
or stable organic nitroxyl radicals with cooxidants.[10Ϫ30]
The sterically shielded nitrosonium ion, generated from the
nitroxyl radical by one-electron oxidation, selectively con-
verts primary hydroxy groups in the presence of secondary
ones. Preparative oxidations of carbohydrates to uronic ac-
ids are usually performed at room temperature, with so-
dium hypochlorite as oxidant and TEMPO (2,2,6,6-tetra-
methylpiperidin-1-oxyl) or its derivatives and sodium brom-
ide as a double mediatory system. Under these conditions,
hypochlorite or the intermediate bromine can cause side re-
actions with sensitive functional groups. Furthermore, the
separation of the polar uronic acids from aqueous solutions
of sodium halides is frequently difficult.
Preparation of Methyl Glycosides
Methyl α--glucopyranoside (9) was obtained from -glu-
cose in 34% yield by heating the carbohydrate at reflux in
methanol with a Dowex cation-exchange resin as cata-
1
lyst.[33] In the H NMR spectrum the coupling constant of
3J1,2 ϭ 3.6 Hz supports the assigned α configuration. The
only -sugar available in reasonable amounts is -sorbose,
because it is an intermediate in the technical production of
vitamin C.[9,34] When a solution of -sorbose was stirred in
methanol with 0.1% 2  hydrochloric acid at room temper-
ature for 24 h, only 11% of methyl α--sorbopyranoside (10)
was obtained, together with 37% of α- and β--sorbofur-
anoside. After an increase in the added 2  hydrochloric
acid to 1% and 4 d of stirring, 10 was obtained in 76%
yield.[35] -Fructose was also stirred for 4 d in methanol
with 0.1% concd. hydrochloric acid. Besides two methyl fur-
anosides, the target methyl β--fructopyranoside (11) was
obtained in 48% yield after isolation by flash chromato-
graphy.[35] -Glucosamine was converted into the pentaa-
cetate in 66% yield with pyridine/acetic anhydride, and this
was subsequently converted into a mixture of α- and β-
The use of anodic oxidation is an advantageous alternat-
ive. The electrode does not interfere with the alcohol oxida-
tion and the electrolysis system is easy to work up and to
scale up. First examples of selective anodic oxidations on
preparative scale with TEMPO as mediator have been re-
ported recently.[31,32]
[a]
Institute of Organic Chemistry, Westfälische Wilhelms-
Universität, Münster
Corrensstraße 40, 48149 Münster, Germany
Fax: (internat.) ϩ 49-(0)251/83-36523
E-mail: schafeh@uni-muenster.de
Eur. J. Org. Chem. 2003, 351Ϫ358  2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0102Ϫ0351 $ 20.00ϩ.50/0
351

M. Schämann, H. J. Schäfer
FULL PAPER
In these cases, interference with the oxidation at the an-
omeric center was precluded by acetal formation. With re-
ducing disaccharides, such an oxidation has to be prevented
by conversion of these carbohydrates into their 1-methoxy
or 1-azido derivatives. For that purpose the corresponding
methyl glycosides of cellobiose (19), lactose (20), and malt-
ose (21) were prepared.
methyl glycosides (α/β ϭ 1:1.4) by acid catalysis in meth-
anol and deacylated with sodium methoxide to provide
methyl N-acetylglucosaminopyranoside (12) in 76% yield
after purification by flash chromatography.[36,37] -Glucose
was converted into the triacetylglucal 13a in 98% yield in a
one-pot reaction via the 1-bromotetraacetate and reductive
elimination with zinc.[38] The glucal was then deacylated
with sodium methoxide in 96% yield to afford the glucal
13b. When the same reaction conditions were applied to
galactose, the triacetylgalactal 14a was obtained in a lower
yield of 53% yield[38] and deacylated to give 14b in 98%
yield. With boron trifluoride؊diethyl ether in benzene/
methanol, 13a was transformed Ϫ by SN2Ј substitution of
the 3-acetoxy group by the methoxy group Ϫ into 15a in
90% yield.[39] This was subsequently deacylated with so-
dium methoxide to afford 96% of 15b.
The synthesis of the methyl glycosides 19Ϫ21 involved
a four-step sequence:[40Ϫ42] conversion into the octaacetate
(90Ϫ98% yield), exchange of 1-acetoxy for bromide
(82Ϫ89% yield), substitution of bromide for methoxy
(50Ϫ98% yield), and deacylation to afford 19Ϫ21 (92Ϫ98%
yield). In this way, 19, 20, and 21 were obtained in 78, 63,
and 39% overall yields, respectively.
Glycosyl azides are used in carbohydrate chemistry as an
entry to N-glycosides.[43,44] TEMPO oxidations with so-
dium hypochlorite as cooxidant have been described for a
number of azido monosaccharides, affording the corres-
ponding uronic acids in good yields.[13,45] The oxidation of
azido disaccharides, however, has not yet been reported.
The same is true for the TEMPO-catalyzed anodic oxida-
tion of 1-azido carbohydrates.
Preparation of Glycosyl Azides
Preparation of Methyl Glycosides of
Disaccharides
The azides 22Ϫ24 were prepared from cellobiose, lactose,
and maltose by treatment of the corresponding per-O-
acetylated bromides with sodium azide to afford the per-O-
The nonreducing disaccharides trehalose (16), sucrose acetylated β-1-azido carbohydrates (49Ϫ95%). These were
(17), and β-cyclodextrin (18) have been oxidized at C-6 to subsequently deacetoxylated with sodium methoxide in
give the corresponding dicarboxylic acids.[31]
methanol (87Ϫ99%).[46] In this way the 1-azido disacchar-
352
Eur. J. Org. Chem. 2003, 351Ϫ358

TEMPO-Mediated Anodic Oxidation of Glycosides and Disaccharide Derivatives
FULL PAPER
ides 22Ϫ24 were obtained in 63, 40 and 37% overall lutions to pH ϭ 4Ϫ5 and treatment with diazomethane
yields, respectively.
yielded only about 25% of 29. With freshly prepared 2,2-
dimethoxypropane and a drop of concd. hydrochloric acid,
however, the ester 29 could be isolated in 80% yield. The
oxidation of α-methyl N-acetylglucosaminopyranoside with
oxygen and platinum oxide has been reported to proceed in
89% yield.[47]
Anodic Oxidation of Mono- and Disaccharides
with TEMPO (25) as Mediator and the Anode
as Cooxidant
Conversion of 15b and acidification of the produced so-
dium carboxylate yielded a uronic acid that underwent fast
elimination to 31. To suppress this unwanted reaction, the
labile uronic acid had to be rapidly converted into the ester.
For that purpose the salt solution was concentrated to dry-
ness, the residue was redissolved in methanol/water (2:1),
and the solution was then treated with small portions of a
cation-exchange resin and diazomethane. After removal of
the resin and flash chromatography, 23% of 30 and 15%
of 31 were isolated. Compound 30 is still very labile and
decomposes into 31 within 3 d at room temperature. Oxida-
tion of the glucals 13b and 14b under the same conditions
afforded mixtures of many compounds in low yield. As the
selectivity could not be improved, these products were not
characterized.
The carbohydrates were oxidized at a controlled potential
of 0.53 V (versus Ag/AgCl electrode) in an undivided cell
with a graphite anode and a platinum cathode, in the pres-
ence of 0.20Ϫ0.25 equiv. of TEMPO. For isolation and
characterization, the uronic acids were converted into their
corresponding methyl esters [Equation (1), Table 1].
Table 1. TEMPO-mediated anodic oxidation of methyl glycosides
9Ϫ12 and 15b to the corresponding uronic acids
Table 2. TEMPO-mediated anodic oxidation of 1-methoxy disacch-
arides 19Ϫ21 and 1-azido disaccharides 22Ϫ24 to the correspond-
ing dicarboxylic acids
[a]
Conditions as described in the Exp. Sect.
From 9 and 10, the methyl esters of the uronic acids were
obtained in good yields. The yield in the case of the conver-
sion of 11 into 28 was only moderate, possibly due to the
presence of the secondary axial 4-OH group, which is more
sensitive to oxidation than the secondary equatorial hy-
droxy groups. The formed hydroxy ketone can subsequently
undergo a retro-aldol cleavage in the alkaline medium.[8] In
the oxidation of 12 to 29, the yield of the uronic acid in
the crude product was high according to HPLC analysis.
However, isolation proved to be difficult. Methylation of
the carboxylate with dimethyl sulfate or acidification of so-
[a]
Conditions as described in the Exp. Sect.
Eur. J. Org. Chem. 2003, 351Ϫ358
353

M. Schämann, H. J. Schäfer
FULL PAPER
TEMPO-mediated anodic oxidation of the disaccharides
19Ϫ21 and 22Ϫ24 afforded the corresponding diuronic ac-
ids 32Ϫ37 (Table 2).
Experimental Section
General Remarks: All starting chemicals are commercially available
and were used without further purification. Methanol was dried
and all solvents were distilled before use. Melting points were deter-
mined with a Kofler Micro hot stage and are not corrected. Solu-
tions were concentrated in a rotary evaporator at bath temperatures
Ͻ 50 °C. IR spectra were obtained with a Bruker IFS 28 FT-IR
spectrometer. NMR spectra were recorded with a Bruker AMX
400 spectrometer at 400 MHz (for 1H NMR), at 100 MHz (for 13C
NMR), and with a Varian Unityplus spectrometer, at 600 MHz (for
1H NMR) and 151 MHz (for 13C NMR). D2O, CDCl3, and
CD3OD were used as solvents. Chemical shifts (δ) are given in ppm
With the 1-methoxy disacharides, good yields of the di-
methyl diesters 32Ϫ34 could be obtained. The conversion
of 21 into 34 with oxygen and platinum as catalyst has also
been described, but in only 7% yield.[48] With the corres-
ponding 1-azido derivatives 22Ϫ24 the yields are good, too.
Only in the case of 23, in which the axial secondary 4-OH
group in the galactopyranosyl part of the disaccharide is
more sensitive to oxidation (see the conversion 11 into 27
above), was the yield somewhat lower.
1
and coupling constants (J) are given in Hz. Two-dimensional H-
1H-COSY and C,H-correlation (1JC,H
,
J
C,H
) experiments were
2,3
performed for complete signal assignments wherever necessary. The
measurement of GC/MS spectra was conducted with a Finnigan-
MAT 312 machine (EI, 70 eV) with an HP 5 (25 m, 0.20 mm i.d.,
0.33 µm film) capillary column. ESI mass spectra were recorded
with a Quattro LC-Z micromass quadrupole mass spectrometer.
Gas chromatography was carried out with a HewlettϪPackard HP
6890 Series plus with the HP 5 capillary column (30 m, 0.32 mm
i.d., 0.25 µm film). Optical rotations were recorded at the Na -
line (589 nm, 20 °C, cell length 10 cm). Elemental analyses were
obtained by the analytical laboratory of the Organisch-Chemisches
Institut der Universität Münster. Preparative-scale electrolyses were
carried out in an undivided or in a divided beaker-type cell with
NS 14.5 joint for a reflux condenser and/or a fermentation tube.
The undivided cell had an inner diameter of 4 cm and a capacity
of 100 mL. It was closed with a Teflon stopper (NS 45), which had
three bore holes: two for the current feeders and one for the Luggin
capillary, which was connected with the reference electrode and the
tip of which was positioned close to the anode. The area of the
graphite anode was 8 cm2 (electrographite, Sigri). A platinum foil
(8 cm2) on a Teflon frame was used as cathode. Both electrodes
were connected to the current source through steel rods. The inner
diameter of the divided beaker type cell was 2.8 cm (capacity 60
mL). The divided cell was closed with a Teflon stopper (NS 45),
which had three bore holes for the anodic current feeder, the Lug-
gin capillary, and the cathode chamber. The cathode chamber had
an inner diameter of 1.5 cm and was separated from the anode
chamber by a glass frit (D3). Within the cathode chamber a plat-
inum foil cathode (1 cm2) was fixed next to the glass frit. The tip
of the Luggin capillary was placed between the glass frit and the
graphite anode (4 cm2, electrographite, Sigri). In both cases the
reference electrode was Ag/AgCl/3  KCl in water (ϩ0.21 V vs.
NHE). The current source was a Wenking ST 88.
In addition, β--glucopyranosyl azide (38), prepared
analogously to 22Ϫ24 in 59% overall yield,[46] was an-
odically oxidized with TEMPO as mediator to the corres-
ponding uronic acid, isolated as the methyl ester 39 in 82%
yield. This is superior to the 74% yield obtained with
TEMPO and sodium hypochlorite as cooxidant.[13]
Conclusion
In the previous paper,[31] TEMPO-mediated anodic ox-
idations of alkyl glucopyranosides, methyl galactopyranos-
ides, and methyl mannopyranosides Ϫ together with those
of the non-reducing di-, oligo- and polysaccharides tre-
halose, sucrose, β-cyclodextrin, and starch Ϫ were reported.
In this contribution the scope of application has been ex-
tended and the use of indirect anodic oxidation of carbo-
hydrates with TEMPO as mediator consolidated.
The range of convertible carbohydrates has been ex-
panded to methyl glycosides of ketohexoses with oxidation
at the 1-OH group and to a glucosaminopyranoside, dem-
onstrating the compatibility of the amino group with the
anodic reaction conditions. Unsaturated carbohydrates Ϫ
with the exception of enol ethers Ϫ can be converted too,
but acidic media have to be avoided during workup to pre-
vent elimination reactions resulting in dienes.
Electrochemical Oxidation of Methyl Glycosides (General Procedure
A): The stated amounts of glycoside (0.025 to 0.050 mol/L) and
2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO, 25, 0.005Ϫ0.010
mol/L, for details see individual procedures) were dissolved in car-
Methyl glycosides and glycosyl azides of reducing disac-
charides can be selectively oxidized at the primary hydroxy
groups to provide the corresponding diuronic acids in good bonate-buffered water (42.80 g/L, 0.40 mol/L Na2CO3, 24.80 g/L,
0.30 mol/L NaHCO3). The solution was electrolyzed at a potential
of 0.53 V versus Ag/AgCl electrode (corresponding to 0.56 V versus
SCE) in an undivided cell at 20 °C. After the electrolysis, a suffi-
cient amount of acidic cation-exchange resin (80 mL, Amberlite IR
120) was added. After the mixture had been stirred for 0.5 h, the
resin was filtered off and the solvent was removed at 50 °C in va-
cuo. For the isolation and characterization of the reaction products,
the uronic acids were usually converted into their corresponding
methyl esters as follows. A proportion of the crude product was
dissolved in methanol (10 mL) and treated with 2,2-dimethoxypro-
pane (1.0 mL, 8.20 mmol) and one drop of concd. aq. hydrochloric
yield. The azido group also proved to be compatible with
the anode.
With regard to the reagent, anodic oxidation has proven
to be an interesting alternative to chemical cooxidants in
conversions with TEMPOϩ. The sodium carbonate used
both as buffer and electrolyte can easily be removed by
treatment with a cation-exchange resin. The method allows
easy scale-up by increasing the electrode area, and perman-
ent immobilization of TEMPO at the electrode surface may
be achievable.[32]
354
Eur. J. Org. Chem. 2003, 351Ϫ358

TEMPO-Mediated Anodic Oxidation of Glycosides and Disaccharide Derivatives
FULL PAPER
acid (p.a., approximately 0.32 mmol, corresponding to 0.03 mol/L).
After the mixture had been stirred for 1 d, the solvent was removed
under reduced pressure and the crude product was purified by flash
chromatography on silica gel.
133 (18), 89 (12) [OSi(CH3)3ϩ], 73 (100) [Si(CH3)3ϩ]. C8H14O7
(222.19): calcd. C 43.24, H 6.35; found C 42.60, H 6.15. The ana-
lyses were affected by residual methanol that could not be removed
after drying for 2 d at room temperature and 0.1 Torr. The ele-
mental composition is additionally supported by high-resolution
MS (HRMS). HRMS (ESI): calcd. for C8H14O7 ϩ Naϩ 245.0637;
found 245.0669.
Electrochemical Oxidation of Glycosyl Azides (General Procedure
B): The stated amounts of glycosyl azide were electrolyzed and
worked up as described in General Procedure A, with the exception
that a divided cell was used.
Methyl (Methyl β-D-fructopyranoside)uronate (28): Methyl β--
Methyl (Methyl α-L-glucopyranoside)uronate (26): Methyl α--gluc-
fructopyranoside (11, 730 mg, 3.76 mmol) and TEMPO (25,
118 mg, 0.75 mmol) were electrolyzed in carbonate-buffered water
(75 mL) and, after a charge of 2945 C (8.1 F/mol) had been con-
sumed, worked up according to General Procedure A. A propor-
tion (152 mg) of the crude product (771 mg) was esterified. Product
28 (92 mg, 0.41 mmol, corresponding to 2.11 mmol in the crude
product, 56%, current yield 28%) was isolated as a colorless syrup
opyranoside (9, 710 mg, 3.66 mmol) and TEMPO (25, 110 mg,
0.72 mmol) were dissolved in 72 mL of carbonate buffer. The solu-
tion was electrolyzed according to General Procedure A. After con-
sumption of 2120 C (6.0 F/mol), the electrolysis was stopped and
the system was worked up; 790 mg of crude product was obtained,
of which 171 mg was esterified. The methyl ester 26 (151 mg,
0.68 mmol, corresponding to 3.17 mmol in the crude product, 87%,
current yield 58%) was isolated by flash chromatography (ethyl
acetate/methanol, 3:1) as a yellow syrup. [α]2D0 ϭ Ϫ95.0 (c ϭ 1.00,
by flash chromatography (ethyl acetate/methanol, 3:1). [α]2D0
ϭ
Ϫ90.9 (c ϭ 1.00, MeOH). IR (film): ν˜ ϭ 3395 (br. s, OϪH), 1742
1
(s, CϭO) cmϪ1. H NMR (400 MHz, CD3OD): δ ϭ 3.38 (s, 3 H,
H2O). IR (film): ν˜ ϭ 3390 (s, OϪH), 1745 (s, CϭO) cmϪ1
.
1H
ϭ
3
2
OCH3), 3.70 (dd, J5,6b ϭ 1.4, J6a,6b ϭ 12.4 Hz, 1 H, 6b-H), 3.77
(m, 5 H, 5-H, 6a-H, COOCH3), 3.91Ϫ3.94 (m, 2 H, 4-H, 3-H)
ppm. 13C NMR (100 MHz, CD3OD): δ ϭ 51.8 (q, OCH3), 53.1 (q,
COOCH3), 66.5 (t, C-6), 70.7 (d, C-4), 71.3 (d, C-5), 72.1 (d, C-3),
102.3 (s, C-2), 170.0 (s, C-1) ppm. MS (GC/MS coupling,
70 eV, EI, silylation with MSTFA in pyridine): m/z (%) ϭ
379 (12) [Mϩ Ϫ CH3 Ϫ CO2], 319 (2), 305 (8) [Mϩ Ϫ Si(CH3)3 Ϫ
CH3OH Ϫ CO], 289 (20) [Mϩ Ϫ OSi(CH3)3 Ϫ CH3OH Ϫ
CO], 257 (32) [Mϩ Ϫ OSi(CH3)3 Ϫ 2 ϫ CH3OH Ϫ CO],
3
NMR (400 MHz, D2O): δ ϭ 3.37 (s, 3 H, OCH3), 3.49 (d, J4,5
3
3
9.3 Hz, 1 H, 4-H), 3.54 (dd, J1,2 ϭ 3.1, J2,3 ϭ 9.8 Hz, 1 H, 2-H),
3.64 (t, 3J2,3 ϭ 9.1 Hz, 1 H, 3-H), 3.77 (s, 3 H, COOCH3), 4.15 (d,
1 H, 5-H), 4.81 (d, 1 H, 1-H) ppm. 13C NMR (100 MHz, D2O):
δ ϭ 53.6 (q, COOCH3), 56.1 (q, OCH3), 71.2 (d, C-5), 71.3 (d, C-
2), 71.8 (d, C-4), 73.1 (d, C-3), 100.2 (d, C-1), 172.2 (s, C-6) ppm.
MS (GC/MS coupling, 70 eV, EI, silylation with MSTFA in
pyridine): m/z (%) ϭ 423 (5) [Mϩ Ϫ CH3], 391 (8) [Mϩ Ϫ CH3 Ϫ
CH3OH], 333 (10) [Mϩ Ϫ CH3 Ϫ Si(CH3)3OH], 317 (12) [Mϩ
OCH3 OSi(CH3)3
Si(CH3)3OH], 259 (12) [Mϩ
Ϫ
217
(28)
[(CH3)3SiOCHCHCHOSi(CH3)3ϩ],
204
(35)
[(CH3)3SiOCHCHOSi(CH3)3ϩ], 191 (10), 189 (8), 159 (3)
[(CH3)3SiOCHCHCHOCH3ϩ], 147 (30) [(CH3)3SiOSi(CH3)2ϩ],
133 (15), 89 (14) [OSi(CH3)3ϩ], 73 (100) [Si(CH3)3ϩ], 45 (8).
C8H14O7 (222.19): calcd. C 43.24, H 6.35; found C 42.65, H 6.08.
The analyses were affected by residual methanol that could not be
removed after drying for 2 d at room temperature and 0.1 Torr. The
elemental composition is additionally supported by high-resolution
MS (HRMS). HRMS (ESI): calcd. for C8H14O7 ϩ Naϩ 245.0637;
found 245.0621.
Ϫ
Ϫ
Ϫ
Si(CH3)3OH], 217 (100) [(CH3)3SiOCHCHCHOSi(CH3)3ϩ],
204 (90) [(CH3)3SiOCHCHOSi(CH3)3ϩ], 159 (45) [(CH3)3-
SiOCHCHCHOCH3ϩ], 147 (57) [(CH3)3SiOSi(CH3)2ϩ], 73 (92)
[Si(CH3)3ϩ]. C8H14O7 (222.19): calcd. C 43.24, H 6.35; found
C 42.60, H 6.15. The analyses were affected by residual methanol
that could not be removed after drying for 2 d at room temperature
and 0.1 Torr. The elemental composition is additionally supported
by high-resolution MS (HRMS). HRMS (ESI): calcd. for C8H14O7
ϩ Naϩ 245.0637; found 245.0620.
Methyl (Methyl β-L-sorbopyranoside)uronate (27): Methyl β--
Methyl (Methyl N-acetyl-D-glucosaminopyranoside)uronate (29):
sorbopyranoside (10, 730 mg, 3.76 mmol) and TEMPO (25, Methyl
N-acetyl--glucosaminopyranoside
(12, 941 mg,
118 mg, 0.76 mmol) were electrolyzed in 75 mL of buffer according
to General Procedure A. After consumption of 2976 C (8.2 F/mol),
the electrolysis was stopped and the system was worked up to pro-
vide 730 mg of crude product, of which 150 mg was esterified. The
methyl ester 27 (131 mg, 0.57 mmol, corresponding to 2.86 mmol
in the crude product, 76%, current yield 37%) was isolated by flash
4.00 mmol, α/β ϭ 1:1.4 by NMR) was electrolyzed with TEMPO
(156 mg, 1.00 mmol) in 80 mL of carbonate buffer according to
General Procedure A until 3214 C (8.3 F/mol) of charge had been
consumed. A proportion (249 mg) of the crude product (1.11 g)
was esterified. Subsequent isolation of the ester by flash chromato-
graphy (ethyl acetate/methanol, 6:1, stained with 1.0% bromocresol
green in ethanol) afforded the methyl ester 29 (188 mg, 0.71 mmol,
corresponding to 3.80 mmol in the crude product, 80%, current
chromatography (ethyl acetate/methanol, 1:2) as a white solid. [α]
20
ϭ Ϫ25.2 (c ϭ 0.98, MeOH). M.p. 193 °C. IR (film): ν˜ϭ 3387
D
(br. s, OϪH), 1746 (s, CϭO) cmϪ1. 1H NMR (400 MHz, CD3OD): yield 39%) as a colorless syrup. [α]2D0 ϭ ϩ58.0 (c ϭ 1.00, MeOH).
δ ϭ 3.33Ϫ3.35 (m, 1 H, 6b-H), 3.37 (s, 3 H, OCH3), 3.47 (d, 3J3,4 ϭ
IR (film): ν˜ ϭ 3351 (s, br. OϪH), 1785 (s, CϭO), 1742 (s, CϭO)
9.4 Hz, 1 H, 3-H), 3.54Ϫ3.58 (m, 2 H, 4-H, 5-H), 3.72Ϫ3.76 (m, 1 cmϪ1. 1H NMR (400 MHz, CD3OD): δ ϭ 1.96 (s, 3 H, CH3), 3.37
H, 6a-H), 3.79 (s, 3 H, COOCH3) ppm. 13C NMR (100 MHz, (s, 3 H, OCH3), 3.56Ϫ3.65 (m, 2 H, 3-H, 4-H), 3.76 (s, 3 H, CO-
CD3OD): δ ϭ 51.6 (q, OCH3), 53.3 (q, COOCH3), 65.3 (t, C-6),
71.3 (d, C-5), 75.7 (2d, C-3, C-4), 101.9 (s, C-2), 170.1 (s, C-1) 1 H, 5-H), 4.68 (d. 3J1,2 ϭ 3.4 Hz, 1 H, 1-H) ppm. 13C NMR (100-
ppm. MS (GC/MS coupling, 70 eV, EI, silylation with MSTFA in MHz, CD3OD): δ ϭ 22.8 (q, CH3), 53.1 (q, COOCH3), 55.3 (d, C-
pyridine): m/z (%) ϭ 423 (1) [Mϩ Ϫ CH3], 391 (2) [Mϩ Ϫ CH3 Ϫ 2), 56.3 (q, OCH3), 72.7 (d, C-3), 73.2 (d, C-5), 74.0 (d, C-4), 100.7
OCH3), 3.93 (dd, 3J2,3 ϭ 10.0 Hz, 1 H, 2-H), 4.01 (d, 3J4,5 ϭ 9.3 Hz,
CH3OH], 379 (34) [Mϩ Ϫ CH3 Ϫ CO2], 319 (3), 305 (5) [Mϩ
Ϫ
(d, C-1), 172.0 (s, C-6), 174.0 (s, COOCH3) ppm. MS (ESI/MS
Si(CH3)3 Ϫ CH3OH Ϫ CO], 289 (11) [Mϩ Ϫ OSi(CH3)3 Ϫ CH3OH coupling, ESϩ): m/z (%) ϭ 264 (25) [M ϩ Hϩ], 246 (5) [M ϩ Hϩ
Ϫ CO], 257 (14) [Mϩ Ϫ OSi(CH3)3 Ϫ 2 ϫ CH3OH Ϫ CO], 217 Ϫ H2O], 232 (100) [M ϩ Hϩ Ϫ CH3OH], 214 (32) [232 Ϫ H2O],
(20)
[(CH3)3SiOCHCHCHOSi(CH3)3ϩ],
204
(63) 196 (5) [323 Ϫ 2 ϫ H2O], 172 (7) [232 Ϫ CH3OH Ϫ CO], 154 (12)
[(CH3)3SiOCHCHOSi(CH3)3ϩ], 191 (15), 189 (15), 159 (4) [214 Ϫ CH3OH Ϫ CO], 126 (35). C10H17NO7 (263.25): calcd. C
[(CH3)3SiOCHCHCHOCH3ϩ], 147 (35) [(CH3)3SiOSi(CH3)2ϩ], 45.63, H 6.51, N 5.32; found C 45.46, H 6.57, N 5.00.
Eur. J. Org. Chem. 2003, 351Ϫ358
355

M. Schämann, H. J. Schäfer
FULL PAPER
Methyl (Methyl 2,3-dehydro-2,3-dideoxy-α-glucopyranoside)uronate
(30) and (2S)-3-Hydroxy-2-methoxycarbonyl-2H-pyran (31): Methyl
(15) [M ϩ NH4ϩ], 413 (7) [M ϩ NH4 Ϫ NH3], 395 (10) [413 Ϫ
ϩ
H2O], 381 (40) [413 Ϫ CH3OH], 363 (15) [381 Ϫ H2O], 345 (15)
2,3-dehydro-2,3-dideoxy-α-glucopyranoside
(15b,
499 mg, [381 Ϫ 2 ϫ H2O], 223 (65) [H3COOCϪC6H11O5 ϩ Hϩ, β-cleavage],
3.10 mmol) and TEMPO (25, 87 mg, 0.62 mmol) were dissolved in
65 mL of carbonate buffer. The solution was electrolyzed according
to General Procedure A. After consumption of 1836 C (6.1 F/mol),
205 (40) [223 Ϫ H2O], 191 (100) [223 Ϫ CH3OH], 173 (35) [191 Ϫ
H2O], 155 (20) [191 Ϫ 2 ϫ H2O]. C15H24O13 (412.34): calcd. C
43.69, H 5.87; found C 42.66, H 6.10. The analyses were affected
the electrolysis was stopped and the mixture was worked up. For by residual methanol that could not be removed after drying for
half of the electrolyte, the solvent was evaporated under vacuum
and the crude product was dissolved in 45 mL of methanol/water,
2 d at room temperature and 0.1 Torr. The elemental composition
is additionally supported by high-resolution MS (HRMS). HRMS
2:1. Diazomethane in diethyl ether (0.5 , 60 mL) and acidic cat- (ESI): calcd. for C15H24O13 ϩ Naϩ 435.1115; found 435.1089.
ion-exchange resin were added alternately until gas evolution
Methyl [Methyl 4-O-(methyl β-D-galactopyranosyluronate)-β-D-glu-
ceased. After 1 h, the resin was filtered off and the solvent was
evaporated. Flash chromatography (petroleum ether/diethyl ether,
2:1) provided the labile methyl ester 30 (66 mg, 0.35 mmol, corres-
ponding to 0.70 mmol in the crude product, 23%, current yield
15%) as a colorless syrup. Additionally, the methyl ester 31 (37 mg,
0.23 mmol, corresponding to 0.47 mmol in the crude product, 15%,
current yield 10%) was isolated as a white solid. Compound 30
decomposed into 31 within 3 d at room temperature.
copyranoside]uronate (33): Methyl 4-O-(β--galactopyranosyl)-β--
glucopyranoside (20, 676 mg, 1.90 mmol) and TEMPO (25, 58 mg,
0.38 mmol) were dissolved in 75 mL of carbonate buffer. The solu-
tion was electrolyzed according to General Procedure A. After con-
sumption of 1868 C (10.2 F/mol), the electrolysis was stopped and
the system was worked up. Of the crude product obtained (706 mg),
185 mg was esterified. Flash chromatography (ethyl acetate/meth-
anol, 3:1) provided the dimethyl ester 33 (121 mg, 0.29 mmol, cor-
responding to 1.12 mmol in the crude product, 59%, current yield
46%) as a yellow syrup. [α]2D0 ϭ Ϫ23.3 (c ϭ 0.98, MeOH). IR (film):
ν˜ ϭ 3418 (br. s, OϪH), 1743 (s, CϭO) cmϪ1. 1H NMR (400 MHz,
CD3OD): δ ϭ 3.28 (m, 1 H, 2-H), 3.50Ϫ3.54 (m, 5 H, 2Ј-H, 3Ј-H,
1
Methyl Ester 30: H NMR (400 MHz, CDCl3): δ ϭ 3.48 (s, 3 H,
3
OCH3), 3.86 (s, 3 H, COOCH3), 4.24 (d, J4,5 ϭ 9.5 Hz, 1 H, 5-
3
H), 4.37Ϫ4.42 (m, 1 H, 4-H), 4.97 (d, J1,2 ϭ 1.8 Hz, 1 H, 1-H),
5.75Ϫ5.79 (m, 1 H, 3-H), 5.96Ϫ5.99 (m, 1 H, 2-H) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 52.6 (q, COOCH3), 56.1 (q, OCH3), 65.0
(d, C-4), 66.8 (d, C-5), 95.7 (d, C-1), 125.9 (d, C-3), 131.9 (d, C-2),
171.5 (s, COOCH3) ppm. MS (ESI/MS coupling, ESϩ): m/z (%) ϭ
211 (55) [M ϩ Naϩ], 193 (3) [M ϩ Naϩ Ϫ H2O], 179 (7) [M ϩ
Naϩ Ϫ CH3OH], 161 (3) [193 Ϫ CH3OH], 147 (7) [179 Ϫ CH3OH],
133 (7) [161 Ϫ CO], 111 (100) [M ϩ Naϩ Ϫ HO(CH)4OCH3, retro-
DielsϪAlder reaction], 23 (45) [Naϩ].
3
OCH3), 3.59 (t, J3,4 ϭ 8.9 Hz, 1 H, 3-H), 3.72Ϫ3.77 (m, 7 H, 2ϫ
3
COOCH3, 4-H), 4.03 (d, J4,5 ϭ 9.7 Hz, 1 H, 5-H), 4.14 (dd,
3J4Ј,5Ј ϭ 1.5 Hz, 1 H, 4Ј-H), 4.28 (d, 3J1,2 ϭ 8.2 Hz, 1 H, 1 H), 4.30
(d, 3J1Ј,2Ј ϭ 7.2 Hz, 1 H, 1Ј-H), 4.37 (d, 1 H, 5Ј-H) ppm. 13C NMR
(100 MHz, CD3OD): δ ϭ 53.1, 53.4 (2q, COOCH3), 57.9 (q,
OCH3), 71.4 (d, C-4Ј), 71.9 (d, C-2Ј), 74.3 (d, C-3Ј), 74.7 (d, C-2),
75.2 (d, C-5), 75.8 (d, C-5Ј), 76.1 (d, C-3), 83.3 (d, C-4), 105.3 (d,
C-1Ј), 105.9 (d, C-1), 170.4 (s, C-6Ј), 170.8 (s, C-6) ppm. MS (ESI/
MS coupling, ESϩ): m/z (%) ϭ 435 (24) [M ϩ Naϩ], 245 (45)
[H3COOCϪC6H11O5 ϩ Naϩ, β-cleavage], 186 (20), 159 (12), 157
(8), 127 (8), 23 (100) [Naϩ]. C15H24O13 (412.34): calcd. C 43.69, H
5.87; found C 42.92, H 6.12. The analyses were affected by residual
methanol that could not be removed after drying for 2 d at room
temperature and 0.1 Torr. The elemental composition is addition-
ally supported by high-resolution MS (HRMS). HRMS (ESI):
calcd. for C15H24O13 ϩ Naϩ 435.1115; found 435.1086.
Methyl Ester 31: [α]2D0 ϭ ϩ106.3 (c ϭ 1.05, MeOH). M.p. 43 °C.
1
IR (film): ν˜ ϭ 3441 (br. s, OϪH), 1745 (s, CϭO) cmϪ1. H NMR
(400 MHz, CDCl3): δ ϭ 3.82 (s, 3 H, COOCH3), 5.21 (s, 1 H, 5-
3
H), 6.36Ϫ6.39 (m, 2 H, 2-H, 3-H), 7.40 (d, J1,2 ϭ 0.9 Hz, 1 H, 1-
H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 53.2 (q, OCH3), 66.8
(d, C-5), 108.7 (d, C-3), 110.5 (d, C-2), 143.0 (d, C-1), 150.7 (d, C-
4), 171.9 (s, COOCH3) ppm. MS (ESI/MS coupling, ESϩ): m/z
ϩ
(%) ϭ 174 (75) [M ϩ NH4ϩ], 157 (20) [M ϩ NH4 Ϫ NH3], 156
ϩ
ϩ
(25) [M ϩ NH4 Ϫ H2O], 139 (100) [M ϩ NH4 Ϫ NH3 Ϫ H2O],
124 (10) [156 Ϫ CH3OH], 118 (8), 18 (10) [NH4ϩ]. C7H8O4 (156.14)
calcd. C 53.85, H 5.16; found C 54.00, H 5.31.
Methyl [Methyl 4-O-(methyl α-D-glucopyranosyluronate)-β-D-gluco-
pyranoside]uronate (34): Methyl 4-O-(α--glucopyranosyl)-β--glu-
copyranoside (21, 499 mg, 1.40 mmol) was electrolyzed with
TEMPO (25, 44 mg, 0.28 mmol) in 55 mL of carbonate buffer ac-
Methyl [Methyl 4-O-(methyl β-D-glucopyranosyluronate)-β-D-gluco-
pyranoside]uronate (32): Methyl 4-O-(β--glucopyranosyl)-β--glu-
copyranoside (19, 660 mg, 1.85 mmol) and TEMPO (25, 58 mg, cording to General Procedure A until 1572 C (11.6 F/mol) of
0.37 mmol) were electrolyzed in 75 mL of buffer according to Gen-
eral Procedure A. After consumption of 1999 C (11.2 F/mol), the
electrolysis was stopped and the mixture was worked up to provide
720 mg of crude product, of which 185 mg was esterified. The di-
methyl ester 32 (135 mg, 0.33 mmol, corresponding to 1.30 mmol
in the crude product, 69%, current yield 49%) was isolated by flash
charge had been consumed. A proportion (186 mg) of the crude
product (541 mg) was esterified. Subsequent isolation by flash
chromatography (ethyl acetate/methanol, 3:1) afforded the dimethyl
ester 34 (121 mg, 0.29 mmol, corresponding to 0.85 mmol in the
crude product, 61%, current yield 42%) as a colorless syrup. [α]2D0
ϭ
ϩ59.7 (c ϭ 1.03, MeOH). IR (film): ν˜ ϭ 3375 (br. s, OϪH), 1746
(s, CϭO) cmϪ1. 1H NMR (400 MHz, CD3OD): δ ϭ 3.25 (dd, 1 H,
2-H), 3.43Ϫ3.47 (m, 2 H, 2Ј-H, 4Ј-H), 3.49 (s, 3 H, OCH3), 3.57
chromatography (ethyl acetate/methanol, 3:1) as a white solid. [α]
20
ϭ Ϫ37.9 (c ϭ 1.08, MeOH). M.p. 95 °C. IR (film): ν˜ ϭ 3422
D
(br. s, OϪH), 1742 (s, CϭO) cmϪ1
.
1H NMR (600 MHz, D2O): (t, J2Ј,3Ј ϭ 9.7 Hz, 1 H, 3Ј-H), 3.63 (t, J2,3 ϭ 9.2 Hz, 1 H, 3-H),
3
3
3
δ ϭ 3.19Ϫ3.23 (m, 2 H, 2Ј-H, 2-H), 3.36Ϫ3.46 (m, 5 H, OCH3, 4Ј-
3.69Ϫ3.74 (m, 4 H, COOCH3, 4-H), 3.98 (d, J4,5 ϭ 8.9 Hz, 1 H,
3
3
3
H, 3Ј-H), 3.32Ϫ3.37 (m, 2 H, 3Ј-H, 5Ј-H), 3.54 (t, J3,4 ϭ 8.6 Hz, 5-H), 4.01 (d, J4Ј,5Ј ϭ 10.4 Hz, 1 H, 5Ј-H), 4.25 (d, J1,2 ϭ 8.0 Hz,
1 H, 3-H), 3.68Ϫ3.69 (m, 7 H, 2ϫ COOCH3, 4-H), 3.93 (d, 3J4Ј,5Ј
ϭ
1 H, 1-H), 5.16 (d, J1Ј,2Ј ϭ 3.2 Hz, 1 H, 1Ј-H) ppm. 13C NMR
3
3
10.0 Hz, 1 H, 5Ј-H), 4.07 (d, J4,5 ϭ 9.3 Hz, 1 H, 5-H), 4.32Ϫ4.34
(100 MHz, CD3OD): δ ϭ 53.0, 53.5 (2q, COOCH3), 57.9 (q,
(m, 2 H, 1Ј-H, 1-H) ppm. 13C NMR (151 MHz, D2O): δ ϭ 53.1, OCH3), 73.5 (d, C-4Ј), 73.8 (d, C-2Ј), 74.1 (d, C-5Ј), 74.6 (d2, C-2,
53.2 (2q, COOCH3), 58.1 (q, OCH3), 70.0 (d, C-4Ј), 72.3 (d, C-2Ј),
C-3Ј), 76.1 (d, C-5), 77.3 (d, C-3), 82.8 (d, C-4), 103.0 (d, C-1Ј),
72.4 (d, C-2), 73.1 (d, C-5), 73.5 (d, C-3), 74.2 (d, C-5Ј), 74.7 (d, 104.0 (d, C-1), 170.8 (s, C-6), 172.2 (s, C-6Ј) ppm. MS (ESI/MS
C-3Ј), 79.8 (d, C-4), 102.4 (d, C-1Ј), 103.4 (d, C-1), 170.0 (s, C-6), coupling, ESϩ): m/z (%) ϭ 435 (35) [M ϩ Naϩ], 245 (30)
170.7 (s, C-6Ј) ppm. MS (ESI/MS coupling, ESϩ): m/z (%) ϭ 430
[H3COOCϪC6H11O5 ϩ Naϩ, α-cleavage], 186 (13), 159 (8), 157
Eur. J. Org. Chem. 2003, 351Ϫ358
356

TEMPO-Mediated Anodic Oxidation of Glycosides and Disaccharide Derivatives
FULL PAPER
(5), 127 (4), 23 (100) [Naϩ]. C15H24O13 (412.34): calcd. C 43.69, H
5.87; found C 42.86, H 6.21. The analyses were affected by residual
methanol that could not be removed after drying for 2 d at room
temperature and 0.1 Torr. The elemental composition is addition-
ally supported by high-resolution MS (HRMS). HRMS (ESI):
calcd. for C15H24O13 ϩ Naϩ 435.1115; found 435.1108.
[H3COOCϪC5H9O5 ϩ Naϩ, β-cleavage], 213 (25) [231 Ϫ H2O],
210 (2), 164 (5), 151 (4), 113 (10), 23 (15) [Naϩ]. C14H21N3O12
(423.33): calcd. C 39.72, H 5.00, N 9.93; found C 39.61, H 5.32, N
7.95. The analyses were affected by residual methanol that could
not be removed after drying for 2 d at room temperature and
0.1 Torr. The elemental composition is additionally supported by
high-resolution MS (HRMS). HRMS (ESI): calcd. for
C14H21N3O12 ϩ Naϩ 446.1023; found 446.1066.
Methyl [4-O-(Methyl β-D-glucopyranosyluronate)-β-D-glucopyrano-
syl azide]uronate (35): 4-O-(β--Glucopyranosyl)-β--glucopyrano-
syl azide (22, 455 mg, 1.25 mmol) and TEMPO (25, 39 mg,
0.25 mmol) were dissolved in 40 mL of carbonate buffer. The solu-
tion was electrolyzed according to General Procedure B. After con-
sumption of 1822 C (15.1 F/mol), the electrolysis was stopped and
the system was worked up. A proportion (119 mg) of crude product
(482 mg) was esterified. Flash chromatography (ethyl acetate/meth-
anol, 6:1) provided the dimethyl ester 35 (68 mg, 0.16 mmol, corres-
ponding to 0.79 mmol in the crude product, 63%, current yield
33%) as a white solid. [α]2D0 ϭ Ϫ39.9 (c ϭ 1.00, MeOH). M.p. 81
°C. IR (film): ν˜ (cmϪ1) ϭ 3389 (br. s, OϪH), 2122 (s, N3), 1741 (s,
Methyl [4-O-(Methyl α-D-glucopyranosyluronate)-β-D-glucopyrano-
syl azide]uronate (37): 4-O-(α--Glucopyranosyl)-β--glucopyrano-
syl azide (24, 455 mg, 1.25 mmol) was electrolyzed with TEMPO
(25, 39 mg, 0.25 mmol) in 40 mL of carbonate buffer according to
General Procedure B until 1592 C (13.3 F/mol) of charge had been
consumed. A proportion (183 mg) of the crude product (510 mg)
was esterified. Subsequent isolation of the ester by flash chromato-
graphy (ethyl acetate/methanol, 8:1) afforded the dimethyl ester 37
(107 mg, 0.25 mmol, corresponding to 0.71 mmol in the crude
product, 57%, current yield 34%) as a colorless syrup. [α]2D0 ϭ ϩ56.4
(c ϭ 1.00, MeOH). IR (film): ν˜ (cmϪ1) ϭ 3366 (br. s, OϪH), 2122
(s, N3), 1746 (s, CϭO). 1H NMR (400 MHz, CD3OD): δ ϭ
3.14Ϫ3.22 (m, 1 H, 2-H), 3.38Ϫ3.45 (m, 2 H, 2Ј-H, 4Ј-H), 3.55 (t,
3J3Ј,4Ј ϭ 9.6 Hz, 1 H, 3Ј-H), 3.60Ϫ3.65 (m, 1 H, 3-H), 3.71Ϫ3.74
1
CϭO). H NMR (600 MHz, CD3OD): δ ϭ 3.27Ϫ3.32 (m, 2 H, 2-
H, 2Ј-H), 3.42 (s, 6 H, COOCH3), 3.44 (t, 3J3Ј,4Ј ϭ 8.9 Hz, 1 H, 3Ј-
H), 3.63 (t, 3J3,4 ϭ 9.0 Hz, 1 H, 3-H), 3.75 (t, 1 H, 4Ј-H), 3.83Ϫ3.86
3
3
(m, 1 H, 4-H), 4.00 (d, J4Ј,5Ј ϭ 9.9 Hz, 1 H, 5Ј-H), 4.20 (d, J4,5 ϭ
3
(m, 7 H, 2ϫ COOCH3, 4-H), 3.98 (d, J4Ј,5Ј ϭ 9.8 Hz, 1 H, 5Ј-H),
3
10.2 Hz, 1 H, 5-H), 4.47 (d, J1Ј,2Ј ϭ 7.6 Hz, 1 H, 1Ј-H), 4.70 (d,
3
3
4.06 (d, J4,5 ϭ 9.9 Hz, 1 H, 5-H), 4.59 (d, J1,2 ϭ 8.6 Hz, 1 H, 1-
H), 5.15 (d, 3J1Ј,2Ј ϭ 3.4 Hz, 1 H, 1Ј-H) ppm. 13C NMR (100 MHz,
CD3OD): δ ϭ 53.0, 53.6 (2q, COOCH3), 73.5 (d, C-4Ј), 73.8 (d, C-
2Ј), 74.1 (d, C-5Ј), 74.2 (d, C-2), 74.6 (d, C-3Ј), 77.4 (d, C-3), 77.6
(d, C-5), 82.2 (d, C-4), 92.4 (d, C-1), 103.0 (d, C-1Ј), 170.2 (s, C-
6), 172.2 (s, C-6Ј) ppm. MS (ESI/MS coupling, ESϩ): m/z (%) ϭ
446 (98) [M ϩ Naϩ], 418 (10) [M ϩ Naϩ Ϫ N2], 392 (5) [M ϩ
Naϩ Ϫ NaOCH3], 315 (100) [M ϩ Naϩ Ϫ HN3 Ϫ CH3OH Ϫ
2ϫ CO], 231 (55) [H3COOCϪC5H9O5 ϩ Naϩ, α-cleavage], 213 (23)
[231 Ϫ H2O], 210 (20), 164 (15), 151 (13), 112 (12), 23 (42) [Naϩ].
C14H21N3O12 (423.33): calcd. C 39.72, H 5.00, N 9.93; found C
39.75, H 5.82, N 7.77. The analyses were affected by residual meth-
anol that could not be removed after drying for 2 d at room tem-
perature and 0.1 Torr. The elemental composition is additionally
supported by high-resolution MS (HRMS). HRMS (ESI): calcd.
for C14H21N3O12 ϩ Naϩ 446.1023; found 446.1023.
3J1,2 ϭ 8.7 Hz, 1 H, 1-H) ppm. 13C NMR (151 MHz, CD3OD):
δ ϭ 50.2, 53.5 (2q, COOCH3), 73.2 (d, C-4Ј), 74.3 (d, C-2), 74.4
(d, C-2Ј), 75.9 (d, C-3), 76.7 (d, C-5Ј), 76.9 (d, C-5), 77.3 (d, C-3Ј),
81.7 (d, C-4), 92.3 (d, C-1), 104.8 (d, C-1Ј), 170.2 (s, C-6), 171.2 (s,
C-6Ј) ppm. MS (ESI/MS coupling, ESϩ): m/z (%) ϭ 446 (20) [M
ϩ Naϩ], 418 (2) [M ϩ Naϩ Ϫ N2], 392 (3) [M ϩ Naϩ Ϫ NaOCH3],
315 (100) [M ϩ Naϩ Ϫ HN3 Ϫ CH3OH Ϫ 2 ϫ CO], 231 (40)
[H3COOCϪC5H9O5 ϩ Naϩ, β-cleavage], 213 (22) [231 Ϫ H2O],
210 (5), 164 (8), 151 (10), 112 (12), 23 (35) [Naϩ]. C14H21N3O12
(423.33): calcd. C 39.72, H 5.00, N 9.93; found C 39.04, H 5.12, N
7.08. The analyses were affected by residual methanol that could
not be removed after drying for 2 d at room temperature and
0.1 Torr. The elemental composition is additionally supported by
high-resolution MS (HRMS). HRMS (ESI): calcd. for
C14H21N3O12 ϩ Naϩ 446.1023; found 446.1032.
Methyl [4-O-(Methyl β-D-galactopyranosyluronate)-β-D-glucopyr-
Methyl (β-D-Glucopyranosyl azide)uronate (39): β--Glucopyrano-
anosyl azide]uronate (36): 4-O-(β--Galactopyranosyl)-β--glucop- syl azide (38, 419 mg, 2.00 mmol) was electrolyzed with TEMPO
yranosyl azide (23, 455 mg, 1.25 mmol) and TEMPO (25, 39 mg, (63 mg, 0.40 mmol) in 40 mL of carbonate buffer according to
0.25 mmol) were electrolyzed in carbonate-buffered water (40 mL) General Procedure B until 1026 C (5.3 F/mol) of charge had been
until 1026 C (8.6 F/mol) had been consumed, and the system was
worked up according to General Procedure B. A proportion
(141 mg) of the crude product (426 mg) was esterified. The di-
consumed. A proportion (100 mg) of the crude product (407 mg)
was esterified. Subsequent isolation of the ester by flash chromato-
graphy (cyclohexane/ethyl acetate, 1:4) afforded the methyl ester
methyl ester 35 (74 mg, 0.18 mmol, corresponding to 0.53 mmol in 39 (94 mg, 0.44 mmol, corresponding to 1.64 mmol in the crude
the crude product, 42%, current yield 39%) was isolated as a white
product, 82%, current yield 62%) as a white solid. [α]2D0 ϭ Ϫ54.3
solid by flash chromatography (ethyl acetate/methanol, 6:1). [α]2D0
ϭ
(c ϭ 1.50, MeOH). M.p. 102 °C. IR (film): ν˜ ϭ 3389 (br. s, OϪH),
Ϫ32.8 (c ϭ 1.00, MeOH). M.p. 78 °C. IR (film): ν˜ ϭ 3408 (br. s, 2123 (s, N3), 1740 (s, CϭO) cmϪ1. H NMR (400 MHz, CD3OD):
1
OϪH), 2122 (s, N3), 1743 (s, CϭO) cmϪ1
.
1H NMR (400 MHz, δ ϭ 3.17 (t, J1,2 ϭ 8.5, J2,3 ϭ 9.1 Hz, 1 H, 2-H), 3.40 (t, J3,4
ϭ
3
3
3
3
3
CD3OD): δ ϭ 3.34 (t, J1,2 ϭ 8.4 Hz, 1 H, 2-H), 3.58Ϫ3.66 (m, 2
9.4 Hz, 1 H, 3-H), 3.54 (t, J4,5 ϭ 9.7 Hz, 1H 4-H), 3.78 (s, 3 H,
3
3
H, 2Ј-H, 3Ј-H), 3.70 (t, J2,3 ϭ 8.8 Hz, 1 H, 3-H), 3.84 (t, J3,4
ϭ
COOCH3), 3.94 (d, 1 H, 5-H), 4.58 (d, 1 H, 1-H) ppm. 13C NMR
9.1 Hz, 1 H, 4-H), 3.86 (s, 3 H, COOCH3), 3.87 (s, 3 H, COOCH3), (100 MHz, CD3OD): δ ϭ 53.2 (q, COOCH3), 73.0 (d, C-4), 74.6
3
4.22Ϫ4.25 (m, 2 H, 5-H, 4Ј-H), 4.38 (d, J1Ј,2Ј ϭ 6.8 Hz, 1 H, 1Ј-
(d, C-2), 77.6 (d, C-3), 78.7 (d, C-5), 92.4 (d, C-1), 170.9 (s, C-6)
3
3
H), 4.47 (d, J4Ј,5Ј ϭ 1.1 Hz, 1 H, 5Ј-H), 4.73 (d, J1,2 ϭ 8.4 Hz, 1 ppm. MS (ESI/MS coupling, ESϩ): m/z (%) ϭ 256 (45) [M ϩ
H, 1-H) ppm. 13C NMR (100 MHz, CD3OD): δ ϭ 53.1, 53.6 (2q,
COOCH3), 71.3 (d, C-4Ј), 71.8 (d, C-2Ј), 74.2 (d, C-3Ј), 74.4 (d, C-
2), 75.8 (d, C-5Ј), 76.1 (d, C-3), 76.7 (d, C-5), 82.8 (d, C-4), 92.3
Naϩ], 224 (3) [M ϩ Naϩ Ϫ CH3OH], 68 (8), 23 (100) [Naϩ].
C7H11N3O6 (233.18) calcd. C 36.06, H 4.75, N 18.02; found C
35.90, H 4.53, N 16.63. The analyses were affected by residual
(d, C-1), 105.2 (d, C-1Ј), 170.2 (s, C-6), 170.4 (s, C-6Ј) ppm. MS methanol that could not be removed after drying for 2 d at room
(ESI/MS coupling, ESϩ): m/z (%) ϭ 446 (18) [M ϩ Naϩ], 418
temperature and 0.1 Torr. The elemental composition is addition-
(4) [M ϩ Naϩ Ϫ N2], 392 (2) [M ϩ Naϩ Ϫ NaOCH3], 315 ally supported by high resolution MS (HRMS). HRMS (ESI):
(100) [M ϩ Naϩ Ϫ HN3 Ϫ CH3OH Ϫ 2 ϫ CO], 231 (75) calcd. for C7H11N3O6 ϩ Naϩ 256.0546; found 256.0576.
Eur. J. Org. Chem. 2003, 351Ϫ358
357

M. Schämann, H. J. Schäfer
FULL PAPER
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