Studies on the 6-homologation of β-D-idopyranosides

Article abstract of DOI:10.1016/j.carres.2017.04.007

β-D-Idopyranosides are interesting sugars because of their unusual conformational flexibility in the pyranosyl ring, and also their β-1,2-cis-anomeric configuration. Here we report our studies of the regioselective opening of 4,6-O-benzylidene-protected β-D-idopyranosides under reducing conditions, and the subsequent 6-homologation via Swern oxidation and Wittig olefination to afford a 6,7-dideoxy-β-D-ido-hept-6-enopyranoside. This olefination product was found to adopt predominantly ¹C₄ conformation in solution by NMR experiments, which places the vinyl group at a more sterically hindered axial position and creates difficulty in subsequent hydroborations.

Full text of DOI:10.1016/j.carres.2017.04.007

Carbohydrate Research 445 (2017) 65e74
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Studies on the 6-homologation of b-D-idopyranosides
Rachel Hevey 1, Chang-Chun Ling*
Alberta Glycomics Centre, Department of Chemistry, University of Calgary, Calgary, Alberta T2N 1N4, Canada
a r t i c l e i n f o
a b s t r a c t
Article history:
b
-D-Idopyranosides are interesting sugars because of their unusual conformational flexibility in the
pyranosyl ring, and also their -1,2-cis-anomeric configuration. Here we report our studies of the
regioselective opening of 4,6-O-benzylidene-protected -D-idopyranosides under reducing conditions,
and the subsequent 6-homologation via Swern oxidation and Wittig olefination to afford a 6,7-dideoxy-
-D-ido-hept-6-enopyranoside. This olefination product was found to adopt predominantly 1C4 confor-
Received 12 March 2017
Received in revised form
7 April 2017
Accepted 7 April 2017
Available online 8 April 2017
b
b
b
mation in solution by NMR experiments, which places the vinyl group at a more sterically hindered axial
position and creates difficulty in subsequent hydroborations.
Keywords:
Idopyranoside
© 2017 Elsevier Ltd. All rights reserved.
6-Homologation
4,6-O-benzylidene
Reductive opening
O-benzyl ether
Heptopyranosides
1. Introduction
flexible. Indeed, apart from the two chair conformers, idopyranose
is also found to adopt other conformations, depending on its
Idoses are sugars with a limited distribution in nature, which
play crucial roles in different biological processes. For example, L-
idose is found in the repeating disaccharides of both heparin and
heparan sulfate, which are part of glycosaminoglycans that play an
important role in cell differentiation, viral infection, and cancer
metastasis [1e4]. In both heparin and heparan sulfate, the L-idose
particular structural environment [6,7].
Recently, the development of an efficient synthesis for the 6-
deoxy-b-D-ido-heptopyranose and related oligosaccharides of
Campylobacter jejuni HS:4 CPs has drawn our interest due to its
unique structure and potential immunological properties. The 6-
deoxy-
b
-D-ido-heptopyranose is also a very challenging mono-
-1,2-cis-glycosidic linkage and
exists in the
a
-pyranose form and is oxidized at the C6-position to
saccharide to synthesize due to its b
form a uronic acid; extensive sulfation also occurs at the O2-
positions (Fig. 1). Conversely, the D-idose is found in the
repeating disaccharide of bacterial capsular polysaccharides (CPs)
the presence of axial hydroxyl groups at each of the C2, C3, and C4
positions in the monosaccharide 4C1 chair, and as well an unusual
7-carbon backbone with 6-deoxygenation. Previously, we pub-
of Campylobacter jejuni HS:4, in the form of 6-deoxy-
b
-D-hepto-
lished a short, scalable synthesis of
galactopyranosides by carrying out a double inversion at both C2
and C3 of 2,3-di-O-sulfonyl- -D-galactopyranosides via 2,3-
anhydro- -D-talopyranoside intermediates (Scheme 1) [8,9]; the
opening of the 2,3-anhydro- -D-talopyranoside by an alkoxide was
very regio- and stereoselective to afford the orthogonally protected
-D-idopyranoside typically with an O-alkyl group at O3 and a
fused O-benzylidene at O4 and O6. The method was compatible
with a series of nucleophilic alkoxides (MeOꢀ, AllOꢀ, BnOꢀ), and
more importantly, this methodology was also found to be appli-
b-D-idopyranosides from b-D-
pyranose with partial O-phosphoramidation at O2 and O7 [5].
Compared to other monosaccharides, the pyranosyl forms of idoses
are unique due to their enhanced conformational flexibility
because both their 4C1 and 1C4 chair conformers experience
extensive 1,3-diaxial interactions, resulting in relatively high en-
ergy chair conformations. This effectively lowers the energy barrier
between the chair and half-chair conformers during ring flipping,
making polysaccharides containing idopyranose units more
b
b
b
b
cable to the synthesis of oligosaccharides containing
pyranosides. Here we report our initial studies on the 6-
homologation of -linked idopyranosides.
b-linked ido-
* Corresponding author.
b
E-mail address: ccling@ucalgary.ca (C.-C. Ling).
1
Current address: Molecular Pharmacy, Department of Pharmaceutical Sciences,
University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
http://dx.doi.org/10.1016/j.carres.2017.04.007
0008-6215/© 2017 Elsevier Ltd. All rights reserved.

66
R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
compounds (8e11) were purified by chromatography on silica gel.
Unfortunately, the significant overlapping of signals and weak
correlations to OH peaks in the 1H-1H COSY spectra prevented a full
determination of the position (O4 or O6) of the benzyl group in
each case. An acetylation was then performed for each isomer
(8e11), and based on the significant deshielding of the proton at
either C4 or C6 in the acetylated products (12e15). It was disap-
pointing to discover that in fact the desired 4-O-benzylated
regioisomer had been the one formed in only a minor amount in
each case (10, 27%; 11, 19%), and that the major product obtained
was in fact the undesired 6-O-benzylated isomer (8, 61%; 9, 54%).
Similar regioselectivities were observed when the DIBAL-H
reduction was performed in anhydrous hexanes. This is in sharp
contrast with the literature reported on the reductive opening of
4,6-O-benzylidene derivatives of
a-D-gluco- and a-D-mannopyr-
anosides, which afforded the 4-O-benzylated regioisomers in high
yields (>69%). However, our results were consistent with the 4,6-O-
benzylidene-protected a-D-galactopyranoside, which gave the 6-
O-benzylated regioisomer in 80% yield [10]. It is likely that the
axially oriented O4 in both galacto- and idopyranosides (6 and 7)
plays a crucial role in determining regioselectivity. This suggests
that the O4 coordinates the aluminum centre of DIBAL-H prefer-
entially, which selectively activates the O4-side of the acetal; a
subsequent hydride is delivered to O4 to afford the observed 6-O-
benzylated regioisomers (8 and 9).
Since O2 in both substrates 6 and 7 is also axially oriented and
present at the same face of the pyranosyl ring as O4, it was
postulated that a change in the regioselectivity of the DIBAL-H re-
action may occur if an unprotected 2-OH substrate, such as 3-O-
benzylated compound 16, was utilized (Scheme 3). Unfortunately,
formation of the undesired 6-O-benzylated isomer 17 (66% yield)
was still observed as the major product upon reacting compound 16
with DIBAL-H under similar conditions, along with the desired 4-O-
benzyl regioisomer (18, 19% yield) as a minor product. Respective
acetylation of the formed products (/19, /20) helped to confirm
the regiochemistry of the isomers unambiguously. Modification of
the reaction temperatures (from ꢀ72 ꢁC to rt) and solvent (hexanes,
toluene) were again unsuccessful in altering the observed
regioselectivity.
It was therefore decided to try switching from DIBAL-H as re-
agent, to borane as the source of hydride together with a Lewis acid
activator. Using the 3-O-benzyl derivative 7 as a substrate and
BH3$THF/TMSOTf as reagents [11], the desired regioisomer 11 was
obtained without the 4-OH regioisomer (as determined by TLC).
However, the product formation was found to be very sensitive to
the reaction conditions applied (Scheme 4): the desired product 11
was observed to easily undergo over-reduction to form the linear
iditol 21. Carrying out the reduction at lower temperatures (below
0 ꢁC) was not helpful, as the initial reduction did not proceed. It was
found that the reaction temperature needed to be monitored very
Fig. 1. Examples of D- and L-idopyranosides found in nature.
2. Results and discussion
The studies on 6-homologation required the synthesis of ido-
pyranoside substrates with a free 6-OH substituent. Since regiose-
lective reductive acetal openings have been well studied in other
hexose systems, it was envisaged that using methyl 3-O-alkyl-2-O-
benzyl-4,6-O-benzylidene-b-D-idopyranoside derivatives (6 and 7)
[8] could afford the desired substrates. In the literature, DIBAL-H
was reported to reductively open the 4,6-O-benzylidene of
several hexopyranosides in toluene without the need for a Lewis
acid, to afford the 6-OH-4-O-benzyl isomer as a major product in a
regioselective manner [10]. Thus, both compounds 6 and 7 were
subjected to reaction with DIBAL-H using anhydrous toluene as
solvent (Scheme 2). The reactions afforded two products in a
roughly 2:1 ratio yield in each case, as evidenced by TLC, and the
Scheme 1. Key step involving the di-inversion of C2 and C3 in the regio- and stereoselective conversion of D-galactopyranosides into D-idopyranosides.

R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
67
Scheme 2. Attempts at opening methyl 3-O-alkyl-2-O-benzyl-4,6-O-benzylidene-b-D-idopyranosides 6 and 7 with DIBAL-H favoured formation of the undesired regioisomer.
Reagents and Conditions: (a) DIBAL-H, hexanes or toluene; (b) Ac2O/pyridine.
Scheme 3. Reduction of 16 with DIBAL-H again afforded the undesired 6-O-benzyl 17 as the major regioisomer and desired 4-O-benzyl 18 as the minor isomer. Reagents and
Conditions: (a) DIBAL-H, toluene; (b) Ac2O/pyridine.
Scheme 4. Reductive acetal openings of 7 using BH3$THF. Reagents and conditions: (a) BH3$THF, TMSOTf, CH2Cl2, ambient temperature or 0 ꢁC.

68
R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
Scheme 5. A protection-deprotection sequence could be utilized to prepare methyl 2,3,4-tri-O-benzyl-
b-D-idopyranoside 11 in excellent yield. Reagents and conditions: (a) 80%
AcOHeH2O, 60 ꢁC, 3 h; (b) TBDMSCl, pyridine; (c) BnBr, NaH, THF; (d) TBAF, THF.
closely at 0 ꢁC in order to obtain the desired product (11, ~80%);
allowing the reaction to warm up above 5 ꢁC resulted in over
reduction, and after stirring at ambient temperature for 30 min
afforded the undesired iditol 21 in 83% yield (isolated). Unfortu-
nately, at larger scales the method was also found to be difficult to
control and always afforded amounts of the undesired iditol, which
in addition displayed very similar retention on silica to desired
idopyranose 11 resulting in difficult separations, and thus the
method was deemed unsuitable for larger scale synthesis.
could be performed at gram-scale.
With the desired 6-hydroxyl 11 in hand, we attempted to carry
out a 6-homologation via Wittig olefination (Scheme 6). Thus, a
Swern oxidation was initially carried out. Compound 11 was treated
with oxalyl chloride (2.1 equiv.) and DMSO (3.2 equiv.) in
dichloromethane at ꢀ78 ꢁC, followed by treatment with triethyl-
amine for 15 min [12,13]; after warming to ambient temperature,
the starting material was completely consumed. However, the
crude 1H NMR spectrum showed the crude reaction mixture con-
tained two major products in approximately 1:1 ratio. The desired
aldehyde 25 was clearly observed to have formed as a signal at
9.86 ppm (aldehyde proton) was observed in the 1H NMR spec-
trum; however, a second product, presumably the hydrate form of
compound 25 was also observed (this hydration might be due to
contact with trace amounts of water in deuterated chloroform).
Since the aldehyde functionality is known to be unstable, the crude
aldehyde mixture was used directly without further purification.
Crude mixture containing aldehyde 25 was reacted with an ylide
derived from benzyloxymethyltriphenylphosphonium chloride by
treatment with n-butyllithium [14]. However, the reaction afforded
In the face of significant challenge to prepare the desired 6-OH
derivatives of b-D-idopyranosides directly from the 4,6-O-benzy-
lidene-protected derivatives, a multi-step protection-deprotection
strategy was attempted (Scheme 5). Using the 4,6-O-benzylidene
acetal 7 as a starting material, a mild hydrolysis was carried out by
heating a solution of compound 7 in 80% acetic acid-H2O for 3 h.
The resulting 4,6-diol 22 was isolated in 86% yield. The primary
hydroxyl group of compound 22 was then regioselectively pro-
tected using tert-butyldimethylsilyl chloride (TBDMSCl) in anhy-
drous pyridine to afford the desired compound 23 in excellent yield
(95%). The O4 position was subsequently benzylated using standard
conditions (BnBr/NaH) to afford fully protected compound 24 in
quantitative yield. The 6-O-desilylation was finally carried out us-
ing tetra-n-butylammonium fluoride (TBAF) in THF to give the
only a b-elimination product 27 (58% yield) which was formed via
loss of the 4-benzyloxy group of aldehyde 25, and disappointingly
no desired benzyl enolether 26 was identified. It was thought that
the Ph3P]CHOBn might be too bulky, thus presenting significant
steric hindrance for the olefination; therefore, a less sterically
desired methyl 2,3,4-tri-O-benzyl-b-D-idopyranoside 11 in quan-
titative yield. This indirect reaction sequence worked very well and
Scheme 6. Synthetic route for obtaining b-D-ido-heptopyranoside 28 from compound 11 using Wittig olefination, and another attempted olefination with a benzyloxy ylide.
Reagents and conditions: (a) oxalyl chloride, DMSO, Et3N, CH2Cl2; (b) BnOCH2PPhþ3 Clꢀ, n-BuLi, toluene; (c) CH3PPh3þBrꢀ, n-BuLi, toluene; (d) (i) BH3$THF or 9-BBN, (ii) H2O2, NaOH,
MeOH.

R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
69
Fig. 2. 1H-13C HSQC NMR correlation spectrum of methyl 2,3,4-tri-O-benzyl-6,7-dideoxy-
b-D-ido-hept-6-enopyranoside 28 (CDCl3, 400 MHz).
hindered ylide, the methylidenetriphenylphosphorane (generated
in situ by reacting methyl triphenylphosphonium bromide and n-
BuLi) was used to react with the crude aldehyde 25 in anhydrous
toluene [15]. After one hour, the desired heptose 28 was success-
fully formed and isolated in moderate yield (54% yield over two
steps from 11) by column chromatography on silica gel (8 / 15%
EtOAc e hexanes).
substrates related to D-glucopyranosides [15e17]. For example,
Zhang and co-workers reported the hydroboration of methyl 2,3,4-
tri-O-benzyl-6,7-dideoxy-a-D-gluco-hept-6-enopyranoside with 9-
BBN followed by conventional oxidation with hydrogen peroxide;
this afforded the corresponding primary alcohol in 80% yield [17].
The significant difficulty observed during hydroboration of
compound 28 might be due to unfavourable steric interactions as a
result of ring flipping. Many idopyranosides prepared in this and
other work were observed to exist predominantly in one chair
conformer, depending on the nature and position of substituents on
the idopyranosyl rings as well as the compound's ability to form
intramolecular hydrogen bonds [8,18]. Table 1 summarizes the
observed coupling constants of ido-heptopyranoside 28 and
another two representative idopyranosides 9 and 11. As can be seen
for compound 9 that has a 4-hydroxyl group, we observed consis-
The structure of the vinylic derivative 28 was confirmed using
NMR spectroscopy. In support of the structural assignment, the
alkenic proton H-6 was observed at 6.28 ppm as ddd (J ¼ 17.0, 9.8,
9.8 Hz) while the other two alkenic protons H-7a and H-7b were
observed in the 5.24e5.34 ppm region. In the 1H-13C HSQC spec-
trum (Fig. 2), the above alkenic protons were found to correlate
respectively with carbon signals at 136.43 ppm (C-6) and
120.05 ppm (C-7). Furthermore, electrospray high-resolution mass
spectrometry also led further support to the identity of compound
28 (m/z for (MþNa)þ: expected: 483.2142; found: 483.2143).
Unfortunately, subsequent attempts at hydroboration-oxidation
of the alkene functionality of 28 using BH3$THF, followed by H2O2/
HOꢀ oxidation were unsuccessful. The reaction mixture was found
to be a complex mixture which could not be further identified.
Thus, no desired compound 29 was formed. Since one molecule of
BH3 reagent is capable of reacting with up to three molecules of
substrate, we thought that a switch to 9-BBN could help resolve the
problem, as it is only capable of hydroborating one substrate
molecule at a time; in addition, 9-BBN has a larger size which could
result in improved regioselectivity. Unfortunately, even with pro-
longed heating only unreacted starting material was recovered.
These results contrast sharply with the hydroborations of similar
tently small 3J coupling constants (<3.0 Hz) for all JH-1,H-2, JH-2,H-3
,
JH-3,H-4, and JH-4,H-5, which suggests the presence of axial sub-
stituents at C2, C3, and C4, confirming that compound 9 exists
predominantly in a 4C1 chair conformation in solution. This
preferred conformation is probably stabilized by an intramolecular
hydrogen bond between OH-4…O2, as both O2 and OH-4 are
occupying axial positions (Fig. 3). On the other hand, in the case of
analogous compounds 11 and 28, which have small JH-1,H-2
(3.3e3.6 Hz) and intermediate JH-4,H-5 (5.5e5.9 Hz), but large JH-2,H-
3, JH-3,H-4 coupling constants (7.9e8.8 Hz), these coupling patterns
suggest that both compounds exist predominantly in 1C4 chair
conformers in solution; thus, the substituents at C2, C3, and C4
occupy an equatorial position while the substituents at C1 and C5
occupy an axial position. This explains the lower reactivity of

70
R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
1C4 conformer, which places the 5-vinyl group at a more sterically
hindered axial position. We are currently studying other 6-
homologation methods. However, considering the inherent
Table 1
Typical conformations of b
-D-idopyranosides 9, 11, and 28 based on observed 3JH-1,H-
,
2
3JH-2,H-3 3JH-3,H-4 3JH-4,H-5 coupling constants.
, ,
Coupling Constants
Predominantly 4C1
Predominantly 1C4
conformational flexibility issues associated with the b-D-idopyr-
anosides, it is likely that alternative strategies will need to be
developed in order to succeed with the total synthesis of the
desired 6-deoxy-b-D-ido-heptopyranosides.
Compound 9
Compound 11
Compound 28
3JH-1,H-2
3JH-2,H-3
3JH-3,H-4
3JH-4,H-5
0.9 Hz
3.0 Hz
3.0 Hz
<1 Hz
3.3 Hz
7.9 Hz
7.9 Hz
5.5 Hz
3.6 Hz
8.8 Hz
8.7 Hz
5.9 Hz
4. Experimental data
4.1. General methods
All commercial reagents were used as supplied unless otherwise
stated. Thin layer chromatography was performed on Silica Gel 60-
F254 (E. Merck, Darmstadt) with detection by fluorescence, char-
ring with 5% aqueous sulfuric acid, or a ceric ammonium molybdate
solution. Column chromatography was performed on Silica Gel 60
(Silicycle, Ontario) and solvent gradients given refer to stepped
gradients and concentrations are reported as % v/v. Organic solu-
tions were concentrated and/or evaporated to dry under vacuum in
a water bath (<60 ꢁC). Molecular sieves were stored in an oven at
100 ꢁC and flame-dried under vacuum before use. Amberlite IR-
120H ion exchange resin was washed multiple times with MeOH
prior to use. Optical rotations were determined in a 5 cm cell at
20
20
2
ꢁC; [
a]
values are given in units of 10ꢀ1 deg$cm2/g. NMR
D
spectra were recorded on Bruker spectrometers at either 400 MHz
or 600 MHz (as indicated), and the first-order proton chemical
shifts dH and dC are reported in
d (ppm) and referenced to residual
CHCl3
(
dH 7.24, dC 77.23, CDCl3). 1H and 13C NMR spectra were
assigned with the assistance of 2D gCOSY and 2D gHSQC experi-
ments. High-resolution ESI-QTOF mass spectra were recorded on
an Agilent 6520 Accurate Mass Quadrupole Time-of-Flight LC/MS
spectrometer. All of the data were obtained with the assistance of
the analytical services of the Department of Chemistry, University
of Calgary.
4.2. Methyl 3-O-allyl-2,6-di-O-benzyl-
b-D-idopyranoside (8) and
Methyl 3-O-allyl-2,4-di-O-benzyl- -D-idopyranoside (10)
b
A solution of the starting material [8] (6, 1.677 g, 4.065 mmol) in
dry toluene (20 mL) was cooled to ꢀ10 ꢁC, and then DIBAL-H so-
lution (1 M in toluene, 12 mL, 12 mmol) was added portionwise
over 10 min. After 45 min, the reaction solution was diluted with
CH2Cl2 (50 mL), quenched with MeOH (20 mL), and then evapo-
rated to dry. The crude mixture was redissolved into EtOAc
(100 mL), washed with 2 N HCl(aq) solution (3 ꢂ 100 mL), H2O
(100 mL), dried with Na2SO4, filtered, and evaporated to dry. The
crude mixture was purified via column chromatography on silica
using 8 / 10/15% EtOAc e hexanes to afford first 6-O-benzyl
regioisomer 8 as a colourless syrup (1.033 g, 2.492 mmol, 61%
yield), unreacted starting material (134 mg, 0.324 mmol, 8%
recovered), and 4-O-benzyl regioisomer 10 as a colourless syrup
(456 mg, 1.10 mmol, 27% yield). Data for 8: Rf 0.77 (EtOAc: hexanes
Fig. 3. Preferred solution conformations of exemplary
b
-D-idopyranosides 9, 11, and 28
based on 1H NMR spectra. Other compounds such as 8, 14, 15, 17, 18, 19, and 20 were
also found to adopt a 4C1 chair, while compounds 10, 12, and 13 were found to adopt
the 1C4 chair conformation (not shown, see Experimental section).
compound 28 during hydroborations, because it has an axial vinyl
group that experiences increased steric hindrance.
3. Conclusions
We have studied the reductive acetal opening of 4,6-O-benzy-
lidene-protected
b-D-idopyranosides with DIBAL-H and borane/
TMSOTf. It was found that the DIBAL-H-mediated reductive open-
ing in toluene consistently favoured the formation of a secondary
alcohol (4-OH), while the borane/TMSOTf-mediated reductive
opening in dichloromethane favoured the formation of a primary
alcohol (6-OH). However, the latter method was found to be diffi-
cult to control and thus, unsuitable for large scale synthesis. To
prepare the desired regioisomer with a primary hydroxyl group (6-
OH) of the b-D-idopyranosides, it was preferable to follow a more
conventional method using a bulky silyl ether as a temporary
protecting group of the primary hydroxyl position (6-OH). We were
2:3). [
a
]
20: ꢀ81.5ꢁ (c 1.00, CHCl3). 1H NMR (CDCl3, 400 MHz)
dH:
D
7.36e7.25 (m, 10H, Ar), 5.76 (dddd, 1H, J ¼ 17.2, 10.5, 5.6, 5.6 Hz,
OCH2CH]CH2), 5.16 (dddd, 1H, J ¼ 17.5, 1.6, 1.6, 1.6 Hz, OCH2CH¼-
CHaHb), 5.12 (dddd, 1H, J ¼ 10.6, 1.3, 1.3, 1.3 Hz, OCH2CH¼CHaHb),
4.88 (d, 1H, J ¼ 12.2 Hz, PhCHaHb), 4.64 (d, 1H, J ¼ 0.6 Hz, H-1), 4.64
(d, 1H, J ¼ 12.1 Hz, PhCHaHb), 4.61 (d, 1H, J ¼ 11.7 Hz, PhCHaHb),
4.56 (d, 1H, J ¼ 12.0 Hz, PhCHaHb), 4.01 (ddd, 1H, J ¼ 6.4, 5.4, 1.0 Hz,
H-5), 3.95 (dddd, 1H, J ¼ 12.9, 5.5, 1.4, 1.4 Hz, OCHaHbCH]CH2),
3.90 (dddd, 1H, J ¼ 12.9, 5.7, 1.4, 1.4 Hz, OCHaHbCH]CH2), 3.80 (dd,
1H, J ¼ 10.2, 5.2 Hz, H-6a), 3.75 (dd, 1H, J ¼ 10.2, 6.8 Hz, H-6b), 3.70
(dd,1H, J ¼ 3.1, 3.1 Hz, H-3), 3.59e3.58 (m, 2H, H-2 and H-4), 3.57 (s,
3H, OMe), 3.50 (d, 1H, J ¼ 11.1 Hz, 4-OH). 13C NMR (CDCl3, 100 MHz)
successful at 6-homologation of a
olefination, but the obtained -D-ido-heptopyranoside was found
to experience increased conformational flexibility in favour of the
b-D-idopyranoside using Wittig
b

R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
71
d
C: 138.60 (Ar), 137.75 (Ar), 134.18 (OCH2CH]CH2), 128.59 (Ar),
(ddd, 1H, J ¼ 12.0, 5.1, 5.1 Hz, H-6a), 3.82 (ddd, 1H, J ¼ 12.0, 8.2,
5.3 Hz, H-6b), 3.63 (dd, 1H, J ¼ 7.8, 5.5 Hz, H-4), 3.47 (dd, 1H, J ¼ 7.9,
3.5 Hz, H-2), 3.47 (s, 3H, OMe), 2.68 (dd, 1H, J ¼ 8.1, 5.0 Hz, 6-OH).
128.51 (Ar), 128.26 (Ar), 128.12 (Ar), 127.86 (Ar), 127.72 (Ar), 117.69
(OCH2CH]CH2), 101.05 (C-1), 75.78 (C-3), 74.80 (C-2), 74.73 (C-5),
74.39 (PhCH2), 73.77 (PhCH2), 71.21 (OCH2CH]CH2), 70.14 (C-6),
67.11 (C-4), 57.18 (OMe). Anal. calc'd for C24H30O6: C, 69.54; H, 7.30;
found: C, 69.68; H, 7.46. HRMS m/z calc'd for C24H30O6 (MþNa)þ:
437.1935; found: 437.1927.
13C NMR (CDCl3, 100 MHz):
dC 138.63 (Ar), 138.47 (Ar), 138.04 (Ar),
128.71 (Ar), 128.65 (Ar), 128.64 (Ar), 128.30 (Ar), 128.24 (Ar), 128.16
(Ar), 128.09 (Ar), 127.96 (Ar), 100.16 (C-1), 78.45 (C-2), 78.08 (C-4),
77.17 (C-3), k75.30 (C-5), 75.11 (PhCH2), 74.01 (PhCH2), 73.95
(PhCH2), 63.38 (C-6), 57.14 (OMe). HRMS m/z calc'd for C28H32O6
(MþNa)þ: 487.2091; found: 487.2082.
Data for 10: Rf 0.22 (EtOAc: hexanes 2:3). [
a]
20: ꢀ39ꢁ (c 0.97,
D
CHCl3). 1H NMR (CDCl3, 400 MHz)
dH: 7.36e7.24 (m, 10H, Ar), 5.92
(dddd, 1H, J ¼ 17.2, 10.6, 5.6, 5.6 Hz, OCH2CH]CH2), 5.25 (dddd, 1H,
J ¼ 17.2, 1.5, 1.5, 1.5 Hz, OCH2CH¼CHaHb), 5.15 (dddd, 1H, J ¼ 10.4,
1.4, 1.4, 1.4 Hz, OCH2CH¼CHaHb), 4.76 (d, 1H, J ¼ 11.7 Hz, PhCHaHb),
4.73 (d, 1H, J ¼ 12.4 Hz, PhCHaHb), 4.68 (d, 1H, J ¼ 12.3 Hz,
PhCHaHb), 4.58 (d, 1H, J ¼ 11.7 Hz, PhCHaHb), 4.52 (d, 1H, J ¼ 3.3 Hz,
H-1), 4.25 (dddd, 1H, J ¼ 12.6, 5.6, 1.3, 1.3 Hz, OCHaHbCH]CH2),
4.18 (dddd,1H, J ¼ 12.6, 5.7,1.3,1.3 Hz, OCHaHbCH]CH2), 3.95 (ddd,
1H, J ¼ 5.4, 5.4, 5.4 Hz, H-5), 3.89 (dd, 1H, J ¼ 7.7, 7.7 Hz, H-3),
3.91e3.86 (m, 1H, H-6a), 3.81 (ddd, 1H, J ¼ 12.0, 7.5, 5.6 Hz, H-6b),
3.58 (dd, 1H, J ¼ 7.6, 5.5 Hz, H-4), 3.44 (s, 3H, OMe), 3.41 (dd, 1H,
J ¼ 7.9, 3.3 Hz, H-2), 2.82 (dd, 1H, J ¼ 7.4, 5.1 Hz, 6-OH). 13C NMR
4.4. Methyl 6-O-acetyl-3-O-allyl-2,4-di-O-benzyl-b-D-
idopyranoside (12)
The starting material (10, 64 mg, 0.15 mmol) was dissolved into
pyridine (0.50 mL) and Ac2O (0.50 mL) and left mixing at rt. After
18 h, the reaction mixture was heated at 60 ꢁC. After 4 h of heating,
the reaction mixture was concentrated and co-evaporated with
toluene (3 ꢂ 0.5 mL). The crude product was purified via column
chromatography on silica gel using 15% EtOAc e hexanes to afford
the pure product 12 as a colourless syrup (69 mg, 0.15 mmol, quant.
(CDCl3, 100 MHz) dC: 138.29 (Ar), 137.90 (Ar), 134.90 (OCH2CH]
CH2), 128.40 (Ar), 128.33 (Ar), 127.95 (Ar), 127.91 (Ar), 127.84 (Ar),
127.74 (Ar), 116.80 (OCH2CH]CH2), 99.93 (C-1), 77.90 (C-2), 77.53
(C-4), 76.44 (C-3), 75.06 (C-5), 73.66 (PhCH2), 73.58 (PhCH2), 73.32
(OCH2CH]CH2), 62.92 (C-6), 56.78 (OMe). HRMS m/z calc'd for
yield). Rf 0.22 (EtOAc: hexanes 2:3). [
NMR (CDCl3, 400 MHz):
a
]
20: ꢀ16ꢁ (c 0.99, CHCl3). 1H
D
d
H 7.36e7.24 (m, 10H, Ar), 5.88 (dddd, 1H,
J ¼ 17.2, 10.4, 5.7, 5.7 Hz, OCH2CH]CH2), 5.21 (dddd, 1H, J ¼ 17.2, 1.7,
1.6,1.6 Hz, OCH2CH]CHaHb), 5.13 (dddd,1H, J ¼ 10.4,1.7,1.2,1.2 Hz,
OCH2CH]CHaHb), 4.72 (s, 2H, PhCH2), 4.70 (d, 1H, J ¼ 12.0 Hz,
PhCHaHb), 4.59 (d, 1H, J ¼ 11.9 Hz, PhCHaHb), 4.55 (d, 1H, J ¼ 3.2 Hz,
H-1), 4.48 (dd, 1H, J ¼ 11.6, 4.8 Hz, H-6a), 4.35 (dd, 1H, J ¼ 11.6,
8.4 Hz, H-6b), 4.17 (dddd, 1H, J ¼ 12.6, 5.7, 1.4, 1.4 Hz, OCHaHbCH]
CH2), 4.12 (dddd,1H, J ¼ 12.6, 5.8,1.3,1.3 Hz, OCHaHbCH]CH2), 4.10
(ddd, 1H, J ¼ 8.4, 5.1, 4.9 Hz, H-5), 3.75 (dd, 1H, J ¼ 7.4, 7.4 Hz, H-3),
3.52 (dd, 1H, J ¼ 7.3, 5.2 Hz, H-4), 3.46 (s, 3H, OMe), 3.42 (dd, 1H,
C
24H30O6 (MþNa)þ: 437.1946; found: 437.1953.
4.3. Methyl 2,3,6-tri-O-benzyl-
b-D-idopyranoside (9) and Methyl
2,3,4-tri-O-benzyl- -D-idopyranoside (11)
b
A solution of the starting material [8] (7, 110 mg, 0.239 mmol) in
dry toluene (1.0 mL) was cooled to ꢀ30 ꢁC, and then DIBAL-H so-
lution (1.5 M in toluene, 0.56 mL, 0.84 mmol) was added portion-
wise over 10 min. After 2 h, the reaction solution was diluted with
CH2Cl2 (10 mL), quenched with H2O (2 mL), and then evaporated to
dry. The crude mixture was redissolved into EtOAc (20 mL) and H2O
(20 mL), washed with saturated NaCl(aq) solution (2 ꢂ 20 mL), dried
with Na2SO4, filtered, and evaporated to dry. The crude mixture was
purified via column chromatography on silica using 8 / 10/15%
EtOAc e hexanes to afford 6-O-benzyl regioisomer 9 as a colourless
syrup (60 mg, 0.13 mmol, 54% yield) and 4-O-benzyl regioisomer 11
as a colourless syrup (21 mg, 0.045 mmol, 19% yield). Data for 9: Rf
J ¼ 7.4, 3.2 Hz, H-2), 2.01 (s, 3H, Ac). 13C NMR (CDCl3, 100 MHz):
dC
170.95 (Ac), 138.62 (Ar), 138.19 (Ar), 135.02 (OCH2CH]CH2), 128.52
(Ar), 128.19 (Ar), 128.04 (Ar), 127.92 (Ar), 117.19 (OCH2CH]CH2),
100.75 (C-1), 77.44 (C-2), 76.67 (C-4), 75.96 (C-3), 73.93 (PhCH2),
73.43 (OCH2CH]CH2), 73.10 (PhCH2), 72.77 (C-5), 64.43 (C-6),
56.73 (OMe), 21.10 (Ac). HRMS m/z calc'd for C26H32O7 (MþNa)þ:
479.2040; found: 479.2042.
4.5. Methyl 2,3,4-tri-O-benzyl-6-O-acetyl-b-D-idopyranoside (13)
0.67 (EtOAc: hexanes 2:3). [
(CDCl3, 400 MHz)
a
]
20: ꢀ30ꢁ (c 0.94, CHCl3). 1H NMR
D
d
H: 7.35e7.28 (m, 13H, Ar), 7.23e7.20 (m, 2H, Ar),
The starting material (11, 12 mg, 0.025 mmol) was dissolved into
pyridine (0.30 mL) and Ac2O (0.30 mL) and left mixing at 60 ꢁC.
After 1 h, the reaction mixture was concentrated and co-evaporated
with toluene (1 mL). The crude product was purified via column
chromatography on silica gel using 15% acetone e hexanes to afford
the pure product 13 as a colourless syrup (13 mg, 0.026 mmol,
4.84 (d, 1H, J ¼ 12.2 Hz, PhCHaHb), 4.69 (d, 1H, J ¼ 0.9 Hz, H-1), 4.63
(d, 1H, J ¼ 11.9 Hz, PhCHaHb), 4.62 (d, 1H, J ¼ 12.2 Hz, PhCHaHb),
4.57 (d, 1H, J ¼ 12.0 Hz, PhCHaHb), 4.50 (d, 1H, J ¼ 11.9 Hz,
PhCHaHb), 4.45 (d, 1H, J ¼ 11.9 Hz, PhCHaHb), 4.07 (ddd, 1H, J ¼ 6.7,
5.5, <1.0 Hz, H-5), 3.82 (dd, 1H, J ¼ 10.2, 5.2 Hz, H-6a), 3.78 (dd, 1H,
J ¼ 3.0, 3.0 Hz, H-3), 3.77 (dd, 1H, J ¼ 10.1, 6.7 Hz, H-6b), 3.65 (dd,
1H, J ¼ 2.6, <1.0 Hz, H-4), 3.62 (dd, 1H, J ¼ 3.3, <1.0 Hz, H-2), 3.57 (s,
quant. yield). Rf 0.55 (acetone: hexanes 2:3). [
a
]
20: ꢀ5.4ꢁ (c 1.03,
D
CHCl3). 1H NMR (CDCl3, 400 MHz):
dH 7.34e7.24 (m, 15H, Ar), 4.72
3H, OMe). 13C NMR (CDCl3, 100 MHz)
dC: 138.61 (Ar), 137.70 (Ar),
(d, 1H, J ¼ 12.4 Hz, PhCHaHb), 4.70 (d, 1H, J ¼ 10.6 Hz, PhCHaHb),
4.69 (d, 1H, J ¼ 12.4 Hz, PhCHaHb), 4.66 (d, 1H, J ¼ 11.7 Hz,
PhCHaHb), 4.63 (d,1H, J ¼ 10.9 Hz, PhCHaHb), 4.57 (d,1H, J ¼ 3.2 Hz,
H-1), 4.55 (d,1H, J ¼ 11.8 Hz, PhCHaHb), 4.49 (dd,1H, J ¼ 11.7, 4.8 Hz,
H-6a), 4.37 (dd, 1H, J ¼ 11.7, 8.4 Hz, H-6b), 4.13 (ddd, 1H, J ¼ 8.4, 4.9,
4.9 Hz, H-5), 3.86 (dd, 1H, J ¼ 7.3, 7.3 Hz, H-3), 3.56 (dd, 1H, J ¼ 7.2,
5.1 Hz, H-4), 3.48 (dd,1H, J ¼ 7.4, 3.1 Hz, H-2), 3.47 (s, 3H, OMe), 2.02
137.68 (Ar), 128.66 (Ar), 128.59 (Ar), 128.52 (Ar), 128.25 (Ar), 128.12
(Ar), 127.86 (Ar), 127.73 (Ar), 101.02 (C-1), 75.93 (C-3), 74.76 (C-5),
74.72 (C-2), 74.33 (PhCH2), 73.78 (PhCH2), 72.23 (PhCH2), 70.15 (C-
6), 67.07 (C-4), 57.17 (OMe). Anal. calc'd for C28H32O6: C, 72.39; H,
6.94; found: C, 72.28; H, 7.10. HRMS m/z calc'd for C28H32O6
(MþNa)þ: 487.2091; found: 487.2084.
Data for 11: Rf 0.42 (acetone: hexanes 2:3). [
CHCl3). 1H NMR (CDCl3, 400 MHz):
a
]
20: ꢀ20.5ꢁ (c 1.03,
(s, 3H, Ac). 13C NMR (CDCl3, 100 MHz):
dC 171.01 (Ac), 138.61 (Ar),
D
d
H 7.37e7.24 (m, 15H, Ar), 4.80
138.51 (Ar), 138.14 (Ar), 128.62 (Ar), 128.60 (Ar), 128.57 (Ar), 128.27
(Ar), 128.18 (Ar), 128.15 (Ar), 128.00 (Ar), 127.98 (Ar), 100.77 (C-1),
77.61 (C-2), 76.76 (C-4), 76.29 (C-3), 74.80 (PhCH2), 73.97 (PhCH2),
73.07 (PhCH2), 72.80 (C-5), 64.49 (C-6), 56.80 (OMe), 21.16 (Ac).
(d, 1H, J ¼ 11.1 Hz, PhCHaHb), 4.76 (d, 1H, J ¼ 11.7 Hz, PhCHaHb),
4.74 (d, 1H, J ¼ 12.1 Hz, PhCHaHb), 4.71 (d, 1H, J ¼ 11.0 Hz,
PhCHaHb), 4.67 (d, 1H, J ¼ 12.2 Hz, PhCHaHb), 4.55 (d, 1H,
J ¼ 11.6 Hz, PhCHaHb), 4.53 (d, 1H, J ¼ 3.3 Hz, H-1), 4.03 (dd, 1H,
J ¼ 7.9, 7.9 Hz, H-3), 3.96 (ddd, 1H, J ¼ 5.4, 5.4, 5.4 Hz, H-5), 3.90
HRMS m/z calc'd for
529.2199.
C
30H34O7 (MþNa)þ: 529.2197; found:

72
R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
4.6. Methyl 4-O-acetyl-3-O-allyl-2,6-di-O-benzyl-
idopyranoside (14)
b
-D-
column chromatography on silica gel using 10 / 15% acetone e
hexanes to afford both the 6-O-benzyl isomer 17 (127 mg,
0.340 mmol, 66% yield), followed by the 4-O-benzyl isomer 18
(38 mg, 0.10 mmol, 19% yield). Data for 17: Rf 0.39 (EtOAc: hexanes
The starting material (8, 63 mg, 0.15 mmol) was dissolved into
pyridine (0.50 mL) and Ac2O (0.50 mL) and left mixing at 45 ꢁC.
After 18 h, the reaction mixture was concentrated and co-
evaporated with toluene (2 ꢂ 1 mL). The crude product was puri-
fied via column chromatography on silica gel using 10% acetone e
hexanes to afford the pure product 14 as a colourless syrup (69 mg,
1:1). [
a]
20: ꢀ12.9ꢁ (c 1.01, CHCl3). 1H NMR (CDCl3, 400 MHz):
dH
D
7.37e7.25 (m, 10H, Ar), 4.65 (d, 1H, J ¼ 0.8 Hz, H-1), 4.61 (d, 1H,
J ¼ 12.0 Hz, PhCHaHb), 4.59 (s, 2H, PhCH2), 4.57 (d, 1H, J ¼ 11.9 Hz,
PhCHaHb), 4.02 (ddd, 1H, J ¼ 5.9, 4.9, 0.9 Hz, H-5), 3.87 (dd, 1H,
J ¼ 3.0, 3.0 Hz, H-3), 3.82 (dd, 1H, J ¼ 10.3, 4.8 Hz, H-6a), 3.83e3.81
(m, 1H, H-2), 3.77 (dd, 1H, J ¼ 10.3, 6.0 Hz, H-6b), 3.74 (dddd, 1H,
J ¼ 9.0, 2.8,1.1,1.0 Hz, H-4), 3.69 (d,1H, J ¼ 9.0 Hz, 4-OH), 3.57 (s, 3H,
0.15 mmol, quant. yield). Rf 0.38 (acetone: hexanes 1:4). [
a]
20: ꢀ66ꢁ
D
(c 0.97, CHCl3). 1H NMR (CDCl3, 400 MHz):
dH 7.34e7.22 (m, 10H,
Ar), 5.77 (dddd, 1H, J ¼ 17.2, 10.4, 5.5, 5.5 Hz, OCH2CH]CH2), 5.18
(dddd,1H, J ¼ 17.2, 1.5, 1.5,1.5 Hz, OCH2CH]CHaHb), 5.11 (dddd,1H,
J ¼ 10.4, 1.4, 1.4, 1.4 Hz, OCH2CH]CHaHb), 4.79 (d, 1H, J ¼ 12.5 Hz,
PhCHaHb), 4.74e4.73 (m, 1H, H-4), 4.60 (d, 1H, J ¼ 1.9 Hz, H-1), 4.59
(d, 1H, J ¼ 12.0 Hz, PhCHaHb), 4.55 (d, 1H, J ¼ 12.7 Hz, PhCHaHb),
4.45 (d, 1H, J ¼ 12.0 Hz, PhCHaHb), 4.15 (ddd, 1H, J ¼ 6.4, 6.4, 2.4 Hz,
H-5), 4.04 (dddd, 1H, J ¼ 12.9, 5.3, 1.4, 1.4 Hz, OCHaHbCH]CH2),
3.98 (dddd, 1H, J ¼ 12.9, 5.7, 1.4, 1.4 Hz, OCHaHbCH]CH2), 3.73 (dd,
1H, J ¼ 3.7, 3.7 Hz, H-3), 3.69 (dd, 1H, J ¼ 9.8, 6.3 Hz, H-6a), 3.65 (dd,
1H, J ¼ 9.8, 6.5 Hz, H-6b), 3.52 (s, 3H, OMe), 3.44 (ddd, 1H, J ¼ 3.8,
OMe), 2.93 (d, 1H, J ¼ 3.3 Hz, 2-OH). 13C NMR (CDCl3, 100 MHz):
dC
138.25 (Ar), 137.80 (Ar), 128.72 (Ar), 128.63 (Ar), 128.20 (Ar), 127.96
(Ar),127.93 (Ar), 127.77 (Ar), 99.84 (C-1), 76.21 (C-3), 73.94 (PhCH2),
73.71 (C-5), 72.54 (PhCH2), 70.69 (C-6), 68.86 (C-2), 67.54 (C-4),
56.87 (OMe). HRMS m/z calc'd for C21H26O6 (MþNa)þ: 397.1622;
found: 397.1616.
Data for 18: Rf 0.27 (EtOAc: hexanes 1:1). [
a]
20: ꢀ36.2ꢁ (c 1.08,
D
CHCl3). 1H NMR (CDCl3, 400 MHz):
dH 7.39e7.26 (m, 8H, Ar),
7.24e7.19 (m, 2H, Ar), 4.65 (d, 1H, J ¼ 1.4 Hz, H-1), 4.65e4.62 (m, 1H,
PhCHaHb), 4.61 (d, 1H, J ¼ 11.8 Hz, PhCHaHb), 4.53 (d, 1H,
J ¼ 11.9 Hz, PhCHaHb), 4.35 (d, 1H, J ¼ 11.7 Hz, PhCHaHb), 3.96e3.92
(m, 1H, H-5), 3.93 (dd, 1H, J ¼ 3.4, 3.4 Hz, H-3), 3.89 (ddd, 1H,
J ¼ 11.0, 7.2, 3.9 Hz, H-6a), 3.77 (dddd, 1H, J ¼ 10.8, 3.6, 1.3, 1.3 Hz, H-
2), 3.60 (ddd, 1H, J ¼ 11.0, 8.6, 4.5 Hz, H-6b), 3.56 (s, 3H, OMe),
3.43e3.39 (m, 1H, H-4), 3.22 (d, 1H, J ¼ 10.8 Hz, 2-OH), 1.80 (dd, 1H,
1.7, <1 Hz, H-2), 1.94 (s, 3H, Ac). 13C NMR (CDCl3, 100 MHz):
dC
171.01 (Ac), 138.71 (Ar), 138.30 (Ar), 134.28 (OCH2CH]CH2), 128.61
(Ar), 128.48 (Ar), 128.02 (Ar), 127.99 (Ar), 127.90 (Ar), 127.84 (Ar),
117.71 (OCH2CH]CH2), 101.10 (C-1), 74.90 (C-2), 74.20 (PhCH2),
74.12 (C-3), 73.69 (PhCH2), 72.35 (C-5), 71.82 (OCH2CH]CH2), 68.97
(C-6), 68.00 (C-4), 57.04 (OMe), 21.18 (Ac). HRMS m/z calc'd for
J ¼ 8.6, 3.9 Hz, 6-OH). 13C NMR (CDCl3, 100 MHz):
dC 137.70 (Ar),
C
26H32O7 (MþNH4)þ: 474.2486; found: 474.2493.
136.90 (Ar), 128.86 (Ar), 128.82 (Ar), 128.63 (Ar), 128.59 (Ar), 128.36
(Ar), 127.97 (Ar), 100.82 (C-1), 74.85 (C-5), 73.97 (C-3), 73.65 (C-4),
72.76 (PhCH2), 68.78 (C-2), 62.56 (C-6), 57.21 (OMe). HRMS m/z
calc'd for C21H26O6 (MþNa)þ: 397.1622; found: 397.1624.
4.7. Methyl 4-O-acetyl-2,3,6-tri-O-benzyl-b-D-idopyranoside (15)
The starting material (9, 43 mg, 0.093 mmol) was dissolved into
pyridine (0.50 mL) and Ac2O (0.50 mL) and left mixing at 60 ꢁC.
After 3 h, the reaction mixture was concentrated and co-evaporated
with toluene (3 ꢂ 1 mL). The crude product was purified via column
chromatography on silica gel using 10% acetone e hexanes to afford
the pure product 15 as a colourless syrup (44 mg, 0.087 mmol, 94%
4.9. Methyl 2,4-di-O-acetyl-3,6-di-O-benzyl-b-D-idopyranoside
(19)
The starting material (17, 82 mg, 0.22 mmol) was dissolved into
pyridine (0.50 mL) and Ac2O (0.50 mL) and left mixing at 60 ꢁC.
After 3 h, the reaction mixture was evaporated to dry via co-
evaporation with toluene (2 ꢂ 1 mL). The crude product was pu-
rified via column chromatography on silica gel using 15% acetone e
hexanes to afford the pure product 19 as a colourless syrup (102 mg,
yield). Rf 0.72 (acetone: hexanes 2:3). [
a
]
20: ꢀ54ꢁ (c 0.95, CHCl3). 1H
D
NMR (CDCl3, 400 MHz):
dH 7.34e7.20 (m, 15H, Ar), 4.82 (ddd, 1H,
J ¼ 3.6, 2.5, <1 Hz, H-4), 4.71 (d, 1H, J ¼ 12.5 Hz, PhCHaHb), 4.63 (d,
1H, J ¼ 1.8 Hz, H-1), 4.62 (d, 1H, J ¼ 11.9 Hz, PhCHaHb), 4.59, (d, 1H,
J ¼ 12.2 Hz, PhCHaHb), 4.52 (d, 1H, J ¼ 11.8 Hz, PhCHaHb), 4.50 (d,
1H, J ¼ 12.5 Hz, PhCHaHb), 4.45 (d, 1H, J ¼ 12.0 Hz, PhCHaHb), 4.20
(ddd, 1H, J ¼ 6.4, 6.4, 2.5 Hz, H-5), 3.83 (dd, 1H, J ¼ 3.7, 3.7 Hz, H-3),
3.69, (dd, 1H, J ¼ 9.9, 6.3 Hz, H-6a), 3.66 (dd, 1H, J ¼ 9.9, 6.5 Hz, H-
6b), 3.51 (s, 3H, OMe), 3.45 (ddd, 1H, J ¼ 3.8, 1.8, <1 Hz, H-2), 1.92 (s,
0.22 mmol, quant. yield). Rf 0.59 (EtOAc: hexanes 1:1). [
a
]
20: ꢀ37.2ꢁ
D
(c 1.02, CHCl3). 1H NMR (CDCl3, 400 MHz):
dH 7.38e7.24 (m, 10H,
Ar), 4.98 (ddd, 1H, J ¼ 3.1, 1.7, 0.9 Hz, H-2), 4.90 (ddd, 1H, J ¼ 2.9, 2.0,
0.9 Hz, H-4), 4.75 (d, 1H, J ¼ 1.7 Hz, H-1), 4.72 (d, 1H, J ¼ 11.8 Hz,
PhCHaHb), 4.68 (d, 1H, J ¼ 11.8 Hz, PhCHaHb), 4.59 (d, 1H,
J ¼ 12.0 Hz, PhCHaHb), 4.44 (d, 1H, J ¼ 12.0 Hz, PhCHaHb), 4.23
(ddd, 1H, J ¼ 6.4, 6.4, 1.9 Hz, H-5), 3.83 (dd, 1H, J ¼ 3.1, 3.1 Hz, H-3),
3.67 (dd, 1H, J ¼ 9.8, 6.3 Hz, H-6a), 3.64 (dd, 1H, J ¼ 9.8, 6.6 Hz, H-
6b), 3.52 (s, 3H, OMe), 2.07 (s, 3H, Ac), 1.96 (s, 3H, Ac). 13C NMR
3H, Ac). 13C NMR (CDCl3, 100 MHz):
dC 171.02 (Ac), 138.61 (Ar),
138.31 (Ar), 137.94 (Ar), 128.64 (Ar), 128.62 (Ar), 128.47 (Ar), 128.08
(Ar), 128.01 (Ar), 127.99 (Ar), 127.92 (Ar), 127.90 (Ar), 127.83 (Ar),
101.03 (C-1), 75.07 (C-2), 74.35 (C-3), 74.09 (PhCH2), 73.70 (PhCH2),
72.95 (PhCH2), 72.37 (C-5), 68.99 (C-6), 67.95 (C-4), 57.04 (OMe),
21.16 (Ac). HRMS m/z calc'd for C30H34O7 (MþNa)þ: 529.2197;
found: 529.2192.
(CDCl3, 100 MHz): dC 170.33 (Ac), 170.29 (Ac), 138.15 (Ar), 137.51
(Ar), 128.69 (Ar), 128.64 (Ar), 128.23 (Ar), 128.03 (Ar), 127.97 (Ar),
127.89 (Ar), 98.98 (C-1), 73.86 (C-3), 73.76 (PhCH2), 73.05 (PhCH2),
72.32 (C-5), 68.62 (C-6), 67.88 (C-2), 66.99 (C-4), 57.30 (OMe), 21.18
(Ac), 20.97 (Ac). HRMS m/z calc'd for C25H30O8 (MþNa)þ: 481.1833;
found: 481.1829.
4.8. Methyl 3,6-di-O-benzyl-
b-D-idopyranoside (17) and Methyl
3,4-di-O-benzyl- -D-idopyranoside (18)
b
A solution of the starting material [8] (16, 192 mg, 0.516 mmol)
in dry toluene (2.0 mL) was flushed with Ar, cooled to 0 ꢁC in an ice-
H2O bath, and then DIBAL-H solution (1.5 M in toluene, 1.6 mL,
2.4 mmol) was added dropwise. The reaction flask was warmed to
rt, and after 2 d diluted with CH2Cl2 (100 mL). The reaction was
quenched with MeOH (5 mL), then washed with 2 N HCl(aq) solution
(2 ꢂ 100 mL), H2O (2 ꢂ 100 mL), dried with Na2SO4, filtered, and
evaporated to dry. The crude reaction mixture was purified via
4.10. Methyl 2,6-di-O-acetyl-3,4-di-O-benzyl-b-D-idopyranoside
(20)
The starting material (18, 27 mg, 0.072 mol) was dissolved into
pyridine (0.40 mL) and Ac2O (0.40 mL) and left mixing at 60 ꢁC.
After 3 h, the reaction mixture was concentrated and co-evaporated
with toluene (2 ꢂ 1 mL). The crude product was purified via column
chromatography on silica gel using 15% acetone e hexanes to afford

R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
73
the pure product 20 as a colourless syrup (33 mg, 0.071 mmol, 98%
1H, J ¼ 8.9, 6.4 Hz, H-6a), 3.86 (ddd, 1H, J ¼ 7.2, 6.3, 1.0 Hz, H-5),
3.81e3.76 (m, 2H, H-6b and H-3), 3.66 (dddd, 1H, J ¼ 11.8, 2.9, 1.2,
1.2 Hz, H-4), 3.59 (ddd,1H, J ¼ 3.3,1.1,1.1 Hz, H-2), 3.54 (s, 3H, OMe),
3.42 (d, 1H, J ¼ 11.8 Hz, 4-OH), 0.89 (s, 9H, C(CH3)3), 0.07 (s, 6H,
yield). Rf 0.60 (EtOAc: hexanes 1:1). [
NMR (CDCl3, 400 MHz):
a
]
20: ꢀ19.6ꢁ (c 1.02, CHCl3). 1H
D
d
H 7.38e7.24 (m, 8H, Ar), 7.23e7.18 (m, 2H,
Ar), 4.90 (ddd, 1H, J ¼ 4.8, 2.4, <1 Hz, H-2), 4.77 (d, 1H, J ¼ 2.4 Hz, H-
1), 4.70 (d, 1H, J ¼ 11.8 Hz, PhCHaHb), 4.62 (d, 1H, J ¼ 11.8 Hz,
PhCHaHb), 4.49 (d, 1H, J ¼ 11.7 Hz, PhCHaHb), 4.38 (d, 1H,
J ¼ 11.8 Hz, PhCHaHb), 4.37 (dd, 1H, J ¼ 11.4, 7.4 Hz, H-6a), 4.33 (dd,
1H, J ¼ 11.5, 5.6 Hz, H-6b), 4.11 (ddd, 1H, J ¼ 7.3, 5.6, 3.2 Hz, H-5),
3.94 (dd, 1H, J ¼ 4.8, 4.8 Hz, H-3), 3.50 (s, 3H, OMe), 3.43e3.40 (m,
1H, H-4), 2.02 (s, 3H, Ac), 2.00 (s, 3H, Ac). 13C NMR (CDCl3,
SiMe). 13C NMR (CDCl3,100 MHz):
dC 137.83 (Ar),137.82 (Ar),128.69
(Ar), 128.61 (Ar), 128.25 (Ar), 128.15 (Ar), 128.10 (Ar), 127.82 (Ar),
101.21 (C-1), 76.08 (C-3), 76.00 (C-5), 75.03 (C-2), 74.31 (PhCH2),
72.27 (PhCH2), 66.23 (C-4), 62.26 (C-6), 57.12 (OMe), 26.10
(C(CH3)3), 18.49 (C(CH3)3), ꢀ5.10 (SiMe), ꢀ5.17 (SiMe). HRMS m/z
calc'd for C27H40O6Si (MþNa)þ: 511.2486; found: 511.2490.
100 MHz):
dC 171.06 (Ac), 170.92 (Ac), 137.88 (Ar), 137.70 (Ar),
128.73 (Ar), 128.61 (Ar), 128.24 (Ar), 128.20 (Ar), 128.15 (Ar), 128.08
(Ar), 99.04 (C-1), 74.25 (C-4), 73.59 (PhCH2), 72.90 (C-3), 72.65 (C-
5), 72.62 (PhCH2), 69.23 (C-2), 63.76 (C-6), 57.04 (OMe), 21.27 (Ac),
21.07 (Ac). HRMS m/z calc'd for C25H30O8 (MþNa)þ: 481.1833;
found: 481.1831.
4.13. Methyl 2,3,4-tri-O-benzyl-6-O-(tert-butyldimethylsilyl)-b-D-
idopyranoside (24)
The starting material (23, 402 mg, 0.823 mmol), benzyl bromide
(0.18 mL, 1.5 mmol), and NaH (57e63% oil dispersion, 85 mg,
2.1 mmol) in dry THF (5 mL) were left mixing at rt under Ar. After
14 h, the reaction mixture was quenched with MeOH (1 mL),
evaporated to dry, and then redissolved into EtOAc (50 mL). The
organic phase was washed with saturated NaCl(aq) solution
(2 ꢂ 50 mL), dried with Na2SO4, filtered, and evaporated to dry. The
crude material was purified via column chromatography on silica
using 10% acetone e hexanes to afford the pure product 24 as a
colourless syrup (495 mg, 0.856 mmol, quant. yield). Rf 0.78
4.11. Methyl 2,3,4-tri-O-benzyl-b-D-idopyranoside (11) and 2,3,4-
tri-O-benzyl-1-O-methyl-D-iditol (21)
The starting material [8] (7, 103 mg, 0.222 mmol) was dissolved
into dry CH2Cl2 (1.0 mL), cooled to 0 ꢁC, and then BH3$THF solution
(1 M in THF, 1.00 mL, 1.00 mmol) and TMSOTf (6 mL, 0.03 mmol)
were added dropwise. The solution was slowly warmed back to rt,
and after 2 h was neutralized with Et3N (to pH 8), quenched with
H2O (2 mL), and diluted with CH2Cl2 (30 mL). The organic phase
was washed with saturated NaCl(aq) solution (2 ꢂ 30 mL), H2O
(30 mL), dried with Na2SO4, filtered, and evaporated to dry. The
crude mixture was purified via column chromatography on silica
using 10 / 15/20% acetone e hexanes to afford by-product 21 as
a colourless syrup (86 mg, 0.18 mmol, 83% yield). Alternatively, if
the same reaction was left at 0 ꢁC instead of warmed to rt, the
desired product 11 was obtained in similar yields. Data for 21: Rf
(acetone: hexanes 2:3). [
a
]
20: ꢀ22.4ꢁ (c 1.02, CHCl3). 1H NMR
D
(CDCl3, 400 MHz):
dH 7.34e7.20 (m, 15H, Ar), 4.74 (d, 1H,
J ¼ 12.5 Hz, PhCHaHb), 4.66 (d, 1H, J ¼ 12.5 Hz, PhCHaHb), 4.61 (d,
1H, J ¼ 11.9 Hz, PhCHaHb), 4.59 (d, 1H, J ¼ 2.7 Hz, H-1), 4.56 (d, 1H,
J ¼ 11.5 Hz, PhCHaHb), 4.52 (d, 1H, J ¼ 11.9 Hz, PhCHaHb), 4.50 (d,
1H, J ¼ 11.4 Hz, PhCHaHb), 3.94e3.89 (m, 3H, H-5, H-6a, and H-6b),
3.77 (dd, 1H, J ¼ 5.8, 5.8 Hz, H-3), 3.54e3.50 (m, 4H, H-4 and OMe),
3.48 (dd, 1H, J ¼ 5.9, 2.7 Hz, H-2), 0.89 (s, 9H, C(CH3)3), 0.06 (s, 3H,
SiMe), 0.05 (s, 3H, SiMe). 13C NMR (CDCl3, 100 MHz):
dC 138.90 (Ar),
0.50 (acetone: hexanes 2:3). [
(CDCl3, 400 MHz):
a
]
20: ꢀ20ꢁ (c 0.99, CHCl3). 1H NMR
138.60 (Ar), 138.46 (Ar), 128.58 (Ar), 128.48 (Ar), 128.46 (Ar), 128.24
(Ar), 128.20 (Ar), 128.06 (Ar), 127.93 (Ar), 127.80 (Ar), 127.79 (Ar),
100.84 (C-1), 76.76 (C-2), 76.21 (C-5), 75.94 (C-3), 75.64 (C-4), 73.88
(PhCH2), 73.00 (PhCH2), 62.57 (C-6), 56.79 (OMe), 26.16 (C(CH3)3),
18.50 (C(CH3)3), ꢀ5.06 (SiMe), ꢀ5.11 (SiMe). HRMS m/z calc'd for
D
d
H 7.34e7.24 (m,15H, Ar), 4.79 (d,1H, J ¼ 11.2 Hz,
PhCHaHb), 4.73 (d, 1H, J ¼ 11.8 Hz, PhCHaHb), 4.70 (d, 1H,
J ¼ 11.6 Hz, PhCHaHb), 4.62 (d, 1H, J ¼ 11.4 Hz, PhCHaHb), 4.54 (d,
1H, J ¼ 11.8 Hz, PhCHaHb), 4.52 (d, 1H, J ¼ 11.2 Hz, PhCHaHb), 3.88
(dd, 1H, J ¼ 7.2, 3.9 Hz, H-3), 3.77 (ddd, 1H, J ¼ 5.1, 5.1, 4.0 Hz, H-2),
3.64 (dd, 1H, J ¼ 7.2, 3.0 Hz, H-4), 3.59e3.51 (m, 3H, H-1a, H-1b, and
H-5), 3.50 (ddd, 1H, J ¼ 11.0, 6.2, 4.5 Hz, H-6a), 3.38 (ddd, 1H,
J ¼ 11.0, 8.4, 4.4, H-6b), 3.27 (s, 3H, OMe), 2.61 (d, 1H, J ¼ 6.7 Hz, 5-
OH), 1.85 (dd, 1H, J ¼ 8.3, 4.4 Hz, 6-OH). 13C NMR (CDCl3, 100 MHz):
C
34H46O6Si (MþNa)þ: 601.2956; found: 601.2951.
4.14. Methyl 2,3,4-tri-O-benzyl-b-D-idopyranoside (11)
The starting material (24, 508 mg, 0.877 mmol) and tetrabutyl
ammonium fluoride solution (1 M in THF, 1.00 mL, 1.00 mmol) in
dry THF (5.0 mL) were left mixing at rt under Ar. After 2 h the re-
action mixture was evaporated to dry, and the crude material pu-
rified via column chromatography on silica using 14 / 20% acetone
e hexanes to afford the pure product 11 as a colourless syrup
(405 mg, 0.872 mmol, quant. yield); characterization of the product
agreed with the previously published literature [12,13]. Rf 0.42
dC 138.35 (Ar), 138.33 (Ar), 138.16 (Ar), 128.73 (Ar), 128.67 (Ar),
128.63 (Ar), 128.58 (Ar), 128.57 (Ar), 128.51 (Ar), 128.21 (Ar), 128.08
(Ar), 128.05 (Ar), 79.50 (C-4), 78.97 (C-3), 76.83 (C-2), 75.02
(PhCH2), 74.83 (PhCH2), 72.98 (PhCH2), 72.45 (C-1), 71.24 (C-5),
64.52 (C-6), 59.24 (OMe). HRMS m/z calc'd for C28H34O6 (MþNa)þ:
489.2248; found: 489.2264.
4.12. Methyl 2,3-di-O-benzyl-6-O-(tert-butyldimethylsilyl)-
b-D-
(acetone: hexanes 2:3). [
a
]
20: ꢀ20.5ꢁ (c 1.03, CHCl3). 1H NMR
D
idopyranoside (23)
(CDCl3, 400 MHz):
dH 7.37e7.24 (m,15H, Ar), 4.80 (d,1H, J ¼ 11.1 Hz,
PhCHaHb), 4.76 (d, 1H, J ¼ 11.7 Hz, PhCHaHb), 4.74 (d, 1H,
J ¼ 12.1 Hz, PhCHaHb), 4.71 (d, 1H, J ¼ 11.0 Hz, PhCHaHb), 4.67 (d,
1H, J ¼ 12.2 Hz, PhCHaHb), 4.55 (d, 1H, J ¼ 11.6 Hz, PhCHaHb), 4.53
(d, 1H, J ¼ 3.3 Hz, H-1), 4.03 (dd, 1H, J ¼ 7.9, 7.9 Hz, H-3), 3.96 (ddd,
1H, J ¼ 5.4, 5.4, 5.4 Hz, H-5), 3.90 (ddd, 1H, J ¼ 12.0, 5.1, 5.1 Hz, H-
6a), 3.82 (ddd, 1H, J ¼ 12.0, 8.2, 5.3 Hz, H-6b), 3.63 (dd, 1H, J ¼ 7.8,
5.5 Hz, H-4), 3.47 (dd, 1H, J ¼ 7.9, 3.5 Hz, H-2), 3.47 (s, 3H, OMe),
The starting material [8] (22, 323 mg, 0.864 mmol) and tert-
butyldimethylsilyl chloride (219 mg, 1.45 mmol) in dry pyridine
(3.0 mL) were left mixing at rt under Ar. After 12 h, the reaction
mixture was quenched with MeOH (1 mL), and then evaporated to
dry via co-evaporation with toluene (2 ꢂ 1 mL). The crude mixture
was purified via column chromatography on silica using 10%
acetone e hexanes to afford the pure product 23 as a colourless
syrup (402 mg, 0.823 mmol, 95% yield). Rf 0.79 (acetone: hexanes
2.68 (dd, 1H, J ¼ 8.1, 5.0 Hz, 6-OH). 13C NMR (CDCl3, 100 MHz):
dC
138.63 (Ar), 138.47 (Ar), 138.04 (Ar), 128.71 (Ar), 128.65 (Ar), 128.64
(Ar), 128.30 (Ar), 128.24 (Ar), 128.16 (Ar), 128.09 (Ar), 127.96 (Ar),
100.16 (C-1), 78.45 (C-2), 78.08 (C-4), 77.17 (C-3), k75.30 (C-5), 75.11
(PhCH2), 74.01 (PhCH2), 73.95 (PhCH2), 63.38 (C-6), 57.14 (OMe).
2:3). [
a
]
20: ꢀ77.2ꢁ (c 1.06, CHCl3). 1H NMR (CDCl3, 400 MHz):
dH
D
7.36e7.20 (m, 10H, Ar), 4.82 (d, 1H, J ¼ 12.2 Hz, PhCHaHb), 4.64 (d,
1H, J ¼ 0.9 Hz, H-1), 4.60 (d, 1H, J ¼ 12.2 Hz, PhCHaHb), 4.49 (d, 1H,
J ¼ 11.9 Hz, PhCHaHb), 4.44 (d, 1H, J ¼ 11.9 Hz, PhCHaHb), 3.91 (dd,
HRMS m/z calc'd for
C
28H32O6 (MþNa)þ: 487.2091; found:

74
R. Hevey, C.-C. Ling / Carbohydrate Research 445 (2017) 65e74
487.2082.
the reaction mixture was diluted with EtOAc (60 mL), washed with
saturated NaCl(aq) solution (2 ꢂ 60 mL), dried with Na2SO4, filtered,
and evaporated to dry. The crude product was purified by column
chromatography on silica gel using 8 / 10/15% EtOAc e hexanes
to afford the desired product 28 as a colourless syrup (181 mg,
0.393 mmol, 54% yield over 2 steps); characterization agreed with
the previously published literature [12,13]. Rf 0.75 (acetone: hex-
4.15. Methyl 2,3,4-tri-O-benzyl-b-D-ido-hexodialdo-1,5-pyranoside
(25)
A solution of oxalyl chloride (0.13 mL, 1.5 mmol) in dry CH2Cl2
(2.0 mL) was cooled to ꢀ78 ꢁC, and then a solution of DMSO
(0.16 mL, 2.3 mmol) in dry CH2Cl2 (1.0 mL) was slowly added. The
mixture was left at ꢀ78 ꢁC for 10 min, and then a solution of alcohol
11 (338 mg, 0.728 mmol) in dry CH2Cl2 (3.0 mL) was added to the
reaction mixture, and the latter flask rinsed with CH2Cl2
(2 ꢂ 0.3 mL). After an additional 15 min at ꢀ78 ꢁC, Et3N (0.60 mL,
4.3 mmol) was added, and then the reaction mixture warmed back
to rt. Saturated NaCl(aq) solution (50 mL) was added to quench the
reaction, the mixture diluted further with CH2Cl2 (50 mL), and then
the aqueous layer drained. The organic phase was washed further
with saturated NaCl(aq) solution (50 mL), H2O (50 mL), dried with
Na2SO4, filtered, and evaporated to dry to obtain the crude product
25 as a colourless syrup, which was used directly for the subse-
quent step; characterization based on the crude 1H NMR agreed
with the previously published literature [12,13].
anes 2:3). [
a]
20: ꢀ6.0ꢁ (c 0.98, CHCl3). 1H NMR (CDCl3, 400 MHz):
dC
D
7.37e7.24 (m, 15H, Ar), 6.28 (ddd, 1H, J ¼ 17.0, 9.8, 9.8 Hz, H-6),
5.34e5.24 (m, 2H, H-7a and H-7b), 4.82 (d, 1H, J ¼ 10.9 Hz,
PhCHaHb), 4.78 (d, 1H, J ¼ 10.9 Hz, PhCHaHb), 4.77 (d, 1H,
J ¼ 12.4 Hz, PhCHaHb), 4.67 (d, 1H, J ¼ 12.2 Hz, PhCHaHb), 4.61 (d,
1H, J ¼ 11.7 Hz, PhCHaHb), 4.57 (d, 1H, J ¼ 11.5 Hz, PhCHaHb), 4.56
(d, 1H, J ¼ 3.6 Hz, H-1), 4.27 (dd, 1H, J ¼ 9.6, 6.0 Hz, H-5), 4.02 (dd,
1H, J ¼ 8.7, 8.7 Hz, H-3), 3.61 (dd, 1H, J ¼ 8.7, 5.9 Hz, H-4), 3.48 (dd,
1H, J ¼ 8.8, 3.6 Hz, H-2), 3.36 (s, 3H, OMe). 13C NMR (CDCl3,
100 MHz): dC 138.94 (Ar), 138.59 (Ar), 138.37 (Ar), 136.43 (C-6),
128.60 (Ar), 128.57 (Ar), 128.52 (Ar), 128.28 (Ar), 128.22 (Ar), 128.00
(Ar), 127.92 (Ar), 127.84 (Ar), 120.05 (C-7), 99.99 (C-1), 79.04 (C-2),
78.95 (C-4), 77.62 (C-3), 77.01 (C-5), 75.60 (PhCH2), 73.79 (PhCH2),
72.92 (PhCH2), 56.12 (OMe). HRMS m/z calc'd for C16H22O7
(MþNa)þ: 483.2142; found: 483.2143.
4.16. Methyl 2,3-di-O-benzyl-4-deoxy-b-D-arabino-hex-4-en-
dialdo-1,5-pyranoside (27)
Acknowledgments
A
solution of the benzyloxymethyltriphenylphosphonium
We thank the Natural Sciences and Engineering Research
Council of Canada (grant number: 341532-2012), Alberta Innovates,
Canadian Foundation for Innovation, and Government of Alberta
for support of the current project.
chloride salt (prepared by refluxing a solution of benzyl chlor-
omethyl ether and PPh3 in toluene, 423 mg, 1.01 mmol) and n-BuLi
(1.6 M in hexanes, 0.67 mL, 1.1 mmol) in toluene (1.00 mL) was left
under Ar for 30 min, and then a solution of the aldehyde (25, 95 mg,
0.21 mmol) in dry toluene (0.40 mL) was added. After 1 h, the re-
action mixture was diluted with EtOAc (60 mL), washed with
saturated NaCl(aq) solution (2 ꢂ 60 mL), water (60 mL), dried with
Na2SO4, filtered, and evaporated to dry. The crude product was
purified by column chromatography on silica gel using 10 / 15%
acetone e hexanes to unexpectedly afford by-product 27 (67 mg,
0.12 mmol, 58% yield). Data for 27: Rf 0.93 (EtOAc: toluene 1:1).
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.carres.2017.04.007.
References
[
a]
20: (1.3 ꢂ 102)ꢁ (c 1.1, CHCl3). 1H NMR (CDCl3, 600 MHz):
dH 9.17
D
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(s, 1H, H-6), 7.36e7.27 (m, 10H, Ar), 5.85 (d, 1H, J ¼ 2.7 Hz, H-4), 4.92
(d, 1H, J ¼ 2.6 Hz, H-1), 4.81 (d, 1H, J ¼ 12.1 Hz, PhCHaHb), 4.75 (d,
1H, J ¼ 11.6 Hz, PhCHaHb), 4.71 (d, 1H, J ¼ 12.1 Hz, PhCHaHb), 4.70
(d, 1H, J ¼ 11.6 Hz, PhCHaHb), 4.47 (dd, 1H, J ¼ 8.1, 2.7 Hz, H-3), 3.79
(dd, 1H, J ¼ 8.1, 2.6 Hz, H-2), 3.45 (s, 3H, OMe). 13C NMR (CDCl3,
150 MHz): dC 186.23 (C-6), 148.60 (C-5), 138.08 (Ar), 137.94 (Ar),
128.79 (Ar), 128.78 (Ar), 128.35 (Ar), 128.20 (Ar), 128.06 (Ar), 120.57
(C-4), 100.05 (C-1), 76.56 (C-2), 73.72 (PhCH2), 73.51 (C-3), 72.85
(PhCH2), 57.18 (OMe). HRMS m/z calc'd for C21H22O5 (MþNH4)þ:
372.1806; found: 372.1806.
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4.17. Methyl 2,3,4-tri-O-benzyl-6,7-dideoxy-b-D-ido-hept-6-
enopyranoside (28)
ꢀ
ꢀ
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A solution of the phosphonium salt (1092 mg, 3.06 mmol) and
n-BuLi (1.5 M in hexanes, 1.8 mL, 2.7 mmol) in toluene (4.0 mL) was
left under Ar for 30 min, and then a solution of the crude aldehyde
(25, began previous step with 0.728 mmol) was added. After 1 h,