Metal trifluoromethanesulfonate-catalyzed regioselective reductive ring opening of benzylidene acetals

Article abstract of DOI:10.1002/jccs.200900076

A systematic study of various metal trifluoromethanesulfonates as efficient catalysts in the regioselective reductive ring opening of benzylidene acetals is described, including the effects of solvents, reducing agents, and temperature. These catalysts are found to be effective in cleaving the 4,6-O-acetal rings of hexopyranosides at either O4 or O6, respectively. When used in conjunction with a 1 M solution of BH₃.THF in THF without extra addition of any solvent, it affects the ring fission at the O6 position to generate the corresponding primary alcohols, whereas O4-opening takes place in acetonitrile in the presence of dimethylethylsilane as the reductant leading to the secondary hydroxyl derivatives in high selectivity and yields. These methodologies can be applied to a wide range of substrates containing various functional groups.

Full text of DOI:10.1002/jccs.200900076

510
Journal of the Chinese Chemical Society, 2009, 56, 510-523
Metal Trifluoromethanesulfonate-Catalyzed Regioselective Reductive Ring
Opening of Benzylidene Acetals
Chi-Rung Shieb (
Cheng-Chung Wangb,c
), Zheng-Hao Tzengb (
) and Shang-Cheng Hunga,b,c,* (
),
(
)
aGenomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei 115, Taiwan, R.O.C.
bDepartment of Chemistry, National Tsing Hua University, 101, Section 2, Kuang-Fu Road,
Hsinchu 300, Taiwan, R.O.C.
cChemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program (TIGP),
Academia Sinica, 128, Section 2, Academia Road, Taipei 115, Taiwan, R.O.C.
A systematic study of various metal trifluoromethanesulfonates as efficient catalysts in the regiose-
lective reductive ring opening of benzylidene acetals is described, including the effects of solvents, reduc-
ing agents, and temperature. These catalysts are found to be effective in cleaving the 4,6-O-acetal rings of
hexopyranosides at either O4 or O6, respectively. When used in conjunction with a 1 M solution of
BH3·THF in THF without extra addition of any solvent, it affects the ring fission at the O6 position to gen-
erate the corresponding primary alcohols, whereas O4-opening takes place in acetonitrile in the presence
of dimethylethylsilane as the reductant leading to the secondary hydroxyl derivatives in high selectivity
and yields. These methodologies can be applied to a wide range of substrates containing various func-
tional groups.
Keywords: Metal trifluoromethanesulfonates; Catalysis; Cleavage reactions; Benzylidene
acetals; Reduction; Regioselectivity.
INTRODUCTION
Carbohydrates and glycoconjugates play significant
idene acetals 1, as illustrated in Fig. 1, can be selectively
cleaved under appropriate reaction conditions to furnish
the primary alcohols 2 (path a) and the secondary alcohols
3 (path b), respectively. The corresponding substituted5
and unsubstituted benzyl groups are known to be differen-
tiated easily and offer an excellent opportunity to establish
roles in a diverse set of biological processes, including vi-
ral and bacterial infections, cell growth and proliferation,
and cell-cell communication, as well as immuno-responses.1
Characterization of the molecular properties within the car-
bohydrates and their binding biomolecules, responsible for
specific recognition, is an urgent issue. Due to the difficul-
ties in obtaining homogeneous materials in workable quan-
tities from natural sources, synthetic methods to construct
these biologically potent domains have acquired immense
importance.2
The distinction of all hydroxyl groups present on a
monosaccharide is one of the major challenges toward the
preparation of oligosaccharides and glycoconjugates. The
development of a successful protecting group scheme that
allows for the manipulation of individual hydroxyls has re-
ceived much attention.3 Substituted and unsubstituted ben-
zylidene acetals are valuable protecting groups4 that block
the 4,6-dihydroxyl groups of hexopyranosides. The aryl-
Fig. 1. Metal trifluoromethanesulfonate-catalyzed re-
gioselective reductive ring opening of benzyl-
idene acetals 1 to the primary alcohols 2 (path
a) and the secondary alcohols 3 (path b), re-
spectively.
* Corresponding author. Fax: +886-2-27898771; E-mail: schung@gate.sinica.edu.tw

Regioselective Ring Opening of Benzylidene Acetals
J. Chin. Chem. Soc., Vol. 56, No. 3, 2009 511
orthogonal protecting group patterns. A number of effec-
tive reagents for regioselective ring opening of 4,6-O-ben-
zylidene acetals have been documented in the literature.
AlH36 and DIBAL-H7 are often used for O6-cleavage, ex-
cept with the substrates containing base-sensitive function-
alities. The acid-activated reductive cleavage is an alterna-
tive solution in opening the acetal ring at either O6 or O4. A
variety of combinations, for example, BH3·THF/Ph2BBr8
or Bu2BOTf,9 BH3·Me3N/AlCl3 in toluene,10 BH3·Me2NH/
BF3·OEt2 in dichloromethane,11 Et3SiH/PhBCl2,12 and
polymethylhydrosiloxane/AlCl313 give the desired 6-alco-
hols as the major isomers. For the synthesis of the corre-
sponding 4-alcohols, BH3·Me3N/AlCl3 in tetrahydrofu-
ran,10 BH3·Me2NH/BF3·OEt2 in acetonitrile,11 NaCNBH3/
HCl14 or TfOH,15 Et3SiH/CF3CO2H,16 TfOH12 or BF3·
OEt2,11b,17 and Bu3SnH/MgBr2·OEt218 have been reported.
However, most of these traditional acids are moisture-un-
stable and have to be used in stoichiometric or excess
amounts, yielding the hydrolyzed 4,6-diol as a major side
product. There is a need to search for new Lewis acids as
efficient catalysts for selective cleavage. We report herein a
systematic screening of various metal trifluoromethanesul-
fonates [M(OTf)n] to open the benzylidine acetals at either
O4 or O6 via altering the reactivity of reducing agents (Fig.
1). The amounts of catalysts and the effects of reducing
agents and solvents, as well as temperature, are also de-
scribed.
reagent was prepared as a 1 M solution in tetrahydrofuran,
it was realized that the use of additional solvent, dichloro-
methane, was not necessary, and its exclusion gave similar
results (entry 14, 92%).
A set of experiments was performed to determine the
minimum catalytic amount of Cu(OTf)2 required for opti-
mum activity. When the concentration of catalyst was low-
ered to 10 mol% (entry 15) and 5 mol% (entry 16), similar
selectivity and yields were obtained. Decreasing it to 1
mol% caused an extension of reaction time and a drop in
yield (entry 17).
Acombination of 5 mol% Cu(OTf)2 with various bor-
ane reagents was further studied. Treatment of 4 with BH3·
Me2S complex (entry 18) led to the 6-alcohol 523 and 4-al-
cohol 614a in 78% and 3% yields, respectively. A ten-fold
increase of the catalyst amount effected this transformation
in a much shorter time and gave 5 in a similar yield (entry
19). In entry 20, when BH3·NMe3 complex was used as the
reductant, compound 6 (40%) was isolated as the sole prod-
uct along with recovery of the starting material (55%). A
change in the catalyst concentration did show a deviation in
the product ratio (entries 21 and 22). Reaction of 4 using a
combination of 5 mol% Cu(OTf)2 and a bulkier reagent
9-BBN was sluggish (entry 23), and it took overnight stir-
ring to furnish 5 in a modest yield (40%) together with the
hydrolyzed 4,6-diol (40%) and unreacted starting material
(15%). While employment of a stoichiometric amount of
Cu(OTf)2 resulted in a considerable decrease in reaction
time (7.5 h, entry 24), the other isomer 6 was also isolated
in 15% yield along with the major 6-alcohol 5 (65%).
These results have revealed that different borane reagents
may affect the regioselective outcome of the reactions.
We further proceeded to investigate the scope and
possible limitations of this methodology in a wide range of
substrates. To test the compatibility of different protecting
groups, under this set of optimized conditions [1 M BH3·
THF in THF, 5 mol% Cu(OTf)2, without additional sol-
vent], a variety of hexopyranoside, furanoside and non-car-
bohydrate compounds were selected for the reductive ring
cleavage of benzylidene acetals. As depicted in Table 2,
facile conversions to the corresponding primary alcohols
were observed in most of the cases, while lowering the re-
action temperature to 0 °C or use of an additional amount of
catalyst, in a few instances, was beneficial.
RESULTS AND DISCUSSION
Regioselective Ring Opening of Benzylidene Acetals
to the Primary Alcohols
M(OTf)n are water-stable and reusable Lewis acid
catalysts and have been widely applied in numerous or-
ganic reactions.19 However, the reports on use of these
M(OTf)n in conjunction with a reducing agent are rare.20
In our preliminary investigation, borane-reductive O6-
ring opening of the benzylidene acetal 4 catalyzed by
V(O)(OTf)221 or Cu(OTf)222 could provide the correspond-
ing primary alcohol 5 in excellent selectivity. An extensive
study of various M(OTf)n and reducing agents at room tem-
perature is outlined in Table 1. All M(OTf)n using 15 mol%
were found to effectively catalyze the bond cleavage (en-
tries 1-13). Amongst these, Cu(OTf)2 and Zn(OTf)2 are
cheaper and the former has an edge over the latter on the
basis of reactivity; the reaction was completed in 45 min
(entry 13, 94%). Since commercially available BH3·THF
In the D-glucose series, compound 7 could be con-
verted into the expected 4-OBn derivative 8 (entry 1, 4.5 h,
87%), while the 2,3-di-OBz 9 gave the corresponding 6-al-

512 J. Chin. Chem. Soc., Vol. 56, No. 3, 2009
Shie et al.
Table 1. M(OTf)n-catalyzed regioselective borane-reductive O6-ring opening of 4,6-O-
benzylidene acetal 4 to the corresponding 6-alcohol 5
HO
BnO
BnO
BnO
x mol% M(OTf)n,
borane
Ph
O
O
BnO
O
O
O
HO
BnO
+
solvent, rt, t (h)
BnO
BnO
BnO
OMe
OMe
OMe
4
5
6
Yield (%)
Entry M(OTf)n
x mol%
Borane
Solvent
t (h)
5
6
1
2
3
4
5
6
7
8
La(OTf)3
Pr(OTf)3
Nd(OTf)3
Sm(OTf)3
Eu(OTf)3
Gd(OTf)3
Yb(OTf)3
Sc(OTf)3
In(OTf)3
V(O)(OTf)2
Zn(OTf)2
AgOTf
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
15
15
15
15
15
15
15
15
15
15
15
15
15
15
10
5
BH3•THFa CH2Cl2
21
5
4
3.5
3
3
2
5
2.5
3
4
86
91
94
92
87
88
94
94
82
94
94
88
94
92
93
95
70
78
75
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•THF
BH3•Me2Sb
BH3•Me2S
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
-
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4
0.75
0.75
1.5
2.5
27
10
5
25
26
25
27
7.5
-
-
-
-
1
5
3
5
40
55
55
0
50
5
50
100
5
-
BH3•Me3N CH2Cl2
BH3•Me3N CH2Cl2
BH3•Me3N CH2Cl2
15
20
40
65
9-BBNc
9-BBN
-
-
100
15
a 1 M solution in THF.
b 2 M solution in THF.
c 0.5 M solution in THF.
cohol 1010 in modest yield (entry 2, 23 h, 53%). By increas-
ing the catalyst concentration to 15 mol%, the latter trans-
formation was carried out in a short period (5 h) and the
product 10 was generated in very high yield (91%, entry 3).
As compared to their 2,3-di-OBn analog 4 (0.75 h), these
reactions took a longer time for completion. It is evident
that the electron-donating groups in the substrate speed up
the reaction, while the electron-withdrawing groups slow it
down. Obviously, the reaction rate is closely associated
with the nucleophilicity of the oxygen atom at C6 for the
Lewis acid catalyst. Similarly, the b-form glucopyranoside
11 (entry 4) and thioglycoside 13 (entry 5) underwent a
high-yielding ring fission to generate the 6-OH derivatives
125b (92%) and 14 (93%), respectively. The reaction condi-
tions were also found to be suitable for substituted benzyli-
dene acetals, as exemplified by cleavage of the PMP-acetal
15 (PMP = p-methoxyphenyl, entry 6, 0.75 h) that rapidly
produced the primary alcohol 16 in excellent yield (97%).
The structural assignment of all the products was unambig-
uously done through a series of NMR experiments. First,
1H-13C COSY was performed to mark the anomeric carbon
and the doublet anomeric proton. 1H-1H COSY then estab-
lished the correlation between all of the ring protons start-
ing from H1. The regioselectivity was confirmed by ob-
serving the correlation between OH and H6/H4 protons.
This general protocol was followed throughout the study.
In the D-glucosamine series, the a-form 3-OBn 17
(entry 7) and 3-OBz 19 (entry 10) gave the O6-ring opened

Regioselective Ring Opening of Benzylidene Acetals
J. Chin. Chem. Soc., Vol. 56, No. 3, 2009 513
Table 2. BH3•THF-reductive ring opening of various benzylidene acetals at O6 using Cu(OTf)2 as the catalyst
Entry
Acetal
x mol% T (°C)
t (h)
Product
Yield (%)
1
2
3
7 : R = H0
9 : R = Bz
9 : R = Bz
5
5
15
rt
rt
rt
4.5
23
5
8 : R = H
10 : R = Bz
10 : R = Bz
87
53
91
4
5
rt
4
92
5
6
13 : R = Tol, Ar = Ph
15 : R = Et, Ar = PMP
5
5
rt
rt
3.5
0.75
14 : R = Tol, Ar = Ph
16 : R = Et, Ar = PMP
93
97
7
8
9
10
11
17 : R = Bn
17 : R = Bn
17 : R = Bn
19 : R = Bz
19 : R = Bz
5
rt
rt
0
rt
0
6.5
3.5
14
5
18 : R = Bn
18 : R = Bn
18 : R = Bn
20 : R = Bz
20 : R = Bz
55
67
86
56
57
15
15
5
15
9
12
13
14
15
16
17
18
21 : R = OBn, R1 = H, Ar = Ph
23 : R = OBz, R1 = H, Ar = Ph
23 : R = OBz, R1 = H, Ar = Ph
25 : R = OBn, R1 = H, Ar = 2-Naph
27 : R = OBz, R1 = H, Ar = 2-Naph
29 : R = H, R1 = OBn, Ar = Ph
29 : R = H, R1 = OBn, Ar = Ph
5
5
15
5
5
5
rt
rt
rt
rt
rt
rt
0
3
22 : R = OBn, R1 = H, Ar = Ph
24 : R = OBz, R1 = H, Ar = Ph
24 : R = OBz, R1 = H, Ar = Ph
26 : R = OBn, R1 = H, Ar = 2-Naph
28 : R = OBz, R1 = H, Ar = 2-Naph
30 : R = H, R1 = OBn, Ar = Ph
30 : R = H, R1 = OBn, Ar = Ph
82
63
90
86
89
62
90
21
4.5
8
16
4.5
20
15
19
20
5
5
14
rt
2.5
3.5
89
84
21
22
23
35 : R = R1 = H
5
5
5
rt
rt
rt
0.75
0.75
1.5
36 : R = R1 = H
89
92
90
37 : R = Me, R1 = H
39 : R = H, R1 = Me
38 : R = Me, R1 = H
40 : R = H, R1 = Me

514 J. Chin. Chem. Soc., Vol. 56, No. 3, 2009
Shie et al.
products 18 and 20 in 55% and 56% yields, respectively.
Increasing the catalyst concentrations to 15 mol% and con-
ducting the reaction at 0 °C improved the yield remarkably
in the case of the former (entry 9, 86%), whereas a substan-
tial amount of the hydrolyzed 4,6-diol (30%) still prevailed
in the latter (entry 11, 57%). The b-form benzoates 21, 25,
and 27, individually, delivered the desired products 22 (en-
try 12, 82%), 2624 (entry 15, 82%), and 2825 (entry 16, 82%)
at ambient temperature. The absolute configuration of
compound 22 was determined through X-ray single-crystal
analysis (see Supporting Information). The 3-OBz analog
23, although sluggish to react under the optimized condi-
tions (entry 13, 63%), successfully furnished the expected
24 rapidly and in excellent yield (90%), when 15 mol%
Cu(OTf)2 was used (entry 14). A similar phenomenon was
observed in the case of the allosamine derivative 29 (en-
tries 17 and 18), and the corresponding 6-alcohol 3026 was
obtained in 90% yield. In entries 19 and 20, the D-galacto-
and D-manno-configured 4,6-O-benzylidene acetals 31
and 33 also yielded the desired 4-OBn derivatives 3210
(89%) and 3427 (84%), respectively.
Table 3. Cu(OTf)2-catalyzed silane-reductive ring opening of
compound 4 to the corresponding 4-alcohol 6 in various
solvents
x mol% Cu(OTf)2, silane
4
+
5
6
solvent, 0 o
C
rt
Yield (%)
mol% of
Cu(OTf)2
Entry
Silanea
Solvent
t (h)
5
6
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0.5
5
Et3SiH
Me2EtSiH
Et3SiH
Me2EtSiH
Et3SiH
Me2EtSiH
Et3SiH
Me2EtSiH
Et3SiH
Me2EtSiH
Me2EtSiH
Me2EtSiH
Et3SiH
Me2EtSiH
(i-Pr)3SiH
NaCNBH3
Me2EtSiH
Me2EtSiH
Me2EtSiH
CH2Cl2
CH2Cl2
CH3NO2
CH3NO2
THF
15
9
1
0
0
0
0
0
0
0
0
7
0
0
1
2
3
9
0
3
3
2
62
65
60
68
0
14
0
0
1
21
21
16
16
1
0.5
15
16
8
6
4
21
4
0.5
0.5
THF
Toluene
Toluene
CH3CN
CH3CN
CH3CNb
CH3CNc
EtCN
9
76
84
0
10
11
12
13
14
15
16
17
18
19
5
75
83
29
0
75
80
82
EtCN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Finally, we examined ring opening of some common
non-sugar substrates. The symmetrical 1,3-O-benzylidene
acetals 35 (entry 21) and 37 (entry 22) underwent a smooth
cleavage in a rapid manner to afford the primary alcohols
3628 (89%) and 3829 (92%), respectively. Likewise, in the
case of the unsymmetrical acetal 39, excellent regioselec-
tivity was observed, and the expected compound 4030 was
obtained in 90% yield (entry 23).
10
a Two equivalents of silane were used.
b Anhydrous 4 Å MS were added extra.
c Anhydrous CuSO4 was added extra.
concentrations. The addition of catalyst was carried out at 0
°C, and the reaction was gradually warmed up to room tem-
perature. When 1 mol% Cu(OTf)2 was used together with
triethylsilane in dichloromethane (entry 1), the reaction
took 15 h to provide the secondary alcohol 614b (62%) as
the only regioisomer. A smaller reducing agent Me2EtSiH
offered a marginally improved yield of 6 (65%) in a much
shorter reaction time (entry 2, 9 h). Use of a more polar sol-
vent like nitromethane speeded up the reactions of 4 with
Et3SiH (entry 3, 1 h) and Me2EtSiH (entry 4, 1 h), affording
6 as the sole product in 60% and 68% yields, respectively.
Although no other regioisomer was detected, hydrolysis of
compound 4 to the corresponding 4,6-diol seemed to be-
come a dominant factor in limiting the yield. Tetrahydro-
furan and toluene gave disappointing results (entries 5-8).
Nevertheless, reduction of 4 in acetonitrile using Et3SiH
(entry 9, 1 h) readily furnished the expected compound 6
(76%) along with the minor isomer 5 (7%), while Me2EtSiH
led to 6 in 84% yield (entry 10, 0.5 h), exclusively. The hy-
Regioselective Ring Opening of Benzylidene Acetals
to the Secondary Alcohols
The catalytic properties of M(OTf)n for the regio-
selective reductive cleavage of benzylidene acetal at O4
were further investigated. Apreliminary screening was car-
ried out using three representative members, V(O)(OTf)2,
Sc(OTf)3 and Cu(OTf)2. Initial trial experiments with the
model compound 4 were conducted in dichloromethane at
ambient temperature in the presence of 30 mol% catalyst
and 5 equiv of triethylsilane. Of these, V(O)(OTf)2 and
Sc(OTf)3 virtually remained inert under the conditions, and
only Cu(OTf)2 provided the 4-alcohol 6 in 68% yield.
These results guided us to discover the inherent potential of
Cu(OTf)2 first.
Table 3 summarizes a systematic study of Cu(OTf)2-
catalyzed silane-reductive O4-opening of the acetal 4, in-
cluding the effects of solvents, silane agents, and catalyst

Regioselective Ring Opening of Benzylidene Acetals
J. Chin. Chem. Soc., Vol. 56, No. 3, 2009 515
drolyzed product was encountered to the extent of 10% in
these cases. Extra addition of anhydrous 4 Å MS (entry 11)
or CuSO4 (entry 12), for avoiding this side reaction, proved
to be futile exercises. Surprisingly, the former gave back
unchanged starting material, whereas the latter generated 6
in a negligibly small amount (5%). Propionitrile was found
to be a good solvent for this type of reaction with either
Et3SiH (entry 13, 75%, 8 h) or Me2EtSiH (entry 14, 83%, 6
h). Similar results were obtained as those with acetonitrile,
except that a longer time was needed to complete the reac-
tion, and compound 5 also appeared in trace amounts.
We further examined (i-Pr)3SiH (entry 15) and
NaCNBH3 (entry 16) as reducing agents in acetonitrile.
However, both cases displayed poor yields and selectivity.
In order to fine-tune the reaction conditions, different cata-
lytic amounts of Cu(OTf)2 were investigated. In entry 17,
when the catalyst concentration was halved, the transfor-
mation took place gradually (4 h) to afford compound 6 in
75% yield, whereas increasing the concentration of catalyst
to either 5 mol% (entry 18) or 10 mol% (entry 19) did not
improve the yields of 6 (80-82%). From the above studies,
1 mol% of Cu(OTf)2 turned out to be the minimum require-
ment for optimum activity.
Table 4. Me2EtSiH-reductive ring opening of compound 4 to the
corresponding 4-alcohol 6 in acetonitrile using 1 mol%
M(OTf)n as the catalyst
Yield (%)
Entry
M(OTf)n
t (h)
5
6
1
2
3
4
5
6
7
8
La(OTf)3
Pr(OTf)3
Nd(OTf)3
Sm(OTf)3
Eu(OTf)3
Gd(OTf)3
Yb(OTf)3
Sc(OTf)3
In(OTf)3
V(O)(OTf)2
Zn(OTf)2
AgOTf
20
18
18
18
18
18
20
1
1.5
20
18
0.5
0
0
0
0
0
0
0
8
5
0
0
5
0
0
0
0
0
0
0
75
73
30
0
9
10
11
12
75
glucopyranoside 11 and thioglycoside 13, providing the
secondary alcohols 43 (entry 3, 74%) and 44 (entry 4,
79%), individually, in good yields. In the D-glucosamine
series, the a-methyl 3-OBn and 3-OBz acetals 17 (entry 5)
and 19 (entry 6) furnished the desired adducts 45 (80%)
and 46 (83%), respectively. Similarly, the 1,3-di-OBz ana-
log 23 afforded compound 47 in 87% yield (entry 7). These
experiments revealed that the electron-withdrawing group
at the O3 position does not affect the reactivity of sub-
strates, in contrast to that observed in the borane-reductive
O6-opening reactions. In entry 8, the D-mannopyranosyl
sugar 33 successfully underwent a facile regioselective
cleavage to give the 6-OBn derivative 4831 (70%), while
the non-carbohydrate compound 39 (entry 9) yielded the
regioisomers 1-OH-3-OBn 40 (22%) and 1-OBn-3-OH
4932 (24%), along with the 1,3-di-OBn ether 50 (36%) as
the major product.Interestingly, extra additions of 1 equiv
benzaldehyde and 1 equiv Me2EtSiH to the reaction mix-
ture could increase the yield of 50 to 52%.
Finally, a variety of M(OTf)n was screened to esti-
mate their catalytic activities in the regioselective O4-
opening of acetal 4 with Me2EtSiH in acetonitrile (Table 4).
None of the lanthanide series metal trifluoromethanesulfo-
nates (entries 1-7) or Zn(OTf)2 (entry 11) produced the ex-
pected alcohol 6. Interestingly, Sc(OTf)3, which was inert
in dichloromethane in our preliminary studies, was found
to be effective in CH3CN, and compound 6 was isolated in
75% yield (entry 8). In(OTf)3 (entry 9, 73%) and AgOTf
(entry 12, 75%) also worked well, while V(O)(OTf)2 gave
poor results (entry 10, 30%). In comparison with the above
catalysts, Cu(OTf)2 exhibited the best yields in all our
attempts (Table 3, entry 10, 84%).
With this optimized set of reaction conditions [1
mol% Cu(OTf)2, Me2EtSiH, CH3CN, 0 °C ® rt], a number
of a- and b-hexopyranosides bearing different protecting
groups were examined to check the generality of this proto-
col. As described in Table 5, a rapid conversion (1-2 h) of
the 4,6-O-benzylidene acetals to the corresponding 4-OH-
6-OBn derivatives was observed. In entries 1 and 2, reac-
tions of the benzoates 7 and 9 led to the O4-opened prod-
ucts 41 and 4214a in 71% and 85% yields, respectively. Sim-
ilar high selectivity was realized in cases of the b-form
CONCLUSIONS
Metal trifluoromethanesulfonates have been devel-
oped as versatile catalysts for regioselective borane- and
dimethylethylsilane-reductive ring cleavages of various
benzylidene acetals to the corresponding primary and sec-
ondary alcohols, respectively. The selectivity is very high
and the reaction conditions are mild enough to apply to a
wide range of substrates containing various protecting
groups.

516 J. Chin. Chem. Soc., Vol. 56, No. 3, 2009
Shie et al.
used without purification, unless otherwise mentioned.
Flash column chromatography was carried out on Silica
Gel 60 (230-400 mesh, E. Merck). TLC was performed on
pre-coated glass plates of Silica Gel 60 F254 (0.25 mm, E.
Merck); detection was executed by spraying with a solution
of Ce(NH4)2(NO3)6 (0.5 g), (NH4)6Mo7O24 (24 g) and
H2SO4 (28 mL) in water (500 mL) and subsequent heating
on a hot plate. Melting points were determined with a Büchi
B-540 apparatus and are uncorrected. Optical rotations
were measured with Jasco DIP-370 and Horiba Sepa-300
Table 5. 1 Mol% Cu(OTf)2-catalyzed Me2EtSiH-reductive O4-
ring opening of various benzylidene acetals in aceto-
nitrile
Entry Acetal
t (h)
Product
Yield (%)
1
2
7
9
1
1
41 : R = H-
42 : R = Bz
71
85
1
3
4
11
13
0.5
1.5
74
79
polarimeters at 589 nm (Na) at ~25 °C. H, 13C NMR,
DEPT, 1H-1H COSY, 1H-13C COSY, and NOESY spectra
were recorded with Bruker AMX400, AV400, AV500, and
AV600 MHz instruments. Chemical shifts are in ppm from
Me4Si, generated from the CDCl3 lock signal at d 7.24. IR
spectra were taken with a Perkin-Elmer Paragon 1000 FT-
IR spectrometer using NaCl plates. Elemental analyses
were measured with a Perkin-Elmer 2400CHN instrument.
Mass spectra were obtained with a FAB JMS-700 double
focusing mass spectrometer (JEOL, Tokyo, Japan).
General Procedure for Regioselective Ring Opening
of Benzylidene Acetals to the Primary Alcohols
A 1 M solution of borane/tetrahydrofuran complex in
tetrahydrofuran (5 mL, 5 mmol) was added to a benzyli-
dene acetal (1 mmol) at room temperature under nitrogen.
The mixture was stirred for 10 min, and freshly dried cop-
per(II) trifluoromethanesulfonate (18 mg, 0.05 mmol) was
added to the solution. After stirring for a period of time (Ta-
bles 1 and 2), the mixture was cooled down to 0 °C, and the
reaction was quenched by sequential additions of triethyl-
amine (0.14 mL, 1 mmol) and methanol (1.8 mL, caution:
hydrogen gas was evolved). The resultant mixture was con-
centrated at reduced pressure followed by coevaporation
with methanol. The residue was purified by flash column
chromatography on silica gel to give the expected primary
alcohol (Tables 1 and 2).
5
6
17
19
1
0.5
45 : R = Bn
46 : R = Bz
80
83
7
8
23
33
0.5
1
87
70
9
39
2
40 : R1 = H, R2 = Bn
49 : R1 = Bn, R2 = H
50 : R1 = R2 = Bn
22
24
36
EXPERIMENTAL SECTION
General
Methyl 2,3,4-Tri-O-benzyl-a-D-glucopyranoside (5)
[a] 2D9 +26.3 (c 1.1, CHCl3); IR (CHCl3) n 3475, 3027,
1
2905, 1452, 1363, 1055, 1026, 735, 695 cm-1; H NMR
All reactions were conducted in flame-dried glass-
ware, under dry nitrogen atmosphere. Cu(OTf)2 was desic-
cated with anhydrous P2O5 under a high vacuum system
overnight. Dichloromethane was purified and dried from a
safe purification system containing activated Al2O3. Aceto-
nitrile was freshly distilled from calcium hydride under ni-
trogen. Anhydrous N,N-dimethylformamide, pyridine, and
methanol were purchased from Sigma-Aldrich and used as
such. All reagents obtained from commercial sources were
(400 MHz, CDCl3) d 7.35-7.25 (m, 15H, ArH), 4.98 (d, J =
11.0 Hz, 1H, CH2Ph), 4.86 (d, J = 11.1 Hz, 1H, CH2Ph),
4.82 (d, J = 11.0 Hz, 1H, CH2Ph), 4.78 (d, J = 12.1 Hz, 1H,
CH2Ph), 4.64 (d, J = 12.1 Hz, 1H, CH2Ph), 4.62 (d, J = 11.1
Hz, 1H, CH2Ph), 4.56 (d, J = 3.6 Hz, 1H, H-1), 3.99 (t, J =
9.4 Hz, 1H, H-3), 3.75 (ddd, J = 11.6, 5.4, 2.7 Hz, 1H, H-
6a), 3.70-3.61 (m, 2H, H-6b, H-5), 3.50 (dd, J = 9.6, 9.4
Hz, 1H, H-4), 3.48 (dd, J = 9.4, 3.6 Hz, 1H, H-2), 3.35 (s,

Regioselective Ring Opening of Benzylidene Acetals
J. Chin. Chem. Soc., Vol. 56, No. 3, 2009 517
3H, OCH3), 1.60 (dd, J = 7.4, 5.4 Hz, 1H, 6-OH); 13C NMR
(100 MHz, CDCl3) d 138.7 (C), 138.1 (2 ´ C), 128.5 (CH),
128.4 (CH), 128.1 (CH), 128.0 (CH), 127.93 (CH), 127.85
(CH), 127.6 (CH), 98.1 (CH), 81.9 (CH), 79.9 (CH), 77.4
(CH), 75.7 (CH2), 75.0 (CH2), 73.4 (CH2), 70.6 (CH), 61.8
(CH2), 55.2 (CH3); HRMS [FAB, (M-H)+] calcd for
C28H31O6 463.2121, found 463.2111.
2928, 1726, 1269, 1212, 1209, 1147, 1094 cm-1; 1H NMR
(500 MHz, CDCl3) d 8.01 (dd, J = 7.2, 1.2 Hz, 2H, BzH),
7.56 (dt, J = 7.2, 1.2 Hz, 1H, BzH), 7.43 (t, J = 7.2 Hz, 2H,
BzH), 7.35-7.28 (m, 5H, ArH), 7.12 (s, 5H, ArH), 5.23 (dd,
J = 9.2, 8.0 Hz, 1H, H-2), 4.86 (d, J = 11.0 Hz, 1H, CH2Ph),
4.75 (d, J = 11.2 Hz, 1H, CH2Ph), 4.67 (d, J = 11.0, 1H,
CH2Ph), 4.67 (d, J = 11.2 Hz, 1H, CH2Ph), 4.48 (d, J = 8.0
Hz, 1H, H-1), 3.91 (dd, J = 12.0, 2.5 Hz, 1H, H-6a), 3.85 (t,
J = 9.2 Hz, 1H, H-3), 3.76 (dd, J = 12.0, 4.4 Hz, 1H, H-6b),
3.74 (t, J = 9.2 Hz, 1H, H-4), 3.48-3.44 (m, 1H, H-5), 3.45
(s, 3H, OCH3), 2.01 (bs, 1H, 6-OH); 13C NMR (125 MHz,
CDCl3) d 165.2 (C), 137.8 (C), 137.7 (C), 133.1 (CH),
129.9 (C), 129.8 (CH), 128.5 (CH), 128.4 (CH), 128.2
(CH), 128.1 (CH), 128.0 (CH), 127.6 (CH), 102.1 (CH),
82.6 (CH), 77.6 (CH), 75.4 (CH), 75.1 (CH2), 75.1 (CH2),
73.7 (CH), 61.8 (CH2), 57.0 (CH3); HRMS (FAB, MH+)
calcd for C28H31O7 479.2070, found 479.2079.
Methyl 2-O-Benzoyl-4-O-benzyl-a-D-glucopyranoside
(8)
[a] 3D0 +151.3 (c 1.2, CHCl3); IR (CHCl3) n 3448,
2926, 1721, 1454, 1277, 1103, 1029 cm-1; 1H NMR (500
MHz, CDCl3) d 8.07 (d, J = 7.2 Hz, 2H, BzH), 7.57 (t, J =
7.2 Hz, 1H, BzH), 7.44 (t, J = 7.2 Hz, 2H, BzH), 7.36-7.33
(m, 4H, ArH), 7.31-7.28 (m, 1H, ArH), 5.00 (d, J = 3.6 Hz,
1H, H-1), 4.89 (dd, J = 10.0, 3.6 Hz, 1H, H-2), 4.86 (d, J =
11.4 Hz, 1H, CH2Ph), 4.76 (d, J = 11.4 Hz, 1H, CH2Ph),
4.27 (td, J = 10.0, 3.3 Hz, 1H, H-3), 3.86 (ddd, J = 11.5, 7.7,
3.3 Hz, 1H, H-6a), 3.79 (ddd, J = 11.5, 7.7, 3.3 Hz, 1H,
H-6b), 3.72 (dt, J = 10.0, 3.3 Hz, 1H, H-5), 3.59 (t, J = 10.0
Hz, 1H, H-4), 3.34 (s, 3H, OCH3), 2.26 (d, J = 3.3 Hz, 1H,
3-OH), 1.80 (t, J = 7.7 Hz, 1H, 6-OH); 13C NMR (100
MHz, CDCl3) d 166.4 (C), 138.1 (C), 133.4 (CH), 129.9
(CH), 129.5 (C), 128.6 (CH), 128.4 (CH), 128.1 (CH),
128.0 (CH), 97.1 (CH), 77.8 (CH), 74.7 (CH2), 74.1 (CH),
72.0 (CH), 70.5 (CH), 61.8 (CH2), 55.3 (CH3); HRMS
(FAB, MH+) calcd for C24H25O7 389.1600, found
389.1597.
p-Methylphenyl 2,3,4-Tri-O-benzyl-1-thio-b-D-gluco-
pyranoside (14)
[a] 2D2 –10.9 (c 1.2, CHCl3); IR (CHCl3) n 3502, 2919,
2858, 1454, 1399, 1274, 1209, 1155, 1071 cm-1; 1H NMR
(600 MHz, CDCl3) d 7.45-7.36 (m, 4H, ArH), 7.35-7.25
(m, 13H, ArH), 7.14 (d, J = 7.9 Hz, 2H, ArH), 4.91 (d, J =
10.1 Hz, 1H, CH2Ph), 4.89 (d, J = 8.9 Hz, 1H, CH2Ph), 4.85
(d, J = 8.9 Hz, 1H, CH2Ph), 4.84 (d, J = 9.0 Hz, 1H,
CH2Ph), 4.75 (d, J = 10.1 Hz, 1H, CH2Ph), 4.65 (d, J = 9.0
Hz, 1H, CH2Ph), 4.65 (d, J = 9.3 Hz, 1H, H-1), 3.85 (d, J =
11.9 Hz, 1H, H-6a), 3.70 (t, J = 9.3 Hz, 1H, H-3), 3.68 (m,
1H, H-6b), 3.54 (t, J = 9.3 Hz, 1H, H-4), 3.45 (t, J = 9.3 Hz,
1H, H-2), 3.35 (ddd, J = 9.3, 4.7, 2.6 Hz, 1H, H-5), 2.33 (s,
3H, CH3), 1.94 (bs, 1H, 6-OH); 13C NMR (125 MHz, CDCl3)
d 138.3 (C), 138.0 (C), 137.9 (C), 137.8 (C), 132.6 (CH),
129.8 (CH), 129.4 (C), 128.5 (CH), 128.5 (CH), 128.4
(CH), 128.2 (CH), 128.0 (CH), 128.0 (CH), 127.9 (CH),
127.8 (CH), 127.7 (CH), 87.8 (CH), 86.5 (CH), 81.1 (CH),
79.2 (CH), 77.6 (CH), 75.8 (CH2), 75.5 (CH2), 75.1 (CH2),
62.1 (CH2), 21.1 (CH3); HRMS (FAB, MNa+) calcd for
C34H36O5SNa 579.2181, found 579.2185.
Methyl 2,3-Di-O-benzoyl-4-O-benzyl-a-D-glucopyrano-
side (10)
[a] 2D9 +140.9 (c 0.8, CHCl3); IR (CHCl3) n 3445,
2848, 1725, 1447, 1280, 1106, 1068 cm-1; 1H NMR (400
MHz, CDCl3) d 7.95 (dt, J = 7.2, 1.4 Hz, 4H, BzH), 7.48
(tq, J = 7.2, 1.4 Hz, 2H, BzH), 7.35 (dt, J = 7.2, 2.8 Hz, 4H,
BzH), 7.18-7.15 (m, 5H, ArH), 6.04 (t, J = 9.2 Hz, 1H,
H-3), 5.12 (d, J = 3.4 Hz, 1H, H-1), 5.10 (dd, J = 9.2, 3.4
Hz, 1H, H-2), 4.62 (d, J = 11.1 Hz, 1H, CH2Ph), 4.60 (d, J =
11.1 Hz, 1H, CH2Ph), 3.93 (t, J = 9.2 Hz, 1H, H-4), 3.90-
3.86 (m, 3H, H-5, H-6a, H-6b), 3.38 (s, 3H, OCH3), 1.92
(bs, 1H, 6-OH); 13C NMR (100 MHz, CDCl3) d 166.1 (C),
165.6 (C), 137.4 (C), 133.3 (CH), 133.0 (CH), 129.9 (C),
129.8 (CH), 129.2 (C), 128.5 (CH), 128.3 (CH), 128.0
(CH), 97.0 (CH), 75.8 (CH), 74.7 (CH2), 72.5 (CH), 72.4
(CH), 70.7 (CH), 61.5 (CH2), 55.3 (CH3); HRMS (FAB,
MH+) calcd for C28H29O8 493.1862, found 493.1850.
Methyl 2-O-Benzoyl-3,4-di-O-benzyl-b-D-glucopyrano-
side (12)
Ethyl 2,3-Di-O-benzyl-4-O-(p-methoxybenzyl)-1-thio-
b-D-glucopyranoside (16)
[a] 2D2 –7.2 (c 0.6, CHCl3); IR (CHCl3) n 3320, 2896,
1514, 1452, 1391, 1353, 1250 cm-1; 1H NMR (500 MHz,
CDCl3) d 7.34-7.26 (m, 10H, ArH), 7.18 (d, J = 8.6 Hz, 2H,
4-OMePhH), 6.83 (d, J = 8.6 Hz, 2H, 4-OMePhH), 4.91 (d,
J = 11.0 Hz, 1H, CH2Ph), 4.89 (d, J = 10.4 Hz, 1H, CH2Ph),
4.86 (d, J = 11.0 Hz, 1H, CH2Ph), 4.76 (d, J = 10.6 Hz, 1H,
CH2Ph), 4.72 (d, J = 10.4 Hz, 1H, CH2Ph), 4.56 (d, J = 10.6
[a] 2D9 +53.6 (c 0.5, CHCl3); IR (CHCl3) n 3487, 3059,

518 J. Chin. Chem. Soc., Vol. 56, No. 3, 2009
Shie et al.
Hz, 1H, CH2Ph), 4.47 (d, J = 9.6 Hz, 1H, H-1), 3.83 (ddd, J
= 12.0, 6.0, 2.7 Hz, 1 H, H-6a), 3.77 (s, 3H, ArOCH3), 3.67
(t, J = 9.6 Hz, 1H, H-3), 3.68-3.62 (m, 1H, H-6b), 3.53 (t, J
= 9.6 Hz, 1H, H-4), 3.38 (t, J = 9.6 Hz, 1H, H-2), 3.33 (ddd,
J = 9.6, 4.7, 2.7 Hz, 1H, H-5), 2.73 (ddt, J = 14.9, 7.4, 5.2
Hz, 2H, SCH2CH3), 1.88 (t, J = 6.0 Hz, 1H, 6-OH), 1.30 (t,
J = 7.4 Hz, 3H, SCH2CH3); 13C NMR (100 MHz, CDCl3) d
159.4 (C), 138.5 (C), 137.9 (C), 130.1 (C), 129.8 (CH),
128.5 (CH), 128.4 (CH), 128.3 (CH), 127.9 (CH), 127.7
(CH), 113.9 (CH), 86.5 (CH), 85.3 (CH), 81.8 (CH), 79.3
(CH), 77.4 (CH), 75.7 (CH2), 75.6 (CH2), 74.8 (CH2), 62.2
(CH2), 55.3 (CH3), 25.2 (CH2), 15.2 (CH3); HRMS (FAB,
MH+) calcd for C30H37O6S 525.2311, found 525.2315.
Methyl 2-Azido-3,4-di-O-benzyl-2-deoxy-a-D-gluco-
pyranoside (18)
2-Azido-3,4-di-O-benzyl-2-deoxy-b-D-glucopyranosyl
Benzoate (22)
[a] 2D2 –79.4 (c 1.0, CHCl3); IR (CHCl3) n 3510, 3029,
2880, 2114, 1726, 1453, 1260, 1075, 1036 cm-1; 1H NMR
(500 MHz, CDCl3) d 8.08 (dd, J = 8.0, 1.2 Hz, 2H, BzH),
7.60 (dt, J = 8.0, 1.2 Hz, 1H, BzH), 7.46 (t, J = 8.0 Hz, 2H,
BzH), 7.38-7.27 (m, 10H, ArH), 5.71 (d, J = 8.5 Hz, 1H,
H-1), 4.91 (d, J = 11.0 Hz, 1H, CH2Ph), 4.89 (d, J = 11.0
Hz, 1H, CH2Ph), 4.87 (d, J = 11.6 Hz, 1H, CH2Ph), 4.69 (d,
J = 11.6 Hz, 1H, CH2Ph), 3.87 (dd, J = 12.0, 2.5 Hz, 1H,
H-6a), 3.72-3.67 (m, 3H, H-2, H-4, H-6b), 3.61 (t, J = 9.6
Hz, 1H, H-3), 3.54 (ddd, J = 9.6, 3.7, 2.5 Hz, 1H, H-5), 1.69
(bs, 1H, 6-OH); 13C NMR (125 MHz, CDCl3) d 164.6 (C),
137.6 (2 ´ C), 133.9 (CH), 130.1 (CH), 128.8 (C), 128.7
(CH), 128.6 (CH), 128.53 (CH), 128.49 (CH), 128.1 (CH),
128.0 (CH), 93.5 (CH), 82.9 (CH), 76.7 (CH), 76.3 (CH),
75.7 (CH2), 75.1 (CH2), 65.5 (CH), 61.2 (CH2); HRMS
(FAB, MH+) calcd for C27H28O6N3 490.1978, found
490.1974.
[a] 2D2 +87.3 (c 1.0, CHCl3); IR (CHCl3) n 3467, 2916,
2105, 1496, 1454, 1361, 1258, 1148, 1119, 1051, 1029
1
cm-1; H NMR (600 MHz, CDCl3) d 7.44-7.20 (m, 10H,
ArH), 4.90 (d, J = 10.8 Hz, 1H, CH2Ph), 4.88 (d, J = 10.8
Hz, 1H, CH2Ph), 4.88 (d, J = 11.0 Hz, 1H, CH2Ph), 4.79 (d,
J = 3.5 Hz, 1H, H-1), 4.68 (d, J = 11.0 Hz, 1H, CH2Ph),
4.00 (dd, J = 10.1, 9.5 Hz, 1H, H-3), 3.81 (d, J = 11.5 Hz,
1H, H-6a), 3.74 (d, J = 11.5 Hz, 1H, H-6b), 3.70 (dt, J = 9.5,
3.0 Hz, 1H, H-5), 3.62 (t, J = 9.5 Hz, 1H, H-4), 3.42 (s, 3H,
OCH3), 3.40 (dd, J = 10.1, 3.5 Hz, 1H, H-2), 1.71 (bs, 1H,
6-OH) ppm; 13C NMR (125 MHz, CDCl3) d 137.8 (C),
137.1 (C), 128.5 (CH), 128.5 (CH), 128.1 (CH), 128.0
(CH), 127.9 (CH), 98.7 (CH), 80.3 (CH), 77.9 (CH), 75.5
(CH2), 75.0 (CH2), 71.2 (CH), 63.7 (CH), 61.6 (CH2), 55.2
(CH3); HRMS [FAB, (M-H)+] calcd for C21H24O5N3
398.1716, found 398.1729.
2-Azido-3-O-benzoyl-4-O-benzyl-2-deoxy-b-D-gluco-
pyranosyl Benzoate (24)
o
[a] 3D0 +46.3 (c 1.0, CHCl3); mp 137-138 C; IR
(CHCl3) n 3372, 2950, 2097, 1720, 1646, 1538, 1259, 1082
1
cm-1; H NMR (400 MHz, CDCl3) d 8.09-8.04 (m, 4H,
Bz-H), 7.62-7.58 (m, 2H, Bz-H), 7.48-7.44 (m, 4H, Bz-H),
7.17-7.12 (m, 5H, Ar-H), 5.87 (d, J = 8.4 Hz, 1H, H-1),
5.49 (dd, J = 10.2, 9.2 Hz, 1H, H-3), 4.59, 4.58 (ABq, J =
11.1 Hz, 2H, CH2Ph), 3.95-3.91 (m, 2H, H-4, H-6a), 3.82-
3.77 (m, 2H, H-2, H-6b), 3.68 (dt, J = 9.7, 2.8 Hz, 1H, H-5),
1.77 (bs, 1H, 6-OH); 13C NMR (100 MHz, CDCl3) d 165.3
(C), 164.4 (C), 137.0 (C), 134.0 (C), 133.5 (CH), 130.1
(CH), 129.8 (CH), 129.4 (C), 129.3 (CH), 128.6 (CH),
128.5 (CH), 128.4 (CH), 128.2 (CH), 128.0 (CH), 93.6
(CH), 76.2 (CH), 74.7 (CH2), 74.6 (2 ´ CH), 63.7 (CH),
60.9 (CH2); HRMS (FAB, MH+) calcd for C27H26O7N3
504.1771, found 504.1785.
Methyl 2-Azido-3-O-benzoyl-4-O-benzyl-2-deoxy-a-D-
glucopyranoside (20)
[a] 2D9 +137.8 (c 1.5, CHCl3); IR (CHCl3) n 3487,
2925, 2108, 1728, 1269, 1094, 1070, 1053 cm-1; 1H NMR
(600 MHz, CDCl3) d 8.04 (d, 2H, J = 7.5 Hz, 2H, BzH),
7.56 (t, J = 7.5 Hz, 1H, BzH), 7.43 (t, J = 7.5 Hz, 2H, BzH),
7.20-7.11 (m, 5H, ArH), 5.85-5.77 (m, 1H, H-3), 4.88 (d, J
= 3.4 Hz, 1H, H-1), 4.60 (d, J = 11.0 Hz, 1H, CH2Ph), 4.56
(d, J = 11.0 Hz, 1H, CH2Ph), 3.81 (m, 4H, H-4, H-5, H-6a,
H-6b), 3.45 (s, 3H, OCH3), 3.27 (dd, J = 10.6, 3.4 Hz, 1H,
H-2), 1.74 (bs, 1H, 6-OH); 13C NMR (150 MHz, CDCl3) d
165.5 (C), 137.3 (C), 133.3 (CH), 129.9 (CH), 129.6 (C),
128.5 (CH), 128.4 (CH), 128.9 (CH), 128.0 (CH), 99.3
(CH), 75.7 (CH), 74.8 (CH2), 72.9 (CH), 71.0 (CH), 61.7
(CH), 61.4 (CH2), 55.4 (CH3); HRMS (FAB, MH+) calcd
for C21H24O6N3 414.1665, found 414.1660.
2-Azido-3-O-benzyl-2-deoxy-4-O-(2-naphthylmethyl)-b-
D-glucopyranosyl Benzoate (26)
o
[a] 2D8 –101.2 (c 0.60, CHCl3); mp 137-139 C; IR
(CHCl3) n 3500, 2896, 2108, 1736, 1261, 1074, 1049, 703
cm-1; 1H NMR (400 MHz, CDCl3) d 8.10 (d, J = 8.5 Hz, 2H,
BzH), 7.84-7.78 (m, 3H, ArH), 7.73 (s, 1H, ArH), 7.61 (dt,
J = 7.4, 1.2 Hz, 1H, ArH), 7.50-7.45 (m, 4H, ArH), 7.42-
7.31 (m, 6H, ArH), 5.75 (d, J = 8.2 Hz, 1H, H-1), 5.02 (d, J
= 11.2 Hz, 1H, CH2Ar), 4.96-4.85 (m, 3H, CH2Ar), 3.92
(dd, J = 12.3, 2.4 Hz, 1H, H-6a), 3.79-3.63 (m, 4H, H-2,
H-3, H-4, H-6b), 3.59 (ddd, J = 9.7, 3.8, 2.4 Hz, 1H, H-5),

Regioselective Ring Opening of Benzylidene Acetals
J. Chin. Chem. Soc., Vol. 56, No. 3, 2009 519
1.77 (s, 1H, OH-6); 13C NMR (75 MHz, CDCl3) d 164.6
(C), 137.6 (C), 135.1 (C), 133.9 (CH), 133.2 (C), 133.0
(C), 130.1 (CH), 128.7 (C), 128.6 (CH), 128.5 (C), 128.3
(CH), 128.03 (CH), 127.95 (CH), 127.9 (CH), 127.7 (CH),
126.7 (CH), 126.2 (CH), 126.1 (CH), 125.7 (CH), 93.5
(CH), 82.9 (CH), 76.9 (CH), 76.3 (CH), 75.7 (CH2), 75.1
(CH2), 65.5 (CH), 61.2 (CH2); HRMS (FAB, MH+) calcd
for C31H30N3O6 540.2134, found 540.2148.
74.94 (CH2), 74.86 (CH), 74.7 (CH), 73.9 (CH2), 72.1
(CH), 62.4 (CH), 61.5 (CH2); HRMS (FAB, M-H+) calcd
for C27H26N3O6 488.1822, found 488.1826. Anal. Calcd for
C27H27N3O6: C, 66.25; H, 5.56; N, 8.58. Found: C, 66.19;
H, 5.28; N, 8.44.
Methyl 2,3,4-Tri-O-benzyl-a-D-galactopyranoside (32)
[a] 2D9 +5.2 (c 1.8, CHCl3); IR (CHCl3) n 3483, 3064,
2919, 1496, 1454, 1399, 1351, 1196, 1096, 1055 cm-1; 1H
NMR (400 MHz, CDCl3) d 7.41-7.26 (m, 15H, ArH), 4.96
(d, J = 11.6 Hz, 1H, CH2Ph), 4.88 (d, J = 11.8 Hz, 1H,
CH2Ph), 4.83 (d, J = 12.0 Hz, 1H, CH2Ph), 4.74 (d, J = 11.8
Hz, 1H, CH2Ph), 4.70 (d, J = 3.6 Hz, 1H, H-1), 4.68 (d, J =
12.0 Hz, 1H, CH2Ph), 4.62 (d, J = 11.6 Hz, 1H, CH2Ph),
4.04 (dd, J = 10.0, 3.6 Hz, 1H, H-2), 3.92 (dd, J = 10.0, 2.8
Hz, 1H, H-3), 3.86 (d, J = 2.8 Hz, 1H, H-4), 3.73-3.69 (m,
2H, H-5, H-6a), 3.49-3.47 (m, 1H, H-6b), 3.35 (s, 3H,
OCH3), 1.69 (d, J = 7.0 Hz, 1H, 6-OH); 13C NMR (100
MHz, CDCl3) d 138.7 (C), 138.4 (C), 138.2 (C), 128.6
(CH), 128.5 (CH), 128.43 (CH), 128.36 (CH), 128.1 (CH),
128.0 (CH), 127.7 (CH), 127.61 (CH), 127.56 (CH), 98.8
(CH), 79.1 (CH), 76.5 (CH), 75.1 (CH), 74.4 (CH2), 73.62
(CH2), 73.58 (CH2), 70.2 (CH), 62.4 (CH2), 55.4 (CH3);
HRMS [FAB, (M-H)+] calcd for C28H31O6 463.2121, found
463.2112.
2-Azido-3-O-benzoyl-2-deoxy-4-O-(2-naphthylmethyl)-
b-D-glucopyranosyl Benzoate (28)
[a] 2D4 -84.9 (c 1.06, CHCl3); IR (CHCl3) n 3442,
2111, 1732, 1265, 1086 cm-1; 1H NMR (500 MHz, CDCl3)
d 8.07 (dd, J = 8.3, 1.1 Hz, 2H, BzH), 7.95 (dd, J = 8.3, 1.1
Hz, 2H, BzH), 7.67-7.64 (m, 2H, BzH), 7.61-7.51 (m, 4H,
BzH), 7.47-7.44 (m, 2H, ArH), 7.41-7.35 (m, 4H, ArH),
7.25-7.22 (m, 1H, ArH), 5.89 (d, J = 8.4 Hz, 1H, H-1), 5.50
(dd, J = 10.0, 9.4 Hz, 1H, H-3), 4.78, 4.72 (ABq, J = 11.3
Hz, 2H, CH2Naph), 3.99 (t, J = 9.4 Hz, 1H, H-4), 3.98 (ddd,
J = 12.5, 4.9, 2.8 Hz, 1H, H-6a), 3.85 (dd, J = 10.0, 8.4 Hz,
1H, H-2), 3.84 (ddd, J = 12.5, 8.4, 2.8 Hz, 1H, H-6b), 3.72
(dt, J = 9.4, 2.8 Hz, 1H, H-5), 1.83 (dd, J = 8.4, 4.9 Hz, 1H,
OH-6); 13C NMR (125 MHz, CDCl3) d 165.3 (C), 164.4
(C), 134.5 (C), 134.0 (CH), 133.5 (CH), 133.04 (C), 132.98
(C), 130.1 (CH), 129.8 (CH), 129.2 (C), 128.6 (CH), 128.5
(C), 128.4 (CH), 128.3 (CH), 127.9 (CH), 127.7 (CH),
127.2 (CH), 126.1 (CH), 126.00 (CH), 125.97 (CH), 93.6
(CH), 76.3 (CH), 74.9 (CH2), 74.7 (CH), 74.5 (CH), 63.8
(CH), 61.0 (CH2); HRMS (FAB, M+) calcd for C31H27N3O7
553.1849, found 553.1842. Anal. Calcd for C31H27N3O7: C,
67.26; H, 4.92; N, 7.59. Found: C, 67.06; H, 4.92; N, 7.59.
2-Azido-3,4-di-O-benzyl-2-deoxy-b-D-allopyranosyl
Benzoate (30)
[a] 2D9 –130.3 (c 1.0, CHCl3); mp 155-156 °C; IR
(CHCl3) n 3510, 2913, 2098, 1736, 1596, 1347, 1261,
1066, 702 cm-1; 1H NMR (400 MHz, CDCl3) d 8.07-8.05
(m, 2H, ArH), 7.59-7.55 (m, 1H, ArH), 7.45-7.25 (m, 12H,
ArH), 6.28 (d, J = 8.4 Hz, 1H, H-1), 4.88 (d, J = 11.2 Hz,
1H, PhCH2), 4.80 (d, J = 11.2 Hz, 1H, PhCH2), 4.62 (d, J =
11.6 Hz, 1H, PhCH2), 4.54 (d, J = 11.6 Hz, 1H, PhCH2),
4.22 (t, J = 2.4 Hz, 1H, H-3), 4.18 (ddd, J = 9.6, 6.0, 3.0 Hz,
1H, H-5), 3.90 (ddd, J = 12.2, 5.1, 3.0 Hz, 1H, H-6a), 3.75
(ddd, J = 12.2, 8.0, 6.0 Hz, 1H, H-6b), 3.62 (dd, J = 9.6, 2.4
Hz, 1H, H-4), 3.49 (dd, J = 8.4, 2.4 Hz, 1H, H-2), 1.71 (dd,
J = 8.0, 5.1 Hz, 1H, OH); 13C NMR (100 MHz, CDCl3) d
164.6 (C), 137.9 (C), 137.4 (C), 133.7 (CH), 130.0 (CH),
128.9 (C), 128.6 (CH), 128.5 (CH), 128.3 (CH), 128.1
(CH), 128.0 (CH), 127.9 (CH), 127.8 (CH), 92.3 (CH),
Methyl 2,3,4-Tri-O-benzyl-a-D-mannopyranoside (34)
[a] 2D1 +27.6 (c 2.6, CHCl3); IR (CHCl3) n 3409, 2923,
1454, 1274, 1113, 1068, 1026 cm-1; 1H NMR (400 MHz,
CDCl3) d 7.35-7.25 (m, 15H, ArH), 4.92 (d, J = 11.0 Hz,
1H, CH2Ph), 4.76 (d, J = 12.0 Hz, 1H, CH2Ph), 4.68 (d, J =
2.0 Hz, 1H, H-1), 4.67 (d, J = 12.0, 1H, CH2Ph), 4.63 (d, J =
11.0, 1H, CH2Ph), 4.62 (s, 2H, CH2Ph), 3.95 (m, 1H, H-
6a), 3.88 (dd, J = 9.5, 3.0 Hz, 1H, H-6b), 3.83 (dd, J = 11.8,
3.0 Hz, 1H, H-3), 3.78 (dd, J = 3.0, 2.0 Hz, 1H, H-2), 3.76
(dd, J = 11.8, 9.5 Hz, 1H, H-4), 3.60 (ddd, J = 9.5, 4.5, 3.0
Hz, 1H, H-5), 3.29 (s, 3H, OCH3), 1.99 (bs, 1H, 6-OH); 13C
NMR (100 MHz, CDCl3) d 138.60 (C), 138.56 (C), 138.4
(C), 128.5 (CH), 128.1 (CH), 127.9 (CH), 127.8 (CH),
127.7 (CH), 99.3 (CH), 80.1 (CH), 75.1 (CH2), 74.9 (CH),
74.8 (CH), 73.0 (CH2), 72.2 (CH2), 72.0 (CH), 69.3 (CH2),
54.7 (CH3); HRMS [FAB, (M-H)+] calcd for C28H31O6
463.2121, found 463.2115.
3-Benzyloxy-1-propanol (36)
IR (CHCl3) n 3397, 2930, 2868, 1454, 1101, 1075
1
cm-1; H NMR (400 MHz, CDCl3) d 7.27-7.16 (m, 5H,
ArH), 4.43 (s, 2H, CH2Ph), 3.69 (t, J = 5.7 Hz, 2H, CH2O),
3.57 (t, J = 5.7 Hz, 2H, CH2O), 1.90 (t, J = 9.0 Hz, 1H, OH),
1.77 (quin, J = 5.7 Hz, 2H, CH2); 13C NMR (100 MHz,

520 J. Chin. Chem. Soc., Vol. 56, No. 3, 2009
Shie et al.
CDCl3) d 138.1 (C), 128.4 (CH), 127.7 (CH), 127.6 (CH),
73.3 (CH2), 69.4 (CH2), 61.9 (CH2), 32.1 (CH2); HRMS
(FAB, MH+) calcd for C10H15O2 167.1702, found 167.1701.
3-Benzyloxy-2,2-dimethyl-1-propanol (38)
IR (CHCl3) n 3427, 2957, 2871, 1099 cm-1; 1H NMR
(400 MHz, CDCl3) d 7.33-7.23 (m, 5H, ArH), 4.50 (s, 2H,
CH2Ph), 3.44 (s, 2H, CH2O), 3.31 (s, 2H, CH2O), 2.56 (bs,
1H, OH), 0.91 (s, 6H, 2 ´ CH3); 13C NMR (100 MHz,
CDCl3) d 138.1 (C), 128.4 (CH), 127.7 (CH), 127.5 (CH),
79.5 (CH2), 73.5 (CH2), 71.8 (CH2), 36.2 (C), 21.9 (2 ´
CH3); HRMS (FAB, MH+) calcd for C12H19O2 195.1385,
found 195.1384.
1H, H-2), 3.37 (s, 3H, OCH3), 2.30 (d, J = 2.2 Hz, 1H, 4-
OH); 13C NMR (125 MHz, CDCl3) d 138.8 (C), 138.1 (C),
138.0 (C), 128.6 (CH), 128.5 (CH), 128.4 (CH), 128.1
(CH), 128.0 (CH), 127.9 (CH), 127.8 (CH), 127.6 (CH),
98.2 (CH), 81.5 (CH), 79.6 (CH), 75.4 (CH2), 73.6 (CH2),
73.2 (CH2), 70.8 (CH), 69.9 (CH), 69.5 (CH2), 55.2 (CH3).
Methyl 2-O-Benzoyl-6-O-benzyl-a-D-glucopyranoside
(41)
[a] 2D5 +88.7 (c 1.9, CHCl3); IR (CHCl3) n 3430, 3062,
1
2920, 1718, 1601, 1450, 1276, 1046, 909, 713 cm-1; H
NMR (400 MHz, CDCl3) d 8.06 (d, J = 7.4 Hz, 2H, BzH),
7.54 (t, J = 7.4 Hz, 1H, BzH), 7.41 (t, J = 7.4 Hz, 2H, BzH),
7.25-7.34 (m, 5H, ArH), 5.00 (d, J = 3.7 Hz, 1H, H-1), 4.92
(dd, J = 9.3, 3.7 Hz, 1H, H-2), 4.62, 4.57 (ABq, J = 12.1 Hz,
2H, CH2Ph), 4.10 (t, J = 9.3 Hz, 1H, H-3), 3.83-3.63 (m,
4H, H-4, H-5, H-6a, H-6b), 3.36 (s, 3H, OCH3), 3.09 (d, J =
2.1 Hz, 1H, 4-OH), 2.83 (bs, 1H, 3-OH); 13C NMR (125
MHz, CDCl3) d 166.4 (C), 137.8 (C), 133.3 (CH), 129.9
(CH), 129.5 (C), 128.43 (CH), 128.38 (CH), 127.8 (CH),
127.7 (CH), 97.2 (CH), 73.8 (CH), 73.7 (CH2), 71.9 (CH),
71.8 (CH), 69.7 (CH2), 69.6 (CH), 55.3 (CH3); HRMS
(FAB, MH+) calcd for C21H25O7 389.1600, found 389.1597.
Methyl 2,3-Di-O-benzoyl-6-O-benzyl-a-D-glucopyrano-
side (42)
1H NMR (400 MHz, CDCl3) d 8.00-7.23 (m, 15H,
ArH), 5.73 (dd, J = 10.1, 8.8 Hz, 1H, H-3), 5.24 (dd, J =
10.1, 3.6 Hz, 1H, H-2), 5.12 (d, J = 3.6 Hz, 1H, H-1), 4.65,
4.60 (ABq, J = 12.0 Hz, 2H, CH2Ph), 4.00-3.92 (m, 2H,
H-4, H-5), 3.84 (dd, J = 10.4, 3.9 Hz, 1H, H-6a), 3.79 (dd, J
= 10.4, 3.2 Hz, 1H, H-6b), 3.41 (s, 3H, OCH3), 3.05 (bs,
1H, 4-OH); 13C NMR (125 MHz, CDCl3) d 167.2 (C),
165.9 (C), 137.8 (C), 133.3 (CH), 129.8 (CH), 129.3 (C),
129.2 (C), 128.4 (CH), 128.3 (CH), 127.8 (CH), 127.7
(CH), 97.1 (CH), 74.1 (CH), 73.7 (CH2), 71.4 (CH), 70.5
(CH), 70.2 (CH), 69.5 (CH2), 55.4 (CH3).
3-Benzyloxy-1-butanol (40)
IR (CHCl3) n 3422, 2932, 1206, 1087, 1055 cm-1; 1H
NMR (500 MHz, CDCl3) d 7.34-7.24 (m, 5H, ArH), 4.61
(d, J = 11.6 Hz, 1H, CH2Ph), 4.42 (d, J = 11.6 Hz, 1H,
CH2Ph), 3.80-3.70 (m, 3H, OCH2, OCH), 2.57 (bs, 1H,
OH), 1.81-1.70 (m, 2H, CH2), 1.24 (d, J = 6.2 Hz, 3H,
CH3); 13C NMR (125 MHz, CDCl3) d 138.4 (C), 128.4
(CH), 127.7 (CH), 127.6 (CH), 74.5 (CH), 70.4 (CH2), 60.8
(CH2), 38.8 (CH2), 19.3 (CH3); HRMS (FAB, MH+) calcd
for C11H17O2 181.1229, found 181.1232.
General Procedure for Regioselective Ring Opening
of Benzylidene Acetals to the Secondary Alcohols
To a solution of a benzylidene acetal (1 mmol) in ace-
tonitrile (2.3 mL per mmol of acetal) was added dimethyl-
ethylsilane (0.26 mL, 2 mmol) at room temperature under
nitrogen. The reaction flask was immersed in an ice-bath, a
solution of freshly dried copper(II) trifluoromethanesulfo-
nate (3.6 mg, 0.01 mmol) in acetonitrile (2.3 mL per mmol
of acetal) was added to the mixture, and the resultant solu-
tion was gradually warmed up to room temperature. After
stirring for a period of time (Tables 3 and 4), the mixture
was diluted with EtOAc (5 mL per mmol of acetal), and the
reaction solution was opened to the air and continuously
stirred for 2 h (pH = 5~6). The resultant mixture was washed
by sat’d NaHCO3(aq), dried over anhydrous MgSO4, and
concentrated in vacuo. Purification of the residue via flash
column chromatography on silica gel provided the ex-
pected secondary alcohol (Tables 3 and 4).
Methyl 2-O-Benzoyl-3,6-di-O-benzyl-b-D-glucopyrano-
side (43)
[a] 3D2 –170.7 (c 0.5, CHCl3); IR (CHCl3) n 3493,
2870, 1726, 1601, 1451, 1270, 1069, 1027, 985, 739, 711
cm-1; 1H NMR (400 MHz, CDCl3) d 8.02 (d, J = 7.4 Hz, 2H,
BzH), 7.56 (t, J = 7.4 Hz, 1H, BzH), 7.43 (t, J = 7.4 Hz, 2H,
BzH), 7.40-7.10 (m, 10H, ArH), 5.22 (dd, J = 9.4, 7.9 Hz,
1H, H-2), 4.71, 4.66 (ABq, J = 11.5 Hz, 2H, CH2Ph), 4.63,
4.57 (ABq, J = 12.0 Hz, 2H, CH2Ph), 4.44 (d, J = 7.9 Hz,
1H, H-1), 3.79 (td, J = 9.4, 2.2 Hz, 1H, H-4), 3.79 (m, 2H,
H-6a, H-6b), 3.66 (t, J = 9.4 Hz, 1H, H-3), 3.53 (dt, J = 9.4,
4.8 Hz, 1H, H-5), 3.44 (s, 3H, OCH3), 2.71 (d, J = 2.2 Hz,
Methyl 2,3,6-Tri-O-benzyl-a-D-glucopyranoside (6)
1H NMR (400 MHz, CDCl3) d 7.35-7.24 (m, 15H,
ArH), 4.98, 4.72 (ABq, J = 11.4 Hz, 2H, CH2Ph), 4.75, 4.64
(ABq, J = 12.3 Hz, 2H, CH2Ph), 4.62 (d, J = 3.5 Hz, 1H,
H-1), 4.57, 4.52 (ABq, J = 12.1 Hz, 2H, CH2Ph), 3.77 (t, J
= 9.2 Hz, 1H, H-3), 3.70-3.60 (m, 3H, H-5, H-6a, H-6b),
3.58 (td, J = 9.2, 2.2 Hz, 1H, H-4), 3.51 (dd, J = 9.2, 3.5 Hz,

Regioselective Ring Opening of Benzylidene Acetals
J. Chin. Chem. Soc., Vol. 56, No. 3, 2009 521
1H, 4-OH); 13C NMR (125 MHz, CDCl3) d 165.2 (C),
137.9 (C), 137.7 (C), 133.1 (CH), 129.9 (C), 129.8 (CH),
128.5 (CH), 128.4 (CH), 128.0 (CH), 127.9 (CH), 127.8
(CH), 102.0 (CH), 82.2 (CH), 74.4 (CH2), 74.1 (CH), 73.8
(CH2), 73.3 (CH), 72.3 (CH), 70.3 (CH2), 56.8 (CH3);
HRMS [FAB, (M-H)+] calcd for C28H29O7 477.1913, found
477.1922.
7.57 (t, J = 7.8 Hz, 1H, BzH), 7.44 (t, J = 7.8 Hz, 2H, BzH),
7.33-7.24 (m, 5H, ArH), 5.52 (m, 1H, H-3), 4.90 (d, J = 3.5
Hz, 1H, H-1), 4.62, 4.57 (ABq, J = 12.0 Hz, 2H, CH2Ph),
3.90-3.72 (m, 4H, H-4, H-5, H-6a, H-6b), 3.46 (s, 3H,
OCH3), 3.42 (d, J = 10.5, 3.5 Hz, 1H, H-2), 3.10-3.00 (bs,
1H, 4-OH); 13C NMR (125 MHz, CDCl3) d 167.1 (C),
137.7 (C), 133.5 (CH), 130.0 (CH), 129.2 (CH), 128.43
(CH), 128.38 (CH), 127.7 (CH), 127.6 (CH), 98.9 (CH),
74.3 (CH), 73.7 (CH2), 70.6 (CH), 70.3 (CH), 69.1 (CH2),
61.2 (CH), 55.3 (CH3); HRMS (FAB, MH+) calcd for
C21H24N3O6 414.1665, found 414.1675. Anal. Calcd for
C21H23N3O6: C, 61.01; H, 5.61; N, 10.16. Found: C, 61.02;
H, 5.71; N, 9.99.
p-Methylphenyl 2,3,6-Tri-O-benzyl-1-thio-b-D-gluco-
pyranoside (44)
[a] 2D6 +2.6 (c 1.5, CHCl3); IR (CHCl3) n 3437, 2913,
2867, 1452, 1210, 1061, 806, 734, 696 cm-1; 1H NMR (400
MHz, CDCl3) d 7.43-7.24 (m, 17H, ArH), 7.03 (d, J = 7.9
Hz, 2H, ArH), 4.90, 4.72 (ABq, J = 10.3 Hz, 2H, CH2Ph),
4.88, 4.76 (ABq, J = 11.3 Hz, 2H, CH2Ph), 4.60 (d, J = 9.5
Hz, 1H, H-1), 4.57, 4.53 (ABq, J = 11.9 Hz, 2H, CH2Ph),
3.77 (dd, J = 10.4, 4.2 Hz, 1H, H-6a), 3.73 (dd, J = 10.4, 5.1
Hz, 1H, H-6b), 3.62 (td, J = 8.7, 2.0 Hz, 1H, H-4), 3.51 (t, J
= 8.7 Hz, 1H, H-3), 3.43 (dd, J = 9.5, 8.7 Hz, 1H, H-2), 3.43
(m, 1H, H-5), 2.53 (d, J = 2.0 Hz, 1H, 4-OH), 2.29 (s, 3H,
CH3); 13C NMR (125 MHz, CDCl3) d 138.5 (C), 138.0 (C),
137.9 (C), 137.8 (C), 132.6 (CH), 129.8 (C), 129.7 (CH),
128.6 (CH), 128.42 (CH), 128.41 (CH), 128.3 (CH), 127.94
(CH), 127.91 (CH), 127.9 (CH), 127.7 (CH), 88.0 (CH),
86.2 (CH), 80.5 (CH), 78.0 (CH), 75.5 (CH2), 75.3 (CH2),
73.7 (CH2), 71.8 (CH), 70.4 (CH2), 21.1 (CH3); HRMS
(FAB, MH+) calcd for C34H37O5S 557.2362, found 557.2367.
Methyl 2-Azido-3,6-di-O-benzyl-2-deoxy-a-D-gluco-
pyranoside (45)
2-Azido-3-O-benzoyl-6-O-benzyl-2-deoxy-b-D-gluco-
pyranosyl Benzoate (47)
[a] 2D6 –115.6 (c 2.0, CHCl3); IR (CHCl3) n 3485,
2918, 2871, 2110, 1736, 1600, 1451, 1266, 1069, 711 cm-1;
1H NMR (400 MHz, CDCl3) d 8.10 (m, 4H, BzH), 7.62 (m,
2H, BzH), 7.47 (m, 4H, BzH), 7.32 (m, 5H, ArH), 5.85 (d, J
= 8.7 Hz, 1H, H-1), 5.25 (dd, J = 10.1, 9.2 Hz, 1H, H-3),
4.60, 4.53 (ABq, J = 12.0 Hz, 2H, CH2Ph), 4.00 (t, J = 9.2
Hz, 1H, H-4), 3.93 (dd, J = 10.1, 8.7 Hz, 1H, H-2), 3.86-
3.81 (m, 1H, H-6a), 3.79-3.73 (m, 2H, H-6b, H-5), 3.10-
3.20 (bs, 1H, 4-OH); 13C NMR (125 MHz, CDCl3) d 166.7
(C), 164.4 (C), 137.5 (C), 133.9 (CH), 133.7 (CH), 130.1
(CH), 130.0 (CH), 129.0 (C), 128.62 (C), 128.56 (CH),
128.55 (CH), 128.45 (CH), 127.9 (CH), 127.8 (CH), 93.6
(CH), 76.3 (CH), 75.4 (CH), 73.8 (CH2), 70.1 (CH), 69.0
(CH2), 63.3 (CH); HRMS (FAB, MH+) calcd for C27H26N3O7
504.1775, found 504.1771.
[a] 2D6 –19.9 (c 2.2, CHCl3); IR (CHCl3) n 3474, 2913,
1
2105, 1601, 1452, 1260, 1053, 736, 697 cm-1; H NMR
(400 MHz, CDCl3) d 7.42-7.25 (m, 10H, ArH), 4.91, 4.78
(ABq, J = 11.2 Hz, 2H, CH2Ph), 4.77 (d, J = 3.5 Hz, 1H,
H-1), 4.60, 4.54 (ABq, J = 12.4 Hz, 2H, CH2Ph), 3.79 (dd, J
= 10.0, 8.2 Hz, 1H, H-3), 3.76-3.63 (m, 4H, H-4, H-5,
H-6a, H-6b), 3.41 (s, 3H, OCH3), 3.35 (dd, J = 10.0, 3.5 Hz,
1H, H-2), 2.49 (d, J = 1.9 Hz, 1H, 4-OH); 13C NMR (125
MHz, CDCl3) d 138.1 (C), 137.7 (C), 128.6 (CH), 128.4
(CH), 128.1 (CH), 128.0 (CH), 127.8 (CH), 127.7 (CH),
98.8 (CH), 80.0 (CH), 75.1 (CH2), 73.7 (CH2), 72.1 (CH),
69.9 (CH), 69.7 (CH2), 63.0 (CH), 55.3 (CH3); HRMS
(FAB, MH+) calcd for C21H26N3O5 400.1872, found
400.1882.
Methyl 2,3,6-Tri-O-benzyl-a-D-mannopyranoside (48)
1H NMR (400 MHz, CDCl3) d 7.22-7.35 (m, 15H,
ArH), 4.77 (d, J = 1.6 Hz, 1H, H-1), 4.66, 4.65 (ABq, J =
12.3 Hz, 2H, CH2Ph), 4.60, 4.59 (ABq, J = 12.1 Hz, 2H,
CH2Ph), 4.57, 4.51 (ABq, J = 11.8 Hz, 2H, CH2Ph), 4.03
(td, J = 9.4, 1.8 Hz, 1H, H-4), 3.80-3.67 (m, 5H, H-2, H-3,
H-5, H-6a, H-6b), 3.34 (s, 3H, OCH3), 2.48 (d, J = 1.8 Hz,
1H, 4-OH); 13C NMR (125 MHz, CDCl3) d 138.3 (C),
138.2 (C), 128.5 (CH), 128.3 (CH), 127.84 (CH), 127.76
(CH), 127.72 (CH), 127.65 (CH), 127.6 (CH), 127.5 (CH),
99.1 (CH), 79.7 (CH), 73.8 (CH), 73.5 (CH2), 72.6 (CH2),
71.8 (CH2), 71.4 (CH), 70.4 (CH2), 67.8 (CH), 54.9 (CH3).
1-Benzyloxy-3-butanol (49)
Methyl 2-Azido-3-O-benzoyl-6-O-benzyl-2-deoxy-a-D-
glucopyranoside (46)
1H NMR (500 MHz, CDCl3) d 7.35-7.22 (m, 5H,
ArH), 4.51 (s, 2H, CH2Ph), 4.95-4.05 (m, 1H, H-3), 3.72-
3.59 (m, 2H, H-1), 2.80-2.79 (bs, 1H, 3-OH), 1.81-1.65 (m,
2H, H-2), 1.18 (d, J = 6.2 Hz, 3H, H-4); 13C NMR (125
[a] 3D2 +2.5 (c 0.5, CHCl3); IR (CHCl3) n 3477, 2910,
2107, 1724, 1602, 1450, 1272, 1051, 740, 710 cm-1; H
1
NMR (400 MHz, CDCl3) d 8.06 (d, J = 7.8 Hz, 2H, BzH),

522 J. Chin. Chem. Soc., Vol. 56, No. 3, 2009
Shie et al.
3. (a) Wang, C.-C.; Kulkarni, S. S.; Lee, J.-C.; Luo, S.-Y.;
Huang, Y.-W.; Lee, C.-C.; Chang, K.-L.; Hung, S.-C. Nature
2007, 446, 896-899. (b) Wang, C.-C.; Kulkarni, S. S.; Lee,
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4. (a) Hanessian, S. Total Synthesis of Natural Products: The
“Chiron” Approach; Pergamon Press: Oxford, 1983. (b)
Kocienski, P. J. Protecting Groups, 3rd ed.; Georg Thieme
Verlag: Stuttgart, 2005. (c) Preparative Carbohydrate
Chemistry; Hanessian, S., Ed.; Marcel Dekker: New York,
1997. (d) Greene, T. W.; Wuts, P. G. M. Protective Groups in
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MHz, CDCl3) d 137.9 (C), 128.5 (CH), 127.7 (CH), 127.6
(CH), 73.3 (CH2), 69.2 (CH2), 67.7 (CH), 38.1 (CH2), 23.3
(CH3).
1,3-Dibenzyloxybutane (50)
IR (CHCl3) n 2970, 2926, 1603, 1454, 1110, 1027,
735, 697 cm-1; 1H NMR (400 MHz, CDCl3) d 7.32-7.23 (m,
10H, ArH), 4.57, 4.41 (ABq, J = 11.6 Hz, 2H, CH2Ph),
4.47, 4.46 (ABq, J = 11.9 Hz, 2H, CH2Ph), 3.77-3.68 (m,
1H, H-3), 3.65-3.51 (m, 2H, H-1), 1.92-1.72 (m, 2H, H-2),
1.21 (d, J = 6.4 Hz, 3H, H-4); 13C NMR (100 MHz, CDCl3)
d 139.0 (C), 138.6 (C), 129.5 (CH), 128.33 (CH), 128.29
(CH), 127.7 (CH), 127.5 (CH), 127.4 (CH), 73.0 (CH2),
72.2 (CH), 70.5 (CH2), 67.0 (CH2), 37.0 (CH2), 19.8 (CH3);
HRMS (FAB, MH+) calcd for C18H23O2 271.1698, found
271.1700.
5. Selective deprotections. (a) Greene, T. W.; Wuts, P. G. M.
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ACKNOWLEDGEMENTS
This work was supported by the National Science
Council of Taiwan (NSC 95-2113-M-007-028-MY3, NSC
96-2627-M-007-002, NSC 96-2321-B-007-003, NSC
96-2752-B-007-002-PAE, NSC 96-3011-P-007-005) and
Academia Sinica (94C007 and AS-95-TP-AB1).
Received December 31, 2008.
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