Stereoselective synthesis of dioxabicycles from 1-C-allyl-2-O-benzyl- glycosides - An intramolecular cyclization between 2-O-benzyl oxygen and the allyl double bond

Article abstract of DOI:10.1139/V06-046

Addition of a proton to the double bond of 1-C-allyl-O-benzylglycosides gave a 2′-carbonium ion, which in turn reacted intramolecularly, in a regio- and diastereo-selective manner, with the nucleophilic oxygen of the 2-O-benzyl group to form an oxonium in

Full text of DOI:10.1139/V06-046

597
Stereoselective synthesis of dioxabicycles from 1-
C-allyl-2-O-benzyl-glycosides — An intramolecular
cyclization between 2-O-benzyl oxygen and the
allyl double bond1
An-Tai Wu, Tian Yi, Huawu Shao, Shih-Hsiung Wu, and Wei Zou
Abstract: Addition of a proton to the double bond of 1-C-allyl-O-benzylglycosides gave a 2′-carbonium ion, which in
turn reacted intramolecularly, in a regio- and diastereo-selective manner, with the nucleophilic oxygen of the 2-O-
benzyl group to form an oxonium intermediate. Subsequent cleavage of the benzyl C—O bond led to dioxabicycles in
moderate yields. Surprisingly, opposite diastereoselectivities were observed from 1-C-allylglycofuranosides and 1-C-
allylglycopyranosides, which produced 2,2′-trans- and 2,2′-cis-dioxabicycles, respectively.
Key words: C-glycoside, olefin, cyclization, oxocarbonium, dioxabicycles.
Résumé : L’addition d’un proton sur la double liaison 1-C-allylglycosides de O-benzyle conduit à la formation d’un
ion carbonium en 2′ qui réagit ensuite d’une façon intramoléculaire, régio- et diastéréosélective, avec l’oxygène nucléo-
phile du groupe 2-O-benzyle pour conduire à la formation d’un intermédiaire oxonium. Un clivage subséquent de la
liaison C—O du benzyle conduit à des dioxabicycles avec des rendements modérés. D’une façon surprenante, on a ob-
servé des diastéréosélectivités opposées les 1-C-allylglycofuranosides et les 1-C-allylglycopyranosides qui ont conduit
respectivement aux 2,2′-trans- et 2,2′-cis-dioxabicycles.
Mots clés : C-glycoside, oléfine, cyclisation, oxocarbonium, dioxabicycles.
[Traduit par la Rédaction] Wu et al. 602
Introduction
we also isolated 5-O-debenzylated 3 in 17% yield (Scheme 1),
a useful intermediate obtained previously from 2 by regio-
selective 5-O-acetolysis followed by de-O-acetylation (6).
This result prompted us to investigate if TMSOTf can selec-
tively remove the 5-O-benzyl group from 2 (7). However,
when compound 2 was treated with TMSOTf in ace-
tonitrile, instead of the desired 3, we obtained a dioxabicyclic
compound as the only major product. Further studies using
1-C-allylglycofuranosides and 1-C-allylglycopyranosides as
substrates revealed that the formation of dioxabicycles was
both highly regioselective and diastereoselective. Here, we
wish to describe this stereoselective intramolecular cycliz-
ation between 2-O-Bn and the allyl double bond.
The electrophile-promoted addition to an olefinic double
bond is one of the most investigated reactions (1). The inter-
mediate can be a carbonium ion or more often a bridged cat-
ion, which then reacts with a nucleophile, e.g., alcohol, acid,
amine, and amide, to form an addition product. The stereo-
selectivity of the addition to a double bond can be achieved
using selenium reagents (2), iodo complexes (3), mercury
complexes (4), and Ru reagents (5). In certain cases, the
stereochemistry may be guided by the asymmetric substrates
(1).
Recently, during a large-scale preparation of 1-C-allyl-
2,3,5-tri-O-benzyl-α-D-ribofuranoside (2) using ribofurano-
side 1 and allyltrimethylsilane in the presence of TMSOTf,
Results and discussion
Received 19 August 2005. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 5 May 2006.
The dioxabicylic compound obtained by treatment of 2
with TMSOTf (1 equiv.) in acetonitrile was characterized as
4-trans (Scheme 2). The newly formed ring and the
stereochemistry at C2′ were established by NMR analysis.
Because of the observation of NOE between H-1 and H-3,
the cyclization must have occurred at the 2-O-position. In
addition, the 2,2′-trans configuration was assigned on the
basis of the NOE observed between H-2′ and H-4 and the
lack of NOE between H-2′ and H-2/H-1. This stereochem-
istry was further confirmed by NMR analysis on acetylated
derivative 5, as we observed a downfield shift of the H-3 res-
onance from 3.85 to 4.87 ppm owing to acetylation, and the
A.-T. Wu and S.-H. Wu.2 Institute of Biological Chemistry,
Academia Sinica, Taipei 115, Taiwan, ROC.
T. Yi, H. Shao, and W. Zou.3,4 Institute for Biological
Sciences, National Research Council of Canada, Ottawa,
ON K1A 0R6, Canada.
1This article is part of a Special Issue dedicated to Professor
Walter A. Szarek.
2Corresponding author (e-mail: shwu@gate.sinica.edu.tw).
3Corresponding author (e-mail: wei.zou@nrc-cnrc.gc.ca).
4Dr. Wei Zou was a postdoctoral fellow with Professor Walter
Szarek (1990–1993).
Can. J. Chem. 84: 597–602 (2006)
doi:10.1139/V06-046
© 2006 NRC Canada

598
Can. J. Chem. Vol. 84, 2006
Scheme 1. 1-C-Allylation promoted by TMSOTf.
Scheme 3.
BnO
BnO
BnO
O
O
O
BnO
TMSOTf
MeCN
Ha
Hb
O
BnO
+
BnO
BnO
OBn
OBn
O
BnO
OBn
O
OBn
OMe
2 (80%)
Allyl-TMS/TMSOTf
7-trans (37%)
6 (α/β 1:1)
6α (35%)
+
OBn
OBn
1
HO
O
OBn
O
OBn
O
BnO
BnO
OBn
O
BnO
TMSOTf
MeCN
Ha
Hb
OBn
OBn
+
OBn
O
3 (17%)
OBn
8β (42%)
8 (α/β 1:1)
9-trans (35%)
Scheme 2. Regioselective cyclofunctionalization.
duced by the cyclization between the 2-O-Bn and the cis-1-
C-β-allyl group (Scheme 3). Again, the 2,2′-trans configura-
tion was assigned on the basis of NOE analysis. The remain-
ing starting material (6␣), contaminated only with very
small amount of 6␤, was recovered, which did not produce a
six-membered ring product.
BnO
1. H /Pd-C
2
1
AcO
O
4
2. Ac O/Py
2
O
Promoter
MeCN
Ha
Hb
3
2
2
1'
OBn
O
OAc
O
2'
5
4-trans
Promoter
T/t
Isolated yield of 4-trans
Because of the close distance between C2′ and C4 as in-
dicated by the observation of NOE between H-2′ and H-4 in
4-trans, one might speculate that the 2,2′-trans selectivity in
4-trans and 7-trans may have resulted from the steric hin-
drance exerted by 3-O-Bn in 2 or 5-O-Bn in 6, which could
prevent the methyl group at C2′ from adopting a cis config-
uration in the transition state. However, this argument was
proven not true because 1-C-allyl-D-xylofuranoside (8),
which lacks such steric effect, under the above conditions
produced 9-trans as the only major product (35%) and the
recovery of its 1,2-trans starting material (8␤) (42%) (see
Scheme 3).
Besides the 1-C-allylglycofuranosides, the cyclization
between the 1-C-allyl and the 2-O-Bn also occurred with 1-
C-allylglycopyranosides under the above conditions. Re-
markably, however, in contrast to the 2,2′-trans diastero-
selectivity observed in 1-C-allylglycofuranosides, when 1-C-
allylgalactoside (10) and 1-C-allylglucosides (12) were
treated with TMSOTf in acetonitrile, we only obtained the
respective products with the 2,2′-cis configurations, 11-cis
(56%) and 13-cis (62%) (see Table 1). The cyclization also
proceeded with 2-OH glucoside (14) to give 13-cis (59%) as
the major product and a 2-O-acetylated 15 (15%) as a minor
one (8). The 2-O-acetylation resulted from the reaction be-
tween 2-OH and acetonitrile followed by hydrolysis. No
cyclization occurred when 15 was used as a substrate be-
cause of the diminished 2-O-nucleophicility owing to the
electron-withdrawing effect by 2-O-acetylation.
Although this acid-promoted cyclization was never reported,
the iodonium-promoted cyclization between the olefin dou-
ble bond and O-Bn are known. For example, Rychnovsky
and Bartlett (9) prepared 2,5-cis disubstituted tetrahydro-
furans by cyclizing olefinic ether in the presence of iodine
and suggested that the 2,5-cis stereoselectivity was con-
trolled by an oxonium ion intermediate with the 1,2-trans,
1,5-trans configurations. Nicotra and co-workers (10) also
subjected 1-C-allyl-2-O-benzylglycoside to similar condi-
tions to obtain a mixture of two diastereomers at C2′. The
oxonium ion was also an intermediate in Fraser-Reid’s
glycosylation using n-pentenyl glycoside in which the for-
mation of a bridged olefin halogenium ion was followed by
o
TMSOTf (1equiv.)
TfOH (1equiv.)
0
0
C-rt/16h
61%
41%
-
o
C/4h
o
p-TsOH (1equiv.) 60 C/24h
o
TfOH/p-TsOH
(0.2/1 equiv.)
0
C-rt/16h
53%
strong NOEs between H-1 and H-1′a and between H-2′ and
H-1′b.
This regio- and diastereo-selective conversion of 2 to 4-
trans can also be promoted by TfOH (1 equiv.) at 0 °C, but
with lower yield (see Scheme 2) because of the decomposi-
tion caused by nonselective de-O-benzylation. No significant
transformation occurred when p-TsOH (1 equiv.) was used
alone even at elevated temperature (60 °C, 24 h), but addi-
tional TfOH (0.2 equiv.) facilitated the formation of 4-trans.
Hence, this cyclization was likely acid-promoted. The proton
source in the case of TMSOTf as a promoter might be the
residual water from acetonitrile because when we performed
the experiment under dry, but otherwise the same conditions,
the reaction became very sluggish.5 Additionally, acetonitrile
as the proton source was excluded because when the reac-
tion was performed in MeCN-d3, no deuterium substitution
on the methyl group of 4-trans was detected by NMR and
MS analyses.
The formation of a five-membered ring indicates that the
reaction proceeded through a kinetic process. We were inter-
ested to know if six-membered ring products could also be
formed under certain circumstances. For instance, using 1-C-
allyl-L-arabinofuranoside (6), a mixture of two anomers
(α/β, 1:1) as a substrate, we expected a similar cyclization
occurred in 6␤ because of its 1,2-cis configuration, but we
were also interested to see if the 1-C-allyl group in the α
anomer (6␣) would react to the 3-O-Bn, which is sterically
possible, to form a six-membered ring. Thus, a mixture of
6␣/␤ was treated with TMSOTf in acetonitrile under the
aforementioned conditions. TLC analysis showed the forma-
tion of a new product, but a significant amount of starting
material remained. After the separation, the newly formed
product with a lower Rf was characterized as dioxabicyclic
7-trans (37% yield based on total starting material), pro-
5 Compound 2 and TMSOTf were separately dissolved in acetonitrile and dried over 3 Å molecular sieves. Equivalents of 2 and TMSOTf in
acetonitrile were then mixed and kept at 0 °C overnight.
© 2006 NRC Canada

Wu et al.
599
Table 1. Dioxabicycles from 1-C-allyl-C-glycosides.
Entry
1
Substrate
Product(s) (isolated yield)
BnO
BnO
O
O
61%
O
OBn
OBn
OBn
2
4-trans
BnO
BnO
2
O
BnO
O
O
BnO
37%
35%
35%
42%
BnO
BnO
O
BnO
OBn
OBn
OBn
7-trans
6α
6 (α/β 1:1)
OBn
O
OBn
O
BnO
3
4
OBn
O
BnO
OBn
O
9-trans
8 (α/β 1:1)
8β
Ph
Ph
O
O
O
O
O
O
BnO
BnO
10
BnO
56%
O
Ha
Hb
11-cis
BnO
BnO
BnO
BnO
BnO
BnO
5
O
O
O
BnO
62%
12
13-cis
BnO
BnO
BnO
BnO
BnO
BnO
6
7
O
O
13-cis (59%)
(15%)
HO
AcO
15
14
15
N/A
Scheme 4. Regioselective cyclization promoted by NIS–TMSOTf.
nucleophilic attack from the glycosidic oxygen leading to a
glycosyl oxocarbonium ion as a glycosyl donor and the con-
current formation of a tetrahydrofuran (11).
BnO
NIS/TMSOTf
BnO
O
O
Ha
Hb
Ha
Hb
2
+
MeCN
O
OBn
O
OBn
The poor stereoselection in the iodine-promoted cycliza-
tions contrasts with those obtained from acid-promoted
cyclization. Such a difference is not substrate dependent be-
cause when 2 and 10 were treated with NIS–TMSOTf in
acetonitrile a mixture of diasteromers (16-trans/cis and 17-
trans/cis) were also obtained, respectively, in a 1:2 to 3
trans:cis ratio (Scheme 4). The NOE between H-2′ and H-4
in 16-trans, similar to 4-trans, was observed, but not be-
tween H-4 and CH2I in 16-cis.6 The chemical shifts of H-1′a
(cis to H-1) and H-1′b (trans to H-1) and the pattern of pro-
ton couplings were also similar to those observed in 2′-
methyl dioxabicycles (4-trans, 7-trans, 9-trans, 11-cis, and
13-cis). The double doublet H-1′b resonance in the 2,2′-
trans compounds always appears downfield (2.2–2.4 ppm)
I
I
16-cis (39%)
16-trans (19%)
Ph
Ph
O
O
O
O
NIS/TMSOTf
MeCN
O
O
10
BnO
+
BnO
O
O
Ha
Hb
Ha
Hb
I
I
17-cis (60%)
17-trans (20%)
from that of the H-1 a resonance (1.5–2.0 ppm), and are re-
versed in the 2,2′-cis compounds likely because of the
change of conformation from one envelope to another.
′
6 Due to the overlap of the proton signals of H-2′ and H-4, this result was obtained from a TOCSY (H-5 to H-4) – NOESY (H-4) experiment.
© 2006 NRC Canada

600
Can. J. Chem. Vol. 84, 2006
Scheme 5. Stereoselective cyclization.
ing voltage of 3 kV. m-Nitrobenzyl alcohol (m-NBA) was
used as the matrix, and polyethylene glycol (PEG) was the
internal calibrant. All chemicals were purchased from the
Sigma-Aldrich Chemical Co. and used without further puri-
fication.
BnO
BnO
O
O
4-exo
+
+
H
+
BnO
Bn
MeCN
O
OBn
OBn
Me
2
BnO
BnO
O
General procedure for cyclization
+
+
O
I
I
To a solution of substrate (50–100 mg) in CH3CN (2 mL)
was added dropwise TMSOTf (1 equiv.) at 0 °C. The mix-
ture was stirred and allowed to warm to room temperature
overnight. The reaction was quenched by the addition of
Et3N and the solvent was removed under reduced pressure.
Product purification was performed by silica gel column
chromatography (hexane–EtOAc, 3:1).
*
16-endo + 16-exo
OBn
OBn
+
BnO
Bn
O
I
Unlike proton-promoted electrophilic addition, which fol-
lows Markovnikov’s rule leading to a carbonium ion, the ad-
dition of an iodonium ion to a double bond can result in two
bridged iodonium intermediates (Scheme 5). Consequently,
the subsequent SN2 displacement by 2-O-Bn produced two
respective diastereoisomers (2,2′-cis and 2,2′-trans) (11)
(see Scheme 4). Acetonitrile likely also plays a role by facil-
itating the cleavage of the O—Bn bond from the oxonium
intermediate by forming a benzylacetonium ion (12) because
the same reaction did not occur in dichloromethane.
The opposite stereochemistry obtained from 1-C-allyl-
glycofuranosides and -glycopyranosides suggests two dis-
tinctive transition states. It is conceivable that the parent ring
structure, the chair form in the pyranosides and the envelope
form in the furanosides, may play a critical role in the stabi-
lization of the respective oxonium ion transition states. It is
also possible that the stereochemistry at C2′ may simply be
predetermined by the orientation of the 2-O-Bn, which the
2′-carbonium ion must approach from the less-hindered side
to form a 1,2-trans oxonium intermediate. Unfortunately, at
this moment, we have no convincible explanation for those
experimental results. Molecular modeling and calculation of
the minimum energies of the possible oxonium transition
states may provide the information on the most likely reac-
tion pathway.
1-C-(R-Propan-2′-ol)-3,5-di-O-benzyl-2,2′-anhydro-␣-D-
ribofuranoside (4-trans)
This compound was obtained as an oil in 61% yield. [α]D
1
+79.4° (c 7.0, CHCl3). H NMR (CDCl3) δ: 4.80 (d, J =
12 Hz, 1H, PhCH2), 4.77 (dd, J = 4.8, 4.8 Hz, 1H, H-1),
4.60 (dd, J = 4.8, 4.8 Hz, 1H, H-2), 4.54–4.50 (m, 3H,
PhCH2), 4.29 (m, 1H, H-2′), 4.00 (ddd, J = 8.4, 5.2, 2.4 Hz,
1H, H-7), 3.83 (dd, J = 8.4, 5.2 Hz, 1H, H-3), 3.66 (dd, J =
10.8, 2.4 Hz, 1H, H-5a), 3.45 (dd, J = 10.8, 5.2 Hz, 1H, H-
5b), 2.23 (dd, J = 13.2, 4.8 Hz, 1H, H-1′b), 1.58 (ddd, J =
13.2, 10.4, 4.8 Hz, 1H, H-1′a), 1.30 (d, J = 6.0 Hz, 3H,
CH3). 13C NMR (CDCl3) δ: 83.6 (C-2), 80.8 (C-3), 80.5 (C-
4), 79.9 (C-1), 77.0 (C-2′), 73.4 (PhCH2), 72.0 (PhCH2),
70.1 (C-5), 43.2 (C-1′), 20.7 (CH3). HRFABMS calcd. for
C22H27O4 m/z: 355.1831 (MH+); found: 355.2230. Starting
material 2 (10 mg, 10%) was also recovered.
1-C-(R-Propan-2′-ol)-3,5-di-O-acetyl-2,2′-anhydro-␣-D-
ribofuranoside (5)
A solution of compound 4-trans (120 mg, 0.33 mmol) in
methanol (15 mL) was hydrogenated with 10% Pd/C
(50 mg) under 50 psi (1 psi = 6.894 757 kPa) overnight. The
filtrate was concentrated to a residue. To a solution of this
residue in CH2Cl2 (10 mL) was added TEA (1 mL) and ace-
tic anhydride (210 mg, 2.11 mmol), and the mixture was
stirred overnight. Work-up and purification by chromatogra-
In summary, we described an intramolecular cyclization
from 1-C-allyl-O-benzylglycosides in moderate to good yields.
The allyl double bond was activated by electrophiles to gen-
erate a carbonium at C2′, which reacted with nucleophilic
benzyl ether giving dioxabicyclic derivatives. The cycliza-
tion is highly regioselective in favor of five-membered prod-
ucts. The reaction is also highly diastereoselective to form
2,2′-cis and 2,2′-trans dioxabicycles from 1-C-pyranosides
and 1-C-furanosides, respectively.7
1
phy gave 5 (60 mg, 68%). [α]D +113.9° (c 1.5, CHCl3). H
NMR (CDCl3) δ: 4.87 (dd, 1H, J = 4.8, 7.6 Hz), 4.81 (dd,
1H, J = 4.8 Hz), 4.76 (dd, 1H, J = 4.8 Hz), 4.28 (dd, 1H, J =
11.6, 2.8 Hz), 4.20 (m, 1H), 4.14 (m, 1H), 4.05 (dd, 1H, J =
11.6, 5.6 Hz), 2.23 (dd, 1H, J = 13.2, 4.8 Hz), 2.13 (s, 3H),
2.09 (s, 3H), 1.59 (m, 1H), 1.28 (d, 3H, J = 6.0 Hz). 13C
NMR (CDCl3) δ: 170.8, 170.4, 84.0, 80.6, 78.7, 77.3, 75.2,
64.0, 42.9, 20.9, 20.8, 20.6. ESMS: 259.2 (MH+).
Experimental section
General methods
1H and 13C NMR spectra were recorded at 400 and
100 MHz, respectively, with a Varian instrument at 293 K.
Chemical shifts are given in ppm downfield from the signal
of internal TMS and are assigned on the basis of 2D COSY,
1-C-(R-Propan-2′-ol)-3,5-di-O-benzyl-2,2′-anhydro-␤-L-
arabinofuranoside (7-trans)
Under the same conditions, 7-trans (37%) and 6␣ (35%)
were obtained from 6 (α:β, 1:1).
TOCSY, and H–13C chemical-shift correlated experiments.
1
High-resolution fast atom bombardment mass spectrometry
(HRFABMS) was carried out on a JEOL JMS-AX505H
mass spectrometer using a 6 kV xenon beam at an accelerat-
For 7-trans: [α]D –44.0° (c 1.12, CHCl3). 1H NMR
(CDCl3) δ: 7.37–7.24 (m, 10H), 4.72 (m, 1H), 4.71 (d, 1H,
J = 11.6 Hz), 4.63 (dd, 1H, J = 4.8, 1.6 Hz), 4.56 (s, 2H),
7 Supplementary data for this article are available on the journal Web site (http://canjchem.nrc.ca) or may be purchased from the Depository
of Unpublished Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0R6, Canada. DUD 5025. For more
information on obtaining material refer to http://cisti-icist.nrc-cnrc.gc.ca/irm/unpub_e.shtml.
© 2006 NRC Canada

Wu et al.
601
4.52 (d, 1H, J = 11.6 Hz), 4.15 (m, 1H), 3.95 (dt, 1H, J =
3.2, 6.4 Hz), 3.78 (dd, 1H, J = 7.2, 2.0 Hz), 3.65 (dd, 1H,
J = 10.4, 3.2 Hz), 3.56 (dd, 1H, J = 10.8, 6.4 Hz), 2.17 (dd,
1H, J = 13.2, 4.4 Hz), 1.42 (m, 1H), 1.27 (d, 3H, J =
6.0 Hz). 13C NMR (CDCl3) δ: 138.2, 137.8, 128.5, 128.4,
127.9, 127.7, 88.5, 85.9, 83.8, 82.6, 74.7, 73.5, 72.1, 70.2,
41.0, 19.9. ESMS: 355.3 (MH+).
CH2Ph, J = 12.4 Hz), 3.95 (m, 1H, H-2′), 3.77–3.85 (m, 3H,
H-2, H-3, H-5), 3.55–3.67 (m, 3H, H-4, H-6, 6′), 2.25 (m,
1H, H-1′a), 1.62 (m, 1H, H-1′b), 1.34 (d, 3H, H-3′, J =
6.0 Hz). 13C NMR (CDCl3) δ: 138.9, 138.7, 138.4 (Ph),
128.6, 128.4, 127.9, 127.8, 127.6 (Ph), 83.4 (C-3), 83.3 (C-
2), 76.1 (C-1), 75.5 (C-4), 75.2 (C-5), 74.7 (C-2′), 74.6
(CH2Ph), 73.5 (CH2Ph), 73.0 (CH2Ph), 70.1 (C-6), 39.4
(C-1′), 21.6 (C-3′). ESMS: 475.3 (MH+).
1
For 6␣: [α]D –19.5° (c 1.4, CHCl3). H NMR (CDCl3) δ:
7.37–7.22 (m, 15H), 5.58 (m, 1H), 5.10 (m, 2H), 4.50 (m,
6H), 4.21 (m, 1H), 4.07 (m, 1H), 4.06 (dd, 1H, J = 3.2 Hz),
3.87 (dd, 1H, J = 4.4, 2.8 Hz), 3.57 (m, 2H). 13C NMR
(CDCl3) δ: 138.4, 138.0, 134.4, 128.5, 128.4, 128.3, 127.8,
127.7, 87.0, 85.4, 82.0, 81.6, 73.4–71.9, 70.3, 37.7. ESMS:
445.2 (MH+).
1-C-(3′-Iodo-R/S-propan-2′-ol)-3,5-di-O-benzyl-2,2′-
anhydro-␣-D-ribofuranoside (16-trans and 16-cis)
Compounds 16-trans (19%) and 16-cis (39%) obtained
from 2 were separated by chromatography.
1
For 16-trans: oil. [α]D +51.7° (c 0.12, CHCl3). H NMR
(CDCl3) δ: 4.79–4.76 (m, 2H, PhCH2, H-1), 4.66 (dd, J =
4.0, 4.0 Hz, 1H, H-2), 4.57–4.49 (m, 3H, PhCH2), 4.17 (m,
1H, H-2′), 4.02 (m, 1H, H-4), 3.86 (dd, J = 8.0, 4.4 Hz, 1H,
H-3), 3.66 (dd, J = 10.4, 1.6 Hz, 1H, H-5a), 3.46 (dd, J =
10.4, 4.8 Hz, 1H, H-5b), 3.38–3.30 (m, 2H, CH2I), 2.37 (dd,
J = 13.6, 5.2 Hz, 1H, H-1′b), 1.79 (ddd, J = 13.6, 10.0,
5.2 Hz, 1H, H-1′a). 13C NMR (CDCl3) δ: 83.1 (C-2), 81.9
(C-3), 80.7 (C-4), 80.1 (C-1), 79.5 (C-2′), 73.5 (PhCH2), 72.2
(PhCH2), 70.0 (C-5), 41.9 (C-1′), 10.2 (CH2-I). HRFABMS
calcd. for C22H25IO4 m/z: 480.0797 (M+); found: 479.0749.
For 16-cis: oil. [α]D +79.5° (c 0.2, CHCl3). 1H NMR
(CDCl3) δ: 4.79–4.73 (m, 2H, PhCH2, H-1), 4.57–4.49 (m,
3H, PhCH2), 4.45 (dd, J = 4.4, 4.4 Hz, 1H, H-2), 4.20–4.15
(m, 2H, H-2 H-4), 3.89 (dd, J = 8.4, 4.4 Hz, 1H, H-3), 3.67
(dd, J = 10.8, 1.6 Hz, 1H, H-5a), 3.50 (dd, J = 10.8, 4.8 Hz,
1H, H-5b), 3.41 (dd, J = 10.0, 5.2 Hz, 1H, CH2I), 3.32 (dd,
J = 9.2, 8.4 Hz, 1H, CH2I), 2.42 (dt, J = 14.0, 6.8 Hz, 1H,
H-1), 1.99 (ddd, J = 14.0, 6.8, 2.4 Hz, 1H, H-1). 13C NMR
1-C-(R-Propan-2′-ol)-3,5-di-O-benzyl-2,2′-anhydro-␣-D-
xylofuranoside (9-trans)
Under the same conditions, 9-trans (35%) and 8␤ (42%)
were obtained from 8 (α:β, 1:1).
For 9-trans: [α]D –44.0° (c 1.12, CHCl3). 1H NMR
(CDCl3) δ: 7.37–7.24 (m, 10H), 4.87 (dd, 1H, J = 4.4 Hz),
4.67 (d, 1H, J = 12.0 Hz), 4.63 (d, 1H, J = 11.6 Hz), 4.59
(m, 1H), 4.52 (d, 1H, J = 6.4 Hz), 4.49 (d, 1H, J = 6.4 Hz),
4.18 (m, 1H), 4.12 (m,1H), 3.97 (d, 1H, J = 4.0 Hz), 3.68 (d,
2H, J = 5.6 Hz), 2.25 (dd, 1H, J = 13.6 Hz, 5.2 Hz), 1.50
(m, 1H), 1.24 (d, 3H, J = 6.4 Hz). 13C NMR (CDCl3) δ:
128.5, 128.4, 127.9, 127.7, 85.9, 83.8, 83.5, 81.3, 75.9, 73.6,
72.2, 68.9, 42.5, 20.6. ESIMS: 355.3 (MH+).
1
For 8␤: [α]D –19.5° (c 1.4, CHCl3). H NMR (CDCl3) δ:
7.37–7.22 (m, 15H), 5.80 (m, 1H), 5.08 (m, 2H), 4.63–4.44
(m, 6H), 4.20 (dt, 1H, J = 1.6, 4.4 Hz), 3.96 (d, 1H, J =
3.6 Hz), 3.90 (dt, 1H, J = 3.6, 6.8 Hz), 3.79 (dd, 1H, J = 9.6,
5.6 Hz), 3.76 (m, 1H), 3.73 (dd, 1H, J = 9.6, 6.0 Hz), 2.49–
2.32 (m, 2H). 13C NMR (CDCl3) δ: 138.4, 138.0, 134.4,
128.5, 128.4, 127.9, 127.8, 127.7, 87.0, 85.4, 82.0, 81.6,
73.4–71.9, 70.3, 37.7. ESMS: 455.3 (MH+).
(CDCl ) : 82.9 (C-1), 82.2 (C-2), 80.8 (C-2 ), 79.2 (C-3),
δ
′
3
79.0 (C-4), 73.4 (PhCH2), 72.1 (PhCH2), 69.6 (C-5), 40.2
(C-1 ), 8.5 (CH I). HRFABMS calcd. for C H IO m/z:
′
2
22 25
4
480.0797 (M+); found: 479.0711.
1-C-(S-Propan-2′-ol)-3-O-benzyl-4,6-O-benzylidene-2,2′-
anhydro-␣-D-galactopyranoside (11-cis)
1-C-(3′-Iodo-R/S-propan-2′-ol)-3-O-benzyl-4,6-O-
benzylidene-2,2′-anhydro-␣-D-galactopyranoside (17-
This compound was obtained from 10 as an oil in 56%
trans and 17-cis)
Compounds 17-trans (20%) and 17-cis (60%) obtained
from 10 were separated by chromatography.
1
yield. [α]D +44.8° (c 0.67, CHCl3). H NMR (CDCl3) δ:
5.47 (s, 1H, PhCH), 5.07 (m, 1H, H-1), 4.87 (d, J = 12.4 Hz,
1H, CH2Ph), 4.73 (d, J = 12.4 Hz, 1H, CH2Ph), 4.39 (bd, J =
2.4 Hz, 1H, H-4), 4.33 (d, J = 12.4 Hz, 1H, H-6a), 4.08–4.03
(m, 2H, H-6b, H-2), 3.92 (m, 1H, H-2, 3.71 (dd, J = 5.6,
2.0 Hz, 1H, H-3), 3.58 (bs, 1H, H-5), 2.38 (m, 1H, H-1),
1.82 (ddd, J = 13.6, 8.4, 3.2 Hz, 1H, H-1), 1.34 (d, J = 6 Hz,
3H, CH3). 13C NMR (CDCl3) δ: 100.5 (PhCH), 82.8 (C-2),
79.5 (C-3), 78.0 (C-1), 74.2 (C-2′), 73.3 (C-4), 72.6 (C-6),
71.1 (PhCH2), 67.5 (C-5), 40.8 (C-1′), 21.0 (CH3).
HRFABMS calcd. for C23H27O5 m/z: 383.1780 (MH+);
found: 383.2146.
For 17-trans: oil. [α]D –8° (c 5.8, CHCl3). 1H NMR
(CDCl3) δ: 5.48 (s, 1H, PhCH), 5.20 (dd, J = 8.8, 4.4 Hz,
1H, H-1), 4.86 (d, J = 12.4 Hz, 1H, CH2Ph), 4.73 (d, J =
12.8 Hz, 1H, CH2Ph), 4.48 (dd, J = 9.2, 4.4 Hz, 1H, H-2),
4.40 (bs, 1H, H-4), 4.33 (d, J = 12.4 Hz, 1H, H-6a), 4.23 (m,
1H, H-2, 4.05 (d, J = 12.8 Hz, 1H, H-6b), 3.63 (d, J =
5.2 Hz, 1H, H-3), 3.56 (bs, 1H, H-5), 3.34–3.25 (m, 2H,
CH2I), 2.23 (dd, J = 13.6, 5.6 Hz, 1H, H-1), 1.82 (ddd, J =
13.6, 9.2, 5.6 Hz, 1H, H-1). 13C NMR (CDCl3) δ: 100.5
(PhCH), 84.0 (C-2), 79.2 (C-3), 78.1 (C-1), 77.7 (C-2′), 73.5
(C-4), 72.6 (C-6), 70.8 (PhCH2), 67.4 (C-5), 39.8 (C-1′),
10.1 (CH2I). HRFABMS calcd. for C23H25IO5 m/z: 508.0747
(M+); found: 507.0730.
1-C-(S-Propan-2′-ol)-3,4,6-tri-O-benzyl-2,2′-anhydro-␣-
D-glucopyranoside (13-cis)
This compound was obtained from 12 as an oil in 62%
For 17-cis: oil. [α]D +6.8° (c 9.4, CHCl3). 1H NMR
(CDCl3) δ: 5.48 (s, 1H, PhCH), 5.15 (m, 1H, H-1), 4.86 (d,
J = 12.4 Hz, 1H, CH2Ph), 4.73 (d, J = 12.4 Hz, 1H, CH2Ph),
4.39 (bs, 1H, H-4), 4.33 (d, J = 12.4 Hz, 1H, OCH2), 4.25
(dd, J = 9.6, 4.8 Hz, 1H, H-2), 4.23 (m, 1H, H-2′), 4.05 (d,
J = 12.4 Hz, 1H, H-6a), 3.66 (bd, J = 5.2 Hz, 1H, H-3), 3.57
1
yield. [α]D +76° (c 0.1, CHCl3). H NMR (CDCl3) δ: 7.18–
7.40 (m, 15H, 3 × Ph), 4.90 (d, 1H, CH2Ph, J = 11.6 Hz),
4.83 (d, 1H, CH2Ph, J = 11.2 Hz), 4.73 (d, 1H, CH2Ph, J =
11.6 Hz), 4.59 (d, 1H, H-1), 4.53 (d, 1H, CH2Ph, J =
12.4 Hz), 4.46 (d, 1H, CH2Ph, J = 11.2 Hz), 4.43 (d, 1H,
© 2006 NRC Canada

602
Can. J. Chem. Vol. 84, 2006
4. (a) S.H. Kang, M. Kim, and S.Y. Kang. Angew. Chem. Int. Ed.
43, 6177 (2004); (b) S.H. Kang and M. Kim. J. Am. Chem.
Soc. 125, 4684 (2003); (c) H.B. Vardhan and R.D. Bach. J.
Org. Chem. 57, 4948 (1992).
5. Y. Oe, T. Ohta, and Y. Ito. Synthesis, 179 (2005).
6. (a) W. Zou, E. Lacroix, Z. Wang, and S.-H. Wu. Tetrahedron
Lett. 44, 4431 (2003); (b) T. Yi, S.-H. Wu, and W. Zou.
Carbohydr. Res. 340, 235 (2005).
(bs, 1H, H-5), 3.34–3.25 (m, 2H, CH2I), 2.23 (m, 1H, H-
1′a), 1.82 (dd, J = 14, 5.6 Hz, 1H, H-1′b). 13C NMR
(CDCl3) δ: 100.5 (PhCH), 84.2 (C-2), 79.7 (C-3), 78.8 (C-
2′), 77.6 (C-1), 73.4 (C-4), 72.5 (C-6), 70.9 (PHCH2), 67.4
(C-5), 38.3 (C-1), 9.8 (CH2I). HRFABMS calcd. for
C23H25IO5 m/z: 508.0747 (M+); found: 507.0781.
7. Lewis acid mediated removal of the O-benzyl group is known
and the regioselectivity may also be achieved in some cases
using TMSI, NIS, TIBAL, and BCl3. See: (a) J. Stanek, Jr.
Top. Curr. Chem. 154, 211 (1990); (b) J. Madsen and M. Bols.
Angew. Chem. Int. Ed. 37, 3177 (1998); (c) J. Madsen, C.
Viuf, and M. Bols. Chem. Eur. J. 6, 1140 (2000); (d) B. Che-
valier-du Roizel, E. Cabianca, P. Rollin, and P. Sinay. Tetrahe-
dron, 58, 9579 (2002); (e) T. Lecourt, A. Herault, A.J. Pearce,
M. Sollogoub, and P. Sinay. Chem. Eur. J. 11, 2960 (2004);
( f ) J. Xie, M. Menand, and J.-M. Valery. Carbohydr. Res.
340, 481 (2005).
Acknowledgments
This is NRCC publication No. 42508. The authors thank
Ms. Milan Bhasin for technical assistance, Dr. Jean-Robert
Brisson for assistance in NMR analysis, and Lisa Morrison
and Dr. Jianjun Li for MS analysis.
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© 2006 NRC Canada