A facile method for oxidation of primary alcohols to carboxylic acids and its application in glycosaminoglycan syntheses

Article abstract of DOI:10.1002/chem.200600290

A convenient two-step, one-pot procedure was developed for the conversion of primary alcohols to carboxylic acids. The alcohol was first treated with NaOCl and TEMPO under phase-transfer conditions, followed by NaClO₂ oxidation in one pot. This reaction is applicable to a wide range of alcohols and the mild reaction conditions are compatible with many sensitive functional groups, including electron-rich aromatic rings, acid-labile isopropylidene ketal and glycosidic linkages, and oxidation-prone thioacetal, p-methoxybenzyl, and allyl moieties. Several glycosaminoglycans such as heparin, chondroitin, and hyaluronic acid oligosaccharides have been synthesized in high yields by using this new oxidation protocol.

Full text of DOI:10.1002/chem.200600290

DOI: 10.1002/chem.200600290
A Facile Method for Oxidation of Primary Alcohols to Carboxylic Acids and
Its Application in Glycosaminoglycan Syntheses
[
a]
Lijun Huang, Nardos Teumelsan, and Xuefei Huang*
Dedicated to Prof. Koji Nakanishi on the occasion of his 80th birthday
Abstract: A convenient two-step, one-
pot procedure was developed for the
conversion of primary alcohols to car-
boxylic acids. The alcohol was first
treated with NaOCl and TEMPO
under phase-transfer conditions, fol-
conditions are compatible with many
sensitive functional groups, including
electron-rich aromatic rings, acid-labile
isopropylidene ketal and glycosidic
linkages, and oxidation-prone thioace-
tal, p-methoxybenzyl, and allyl moiet-
ies. Several glycosaminoglycans such as
heparin, chondroitin, and hyaluronic
acid oligosaccharides have been syn-
thesized in high yields by using this
new oxidation protocol.
Keywords: carbohydrates · glycos-
aminoglycan · oxidation · synthetic
methods
lowed by NaClO oxidation in one pot.
2
This reaction is applicable to a wide
range of alcohols and the mild reaction
Introduction
amino sugars and uronic acids, the GAG family can be div-
ided to hyaluronic acid, heparin/heparan sulfate, chondroi-
tin/chondroitin sulfate, and dermatan. GAGs play diverse
and critical roles in many important biological processes
such as lymphocyte trafficking, inflammatory response,
Oxidation of primary alcohols to carboxylic acids is a funda-
mental transformation in organic synthesis, albeit with rela-
[1]
tively few good general methods available. This is particu-
lar the case for assembly of complex oligosaccharides such
as glycosaminoglycans (GAGs). The existence of a large
number of protective groups for selective GAG functionali-
zation in addition to the acid lability of glycosidic linkages,
severely limits available methodologies due to cross-reactivi-
ty. Furthermore, in GAG synthesis, the need to simultane-
ously convert multiple primary alcohols to carboxylic acids
demands a robust and high-yielding method. Herein, we
report a new convenient two-step, one-pot protocol for oxi-
dizing primary alcohols to carboxylic acids and its applica-
tion.
[3]
wound healing, and tumor metastasis. Biomedical applica-
tions of GAGs in areas such as antiviral, anti-angiogenesis,
and anticoagulation are enormous, exemplified by the devel-
opment of Arixtra, a fully synthetic heparin pentasaccharide
[4]
drug, for the treatment of deep vein thrombosis.
With the recognition of their biological importance, chem-
[2,5]
ical syntheses of GAGs are undergoing extensive studies;
such syntheses are typically carried out following two gener-
al approaches. In the first method, protected pyranosyl
uronic acids are directly utilized. However, with the strongly
electron-withdrawing 6-carboxyl moiety, these building
blocks often have low reactivities both as donors and as ac-
ceptors, resulting in low glycosylation yields. Furthermore,
base sensitivity of these compounds conferred by the car-
GAGs are a family of highly functionalized, linear and
negatively charged oligosaccharides, consisting of repeating
disaccharide units of a 2-deoxy-2-amino hexose linked to a
[
2]
[6,7]
pyranosyl uronic acid. Depending upon the identity of the
boxyl group complicates protective group manipulations.
These limitations also preclude the direct usage of uronic
[
8]
[
a] Dr. L. Huang, N. Teumelsan, Prof. X. Huang
Department of Chemistry, The University of Toledo
acids in solid-phase oligosaccharide syntheses. An attrac-
tive alternative is to use pyranosides as building blocks,
which can give high glycosylation yields. With this strategy,
one of the key challenges is the need to convert primary hy-
droxyl groups at C-6 positions into carboxylic acids post
glyco-assembly. The traditional pyridinium dichromate
2
801 W. Bancroft St. MS 602, Toledo, OH 43606 (USA)
Fax : (+1)419-530-4033
E-mail: xuefei.huang@utoledo.edu
1
13
Supporting information (copies of H NMR and C NMR spectra)
for this article is available on the WWW under http://www.chem
eurj.org/ or from the author.
[9–11]
(PDC) mediated oxidation,
was found to be inefficient;
5246
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Chem. Eur. J. 2006, 12, 5246 – 5252

FULL PAPER
it often required large excess of PDC subsequently resulting
Table 1. Oxidation of primary alcohols and monosaccharides.
[6,9]
in separation difficulties and low yields.
Two-step proto-
cols, such as Swern oxidation followed by treatment of
[7,12]
Alcohol
Carboxylic acids/esters
Yield [%]
100
NaClO or PDC,
not only are inconvenient, but also can
2
produce elimination side products due to the strongly basic
[
6,7]
condition utilized.
Besides the undesirable usage of toxic
1
[13]
chromium(vi) agents, Jones oxidation
and the combina-
[6]
tion of chromium trioxide and periodic acid are less useful
in oligosaccharide synthesis with the employment of strong
acids. Recently, TEMPO (2,2,6,6-tetramethylpiperidinyl-1-
2
3
95
90
[14–16]
oxy)-catalyzed oxidations with a co-oxidant (e.g. NaOCl
[17,18]
and bis
A
C
H
T
R
E
U
N
G
(acetoxy)iodobenzene (BAIB)
) have become a
popular choice. However, substantial side reactions with
[13]
[9]
thio
methoxybenzyl
reduced oxidation efficiencies were observed with large oli-
A
C
H
T
R
E
U
N
G
acetal, allyl and electron-rich aromatic rings such as
4
5
90
82
[19]
moieties have been reported. Moreover,
[15]
gosaccharides.
Results and Discussion
6
7
8
85
86
92
During our study of GAG synthesis, we were faced with the
task of oxidation state adjustment of hexasaccharide 1. De-
spite prolonged reaction time and repeated trials, the reac-
[14–16]
tion of 1 with TEMPO/NaOCl
led to multiple partially
oxidized products with a trace amount of the desired tricar-
[18]
boxylic acid 2. Attempts with TEMPO/BAIB or NaClO2
[19]
catalyzed by NaOCl/TEMPO
met with similar fate. A
two-step process of Dess–Martin oxidation followed by
[20]
NaClO2
gave inconsistent results. Finally, we discovered
[
a]
9
0
75
that a convenient two-step, one-pot protocol with TEMPO/
NaOCl followed by treatment of NaClO afforded the de-
2
sired carboxylic acid in high yield and good purity; this
result led us to further explore the scope of this method.
1
100
[
a] Ester 22 (10%) was isolated from the reaction mixture.
8
2–92% yields (Table 1, entries 4–8). Acid-sensitive isopro-
pylidene and p-methoxybenzyl (PMB) groups were stable
under reaction conditions (Table 1, entries 4 and 6). Thiogly-
cosides have been extensively used in oligosaccharide as-
[18,23]
A
panel of primary alcohols and monosaccharides
sembly.
The presence of thioacetal in thioglycosides pre-
(
Table 1) were examined first to test the functional group
cludes the usage of noble-metal oxidation conditions, such
as PtO and O . Previous attempts of TEMPO/NaOCl ox-
2 2
[13]
compatibility. Simple benzylic alcohols (Table 1, entries 1,2)
including the electron-rich p-methoxy benzyl alcohol (5;
Table 1, entry 2) can be oxidized in high yields without
chlorinating the aromatic rings. Aliphatic alcohol 1-decanol
idation of thioglycosides generated a mixture of sulfoxides
[13]
and sulfones in preference to alcohol oxidation. By using
our reaction protocol, both disarmed (compound 11) and
armed (compounds 13 and 16) thioglycosides were oxidized
in 82, 85, and 86% yields respectively (Table 1, entries 5–7).
No glycosyl sulfoxides or sulfones were identified from
these reactions, with trace amount (~6%) of lactone 15 iso-
lated from oxidation of thioglycoside 13. The allyl group,
which is a popular linker for the bioconjugation of carbohy-
(
7; Table 1, entry 3) was converted in 90% yield to decanoic
acid (8). Pyranosyl uronic acids such as glucoronic acid, gal-
actonic acid, and mannosinic acid often exist in oligosac-
charides and selectively protected uronic acids are useful for
carbohydrate synthesis.
hydroxyl groups in galactoside 9, glucoside 11, 2-deoxy-2-
[11,18]
Conversion of the free primary
[21]
[22]
[24]
amino-glucoside derivatives 13 and 16, and mannoside 18
to the corresponding uronic acids proceeded smoothly in
drates with proteins, remained intact following oxidation
[22]
of mannosyl pyranoside 18 (Table 1, entry 8). A primary
Chem. Eur. J. 2006, 12, 5246 – 5252
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5247

X. Huang et al.
substrates. The successful introduction of carboxyl groups
after glyco-assembly makes this alternative strategy for
GAG synthesis highly attractive.
The fact that the previously reported TEMPO/NaOCl
[14–16]
procedure
failed to produce desired carboxylic acids is
most likely due to hydrophobicities of our substrates. It has
been proposed that aldehydes are intermediates in TEMPO-
alcohol can be selectively converted to a carboxylic acid in
the presence of a free secondary hydroxyl group as 21 was
catalyzed NaOCl oxidation of primary alcohols to carboxylic
[25]
[14]
obtained in 75% yield following oxidation of diol 20 and
acids.
With a hydrophilic aldehyde, the carbonyl group
[
26]
[27]
benzyl ester formation
Table 1, entry 9). A small amount (~10%) of ester 22 was
also isolated from the reaction mixture. In addition to py-
with phenyl diazomethane
can be hydrated to form a vicinal diol under phase-transfer
conditions, which is subsequently oxidized by TEMPO/
NaOCl to produce a carboxylic acid (Scheme 1). However,
(
[
28]
A
C
H
T
R
E
U
N
G
ranosides, furanoside 23 was successfully transformed into
carboxylic acid 24 in quantitative yield (Table 1, entry 10).
Next we examined the application of this new protocol in
GAG syntheses. A hyaluronic acid disaccharide 26 was ob-
[29]
tained in 95% yield by oxidizing disaccharide 25 (Table 2,
entry 1). The oxidation was highly efficient even for large
[
29]
oligosaccharides, converting the tetrasaccharide 28
and
[29]
hexasaccharide 1 to oligocarboxylic acids, which were sub-
[26]
[27]
sequently benzylated with phenyl diazomethane to pro-
duce hyaluronic acid tetrasaccharide diester 29 and hexasac-
charide triester 30 in 86 and 82% overall yields, respectively
Table 2, entries 2 and 3). Trisaccharide 31 was also oxi-
dized and benzylated to produce chondroitin trisaccharide
2 in 76% yield (Table 2, entry 4). In addition, a heparin tri-
saccharide 34 was obtained in a similar manner in 81%
yield from diol 33 (Table 2, entry 5). Glycosidic linkages
were not affected during oxidation and no epimerization or
elimination products were identified with these sensitive
Scheme 1. Proposed intermediates for our new oxidation method.
[29]
(
due to the hydrophobic nature of fully protected oligosac-
charides, hydration of newly-formed aldehydes is presum-
3
A
H
R
U
G
conversion of an aldehyde to the carboxylic acid without
going through vicinal diol was apparently difficult with
TEMPO/NaOCl and prolonged treatment did not yield the
desired carboxylic acid. The major product isolated from
TEMPO/NaOCl oxidation of disaccharide 25 under phase-
transfer conditions was aldehyde 27. Attempt to enhance al-
dehyde hydration by performing TEMPO/NaOCl oxidation
in an acetonitrile and water mixture did not alleviate the
problem. In contrast, the aldehyde was quickly converted to
[29]
the carboxylic acid with addition of NaClO to the reaction
2
mixture following TEMPO/NaOCl oxidation. A one-step
procedure that involved the used of a combination of
TEMPO, NaOCl, and NaClO together was not successful,
2
[19]
probably due to the instability of NaClO /NaOCl mixture.
2
The excellent yields and extraordinary functional group
compatibility achieved by using our oxidation procedure are
related with the relatively high loading of TEMPO em-
ployed (0.3 equiv per hydroxyl group), as slower reaction
was observed with less TEMPO. Furthermore, the two-
phase condition (methylene chloride and water) for the
TEMPO/NaOCl oxidation is crucial. When oxidation of
thioglycoside 13 was carried out in a homogeneous acetoni-
A
H
R
U
G
trile/water mixture with TEMPO/NaOCl, multiple side
products without the thiotolyl moieties were obtained with
no desired carboxylic acid 14 or the corresponding aldehyde.
This indicates that the single-phase homogenous condition
for TEMPO/NaOCl oxidation is less selective and can affect
sensitive functional groups.
The formation of side product ester 22 in oxidation of
diol 20 (Table 1, entry 9) can be explained with the interme-
diacy of aldehyde as well. Upon generation of aldehyde 35
Table 2. Oxidation of primary alcohols for GAG synthesis.
Alcohol
GAG derivative
Yield [%]
1
2
3
4
5
25
28
1
31
33
26
29
30
32
34
95
86
82
76
81
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Chem. Eur. J. 2006, 12, 5246 – 5252

Carbohydrate Chemistry
FULL PAPER
from 20, intermolecular nucleophilic attack of the carbonyl
group by the free secondary hydroxyl group produced hemi-
acetal 36, oxidation and benzylation of which led to carbox-
ylic ester 22 (Scheme 2).
The reaction media was neutralized with HCl (1n, about 50 mL) to pH 6–
7
. It is important to keep the acidity of the reaction close to neutral as
lower pH resulted in formation of large amount of hemiacetal side prod-
uct in oxidation of diol 20. After neutralization, tBuOH (0.7 mL), 2-
methylbut-2-ene
in
and a solution of NaClO
50 mg, 0.44 mm) and NaH PO
THF
(2m,
[30]
1
.4 mL)
2
(
(
2
4
40 mg, 0.34 mm) in water (200 mL)
were added. The reaction mixture was
kept at room temperature for 1–2 h,
diluted
NaH PO
with
saturated
aqueous
2
4
solution (5 mL), and extract-
ed with EtOAc (3”10 mL). The or-
ganic layers were combined and dried
Scheme 2. Proposed mechanism for the formation of ester 22.
over MgSO
vent, the desired compound was puri-
fied by flash column chromatography.
4
. After removal of the sol-
Conclusion
General procedure for benzyl ester formation: The crude product from
the oxidation reaction was dissolved in dichloromethane (5 mL) and
treated with phenyl diazomethane solution in diethyl ether (~2 equiv per
In summary, we have established a new two-step, one-pot
oxidation protocol, which efficiently converts a wide range
of primary alcohols to carboxylic acids. This convenient pro-
cedure does not require an inert atmosphere, anhydrous sol-
vents, or an extremely low reaction temperature. It does not
generate toxic heavy-metal or malodorous side products;
this fact is important with respect to increasing environmen-
tal awareness. A remarkably wide range of sensitive func-
tional groups, such as electron-rich aromatic rings, acid-
labile isopropylidene ketal and glycosidic linkages, and oxi-
dation-prone thioacetal, PMB, and allyl moieties are little
affected by the oxidation. Several GAGs, including hyalur-
onic acid, chondroitin, and heparin oligosaccharides were
prepared in high yields by using this procedure. Further ap-
plications of this new protocol in solution and solid-phase
syntheses of complex oligosaccharides are ongoing.
[
27]
acid)
for 2–3 h until the disappearance of all starting material as
judged by TLC. The residue after evaporation was purified by flash
column chromatography to provide the benzyl ester.
[
31]
General procedure for regioselective opening of 4,6-O-benzylidene:
Bu BOTf in dichloromethane (1m, 1 equiv) was added to a solution of
,6-O-benzylidene containing glycoside in borane in THF (1m, 10 equiv)
in a flame dried flask at 08C under N . The reaction mixture was stirred
2
4
2
for 3 h. Triethylamine (~0.5 mL) was added followed by careful addition
of methanol until the evolution of gas had ceased. All solvents were
evaporated and the desired product was isolated by flash column chroma-
tography.
Benzoic acid (4): Compound
4 was obtained from benzyl alcohol
(
0.100 g, 0.92 mmol) following general oxidation procedure in 100%
1
13
yield. Comparison of the H and C NMR data with the Aldrich NMR li-
brary confirmed the identity of benzoic acid 4. H NMR (600 MHz,
1
CDCl ): d=7.45–7.49 (m, 1H), 7.58–7.62 (m, 2H), 8.09–8.13 ppm (m,
3
1
3
2H); C NMR (100 MHz, CDCl
3
): d=128.75, 129.54, 130.47, 134.09,
+
172.75 ppm; ESI-MS: m/z calcd for C
45.0.
7 6 2
H NaO [M+Na] : 145.1; found:
1
p-Anisic acid (6): Compound 6 was obtained from 4-methoxy benzyl al-
cohol (0.100 g, 0.72 mmol) following general oxidation procedure in 95%
Experimental Section
1
13
yield. Comparison of the H and C NMR data with the Aldrich NMR li-
1
brary confirmed the identity of compound 6. H NMR (600 MHz,
General conditions: Chemicals used were reagent grade as supplied
except where noted. Analytical thin-layer chromatography was per-
formed using silica gel 60 F254 glass plates (EM Science); compound
spots were visualized by UV light (254 nm) and/or by staining with a sol-
CDCl
3
): d=3.87 (s, 3H), 6.92–6.96 (m, 2H), 8.03–8.07 ppm (m, 2H);
1
3
C NMR (100 MHz, CDCl ): d=55.73, 113.97, 121.85, 132.59, 164.27,
3
+
1
1
8 8 3
71.90 ppm; ESI-MS: cm/z calcd for C H NaO [M+Na] : 175.2; found:
75.4.
ution containing Ce
A
C
H
T
R
E
U
N
G
(NH
4
)
2
A
H
R
U
G
3
)
6
(0.5 g) and (NH
4
)
6
Mo
(3 g), K CO
7 2
O24·4H O
Decanoic acid (8): Compound 8 was obtained from 1-decyl alcohol
0.100 g, 0.63 mmol) following general oxidation procedure in 90% yield.
(
(
24.0 g) in 6% H
2
SO
4
(500 mL) or a solution of KMnO
4
2 3
(
20 g) and NaOH (0.25 g) in water (300 mL). Flash column chromatogra-
phy was performed on silica gel 60 (230–400 Mesh, EM Science).
H NMR and C NMR spectra were recorded on a Varian VXRS-400 or
1
13
Comparison of the H and C NMR data with the Aldrich NMR library
confirmed the identity of compound 8. H NMR (400 Hz, CDCl ): d=
1
1
13
3
3
0
.88 (t,
2.35 ppm (t,
14.33, 22.89, 24.92, 29.29, 29.49, 29.62, 32.09, 34.37, 180.52 ppm; ESI-MS:
J
A
H
R
U
(H,H)=6.8 Hz, 3H), 1.24–1.32 (m, 12H), 1.61–1.66 (m, 2H),
Inova-600 instrument and were referenced to Me
4
Si (0 ppm), residual
3
13
1
13
A
H
R
U
G
3
J(H,H)=7.6 Hz, 2H); C NMR (100 MHz, CDCl ): d=
CHCl
CH Cl
3
( H NMR d=7.26 ppm) CDCl
3
( C NMR d=77.0 ppm), residual
1
13
2
2
( H NMR d=5.32 ppm), and CD
2
Cl
2
( C NMR d=54.0 ppm).
+
2
m/z calcd for C10H20NaO [M+Na] : 195.3; found: 195.5.
ESI mass spectra were recorded on an ESQUIRE LC-MS operated in
both positive and negative ion mode. High-resolution mass spectra were
1,2,3,4-Di-O-isopropylidene-a-d-galacturonic acid (10): Compound 10
was obtained from 1,2,3,4-di-O-isopropylidene-a-d-galactopyranose
(0.100 g, 0.38 mmol) following the general oxidation procedure in 90%
TM
recorded on a Micromass electrospray Tof
II (Micromass, Wythen-
shawe, UK) mass spectrometer equipped with an orthogonal electrospray
source (Z-spray) operated in positive ion mode, which is located at the
Mass Spectrometry and Proteomics Facility at the Ohio State University.
1
[32]
yield. Comparison of the H NMR data with literature confirmed the
1
3
identity of compound 10. H NMR (600 MHz, CDCl ): d=1.33 (s, 6H),
3
3
1
.44 (s, 3H), 1.52 (s, 3H), 4.39 (dd, J
A
H
R
U
G
General procedure for oxidation: An aqueous solution of NaBr (1m,
3
ACHTREUNG
A
H
R
U
G
2
5
5 mL), an aqueous solution of tetrabutylammonium bromide (1m,
0 mL), TEMPO (2.2 mg, 0.014 mmol, 0.3 equiv per hydroxyl group) and
1
3
1
7
H); C NMR (100 MHz, CDCl
3
a saturated aqueous solution of NaHCO
tion of alcohol (0.045 mmol) in CH Cl
3
(125 mL) were added to a solu-
(1 mL) and H O (170 mL) in an
+
for C12
7
H18NaO [M+Na] : 297.3; found: 297.1.
2
2
2
ice–water bath. The resulted mixture was treated with an aqueous solu-
tion of NaOCl (150 mL, chlorine content not less than 4%) and continu-
ously stirred for 1 hour as the temperature increased from 08C to RT.
p-Tolyl 2,3,4-tri-O-benzoyl-1-thio-b-d-glucopyranosyluronic acid (12):
[
21]
Compound 12 was synthesized from compound 11 (50 mg, 84 mmol) ac-
1
cording to the general oxidation procedure in 82% yield. H NMR
Chem. Eur. J. 2006, 12, 5246 – 5252
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5249

X. Huang et al.
3
(
1
(
(
7
1
400 MHz, CDCl
3
): d=2.33 (s, 3H; p-MePh), 4.34 (d,
J
A
H
R
U
G
Allyl 2,3,4-tri-O-benzoyl-1-thio-a-d-mannopyranosyluronic acid (19):
3
3
[22]
H), 5.01 (d,
J
A
C
H
T
R
E
U
N
G
(H,H)=9.6 Hz, 1H), 5.48 (t,
J
A
H
R
U
G
Compound 19 was synthesized from compound 18 (50 mg, 94 mmol) ac-
3
3
1
t,
J
A
C
H
T
R
E
U
N
G
(H,H)=9.6 Hz, 1H), 5.90 (t,
J
A
H
R
U
G
cording to the general oxidation procedure in 92% yield. H NMR
1
3
3
m, 19H); C NMR (100 MHz, CDCl
3
): d=21.47, 70.11, 70.32, 73.74,
6.35, 86.87, 127.48–139.30 (aromatic carbon atoms), 165.15, 165.71,
(400 MHz, CDCl
3
): d=4.18 (dd?J=6.0, 12.8 Hz, 1H), 4.35 (dd, J-
3
A
H
R
U
G
J(H,H)=9.2 Hz, 1H), 5.28–5.30 (m,
A
H
R
U
ꢀ
3
3
ACHTREUNG
65.91, 170.65 ppm; ESI-MS: m/z calcd for C34
H
27
O
9
S [Mꢀ1] : 611.2;
2H), 5.40 (dd, J
A
H
R
U
G
+
13
found: 611.3; HRMS: m/z calcd for C34
found: 635.1376.
p-Tolyl 2-deoxy-2-N-phthalimido-3-O-p-methoxybenzyl-4-O-benzyl-1-
H
28NaO
9
S [M+Na] : 635.1352;
1H), 5.91–6.03 (m, 3H), 7.26–8.09 ppm (m, 15H; ArH); C NMR
(100 MHz, CDCl
3
): d=67.83, 69.64, 69.69, 69.86, 70.25, 97.05, 119.05,
1
1
28.60–133.84 (aromatic carbon atoms), 165.53, 165.77, 165.86,
+
77.74 ppm; HRMS: m/z calcd for C30
H
26NaO10 [M+Na] : 569.1424;
thio-b-d-glucopyranoside (13): Compound 13 was synthesized from p-
tolyl 2-deoxy-2-N-phthalimido-3-O-p-methoxybenzyl-4,6-O-benzylidene-
(62 mg, 100 mmol) following the general
procedure of regioselective opening of benzylidene ring in 68% yield.
found: 569.1431.
[
33]
1
-thio-b-d-glucopyranoside
Benzyl 1-methoxy-2-deoxy-2-N-phthalimido-3-O-benzyl-b-d-glucopyrano-
[
25]
syluronate (21): Compound 21 was synthesized from compound 20
1
3
ACHTREUNG
H NMR (400 MHz, CDCl
3
): d=1.92 (t,
J
(H,H)=6.8 Hz, 3H), 2.29 (s,
(26 mg, 63 mmol) in 75% yield according to the general procedures of ox-
3
3
3
4
H), 3.52–3.58 (m, 1H), 3.58 (s, 3H), 3.66 (t,
J
A
H
R
U
G
idation and benzyl ester formation, along with compound 22 (~10%).
3
3
1
.72–3.78 (m, 1H), 3.88–3.96 (m, 1H), 4.14 (t,
J
A
H
R
U
G
3
H NMR (600 MHz, CDCl ): d=3.08?s, 1H; 4-OH), 3.39 (s, 3H; MeO),
3
3
3
ACHTREUNG
.34 (dd,
.70 (d, J
J
A
C
H
T
R
E
U
N
G
(H,H)=8.8, 10.0 Hz, 1H), 4.38 (d,
J
A
H
R
U
G
4.0–4.05 (m, 2H), 4.16
7.2, 10.8 Hz, 1H), 4.53 (d,
(H,H)=12.6 Hz, 1H; PhCH), 5.09 (d, J(H,H)=8.4 Hz, 1H), 5.26 (d, J-
A
H
R
U
G
A
H
R
U
3
3
3
3
4
A
C
H
T
R
E
U
N
G
(H,H)=12.4 Hz, 1H), 4.72 (d, J
A
H
R
U
G
J(H,H)=12.6 Hz, 1H; PhCH), 4.44 (d, J-
A
H
R
U
G
3
3
3
3
J
A
C
H
T
R
E
U
N
G
(H,H)=12.4 Hz, 1H), 5.50 (d,
J
A
H
R
U
G
A
H
R
N
A
H
R
N
3
ACHTREUNG
2
(
5
1
A
H
R
U
G
J
1
3
13
m, 5H), 7.58–7.84 ppm (m, 4H); C NMR (100 MHz, CDCl
3
): d=21.07,
4.74, 55.00, 61.92, 74.44, 75.08, 79.21, 79.35, 79.66, 83.31, 113.32, 123.05,
23.29, 127.73–133.71, 137.75, 138.32, 158.73, 167.27, 167.90 ppm; ESI-
3
+
carbon atoms), 169.53 ppm; HRMS: m/z calcd for
[M+Na] : 540.1634; found: 540.1628.
29 8
C H27NNaO
+
+
MS: m/z calcd for C36
H
35NNaO
7
S [M+Na] : 648.2; found: 648.3.
p-Tolyl 2-deoxy-2-N-phthalimido-3-O-p-methoxybenzyl-4-O-benzyl-1-
Benzyl 4-O-(benzyl-1-methoxy-2-deoxy-2-N-phthalimido-3-O-benzyl-b-d-
thio-b-d-glucopyranosyluronic acid (14): Compound 14 was synthesized
from compound 13 (40 mg, 66 mmol) according to the general oxidation
glucopyranosyluronate)-1-methoxy-2-deoxy-2-N-phthalimido-3-O-benzyl-
1
b-d-glucopyranosyluronate (22): H NMR (400 MHz, CDCl
3
): d=3.35s,
3
ACHTREUNG
procedure in 85% yield with 6% of the glycosyl lactone 15 isolated.
3H; OMe), 3.41 (s, 3H; OMe), 3.75 (t,
J
(H,H)=5.4 Hz, 1H), 3.86 (dt,
1
3
3
ACHTREUNG
H NMR (400 MHz, CDCl
3
): d=2.33 (s, 3H; p-MePh), 3.57 (s, 3H), 3.86
J(H,H)=3.6, 8.0 Hz, 1H), 4.10–4.22 (m, 3H), 4.31 (dd, J(H,H)=8.4,
A
H
R
U
G
3
3
3
3
3
ACHTREUNG
(
t,
J
A
C
H
T
R
E
U
N
G
(H,H)=9.2 Hz, 1H), 4.10 (d,
J
A
H
R
U
G
10.4 Hz, 1H), 4.39 (d, J
8.8, 10.8 Hz,1H), 4.58 (d,
(H,H)=12.4 Hz, PhCH, 1H), 4.86 (d, J(H,H)=12.4 Hz, PhCH, 1H),
A
H
R
U
G
3
3
A
C
H
T
R
E
U
N
G
(H,H)=10.2 Hz, 1H), 4.30–4.37 (m, 2H), 4.68–4.74 (m, 3H), 5.52 (d, J=
J(H,H)=12.4 Hz, PhCH, 1H), 4.68 (d, J-
A
H
R
U
G
1
3
3
ACHTREUNG
1
0.8 Hz, 1H), 6.33–7.81 ppm (m, 17H; ArH); C NMR (100 MHz,
CDCl ): d=21.36, 54.65, 55.00, 74.72, 75.48, 79.29, 81.09, 84.65, 113.58–
58.99 (aromatic carbon atoms), 167.39, 168.10, 177.56 ppm; HRMS: m/z
A
H
E
G
3
3
3
3
5.03 (d, J
A
H
R
U
G
A
H
R
U
G
3
ACHTREUNG
1
A
H
E
G
J
+
3
ACHTREUNG
calcd for C36
H
33NaO
8
S [M+Na] : 662.1825; found: 662.1826.
5.42 (dd,
J
1
3
2
-Deoxy-2-N-phthalimido-3-O-p-methoxybenzyl-4-O-benzyl-b-d-gluco-
3
1
73.84, 74.32, 74.45, 74.71, 74.81, 76.15, 99.44, 99.61, 127.56–138.29 (aro-
pyranosidurono-6,1-lactone (15): H NMR (400 MHz, CDCl
3
3
): d=3.56 (s,
(H,H)=9.6 Hz, 1H), 4.31
(H,H)=12.0 Hz, 1H), 4.61 (d,
3
3
ACHTREUNG
matic carbon atoms), 168.75, 169.51 ppm; HRMS: m/z calcd for
H), 3.91 (d, J
A
C
H
T
R
E
U
N
G
(H,H)=6.8 Hz, 1H), 4.22 (d, J
+
+
3
3
C H N NaO
15
[M+Na] : 949.2796; found: 949.2794.
(
J
dd,
J
A
C
H
T
R
E
U
N
G
(H,H)=7.2, 10 Hz, 1H), 4.42 (d,
J
A
H
R
U
G
51 46
2
3
3
ACHTREUNG
A
C
H
T
R
E
U
N
G
(H,H)=12.0 Hz, 1H), 4.64 (s, 1H), 4.68 (d,
J
(H,H)=11.6 Hz, 1H),
1-Methoxy-2,3-O-isopropylidene-b-d-ribofuranosyl-5-carboxylic acid (24):
3
[28]
4
.82 (d,
ESI-MS: m/z calcd for C29
HRMS: m/z calcd for
38.1501.
p-Tolyl 2-deoxy-2-N-phthalimido-3-O-tert-butyldimethylsilyl-4-O-benzyl-
-thio-b-D-glucopyranoside (16): Compound 16 was synthesized from p-
tolyl 2-deoxy-2-N-phthalimido-3-O-tert-butyldimethylsilyl-4,6-O-benzyli-
J
A
C
H
T
R
E
U
N
G
(H,H)=11.6 Hz, 1H), 5.96 (s, 1H), 6.32–7.72 ppm (m, 13H);
Compound 24 was synthesized from compound 23 (40 mg, 96 mmol) ac-
+
1
H
25NaNO
25NaNO
8
[M+Na] : 538.1; found: 538.2;
cording to the general oxidation procedure in 100% yield. H NMR
+
3
C
29
H
8
[M+Na] : 538.1478; found:
(600 MHz, CDCl
3
): d=1.31 (s, 3H), 1.47 (s, 3H), 3.40 (s, 3H), 4.55 (d, J-
3
5
A
H
R
U
G
J
A
C
H
T
R
E
U
N
G
(H,H)=
): d=25.15, 26.56, 55.89, 82.41,
4.33, 109.91, 113.11, 175.41 ppm; HRMS: m/z calcd for C30
1
3
5
8
[
.4 Hz, 1H); C NMR (150 MHz, CDCl
3
H
26NaO10
1
+
M+Na] : 569.1424; found: 569.1431.
Methyl (2-O-benzoyl-3,4-di-O-benzyl-b-d-glucopyranosyluronic acid-
3)-(2-deoxy-2-N-phthalimido-4,6-O-benzylidene-b-d-glucopyranoside)
[
33]
dene-1-thio-b-d-glucopyranoside (62 mg, 100 mmol) following the gen-
A
C
H
T
R
E
U
N
G
(1!
eral procedure of regioselective opening of benzylidene ring in 77%
1
[29]
yield. H NMR (600 MHz, CDCl
3
): d=ꢀ0.44 (s, 3H), ꢀ0.06 (s, 3H), 0.71
(26): Compound 26 was synthesized from compound 25
(28 mg,
3
(
s, 9H), 1.95 (t,
.64–3.72 (m, 1H), 3.83–3.90 (m, 1H), 4.22 (t,
.48 (dd, J
J
A
C
H
T
R
E
U
N
G
(H,H)=6.6 Hz, 3H), 2.28 (s, 3H), 3.48–3.58 (m, 2H),
33 mmol) following the general oxidation procedure in 95% yield.
3
1
3
3
4
J
A
H
R
U
G
H NMR (400 MHz, CDCl
3
): d=3.37 (s, 3H; OMe), 3.56 (dd,
J
J
A
C
H
T
R
E
U
N
G
(H,H)=
3
3
ACHTREUNG
3
A
C
H
T
R
E
U
N
G
(H,H)=8.4, 9.6 Hz, 1H), 4.64 (d, J
4.2, 6.4 Hz, 1H), 3.65 (m, 1H), 3.80–3.89 (m, 3H), 3.94 (d,
6.0 Hz, 1H), 4.30 (dd, J(H,H)=8.4, 10.4 Hz, 1H), 4.37–4.51 (m, 5H),
ACHTREUNG
(H,H)=
3
3
3
ACHTREUNG
(
d, J
A
C
H
T
R
E
U
N
G
(H,H)=12.0 Hz, 1H), 5.55 (d, J
A
H
R
U
G
3
3
ACHTREUNG
2
H), 7.21–7.36 (m, 7H), 7.72–7.92 ppm (m, 4H); ESI-MS: m/z calcd for
4.73 (t,
8.8 Hz, 1H), 5.57 (s, 1H), 7.01–7.53 ppm (m, 24H; ArH); C NMR
100 MHz, CDCl ): d=55.45, 57.23, 66.46, 68.95, 73.56, 73.69, 73.89,
4.28, 76.41, 79.45, 81.08, 99.49, 99.78, 102.42, 126.54–137.34 (aromatic
J
A
H
R
U
G
+
13
C
34
H
31NNaO
p-Tolyl 2-deoxy-2-N-phthalimido-3-O-tert-butyldimethylsilyl-4-O-benzyl-
-thio-b-d-glucopyranosyluronic acid (17): Compound 17 was synthesized
from compound 16 (55 mg, 89 mmol) according to the general oxidation
6
SSi [M+Na] : 642.2; found: 642.7.
(
7
3
1
carbon atoms), 164.77, 169.45 ppm (carbonyl groups); HRMS: m/z calcd
+
1
for C H NaO [M+Na] : 894.2738; found: 894.2701.
procedure in 86% yield. H NMR (600 MHz, CDCl
3
): d=ꢀ0.44 (s, 3H),
49 45
14
3
ꢀ
0.09 (s, 3H), 0.71 (s, 9H), 2.28 (s, 3H), 3.67 ?t,
J
A
H
E
N
Methyl
(2-O-benzoyl-3,4-di-O-benzyl-b-d-glucohexodialdo-1,5-pyrano-
3
3
3
4
.11 (d, J
A
C
H
T
R
E
U
N
G
(H,H)=9.6 Hz, 1H), 4.31 (t, J
A
H
R
U
G
syl)-(1!3)-(2-deoxy-2-N-phthalimido-4,6-O-benzylidene-b-d-glucopyran-
3
3
[29]
A
C
H
T
R
E
U
N
G
(H,H)=9.2 Hz, 1H), 4.58 (d,
J
A
H
R
N
J
A
H
R
U
G
A
H
R
U
G
3
1
0.8 Hz, 1H), 5.57 (d,
J
A
T
E
N
2
the general oxidation procedure without the NaClO oxidation step.
1
3
1
3
ACHTREUNG
3
H NMR (600 MHz, CDCl
3
): d=3.35 (s, 3H; OMe), 3.46 (d,
J(H,H)=
3
ACHTREUNG
5
7.8 Hz, 1H), 3.58 (t, J
(m, 2H), 4.28 (dd,
10.8 Hz, 1H), 4.39–4.51 (m, 5H), 4.72 (t, J
(H,H)=7.8 Hz, 1H), 3.62–3.64 (m, 2H), 3.84–3.87
+
3
3
ACHTREUNG
carbon atoms); HRMS: m/z calcd for
56.2114; found: 656.2072.
C
34
H
39NaO
7
SSi [M+Na] :
J
A
H
R
U
G
J
3
ACHTREUNG
6
5250
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 5246 – 5252

Carbohydrate Chemistry
FULL PAPER
3
3
3
ACHTREUNG
J
A
C
H
T
R
E
U
N
G
(H,H)=7.2 Hz, 1H), 4.97 (t,
J
A
H
R
U
G
J
(H,H)=
ꢀ4.04, 18.07, 25.93, 52.39, 57.38, 66.73, 67.19, 67.44, 68.86, 71.73, 73.66,
73.97, 74.46, 74.55, 74.89, 75.41, 75.54, 76.84, 81.51, 82.41, 82.64, 98.29,
100.66, 101.06, 104.88, 122.92–139.17 (aromatic carbon atoms), 164.54,
8
1
9
.4 Hz, 1H), 5.51 (s, 1H; PhCH), 6.95–7.55 (m, 24H; ArH), 9.39 ppm (s,
H; CHO); ESI-MS: m/z calcd for C50H49NNaO14 [M+Na+MeOH] :
+
10.3; found: 910.6.
167.84, 168.40, 169.41 ppm (carbonyl groups); ESI-MS: m/z calcd for
+
C
C
82
H
H
85NNaO20Si [M+Na] : 1454.5; found: 1454.6; HRMS: m/z calcd for
Methyl (benzyl-2-O-benzoyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-b-d-
glucopyranosyluronate)-
(1!3)-(2-deoxy-2-N-phthalimido-4,6-O-benzyli-
dene-b-d-glucopyranosyl)-
+
82
85NNaO20Si [M+Na] : 1454.5170; found: 1454.5332.
ACHTREUNG
A
H
R
U
G
Methyl (benzyl-2-O-benzoyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-b-d-
glucopyranosyluronate)-
(1!4)-(2-deoxy-2-azido-3,6-O-dibenzyl-a-d-glu-
copyranosyl)-
(1!4)-benzyl-2,3-O-dibenzyl-b-d-glucopyranosyluronate
(34): Compound 34 was synthesized from compound 33 (40 mg,
33 mmol) following the general procedures of oxidation and benzyl ester
glucopyranosyluronate)-(1!3)-2-deoxy-2-N-phthalimido-4,6-O-benzyli-
ACHTREUNG
dene-b-d-glucopyranoside (29): Compound 29 was synthesized from com-
AHCTREUNG
[
29]
[29]
pound 28 (136 mg, 84 mmol) following the general procedures of oxida-
tion and benzyl ester formation in 86% overall yield. H NMR
(
(
9
(
1
1
600 MHz, CD
s, 9H; (CH
.6 Hz, 1H), 3.41 (t, J
2
Cl
2
): d=ꢀ0.24 (s, 3H; CH
Si), ꢀ0.13 (s 3H; CH
3
Si), 0.75
formation in 81% overall yield. H NMR (600 MHz, CDCl
3
): d=ꢀ0.04
3
(
s, 3H; CH
3
Si), ꢀ0.04 (s 3H; CH
3
Si), 0.85 (s, 9H; (CH ) CSi), 3.15 (dd,
3
3
3
)
3
CSi), 2.25 (m, 1H), 3.28 (s, 3H; CH
O), 3.37 (d, J
A
H
R
U
G
3
3
3
3
J
A
H
R
U
G
J(H,H)=10.2 Hz, 1H), 3.29 (t, J-
A
H
R
U
A
C
H
T
R
E
U
N
G
(H,H)=7.8 Hz, 1H), 3.44-.3.49 (m, 3H), 3.58–3.61
(H,H)=8.4 Hz, 1H), 3.93–4.13 (m, 5H), 4.18 (dd, J-
3
3
A
H
R
U
G
m, 2H), 3.67 (d, J
A
C
H
T
R
E
U
N
G
3
3
ACHTREUNG
(m, 2H), 3.73 (d, J
3.79 (d,
A
C
H
T
R
E
U
N
G
(H,H)=5.4, 9.6 Hz, 1H), 4.32–4.39 (m, 3H), 4.52 (d,
J(H,H)=10.8 Hz,
3
1
1
1
(
1
H), 4.51 (dd,
H), 4.66 (dd,
H), 4.79 (t,
dd, J
J
A
C
H
T
R
E
U
N
G
(H,H)=9.0, 10.2 Hz, 1H), 4.61 (d,
(H,H)=8.4, 10.2 Hz, 1H), 4.68 (d,
(H,H)=7.8 Hz, 1H), 4.80 (d,
(H,H)=8.4, 10.2 Hz, 1H), 4.94 (s, 2H), 5.03 (d, J
3
9.0 Hz, 1H), 4.26–4.29 (m, 3H), 4.42 (d, J
J
A
C
H
T
R
E
U
N
G
3
3
J
A
C
H
T
R
E
U
N
G
3
A
C
H
T
R
E
U
N
G
3
1H), 5.01 (d,
H), 5.05 (d, J
A
C
H
T
R
E
U
N
G
(H,H)=8.4 Hz, 1H), 5.06 (d, J
s, 1H; PhCH), 5.32 (s, 1H; PhCH), 6.92–7.81 ppm (m, 48H; ArH);
A
H
R
U
G
(
1
3
40H; ArH); C NMR (150 MHz, CDCl ): d ꢀ4.77, ꢀ3.81, 18.17, 26.06,
C NMR (100 MHz, CD
2
Cl
2
): d=ꢀ5.20, ꢀ4.29, 19.22, 25.72, 55.16, 55.69,
5
7
9
1
5
7
9
1
6.98, 65.85, 66.32, 67.31, 68.43, 68.55, 71.91, 72.99, 73.96, 74.24, 74.68,
5.80, 76.12, 76.96, 77.56, 79.88, 80.96, 81.71, 82.20, 98.30, 99.57, 99.59,
9.84, 101.15, 101.48, 123.19–138.38 (aromatic carbon atoms), 164.53,
64.66, 166.93, 168.11 ppm (carbonyl groups); HRMS: m/z calcd for
+
C
C
103
H
100NaN
2
O
27Si [M+Na] : 1847.6180; found: 1847.6165.
Methyl (benzyl-2-O-benzoyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-b-d-
glucopyranosyluronate)-
(1!3)-(2-deoxy-2-N-phthalimido-4,6-O-benzyli-
dene-b-d-glucopyranosyl)-(1!4)-(benzyl-2-O-benzoyl-3-O-benzyl-b-d-
glucopyranosyluronate)-
(1!3)-(2-deoxy-2-N-phthalimido-4,6-O-benzyli-
dene-b-d-glucopyranosyl)-
ACHTREUNG
ACHTREUNG
Acknowledgements
A
H
R
U
(1!4)-(benzyl-2-O-benzoyl-3-O-benzyl-b-d-
glucopyranosyluronate)-(1!3)-(2-deoxy-2-N-phthalimido-4,6-O-benzyli-
dene-b-d-glucopyranoside) (30): Compound 30 was synthesized from
This work was supported by the University of Toledo and the National
Institutes of Health (R01-GM-72667).
[
29]
compound 1 (70 mg, 30 mmol) following the general procedures of oxi-
1
dation and benzyl ester formation in 82% overall yield. H NMR
(
(
3
2
3
1
600 MHz, CD
s, 9H; (CH
2
Cl
2
): d=ꢀ0.14 (s, 3H; CH
3
Si), ꢀ0.26 (s, 3H; CH
3
Si), 0.72
3
[1] R. C. Larock in Comprehensive Organic Transformations, Wiley-
VCH, New York, 1999, pp. 1646–1650.
[2] B. K. S. Yeung, P. Y. C. Chong, P. A. Petillo in Glycochemistry. Prin-
ciples, Synthesis, and Applications, (Eds.: P. G. Wang and C. R. Ber-
tozzi), Marcel Dekker, New York, 2001, pp. 425–492.
3
)
3
CSi), 3.04 (t,
J(H,H)=10.2 Hz, 1H), 3.11–3.15 (m, 2H),
A
H
R
U
G
.21–3.31 (m, 5H), 3.27 (s, 3H; MeO), 3.38–3.47 (m, 6H), 3.56–3.61 (m,
3
3
H), 3.67 (t, J
A
C
H
T
R
E
U
N
G
(H,H)=8.4 Hz, 1H), 3.84 (dd, J(H,H)=4.2, 10.2 Hz, 1H),
A
H
R
U
G
3
.93–4.04 (m, 6H), 4.07–4.12 (m, 2H), 4.18 (dd,
H), 4.27–4.38 (m, 6H), 4.45 (d,
J(H,H)=4.2, 9.6 Hz,
A
H
R
U
G
3
3
J(H,H)=12 Hz, 1H), 4.48 (dd, J-
A
H
R
U
G
[
3] a) C. I. Gama, L. C. Hsieh-Wilson, Curr. Opin. Chem. Biol. 2005, 9,
609–619; b) R. Raman, V. Sasisekharan, R. Sasisekharan, Chem.
Biol. 2005, 12, 267–277; c) R. J. Linhardt, T. Toida, Acc. Chem. Res.
A
C
H
T
R
E
U
N
G
(H,H)=8.4, 10.2 Hz, 1H),4.52–4.58 (m, 3H), 4.62–4.68 (m, 3H), 4.97 (d,
J
J
3
3
A
C
H
T
R
E
U
N
G
(H,H)=8.4 Hz, 1H), 4.99 (s, 1H; PhCH), 5.01 (s, 1H; PhCH), 5.03 (d,
3
ACHTREUNG
A
C
H
T
R
E
U
N
G
(H,H)=8.4 Hz, 1H), 5.10 (d,
J
2
2
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3
ACHTREUNG
PhCH), 5.17 (d, J
1
3
(
m, 72H; ArH); C NMR (100 MHz, CD
2
Cl
2
): d=ꢀ5.20 , ꢀ4.30, 17.91,
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2
6
7
9
5.71, 53.59, 53.86, 54.13, 55.14, 55.55, 55.65, 56.96, 65.70, 65.87, 66.31,
3
7.28 ,67.31, 68.21, 68.43, 68.53, 71.89, 72.92, 73.94, 72.18, 74.19, 74.59,
4.74, 75.77, 76.11, 76.96, 77.47, 79.83, 79.87, 80.66, 80.96, 81.15, 82.18,
8.18, 99.54, 99.58, 99.71, 99.79, 100.99, 101.13, 101.47, 123.17–138.33 (ar-
[
2
[
[
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+
(
carbonyl groups); HRMS: m/z calcd for C151
686.8758; found: 2686.8855.
Methyl (benzyl-2-O-benzoyl-3-O-benzyl-4-O-tert-butyldimethylsilyl-b-d-
glucopyranosyluronate)-
3
H141NaN O40Si [M+Na] :
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[
29]
1
tion and benzyl ester formation in 76% overall yield. H NMR
(
(
3
(
600 MHz, CDCl
s, 9H; (CH CSi), 2.89 (s, 1H), 3.31 (t,
H; MeO), 3.52–3.55 (m, 3H), 3.59 (d, J
m, 6H), 4.46 (s, 2H), 4.55–4.58 (d, 2H), 4.66 (dd, J
3
): d=ꢀ0.16 (s, 3H; CH
3
Si), ꢀ0.13 (s 3H; CH
(H,H)=9.0 Hz, 1H), 3.36 (s,
(H,H)=10.8 Hz, 1H), 4.01–4.16
3
Si), 0.77
3
3
)
3
J
ACHTREUNG
3
A
H
R
U
G
3
ACHTREUNG
3
3
ACHTREUNG
1
4
6
H), 4.72 (d,
J
A
C
H
T
R
E
U
N
G
(H,H)=10.2 Hz, 1H), 4.75 (d,
J
3
.84 (d,
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.81–7.55 ppm (m, 39H; ArH); C NMR (150 MHz, CDCl
3
): d=ꢀ4.99,
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Received: March 2, 2006
Published online: April 25, 2006
[
5252
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 5246 – 5252