A highly stereoselective construction of 1,2-trans-β-glycosidic linkages capitalizing on 2-azido-2-deoxy-D-glycosyl diphenyl phosphates as glycosyl donors

Article abstract of DOI:10.1016/j.tet.2004.08.076

The scope of TMSOTf-promoted glycosidation of 2-azido-2-deoxyglycopyranosyl diphenyl phosphates is investigated. The 3,4,6-tri-O-benzyl-protected glucosyl and galactosyl donors and the 4,6-O-benzylidene-protected galactosyl donor each react with a range of acceptor alcohols in the presence of a stoichiometric amount of TMSOTf in propionitrile at -78°C to afford 1,2-trans-β-linked disaccharides in high yields with α:β ratios ranging from 9:91 to 1:>99, regardless of the anomeric composition of the donor used. The use of propionitrile as a solvent at -78°C has proven to be among the best choice for the highest levels of β-selectivity reported to date for this type of glycosidation. A plausible reaction mechanism, which features a large equilibrium preference for α-glycosyl-nitrilium ions over β-nitrilium ions, is proposed based on byproducts formed through their intermediacy and accounts for the observed excellent β-selectivities. Graphical Abstract.

Full text of DOI:10.1016/j.tet.2004.08.076

Tetrahedron 60 (2004) 10711–10737
A highly stereoselective construction of 1,2-trans-b-glycosidic
linkages capitalizing on 2-azido-2-deoxy-D-glycosyl diphenyl
phosphates as glycosyl donors
*
Toshifumi Tsuda, Seiichi Nakamura and Shunichi Hashimoto
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Received 10 August 2004; revised 26 August 2004; accepted 26 August 2004
Available online 1 October 2004
Abstract—The scope of TMSOTf-promoted glycosidation of 2-azido-2-deoxyglycopyranosyl diphenyl phosphates is investigated. The
3,4,6-tri-O-benzyl-protected glucosyl and galactosyl donors and the 4,6-O-benzylidene-protected galactosyl donor each react with a range of
acceptor alcohols in the presence of a stoichiometric amount of TMSOTf in propionitrile at K78 8C to afford 1,2-trans-b-linked
disaccharides in high yields with a:b ratios ranging from 9:91 to 1:O99, regardless of the anomeric composition of the donor used. The
use of propionitrile as a solvent at K78 8C has proven to be among the best choice for the highest levels of b-selectivity reported to date for
this type of glycosidation. A plausible reaction mechanism, which features a large equilibrium preference for a-glycosyl-nitrilium ions over
b-nitrilium ions, is proposed based on byproducts formed through their intermediacy and accounts for the observed excellent b-selectivities.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
precluded its wide application for synthesizing complex
oligosaccharides.3
The rapidly growing significance of glycosides and
oligosaccharides as constituents of biologically important
compounds such as antitumor antibiotics and glycoconju-
gates has mandated the rational design and development of
stereocontrolled glycosidation reactions.1 Since 2-aceta-
mido-2-deoxy-D-glycopyranosides, mainly found in b-glyco-
sidic linkage, are ubiquitous building blocks of glycolipids,
glycoproteins, proteoglycans and peptidoglycans, numerous
procedures for synthesizing 1,2-trans-b-linked 2-aceta-
mido-2-deoxy-D-glycosides have been reported.2 In terms
of efficiency and practicality, direct glycosidation using
2-acetamido-2-deoxyglycosyl donors should constitute an
ideal procedure for the stereocontrolled construction of
these linkages. In practice, however, the reactions of these
donors generally lead to the predominant formation of
oxazoline derivatives via a neighboring group participation
and subsequent elimination of an amide proton. Although
oxazolines can react with acceptor alcohols in the presence
of Brfnsted or Lewis acids to afford 1,2-trans-glycosides
with the natural 2-acetamido group (i.e. oxazoline method),
the harsh reaction conditions for this conversion have
To overcome this problem, Lemieux and co-workers
introduced the use of 2-deoxy-2-phthalimidoglycosyl
donors as a reliable method for synthesizing 2-acetamido-
2-deoxy-b-glycosides.4 The phthalimido method generally
gives high yields and virtually complete b-selectivity with
most glycosyl acceptors as demonstrated with numerous
complex oligosaccharide syntheses. However, removing the
phthaloyl group requires basic conditions at elevated
temperatures, which often cause the product to partially
decompose. Therefore, a variety of different 2-amino
protecting groups with an anchimeric assistance such as
N-2,2,2-trichloroethoxycarbonyl (Troc),5a–c N-allyloxycar-
bonyl (Alloc),5c N-benzyloxycarbonyl (Cbz),5c N-trichloro-
acetyl (TCA),5d N-tetrachlorophthaloyl (TCP),5e–g N-
dithiasuccinoyl (Dts),5h,i N,N-diacetyl,5j N-4,5-dichloro-
phthaloyl (DCPhth),5k N-dimethylmaleoyl (DMM),5l N,N-
dibenzyl,5m and N-thiodiglycoloyl (TDG)5n have been
investigated.
An alternative approach to 2-acetamido-2-deoxy-b-glyco-
pyranosides involves using 2-azido-2-deoxyglycopyranosyl
donors. Although the azido group as a latent amino
functionality is incapable of neighboring group partici-
pation, modest to high levels of b-selectivity were observed
with2-azido-2-deoxyglycosyltrichloroacetimidates,6–8 S-xan-
thates,9 isopropenyl carbonate,10 2-pyridinecarboxylates,11
Keywords: 2-Azido-2-deoxyglycopyranosyl diphenyl phosphate; b-Selec-
tive glycosidation; a-Nitrilium ion.
* Corresponding author. Tel.: C81-11-706-3236; fax: C81-11-706-4981;
e-mail: hsmt@pharm.hokudai.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.08.076

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T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
dibutyl phosphates,12 and phenylthio glycosides.13 Of these,
glycosidation of 2-azido-2-deoxyglycosyl trichloroacetimi-
dates in the presence of BF3$OEt2 in CH2Cl2–hexane7 or in
the presence of TMSOTf in acetonitrile8 is the method of
choice for a highly stereoselective construction of 2-azido-
2-deoxy-b-glycosides.14
(1)
We recently developed glycosyl donors that incorporate
various phosphorus-containing leaving groups. The glyco-
sidations constitute mild and efficient methods for the highly
stereocontrolled construction of 1,2-trans-b- and 1,2-cis-a-
glycosidic linkages with or without a participating group at
C2.15 The exceptionally high levels of b-selectivity
observed with 2,3,4,6-tetra-O-benzyl-protected glycosyl
diphenyl phosphates,15a N,N,N0,N0-tetramethylphosphoro-
diamidates,15d and diethyl phosphites15e suggested that
these leaving groups would also be promising candidates
for constructing 2-azido-2-deoxy-b-glycosidic linkages. In
this article, the scope, limitations, and mechanism of
TMSOTf-promoted glycosidation of 2-azido-2-deoxygly-
cosyl diphenyl phosphates (Eq. (1)) are documented.16 In
addition, a comparative study with TMSOTf-promoted
glycosidation of 2-azido-2-deoxyglycosyl trichloroacetimi-
dates is described.
2. Results and discussion
2.1. Preparation of 2-azido-2-deoxy-D-glycosyl donors
2-Azido-2-deoxy-D-glycosyl donors were prepared accord-
ing to the standard procedures used for 2,3,4,6-tetra-O-
benzyl-protected glycosyl donors. Application of Sabesan’s
phosphorylation method17 [ClP(O)(OPh)2, DMAP, CH2Cl2,
0 8C] to the corresponding glycopyranoses 1a–c and 3a–c
afforded 2-azido-2-deoxyglycosyl diphenyl phosphates
2a–c and 4a–c in good to high yields (Table 1). Diphenyl
phosphate 2a with a:b ratio of 2:98 was obtained by
coupling 2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-D-glucosyl
trichloroacetimidate (5a)7b with diphenyl phosphoric acid
in CH2Cl2 at 0 8C (Eq. (2)).18
Table 1. Preparation of 2-azido-2-deoxyglycosyl diphenyl phosphates
Entry
1
Glycopyranose
Phosphate
Yield %
97
a:ba
1a (a:bZ56:44)
2a
2b
72:28
1b (a:bZ61:39)
1c (a:bZ52:48)
3a (a:bZ68:32)
2
3
4
99
99
79
46:54
31:69
58:42
2c
4a
3b (a:bZ44:56)
3c (a:bZ63:37)
4b
4c
5
97
75
24:76
67:33
6
a
Determined by 109 MHz 31P NMR using 85% H3PO4 as an external standard.

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10713
Table 2. TMSOTf-Promoted glycosidation of 2-azido-2-deoxyglycosyl
donors 2aa and 6b
(2)
Tetramethylphosphorodiamidate 6 was prepared by con-
densing a lithium alkoxide derived from 1a with bis(di-
methylamino)phosphorochloridate in THF-HMPA (Eq.
(3)).15d On the other hand, 2-azido-2-deoxyglucosyl
Entry
Donor
a:bc
ROH
Time,
h
Glycoside
Yield,
%
a:bd
1
2
3
4
5
6
2a
2a
2a
2a
6
72:28
2:98
72:28
2:98
67:33
67:33
7
7
8
8
7
8
1.5
1.5
2
2
2.5
3
9
9
10
10
9
84e
85e
90
1:99
1:99
6:94
7:93
2:98
7:93
(3)
diethyl phosphite was inaccessible since it decomposed
upon concentration in vacuo, although the reaction of 1a
with diethyl chlorophosphite and triethylamine proceeded in
CH2Cl2 at 0 8C. The obtained 2-azido-2-deoxyglycosyl
donors were purified by silica gel column chromatography,
and stored without decomposition in the freezer (at K30 8C)
for several months.
92
81e
85
6
10
a
Donor 2a/ROH/TMSOTf molar ratioZ1.0/1.1/1.5.
Donor 6/ROH/TMSOTf molar ratioZ1.0/1.1/1.8.
b
c
Determined by 109 MHz 31P NMR using 85% H3PO4 as an external
standard.
d
e
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 13 or 17% AcOEt in hexane; flow rate 1.0 mL/min).
a-Imidate 11 was obtained in 5–7% yield.
2.2. Reaction optimization
easily hydrolyzed 0upon an acidic aqueous work-up. The 1H
NOE between H1 and CH2 of ethyl group established the
anti stereochemistry of 11. In contrast, such a byproduct was
not detected when less reactive alcohol 8 was used. While
the phosphorodiamidate 6 has a greater shelf-stability than
the diphenyl phosphate 2a, we selected the phosphate
method due to the ease in preparing this type of donor.
At the outset of this study, glycosidations of 2-azido-3,4,6-
tri-O-benzyl-2-deoxy-D-glucosyl diphenyl phosphate 2a
(a:bZ72:28 or 2:98) and N,N,N0,N0-tetramethylphosphoro-
diamidate 6 (a:bZ67:33) were explored with O-6- or O-4-
unprotected glycosides 7 or 8 (1.1 equiv each) as highly
reactive and less reactive acceptor alcohols, respectively
(Table 2). The addition of a 1.0 M solution of TMSOTf
(1.5 equiv) in CH2Cl2 to a cooled solution (K78 8C) of the
donor and acceptor in propionitrile afforded a disaccharide
and the a:b ratio was assayed by HPLC (Zorbaxw Sil
column). As expected from previous work,15a TMSOTf-
promoted glycosidations of the diphenyl phosphate 2a with
7 or 8 in propionitrile at K78 8C proceeded smoothly to
give disaccharides 9 and 10 in high yields with excellent
b-selectivities, regardless of the anomeric composition
of the donor (entries 1–4) (Fig. 1). The reactions of
phosphorodiamidate 6 under the same conditions exhibited
virtually the same b-selectivities as those found with 2a
(entries 5 and 6), although longer reaction times were
required. In either case, the reaction did not go to
completion when a substoichiometric amount of TMSOTf
was used. Upon further examining these reactions, we were
somewhat surprised to find a small amount (5–7%) of the
hydrolysis-prone a-imidate 11, which has an Rf value
comparable to disaccharide 9, was produced as a byproduct
when alcohol 7 was used as an acceptor (entries 1, 2 and 5).
It must be mentioned that imidate byproducts such as 11 are
formed regardless of the nature of 2-azido-2-deoxyglycosyl
donors whenever the reactions with highly reactive O-6-
unprotected glycoside alcohols are conducted in propio-
nitrile (vide infra). Fortunately, their formation did not
prevent the isolation of products since the imidates were
Examining solvents other than propionitrile for the reaction
of diphenyl phosphate 2a (a:bZ72:28) with O-6-unpro-
tected glycoside 7 showed that similar high levels of
b-selectivity could be achieved in CH2Cl2 and toluene
(Table 3, entries 1–5). A further solvent survey with O-4-
unprotected glycoside 8 revealed that propionitrile was
optimal for this glycosidation and has a beneficial effect on
the stereoselectivity as well as the reaction rate (entries
6–8). Consistent with the proposal by Schmidt,8 an
Figure 1. Products of glycosidation reactions of diphenyl phosphate 2a
with 7 and 8.

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T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
Table 3. Effect of solvent in TMSOTf-promoted glycosidation of 2-azido-
2-deoxyglycosyl diphenyl phosphate 2a
Entry
ROH Solvent Temp.a
8C
Time,
h
Glycoside
Yield,
%
a:bb
1
2
3
4
5
6
7
8
7
7
7
7
7
8
8
8
EtCN
K78
K78
K65
K65
K30
K78
K78
K65
1.5
4
2
2
1
2
8
8
9
9
9
9
9
10
10
10
84
88
90
89
88
90
84
81
1:99
1:99
4:96
11:89
38:62
6:94
10:90
24:76
CH2Cl2
Toluene
EtOAc
Et2O
EtCN
CH2Cl2
Toluene
a
Temperature limit for smooth reaction.
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 13% or 17% AcOEt in hexane; flow rate 1.0 mL/min).
b
exceptionally high order of b-selectivity in propionitrile can
be explained by the intermediacy of 2-azido-2-deoxy-a-D-
glucosyl-nitrilium ion associated with triflate as a counter-
ion (vide infra).
As expected the temperature profile of the glycosidation in
propionitrile revealed a descending b-selectivity with
ascending temperature (Table 4). The temperature effect
was more pronounced with less reactive alcohol 8 (entries 4
vs 5) than with 7.
Figure 2. Acceptor alcohols and products in Table 5.
2.3. Glycosidations of 2-azido-3,4,6-tri-O-benzyl-2-
deoxyglycosyl diphenyl phosphates 2a and 4a
TMSOTf-promoted glycosidations in propionitrile at
K78 8C offered a facile and high-yielding entry to 1,2-
trans-b-linked disaccharides, wherein the a:b ratios ranged
from 9:91 to 1:O99.
With the optimal reaction conditions determined, glycosi-
dations of 2-azido-3,4,6-tri-O-benzyl-2-deoxy glycosyl
diphenyl phosphates 2a (a:bZ72:28) and 4a (a:bZ58:42)
in the D-gluco and D-galacto series were explored with a
range of suitably protected glycoside alcohols (Fig. 2). The
results are compiled in Tables 5 and 6. In all cases,
Table 5. TMSOTf-promoted glycosidation of 2-azido-3,4,6-tri-O-benzyl-
2-deoxyglucosyl diphenyl phosphate 2a with acceptor alcoholsa,b
Table 4. Temperature profile of TMSOTf-promoted glycosidation of 2-
azido-2-deoxyglycosyl diphenyl phosphate 2a
Entry
ROH
Time, h
Glycoside
Yield, %
a:bc
2:98
1
2
3
12
13
14
15
16
1.5
2
2
2
2
17
18
20
21
22
79d
91
89
90
88
9:91
1:O99
5:95
Entry
ROH
Temp,
8C
Time,
h
Glycoside
4
5e
7:93f
Yield,
%
a:ba
a
The reaction was carried out on 0.1 mmol scale.
Donor 2a/ROH/TMSOTf molar ratioZ1.0/1.1/1.5 unless otherwise
noted.
b
c
1
2
3
4
5
7
7
7
8
8
K78
K45
K10
K78
K45
1.5
0.5
0.1
2
9
9
9
10
10
84
89
92
90
88
1:99
3:97
8:92
6:94
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 17w20% AcOEt in hexane or 14% THF in hexane; flow rate 1.
0 mL/min), unless otherwise stated.
0.5
13:87
d
e
f
a-Imidate 19 was obtained in 9% yield.
The reaction was performed with 2.0 equiv of TMSOTf.
Determined by 500 MHz 1H NMR.
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 13% or 17% AcOEt in hexane; flow rate 1.0 mL/min).
a

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10715
Table 6. TMSOTf-promoted glycosidation of 2-azido-3,4,6-tri-O-benzyl-
2-deoxygalactosyl diphenyl phosphate 4a with acceptor alcoholsa
Entry
ROH
Time, h
Glycoside
Yield, %
a:bb
1
2
3
4
7
8
23
24
0.2
0.5
0.3
0.5
25
27
28
29
86c
90
81
86
4:96
4:96
6:94
8:92
a
The reaction was carried out on 0.1 mmol scale.
b
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 17% AcOEt in hexane or 17% THF in hexane; flow rate 1.0 mL/
min).
c
Propionate 26 was obtained in 5% yield.
Seeberger and co-workers reported that TMSOTf-promoted
coupling of 2-azido-2-deoxyglucosyl dibutyl phosphate
with glycoside alcohols 12 or 13 in acetonitrile at K40 8C
produced disaccharides 17 and 18 in modest yields with a:b
ratios of 1:5 and 1:4, respectively.12 Clearly, the present
method is superior to the dibutyl phosphate method in terms
of product yield and stereoselectivity (Table 5, entries 1 and
2). Here again, a small amount (9%) of a-imidate byproduct
19 was detected when O-6-unprotected glycoside 12 was
used. It is also noteworthy that glycosylation of O-3-
unprotected galactose derivative 14 exclusively formed
disaccharide 20b, which corresponds to GlcNAcb1/3Gal,
a constituent of biologically important gangliosides such as
sialyl Lewisx (entry 3). Since the fully benzoylated glucosyl
tetramethylphosphorodiamidate is unaffected at tempera-
tures below K5 8C by these reaction conditions,19 chemo-
selective glycosidation was uneventfully realized using
O-6-unprotected glucosyl phosphorodiamidate 16 as a
disarmed acceptor (entry 5). It is interesting to note that
2-azido-2-deoxygalactosyl diphenyl phosphate 4a is even
more reactive than the corresponding glucosyl donor 2a, as
manifested by much shorter reaction times (Table 6). When
alcohols 7 and 8 were used, donor 4a displayed somewhat
lower and higher b-selectivities, respectively, than donor
2a. In the former reaction, 5% of O-6-propionyl-protected
glycoside 26, due to the hydrolysis of the imidate byproduct
(not shown), was obtained. The effectiveness of the present
method was also demonstrated by synthesizing LacdiNAc
equivalent 29, which was achieved by glycosylation of O-4-
unprotected glucosamine derivative 24 in 86% yield with an
a:b ratio of 8:92 (entry 4) (Fig. 3).
Figure 3. Acceptor alcohols and products in Table 6.
chromatography on silica gel, a-imidate 30a was safely
isolated in 79% yield. In this reaction, the corresponding
disaccharide 31 with an a:b ratio of 14:86 was obtained in
only 4% yield. Likewise, the reaction of 2-azido-2-
deoxygalactosyl diphenyl phosphate 4b with 7 afforded
imidate 32 (a:bZ88:12) as a major product, along with 9%
Table 7. TMSOTf-promoted glycosidation of 3,4,6-tri-O-acetyl-2-azido-2-
deoxyglycosyl diphenyl phosphates 2b and 4b with alcohol 7a,b
Entry
Donor
Time,
h
Imidate
a:bc
Glycoside
Yield,
%
a:bc
2.4. Glycosidations of 3,4,6-tri-O-acetyl-2-azido-2-
deoxyglycosyl diphenyl phosphates 2b and 4b
1
2
2b
4b
4
3
30d
32e
85:15
88:12
31
33
4
9
14:86
3:97
While 2-azido-3,4,6-tri-O-benzyl-2-deoxyglycosyl donors
2a and 4a performed well, attempts to employ 3,4,6-tri-O-
acetyl-protected glycosyl donors 2b and 4b met with less
success. 2-Azido-2-deoxyglucosyl diphenyl phosphate 2b
was activated by TMSOTf at K65 8C in propionitrile, but
the reaction with alcohol 7 predominantly formed imidates
30 with an a:b ratio of 85:15 (Table 7, entry 1). Although
some of the b-imidate partially decomposed during column
a
The reaction was carried out on 0.1 mmol scale.
b
c
The anomeric a:b ratio of the phosphates: 2b, 46:54; 4b, 24:76.
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 29% AcOEt–THF (1:1) in hexane or 20% THF in hexane; flow
rate 1.0 mL/min).
d
e
Only a-imidate 30a could be isolated in 79% yield after chromatographic
separation.
Only a-imidate 32a could be isolated in 68% yield after chromatographic
separation.

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T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
of disaccharide 33 (a:bZ3:97), wherein the a-imidate 32a
was isolated in 68% yield (entry 2). These disappointing
results are attributed to the electron-withdrawing effect of
the ester functionality, which deactivates the anomeric
reactivity of nitrilium ion intermediates and favors a
nucleophilic attack by alcohol 7 on a nitrilium carbon
leading to imidates 30 and 32 (vide infra). Although the
fully acyl-protected 2-azido-2-deoxyglycosyl donors are not
suitable for the present coupling reaction, other donors with
partially acyl protection should not be excluded (vide infra).
2.5. Glycosidations of 2-azido-4,6-O-benzylidene-2-
deoxyglycosyl diphenyl phosphates 2c and 4c
It is well documented that 4,6-O-benzylidene-protected
glycosyl donors exhibit reduced reactivities20 and different
stereoselectivities21 compared to the fully benzylated ones.
Therefore, we were driven to investigate glycosidations of
2-azido-4,6-O-benzylidene-2-deoxyglycosyl diphenyl
phosphates. 2-Azido-2-deoxyglucosyl donor 2c was acti-
vated with TMSOTf at K45 8C in propionitrile, but the
reaction with 7 gave disaccharide 35 in only 6% yield with
an a:b ratio of 8:92 and considerable amounts of imidates
36 (a:bZ91:9); the a-imidate 36a was isolated in 84%
yield (Table 8, entry 1). In stark contrast, 2-azido-2-
deoxygalactosyl diphenyl phosphate 4c underwent a smooth
coupling with a range of alcohols even at K78 8C to provide
disaccharides 37, 39, 40 in good yields with excellent
b-selectivities (entries 2–4), although a small amount (10%)
of a-imidate 38 was produced as a byproduct of the reaction
with 7. It is noteworthy that glycosylation of diol 34
produced 1,2-trans-b-linked disaccharide 40 with essen-
tially perfect regioselectivity and excellent stereoselectivity
(a:bZ1:99 and 2:98) (entries 4 and 5).22 The difference in
reaction mode between these donors may be explained by
considering that 2-azido-2-deoxyglucosyl donor 2c is a
trans-fused bicyclic compound whereas 2-azido-2-deoxy-
galactosyl donor 4c has a relatively flexible, cis-decaline-
Figure 4. Acceptor alcohols and products in Table 8.
like architecture (Fig. 4). The greater conformational
rigidity of 2c relative to 4c would serve to torsionally
disarm the nitrilium ion intermediate with respect to
formation of the O-glycosidic linkage.20,23
2.6. Comparative study
While high yields and excellent b-selectivities were
achieved in the reactions of glycosyl diphenyl phosphates
2a, 4a, and 4c with a range of acceptor alcohols, limitations
of the phosphate method were recognized with donors 2b,
2c, and 4b. To verify the effectiveness of the phosphate
method, the scope of TMSOTf-promoted glycosidations of
the corresponding trichloroacetimidates was examined.
Although the exceptional power of the trichloroacetimidate
method developed by Schmidt has been well demonstrated
in numerous aminosugar-containing oligosaccharide syn-
theses,24 a systematic investigation has yet to be described.
The glycosidations were performed under frequently used
conditions [cat. TMSOTf, acetonitrile, K40 8C].8,22,24
Table 9 summarizes the results. TMSOTf (0.1 equiv)-
catalyzed glycosidations of trichloroacetimidates 5a7b or
5b25 with alcohols 7 and 8 proceeded to completion within
20 min, yielding high levels of b-selectivity similar to those
of 2a in propionitrile at K45 8C (entries 1 and 2 vs entry 2 in
Table 4, and entries 3 and 4 vs entry 5 in Table 4). The
stereochemical outcome observed was independent of
the anomeric configuration of the donor similar to the
phosphates. Somewhat surprisingly, evidence of the for-
mation of imidate byproduct such as 11 could not be
detected when alcohol 7 was used. Instead, a small amount
Table 8. TMSOTf-promoted glycosidation of 2-azido-4,6-O-benzylidene-
2-deoxyglycosyl diphenyl phosphates 2c and 4c with acceptor alcoholsa
Entry
Donor
ROH
Time, h
Glycoside
Yield,
%
a:bb
1c
2
3
4
2cd
4cf
4cf
4cf
4ch
7
7
8
34
34
4
3
3
2
2
35
37
39
40
40
6e
78g
90
80
82
8:92
3:97
4:96
1:99
2:98
5
a
The reaction was carried out on 0.1 mmol scale.
b
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 20 or 60% AcOEt in hexane; flow rate 1.0 mL/min).
The reaction was carried out at K45 8C.
a:bZ31:69.
c
d
e
f
a-Imidate 36a was obtained in 84% yield.
a:bZ95:5.
a-Imidate 38 was obtained in 10% yield.
a:bZ0:100.
g
h

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10717
Table 9. TMSOTf-catalyzed glycosidation of 2-azido-2-deoxyglucosyl
trichloroacetimidates 5a and 5b with alcohols 7 and 8 in acetonitrilea
Table 10. TMSOTf-promoted glycosidation of 2-azido-2-deoxyglucosyl
trichloroacetimidates 5a and 5b with alcohol 8 in propionitrilea
Entry
Donor
ROH
Time, h
Glycoside
Yield,
%
a:bb
Entry
Donor
TMSOTf,
equiv
Time, h
Glycoside 10
Yield, % a:b
1
2
3
5a
5b
5a
5b
5a
5b
7
7
8
8
8
8
0.1
0.1
0.3
0.3
0.3
0.3
9
9
10
10
10
10
82c
85
3:97
3:97
10:90
11:89
12:88
12:88
50d
68e
51g
84
1
2
3
4
5a
5b
5a
5b
0.2
0.2
1.5
1.5
1
1
0.3
0.3
15
39
54c
85
8:92b
8:92b
7:93d
9:91d
4
5f
6f
a
The reaction was carried out on 0.1 mmol scale.
a
The reaction was carried out on 0.1 mmol scale.
Determined by 500 MHz 1H NMR.
Amidine 42 was obtained in 20% yield.
b
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 17% AcOEt in hexane; flow rate 1.0 mL/min).
b-Trichloroacetamide 41 was obtained in 4% yield.
Amide 41 and lactol 1a were obtained in 28% and 4% yields,
respectively.
b
c
d
c
Determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm; eluent, 17%
d
AcOEt in hexane; flow rate 1.0 mL/min).
e
Amide 41 and lactol 1a were obtained in 10% and 5% yields,
respectively.
In the presence of MS4A.
f
g
Amide 41 was obtained in 35% yield.
5a was used, but b-trichloroacetamide 41 was not formed
from either 5a or 5b. It is noteworthy that the formation of
an amidine byproduct has not been reported in glycosidation
reactions using trichloroacetimidates as glycosyl donors.
It is also interesting that the reaction of 5a with 8 in
acetonitrile at K40 8C gave b-trichloroacetamide 41 as a
major byproduct, whereas the same reaction in propionitrile
at K78 8C afforded a-amidine 42 as a major one, but the
reason is unclear. These results again demonstrated the
superiority of donor 5b over 5a. From the results with 4a,
2-azido-2-deoxygalactosyl trichloroacetimidates 43a7a and
43b28 are anticipated to have greater reactivities than
the corresponding glucosyl donors 5a and 5b. Indeed, the
reactions with alcohol 8 in propionitrile at K78 8C in the
presence of 1.5 equiv of TMSOTf proceeded to completion
within 5 min (Table 11). Although virtually the same
b-selectivities as those observed with phosphate 4a were
achieved, the product yields (48% from 43a and 66% from
43b) were unsatisfactory (Table 11 vs entry 2 in Table 6),
due to the inevitable formation of b-trichloroacetamide 44
(37% from 43a and 7% from 43b) and a-amidine 45 (7%
from 43a and 7% from 43b).
(4%) of b-trichloroacetamide 41 was obtained as a
byproduct of the reaction of 5a with 7 (entry 1), whereas
41 was not formed from 5b (entry 2).26 A moderate product
yield in the reaction of 5a with less reactive alcohol 8 was
due to the formation of b-trichloroacetamide 41 (28%) and
lactol 1a (4%) (entry 3). The yield of byproduct 41
decreased to 10% with 5b, thereby allowing a higher
product yield (entry 4). A significant improvement in
product yield (68/84%) was achieved when the reaction
of 5b with 8 was carried out in the presence of MS4A,
whereas the beneficial effect was not observed with 5a
(entries 5 and 6). Although discrepancies between the
behavior of a- and b-glycosyl trichloroacetimidates were
observed in some cases,27 the reason is currently unclear.
Next, glycosidation of trichloroacetimidates 5a or 5b with
alcohol 8 in propionitrile at K78 8C were explored in order
to determine whether the b-selectivity (a:bZ12:88–10:90)
observed in acetonitrile at K40 8C could be enhanced to the
ratio (a:bZ6:94) achieved with the phosphate method.
Although the goal in terms of stereoselectivity could be
virtually achieved using 0.2 equiv of TMSOTf, product
yields were not preparatively useful (Table 10, entries 1 and
2). When using 1.5 equiv of TMSOTf, product yields from
5a and 5b were improved to 54 and 85%, respectively,
without affecting the stereoselectivity (entries 3 and 4).
a-Amidine byproduct 42 was obtained in 20% yield when
Two key findings emerged from this comparative study. (1)
2-Azido-2-deoxyglycosyl trichloroacetimidates generally
exhibit higher reactivities than the corresponding diphenyl
phosphates. (2) Only using b-imidates gives coupling
products in good to high yields and with exceptionally

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T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
Table 11. TMSOTf-promoted glycosidation of 2-azido-2-deoxygalactosyl
trichloroacetimidates 43a and 43b with alcohol 8 in propionitrilea
Entry
Donor
Glycoside 27
Yield, %
a:bb
44
45
Yield, %
Yield, %
1
2
43a
43b
48
66
4:96
4:96
37
7
7
7
a
The reaction was carried out on 0.1 mmol scale.
The ratio was determined by HPLC (column, Zorbaxw Sil, 4.6!250 mm;
eluent, 17% AcOEt in hexane; flow rate 1.0 mL/min).
b
Scheme 1. A mechanistic rationale for TMSOTf-promoted glycosidation of
2-azido-2deoxyglycosyl diphenyl phosphates.
respectively, whereas capture of 49a and 49b by alcohols at
the nitrilium carbon leads to the formation of imidate
byproducts 51a and 51b, respectively. The chemoselectivity
depends on the anomeric reactivity of glycosyl-nitrilium
ions 49 influenced by the choice of protecting groups on
2-azido-2-deoxy-sugar components as well as the reactivity
of acceptor alcohols, as is demonstrated by the foregoing
experimental results. The exclusive formation of disacchar-
ides was realized when the 3,4,6-tri-O-benzyl-protected
glucosyl and galactosyl donors 2a and 4a, and the 4,6-O-
benzylidene-protected galactosyl donor 4c were used,
although a small amount of imidates was produced as
byproducts in the reaction with highly reactive O-6-
unprotected glycoside alcohols. Hence, the high levels of
b-selectivity observed here are attributed to a large
equilibrium preference for 49a as well as a high propensity
of 49a for an SN2-like displacement.6c The stereochemical
reaction course via a common oxocarbenium ion 48 is
consistent with the fact that the stereoselectivities are
irrespective of the anomeric configuration of the diphenyl
phosphates used. Actually, it was found that glycosidation
of 2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-glucosyl diphenyl
phosphate 2a (a:bZ2:98) competes with the anomerization
to a-phosphate via an internal return of the departing
diphenyl phosphate group under the present reaction
conditions. Of prime importance in terms of a mechanism
is that only a-imidates 11, 19, and 38 were obtained as
byproducts (5–10%) in the reaction of 2a or 4c with O-6-
unprotected alcohols. Assuming that the much less stable
b-nitrilium ion 49b would have a reactivity comparable to
49a toward the imidate formation, these results, along with
high levels of b-selectivity comparable to those found with
an anomeric mixture of diphenyl phosphates, when the
reactions are conducted in the presence of 1.5 equiv of
TMSOTf in propionitrile at K78 8C.29
2.7. Mechanistic considerations
The beneficial effect of nitrile as a solvent on 1,2-trans-b-
glycosidations without neighboring participation observed
by Noyori and co-workers in 198430 is now a well-
appreciated phenomenon in carbohydrate chemistry. In
1990 Fraser-Reid31 and Schmidt8 separately proposed that
the b-selectivity could be given by an SN2-like displacement
at the anomeric carbon of kinetically formed a-nitrilium
ion, which has been widely accepted.32 It is evident that the
so-called ‘nitrile effect’ plays a pivotal role in the TMSOTf-
promoted glycosidations with 2-azido-2-deoxyglycosyl
diphenyl phosphates since propionitrile at K78 8C is an
excellent solvent for high levels of b-selectivity.33 Scheme 1
outlines the possible reaction pathways. Diphenyl phosphate
46 is activated by silylation on the phosphoryl oxygen atom
to cleave off the phosphate group, producing oxocarbenium
ion 48 as a common intermediate. Intermediate 48 is rapidly
trapped by propionitrile to form an anomeric mixture of
nitrilium ions 49a and 49b associated with triflate as a
counterion. In this step, the a-nitrilium ion 49a preferen-
tially forms over 49b because of the stereoelectronically
favored axial attack of propionitrile from the a-face.34 In
addition, 49a benefits from anomeric stabilization.35 On the
kinetic and thermodynamic grounds, the equilibrium
between these nitrilium ions would heavily lie to 49a. The
SN2-like displacement by acceptor alcohols at the anomeric
carbon of 49a and 49b affords glycosides 50b and 50a,
1
the H NMR analysis of the crude reaction mixture, which
did not detect traces of b-imidates or their hydrolysates,
provide evidence that a-nitrilium ion 49a exclusively forms
at least in these reactions. Along with the finding that the
proportion of 1,2-cis-a-linked disaccharides slightly
increased with less reactive alcohols compared to highly
reactive ones, it seems likely that their formation would
arise from the kinetically favored a-axial attack of alcohols

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10719
on the transient, solvent separated oxocarbenium ion 48
rather than the SN2-like displacement of any 49b. While the
corresponding imidate byproduct could not be detected due
to its increased hydrolytic lability for 3,4,6-tri-O-benzyl-
protected galactosyl donor 4a, highly efficient glycosida-
tions of 4a are also assumed to proceed in a similar manner
as those of 2a and 4c. On the other hand, the behaviors of
3,4,6-tri-O-acetyl-protected glycosyl donors 2b and 4b, and
4,6-O-benzylidene-protected glucosyl donor 2c are quite
different from those of glycosyl donors 2a, 4a and 4c
mentioned above. Those reactions with alcohol 7 produced
an anomeric mixture of imidates 30 (a:bZ85:15), 32
(a:bZ88:12), and 36 (a:bZ91:9) as main products, along
with small amounts of disaccharides 31, 33, and 35 with a:b
ratios of 14:86, 3:97, and 8:92, respectively. It is interesting
to note that the a:b ratios of imidates 30 and 36 in the
D-gluco series are opposite to those of the corresponding
disaccharides 31 and 35, respectively. These relationships
strongly suggest that glycosidations with electronically or
torsionally disarmed 2-azido-2-deoxyglucosyl diphenyl
phosphates proceed via an SN2-like displacement, where the
glucosyl-nitrilium ions 49 would be too stable to generate the
solvent separated oxocarbenium ion 48. However, this is not
the case with 3,4,6-tri-O-acetyl-protected galactosyl diphenyl
phosphate 4b probably because the galactosyl nitrilium ions
49 may exhibit greater anomeric reactivities to allow for a
dynamic equilibrium than the glucosyl counterparts.20c,d
Scheme 2. Potential pathways in the TMSOTf-promoted glycosidation of
2-azido-2-deoxyglycosyl trichloroacetimidates.
leaving group of 2-azido-2-deoxyglycosyl donors has been
demonstrated. We found that coupling of the 3,4,6-tri-O-
benzyl-protected glucosyl and galactosyl donors and the
4,6-O-benzylidene-protected galactosyl donor with a range
of glycoside alcohols in the presence of 1.5 equiv of
TMSOTf in propionitrile at K78 8C proceeds smoothly to
give 1,2-trans-b-linked disaccharides in high yields with
a:b ratios ranging from 9:91 to 1:O99, regardless of the
anomeric composition of the starting donor. The use of
propionitrile as a solvent at K78 8C proved to be the best
choice for the highest levels of b-selectivity reported to date
for this type of glycosidation. However, limitations of the
phosphate method were recognized for 3,4,6-tri-O-acetyl-
protected glucosyl and galactosyl donors and 4,6-O-
benzylidene-protected glucosyl donor. These results indi-
cate that the properly choosing of protecting groups on
2-azido-2-deoxy-sugar components is crucial for the
success in the present method. It has also been experimen-
tally demonstrated that highly efficient and b-selective
glycosidations proceed through intermediate a-glycosyl-
nitrilium ions followed by an SN2-like displacement, which
is based on the finding that only a-imidates formed through
their intermediate were small amounts of byproducts when
highly reactive O-6-unprotected glycoside alcohols were
used as a glycosyl acceptor. A comparative study with the
corresponding trichloroacetimidates under the present
reaction conditions demonstrated that similar high levels
of b-selectivity are observed, but the phosphate method
generally gives higher product yields than the trichloroace-
timidate method. The latter method is frequently
accompanied by side-products that originate from the
departing trichloroacetamide, particularly when a-imi-
dates are used. While the discrepancy in reaction mode
between a- and b-trichloroacetimidates remains to be
elucidated, only using b-trichloroacetimidates ensures a
successful result. Thus, the present method would be a
Since TMSOTf-promoted glycosidations of 2-azido-2-
deoxyglycosyl trichloroacetimidates exhibit essentially the
same high b-selectivities as those found with diphenyl
phosphates under identical conditions, the stereochemical
reaction course seems to be analogous to that proposed with
the phosphate method in Scheme 1. However, the product
yields in the trichloroacetimidate method highly depends on
the anomeric configuration of the starting donor and the
reactivity of acceptor alcohols. Substantial amounts of
b-trichloroacetamides and a-amidines were frequently
obtained as byproducts when a-trichloroacetimidates were
used as glycosyl donors. Although the striking difference
between the behavior of a- and b-trichloroacetimidates
currently cannot be explained, the formation of b-trichloro-
acetamides 56 and a-amidines 58 can be rationalized by the
mechanism shown in Scheme 2. In glycosidations with
trichloroacetimidates, the departing trichloroacetamide (55)
and/or its TMS derivative 54 competes as a nucleophile with
acceptor alcohols. No such reactions were observed in
the phosphate method due to the low nucleophilicity of
the diphenyl phosphate. The SN2-like displacement by the
amide nitrogen atom of 54 or 55 at the anomeric carbon of
a-nitrilium ion 49a leads to b-amides 56 with inversion of
configuration, whereas the capture of 49a by the amide
oxygen atom of 54 or 55 at the nitrilium carbon followed by
rearrangement produces a-amidines 58. The stereocon-
trolled formation of b-amides 56 and a-amidines 58 again
demonstrates the virtually exclusive intermediacy of
a-nitrilium ion 49a in glycosidations of the 3,4,6-tri-O-
benzyl-protected glucosyl and galactosyl donors.
3. Conclusion
The effectiveness of the diphenyl phosphate group as a

10720
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
potent alternative to Schmidt’s trichloroacetimidate
procedure.
4.2. Preparation of 2-azido-2-deoxy-D-glycosyl donors
4.2.1. Typical procedure for preparation of 2-azido-2-
deoxyglycopyranosyl diphenyl phosphate: 2-azido-3,4,6-
tri-O-benzyl-2-deoxy-D-glucopyranosyl diphenyl phos-
phate (2a). Diphenylphosphoryl chloride (0.55 mL,
2.66 mmol) was added to a stirred solution of 1a7b
(1.10 g, 2.31 mmol) and DMAP (564 mg, 4.62 mmol) in
CH2Cl2 (10 mL) at 0 8C. After 0.5 h, the reaction was
quenched with crushed ice, followed by stirring at room
temperature for 15 min. The mixture was poured into a two-
layer mixture of Et2O (20 mL) and saturated aqueous
NaHCO3 (20 mL), and the whole was extracted with AcOEt
(40 mL). The organic layer was washed with brine (2!
20 mL), and dried over anhydrous Na2SO4. Filtration and
evaporation in vacuo furnished the pale yellow oil (1.70 g),
which was purified by column chromatography (silica gel
30 g, 2:1 hexane/AcOEt with 2% Et3N) to give diphenyl
phosphate 2a (1.59 g, 97%, a:bZ72:28) as a colorless oil.
The anomeric a:b ratio of the diphenyl phosphate was
determined by 31P NMR.
4. Experimental
4.1. General
Melting points were determined on a Bu¨chi 535 digital
melting point apparatus and were uncorrected. Optical
rotations were recorded on a JASCO P-1030 digital
polarimeter. Infrared (IR) spectra were recorded on a
JASCO FT/IR-5300 spectrophotometer and absorbance
bands are reported in wavenumber (cmK1). Proton nuclear
magnetic resonance (1H NMR) spectra were recorded on a
Bruker ARX500 (500 MHz) spectrometer with tetramethyl-
silane (dH 0.00) as an internal standard. Coupling constants
(J) are reported in hertz (Hz). Abbreviations of multiplicity
are as follows: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet; br, broad. Data are presented as follows: chemical
shift, multiplicity, coupling constants, integration and
assignment. Carbon nuclear magnetic resonance (13C
NMR) spectra were recorded on JEOL AL400 (100 MHz)
or Bruker ARX500 (126 MHz) spectrometers with CDCl3
(dC 77.0) as an internal standard. Phosphorus nuclear
magnetic resonance (31P NMR) spectra were recorded on
JEOL EX270 (109 MHz) or Bruker ARX500 (202 MHz)
spectrometers with H3PO4 (dP 0.00) as an external standard.
Fast atom bombardment (FAB) mass spectra were obtained
on a JEOL JMS HX110 spectrometer in the Center for
Instrumental Analysis, Hokkaido University.
Data for a-anomer (2aa): TLC RfZ0.42 (2:1 hexane/
AcOEt); [a]1D4ZC38.18 (c 1.14, CHCl3) (a:bZ85:15); IR
(film) 3022, 2872, 2870, 2116, 1591, 1491, 1288, 1059,
1188, 966 cmK1; 1H NMR (500 MHz, CDCl3) d 3.35 (brd,
JZ10.9 Hz, 1H, H-6a), 3.61 (ddd, JZ3.4, 9.8, 3.3
(JH–P) Hz, 1H, H-2), 3.64 (dd, JZ1.0, 10.9 Hz, 1H, H-6b),
3.79–3.85 (m, 2H, H-4, H-5), 3.88 (m, 1H, H-3), 4.43 (d,
JZ11.1 Hz, 1H, OCHPh), 4.536 (d, JZ11.1 Hz, 1H,
OCHPh), 4.537 (d, JZ10.9 Hz, 1H, OCHPh), 4.78 (d, JZ
10.9 Hz, 1H, OCHPh), 4.82 (d, JZ10.7 Hz, 1H, OCHPh),
4.86 (d, JZ10.7 Hz, 1H, OCHPh), 5.98 (dd, JZ3.4, 6.1
(JH–P) Hz, 1H, H-1), 7.15–7.35 (m, 25H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 63.5 (d, JC–PZ8.6 Hz), 67.4, 73.2,
73.5, 75.1, 75.6, 80.0, 97.3 (d, JC–PZ6.3 Hz, C-1), 120.1 (d,
JC–PZ5.0 Hz), 120.3 (d, JC–PZ5.0 Hz), 125.4, 125.5,
127.7, 127.77, 127.83, 127.9, 128.0, 128.1, 128.4, 128.45,
128.48, 129.7, 129.8, 137.6, 137.66, 137.70, 150.38 (d,
JC–PZ7.5 Hz), 150.44 (d, JC–PZ7.5 Hz); 31P NMR
(109 MHz, CDCl3) d K13.3; FAB-HRMS m/z calcd for
C39H39N3O8P (MCH)C 708.2474, found 708.2476; Anal.
calcd for: C39H38N3O8P: C, 66.19; H, 5.41; N, 5.94, found
C, 66.06; H, 5.54; N, 5.82. Data for b-anomer (2ab): TLC
RfZ0.38 (2:1 hexane/AcOEt); [a]2D2ZC2.698 (c 1.33,
CHCl3) (a:bZ5:95); IR (film) 3022, 2872, 2870, 2116,
Column chromatography was carried out on Kanto silica gel
60 N (40–50 mm or 63–210 mm) or Wakogel C-200 (75–
150 mm). Analytical thin layer chromatography (TLC) was
carried out on Merck Kieselgel 60 F254 plates. Visualization
was accomplished with ultraviolet light and anisaldehyde or
phosphomolybdic acid stain, followed by heating. HPLC
analyses were performed on a JASCO PU-980 and UV-970
(detector, lZ254 nm). Retention times (tR) and peak ratios
were determined with a Shimadzu Chromatopac C-R6A.
Hexane was HPLC grade, and filtered and degassed prior to
use.
Reagents and solvents were purified by standard means or
used as received unless otherwise noted. Dehydrated
stabilizer free THF was purchased from Kanto Chemical
Co., Inc. Dichloromethane and propionitrile were distilled
from P2O5, and redistilled from calcium hydride prior to
1591, 1491, 1288, 1059, 1188, 966 cmK1 1H NMR
;
(500 MHz, CDCl3) d 3.47–3.54 (m, 3H, H-2, H-4, H-5),
3.63 (dd, JZ1.7, 11.1 Hz, 1H, H-6a), 3.73 (dd, JZ3.6,
11.1 Hz, 1H, H-6b), 3.76 (t, JZ9.1 Hz, 1H, H-3), 4.45 (d,
JZ12.0 Hz, 1H, OCHPh), 4.55 (d, JZ12.0 Hz, 1H,
OCHPh), 4.58 (d, JZ10.9 Hz, 1H, OCHPh), 4.78 (d, JZ
10.9 Hz, 1H, OCHPh), 4.82 (d, JZ11.0 Hz, 1H, OCHPh),
4.86 (d, JZ11.0 Hz, 1H, OCHPh), 5.15 (dd, JZ7.3, 7.3
(JH–P) Hz, 1H, H-1), 7.16–7.34 (m, 25H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 66.5 (d, JC–PZ9.2 Hz), 67.9, 73.6,
75.0, 75.7, 75.9, 82.9, 98.2 (d, JC–PZ5.5 Hz, C-1), 120.1 (d,
JC–PZ5.0 Hz), 120.5 (d, JC–PZ5.0 Hz), 125.5, 125.6,
127.68, 127.71, 127.8, 127.9, 128.0, 128.1, 128.4, 128.46,
˚
use. Molecular sieves 4 A was finely ground in mortar and
heated in vacuo at 220 8C for 12 h.
All reactions were conducted under an argon atmosphere.
Lactols 1a,7b 1b,7a 3a,7a 3b36 and 3c37 were prepared
according to literature procedures. For full characterization,
most of the authentic a-glycosides were prepared by
glycosidations of diphenyl phosphates with acceptor
alcohols in Et2O at 0 8C, followed by chromatographic
separation from the b-glycosides. Glycosides 31, 33 and 35
were prepared by reactions of diphenyl phosphates with
alcohol 7 in CH2Cl2 at K30 8C, followed by column
chromatography.
128.48, 129.6, 129.8, 137.6, 137.7, 137.9, 150.3, (d, JC–P
Z
7.5 Hz), 150.5 (d, JC–PZ7.5 Hz); 31P NMR (109 MHz,
CDCl3) d K13.5; FAB-HRMS m/z calcd for C39H39N3O8P
(MCH)C 708.2474, found 708.2490.

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10721
4.2.2. 3,4,6-Tri-O-acetyl-2-azido-2-deoxy-D-glucopyra-
nosyl diphenyl phosphate (2b). The reaction was per-
formed according to the typical procedure (10 mL CH2Cl2,
0 8C, 0.5 h) employing lactol 1b7a (754 mg, 2.28 mmol),
diphenylphosphoryl chloride (0.66 mL, 3.19 mmol), and
DMAP (557 mg, 4.56 mmol). The crude product (1.53 g)
was purified by column chromatography (silica gel 40 g,
1.5:1 hexane/AcOEt with 1% Et3N) to give diphenyl
phosphate 2b (1.28 g, 99%, a:bZ46:54) as a pale yellow
syrup. TLC RfZ0.50 (1:1 hexane/AcOEt); [a]1D8ZC48.08
(c 1.35, CHCl3) (a:bZ46:54); IR (film) 2116, 1753, 1591,
1489, 1188, 970 cmK1; 1H NMR (500 MHz, CDCl3) d 1.99
(s, 1.5H, CH3CO), 2.02 (s, 1.5H, CH3CO), 2.03 (s, 1.5H,
CH3CO), 2.04 (s, 1.5H, CH3CO), 2.08 (s, 1.5H, CH3CO),
2.10 (s, 1.5H, CH3CO), 3.64 (m, 0.5H, H-2b), 3.72 (ddd,
JZ3.4, 10.4, 3.3 (JH–P) Hz, 0.5H, H-2a), 3.76 (m, 0.5H,
H-5b), 3.80 (dd, JZ2.1, 12.6 Hz, 0.5H, H-6aa), 4.00 (dd,
JZ2.3, 12.5 Hz, 0.5H, H-6ab), 4.03 (ddd, JZ2.1, 3.9,
10.4 Hz, 0.5H, H-5a), 4.17 (dd, JZ3.9, 12.6 Hz, 0.5H,
H-6ba), 4.22 (dd, JZ4.8, 12.5 Hz, 0.5H, H-6bb), 5.02–5.11
(m, 1.5H, H-4a, H-3b, H-4b), 5.24 (dd, JZ7.8, 7.8
(JH–P) Hz, 0.5H, H-1b), 5.45 (dd, JZ9.9, 10.4 Hz, 0.5H,
H-3a), 6.01 (dd, JZ3.4, 6.4 (JH–P) Hz, 0.5H, H-1a), 7.20–
7.38 (m, 10H, Ar-H); 13C NMR (126 MHz, CDCl3) d 20.36,
20.38, 20.41, 20.5, 60.8, 60.9 (d, JC–PZ8.9 Hz), 61.2, 63.9
(d, JC–PZ9.8 Hz), 67.4, 67.6, 69.7, 70.3, 72.4, 72.5, 96.1 (d,
JC–PZ5.5 Hz, C-1a), 97.6 (d, JC–PZ5.0 Hz, C-1b), 119.88,
119.92, 120.0, 120.15, 120.19, 120.23, 120.3, 125.56,
125.62, 129.6, 129.7, 129.8, 150.0, 150.06, 150.10,
150.12, 150.15, 150.16, 169.36, 169.39, 169.5, 169.7,
170.2; 31P NMR (109 MHz, CDCl3) d K13.6 (b), K13.2
(a); FAB-HRMS m/z calcd for C24H27N3O11P (MCH)C
564.1383, found 564.1379; Anal. calcd for: C24H26N3O11P:
C, 51.16; H, 4.65; N, 7.46, found C, 51.16; H, 4.71; N, 7.60.
H-3b), 5.35 (brd, JZ3.6 Hz, 0.5H, H-1a), 5.48 (s, 0.5H,
CHPh), 5.50 (s, 0.5H, CHPh), 5.64 (dd, JZ9.6, 10.3 Hz,
0.5H, H-3a), 7.34–7.38 (m, 3H, Ar-H), 7.40–7.45 (m, 2H,
Ar-H); 13C NMR (126 MHz, CDCl3) d 20.8, 62.2, 62.7,
65.7, 66.5, 68.3, 68.8, 69.1, 71.3, 78.6, 79.4, 93.1 (C-1a),
96.6 (C-1b), 101.5, 101.7, 126.1, 126.2, 128.2, 129.2, 136.6,
136.8, 170.0, 170.1; FAB-HRMS m/z calcd for C15H18N3O6
(MCH)C 336.1196, found 336.1193.
4.2.4. 3-O-Acetyl-2-azido-4,6-O-benzylidene-2-deoxy-a-
D-glucopyranosyl diphenyl phosphate (2c). The reaction
was performed according to the typical procedure (8 mL,
CH2Cl2, 0 8C, 0.5 h) employing lactol 1c (621 mg,
1.85 mmol), diphenylphosphoryl chloride (0.50 mL,
2.41 mmol), and DMAP (476 mg, 3.90 mmol). The crude
product (1.14 g) was purified by column chromatography
(silica gel 40 g, 2:1 hexane/AcOEt with 1% Et3N) to give
diphenyl phosphates 2cb (714 mg, 68%, white solid) and
2ca (324 mg, 31%, colorless syrup). Data for a-anomer
(2ca): mp 103.0–105.0 8C (AcOEt–hexane); TLC RfZ0.20
(2:1 hexane/AcOEt); [a]2D2ZC48.18 (c 1.50, CHCl3); IR
(film) 2868, 2114, 1753, 1589, 1489, 1371, 1219, 1186,
954 cmK1 1H NMR (500 MHz, CDCl3) d 2.14 (s, 3H,
;
CH3CO), 3.60–3.66 (m, 3H, H-2, H-4, H-6ax), 3.89–3.95
(m, 2H, H-5, H-6eq), 5.45 (s, 1H, CHPh), 5.58 (t, JZ9.9 Hz,
1H, H-3), 5.99 (dd, JZ3.5, 6.5 (JH–P) Hz, 1H, H-1), 7.21
(m, 2H, Ar-H), 7.25–7.31 (m, 4H, Ar-H), 7.35–7.42 (m, 9H,
Ar-H); 13C NMR (126 MHz, CDCl3) d 20.6, 61.7 (d, JC–P
Z
8.9 Hz), 64.6, 68.0, 68.9, 78.4, 96.9 (d, JC–PZ5.5 Hz, C-1),
101.1, 119.9 (d, JC–PZ5.0 Hz), 120.2 (d, JC–PZ5.0 Hz),
125.6, 126.0, 128.1, 129.1, 129.7, 129.8, 136.5, 150.1, (d,
JC–PZ5.0 Hz), 150.2 (d, JC–PZ5.0 Hz), 169.4; 31P NMR
(109 MHz, CDCl3) d K13.0; FAB-HRMS m/z calcd for
C27H27N3O9P (MCH)C 568.1485, found 568.1467. Data
for b-anomer (2cb): TLC RfZ0.39 (2:1 hexane/AcOEt);
[a]2D2ZK52.88 (c 1.50, CHCl3); IR (film) 2868, 2114, 1755,
4.2.3. 3-O-Acetyl-2-azido-4,6-O-benzylidene-2-deoxy-D-
glucopyranose (1c). Tetrabutylammonium fluoride in
THF (1.0 M, 2.50 mL, 2.50 mmol) was added to a stirred
solution of tert-butyldimethylsilyl 3-O-acetyl-2-azido-4,6-
O-benzylidene-2-deoxy-b-D-glucopyranoside38 (850 mg,
1.89 mmol) in THF (10 mL)—AcOH (0.16 mL) at 0 8C.
After stirring for 15 min, saturated aqueous NaHCO3
(3 mL) was added, and the whole was extracted with
AcOEt (50 mL). The organic layer was successively washed
with saturated aqueous NaHCO3 (10 mL) and brine (2!
10 mL), and dried over anhydrous Na2SO4. Filtration and
evaporation in vacuo furnished the crude product (1.02 g),
which was purified by column chromatography (silica gel
30 g, 2:1 hexane/AcOEt) to give lactol 1c (621 mg, 98%,
a:bZ52:48) as a white amorphous. The anomeric a:b ratio
1589, 1489, 1371, 1219, 1186, 958 cmK1 1H NMR
;
(500 MHz, CDCl3) d 2.13 (s, 3H, CH3CO), 3.56 (ddd, JZ
4.9, 9.6, 10.2 Hz, 1H, H-5), 3.63 (m, 1H, H-2), 3.65 (dd, JZ
9.6, 10.3 Hz, 1H, H-4), 3.67 (dd, JZ10.2, 10.4 Hz, 1H,
H-6ax), 4.23 (dd, JZ4.9, 10.4 Hz, 1H, H-6eq), 5.22 (dd, JZ
8.9, 10.3 Hz, 1H, H-3), 5.31 (dd, JZ7.7, 7.9 (JH–P) Hz, 1H,
H-1), 5.46 (s, 1H, CHPh), 7.20–7.27 (m, 6H, Ar-H), 7.34–
7.41 (m, 9H, Ar-H); 13C NMR (126 MHz, CDCl3) d 20.5,
64.7 (d, JC–PZ8.8 Hz), 66.8, 67.7, 71.1 (d, JC–PZ1.1 Hz),
77.7, 98.0 (d, JC–PZ5.0 Hz, C-1), 101.4, 119.8 (d, JC–P
5.0 Hz), 120.1 (d, JC–PZ5.0 Hz), 125.5, 125.6, 125.9,
128.1, 129.0, 129.6, 129.7, 136.4, 150.05, (d, JC–P
Z
Z
6.3 Hz), 150.11 (d, JC–PZ6.3 Hz), 169.2; 31P NMR
(109 MHz, CDCl3) d K13.8; FAB-HRMS m/z calcd for
C27H27N3O9P (MCH)C 568.1485, found 568.1468; Anal.
calcd for C27H26N3O9P: C, 57.15; H, 4.62; N, 7.40, found C,
57.22; H, 4.61; N, 7.49.
1
of the lactol was determined by H NMR. TLC RfZ0.23
(2:1 hexane/AcOEt); [a]2D3ZK7.498 (c 1.02, CHCl3)
(a:bZ52:48); IR (KBr) 3468, 2868, 2112, 1726, 1452,
1
1371, 1259, 1095 cmK1; H NMR (500 MHz, CDCl3) d
2.14 (s, 3H, CH3CO), 3.33 (dd, JZ3.6, 10.3 Hz, 0.5H,
H-2a), 3.37 (br, 0.5H, OH), 3.45 (dd, JZ8.0, 10.0 Hz, 0.5H,
H-2b), 3.49 (ddd, JZ5.0, 9.6, 10.4 Hz, 0.5H, H-5b), 3.63
(dd, JZ9.5, 9.6 Hz, 1H, H-4a, H-4b), 3.73 (dd, JZ10.3,
10.4 Hz, 0.5H, H-6axa), 3.77 (dd, JZ10.4, 10.6 Hz, 0.5H,
H-6axb), 3.97 (br, 0.5H, OH), 4.19 (ddd, JZ5.0, 9.5,
10.3 Hz, 0.5H, H-5a), 4.28 (dd, JZ5.0, 10.4 Hz, 0.5H,
H-6eqa), 4.32 (dd, JZ5.0, 10.6 Hz, 0.5H, H-6eqb), 4.77 (d,
JZ8.0 Hz, 0.5H, H-1b), 5.17 (dd, JZ9.5, 10.0 Hz, 0.5H,
4.2.5. 2-Azido-3,4,6-tri-O-benzyl-2-deoxy-a-D-galacto-
pyranosyl diphenyl phosphate (4a). The reaction was
performed according to the typical procedure (10 mL
CH2Cl2, 0 8C, 0.5 h) with lactol 3a7a (1.10 g, 2.31 mmol),
diphenylphosphoryl chloride (0.63 mL, 3.02 mmol), and
DMAP (567 mg, 4.63 mmol). The crude product (1.68 g)
was purified by column chromatography (silica gel 40 g, 3:1
hexane/AcOEt with 2% Et3N) to give diphenyl phosphate
4a (1.30 g, 79%, a:bZ58:42) as a colorless syrup. TLC

10722
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
RfZ0.45 (a), 0.31 (b) (2:1 hexane/AcOEt); [a]2D2ZC55.38
(c 1.50, CHCl3) (a:bZ90:10); IR (film) 3032, 2872, 2114,
(4bb): TLC RfZ0.42 (10:1 CH2Cl2/acetone); [a]2D4Z
C5.608 (c 1.50, CHCl3); IR (film) 2116, 1753, 1591,
1489, 1371, 1226, 960 cmK1; 1H NMR (500 MHz, CDCl3)
d 1.98 (s, 3H, CH3CO), 2.05 (s, 3H, CH3CO), 2.16 (s, 3H,
CH3CO), 3.82 (dd, JZ8.2, 10.7 Hz, 1H, H-2), 3.97 (dt, JZ
0.6, 6.5 Hz, 1H, H-5), 4.02 (dd, JZ6.5, 11.0 Hz, 1H, H-6a),
4.10 (dd, JZ6.5, 11.0 Hz, 1H, H-6b), 4.87 (dd, JZ3.3,
10.7 Hz, 1H, H-3), 5.24 (dd, JZ8.2, 7.4 (JH–P) Hz, 1H,
H-1), 5.36 (dd, JZ0.6, 3.3 Hz, 1H, H-4), 7.22 (m, 2H,
Ar-H), 7.26–7.28 (m, 4H, Ar-H), 7.34–7.37 (m, 4H, Ar-H);
13C NMR (126 MHz, CDCl3) d 20.4, 20.5, 60.7, 61.0 (d,
JC–PZ9.4 Hz), 65.9, 71.2 (d, JC–PZ1.6 Hz), 71.8, 98.1 (d,
JC–PZ5.3 Hz, C-1), 120.0 (d, JC–PZ3.4 Hz), 120.3 (d,
1
1591, 1489, 1290, 1188, 958 cmK1; H NMR (500 MHz,
CDCl3) d 3.28 (dd, JZ5.4, 9.0 Hz, 0.6H, H-6aa), 3.39 (dd,
JZ2.7, 10.4 Hz, 0.4H, H-3b), 3.45 (dd, JZ4.7, 8.5 Hz,
0.4H, H-6ab), 3.56 (dd, JZ8.1, 9.0 Hz, 0.6H, H-6ba), 3.58
(dd, JZ8.0, 8.5 Hz, 0.4H, H-6bb), 3.61 (dd, JZ4.7, 8.0 Hz,
0.4H, H-5b), 3.86 (dd, JZ2.5, 10.5 Hz, 0.6H, H-3a), 3.90
(dd, JZ8.0, 10.4 Hz, 0.4H, H-2b), 3.92 (d, JZ2.7 Hz, 0.4H,
H-4b), 4.01 (dd, JZ5.4, 8.1 Hz, 0.6H, H-5a), 4.05 (brs,
0.6H, H-4a), 4.10 (ddd, JZ3.3, 10.5, 3.2 (JH–P) Hz, 0.6H,
H-2a), 4.36 (d, JZ12.6 Hz, 0.6H, OCHPh), 4.38 (d, JZ
12.6 Hz, 0.6H, OCHPh), 4.39 (d, JZ11.6 Hz, 0.4H,
OCHPh), 4.41 (d, JZ11.6 Hz, 0.4H, OCHPh), 4.52 (d,
JZ11.2 Hz, 0.6H, OCHPh), 4.55 (d, JZ11.4 Hz, 0.4H,
OCHPh), 4.64 (d, JZ11.7 Hz, 0.4H, OCHPh), 4.65 (d, JZ
11.4 Hz, 0.6H, OCHPh), 4.69 (d, JZ11.7 Hz, 0.4H,
OCHPh), 4.71 (d, JZ11.4 Hz, 0.6H, OCHPh), 4.85 (d,
JZ11.2 Hz, 0.6H, OCHPh), 4.87 (d, JZ11.4 Hz, 0.4H,
OCHPh), 5.09 (dd, JZ8.0, 7.2 (JH–P) Hz, 0.4H, H-1b), 5.94
(dd, JZ3.3, 5.7 (JH–P) Hz, 0.6H, H-1a), 7.11–7.39 (m, 25H,
JC–PZ3.4 Hz), 125.6, 125.7, 129.7, 129.8, 150.2 (d, JC–P
Z
8.8 Hz), 150.3 (d, JC–PZ8.8 Hz), 169.5, 169.8, 170.2; 31P
NMR (109 MHz, CDCl3) d K13.5; FAB-HRMS m/z calcd
for C24H27N3O11P (MCH)C 564.1383, found 564.1385;
Anal. calcd for: C24H26N3O11P: C, 51.16; H, 4.65; N, 7.46,
found C, 51.02; H, 4.72; N, 7.47.
4.2.7. 3-O-Acetyl-2-azido-4,6-O-benzylidene-2-deoxy-a-
D-galactopyranosyl diphenyl phosphate (4c). The reaction
was performed according to the typical procedure (6 mL
CH2Cl2, 0 8C, 0.5 h) employing lactol 3c37 (350 mg,
1.04 mmol), diphenylphosphoryl chloride (0.28 mL,
1.36 mmol), and DMAP (254 mg, 2.08 mmol). The crude
product (530 mg) was purified by column chromatography
(silica gel 25 g, 2:1/1:1 hexane/AcOEt with 1% Et3N) to
give diphenyl phosphates 4ca (295 mg, 50%) and 4cb
(147 mg, 25%) as white amorphous. Data for a-anomer
(4ca): TLC RfZ0.44 (1:1 hexane/AcOEt); [a]2D4ZC152.58
(c 1.50, CHCl3); IR (KBr) 3069, 2922, 2116, 1747, 1591,
Ar-H); 13C NMR (126 MHz, CDCl3) d 59.4 (d, JC–P
Z
8.4 Hz), 63.1 (d, JC–PZ9.1 Hz), 67.4, 67.5, 71.5, 72.0, 72.4,
72.5, 73.30, 73.34, 74.2, 74.6, 74.8, 77.0, 77.2, 80.4 (d,
JC–PZ2.4 Hz), 97.8 (d, JC–PZ5.9 Hz, C-1a), 98.3 (d,
JC–PZ5.2 Hz, C-1b), 119.9 (d, JC–PZ5.0 Hz), 120.0 (d,
JC–PZ5.0 Hz), 120.1 (d, JC–PZ5.0 Hz), 120.4 (d, JC–P
Z
5.0 Hz), 125.2, 125.3, 125.4, 125.5, 127.60, 127.64, 127.67,
127.73, 127.8, 127.86, 127.89, 128.15, 128.18, 128.3, 128.4,
129.4, 129.5, 129.6, 129.7, 137.08, 137.12, 137.5, 137.9,
138.0, 150.2 (d, JC–PZ7.5 Hz), 150.30 (d, JC–PZ7.5 Hz),
150.31 (d, JC–PZ7.5 Hz), 150.36 (d, JC–PZ7.5 Hz); 31P
NMR (109 MHz, CDCl3) d K13.32 (b), K13.25 (a); FAB-
HRMS m/z calcd for C39H39N3O8P (MCH)C 708.2474,
found 708.2451; Anal. calcd for C39H38N3O8P: C, 66.19; H,
5.41; N, 5.94, found C, 66.35; H, 5.59; N, 5.85.
1
1489, 1224, 1188, 958, 756 cmK1; H NMR (500 MHz,
CDCl3) d 2.14 (s, 3H, CH3CO), 3.66 (brs, 1H, H-5), 3.83
(dd, JZ1.0, 13.0 Hz, 1H, H-6a), 3.95 (dd, JZ0.9, 13.0 Hz,
1H, H-6b), 4.20 (ddd, JZ3.2, 11.0, 3.2 (JH–P) Hz, 1H, H-2),
4.42 (brd, JZ5.4 Hz, 1H, H-4), 5.23 (dd, JZ3.3, 11.0 Hz,
1H, H-3), 5.46 (s, 1H, CHPh), 6.10 (dd, JZ3.2,
6.0 (JH–P) Hz, 1H, H-1), 7.18 (m, 2H, Ar-H), 7.25–7.38
(m, 11H, Ar-H), 7.46 (m, 2H, Ar-H); 13C NMR (126 MHz,
CDCl3) d 20.8, 57.0 (d, JC–PZ8.6 Hz), 64.3, 68.3, 69.4,
4.2.6. 3,4,6-Tri-O-acetyl-2-azido-2-deoxy-D-galactopyra-
nosyl diphenyl phosphate (4b). The reaction was per-
formed according to the typical procedure (10 mL CH2Cl2,
0 8C, 0.5 h) with lactol 3b36 (994 mg, 3.00 mmol), diphen-
ylphosphoryl chloride (0.81 mL, 3.90 mmol), and DMAP
(953 mg, 7.80 mmol). The crude product (1.96 g) was
purified by column chromatography (silica gel 40 g, 2:1
hexane/AcOEt) to give diphenyl phosphate 4b (1.64 g, 97%,
a:bZ24:76) as a colorless syrup. Data for a-anomer (4ba):
TLC RfZ0.58 (10:1 CH2Cl2/acetone); [a]2D4ZC74.28 (c
1.50, CHCl3); IR (film) 2116, 1753, 1591, 1489, 1371, 1226,
72.6, 97.6 (d, JC–PZ5.0 Hz, C-1), 100.6, 120.0 (d, JC–P
5.0 Hz), 120.2 (d, JC–PZ5.0 Hz), 125.4, 125.5, 126.0,
128.1, 129.1, 129.67, 129.72, 137.1, 150.2, (d, JC–P
Z
Z
4.4 Hz), 150.3 (d, JC–PZ4.4 Hz), 170.2; 31P NMR
(202 MHz, CDCl3) d K12.9; FAB-HRMS m/z calcd for
C27H27N3O9P (MCH)C 568.1485, found 568.1501; Anal.
calcd for: C27H26N3O9P: C, 57.15; H, 4.62; N, 7.40, found
C, 57.20; H, 4.64; N, 7.39. Data for b-anomer (4cb): TLC
RfZ0.28 (1:1 hexane/AcOEt); [a]2D6ZC73.88 (c 1.50,
CHCl3); IR (KBr) 3069, 2905, 2118, 1749, 1591, 1491,
1371, 1294, 1186, 1087 cmK1; 1H NMR (500 MHz, CDCl3)
d 2.12 (s, 3H, CH3CO), 3.56 (brs, 1H, H-5), 3.95 (dd, JZ
1.3, 12.5 Hz, 1H, H-6a), 4.00 (dd, JZ8.2, 10.8 Hz, 1H,
H-2), 4.17 (dd, JZ1.2, 12.5 Hz, 1H, H-6b), 4.34 (d, JZ
3.3 Hz, 1H, H-4), 4.78 (dd, JZ3.3, 10.8 Hz, 1H, H-3), 5.25
(dd, JZ8.2, 6.7 (JH–P) Hz, 1H, H-3), 5.49 (s, 1H, CHPh),
7.18 (m, 2H, Ar-H), 7.24–7.43 (m, 11H, Ar-H), 7.51 (m, 2H,
960 cmK1 1H NMR (500 MHz, CDCl3) d 1.90 (s, 3H,
;
CH3CO), 2.07 (s, 3H, CH3CO), 2.14 (s, 3H, CH3CO), 3.86
(dd, JZ6.4, 11.3 Hz, 1H, H-6a), 3.96 (ddd, JZ3.3, 11.0, 3.2
(JH–P) Hz, 1H, H-2), 4.06 (dd, JZ6.8, 11.3 Hz, 1H, H-6b),
4.29 (dd, JZ6.4, 6.8 Hz, 1H, H-5), 5.30 (dd, JZ3.2,
11.0 Hz, 1H, H-3), 5.46 (brd, JZ3.2 Hz, 1H, H-4), 6.04 (dd,
JZ3.3, 6.1 (JH–P) Hz, 1H, H-1), 7.21 (m, 2H, Ar-H), 7.25–
7.28 (m, 4H, Ar-H), 7.34–7.38 (m, 4H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 20.4, 20.47, 20.50, 57.4 (d, JC–P
Z
8.7 Hz), 60.8, 66.7, 68.4, 68.7, 96.7 (d, JC–PZ5.5 Hz, C-1),
120.0 (d, JC–PZ5.0 Hz), 120.2 (d, JC–PZ5.0 Hz), 125.60,
125.63, 129.7, 129.8, 150.2 (d, JC–PZ6.3 Hz), 150.3 (d,
JC–PZ6.3 Hz), 169.6, 169.8, 170.1; 31P NMR (109 MHz,
CDCl3) d K13.1; FAB-HRMS m/z calcd for C24H27N3O11P
(MCH)C 564.1383, found 564.1368. Data for b-anomer
Ar-H); 13C NMR (126 MHz, CDCl3) d 20.8, 60.5 (d, JC–P
Z
10.1 Hz), 67.0, 68.3, 72.0, 72.2 (d, JC–PZ1.5 Hz), 98.2 (d,
JC–PZ5.0 Hz, C-1), 100.8, 120.0 (d, JC–PZ5.0 Hz), 120.7
(d, JC–PZ5.0 Hz), 125.5, 126.2, 128.2, 129.2, 129.6, 129.7,
137.4, 150.2 (d, JC–PZ6.3 Hz), 150.3 (d, JC–PZ7.5 Hz),

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10723
170.1; 31P NMR (202 MHz, CDCl3) d K13.1; FAB-HRMS
m/z calcd for C27H27N3O9P (MCH)C 568.1485, found
568.1470.
75.6, 77.4, 77.9, 80.4, 83.0, 93.5 (d, JC–PZ4.0 Hz, C-1a),
96.1 (d, JC–PZ4.5 Hz, C-1b), 127.66, 127.72, 127.8,
127.88, 127.91, 128.06, 128.11, 128.3, 128.4, 128.45,
128.47, 137.7, 137.76, 137.81, 137.87, 137.94; 31P NMR
(109 MHz, CDCl3) d 19.41 (a), 20.01 (b); FAB-HRMS m/z
calcd for C31H41N5O6P (MCH)C 610.2795, found
610.2795.
4.2.8. 2-Azido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyra-
nosyl diphenyl phosphate (2a) (a:bZ2:98). Diphenyl
phosphate (207 mg, 0.83 mmol) was added to a stirred
solution of 5a7b (514 mg, 0.83 mmol) in CH2Cl2 (7 mL) at
0 8C. After 0.1 h, the mixture was poured into a two-layer
mixture of Et2O (5 mL) and saturated aqueous NaHCO3
(5 mL), and the whole was extracted with AcOEt (30 mL).
The organic layer was successively washed with saturated
aqueous NaHCO3 (10 mL) and brine (2!10 mL), and dried
over anhydrous Na2SO4. Filtration and evaporation in vacuo
furnished the pale yellow oil (735 mg), which was purified
by column chromatography (silica gel 15 g, 2:1 hexane/
AcOEt with 2% Et3N) to give diphenyl phosphate 2a
(507 mg, 86%, a:bZ2:98) as a colorless oil. The anomeric
a:b ratio of the product was determined by 31P NMR.
4.3. Glycosidations of 2-azido-3,4,6-tri-O-benzyl-2-
deoxyglucosyl diphenyl phosphate 2a
4.3.1. Typical procedure for glycosidation of 2-azido-2-
deoxyglucopyranosyl donors: methyl 4-O-(2-azido-3,4,6-
tri-O-benzyl-2-deoxy-D-glucopyranosyl)-2,3,6-tri-O-benz-
yl-a-D-glucopyranoside (10). TMSOTf in CH2Cl2 (1.0 M,
0.15 mL, 0.15 mmol) was added to a stirred solution of
diphenyl phosphate 2a (a:bZ72:28) (70.8 mg, 0.10 mmol)
and alcohol 8 (51.1 mg, 0.11 mmol) in EtCN (1.5 mL) at
K78 8C. After stirring at this temperature for 2 h, the
reaction was quenched with Et3N (0.1 mL). The reaction
mixture was poured into a two-layer mixture of AcOEt
(2 mL) and NaHCO3 (3 mL), and the whole was extracted
with AcOEt (20 mL). The organic layer was successively
washed with saturated aqueous NaHCO3 (5 mL) and brine
(2!5 mL), and dried over anhydrous Na2SO4. Filtration
and evaporation in vacuo furnished the crude product
(108.9 mg), from which an anomeric mixture of disacchar-
ide 10 (82.6 mg, 90%, a:bZ6:94) was obtained as a
colorless oil after column chromatography (silica gel 6 g,
5:1 hexane/AcOEt). The anomeric ratio of the disaccharide
was determined by HPLC analysis [column, Zorbaxw Sil,
4.6!250 mm; eluent, 7:1 hexane/AcOEt; flow rate, 1.0 mL/
min; detection, 254 nm; tR (a-anomer)Z56.6 min, tR
(b-anomer)Z63.5 min]. The a- and b-glycosides were
separated by flash column chromatography with 6:1
hexane/AcOEt.
4.2.9. 2-Azido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyra-
nosyl N,N,N0,N0-tetramethylphosphorodiamidate (6).
Butyllithium in hexane (1.56 M, 0.3 mL, 0.468 mmol) was
added to a stirred solution of 1a (212 mg, 0.446 mmol) in
THF (5.0 mL) at K78 8C. After 15 min, a solution of
bis(dimethylamino)phosphoryl chloride (0.067 mL,
0.450 mmol) in HMPA (0.5 mL) was added, and the
mixture was allowed to warm to K20 8C over 30 min.
After stirring at this temperature for 2 h, the reaction was
quenched with crushed ice, followed by stirring at 0 8C for
30 min. The mixture was poured into a two-layer mixture of
Et2O (5 mL) and saturated aqueous NaHCO3 (5 mL), and
the whole was extracted with AcOEt (20 mL). The organic
layer was washed with brine (2!10 mL), and dried over
anhydrous Na2SO4. Filtration and evaporation in vacuo
furnished the yellow residue (301 mg), which was purified
by column chromatography (silica gel 8 g, 1:1/1:2
hexane/AcOEt) to give diamidate 6 (238 mg, 87%, a:bZ
67:33) as a colorless oil. The anomeric a:b ratio of the
product was determined by 31P NMR. TLC RfZ0.31
(AcOEt); [a]2D2ZC13.98 (c 1.27, CHCl3) (a:bZ67:33);
The following work-up may be employed in those cases
where the highly reactive primary alcohol (7 or 12) was used
as an acceptor. It serves only to remove the imidate as its
hydrolyzed product. After the reaction was quenched with
Et3N (0.1 mL), the mixture was diluted with AcOEt
(20 mL). The whole was successively washed with 10%
aqueous HCl (5 mL), H2O (5 mL), saturated aqueous
NaHCO3 (5 mL) and brine (2!5 mL), and dried over
anhydrous Na2SO4. After filtration, the filtrate was con-
centrated in vacuo to yield the crude product containing
propionated acceptor alcohol.
IR (CHCl3) 3034, 2932, 2114, 1454, 1305, 1215, 995 cmK1
;
1H NMR (500 MHz, CDCl3) d 2.62 (d, JH–PZ10.1 Hz,
4.2H, N(CH3)2), 2.63 (d, JH–PZ10.4 Hz, 1.8H, N(CH3)2),
2.66 (d, JH–PZ10.2 Hz, 4.2H, N(CH3)2), 2.69 (d, JH–P
Z
10.3 Hz, 1.8H, N(CH3)2), 3.44–3.52 (m, 0.9H, H-2b, H-3b,
H-5b), 3.61 (ddd, JZ3.4, 10.1, 1.4 (JH–P) Hz, 0.7H, H-2a),
3.64–3.69 (m, 1H, H-6aa, H-6ab), 3.71–3.79 (m, 2H, H-4a,
H-6ba, H-4b, H-6bb), 3.88 (dd, JZ9.0, 10.1 Hz, 0.7H,
H-3a), 3.94 (ddd, JZ1.8, 3.1, 10.0 Hz, 0.7H, H-5a), 4.49
(d, JZ12.0 Hz, 0.7H, OCHPh), 4.51 (d, JZ12.1 Hz, 0.3H,
OCHPh), 4.561 (d, JZ12.1 Hz, 0.3H, OCHPh), 4.562 (d,
JZ10.7 Hz, 0.7H, OCHPh), 4.60 (d, JZ10.9 Hz, 0.3H,
OCHPh), 4.61 (d, JZ12.0 Hz, 0.7H, OCHPh), 4.80 (d, JZ
10.9 Hz, 0.3H, OCHPh), 4.81 (d, JZ10.7 Hz, 0.7H,
OCHPh), 4.83 (d, JZ10.3 Hz, 0.3H, OCHPh), 4.86 (d,
JZ10.8 Hz, 0.7H, OCHPh), 4.87 (d, JZ10.3 Hz, 0.3H,
OCHPh), 4.90 (d, JZ10.8 Hz, 0.7H, OCHPh), 5.00 (dd, JZ
7.5, 7.6 (JH–P) Hz, 0.3H, H-1b), 5.75 (dd, JZ3.4, 7.9
(JH–P) Hz, 0.7H, H-1a), 7.10–7.17 (m, 3H, Ar-H), 7.26–7.38
(m, 12H, Ar-H); 13C NMR (126 MHz, CDCl3) d 36.3, 36.36,
Data for b-anomer (10b): TLC RfZ0.49 (2:1 hexane/
AcOEt); [a]1D5ZK11.48 (c 1.09, CHCl3); IR (CHCl3) 3009,
2910, 2870, 2112, 1496, 1454, 1361, 1277, 1087, 750 cmK1
;
1H NMR (500 MHz, CDCl3) d 3.18 (ddd, JZ1.7, 4.3,
9.6 Hz, 1H, H-50), 3.24 (dd, JZ8.9, 9.8 Hz, 1H, H-30), 3.31
(dd, JZ8.0, 9.8 Hz, 1H, H-20), 3.38 (s, 3H, OCH3), 3.47–
3.50 (m, 2H, H-2, H-60a), 3.59 (dd, JZ8.9, 9.6 Hz, 1H,
H-40), 3.62 (dd, JZ1.7, 11.1 Hz, 1H, H-60b), 3.70 (dd, JZ
1.6, 10.9 Hz, 1H, H-6a), 3.78 (ddd, JZ1.6, 3.2, 9.8 Hz, 1H,
H-5), 3.89 (dd, JZ8.9, 9.5 Hz, 1H, H-3), 3.92 (dd, JZ3.2,
10.9 Hz, 1H, H-6b), 3.96 (dd, JZ8.9, 9.8 Hz, 1H, H-4), 4.26
(d, JZ8.0 Hz, 1H, H-10), 4.35 (d, JZ12.1 Hz, 1H, OCHPh),
4.40 (d, JZ12.1 Hz, 1H, OCHPh), 4.47 (d, JZ12.1 Hz, 1H,
OCHPh), 4.54 (d, JZ11.0 Hz, 1H, OCHPh), 4.58 (d, JZ
36.41, 36.45, 36.48, 64.2 (d, JC–PZ7.3 Hz), 67.2 (d, JC–P
Z
7.9 Hz), 68.2, 68.3, 72.7, 73.5, 73.6, 75.0, 75.2, 75.3, 75.5,

10724
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
12.1 Hz, 1H, OCHPh), 4.59 (d, JZ3.6 Hz, 1H, H-1), 4.67
(d, JZ12.1 Hz, 1H, OCHPh), 4.74 (d, JZ12.1 Hz, 1H,
OCHPh), 4.76 (d, JZ11.0 Hz, 1H, OCHPh), 4.781 (d, JZ
11.4 Hz, 1H, OCHPh), 4.782 (d, JZ10.7 Hz, 1H, OCHPh),
4.82 (d, JZ10.7 Hz, 1H, OCHPh), 5.02 (d, JZ11.4 Hz, 1H,
OCHPh), 7.17–7.36 (m, 30H, Ar-H); 13C NMR (126 MHz,
CDCl3) d 55.3, 66.9, 68.2, 68.6, 69.7, 73.3, 73.47, 73.51,
74.7, 75.19, 75.24, 75.4, 77.9, 79.1, 80.3, 83.3, 98.3 (C-1),
100.9 (C-10), 127.0, 127.4, 127.5, 127.65, 127.67, 127.70,
127.72, 127.8, 127.95, 127.98, 128.1, 128.2, 128.3, 128.36,
128.42, 128.5, 137.8, 137.9, 138.0, 138.3, 138.4, 139.5;
FAB-HRMS m/z calcd for C55H59N3O10Na (MCNa)C
944.4098, found 944.4083; Anal. calcd for: C55H59N3O10:
C, 71.64; H, 6.45; N, 4.56, found C, 71.45; H, 6.45; N, 4.55.
Data for a-anomer (10a): TLC RfZ0.54 (2:1 hexane/
AcOEt); [a]1D5ZC39.18 (c 0.78, CHCl3); IR (CHCl3) 3013,
CDCl3) d 3.37 (m, 1H, H-50), 3.38 (s, 3H, OCH3), 3.40 (dd,
JZ8.7, 9.8 Hz, 1H, H-30), 3.45 (dd, JZ7.7, 9.8 Hz, 1H,
H-20), 3.55 (dd, J0Z3.5, 9.6 Hz, 1H, H-2), 3.575 (dd, JZ8.7,
9.4 Hz, 1H, H-4 ), 3.576 (dd0, JZ8.09, 10.0 Hz, 1H, H-4),
3.64–3.71 (m, 3H, H-6a, H-6 a, H-6 b), 3.81 (ddd, JZ1.6,
4.3, 10.0 Hz, 1H, H-5), 4.00 (dd, JZ8.9, 9.6 Hz, 1H, H-3),
4.12 (dd, JZ1.6, 10.9 Hz, 1H, H-6b), 4.16 (d, JZ7.7 Hz,
1H, H-10), 4.51 (d, JZ12.1 Hz, 1H, OCHPh), 4.55 (d, JZ
12.4 Hz, 1H, OCHPh), 4.57 (d, JZ12.1 Hz, 1H, OCHPh),
4.62 (d, JZ3.5 Hz, 1H, H-1), 4.65 (d, JZ12.1 Hz, 1H,
OCHPh), 4.66 (d, JZ11.1 Hz, 1H, OCHPh), 4.77–4.80 (m,
3H, OCHPh!3), 4.84 (d, JZ11.0 Hz, 1H, OCHPh), 4.86
(d, JZ10.7 Hz, 1H, OCHPh), 4.93 (d, JZ11.1 Hz, 1H,
OCHPh), 4.98 (d, JZ11.0 Hz, 1H, OCHPh), 7.17 (m, 2H,
Ar-H), 7.24–7.36 (m, 28H, Ar-H); 13C NMR (126 MHz,
CDCl3) d 55.2, 66.4, 68.4, 68.7, 69.7, 73.4, 74.8, 75.0, 75.2,
75.6, 75.7, 77.75, 77.79, 79.8, 82.1, 83.3, 98.2 (C-1), 102.1
(C-10), 127.5, 127.59, 127.63, 127.7, 127.8, 127.85, 127.87,
128.0, 128.06, 128.14, 128.3, 128.35, 128.42, 128.44, 137.9,
138.1, 138.2, 138.4, 138.8; FAB-HRMS m/z calcd for
C55H59N3O10Na (MCNa)C 944.4098, found 944.4080;
Anal. calcd for: C55H59N3O10: C, 71.64; H, 6.45; N, 4.56,
found C, 71.67; H, 6.44; N 4.49. Data for a-anomer (9a):
TLC RfZ0.44 (2:1 hexane/AcOEt), 0.26 (1:1 hexane/Et2O);
[a]2D4ZC84.78 (c 1.18, CHCl3); IR (film) 3030, 2922, 2106,
2910, 2870, 2112, 1602, 1454, 1361, 1221, 1049, 713 cmK1
;
1H NMR (500 MHz, CDCl3) d 3.27 (dd, JZ3.9, 10.4 Hz,
1H, H-20), 3.34 (brd, JZ11.0 Hz, 1H, H-60a), 3.38 (s, 3H,
OCH3), 3.52 (dd, JZ1.4, 11.0 Hz, 1H, H-60b), 3.57 (dd, JZ
3.6, 9.6 Hz, 1H, H-2), 3.65 (dd, JZ1.9, 11.0 Hz, 1H, H-6a),
3.66–3.70 (m, 2H, H-40, H-50), 3.72 (dd, JZ4.3, 11.0 Hz,
1H, H-6b), 3.79 (ddd, JZ1.9, 4.3, 10.0 Hz, 1H, H-5), 3.86
(m, 1H, H-30), 3.91 (dd, JZ8.6, 10.0 Hz, 1H, H-4), 4.08 (dd,
JZ8.6, 9.6 Hz, 1H, H-3), 4.25 (d, JZ12.1 Hz, 1H,
OCHPh), 4.45 (d, JZ10.9 Hz, 1H, OCHPh), 4.49 (d, JZ
12.1 Hz, 1H, OCHPh), 4.50 (s, 2H, OCH2Ph), 4.61 (d, JZ
3.6 Hz, 1H, H-1), 4.62 (d, JZ12.2 Hz, 1H, OCHPh), 4.74
(d, JZ10.9 Hz, 1H, OCHPh), 4.75 (d, JZ12.2 Hz, 1H,
OCHPh), 4.83 (d, JZ10.9 Hz, 1H, OCHPh), 4.85 (d, JZ
10.9 Hz, 1H, OCHPh), 4.86 (d, JZ10.7 Hz, 1H, OCHPh),
5.10 (d, JZ10.7 Hz, 1H, OCHPh), 5.73 (d, JZ3.9 Hz, 1H,
H-10), 7.12 (m, 2H, Ar-H), 7.20–7.35 (m, 28H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 55.3, 63.3, 67.9, 69.3, 69.5,
71.4, 73.27, 73.310, 73.5, 74.9, 75.0, 75.3, 78.1, 80.1, 80.5,
82.0, 97.69 (C-1 ), 97.73 (C-1), 127.2, 127.4, 127.45,
127.53, 127.66, 127.71, 127.8, 127.9, 128.1, 128.26, 128.32,
128.4, 128.5, 137.8, 137.9, 138.0, 138.1, 138.2, 138.7; FAB-
HRMS m/z calcd for C55H59N3O10Na (MCNa)C 944.4098,
found 944.4083.
1496, 1454, 1359, 1207, 1049, 736 cmK1 1H NMR
;
(500 MHz, CDCl3) d 3.33 (dd, JZ3.5, 10.1 Hz, 1H, H-20),
3.37 (s, 3H, OCH3), 3.51–3.55 (m, 2H, H-2, H-60a), 3.56
(dd,0 1H, JZ9.2, 9.4 Hz, H-4), 3.63 (dd, JZ3.3, 10.7 Hz,
H-6 b), 30.67–3.71 (2H, m, H-6a, H-40), 3.74–3.78 (2H, m,
H-5, H-5 ), 3.83 (dd, JZ40.6, 11.4 Hz, 1H, H-6b), 3.92 (dd,
JZ8.8, 10.1 Hz, 1H, H-3 ), 4.00 (t, JZ9.2 Hz, 1H, H-3),
4.43 (d, JZ12.1 Hz, 1H, OCHPh), 4.49 (d, JZ10.9 Hz, 1H,
OCHPh), 4.56–4.61 (m, 3H, H-1, OCHPh!2), 4.66 (d, JZ
12.0 Hz, 1H, OCHPh), 4.78 (d, JZ12.0 Hz, 1H, OCHPh),
4.79 (d, JZ10.9 Hz, 1H, OCHPh), 4.80 (d, JZ10.9 Hz, 1H,
OCHPh), 4.83 (d, JZ10.8 Hz, 1H, OCHPh), 4.86 (d, JZ
10.8 Hz, 1H, OCHPh), 4.94 (d, JZ11.2 Hz, 1H, OCHPh),
4.98 (d, JZ10.9 Hz, 1H, OCHPh), 5.01 (d, JZ3.5 Hz, 1H,
H10), 7.13 (m, 2H, Ar-H), 7.24–7.37 (m, 28H, Ar-H); 13C
NMR (100 MHz, CDCl3) d 55.2, 63.5, 66.4, 68.1, 69.9,
70.7, 73.4, 73.5, 74.9, 75.2, 75.8,0 77.2, 77.7, 78.2, 79.8,
80.0, 82.0, 97.9 (C-1), 98.2 (C-1 ), 127.5, 127.6, 127.7,
127.76, 127.80, 128.0, 128.1, 128.29, 128.31, 128.4, 137.7,
137.8, 137.95, 138.04, 138.2, 138.6; FAB-HRMS m/z calcd
for C55H59N3O10Na (MCNa)C 944.4098, found 944.4109.
4.3.2. Methyl 6-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
glucopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside
(9). The glycosidation was performed according to the
typical procedure (1.5 mL EtCN, K78 8C, 1.5 h) employing
diphenyl phosphate 2a (70.8 mg, 0.10 mmol), alcohol 7
(51.1 mg, 0.11 mmol), and TMSOTf (1.0 M in CH2Cl2,
0.15 mL, 0.15 mmol). An anomeric mixture of disaccharide
9 (77.0 mg, 84%, a:bZ1:99) was obtained as a white solid
from the crude product (108.7 mg) after flash column
chromatography (silica gel 6 g, 6:1 hexane/AcOEt with 1%
Et3N), along with a-imidate 11 (5.3 mg, 5%) as a colorless
oil. The anomeric ratio of the disaccharide was determined
by HPLC analysis [column, Zorbaxw Sil, 4.6!250 mm;
eluent, 5:1 hexane/AcOEt; flow rate, 1.0 mL/min; detection,
254 nm; tR (b-anomer)Z24.1 min, tR (a-anomer)Z
34.7 min]. The a- and b-glycosides were separated by
flash column chromatography with 3:1 hexane/Et2O. Data
for b-anomer (9b): TLC RfZ0.46 (2:1 hexane/AcOEt), 0.30
(1:1 hexane/Et2O); mp 119.0–120.0 8C (colorless fine
needles from AcOEt–hexane); [a]1D9ZK5.278 (c 1.15,
CHCl3); IR (CHCl3) 3009, 2930, 2868, 2112, 1496, 1454,
Data for methyl 6-O-[1-(2-azido-3,4,6-tri-O-benzyl-2-
deoxy-a-D-glucopyranosyl)iminopropyl]-2,3,4-tri-O-benz-
yl-a-D-glucopyranoside (11): TLC RfZ0.49 (2:1 hexane/
AcOEt); [a]2D0ZC47.58 (c 0.40, CHCl3); IR (film) 3030,
2922, 2106, 1664, 1496, 1454, 1359, 1211, 1089 cmK1; 1H
NMR (500 MHz, CDCl3) d 1.15 (t, JZ7.6 Hz, 3H,
CH2CH3), 2.36 (dq, JZ14.6, 7.6 Hz, 1H, CHCH3), 2.38
(dq, JZ14.6, 7.6 Hz, 1H, CHCH3), 3.37 (s, 3H, OCH3), 3.52
(dd, JZ4.1, 10.0 Hz, 1H, H-20), 3.54 (dd, JZ3.6, 9.5 Hz,
1H, H-2), 3.56 (dd, JZ1.7, 10.7 Hz, 1H, H-60a), 3.62 (dd,
JZ9.0, 10.0 Hz, 1H, H-4), 3.73 (dd, JZ3.5, 10.7 Hz, 1H,
H-60b), 3.78 (dd, JZ9.0, 9.9 Hz, 1H, H-40), 3.87 (ddd, JZ
1.8, 4.1, 10.0 Hz, 1H, H-5), 4.00 (dd, JZ9.0, 09.5 Hz, 1H,
H-3), 4.08 (ddd, JZ1.7, 3.5, 9.9 Hz, 1H, H-5 ), 4.09 (dd,
JZ9.0, 10.0 Hz, 1H, H-30), 4.23 (dd, JZ4.1, 12.3 Hz, 1H,
H-6a), 4.30 (dd, JZ1.8, 12.3 Hz, 1H, H-6b), 4.46 (d, JZ
1
1359, 1265, 1222, 1068, 763 cmK1; H NMR (500 MHz,

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10725
12.2 Hz, 1H, OCHPh), 4.51 (d, JZ10.7 Hz, 1H, OCHPh),
4.59 (d, JZ10.6 Hz, 1H, OCHPh), 4.60 (d, JZ3.6 Hz, 1H,
H-1), 4.62 (d, JZ12.2 Hz, 1H, OCHPh), 4.66 (d, JZ
12.1 Hz, 1H, OCHPh), 4.73 (d, JZ10.7 Hz, 1H, OCHPh),
4.789 (d, JZ10.7 Hz, 1H, OCHPh), 4.790 (d, JZ12.1 Hz,
1H, OCHPh), 4.80 (d, JZ10.7 Hz, 1H, OCHPh), 4.82 (d,
JZ10.8 Hz, 1H, OCHPh), 4.84 (d, JZ10.6 Hz, 1H,
OCHPh), 4.97 (0d, JZ10.8 Hz, 1H, OCHPh), 5.20 (d, JZ
4.1 Hz, 1H, H-1 ), 7.12–7.18 (m, 3H, Ar-H), 7.22–7.37 (m,
27H, Ar-H); 13C NMR (126 MHz, CDCl3) d 10.7, 22.9,
55.1, 64.2, 64.7, 68.7, 71.2, 73.4, 73.5, 75.09, 75.14, 75.2,
75.9, 77.8, 78.9, 80.0, 80.9, 82.1, 83.2 (C-10), 98.1 (C-1),
127.6, 127.68, 127.74, 127.76, 127.79, 127.87, 127.91,
128.0, 128.1, 128.35, 128.41, 128.5, 137.9, 138.0, 138.07,
138.13, 138.2, 138.7, 168.8; FAB-HRMS m/z calcd for
C58H65N4O10 (MCH)C 977.4700, found 977.4721.
JZ6.7, 10.3 Hz, 1H, H-6a), 3.73–3.80 (m, 2H, H-40, H-60b),
3.81 (dd, JZ6.4, 10.3 Hz, 1H, H-6b), 3.88 (m, 1H, H-50),
3.98–4.01 (m, 2H, H-5, H-30), 4.31 (dd, JZ2.3, 5.0 Hz, 1H,
H-2), 4.32 (dd, JZ1.8, 8.0 Hz, 1H, H-3), 4.48 (d, JZ
12.1 Hz, 1H, OCHPh), 4.53 (d, JZ11.1 Hz, 1H, OCHPh),
4.61 (dd, JZ2.3, 8.0 Hz, 1H, H-3), 4.64 (d, JZ12.1 Hz, 1H,
OCHPh), 4.79 (d, JZ11.1 Hz, 1H, OCHPh), 4.85 (d, JZ
11.5 Hz, 1H, OCHPh), 4.87 (d, JZ11.5 Hz, 1H, OCHPh),
4.99 (d, JZ3.5 Hz, 1H, H-10), 5.51 (d, JZ5.0 Hz, 1H, H-1),
7.16 (m, 2H, Ar-H), 7.24–7.37 (m, 13H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 24.4, 24.9, 26.0, 26.1, 63.4, 66.2, 66.9,
68.2, 70.6, 70.66, 70.69, 70.8, 73.5, 74.9, 75.3, 78.3, 79.9,
96.3 (C-1), 98.3 (C-10), 108.6, 109.3, 127.70, 127.73, 127.8,
127.9, 128.0, 128.38, 128.43, 137.9, 138.1; FAB-HRMS
m/z calcd for C39H47N3O10Na (MCNa)C 740.3159, found
740.3134.
Data for 6-O-[1-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-D-
glucopyranosyl)iminopropyl]-1,2:3,4-di-O-isopropylidene-
a-D-galactopyranose (19): TLC RfZ0.43 (3:1 hexane/
AcOEt); [a]2D4ZC4.688 (c 0.28, CHCl3); IR (film) 2924,
4.3.3. 6-O-(2-Azido-3,4,6-tri-O-benzyl-2-deoxy-D-gluco-
pyranosyl)-1,2:3,4-di-O-isopropylidene-a-D-galactopyr-
anose (17).12a The glycosidation was performed according
to the typical procedure (1.5 mL EtCN, K78 8C, 1.5 h)
employing diphenyl phosphate 2a (70.8 mg, 0.10 mmol),
alcohol 12 (28.6 mg, 0.11 mmol), and TMSOTf (1.0 M in
CH2Cl2, 0.15 mL, 0.15 mmol). An anomeric mixture of
disaccharide 17 (56.8 mg, 79%, a:bZ2:98) was obtained as
a colorless oil from the crude product (91.4 mg) after
column chromatography (silica gel 8 g, 7:1 hexane/AcOEt
with 1% Et3N), along with a-imidate 19 (7.2 mg, 9%) as a
colorless syrup. The anomeric ratio of the product was
determined by HPLC analysis [eluent, 6:1 hexane/THF;
flow rate, 1.0 mL/min; tR (a-anomer)Z8.9 min, tR (b-
anomer)Z9.6 min]. The a- and b-glycosides were sepa-
rated by flash column chromatography with 30:1 toluene/
acetone. Data for b-anomer (17b): TLC RfZ0.39 (3:1
hexane/AcOEt), 0.49 (10:1 toluene/acetone); [a]1D6Z
K47.98 (c 2.45, CHCl3) (a:bZ2:98); IR (film) 2986,
1
2106, 1658, 1462, 1213, 1072 cmK1; H NMR (500 MHz,
CDCl3) d 1.16 (t, JZ7.6 Hz, 3H, CH2CH3), 1.32 (s, 6H,
CCH3!2), 1.44 (s, 3H, CCH3), 1.50 (s, 3H, CCH3), 2.34
(dq, JZ15.0, 7.6 Hz, 1H, CHCH3), 2.38 (dq, JZ15.0,
7.6 Hz, 1H, CHCH3), 3.57 (dd, JZ4.2, 10.0 Hz, 1H, H-20),
3.58 (dd, JZ1.8, 010.8 Hz, 1H, H-60a), 3.74 (dd, JZ3.5,
10.8 Hz, 1H, H-6 b), 3.78 (t, JZ9.5 Hz, 1H, H-40), 4.05
(ddd, JZ1.6, 5.03, 7.1 Hz, 1H, H-5), 4.10 (dd, JZ9.5,
10.0 Hz, 1H, H-3 ), 4.10–4.14 (m, 2H, H-6a, H-50), 4.27 (dd,
JZ1.6, 7.9 Hz, 1H, H-4), 4.31 (dd, JZ2.4, 5.0 Hz, 1H,
H-2), 4.33 (dd, JZ5.3, 11.2 Hz, 1H, H-6b), 4.47 (d, JZ
12.2 Hz, 1H, OCHPh), 4.53 (d, JZ10.9 Hz, 1H, OCHPh),
4.60 (dd, JZ2.4, 7.9 Hz, 1H, H-3), 4.62 (d, JZ12.2 Hz, 1H,
OCHPh), 4.82 (d, JZ10.9 Hz, 1H, OCHPh), 4.85 (d, JZ
11.7 Hz, 1H, OCHPh), 4.89 (d, JZ11.7 Hz, 1H, OCHPh),
5.22 (d, JZ4.2 Hz, 1H, H-10), 5.55 (d, JZ5.0 Hz, 1H, H-1),
7.17 (m, 2H, Ar-H), 7.24–7.38 (m, 13H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 10.7, 23.0, 24.4, 25.0, 26.0, 26.1, 29.7,
64.0, 65.0, 66.1, 68.7, 70.7, 71.2, 71.3, 73.5, 75.0, 75.3,
79.0, 80.8, 83.4 (C-10), 96.3 (C-1), 108.6, 109.5, 127.65,
127.70, 127.76, 127.80, 127.9, 128.1, 128.3, 128.38, 128.43,
138.0, 138.1, 138.2, 168.0; FAB-HRMS m/z calcd for
C42H53N4O10 (MCH)C 773.3762, found 773.3770.
2906, 2110, 1454, 1381, 1211, 1070 cmK1 1H NMR
;
(500 MHz, CDCl3) d 1.32 (s, 3H, CCH3), 1.33 (s, 3H,
CCH3), 1.44 (s, 3H, CCH3), 1.54 (s, 3H, CCH3), 3.40–3.44
(m, 3H, H-20, H-40, H-50), 3.63 (m, 1H, H-30), 3.70 (dd, JZ
4.1, 11.1 Hz, 1H, H-60a), 3.73 (dd, JZ2.2, 11.1 Hz, 1H, H-
60b), 3.79 (m, 1H, H-6a), 4.04–4.09 (m, 2H, H-5, H-6b),
4.28 (dd, JZ1.2, 7.8 Hz, 1H, H-4), 4.31 (dd, JZ2.4, 5.0 Hz,
1H, H-2), 4.41 (m, 1H, H-10), 4.53 (d, JZ12.1 Hz, 1H,
OCHPh), 4.54 (d, JZ10.9 Hz, 1H, OCHPh), 4.60 (dd, JZ
2.4, 7.8 Hz, 1H, H-3), 4.61 (d, JZ12.1 Hz, 1H, OCHPh),
4.78 (d, JZ10.8 Hz, 1H, OCHPh), 4.79 (d, JZ10.9 Hz, 1H,
OCHPh), 4.89 (d, JZ10.8 Hz, 1H, OCHPh), 5.54 (d, JZ
5.0 Hz, 1H, H-1), 7.16 (m, 2H, Ar-H), 7.25–7.36 (m, 13H,
Ar-H); 13C NMR (126 MHz, CDCl3) d 24.4, 25.0, 25.97,
26.02, 66.4, 67.6, 68.5, 68.8, 70.5, 70.7, 71.2, 73.5, 74.96,
75.02, 75.5, 77.7, 83.1, 96.3 (C-1), 102.4 (C-10), 108.7,
109.3, 127.6, 127.76, 127.79, 127.82, 128.0, 128.35, 128.38,
128.41, 138.0, 138.06, 138.08; FAB-HRMS m/z calcd for
C39H47N3O10Na (MCNa)C 740.3159, found 740.3195;
Anal. calcd for: C39H47N3O10: C, 65.26; H, 6.60; N, 5.85,
found C, 65.26; H, 6.60; N, 5.83. Data for a-anomer (17a):
TLC RfZ0.41 (3:1 hexane/AcOEt), 0.53 (10:1 toluene/
acetone); [a]1D7ZC42.28 (c 0.49, CHCl3); IR (CHCl3) 2924,
4.3.4. Methyl 2-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
glucopyranosyl)-3,4,6-tri-O-benzyl-b-D-glucopyranoside
(18).12b The glycosidation was performed according to the
typical procedure (1.5 mL EtCN, K78 8C, 2 h) employing
diphenyl phosphate 2a (70.8 mg, 0.10 mmol), alcohol 13
(51.1 mg, 0.11 mmol), and TMSOTf (1.0 M in CH2Cl2,
0.15 mL, 0.15 mmol). An anomeric mixture of disaccharide
18 (83.6 mg, 91%, a:bZ9:91) was obtained as a colorless
oil from the crude product (107.4 mg) after column
chromatography (silica gel 5 g, 5:1 hexane/AcOEt). The
anomeric ratio of the product was determined by HPLC
analysis [eluent, 5:1 hexane/AcOEt; flow rate, 1.0 mL/min;
tR (a-anomer)Z12.6 min, tR (b-anomer)Z16.3 min]. The
a- and b-glycosides were separated by flash column
chromatography with 6:1 hexane/AcOEt. Data for b-anomer
(18b):12b TLC RfZ0.61 (2:1 hexane/AcOEt); mp 83.5–
84.5 8C (colorless needles from AcOEt–hexane);
[a]2D8ZK17.98 (c 1.00, CHCl3); IR (KBr) 3030, 2908,
1
2106, 1454, 1381, 1255, 1070 cmK1; H NMR (500 MHz,
CDCl3) d 1.33 (s, 3H, CCH3), 1.34 (s, 3H, CCH3), 1.43 (s,
3H, CCH3), 1.53 (s, 3H, CCH3), 3.33 (dd, JZ3.5, 10.3 Hz,
1H, H-20), 3.66 (dd, JZ1.8, 10.8 Hz, 1H, H-60a), 3.72 (dd,

10726
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
2868, 2112, 1496, 1452, 1359, 1269, 1062,0 750 cmK1; H
NMR (500 MHz, CDCl3) d 3.34 (m, 1H, H-5 ), 3.39 (dd, JZ
9.1, 9.5 Hz, 1H, H-30), 3.46 (dd, JZ8.1, 9.5 Hz, 1H, H-20),
3.48 (s, 3H, OCH3), 3.49 (m, 1H, H-5), 3.64–3.78 (m, 7H,
H-3, H-4, H-6a, H-6b, H-40, H-60a, H-60b), 3.80 (dd, JZ7.2,
8.9 Hz, 1H, H-2), 4.37 (d, JZ7.2 Hz, 1H, H-1), 4.53–4.59
(m, 4H, OCHPh!4), 4.61–4.66 (m, 2H, OCHPh!2), 4.71
(d, JZ8.1 Hz, 1H, H-10), 4.78 (d, JZ10.5 Hz, 1H, OCHPh),
4.79 (d, JZ10.9 Hz, 1H, OCHPh), 4.81 (d, JZ10.8 Hz, 1H,
OCHPh), 4.85 (d, JZ10.8 Hz, 1H, OCHPh), 4.89 (d, JZ
10.6 Hz, 1H, OCHPh), 4.95 (d, JZ10.6 Hz, 1H, OCHPh),
7.16–7.19 (m, 4H, Ar-H), 7.22–7.38 (m, 26H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 56.3, 66.6, 68.3, 68.8, 73.5,
73.6, 74.8, 75.0, 75.2, 75.3, 75.4, 77.8, 78.3, 78.9, 83.4,
85.1, 101,1 (C-10), 102.4 (C-1), 127.5, 127.6, 127.65,
127.67, 127.72, 127.77, 127.81, 127.90, 127.94, 128.0,
128.3, 128.4, 137.9, 138.0, 138.2, 138.3, 138.4; FAB-
HRMS m/z calcd for C55H59N3O10Na (MCNa)C 944.4098,
found 944.4072; Anal. calcd for: C55H59N3O10: C, 71.64; H,
6.45; N, 4.56, found C, 71.58; H, 6.49; N, 4.61. Data for
a-anomer (18a):12b TLC RfZ0.66 (2:1 hexane/AcOEt);
[a]2D8ZC67.48 (c 1.00, CHCl3); IR (film) 3030, 2918, 2864,
(CHCl3) 3024, 2914, 2870, 2112, 1454, 1358, 1273,
1
1
1091 cmK1; H NMR (500 MHz, CDCl3) d 3.32 (s, 3H,
OCH3), 3.38–3.43 (m, 3H, H-20, H-40, H-50), 3.48 (dd, JZ
6.6, 9.5 Hz, 1H, H-6a), 03.51 (dd, JZ6.2, 9.5 Hz, 1H, H-6b),
3.66–3.71 (m, 2H, H-3 , H-60a), 3.74 (dd, JZ3.9, 11.0 Hz,
1H, H-60b), 3.93 (dd, JZ6.2, 6.6 Hz, 1H, H-5), 4.00 (brd,
JZ3.0 Hz, 1H, H-4), 4.06 (dd, JZ3.6, 10.1 Hz, 1H, H-2),
4.19 (dd, JZ3.0, 10.1 Hz, 1H, H-3), 4.38 (d, JZ11.8 Hz,
1H, OCHPh), 4.46 (d, JZ11.8 Hz, 1H, OCHPh), 4.49 (d,
JZ12.2 Hz, 1H, OCHPh), 4.57–4.61 (m, 5H, H-1,
OCHPh!4), 4.73 (m, 1H, H-10), 4.80 (d, JZ10.8 Hz, 1H,
OCHPh), 4.81 (d, JZ10.9 Hz, 1H, OCHPh), 4.88 (d, JZ
10.9 Hz, 1H, OCHPh), 4.90 (d, JZ10.9 Hz, 1H, OCHPh),
4.95 (d, JZ11.4 Hz, 1H, OCHPh), 7.18 (m, 2H, Ar-H),
7.20–7.38 (m, 26H, Ar-H), 7.42 (m, 2H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 55.3, 67.1, 68.5, 69.1, 69.2, 73.4, 73.5,
73.6, 74.7, 75.05,075.14, 75.5, 77.2, 77.4, 77.7, 83.0, 98.3
(C-1), 102.7 (C-1 ), 127.5, 127.59, 127.64, 127.7, 127.79,
127.82, 127.84, 127.9, 128.2, 128.3, 128.35, 128.40, 128.42,
128.5, 137.95, 138.03, 138.10, 138.12, 138.4, 138.7; FAB-
HRMS m/z calcd for C55H59N3O10Na (MCNa)C 944.4098,
found 944.4136; Anal. calcd for: C55H59N3O10: C, 71.64; H,
6.45; N, 4.56, found C, 71.67; H, 6.49; N, 4.56. Data for
a-anomer (20a): TLC RfZ0.44 (2:1 hexane/AcOEt), 0.33
(10:1 toluene/AcOEt); [a]2D4ZC66.58 (c 0.95, CHCl3); IR
(CHCl3) 3022, 2914, 2870, 2112, 1454, 1358, 1209,
1
2104, 1496, 1454, 1359, 1211, 1126, 1055, 734 cmK1; H
NMR (500 MHz, CDCl3) d 3.26 (d, JZ1.6 Hz, 2H, H-60),
3.34 (dd, JZ3.7, 10.4 Hz, 1H, H-20), 3.48 (ddd, JZ2.0, 3.7,
9.4 Hz, 1H, H-5), 3.57 (s, 3H, OCH3), 3.61 (dd, JZ9.0,
9.2 Hz, 1H, H-3), 3.64–3.76 (m, 5H, H-2, H-4, H-6a, H-6b,
H-400), 3.91 (dd, JZ8.9, 10.4 Hz, 1H, H-30), 3.98 (m, 1H,
H-5 ), 4.28 (d, JZ12.0 Hz, 1H, OCHPh), 4.38 (d, JZ
7.4 Hz, 1H, H-1), 4.43 (d, JZ11.0 Hz, 1H, OCHPh), 4.53
(d, JZ12.0 Hz, 1H, OCHPh), 4.55 (d, JZ12.2 Hz, 1H,
OCHPh), 4.56 (d, JZ10.9 Hz, 1H, OCHPh), 4.64 (d, JZ
12.2 Hz, 1H, OCHPh), 4.72 (d, JZ10.8 Hz, 1H, OCHPh),
4.74 (d, JZ11.0 Hz, 1H, OCHPh), 4.79 (d, JZ10.9 Hz, 1H,
OCHPh), 4.85 (d, JZ11.3 Hz, 1H, OCHPh), 4.87 (d, JZ
11.3 Hz, 1H, OCHPh), 4.91 (d, JZ10.8 Hz, 1H, OCHPh),
5.58 (d, JZ3.7 Hz, 1H, H-10), 7.06–7.08 (m, 4H, Ar-H),
7.12–7.18 (m, 3H, Ar-H), 7.22–7.36 (m, 23H, Ar-H); 13C
NMR (100 MHz, CDCl3) d 57.2, 63.3, 67.6, 68.5, 70.4,
73.4, 73.5, 74.8, 74.09, 75.3, 75.8, 76.3, 77.2, 78.1, 78.5,
80.0, 83.1, 96.7 (C-1 ), 104.5 (C-1), 127.4, 127.50, 127.54,
127.6, 127.68, 127.73, 127.8, 127.9, 128.0, 128.1, 128.2,
128.3, 128.4, 137.69, 137.72, 137.8, 137.91, 137.94, 138.3;
FAB-HRMS m/z calcd for C55H59N3O10Na (MCNa)C
944.4098, found 944.4110.
1
1091 cmK1; H NMR (500 MHz, CDCl3) d 3.33 (s, 3H,
OCH3), 3.50–3.57 (m, 4H, H-6a, H-6b, H-20, H-60a), 3.62
(dd, JZ02.8, 11.1 Hz, 1H, H-60b), 3.79 (dd, JZ9.4, 9.6 Hz,
1H, H-4 ), 3.90 (dd, JZ6.5, 6.6 Hz, 1H, H-5), 3.99-4.03 (m,
2H, H-2, H-4), 4.05 (dd, JZ9.4, 9.8 Hz, 1H, H-30), 4.16–
4.19 (m, 2H, H-3, H-50), 4.35 (d, JZ11.9 Hz, 1H, OCHPh),
4.41 (d, JZ11.9 Hz, 1H, OCHPh), 4.489 (d, JZ11.9 Hz,
1H, OCHPh), 4.490 (d, JZ11.0 Hz, 1H, OCHPh), 4.562 (d,
JZ11.7 Hz, 1H, OCHPh), 4.564 (d, JZ11.2 Hz, 1H,
OCHPh), 4.60 (d, JZ11.9 Hz, 1H, OCHPh), 4.70 (d, JZ
3.6 Hz, 1H, H-1), 4.72 (d, JZ11.7 Hz, 1H, OCHPh), 4.77
(d, JZ11.0 Hz, 1H, OCHPh), 4.82 (d, JZ10.8 Hz, 1H,
OCHPh), 4.87 (d, JZ10.8 Hz, 1H, OCHPh), 5.06 (d, JZ
11.2 Hz, 1H, OCHPh), 5.21 (d, JZ3.5 Hz, 1H, H-10), 7.11
(m, 2H, Ar-H), 7.18–7.20 (m, 3H, Ar-H), 7.22–7.35 (m,
25H, Ar-H); 13C NMR (126 MHz, CDCl3) d 55.2, 63.7,
68.1, 68.8, 69.0, 70.5, 73.3, 73.4, 74.4, 74.7, 74.8, 75.1,
75.3, 78.3, 80.2, 94.7 (C-10), 98.4 (C-1), 127.5, 127.55,
127.62, 127.71, 127.74, 127.8, 128.0, 128.1, 128.2, 128.25,
128.28, 128.36, 128.39, 137.87, 137.92, 138.1, 138.3, 138.6;
FAB-HRMS m/z calcd for C55H59N3O10Na (MCNa)C
944.4098, found 944.4097.
4.3.5. Methyl 3-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
glucopyranosyl)-2,4,6-tri-O-benzyl-a-D-galactopyrano-
side (20). The glycosidation was performed according to the
typical procedure (1.5 mL EtCN, K78 8C, 2 h) employing
diphenyl phosphate 2a (70.8 mg, 0.10 mmol), alcohol 14
(51.1 mg, 0.11 mmol), and TMSOTf (1.0 M in CH2Cl2,
0.15 mL, 0.15 mmol). An anomeric mixture of disaccharide
20 (81.7 mg, 89%, a:bZ1:O99) was obtained as a colorless
oil from the crude product (108.5 mg) after column
chromatography (silica gel 6 g, 5:1 hexane/AcOEt). The
anomeric ratio of the product was determined by HPLC
analysis [eluent, 5:1 hexane/AcOEt; flow rate, 1.0 mL/min;
tR (a-anomer)Z29.9 min, tR (b-anomer)Z36.3 min]. The
a- and b-glycosides were separated by flash column
chromatography with 20:1 toluene/AcOEt. Data for
b-anomer (20b): TLC RfZ0.42 (2:1 hexane/AcOEt), 0.28
(10:1 toluene/AcOEt); [a]1D6ZK7.138 (c 1.17, CHCl3); IR
4.3.6. Methyl 4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
glucopyranosyl)-2,3,6-tri-O-benzyl-a-D-galactopyrano-
side (21). The glycosidation was performed according to the
typical procedure (1.5 mL EtCN, K78 8C, 2 h) employing
diphenyl phosphate 2a (70.8 mg, 0.10 mmol), alcohol 15
(51.1 mg, 0.11 mmol), and TMSOTf (1.0 M in CH2Cl2,
0.15 mL, 0.15 mmol). An anomeric mixture of disaccharide
21 (82.5 mg, 90%, a:bZ5:95) was obtained as a colorless
oil from the crude product (100.6 mg) after column
chromatography (silica gel 8 g, 4:1 hexane/AcOEt). The
anomeric ratio of the product was determined by HPLC
analysis [eluent, 4:1 hexane/AcOEt; flow rate, 1.0 mL/min;
tR (a-anomer)Z12.4 min, tR (b-anomer)Z15.5 min]. The
a- and b-glycosides were separated by flash column

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10727
chromatography with 15:1 toluene/AcOEt. Data for
b-anomer (21b): TLC RfZ0.46 (2:1 hexane/AcOEt), 0.34
(10:1 toluene/AcOEt); [a]1D9ZC3.328 (c 0.74, CHCl3); IR
(CHCl3) 3020, 2930, 2868, 2114, 1454, 1358, 1277,
ratio of the product was determined by 1H NMR [integration
of H10, b-anomer (4.27 ppm), a-anomer (4.94 ppm)]. The
a- and b-glycosides were separated by flash column
chromatography with 1:2 hexane/AcOEt. Data for b-anomer
(22b): TLC RfZ0.37 (1:3 hexane/AcOEt); [a]1D6ZC2.068
(c 1.66, CHCl3); IR (CHCl3) 3018, 2978, 2114, 1730, 1452,
1358, 1107, 947 cmK1; 1H NMR (500 MHz, CDCl3) d 2.61
(d, JH–PZ10.4 Hz, 6H, N(CH3)2), 2.71 (d, JH–PZ10.1 Hz,
6H, N(CH3)2), 3.34 (dd, JZ7.9, 9.8 Hz, 1H, H-20), 3.36
(ddd, JZ2.2, 4.1, 9.8 Hz, 1H, H-50), 3.44 (dd, JZ8.9,
9.8 Hz, 1H, H-30), 3.58 (dd, JZ8.9, 9.8 Hz, 1H, H-40), 3.62
(dd, JZ2.2, 11.2 Hz, 1H, H-60a), 3.65 (dd, JZ4.1, 11.2 Hz,
1H, H-60b), 3.76 (dd, JZ5.1, 11.1 Hz, 1H, H-6a), 4.14 (dd,
JZ2.5, 11.1 Hz, 1H, H-6b), 4.27 (d, JZ7.9 Hz, 1H, H-10),
4.45 (d, JZ12.2 Hz, 1H, OCHPh), 4.48 (ddd, JZ2.5, 5.1,
10.1 Hz, 1H, H-5), 4.540 (d, JZ12.2 Hz, 1H, OCHPh),
4.541 (d, JZ10.9 Hz, 1H, OCHPh), 4.78 (d, JZ10.9 Hz,
1H, OCHPh), 4.79 (d, JZ10.8 Hz, 1H, OCHPh), 4.89
(d, JZ10.8 Hz, 1H, OCHPh), 5.39 (ddd, JZ3.3, 10.3, 1.5
(JH–P) Hz, 1H, H-2), 5.72 (dd, JZ9.7, 10.2 Hz, 1H, H-4),
6.15 (dd, JZ3.3, 8.1 (JH–P) Hz, 1H, H-1), 6.19 (dd, JZ9.7,
10.3 Hz, 1H, H-3), 7.16 (m, 2H, Ar-H), 7.25–7.52 (m, 22H,
Ar-H), 7.87 (m, 2H, Ar-H), 7.94–7.97 (m, 4H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 36.4 (d, JC–PZ3.8 Hz), 36.5
(d, JC–PZ4.0 Hz), 66.3, 68.2, 68.4, 69.2, 70.0, 70.8, 71.5
(d, JC–PZ6.4 Hz), 73.4, 74.9, 75.1, 75.6, 77.6, 83.2, 92.0 (d,
JC–PZ3.9 Hz, C-1), 102.1 (C-10), 127.6, 127.7, 127.79,
127.84, 128.0, 128.29, 128.32, 128.33, 128.38, 128.42,
128.95, 129.03, 129.1, 129.7, 129.8, 129.9, 133.16, 133.22,
133.4, 137.87, 137.89, 138.0, 165.2, 165.4, 165.9; 31P NMR
(109 MHz, C6D6) d 19.7; FAB-HRMS m/z calcd for
C58H63N5O14P (MCH)C 1084.4109, found 1084.4150;
Anal. calcd for: C58H62N5O14P: C, 64.26; H, 5.76; N,
6.46, found C, 64.33; H, 5.83; N, 6.41. Data for a-anomer
(22a): TLC RfZ0.25 (1:3 hexane/AcOEt); [a]1D7ZC84.88
(c 1.13, CHCl3); IR (CHCl3) 3026, 2934, 2114, 1730, 1452,
1
1089 cmK1; H NMR (500 MHz, CDCl3) d 3.27 (ddd, JZ
1.9,0 3.9, 9.9 Hz, 1H, H-50), 3.34 (dd, JZ8.8, 9.8 Hz, 1H,
H-3 ), 3.37 (s, 3H, OCH3), 3.40 (dd, JZ7.6, 9.8 Hz, 1H,
H-20), 3.58–3.65 (m, 4H, H-6a, H-40, H-60a, H-60b), 3.73
(dd, JZ4.7, 10.5 Hz, 1H, H-6b), 3.90–3.94 (m, 2H, H-3,
H-5), 4.13 (dd, JZ3.7, 10.1 Hz, 1H, H-2), 4.16 (brd, JZ
3.0 Hz, 1H, H-4), 4.37 (d, JZ12.0 Hz, 1H, OCHPh), 4.44
(d, JZ12.0 Hz, 1H, OCHPh), 4.48 (d, JZ12.1 Hz, 1H,
OCHPh), 4.52 (d, JZ12.1 Hz, 1H, OCHPh), 4.54 (d, JZ
12.1 Hz, 1H, OCHPh), 4.64 (d, JZ3.7 Hz, 1H, H-1), 4.67
(d, JZ12.1 Hz, 1H, OCHPh), 4.69 (d, JZ12.1 Hz, 1H,
OCHPh), 4.73 (d, JZ7.6 Hz, 1H, H-10), 4.77–4.80 (m, 2H,
OCHPh!2), 4.84 (d, JZ12.1 Hz, 1H, OCHPh), 4.91 (d,
JZ10.8 Hz, 1H, OCHPh), 4.92 (d, JZ12.1 Hz, 1H,
OCHPh), 7.15 (m, 2H, Ar-H), 7.24–7.37 (m, 28H, Ar-H);
13C NMR (126 MHz, CDCl3) d 55.3, 66.6, 68.9, 69.4, 70.2,
73.2, 73.4, 73.5, 73.8, 74.3, 74.8, 075.0, 75.5, 76.6, 77.7,
78.4, 83.1, 98.8 (C-1), 101.6 (C-1 ), 127.2, 127.3, 127.4,
127.5, 127.6, 127.7, 127.80, 127.82, 127.9, 128.0, 128.2,
128.27, 128.32, 128.36, 128.42, 128.44, 137.9, 138.05,
138.14, 138.58, 138.61, 138.9; FAB-HRMS m/z calcd for
C55H59N3O10Na (MCNa)C 944.4098, found 944.4102;
Anal. calcd for: C55H59N3O10: C, 71.64; H, 6.45; N, 4.56,
found C, 71.68; H, 6.55; N, 4.55. Data for a-anomer (21a):
TLC RfZ0.43 (2:1 hexane/AcOEt), 0.40 (10:1 toluene/
AcOEt); [a]1D8ZC44.58 (c 0.21, CHCl3); IR (CHCl3) 3018,
2930, 2870, 2114, 1454, 1358, 1277, 1089 cmK1; 1H NMR
(500 MHz, CDCl3) d 3.03 (dd, JZ1.7, 11.1 Hz, 1H, H-60a),
3.28 (dd, JZ2.0, 11.1 Hz, 1H, H-60b), 3.35 (dd, JZ3.6,
9.2 Hz, 1H, H-20), 3.36 (s, 3H, OCH3), 3.54 (dd, JZ10.4,
12.9 Hz, 1H, H-5), 3.75 (dd, JZ9.4, 10.1 Hz, 1H, H-40),
3.83–3.92 (m, 5H, H-2, H-3, H-6a, H-6b, H-30), 4.18 (d, JZ
12.2 Hz, 1H, OCHPh), 4.20 (d, JZ2.9 Hz, 1H, H-4), 4.23
(ddd, JZ1.7, 2.0, 10.1 Hz, 1H, H-50), 4.43 (d, JZ12.2 Hz,
1H, OCHPh), 4.46 (d, JZ12.2 Hz, 1H, OCHPh), 4.52 (d,
JZ11.8 Hz, 1H, OCHPh), 4.55 (d, JZ11.8 Hz, 1H,
OCHPh), 4.69–4.74 (m, 4H, H-1, OCHPh!3), 4.77 (d,
JZ11.9 Hz, 1H, OCHPh), 4.80–4.82 (m, 2H, OCHPh!2),
4.86 (d, JZ10.6 Hz, 1H, OCHPh), 4.94 (d, JZ3.6 Hz, 1H,
H-10), 7.13 (m, 2H, Ar-H), 7.17–7.37 (m, 28H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 55.4, 64.1, 67.3, 67.5, 68.9,
70.7, 73.16, 73.19, 73.3, 73.6, 74.8, 74.9, 75.27, 75.33, 78.2,
80.4, 98.5, 98.6, 127.4, 127.5, 127.6, 127.66, 127.73, 127.8,
127.95, 127.99, 128.03, 128.26, 128.31, 128.33, 128.4,
128.5, 137.6, 137.9, 138.1, 138.2, 138.4, 138.7; FAB-
HRMS m/z calcd for C55H59N3O10Na (MCNa)C 944.4098,
found 944.4136.
1278 cmK1; 1H NMR (500 MHz, CDCl3) d 2.60 (d, JH–P
Z
10.1 Hz, 6H, N(CH3)2), 2.69 (d, JH–PZ10.0 Hz, 6H,
N(CH3)2), 3.35 (dd, JZ3.6, 10.2 Hz, 1H, H-20), 3.45 (dd,
JZ1.4, 10.9 Hz, 1H, H-60a), 3.58 (dd, JZ3.2, 10.9 Hz, 1H,
H-60b), 3.65–3.72 (m, 3H, H-6a, H-40, H-50), 3.92 (dd, JZ
5.0, 11.3 Hz, 1H, H-6b), 4.02 (dd, JZ8.4, 10.2 Hz, 1H,
H-30), 4.37 (d, JZ12.1 Hz, 1H, OCHPh), 4.48 (ddd, JZ1.9,
5.0, 10.3 Hz, 1H, H-5), 4.50 (d, JZ11.1 Hz, 1H, OCHPh),
4.51 (d, JZ12.1 Hz, 1H, OCHPh), 4.80 (d, JZ11.1 Hz, 1H,
OCHPh), 4.86 (d, JZ11.3 Hz, 1H, OCHPh), 4.88 (d, JZ
11.3 Hz, 1H, OCHPh), 4.94 (d, JZ3.6 Hz, 1H, H-10), 5.38
(ddd, JZ3.4, 10.3, 1.5 (JH–P) Hz, 1H, H-2), 5.72 (dd, JZ
9.8, 10.3 Hz, 1H, H-4), 6.13 (dd, JZ3.4, 8.1 (JH–P) Hz, 1H,
H-1), 6.16 (dd, JZ9.8, 10.3 Hz, 1H, H-3), 7.18 (m, 2H,
Ar-H), 7.24–7.50 (m, 22H, Ar-H), 7.87 (m, 2H, Ar-H),
7.93–7.95 (m, 4H, Ar-H); 13C NMR (126 MHz, CDCl3) d
36.4 (d, JC–PZ3.5 Hz), 36.6 (d, JC–PZ3.6 Hz), 63.4, 66.7,
68.1, 68.7, 70.1, 70.5, 70.8, 71.5 (d, JC–PZ6.5 Hz), 73.4,
74.9, 75.4, 78.2, 80.0, 92.2 (d, JC–PZ3.9 Hz, C-1), 98.4
(C-10), 127.6, 127.7, 127.8, 128.1, 128.29, 128.33, 128.34,
128.38, 128.44, 128.9, 129.0, 129.1, 129.7, 129.8, 129.9,
133.2, 133.3, 133.4, 137.8, 138.0, 138.2, 165.0, 165.4,
166.0; 31P NMR (109 MHz, C6D6) d 19.4; FAB-HRMS m/z
calcd for C58H63N5O14P (MCH)C 1084.4109, found
1084.4100.
4.3.7. 2-Azido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyra-
nosyl-(1/6)-2,3,4-tri-O-benzoyl-a-D-glucopyranosyl
N,N,N0,N0-tetramethylphosphorodiamidate (22). The
glycosidation was performed according to the typical
procedure (1.5 mL EtCN, K78 8C, 2 h) employing diphenyl
phosphate 2a (70.8 mg, 0.10 mmol), alcohol 16 (68.9 mg,
0.11 mmol), and TMSOTf (1.0 M in CH2Cl2, 0.20 mL,
0.20 mmol). An anomeric mixture of disaccharide 22
(95.0 mg, 88%, a:bZ7:93) was obtained as a colorless oil
from the crude product (126.0 mg) after column chroma-
tography (silica gel 8 g, 1:2 hexane/AcOEt). The anomeric

10728
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
4.4. Glycosidations of 2-azido-3,4,6-tri-O-benzyl-2-
deoxygalactosyl diphenyl phosphate 4a
12.0 Hz, 1H, OCHPh), 4.80 (d, JZ10.8 Hz, 1H, OCHPh),
4.87 (d, JZ11.3 Hz, 1H, OCHPh), 4.88 (d, JZ11.0 Hz, 1H,
OCHPh), 4.980 (d, JZ10.8 Hz, 1H, OCHPh), 4.982 (d, JZ
3.5 Hz, 1H, H-10), 7.22–7.39 (m, 30H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 55.0, 59.8, 66.7, 68.6, 69.6, 69.9, 72.0,
73.35, 73.37, 73.39, 74.8, 74.9, 75.7, 76.6, 77.9, 80.0, 82.0,
97.9, 98.6, 127.6, 127.65, 127.66, 127.71, 127.72, 127.8,
127.87, 127.90, 128.0, 128.06, 128.07, 128.2, 128.36,
128.40, 128.5, 137.5, 137.9, 138.1, 138.27, 138.29, 138.8;
FAB-HRMS m/z calcd for C55H59N3O10Na (MCNa)C
944.4098, found 944.4079.
4.4.1. Methyl 6-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
galactopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyrano-
side (25).9 The glycosidation was performed according to
the typical procedure (1.5 mL EtCN, K78 8C, 0.2 h)
employing diphenyl phosphate 4a (70.8 mg, 0.10 mmol),
alcohol 7 (51.1 mg, 0.11 mmol), and TMSOTf (1.0 M in
CH2Cl2, 0.15 mL, 0.15 mmol). An anomeric mixture of
disaccharide 25 (79.4 mg, 86%, a:bZ4:96) was obtained as
a white solid from the crude product (108.0 mg) after
column chromatography (silica gel 7 g, 5:1 hexane/AcOEt),
along with propionate 26 (2.7 mg, 5%) as a colorless oil.
The anomeric ratio of 25 was determined by HPLC analysis
[eluent, 5:1 hexane/AcOEt; flow rate, 1.0 mL/min; tR
(a-anomer)Z20.5 min, tR (b-anomer)Z27.2 min]. The a-
and b-glycosides were separated by flash column chroma-
tography with 6:1 hexane/AcOEt. Data for b-anomer
(25b):9 mp 93.5–94.5 8C (colorless needles from AcOEt–
hexane); TLC RfZ0.42 (2:1 hexane/AcOEt); [a]2D3Z
C0.798 (c 1.00, CHCl3); IR (KBr) 3030, 2912, 2856,
2110, 1496, 1454, 1358, 1284, 1105, 1062 cmK1; 1H NMR
(500 MHz, CDCl3) d 3.29 (dd, JZ2.8, 10.4 Hz, 1H, H-30),
3.36 (s, 3H, OCH3), 3.44 (dd, JZ6.1, 7.7 Hz, 1H, H-50),
3.51–3.55 (m, 3H, H-2, H-4, H-60a), 3.61 (dd, JZ7.7,
9.9 Hz, 1H, H-60b), 3.64 (dd, JZ5.0, 10.9 Hz, 1H, H-6a),
3.79 (ddd, JZ1.8, 5.0, 10.1 Hz, 1H, H-5), 3.85 (dd, JZ8.2,
10.4 Hz, 1H, H-20), 3.87 (m, 1H, H-40), 3.98 (t, JZ9.3 Hz,
1H, H-3), 4.07 (dd, JZ1.8, 10.9 Hz, 1H, H-6b), 4.09 (d, JZ
8.2 Hz, 1H, H-10), 4.40 (d, JZ11.8 Hz, 1H, OCHPh), 4.43
(d, JZ11.8 Hz, 1H, OCHPh), 4.53 (d, JZ11.3 Hz, 1H,
OCHPh), 4.60 (d, JZ3.5 Hz, 1H, H-1), 4.639 (d, JZ
11.3 Hz, 1H, OCHPh), 4.640 (d, JZ12.2 Hz, 1H, OCHPh),
4.66 (d, JZ11.7 Hz, 1H, OCHPh), 4.70 (d, JZ11.7 Hz, 1H,
OCHPh), 4.77 (d, JZ12.2 Hz, 1H, OCHPh), 4.80 (d, JZ
10.0 Hz, 1H, OCHPh), 4.86 (d, JZ11.3 Hz, 1H, OCHPh),
4.90 (d, JZ11.1 Hz, 1H, OCHPh), 4.97 (d, JZ10.0 Hz, 1H,
OCHPh), 7.24–7.38 (m, 30H, Ar-H); 13C NMR (126 MHz,
CDCl3) d 55.1, 63.2, 68.27, 68.34, 69.8, 72.2, 72.4, 73.4,
73.52, 73.53, 74.60, 74.8, 75.7, 77.8, 79.9, 80.9, 82.1, 98.0
(C-1), 102.5 (C-1 ), 127.5, 127.6, 127.8, 127.85, 127.86,
128.0, 128.05, 128.13, 128.2, 128.3, 128.42, 128.44, 128.5,
137.6, 137.8, 138.2, 138.4, 138.5, 138.8; FAB-HRMS m/z
calcd for C55H59N3O10Na (MCNa)C 944.4098, found
944.4093; Anal. calcd for: C55H59N3O10: C, 71.64; H,
6.45; N, 4.56, found C, 71.62; H, 6.51; N 4.55. Data for
a-anomer (25a):9 TLC RfZ0.48 (2:1 hexane/AcOEt);
[a]2D1ZC83.38 (c 1.00, CHCl3); IR (film) 3030, 2916,
2108, 1496, 1454, 1358, 1259, 1159, 1095 cmK1; 1H NMR
(500 MHz, CDCl3) d 3.33 (s, 3H, OCH3), 3.49 (dd, JZ6.1,
9.2 Hz, 1H, H-60a), 3.51 (dd, JZ9.0, 9.9 Hz, 1H, H-4), 3.53
(dd,0JZ3.6, 9.6 Hz, 1H, H-2), 3.56 (dd, JZ7.9, 9.2 Hz, 1H,
H-6 b), 3.69 (dd, JZ1.2, 11.2 Hz, 1H, H-6a), 3.75 (ddd, JZ
1.2, 4.9, 9.9 Hz, 1H, H-5), 3.80 (dd, JZ4.9, 11.2 Hz, 1H,
H-6b), 3.83 (dd, JZ3.5, 10.7 Hz, 1H, H-20), 3.89 (dd, JZ
2.5, 10.7 Hz, 1H, H0-30), 3.93 (dd, JZ6.1, 7.9 Hz, 1H, H-50),
3.992 (br, 1H, H-4 ), 3.994 (dd, JZ9.0, 9.6 Hz, 1H, H-3),
4.37 (d, JZ11.8 Hz, 1H, OCHPh), 4.44 (d, JZ11.8 Hz, 1H,
OCHPh), 4.53 (d, JZ11.3 Hz, 1H, OCHPh), 4.56 (d, JZ
11.0 Hz, 1H, OCHPh), 4.58 (d, JZ3.6 Hz, 1H, H-1), 4.649
(d, JZ11.4 Hz, 1H, OCHPh), 4.654 (d, JZ12.0 Hz, 1H,
OCHPh), 4.71 (d, JZ11.4 Hz, 1H, OCHPh), 4.78 (d, JZ
Data for methyl 2,3,4-tri-O-benzyl-6-O-propionyl-a-D-glu-
copyranoside (26): TLC RfZ0.45 (2:1 hexane/AcOEt);
[a]2D5ZC27.18 (c 1.00, CHCl3); IR (film) 3030, 2918, 1738,
1
1454, 1190, 1072 cmK1; H NMR (500 MHz, CDCl3) d
1.11 (t, JZ7.7 Hz, 3H, CH2CH3), 2.30 (m, 2H, CH2CH3),
3.36 (s, 3H, OCH3), 3.47 (dd, JZ8.9, 10.1 Hz, 1H, H-4),
3.53 (dd, JZ3.5, 9.6 Hz, 1H, H-2), 3.82 (ddd, JZ3.0, 3.9,
10.1 Hz, 1H, H-5), 4.01 (dd, JZ8.9, 9.6 Hz, 1H, H-3), 4.26
(dd, JZ3.9, 12.0 Hz, 1H, H-6a), 4.29 (dd, JZ3.0, 12.0 Hz,
1H, H-6b), 4.56 (d, JZ10.8 Hz, 1H, OCHPh), 4.60 (d, JZ
3.5 Hz, 1H, H-1), 4.66 (d, JZ12.1 Hz, 1H, OCHPh), 4.79
(d, JZ12.1 Hz, 1H, OCHPh), 4.83 (d, JZ10.8 Hz, 1H,
OCHPh), 4.88 (d, JZ10.8 Hz, 1H, OCHPh), 5.00 (d, JZ
10.8 Hz, 1H, OCHPh), 7.26–7.36 (m, 15H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 9.0, 27.3, 55.1, 62.8, 68.6, 73.3,
75.0, 75.7, 77.4, 79.9, 82.0, 97.9 (C-1), 127.6, 127.8,
127.87, 127.92, 127.94, 128.0, 128.3, 128.38, 128.39, 137.8,
138.0, 138.5, 174.0; FAB-HRMS m/z calcd for C31H36O7Na
(MCNa)C 543.2359, found 543.2333; Anal. calcd for:
C31H36O7: C, 71.52; H 6.97, found C, 71.40; H, 6.93.
4.4.2. Methyl 4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
galactopyranosyl)-2,3,6-tri-O-benzyl-a-D-glucopyrano-
side (27).10 The glycosidation was performed according to
the typical procedure (1.5 mL EtCN, K78 8C, 0.5 h)
employing diphenyl phosphate 4a (70.8 mg, 0.10 mmol),
alcohol 8 (51.1 mg, 0.11 mmol), and TMSOTf (1.0 M in
CH2Cl2, 0.15 mL, 0.15 mmol). An anomeric mixture of
disaccharide 27 (82.8 mg, 90%, a:bZ4:96) was obtained as
a colorless oil from the crude product (110.6 mg) after
column chromatography (silica gel 5 g, 5:1 hexane/AcOEt).
The anomeric ratio of the product was determined by HPLC
analysis [eluent, 5:1 hexane/AcOEt; flow rate, 1.0 mL/min;
tR (a-anomer)Z15.3 min, tR (b-anomer)Z22.8 min]. The
a- and b-glycosides were separated by flash column
chromatography with 6:1 hexane/AcOEt. Data for b-anomer
(27b):10
TLC
RfZ0.49
(2:1
hexane/AcOEt);
[a]2D5ZK3.128 (c 2.51, CHCl3); IR (film) 3030, 2868,
2112, 1496, 1454, 1361, 1099 cmK1; H NMR (500 MHz,
1
CDCl3) d 3.13 (dd, JZ2.8, 10.3 Hz, 1H, H-30), 3.21 (dd, JZ
5.2, 8.2 Hz, 1H, H-50), 3.30 (dd, JZ5.2, 9.2 Hz, 1H, H-60a),
3.37 (s, 3H, OCH3), 3.47 (dd, JZ3.7, 9.4 Hz, 1H, H-2), 3.48
(dd, JZ8.2, 9.2 Hz, 1H, H-60b), 3.70 (dd, JZ1.5, 10.9 Hz,
1H, H-6a), 3.74 (dd, JZ8.1, 10.3 Hz, 1H, H-20), 3.76 (m,
1H, H-5), 3.849 (dd, JZ8.9, 9.4 Hz, 1H, H-4), 3.852 (brd,
JZ2.8 Hz, 1H, H-40), 3.91 (dd, JZ9.3, 9.4 Hz, 1H, H-3),
3.94 (dd, JZ3.2, 10.9 Hz, 1H, H-6b), 4.14 (d, JZ8.1 Hz,
1H, H-10), 4.22 (d, JZ11.8 Hz, 1H, OCHPh), 4.33 (d, JZ
11.8 Hz, 1H, OCHPh), 4.43 (d, JZ12.0 Hz, 1H, OCHPh),
4.50 (d, JZ11.3 Hz, 1H, OCHPh), 4.58 (d, JZ3.7 Hz, 1H,
H-1), 4.61 (d, JZ11.7 Hz, 1H, OCHPh), 4.62 (d, JZ

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10729
12.1 Hz, 1H, OCHPh), 4.66 (d, JZ12.0 Hz, 1H, OCHPh),
4.68 (d, JZ11.7 Hz, 1H, OCHPh), 4.74 (d, JZ10.7 Hz, 1H,
OCHPh), 4.80 (d, JZ12.1 Hz, 1H, OCHPh), 4.88 (d, JZ
11.3 Hz, 1H, OCHPh), 4.96 (d, JZ10.7 Hz, 1H, OCHPh),
7.13–7.38 (m, 30H, Ar-H); 13C NMR (126 MHz, CDCl3) d
55.2, 63.8, 67.9, 68.3, 69.7, 72.1, 73.2, 73.3, 73.4, 73.06,
74.7, 75.4, 76.7, 79.1, 80.1, 81.0, 98.3 (C-1), 101.2 (C-1 ),
127.5, 127.62, 127.64, 127.68, 127.71, 127.76, 127.78,
127.83, 127.86, 127.91, 127.93, 128.0, 128.2, 128.32,
128.34, 128.4, 137.6, 138.0, 138.4, 138.6, 139.4; FAB-
HRMS m/z calcd for C55H60N3O10 (MCH)C 922.4278,
found 922.4290; Anal. calcd for: C55H59N3O10: C, 71.64; H,
6.45; N, 4.56, found C, 71.42; H, 6.54; N, 4.52. Data for
a-anomer (27a):10 TLC RfZ0.55 (2:1 hexane/AcOEt);
[a]2D3ZC47.58 (c 0.35, CHCl3); IR (film) 3030, 2868, 2112,
1496, 1454, 1361, 1099 cmK1; 1H NMR (500 MHz, CDCl3)
d 3.38 (s, 3H, OCH3), 3.39 (m, 1H, H-60a), 3.47 (dd, JZ8.0,
8.6 Hz, 1H, H-60b), 3.55 (dd, JZ3.5, 9.6 Hz, 1H, H-2), 3.63
(dd, JZ4.0, 11.1 Hz, 1H, H-6a), 3.66 (dd, JZ2.2, 11.1 Hz,
1H, H-6b), 3.76–3.85 (m, 5H, H-4, H-5, H-20, H-30, H-50),
3.96 (brs, 1H, H-40), 4.05 (dd, JZ8.4, 9.6 Hz, 1H, H-3),
4.23 (d, JZ11.7 Hz, 1H, OCHPh), 4.30 (d, JZ11.7 Hz, 1H,
OCHPh), 4.43 (d, JZ12.2 Hz, 1H, OCHPh), 4.49 (d, JZ
11.3 Hz, 1H, OCHPh), 4.56 (d, JZ12.2 Hz, 1H, OCHPh),
4.58 (d, JZ3.5 Hz, 1H, H-1), 4.60 (d, JZ11.2 Hz, 1H,
OCHPh), 4.61 (d, JZ12.0 Hz, 1H, OCHPh), 4.66 (d, JZ
11.2 Hz, 1H, OCHPh), 4.75 (d, JZ12.0 Hz, 1H, OCHPh),
4.81 (d, JZ11.3 Hz, 1H, OCHPh), 4.87 (d, JZ10.6 Hz, 1H,
OCHPh), 5.06 (d, JZ10.6 Hz, 1H, OCHPh), 5.70 (d, JZ
2.8 Hz, 1H, H-10), 7.20–7.39 (m, 30H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 55.3, 59.5, 68.5, 69.5, 69.7, 70.0, 72.1,
73.0, 73.1, 73.3, 73.5, 73.7, 74.8, 75.0, 80.4, 81.9, 97.7,
98.1, 127.39, 127.42, 127.67, 127.73, 127.8, 127.9, 128.0,
128.16, 128.21, 128.24, 128.3, 128.35, 128.37, 128.47,
128.49, 137.6, 137.8, 138.0, 138.2, 138.4, 138.6; FAB-
HRMS m/z calcd for C55H60N3O10 (MCH)C 922.4278,
found 922.4301.
OCHPh), 4.57 (d, JZ11.4 Hz, 1H, OCHPh), 4.67 (d, JZ
12.6 Hz, 1H, OCHPh), 4.70 (d, JZ12.6 Hz, 1H, OCHPh),
4.71 (d, JZ8.1 Hz, 1H, H-10), 4.84 (s, 1H, H-1), 4.89 (d, JZ
11.4 Hz, 1H, OCHPh), 7.25–7.39 (m, 15H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 17.7, 26.4, 27.8, 54.8, 63.4,
64.1, 68.4, 72.6, 73.48, 73.50, 74.7, 76.0, 78.2, 78.5, 80.7,
97.9 (C-1), 100.5 (C-10), 109.2, 127.6, 127.75, 127.78,
127.83, 128.1, 128.2, 128.4, 128.5, 137.76, 137.80, 138.5;
FAB-HRMS m/z calcd for C37H46N3O9 (MCH)C
676.3236, found 676.3252; Anal. calcd for: C37H45N3O9:
C, 65.76; H, 6.71; N, 6.22, found C, 65.65; H, 6.69; N, 6.17.
Data for a-anomer (28a): TLC RfZ0.63 (2:1 hexane/
AcOEt); [a]2D3ZC80.88 (c 0.99, CHCl3); IR (film) 2986,
2934, 2112, 1496, 1454, 1367, 1221, 1091 cmK1; 1H NMR
(500 MHz, CDCl3) d 1.26 (s, 3H, CCH3), 1.34 (d, JZ
6.3 Hz, 3H, H-6), 1.37 (s, 3H, CCH3), 3.32 (dd, JZ6.4,
10.1 Hz, 1H, H-4), 3.35 (s, 3H, OCH3), 3.50 (dd, JZ4.6,
8.4 Hz, 1H, H-60a), 3.67 (dd, JZ8.4, 9.5 Hz, 1H, H-60b),
3.69 (dq, JZ10.1, 6.3 Hz, 1H, H-5), 3.89 (dd, JZ3.04,
10.7 Hz, 1H, H-20), 3.95 (dd, JZ2.5, 10.7 Hz,0 1H, H-3 ),
4.07–4.10 (m, 2H, H-2, H-30), 4.16 (brs, 1H, H-4 ), 4.24 (dd,
JZ4.6, 9.5 Hz, 1H, H-5 ), 4.40 (d, JZ11.9 Hz, 1H,
OCHPh), 4.50 (d, JZ11.9 Hz, 1H, OCHPh), 4.57 (d, JZ
11.2 Hz, 1H, OCHPh), 4.64 (d, JZ11.2 Hz, 1H, OCHPh),
4.72 (d, JZ11.2 Hz, 1H, OCHPh), 4.83 (s, 1H, H-1), 4.89
(d, JZ11.2 Hz, 1H, OCHPh), 4.98 (d, JZ3.4 Hz, 1H, H-10),
7.24–7.40 (m, 15H, Ar-H); 13C NMR (126 MHz, CDCl3) d
17.5, 26.4, 27.9, 54.8, 60.1, 64.8, 67.5, 69.0, 71.9, 73.1,
73.5, 74.9, 76.0, 76.9, 80.4, 97.9, 98.8, 109.1, 127.5, 127.8,
127.9, 128.0, 128.2, 128.45, 128.49, 137.6, 138.0, 138.6;
FAB-HRMS m/z calcd for C37H46N3O9 (MCH)C
676.3234, found 676.3232.
4.4.4. Methyl 2-azido-4-O-(2-azido-3,4,6-tri-O-benzyl-2-
deoxy-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-b-
D-glucopyranoside (29). The glycosidation was performed
according to the typical procedure (1.5 mL EtCN, K78 8C,
0.5 h) employing diphenyl phosphate 4a (70.8 mg,
0.10 mmol), alcohol 24 (43.9 mg, 0.11 mmol), and
TMSOTf (1.0 M in CH2Cl2, 0.15 mL, 0.15 mmol). An
anomeric mixture of disaccharide 29 (73.7 mg, 86%, a:bZ
8:92) was obtained as a colorless oil from the crude product
(100.3 mg) after column chromatography (silica gel 6 g,
30:1 toluene/AcOEt). The anomeric ratio of the product was
determined by HPLC analysis [eluent, 5:1 hexane/AcOEt;
flow rate, 1.0 mL/min; tR (a-anomer)Z10.2 min, tR
(b-anomer)Z14.8 min]. The a- and b-glycosides were
separated by flash column chromatography with 30:1
toluene/AcOEt. Data for b-anomer (29b): TLC RfZ0.53
(2:1 hexane/AcOEt), 0.53 (10:1 toluene/AcOEt);
[a]2D2ZK39.78 (c 0.93, CHCl3); IR (film) 3030, 2868,
4.4.3. Methyl 4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
galactopyranosyl)-2,3-O-isopropylidene-a-L-rhamno-
pyranoside (28). The glycosidation was performed accord-
ing to the typical procedure (1.5 mL EtCN, K78 8C, 0.3 h)
employing diphenyl phosphate 4a (70.8 mg, 0.10 mmol),
alcohol 23 (24.0 mg, 0.11 mmol), and TMSOTf (1.0 M in
CH2Cl2, 0.15 mL, 0.15 mmol). An anomeric mixture of
disaccharide 28 (55.0 mg, 81%, a:bZ6:94) was obtained as
a colorless oil from the crude product (82.5 mg) after
column chromatography (silica gel 7 g, 7:1 hexane/AcOEt).
The anomeric ratio of the product was determined by HPLC
analysis [eluent, 5:1 hexane/THF; flow rate, 1.0 mL/min; tR
(a-anomer)Z6.3 min, tR (b-anomer)Z7.4 min]. The a- and
b-glycosides were separated by flash column chromato-
graphy with 8:1 hexane/AcOEt. Data for b-anomer (28b):
TLC RfZ0.57 (2:1 hexane/AcOEt); [a]2D4ZK33.88 (c 1.47,
CHCl3); IR (film) 2934, 2112, 1454, 1367, 1221, 1091,
2110, 1496, 1454, 1361, 1280, 1059 cmK1 1H NMR
;
(500 MHz, CDCl3) d 3.15 (dd, JZ2.8, 10.4 Hz, 1H, H-30),
3.23 (dd, JZ5.1, 8.4 Hz, 1H, H-50), 3.29 (dd, JZ5.1,
9.0 Hz, 1H, H-60a), 3.35 (dd, JZ7.6, 9.8 Hz, 1H, H-2), 3.38
(dd, JZ8.3, 9.8 Hz, 1H, H-3), 3.43 (ddd, JZ1.2, 3.5,
9.8 Hz, 1H, H-5), 3.48 (dd, JZ8.4, 9.0 Hz, 1H, H-60b), 3.55
(s, 3H, OCH3), 3.75 (dd, JZ8.2, 10.4 Hz, 1H, H-20), 3.80
(dd,0 JZ1.2, 11.1 Hz, 1H, H-6a), 3.87 (d, JZ2.8 Hz, 1H,
H-4 ), 3.92 (dd, JZ3.5, 11.1 Hz, 1H, H-6b), 4.01 (dd, JZ
8.3, 9.8 Hz, 1H, H-4), 4.12 (d, JZ7.6 Hz, 1H, H-1), 4.23 (0d,
JZ11.8 Hz, 1H, OCHPh), 4.25 (d, JZ8.2 Hz, 1H, H-1 ),
4.32 (d, JZ11.8 Hz, 1H, OCHPh), 4.47 (d, JZ12.1 Hz, 1H,
1
1022 cmK1; H NMR (500 MHz, CDCl3) d 1.28 (d, JZ
5.6 Hz, 3H, H-6), 1.33 (s, 3H, CCH3), 1.44 (s, 3H, CCH3),
3.34 (dd, JZ3.0, 10.4 Hz, 1H, H-30), 3.36 (s, 3H, OCH3),
3.47 (m, 1H, H-50), 3.53 (dd, JZ5.3, 9.1 Hz, 1H, H-60a),
3.60–3.66 (m, 3H, H-4, H-5, H-60b), 3.73 (dd0 , JZ8.1,
10.4 Hz, 1H, H-20), 3.86 (d, JZ3.0 Hz, 1H, H-4 ), 4.09 (d,
JZ5.6 Hz, 1H, H-2), 4.25 (dd, JZ5.6, 5.8 Hz, 1H, H-3),
4.42 (d, JZ11.9 Hz, 1H, OCHPh), 4.45 (d, JZ11.9 Hz, 1H,

10730
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
OCHPh), 4.51 (d, JZ11.2 Hz, 1H, OCHPh), 4.62 (d, JZ
11.8 Hz, 1H, OCHPh), 4.65 (d, JZ10.3 Hz, 1H, OCHPh),
4.68 (d, JZ11.8 Hz, 1H, OCHPh), 4.69 (d, JZ12.1 Hz, 1H,
OCHPh), 4.89 (d, JZ11.2 Hz, 1H, OCHPh), 4.98 (d, JZ
10.3 Hz, 1H, OCHPh), 7.12–7.38 (m, 25H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 57.1, 63.8, 65.8, 67.7, 68.0,
72.20, 72.22, 73.20, 73.3, 73.4, 74.8, 74.9, 75.3, 76.1, 80.8,
81.4, 101.1 (C-1 ), 102.8 (C-1), 127.4, 127.5, 127.66,
127.74, 127.8, 127.9, 128.0, 128.2, 128.3, 128.35, 128.39,
128.5, 137.6, 137.9, 138.1, 138.2, 138.6; FAB-HRMS m/z
calcd for C48H53N6O9 (MCH)C 857.3874, found 857.3879;
Anal. calcd for: C48H52N6O9: C, 67.27; H, 6.12; N, 9.81,
found C, 67.36; H, 6.15; N, 9.89. Data for a-anomer (29a):
TLC RfZ0.59 (2:1 hexane/AcOEt), 0.67 (10:1 toluene/
AcOEt); [a]2D2ZC27.48 (c 1.07, CHCl3); IR (film) 3030,
2868, 2110, 1496, 1454, 1361, 1280, 1059 cmK1; 1H NMR
(500 MHz, CDCl3) d 3.39–3.42 (m, 2H, H-2, H-60a), 3.46
(dd, JZ6.4, 9.0 Hz, 1H, H-60b), 3.49 (m, 1H, H-5), 3.51 (dd,
JZ9.1, 9.5 Hz, 1H, H-3), 3.57 (s, 3H, OCH3), 3.66 (dd, JZ
5.0, 11.0 Hz, 1H, H-6a), 3.74 (dd, JZ2.3, 11.0 Hz, 1H,
H-6b), 3.76 (dd, JZ2.3, 10.9 Hz, 1H, H-30), 3.81 (dd, JZ
3.7, 10.9 Hz, 1H, H-20), 3.83 (dd, JZ9.1, 9.2 Hz, 1H, H-4),
3.86 (t, JZ6.4 Hz, 1H, H-50), 3.95 (brs, 1H, H-40), 4.22 (d,
JZ8.0 Hz, 1H, H-1), 4.28 (d, JZ11.7 Hz, 1H, OCHPh),
4.36 (d, JZ11.7 Hz, 1H, OCHPh), 4.46 (d, JZ12.4 Hz, 1H,
OCHPh), 4.49 (d, JZ11.3 Hz, 1H, OCHPh), 4.572 (d, JZ
12.4 Hz, 1H, OCHPh), 4.574 (d, JZ11.2 Hz, 1H, OCHPh),
4.64 (d, JZ11.2 Hz, 1H, OCHPh), 4.80 (d, JZ11.3 Hz, 1H,
OCHPh), 4.84 (d, JZ10.4 Hz, 1H, OCHPh), 5.000 (d, JZ
10.4 Hz, 1H, OCHPh), 5.63 (d, JZ3.7 Hz, 1H, H-1 ), 7.21–
7.39 (m, 25H, Ar-H); 13C NMR (126 MHz, CDCl3) d 57.0,
59.5, 66.7, 68.5, 69.6, 70.2, 72.0, 72.9, 73.3, 73.4, 73.5,
74.6, 74.76, 74.78, 83.7, 97.9 (C-10), 102.9 (C-1), 127.5,
127.6, 127.7, 127.78, 127.80, 127.9, 128.2, 128.3, 128.4,
128.49, 128.51, 137.5, 137.7, 137.8, 138.2, 138.3; FAB-
HRMS m/z calcd for C48H53N6O9 (MCH)C 857.3874,
found 857.3863.
(c 2.01, CHCl3); IR (film) 2922, 2106, 1751, 1660, 1454,
1
1367, 1228, 1049 cmK1; H NMR (500 MHz, CDCl3) d
1.14 (t, JZ7.6 Hz, 3H, CH2CH3), 2.01 (s, 3H, CH3CO),
2.06 (s, 3H, CH3CO), 2.08 (s, 3H, CH3CO), 2.35 (q, JZ
7.6 Hz, 2H, CH2CH3), 3.41 (s, 3H, OCH3), 3.52 (dd, JZ4.1,
10.2 Hz, 1H, H-20), 3.55 (dd, JZ3.5, 9.6 Hz, 1H, H-2), 3.61
(dd, JZ8.9, 10.1 Hz, 1H, H-4), 3.90 (ddd, JZ1.5, 4.0,
10.1 Hz, 1H, H-5), 3.95 (m, 1H, H-6a), 4.01 (dd, JZ8.9,
9.6 Hz, 1H, H-3), 4.22–4.26 (m, 30H, H-6b, H-50, H-60a),
4.42 (dd, JZ1.7, 12.3 Hz, 1H, H-6 b), 4.60 (d, JZ3.5 Hz,
1H, H-1), 4.61 (d, JZ10.7 Hz, 1H, OCHPh), 4.67 (d, JZ
12.0 Hz, 1H, OCHPh), 4.81 (d, JZ12.0 Hz, 1H, OCHPh),
4.84 (d, JZ10.8 Hz, 1H, OCHPh), 4.85 (d, JZ10.7 Hz, 1H,
OCHPh), 4.99 (0d, JZ10.8 Hz, 1H, OCHPh), 5.08 (t, JZ
9.6 Hz, 1H, H-4 ), 5.22 (d, JZ4.1 Hz, 1H, H-10), 5.63 (dd,
JZ9.6, 10.2 Hz, 1H, H-30), 7.26–7.38 (m, 15H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 10.6, 20.6, 20.69, 20.73, 23.0,
55.2, 62.1, 62.2, 64.6, 68.0, 68.7, 69.2, 71.4, 73.4, 75.1,
75.8, 77.6, 80.0, 82.0, 83.0 (C-10), 98.1 (C-1), 127.6, 127.8,
127.9, 128.0, 128.06, 128.11, 128.39, 128.44, 137.9, 138.1,
138.6, 169.7, 169.9, 170.3, 170.6; FAB-HRMS m/z calcd for
C43H53N4O13 (MCH)C 833.3609, found 833.3600; Anal.
calcd for: C43H52N4O13: C, 62.01; H, 6.30; N, 6.73, found
C, 61.85; H, 6.23; N, 6.64. Data for b-anomer (30b): TLC
RfZ0.40 (1:1 hexane/AcOEt); [a]2D1ZC9.078 (c 0.45,
CHCl3); IR (film) 2924, 2112, 1751, 1657, 1454, 1365,
1
1230, 1047 cmK1; H NMR (500 MHz, CDCl3) d 1.16 (t,
JZ7.4 Hz, 3H, CH2CH3), 2.01 (s, 3H, CH3CO), 2.02 (s, 3H,
CH3CO), 2.09 (s, 3H, CH3CO), 2.34 (dq, JZ14.6, 7.4 Hz,
1H, CHCH3), 2.36 (dq, JZ14.6, 7.4 Hz, 1H, CHCH3), 3.37
(s, 3H, OCH3), 3.515 (dd, JZ8.4, 9.4 Hz, 1H, H-20), 3.523
(dd, JZ9.0, 10.1 Hz, 1H, H-4), 3.54 (dd, JZ3.6, 9.5 Hz,
1H, H-2), 3.75 (ddd, JZ2.1, 5.6, 9.7 Hz, 1H, H-50), 3.87
(ddd, JZ1.8, 4.7, 10.1 Hz, 1H, H-5), 4.01 (dd, JZ9.0,
9.5 Hz, 1H, H-3), 4.09 (dd, JZ2.1,0 12.3 Hz, 1H, H-60a),
4.18 (dd, JZ5.6, 12.3 Hz, 1H, H-6 b), 4.30 (dd, JZ1.8,
12.2 Hz, 1H, H-6a), 4.42 (dd,0 JZ4.7, 12.2 Hz, 1H, H-6b),
4.51 (d, JZ8.4 Hz, 1H, H-1 ), 4.56 (d, JZ10.7 Hz, 1H,
OCHPh), 4.61 (d, JZ3.6 Hz, 1H, H-1), 4.67 (d, JZ12.1 Hz,
1H, OCHPh), 4.80 (d, JZ12.1 Hz, 1H, OCHPh), 4.82
(d, JZ10.8 Hz, 1H, OCHPh), 4.87 (d, JZ10.7 Hz, 1H,
OCHPh), 4.99 (d, JZ10.8 Hz, 1H, OCHPh), 5.00 (dd, JZ
8.2, 9.7 Hz, 1H, H-40), 5.04 (dd, JZ8.2, 9.4 Hz, 1H, H-30),
7.26–7.37 (m, 15H, Ar-H); 13C NMR (126 MHz, CDCl3) d
10.8, 20.6, 20.68, 20.74, 23.9, 55.1, 62.6, 64.6, 65.8, 68.08,
73.0, 73.4, 73.7, 75.1, 75.9, 78.0, 80.0, 82.1, 87.8 (C-1 ),
98.0 (C-1), 127.7, 127.8, 127.88, 127.93, 128.07, 128.09,
128.41, 128.43, 128.5, 138.1, 138.2, 138.7, 169.7, 170.1,
170.6, 171.9; FAB-HRMS m/z calcd for C43H53N4O13 (MC
H)C 833.3609, found 833.3580.
4.5. Glycosidations of 3,4,6-tri-O-acetyl-2-azido-2-
deoxyglycosyl diphenyl phosphates 2b and 4b
4.5.1. Methyl 2,3,4-tri-O-benzyl-6-O-[1-(3,4,6-tri-O-
acetyl-2-azido-2-deoxy-D-glucopyranosyl)iminopropyl]-
a-D-glucopyranoside (30). The glycosidation was per-
formed according to the typical procedure (1.5 mL EtCN,
K65 8C, 4 h) employing diphenyl phosphate 2b (56.3 mg,
0.10 mmol), alcohol 7 (51.1 mg, 0.11 mmol), and TMSOTf
(1.0 M in CH2Cl2, 0.15 mL, 0.15 mmol). A mixture of
imidate 30 and disaccharide 31 (79.7 mg) was obtained as a
colorless oil from the crude product (106.9 mg) after short
column chromatography (silica gel 3 g, 2:1 hexane/AcOEt
with 1% Et3N). The anomeric ratio of the products was
determined by HPLC analysis [eluent, 5:1:1 hexane/AcOEt/
THF; flow rate, 1.0 mL/min; tR (30a)Z9.6 min, tR (31a)Z
10.3 min, tR (31b)Z11.1 min, tR (30b)Z11.8 min]. The
mixture was purified by flash column chromatography
(silica gel 6 g, 3:1 hexane/AcOEt with 1% Et3N) to give
a-imidate 30a (65.5 mg, 79%) as a colorless oil, along with
an anomeric mixture of disaccharide 31 (3.4 mg, 4%, a:bZ
14:86) as a colorless oil. The a- and b-glycosides of
disaccharide 31 were separated by flash column chroma-
tography with 15:1 toluene/acetone. Data for a-anomer
(30a): TLC RfZ0.46 (1:1 hexane/AcOEt); [a]2D3ZC87.78
Data for methyl 2,3,4-tri-O-benzyl-6-O-(3,4,6-tri-O-acetyl-
2-azido-2-deoxy-D-glucopyranosyl)-a-D-glucopyranoside
(31). Data for b-anomer (31b): TLC RfZ0.40 (1:1 hexane/
AcOEt), 0.52 (5:1 toluene/acetone); [a]1D7ZK1.418 (c 1.58,
CHCl3); IR (film) 2930, 2112, 1753, 1454, 1365, 1228,
1
1049 cmK1; H NMR (500 MHz, CDCl3) d 2.01 (s, 3H,
CH3CO), 2.04 (s, 3H, CH3CO), 2.08 (s, 3H, CH3CO), 3.38
(s, 3H, OCH3), 3.52 (dd, JZ9.2, 10.1 Hz, 1H, H-4), 3.52–
3.55 (m, 2H, H-2, H-20), 3.57 (ddd, JZ2.4, 3.6, 9.5 Hz, 1H,
H-50), 3.70 (dd, JZ4.7, 10.9 Hz, 1H, H-6a), 3.82 (ddd, JZ
1.7, 4.7, 10.1 Hz, 1H, H-5), 4.00 (dd, JZ9.2, 9.3 Hz, 1H,
H-3), 4.090 (dd, JZ1.7, 10.9 Hz, 1H, H-6b), 4.094 (dd, JZ

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10731
2.4,0 12.1 Hz, 1H, H-60a), 4.22 (dd,0 JZ3.6, 12.1 Hz, 1H,
H-6 b), 4.23 (d, JZ8.1 Hz, 1H, H-1 ), 4.61 (d, JZ3.5 Hz,
1H, H-1), 4.62 (d, JZ11.0 Hz, 1H, OCHPh), 4.65 (d, JZ
12.1 Hz, 1H, OCHPh), 4.79 (d, JZ12.1 Hz, 1H, OCHPh),
4.82 (d, JZ11.0 Hz, 1H, OCHPh), 4.904 (d, JZ11.0 Hz, 1H,
OCHPh), 4.96–5.00 (m, 3H, H-30, H-4 , OCHPh), 7.26–7.37
(m, 15H, Ar-H); 13C NMR (126 MHz, CDCl3) d 20.5, 20.61,
20.63, 55.3, 61.8, 63.8, 68.4, 68.7, 69.7, 71.7, 72.6, 73.4,
74.8, 75.7, 77.6, 79.8, 82.0, 98.2 (C-1), 102.0 (C-10), 127.6,
127.7, 127.90, 127.93, 128.1, 128.2, 128.35, 128.43, 128.5,
138.1, 138.3, 138.7, 169.5, 169.9, 170.5; FAB-HRMS m/z
calcd for C40H47N3O13Na (MCNa)C 800.3007, found
800.3033; Anal. calcd for: C40H47N3O13: C, 61.77; H,
6.09; N, 5.40, found C, 61.64; H, 6.08; N, 5.31. Data for
a-anomer (31a): TLC RfZ0.42 (1:1 hexane/AcOEt), 0.56
(5:1 toluene/acetone); [a]2D0ZC119.68 (c 1.28, CHCl3); IR
1.99 (s, 3H, CH3CO), 2.05 (s, 3H, CH3CO), 2.15 (s, 3H,
CH3CO), 2.35 (q, JZ7.6 Hz, 2H, CH2CH3), 3.40 (s, 3H,
OCH3), 3.55 (dd, JZ3.6, 9.6 Hz, 1H, H-2), 3.60 (dd, JZ9.0,
10.0 Hz, 1H, H-4), 3.81 (dd, JZ4.0, 10.8 Hz, 1H, H-20),
3.88 (ddd, JZ1.6,04.3, 10.0 Hz, 1H, H-5), 3.97 (dd, JZ6.8,
11.3 Hz, 1H, H-6 a), 4.01 (dd, JZ9.0, 9.6 Hz, 1H, H-3),
4.04 (dd, JZ6.6, 11.3 Hz, 1H, H-60b), 4.23 (dd, JZ4.3,
12.1 Hz, 1H, H-6a), 4.36 (dd, JZ1.6, 12.1 Hz, 1H, H-6b),
4.39 (ddd, JZ0.7, 6.6, 6.8 Hz, 1H, H-50), 4.59 (d, JZ
10.7 Hz, 1H, OCHPh), 4.61 (d, JZ3.6 Hz, 1H, H-1), 4.68
(d, JZ12.1 Hz, 1H, OCHPh), 4.81 (d, JZ12.1 Hz, 1H,
OCHPh), 4.83 (d, JZ10.7 Hz, 1H, OCHPh), 4.85 (d, JZ
10.7 Hz, 1H, OCHPh), 4.99 (d, JZ10.7 Hz, 1H, OCHPh),
5.24 (d, JZ4.0 Hz, 1H, H-10), 5.44 (dd, JZ0.7, 3.3 Hz, 1H,
H-40), 5.47 (dd, JZ3.3, 10.8 Hz, 1H, H-30), 7.26–7.38 (m,
15H, Ar-H); 13C NMR (126 MHz, CDCl3) d 10.6, 20.6,
20.66, 20.70, 23.0, 55.2, 58.6, 62.0, 64.5, 67.0, 68.0, 68.7,
69.3, 73.4, 75.2, 75.8, 77.7, 80.0, 82.0, 83.4 (C-10), 98.1
(C-1), 127.6, 127.8, 127.9, 128.00, 128.02, 128.1, 128.4,
128.5, 138.0, 138.1, 138.7, 169.8, 170.0, 170.1, 170.3; FAB-
HRMS m/z calcd for C43H53N4O13 (MCH)C 833.3609,
found 833.3626; Anal. calcd for: C43H52N4O13: C, 62.01; H,
6.30; N, 6.73, found C, 61.95, H, 6.14, N, 6.69. Data for
(film)3030, 2932, 2108, 1751, 1454, 1367, 1226, 1047 cmK1
;
1H NMR (500 MHz, CDCl3) d 2.02 (s, 3H, CH3CO), 2.03 (s,
3H, CH3CO), 2.08 (s, 3H, CH3CO), 3.30 (dd, JZ3.4,
10.7 Hz, 1H, H-20), 3.39 (s, 3H, OCH3), 3.53 (dd, JZ3.5,
9.8 Hz, 1H, H-2), 3.54 (dd, JZ8.7, 10.2 Hz, 1H, H-4), 3.68
(m, 1H, H-6a), 3.77–3.81 (m, 2H, H-5, H-6b), 3.92 (ddd,
JZ2.2, 4.3, 10.1 Hz, 1H, H-50), 3.99 (dd, JZ2.2, 12.5 Hz,
1H, H-60a), 4.01 (dd, JZ8.7, 9.8 Hz, 1H, H-3), 4.15 (dd, JZ
4.3, 12.5 Hz, 1H, H-60b), 4.59 (d, JZ3.5 Hz, 1H, H-1), 4.62
(d, JZ11.5 Hz, 1H, OCHPh), 4.66 (d, JZ12.0 Hz, 1H,
OCHPh), 4.78 (d, JZ12.0 Hz, 1H, OCHPh), 4.81 (d, JZ
11.2 Hz, 1H, OCHPh), 4.97 (d, JZ11.5 Hz, 1H, OCHPh),
4.99 (d, JZ11.20Hz, 1H, OCHPh), 5.00 (dd, JZ9.4,
10.1 Hz, 1H, H-4 ), 5.04 (d,0 JZ3.4 Hz, 1H, H-10), 5.40
(dd, JZ9.4, 10.7 Hz, 1H, H-3 ), 7.26–7.37 (m, 15H, Ar-H);
13C NMR (126 MHz, CDCl3) d 20.57, 20.64, 20.7, 55.2,
61.0, 61.7, 66.7, 67.5, 68.5,0 69.9, 70.3, 73.4, 74.9, 75.7,
77.5, 80.0, 82.0, 97.95 (C-1 ), 98.04 (C-1), 127.6, 127.7,
127.8, 127.9, 128.0, 128.1, 128.37, 128.42, 138.1, 138.3,
138.7, 169.6, 169.9, 170.5; FAB-HRMS m/z calcd for
C40H47N3O13Na (MCNa)C 800.3007, found 800.3034.
1
b-anomer (32b): TLC RfZ0.45 (1:1 hexane/AcOEt); H
NMR (500 MHz, CDCl3) d 1.17 (dd, JZ7.0, 7.3 Hz, 3H,
CH2CH3), 2.01 (s, 3H, CH3CO), 2.06 (s, 3H, CH3CO), 2.15
(s, 3H, CH3CO), 2.35 (dq, JZ14.4, 7.3 Hz, 1H, CHCH3),
2.38 (dq, JZ14.4, 7.0 Hz, 1H, CHCH3), 3.38 (s, 3H, OCH3),
3.545 (dd, JZ3.6, 9.7 Hz, 1H, H-2), 3.546 (dd, JZ8.9,
9.9 Hz, 1H, H-4), 3.80 (dd, JZ8.3, 10.9 Hz, 1H, H-20), 3.88
(ddd, JZ2.1, 4.5, 9.9 Hz, 1H, H-5), 3.94 (dd, JZ6.5,
6.7 Hz, 1H, H-50), 4.01 (dd, J0Z8.9, 9.7 Hz, 1H, H-3), 4.10
(dd, JZ6.5, 11.4 Hz, 1H, H-6 a), 4.12 (dd, JZ6.7, 11.4 Hz,
1H, H-60b), 4.35 (dd, JZ2.1, 12.1 Hz, 1H, H-6a), 4.39 (d0d,
JZ4.5, 12.1 Hz, 1H, H-6b), 4.50 (d, JZ8.3 Hz, 1H, H-1 ),
4.57 (d, JZ10.7 Hz, 1H, OCHPh), 4.61 (d, JZ3.6 Hz, 1H,
H-1), 4.67 (d, JZ12.1 Hz, 1H, OCHPh), 4.80 (d, JZ
12.1 Hz, 1H, OCHPh), 4.82 (d, JZ10.7 Hz, 1H, OCHPh),
4.85 (dd, JZ3.4, 10.9 Hz, 1H, H-30), 4.86 (d, JZ10.7 Hz,
1H, OCHPh), 4.98 (d, JZ10.7 Hz, 1H, OCHPh), 5.38 (d,
JZ3.4 Hz, 1H, H-40), 7.25–7.37 (m, 15H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 10.8, 20.6, 20.66, 20.68, 23.8, 55.1,
61.8, 62.8, 64.7, 66.8, 68.7, 71.3, 72.5, 73.4, 75.2, 75.9,
78.1, 80.1, 82.1, 88.3 (C-10), 98.0 (C-1), 127.67, 127.69,
127.9, 128.06, 128.08, 128.38, 128.42, 128.5, 138.1, 138.2,
138.7, 169.9, 170.2, 170.4, 171.8; FAB-HRMS m/z calcd for
C43H53N4O13 (MCH)C 833.3609, found 833.3614.
4.5.2. Methyl 2,3,4-tri-O-benzyl-6-O-[1-(3,4,6-tri-O-
acetyl-2-azido-2-deoxy-D-galactopyranosyl)iminoprop-
yl]-a-D-glucopyranoside (32). The glycosidation was
performed according to the typical procedure (1.5 mL
EtCN, K65 8C, 3 h) employing diphenyl phosphate 4b
(56.3 mg, 0.10 mmol), alcohol 7 (51.1 mg, 0.11 mmol), and
TMSOTf (1.0 M in CH2Cl2, 0.15 mL, 0.15 mmol). A
mixture of imidate 32 and disaccharide 33 (80.3 mg) was
obtained as a colorless oil from the crude product
(102.4 mg) after short column chromatography (silica gel
3 g, 2:1 hexane/AcOEt with 1% Et3N). The anomeric ratio
of the products was determined by HPLC analysis [eluent,
4:1 hexane/THF; flow rate, 1.0 mL/min; tR (32a)Z
19.3 min, tR (33a)Z21.7 min, tR (33b)Z26.6 min, tR
(32b)Z30.4 min]. The mixture was purified by flash
column chromatography (silica gel 6 g, 4:1 hexane/acetone
with 1% Et3N) to give a-imidate 32a (56.4 mg, 68%) as a
colorless oil, along with an anomeric mixture of disacchar-
ide 33 (6.8 mg, 9%, a:bZ3:97) as a white solid. The a- and
b-glycosides of disaccharide 33 were separated by flash
column chromatography with 1:1 hexane/Et2O. Data for
a-anomer (32a): TLC RfZ0.47 (1:1 hexane/AcOEt);
[a]2D2ZC72.78 (c 1.50, CHCl3); IR (film) 2916, 2108,
Data for methyl 2,3,4-tri-O-benzyl-6-O-(3,4,6-tri-O-acetyl-
2-azido-2-deoxy-D-galactopyranosyl)-a-D-glucopyranoside
(33).9 Data for b-anomer (33b):9 TLC RfZ0.42 (1:1
hexane/AcOEt), 0.24 (1:3 hexane/Et2O); mp 145.0–
146.0 8C (colorless needles from AcOEt–hexane);
[a]2D4ZK9.468 (c 1.00, CHCl3); IR (KBr) 3032, 2926,
2114, 1751, 1454, 1369, 1242, 1076 cmK1 1H NMR
;
(500 MHz, CDCl3) d 2.01 (s, 3H, CH3CO), 2.04 (s, 3H,
CH3CO), 2.11 (s, 3H, CH3CO), 3.39 (s, 3H, OCH3), 3.53
(dd, JZ8.8, 10.2 Hz, 1H, H-4), 3.54 (dd, JZ3.5, 9.6 Hz,
1H, H-2), 3.70 (dd, JZ4.8, 11.0 Hz, 1H, H-6a), 3.72 (dd,
JZ8.1, 10.9 Hz, 1H, H-20), 3.77 (dd, JZ6.8, 7.0 Hz, 1H,
H-50), 3.83 (ddd, JZ1.5, 4.5, 10.2 Hz, 1H, H-5), 4.01 (dd,
JZ8.8, 9.6 Hz, 1H, H-3), 4.07–4.140 (m, 3H, H-6b, H-60a,
H-60b), 4.22 (d, JZ8.1 Hz, 1H, H-1 ), 4.62 (d, JZ3.5 Hz,
1751, 1662, 1454, 1371, 1228, 1078 cmK1
;
1H NMR
(500 MHz, CDCl3) d 1.15 (t, JZ7.6 Hz, 3H, CH2CH3),

10732
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
1
1H, H-1), 4.63 (d, JZ11.1 Hz, 1H, OCHPh), 4.65 (d, JZ
12.4 Hz, 1H, OCHPh), 4.76 (dd, JZ3.3, 10.9 Hz, 1H, H-30),
4.80 (d, JZ12.4 Hz, 1H, OCHPh), 4.82 (d, JZ10.9 Hz, 1H,
OCHPh), 4.94 (d, JZ11.1 Hz, 1H, OCHPh), 4.990 (d, JZ
10.9 Hz, 1H, OCHPh), 5.30 (d, JZ3.3 Hz, 1H, H-4 ), 7.27–
7.37 (m, 15H, Ar-H); 13C NMR (126 MHz, CDCl3) d 20.56,
20.58, 20.61, 55.3, 60.9, 61.1, 66.3, 68.8, 69.7, 70.6, 71.3,
73.4, 75.7, 77.7, 79.8, 82.0, 98.2 (C-1), 102.4 (C-10), 127.6,
127.7, 127.8, 127.9, 128.0, 128.1, 128.4, 128.45, 128.46,
138.1, 138.3, 138.7, 169.8, 170.0, 170.3; FAB-HRMS m/z
calcd for C40H47N3O13Na (MCNa)C 800.3007, found
800.2985; Anal. calcd for: C40H47N3O13: C, 61.77; H,
6.09; N, 5.40, found C, 61.75; H, 6.09; N, 5.30. Data for
a-anomer (33a):9 TLC RfZ0.43 (1:1 hexane/AcOEt), 0.31
(1:3 hexane/Et2O); [a]2D5ZC96.48 (c 1.01, CHCl3); IR
(film) 2928, 2110, 1751, 1454, 1371, 1228, 1074 cmK1; 1H
NMR (500 MHz, CDCl3) d 1.98 (s, 3H, CH3CO), 2.05 (s,
3H, CH3CO), 2.12 (s, 3H, CH3CO), 3.38 (s, 3H, OCH3),
3.51 (dd, JZ9.0, 9.9 Hz, 1H, H-4), 3.52 (dd, JZ3.5, 9.7 Hz,
1H, H-2), 3.62 (dd, JZ3.4, 11.2 Hz, 1H, H-20), 3.70 (m, 1H,
H-6a), 3.75–3.79 (m, 2H, H-5, H-6b), 3.96–4.02 (m, 2H,
H-3, H-60a), 4.05 (dd, JZ6.0, 10.9 Hz, 1H, H-60b), 4.09 (dd,
JZ6.0, 6.9 Hz, 1H, H-50), 4.59 (d, JZ3.5 Hz, 1H, H-1),
4.61 (d, JZ11.3 Hz, 1H, OCHPh), 4.66 (d, JZ12.1 Hz, 1H,
OCHPh), 4.79 (d, JZ12.1 Hz, 1H, OCHPh), 4.81 (d, JZ
10.9 Hz, 1H, OCHPh), 4.94 (d, JZ11.3 Hz, 1H, OCHPh),
4.99 (d, JZ10.9 Hz, 1H, OCHPh), 5.06 (d, JZ3.6 Hz, 1H,
H-10), 5.28 (dd, JZ3.3, 11.2 Hz, 1H, H-30), 5.39 (brd, JZ
3.3 Hz, 1H, H-40), 7.26–7.37 (m, 15H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 20.5, 20.6, 55.2, 57.5, 61.6, 66.6, 66.7,
67.6, 68.0, 69.9, 73.4, 74.9, 75.7, 77.6, 80.0, 82.0, 97.9,
98.1, 127.6, 127.7, 127.85, 127.94, 128.1, 128.3, 128.4,
138.1, 138.2, 138.6, 169.7, 169.9, 170.2; FAB-HRMS m/z
calcd for C40H47N3O13Na (MCNa)C 800.3007, found
800.3007.
1095 cmK1; H NMR (500 MHz, CDCl3) d 2.13 (s, 3H,
CH3CO), 3.38 (s, 3H, OCH3), 3.41 (ddd, JZ5.0, 9.4,
10.1 Hz, 1H, H-50), 3.53 (dd, JZ8.0, 9.8 Hz, 1H, H-20), 3.54
(dd, JZ3.5, 9.4 Hz, 1H, H-2), 3.56 (dd, 0JZ9.1, 9.3 Hz, 1H,
H-4), 3.59 (dd, JZ9.4, 9.7 Hz, 1H, H-4 ), 3.75 (dd, JZ4.2,
10.4 Hz, 1H, H-6a), 3.76 (dd, JZ10.1, 10.5 Hz, 1H,
H-60ax), 3.80 (ddd, JZ1.4, 4.2, 9.3 Hz, 1H, H-5), 4.01
(dd, JZ9.1, 9.4 Hz, 1H, H-3), 4.08 (dd, JZ1.4, 10.4 Hz,
1H, H-6b), 4.30 (dd, JZ5.0, 10.5 Hz, 1H, H-60eq), 4.35 (d,
JZ8.0 Hz, 1H, H-10), 4.61 (d, JZ3.5 Hz, 1H, H-1), 4.64 (d,
JZ11.1 Hz, 1H, OCHPh), 4.65 (d, JZ12.2 Hz, 1H,
OCHPh), 4.80 (d, JZ12.2 Hz, 1H, OCHPh), 4.83 (d, JZ
10.9 Hz, 1H, OCHPh), 4.95 (d, JZ11.1 Hz, 1H, OCHPh),
4.99 (d, JZ10.9 Hz, 1H, OCHPh), 5.15 (dd, JZ9.7, 9.8 Hz,
1H, H-30), 5.46 (s, 1H, CHPh), 7.28–7.36 (m, 18H, Ar-H),
7.41 (m, 2H, Ar-H); 13C NMR (126 MHz, CDCl3) d 20.8,
55.3, 64.8, 66.4, 68.4, 68.8, 69.6, 71.3, 73.4, 74.9, 75.7,
77.6, 78.5, 79.7, 82.0, 98.2 (C-1), 101.5, 102.4 (C-10), 127.6,
127.77, 127.80, 127.9, 128.0, 128.15, 128.23, 128.4, 128.45,
128.49, 129.1, 136.7, 138.1, 138.2, 138.7, 169.7; FAB-
HRMS m/z calcd for C43H47N3O11Na (MCNa)C 804.3109,
found 804.3135; Anal. calcd for: C43H47N3O11: C, 66.06; H,
6.06; N, 5.37, found C, 65.94; H, 6.13; N, 5.27. Data for
a-anomer (35a): TLC RfZ0.32 (2:1 hexane/AcOEt); mp
152.0–153.0 8C (colorless fine needles from AcOEt/
hexane); [a]2D1ZC106.98 (c 0.76, CHCl3); IR (film) 2926,
2112, 1753, 1454, 1369, 1222, 1095 cmK1 1H NMR
;
(500 MHz, CDCl3) d 2.13 (s, 3H, CH3CO), 3.21 (dd, JZ
3.6, 10.4 Hz, 1H, H-20), 3.39 (3H, s, OCH3), 3.54 (dd, JZ
3.5, 9.7 Hz, 1H, H-2), 3.55 (dd, JZ8.9, 10.5 Hz, 1H, H-5),
3.58 (dd, JZ9.5, 9.8 Hz, 1H, H-40), 3.69 (m, 1H, H-6a),
3.70 (dd, JZ10.2, 10.3 Hz, 1H, H-60ax), 3.77–3.83 (0m, 2H,
H-5, H-6b), 3.91 (ddd, JZ4.9, 9.8, 10.2 Hz, 1H, H-5 ), 4.01
(dd, JZ8.9, 9.7 Hz, 1H, H-3), 4.20 (dd, JZ4.9, 10.3 Hz,
1H, H-60eq), 4.59 (d, JZ3.5 Hz, 1H, H-1), 4.63 (d, JZ
11.2 Hz, 1H, OCHPh), 4.65 (d, JZ12.0 Hz, 1H, OCHPh),
4.77 (d, JZ12.0 Hz, 1H, OCHPh), 4.82 (d, JZ11.0 Hz, 1H,
OCHPh), 4.95 (d, JZ11.2 Hz, 1H, OCHPh), 4.99 (d, JZ
11.0 Hz, 1H, OCHPh), 5.02 (d, JZ3.6 Hz, 1H, H-10), 5.48
(s, 1H, CHPh), 5.53 (dd, JZ9.5, 10.4 Hz, 1H, H-30), 7.26–
7.36 (m, 18H, Ar-H), 7.42 (m, 2H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 20.9, 55.3, 61.8, 62.7, 66.9, 68.7, 68.8,
69.9, 73.5, 75.1, 75.7, 77.5, 79.5, 80.0, 82.1, 98.1 (C-1), 99.1
(C-10), 101.7, 127.5, 127.86, 127.87, 127.93, 128.1, 128.2,
128.37, 128.43, 128.5, 129.1, 136.9, 138.1, 138.8, 169.7;
FAB-HRMS m/z calcd for C43H47N3O11Na (MCNa)C
804.3109, found 804.3134.
4.6. Glycosidations of 2-azido-4,6-O-benzylidene-2-
deoxyglycosyl diphenyl phosphates 2c and 4c
4.6.1. Methyl 6-O-(3-O-acetyl-2-azido-4,6-O-benzyl-
idene-2-deoxy-D-glucopyranosyl)-2,3,4-tri-O-benzyl-a-
D-glucopyranoside (35). The glycosidation was performed
according to the typical procedure (1.5 mL EtCN, K45 8C,
4 h) employing diphenyl phosphate 2c (56.7 mg,
0.10 mmol), alcohol 7 (51.1 mg, 0.11 mmol), and TMSOTf
(1.0 M in CH2Cl2, 0.15 mL, 0.15 mmol). A mixture of
disaccharide 35 and imidate 36 (80.3 mg) was obtained as a
colorless oil from the crude product (104.6 mg) after short
column chromatography (silica gel 3 g, 3:1 hexane/AcOEt
with 1% Et3N). The anomeric ratio of the products was
determined by HPLC analysis [eluent, 4:1 hexane/AcOEt;
flow rate, 1.0 mL/min; tR (36a)Z17.4 min, tR (35b)Z
21.5 min, tR (36b)Z25.4 min, tR (35a)Z30.6 min]. The
mixture was purified by flash column chromatography
(silica gel 8 g, 5:1 hexane/AcOEt with 1% Et3N) to give
a-imidate 36 (70.4 mg, 84%) as a white amorphous, along
with an anomeric mixture of disaccharide 35 (5.0 mg, 6%,
a:bZ8:92) as a white solid. The a- and b-glycosides of
disaccharide 35 were separated by flash column chroma-
tography with 6:1 hexane/AcOEt. Data for b-anomer (35b):
TLC RfZ0.38 (2:1 hexane/AcOEt); mp 149.0–149.5 8C
(colorless needles from AcOEt–hexane); [a]2D3ZK35.58 (c
1.01, CHCl3); IR (film) 2928, 2112, 1753, 1454, 1369, 1222,
Data for methyl 6-O-[1-(3-O-acetyl-2-azido-4,6-O-benzyl-
idene-2-deoxy-a-D-glucopyranosyl)iminopropyl]-2,3,4-tri-
O-benzyl-a-D-glucopyranoside (36a): TLC RfZ0.40 (2:1
hexane/AcOEt); [a]2D0ZC81.08 (c 2.30, CHCl3); IR (film)
2926, 2106, 1753, 1660, 1454, 1369, 1224, 1095 cmK1; 1H
NMR (500 MHz, CDCl3) d 1.14 (t, JZ7.6 Hz, 3H,
CH2CH3), 2.15 (s, 3H, CH3CO), 2.35 (q, JZ7.6 Hz, 2H,
CH2CH3), 3.397 (dd, JZ4.2, 10.0 Hz, 1H, H-20), 3.399 (s,
3H, OCH3), 3.52 (dd, JZ3.6, 9.7 Hz, 1H, H-2), 3.63 (dd,
JZ8.8, 10.5 Hz, 1H, H-4), 3.64–3.70 (m, 2H, H-40, H-60ax),
3.88 (ddd, JZ1.6, 4.1, 10.5 Hz, 1H, H-5), 4.00 (dd, JZ8.8,
9.7 Hz, 1H, H-3), 4.14–4.20 (m, 2H, H-50, H-60eq), 4.23 (dd,
JZ4.1, 12.3 Hz, 1H, H-6a), 4.53 (dd, JZ1.6, 12.3 Hz, 1H,
H-6b), 4.617 (d, JZ10.5 Hz, 1H, OCHPh), 4.619 (d, JZ
12.1 Hz, 1H, OCHPh), 4.64 (d, JZ3.6 Hz, 1H, H-1), 4.74

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10733
(d, JZ12.1 Hz, 1H, OCHPh), 4.83 (d, JZ10.8 Hz, 1H,
OCHPh), 4.84 (d, JZ10.5 Hz, 1H, OCHPh), 4.97 (d, JZ
10.8 Hz, 1H, OCHPh), 5.21 (d, JZ4.2 Hz, 1H, H-100), 5.52
(s, 1H, CHPh), 5.76 (dd, JZ9.5, 10.0 Hz, 1H, H-3 ), 7.23
(m, 1H, Ar-H), 7.25–7.36 (m, 17H, Ar-H), 7.44 (m, 2H,
Ar-H); 13C NMR (126 MHz, CDCl3) d 10.7, 20.9, 23.0,
55.2, 62.7, 63.3, 64.4, 68.9, 69.2, 69.8, 73.2, 75.2, 75.8,
77.6, 80.1, 80.3, 82.1, 84.1 (C-10), 97.9 (C-1), 101.5, 126.1,
127.6, 127.79, 127.83, 128.0, 128.1, 128.2, 128.38, 128.40,
128.5, 129.0, 137.1, 138.0, 138.2, 138.7, 169.7, 170.4; FAB-
HRMS m/z calcd for C46H53N4O11 (MCH)C 837.3711,
found 837.3727; Anal. calcd for: C46H52N4O11: C, 66.02; H,
6.26; N, 6.69, found C, 65.90; H, 6.27; N, 6.66.
11.0 Hz, 1H, H-20), 4.01 (t, JZ9.2 Hz, 1H, H-3), 4.13 (0d,
JZ12.5 Hz, 1H, OCHPh), 4.38 (d, JZ3.1 Hz, 1H, H-4 ),
4.59 (d, JZ3.6 Hz, 1H, H-1), 4.60 (d, JZ11.6 Hz, 1H,
OCHPh), 4.66 (d, JZ12.0 Hz, 1H, OCHPh), 4.79 (d, JZ
12.0 Hz, 1H, OCHPh), 4.81 (d, JZ10.9 Hz, 1H, OCHPh),
4.96 (d, JZ11.6 Hz, 1H, OCHPh), 4.990(d, JZ10.9 Hz, 1H,
OCHPh), 5.12 (d, JZ3.1 Hz, 1H, H-1 ), 5.22 (dd, JZ3.1,
11.0 Hz, 1H, H-30), 5.47 (s, 1H, CHPh), 7.27–7.36 (m, 18H,
Ar-H), 7.47 (m, 2H, Ar-H); 13C NMR (126 MHz, CDCl3) d
20.9, 55.1, 57.2, 62.3, 66.6, 69.0, 69.3, 69.9, 73.3, 73.4,
74.8, 75.7, 77.8, 80.0, 82.0, 98.0 (C-1), 98.6 (C-10), 100.7,
126.1, 127.56, 127.63, 127.9, 128.0, 128.07, 128.14, 128.3,
128.4, 129.0, 137.5, 138.1, 138.4, 138.7, 170.5; FAB-
HRMS m/z calcd for C43H47N3O11Na (MCNa)C 804.3108,
found 804.3093.
4.6.2. Methyl 6-O-(3-O-acetyl-2-azido-4,6-O-benzyl-
idene-2-deoxy-D-galactopyranosyl)-2,3,4-tri-O-benzyl-a-
D-glucopyranoside (37).9 The glycosidation was performed
according to the typical procedure (1.5 mL EtCN, K78 8C,
3 h) employing diphenyl phosphate 4c (56.7 mg,
0.10 mmol), alcohol 7 (51.1 mg, 0.11 mmol), and TMSOTf
(1.0 M in CH2Cl2, 0.15 mL, 0.15 mmol). An anomeric
mixture of disaccharide 37 (60.6 mg, 78%, a:bZ3:97) was
obtained as a white solid from the crude product (98.4 mg)
after column chromatography (silica gel 6 g, 40:1/30:1
CH2Cl2/AcOEt with 0.5% Et3N), along with a-imidate 38
(8.5 mg, 10%) as a colorless oil. The anomeric ratio of the
product was determined by HPLC analysis [eluent, 4:1
hexane/AcOEt; flow rate, 1.0 mL/min; tR (a-anomer)Z
29.5 min, tR (b-anomer)Z79.6 min]. The a- and b-glyco-
sides were separated by flash column chromatography with
4:1 hexane/AcOEt. Data for b-anomer (37b):9 TLC RfZ
0.20 (2:1 hexane/AcOEt), 0.40 (10:1 CH2Cl2/AcOEt); mp
149.0–150.0 8C (colorless fine needles from AcOEt–
hexane); [a]2D3ZC31.18 (c 1.01, CHCl3); IR (KBr) 3032,
2918, 2114, 1745, 1454, 1367, 1246, 1059 cmK1; 1H NMR
(500 MHz, CDCl3) d 2.14 (s, 3H, CH3CO), 3.37 (brs, 1H,
H-50), 3.39 (s, 3H, OCH3), 3.53 (dd, JZ8.2, 10.1 Hz, 1H,
H-4), 3.55 (dd, JZ3.6, 9.7 Hz, 1H, H-2), 3.71 (dd, JZ5.1,
11.1 Hz, 1H, H-6a), 3.85 (ddd, JZ1.7, 5.1, 10.1 Hz, 1H,
H-5), 3.95 (dd, JZ8.0, 10.7 Hz, 1H, H-20), 3.99–4.02 (m,
2H, H-3, H-60a), 4.16 (dd, JZ1.7, 11.1 Hz, 1H, H-6b), 40.23
(d, JZ8.0 Hz, 1H, H-10), 4.27–4.29 (m, 2H, H-40, H-6 b),
4.62 (d, JZ3.6 Hz, 1H, H-1), 4.64 (d, JZ11.1 Hz, 1H,
OCHPh), 4.65 (d, JZ12.1 Hz, 1H, OCHPh), 4.68 (dd, JZ
3.5, 10.7 Hz, 1H, H-30), 4.78 (d, JZ12.1 Hz, 1H, OCHPh),
4.82 (d, JZ11.0 Hz, 1H, OCHPh), 4.93 (d, JZ11.1 Hz, 1H,
OCHPh), 4.99 (d, JZ11.0 Hz, 1H, OCHPh), 5.48 (s, 1H,
CHPh), 7.25–7.38 (m, 18H, Ar-H), 7.47 (m, 2H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 20.9, 55.3, 60.3, 66.3, 68.6,
68.8, 69.9, 72.5, 72.6, 73.4, 74.9, 75.7, 77.9, 79.9, 82.1, 98.1
(C-1), 100.9, 102.5 (C-10), 126.2, 127.6, 127.7, 127.8, 127.9,
128.0, 128.1, 128.2, 128.36, 128.44, 129.1, 137.5, 138.1,
138.4, 138.8, 170.5; FAB-HRMS m/z calcd for
C43H47N3O11Na (MCNa)C 804.3108, found 804.3094;
Anal. calcd for: C43H47N3O11: C, 66.06; H, 6.06; N, 5.37,
found C, 66.07; H, 5.92; N, 5.41. Data for a-anomer (37a):9
TLC RfZ0.34 (2:1 hexane/AcOEt), 0.53 (10:1 CH2Cl2/
AcOEt); [a]2D2ZC153.18 (c 1.00, CHCl3); IR (KBr) 3032,
Data for methyl 6-O-[1-(3-O-acetyl-2-azido-4,6-O-benzyl-
idene-2-deoxy-a-D-galactopyranosyl)iminopropyl]-2,3,4-
tri-O-benzyl-a-D-glucopyranoside (38): TLC RfZ0.34 (2:1
hexane/AcOEt); [a]2D2ZC104.28 (c 0.31, CHCl3); IR (film)
3032, 2908, 2108, 1743, 1662, 1454, 1373, 1228, 1095 cmK1
;
1H NMR (500 MHz, CDCl3) d 1.14 (t, JZ7.6 Hz, 3H,
CH2CH3), 2.15 (s, 3H, CH3CO), 2.36 (q, JZ7.6 Hz, 2H,
CH2CH3), 3.39 (s, 3H, OCH3), 3.55 (dd, JZ3.6, 9.6 Hz, 1H,
H-2), 3.59 (dd, JZ8.9, 10.1 Hz, 1H, H-4), 3.807 (ddd, JZ
1.7, 4.5, 10.1 Hz, 1H, H-5), 3.92 (brs, 1H, H-5 ), 3.94 (dd,
JZ1.6, 12.6 Hz, 1H, H-60a), 4.01 (dd, JZ8.9, 9.6 Hz, 1H,
H-3), 4.09 (dd, JZ4.0, 10.9 Hz, 1H, H-20), 4.12 (dd, JZ1.5,
12.6 Hz, 1H, H-60b), 4.20 (dd, JZ4.5, 12.2 Hz, 1H, H-6a),
4.36 (dd, JZ1.7, 12.2 Hz, 1H, H-6b), 4.43 (d, JZ3.5 Hz,
1H, H-40), 4.59 (d, JZ11.0 Hz, 1H, OCHPh), 4.60 (d, JZ
3.6 Hz, 1H, H-1), 4.67 (d, JZ12.0 Hz, 1H, OCHPh), 4.81
(d, JZ12.0 Hz, 1H, OCHPh), 4.84 (d, JZ10.8 Hz, 1H,
OCHPh), 4.86 (d, JZ11.0 Hz, 1H, OCHPh), 4.99 (d, JZ
10.8 Hz, 1H, OCHPh), 5.33 (d, JZ4.0 Hz, 1H, H-10), 5.41
(dd, JZ3.5, 10.9 Hz, 1H, H-30), 5.50 (s, 1H, CHPh), 7.26–
7.39 (m, 18H, Ar-H), 7.51 (m, 2H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 10.8, 21.1, 22.9, 55.2, 58.3, 62.9, 64.4,
68.8, 69.5, 70.7, 73.4, 73.7, 75.2, 75.9, 77.9, 80.0, 82.1, 83.6
(C-10), 98.2 (C-1), 100.8, 126.2, 127.66, 127.73, 127.9,
127.97, 128.04, 128.1, 128.2, 128.4, 128.5, 129.0, 137.7,
138.1, 138.2, 138.7, 169.4, 170.6; FAB-HRMS m/z calcd for
C46H53N4O11 (MCH)C 837.3711, found 837.3692.
4.6.3. Methyl 4-O-(3-O-acetyl-2-azido-4,6-O-benzyl-
idene-2-deoxy-D-galactopyranosyl)-2,3,6-tri-O-benzyl-a-
D-glucopyranoside (39). The glycosidation was performed
according to the typical procedure (1.5 mL EtCN, K78 8C,
3 h) employing diphenyl phosphate 4c (56.7 mg,
0.10 mmol), alcohol 8 (51.1 mg, 0.11 mmol), and TMSOTf
(1.0 M in CH2Cl2, 0.15 mL, 0.15 mmol). An anomeric
mixture of disaccharide 39 (70.1 mg, 90%, a:bZ4:96) was
obtained as a colorless oil from the crude product (97.7 mg)
after column chromatography (silica gel 6 g, 15:1 toluene/
AcOEt). The anomeric ratio of the product was determined
by HPLC analysis [eluent, 4:1 hexane/AcOEt; flow rate,
1.0 mL/min; tR (a-anomer)Z28.6 min, tR (b-anomer)Z
60.0 min]. The a- and b-glycosides were separated by flash
column chromatography with 3:1 hexane/AcOEt. Data for
b-anomer (39b): TLC RfZ0.23 (2:1 hexane/AcOEt), 0.21
(5:1 toluene/AcOEt); [a]2D7ZC24.28 (c 1.17, CHCl3); IR
(film) 3032, 2903, 2114, 1747, 1454, 1367, 1232, 1047,
2914, 2110, 1745, 1496, 1454, 1371, 1228, 1145, 1028 cmK1
;
1H NMR (500 MHz, CDCl3) d 2.14 (s, 3H, CH3CO), 3.38 (s,
3H, OCH3), 3.52–3.56 (m, 2H, H-2, H-4), 3.56 (brs, 1H,
H-50), 3.70 (m, 1H, H-6a), 3.77–3.81 (m, 2H, H-5, H-6b),
3.88 (d, JZ12.5 Hz, 1H, OCHPh), 3.90 (dd, JZ3.1,
912 cmK1 1H NMR (500 MHz, CDCl3) d 2.14 (s, 3H,
;

10734
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
CH3CO), 2.97 (brs, 1H, H-50), 3.39 (s, 3H, OCH3), 3.53 (dd,
JZ3.6, 9.4 Hz, 1H, H-2), 3.72 (dd, JZ1.6, 10.8 Hz, 1H,
H-6a), 3.78 (m, 1H, H-5), 3.81 (dd, JZ8.1, 10.7 Hz, 1H,
H-20), 3.85 (dd, JZ1.7, 12.5 Hz, 1H, H-60a), 3.92 (dd, JZ
9.0, 9.4 Hz, 1H, H-3), 3.98 (dd, JZ9.0, 9.8 Hz, 1H, H-4),
3.99 (dd, JZ2.5,0 10.8 Hz, 1H, H-6b), 4.192 (dd, JZ1.0,
12.5 Hz, 1H, H-6 b), 4.194 (d, JZ3.7 Hz, 1H, H-40), 4.25
(d, JZ8.1 Hz, 1H, H-10), 4.42 (d, JZ12.1 Hz, 1H, OCHPh),
4.47 (dd, JZ3.7, 10.7 Hz, 1H, H-30), 4.60 (d, JZ3.6 Hz,
1H, H-1), 4.63 (d, JZ12.1 Hz, 1H, OCHPh), 4.72 (d, JZ
12.1 Hz, 1H, OCHPh), 4.78 (d, JZ10.6 Hz, 1H, OCHPh),
4.81 (d, JZ12.1 Hz, 1H, OCHPh), 5.10 (d, JZ10.6 Hz, 1H,
OCHPh), 5.46 (s, 1H, CHPh), 7.17–7.22 (m, 3H, Ar-H),
7.25–7.35 (m, 13H, Ar-H), 7.45–7.47 (m, 4H, Ar-H); 13C
NMR (126 MHz, CDCl3) d 20.9, 55.3, 60.9, 66.2, 68.2,
68.6, 69.7, 72.5, 72.8, 73.4, 73.6, 75.9, 77.4, 79.2, 80.3, 98.3
(C-1), 100.9, 101.2 (C-10), 127.8, 127.9, 128.06, 128.08,
128.10, 128.11, 128.2, 128.35, 128.40, 128.5, 129.0, 137.7,
138.0, 138.4, 139.1, 170.4; FAB-HRMS m/z calcd for
C43H48N3O11 (MCH)C 782.3289, found 782.3281; Anal.
calcd for: C43H47N3O11: C, 66.06; H, 6.06; N, 5.37, found
C, 65.94; H, 6.13; N, 5.27. Data for a-anomer (39a): TLC
RfZ0.35 (2:1 hexane/AcOEt), 0.38 (5:1 toluene/AcOEt);
[a]2D4ZC99.58 (c 1.24, CHCl3); IR (film) 3032, 2908, 2110,
1743, 1496, 1454, 1369, 1228, 1143, 1101, 1039 cmK1; 1H
NMR (500 MHz, CDCl3) d 2.14 (s, 3H, CH3CO), 3.40 (s,
3H, OCH3), 3.54 (brs, 1H, H-50), 3.57 (dd, JZ3.5, 9.6 Hz,
1H, H-2), 3.61 (dd, JZ1.2, 12.6 Hz, 1H, H-60a), 3.63 (dd,
JZ1.4, 11.2 Hz, 1H, H-6a), 3.75 (dd, JZ4.2, 11.2 Hz, 1H,
H-6b), 3.80 (ddd, JZ1.4, 4.2, 9.8 Hz, 1H, H-5), 3.85 (dd,
JZ3.6, 11.2 Hz, 1H, H-20), 3.87 (brd, JZ12.6 Hz, 1H,
H-60b), 3.94 (dd, JZ8.7, 9.8 Hz, 1H, H-4), 4.08 (dd, JZ8.7,
9.6 Hz, 1H, H-3), 4.29 (d, JZ3.3 Hz, 1H, H-40), 4.53 (d, JZ
12.2 Hz, 1H, OCHPh), 4.59 (d, JZ12.2 Hz, 1H, OCHPh),
4.60 (d, JZ12.0 Hz, 1H, OCHPh), 4.61 (d, JZ3.5 Hz, 1H,
H-1), 4.73 (d, JZ12.0 Hz, 1H, OCHPh), 4.85 (d, JZ
10.9 Hz, 1H, OCHPh), 5.10 (d, JZ10.9 Hz, 1H, OCHPh),
5.20 (dd, JZ3.3, 11.2 Hz, 1H, H-30), 5.38 (s, 1H, CHPh),
5.85 (d, JZ3.6 Hz, 1H, H-10), 7.26–7.38 (m, 18H, Ar-H),
7.43 (m, 2H, Ar-H); 13C NMR (126 MHz, CDCl3) d 21.0,
55.3, 57.0, 62.7, 69.0, 69.1, 69.45, 69.48, 73.1, 73.3, 73.4,
73.5, 74.8, 80.6, 81.9, 97.8, 98.0, 100.6, 126.1, 127.3,
127.36, 127.39, 127.7, 128.0, 128.1, 128.2, 128.3, 128.48,
128.50, 129.0, 137.5, 137.9, 138.0, 138.7, 170.5; FAB-
HRMS m/z calcd for C43H48N3O11 (MCH)C 782.3289,
found 782.3306.
0.36 (1:3 hexane/AcOEt), 0.36 (3:1 toluene/acetone);
[a]2D1ZC24.28 (c 1.00, CHCl3); IR (KBr) 3514, 2870,
1
2116, 1745, 1454, 1369, 1236, 1051, 916 cmK1; H NMR
(500 MHz, CDCl3) d 2.13 (s, 3H, CH3CO), 3.03 (br, 1H,
OH), 3.40 (brs, 1H, H-5), 3.46 (brs, 1H, H-50), 3.86 (dd, JZ
3.5, 10.0 Hz, 1H, H-3), 3.99 (dd, JZ8.0, 10.8 Hz, 1H, H-20),
4.03 (dd, JZ1.5, 12.5 Hz, 1H, H-60a), 4.05 (dd, JZ1.1,
12.5 Hz, 1H, H-6a), 4.11 (dd, JZ7.8, 10.0 Hz, 1H, H-2),
4.14 (m, 1H, CHCH]CH2), 4.27 (brd, JZ12.5 Hz, 1H,
H-60b), 4.28 (d, JZ3.6 Hz, 1H, H-40), 4.31 (brd, JZ
12.5 Hz, 1H, H-6b), 4.37 (d, JZ7.8 Hz, 1H, H-1), 4.38 (d,
JZ3.5 Hz, 1H, H-4), 4.42 (m, 1H, CHCH]CH2), 4.73 (dd,
JZ3.6, 10.8 Hz, 1H, H-30), 4.98 (1H, d, JZ8.0 Hz, H-10),
5.20 (1H, dd, JZ0.9, 10.6 Hz, CH2CH]CH), 5.32 (1H, dd,
JZ1.2, 17.3 Hz, CH2CH]CH), 5.49 (s, 1H, CHPh), 5.57
(s, 1H, CHPh), 5.95 (m, 1H, CH2CH]CH2), 7.28–7.37 (m,
6H, Ar-H), 7.49 (m, 2H, Ar-H), 7.54 (m, 2H, Ar-H); 13C
NMR (100 MHz, CDCl3) d 21.0, 60.1, 66.2, 66.6, 68.9,
69.0, 69.9, 70.2, 71.9, 72.5, 75.9, 78.9, 100.5, 100.7, 101.6
(C-1), 102.0 (C-10), 117.8, 126.06, 126.09, 127.9, 128.1,
128.5, 129.0, 133.7, 137.4, 137.6, 170.3; FAB-HRMS m/z
calcd for C31H36N3O11 (MCH)C 626.2350, found
626.2353; Anal. calcd for: C31H35N3O11: C, 59.51; H,
5.64; N, 6.72, found C, 59.32; H, 5.64; N, 6.62. Data for
a-anomer (40a): TLC RfZ0.55 (1:3 hexane/AcOEt), 0.44
(3:1 toluene/acetone); [a]2D3ZC165.18 (c 0.36, CHCl3); IR
(film) 3510, 2922, 2864, 2110, 1743, 1452, 1369, 1244,
1
1049 cmK1; H NMR (500 MHz, CDCl3) d 2.14 (s, 3H,
CH3CO), 2.63 (br, 1H, OH), 3.44 (brs, 1H, H-5), 3.80 (dd,
JZ3.7, 9.8 Hz, 1H, H-3), 3.93 (dd, JZ3.4, 11.2 Hz, 1H,
H-20), 3.98 (dd, JZ7.8, 9.8 Hz, 1H, H-2), 4.04 (dd, JZ1.1,
12.6 Hz, 1H, H-60a), 4.11 (dd, JZ1.1, 12.5 Hz,0 1H, H-6a),
4.14 (m, 1H, CHCH]CH2), 4.19 (brs, 1H, H-5 ), 4.24 (dd,
JZ1.2, 12.6 Hz, 1H, H-60b), 4.32 (d, JZ3.7 Hz, 1H, H-4),
4.36 (d, JZ7.8 Hz, 1H, H-1), 4.37 (dd, JZ1.3, 12.5 Hz, 1H,
H-6b), 4.44 (dddd, JZ1.0, 1.1, 5.1, 12.7 Hz, 1H,
CHCH]CH2), 4.50 (d, JZ3.3 Hz, 1H, H-40), 5.23 (dd,
JZ1.0, 11.1 Hz, 1H, CH2CH]CH), 5.30 (d, JZ3.4 Hz,
1H, H-10), 5.32 (m, 1H, CH2CH]CH), 5.40 (dd, JZ3.3,
11.2 Hz, 1H, H-30), 5.52 (s, 1H, CHPh), 5.58 (s, 1H, CHPh),
5.96 (dddd, JZ5.1, 6.0, 11.1, 17.1 Hz, 1H, CH2CH]CH2),
7.30–7.40 (m, 6H, Ar-H), 7.49 (m, 2H, Ar-H), 7.55 (m, 2H,
Ar-H); 13C NMR (126 MHz, CDCl3) d 21.0, 56.7, 62.8,
66.7, 69.1, 69.2, 69.4, 70.0, 72.3, 73.5, 76.8, 95.8 (C-10),
100.7, 101.0, 101.9 (C-1), 118.0, 126.1, 126.2, 128.0, 128.2,
128.8, 129.1, 133.8, 137.6, 170.4; FAB-HRMS m/z calcd for
C31H36N3O11 (MCH)C 626.2350, found 626.2372.
4.6.4. Allyl 3-O-(3-O-acetyl-2-azido-4,6-O-benzylidene-
2-deoxy-D-galactopyranosyl)-4,6-O-benzylidene-b-D-
galactopyranoside (40).22b The glycosidation was per-
formed according to the typical procedure [1.55 mL EtCN–
CH2Cl2 (30:1), K78 8C, 2 h] employing diphenyl phosphate
4c (56.7 mg, 0.10 mmol), alcohol 34 (33.9 mg, 0.11 mmol),
and TMSOTf (1.0 M in CH2Cl2, 0.15 mL, 0.15 mmol). An
anomeric mixture of disaccharide 40 (50.1 mg, 80%, a:bZ
1:99) was obtained as a colorless film from the crude
product (87.4 mg) after column chromatography (silica gel
6 g, 5:1 toluene/AcOEt). The anomeric ratio of the product
was determined by HPLC analysis [eluent, 1:1.5 hexane/
AcOEt; flow rate, 1.0 mL/min; tR (a-anomer)Z9.4 min, tR
(b-anomer)Z14.6 min]. The a- and b-glycosides were
separated by flash column chromatography with 1:1
hexane/AcOEt. Data for b-anomer (40b):22b TLC RfZ
4.7. Comparative study
4.7.1. TMSOTf-catalyzed glycosidation of 2-azido-2-
deoxyglucopyranosyl trichloroacetimidate 5a with alco-
hol 8 in acetonitrile (Table 9, entry 5). The glycosidation
was performed according to the typical procedure (1.5 mL
MeCN, K40 8C, 0.3 h) employing trichloroacetimidate
5a7b (62.0 mg, 0.10 mmol), alcohol
8
0.11 mmol), TMSOTf (1.0 M in CH2Cl2, 0.015 mL,
(51.1 mg,
˚
0.015 mmol), and pulverized molecular sieves 4 A
(60 mg). An anomeric mixture of disaccharide 10
(47.2 mg, 51%, a:bZ12:88) was obtained as a white solid
from the crude product (118.5 mg) after column chroma-
tography (silica gel 6 g, 5:1 hexane/AcOEt with 1% Et3N),

T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
10735
along with b-trichloroacetamide 41 (21.7 mg, 35%) as a
white solid.
deoxygalactopyranosyl trichloroacetimidate 43a with
alcohol 8 in propionitrile (Table 11, entry 1). The
glycosidation was performed according to the typical
procedure (1.5 mL EtCN, K78 8C, 0.1 h) employing
trichloroacetimidate 43a7a (62.0 mg, 0.10 mmol), alcohol
8 (51.1 mg, 0.11 mmol), TMSOTf (1.0 M in CH2Cl2,
0.15 mL, 0.15 mmol), and pulverized molecular sieves
Data for N-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-b-D-gluco-
pyranosyl)trichloroacetamide (41):26b TLC RfZ0.59 (2:1
hexane/AcOEt); mp 129.5–131.0 8C (colorless needles from
Et2O–hexane); [a]2D3ZK3.798 (c 1.00, CHCl3); IR (KBr)
3360, 3032, 2893, 2108, 1699, 1520, 1454, 1363, 1277,
1128, 1060 cmK1; 1H NMR (500 MHz, CDCl3) d 3.46 (dd,
JZ9.4, 9.6 Hz, 1H, H-2), 3.54 (ddd, JZ1.8, 2.9, 10.2 Hz,
1H, H-5), 3.62 (dd, JZ8.9, 9.6 Hz, 1H, H-3), 3.71 (dd, JZ
1.8, 11.0 Hz, 1H, H-6a), 3.75 (dd, JZ2.9, 11.0 Hz, 1H,
H-6b), 3.79 (dd, JZ8.9, 10.2 Hz, 1H, H-4), 4.49 (d, JZ
12.1 Hz, 1H, OCHPh), 4.56 (d, JZ10.9 Hz, 1H, OCHPh),
4.60 (d, JZ12.1 Hz, 1H, OCHPh), 4.80 (d, JZ10.9 Hz, 1H,
OCHPh), 4.88 (s, 2H, OCH2Ph), 4.97 (dd, JZ9.3, 9.4 Hz,
1H, H-1), 7.08 (d, JZ9.3 Hz, 1H, NH), 7.15 (m, 2H, Ar-H),
7.25–7.35 (m, 13H, Ar-H); 13C NMR (126 MHz, CDCl3) d
65.8, 67.8, 73.6, 75.0, 75.7, 77.0, 77.2, 80.4 (C-1), 83.8,
92.0, 127.7, 127.89, 127.90, 128.0, 128.05, 128.14, 128.45,
128.51, 137.4, 137.5, 137.7, 161.7; FAB-HRMS m/z calcd
for C29H30N4O5Cl3 (MCH)C 619.1282, found 619.1271;
Anal. calcd for: C29H29N4O5Cl3: C, 56.19; H, 4.72; N, 9.04,
found C, 56.04; H, 4.62; N, 8.89.
˚
4 A (60 mg). An anomeric mixture of disaccharide 27
(43.8 mg, 48%, a:bZ4:96) was obtained as a white solid
from the crude product (123.4 mg) after column chroma-
tography (silica gel 6 g, 5:1 hexane/AcOEt with 1% Et3N),
along with b-trichloroacetamide 44 (23.0 mg, 37%) and
a-amidine 45 (4.5 mg, 7%) as colorless oils.
Data for N-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-b-D-galac-
topyranosyl)trichloroacetamide (44): TLC RfZ0.59 (2:1
hexane/AcOEt); [a]2D4ZC21.18 (c 1.20, CHCl3); IR (film)
3323, 3032, 2872, 2114, 1724, 1520, 1454, 1361, 1286,
1
1101 cmK1; H NMR (500 MHz, CDCl3) d 3.56 (dd, JZ
2.8, 9.8 Hz, 1H, H-3), 3.56–3.61 (m, 2H, H-6a, H-6b), 3.68
(t, JZ6.6 Hz, 1H, H-5), 3.86 (dd, JZ9.5, 9.8 Hz, 1H, H-2),
4.00 (brd, JZ2.8 Hz, 1H, H-4), 4.43 (d, JZ11.8 Hz, 1H,
OCHPh), 4.47 (d, JZ11.8 Hz, 1H, OCHPh), 4.57 (d, JZ
11.1 Hz, 1H, OCHPh), 4.69 (d, JZ11.6 Hz, 1H, OCHPh),
4.74 (d, JZ11.6 Hz, 1H, OCHPh), 4.87 (d, JZ11.1 Hz, 1H,
OCHPh), 4.91 (dd, JZ9.3, 9.5 Hz, 1H, H-1), 7.07 (d, JZ
9.3 Hz, 1H, NH), 7.27–7.40 (m, 15H, Ar-H); 13C NMR
(126 MHz, CDCl3) d 62.5, 67.7, 71.9, 72.4, 73.5, 75.0, 75.5,
80.4 (C-1), 81.6, 92.0, 127.87, 127.92, 128.1, 128.3, 128.35,
128.44, 128.5, 137.1, 137.5, 137.9, 161.6; FAB-HRMS m/z
calcd for C29H30N4O5Cl3 (MCH)C 619.1282, found
619.1276; Anal. calcd for: C29H29N4O5Cl3: C, 56.19; H,
4.72; N, 9.04, found C, 55.98; H, 4.69; N, 8.93.
4.7.2. TMSOTf-promoted glycosidation of 2-azido-2-
deoxyglucopyranosyl trichloroacetimidate 5a with alco-
hol 8 in propionitrile (Table 10, entry 3). The glycosida-
tion was performed according to the typical procedure
(1.5 mL EtCN, K78 8C, 0.3 h) employing trichloroacetimi-
date 5a7b (62.0 mg, 0.10 mmol), alcohol 8 (51.1 mg,
0.11 mmol), TMSOTf (1.0 M in CH2Cl2, 0.15 mL,
˚
0.15 mmol), and pulverized molecular sieves 4 A (60 mg).
An anomeric mixture of disaccharide 10 (49.6 mg, 54%,
a:bZ7:93) was obtained as a colorless oil from the crude
product (125.4 mg) after column chromatography (silica
gel 6 g, 5:1 hexane/AcOEt with 1% Et3N), along with
a-amidine 42 (13.6 mg, 20%) as a colorless oil.
Data for N-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-D-galac-
topyranosyl)-N-(2,2,2-trichloro-1-iminoethyl)propionamide
(45): TLC RfZ0.43 (2:1 hexane/AcOEt); [a]2D0ZC4.328 (c
1.05, CHCl3); IR (film) 3342, 3032, 2874, 2118, 1637, 1574,
1454, 1367, 1211, 1080 cmK1; 1H NMR (500 MHz, CDCl3)
d 1.22 (t, JZ7.5 Hz, 3H, CH2CH3), 2.55 (dq, JZ15.3,
7.5 Hz, 1H, CHCH3), 2.59 (dq, JZ15.3, 7.5 Hz, 1H,
CHCH3), 3.50 (dd, JZ6.1, 9.2 Hz, 1H, H-6a), 3.56 (dd,
JZ7.1, 9.2 Hz, 1H, H-6b), 3.76–3.79 (m, 2H, H-3, H-5),
4.02 (brs, 1H, H-4), 4.34 (dd, JZ5.1, 10.5 Hz, 1H, H-2),
4.40 (d, JZ11.7 Hz, 1H, OCHPh), 4.45 (d, JZ11.7 Hz, 1H,
OCHPh), 4.51 (d, JZ11.2 Hz, 1H, OCHPh), 4.77 (d, JZ
10.6 Hz, 1H, OCHPh), 4.79 (d, JZ10.6 Hz, 1H, OCHPh),
4.57 (d, JZ11.2 Hz, 1H, OCHPh), 5.44 (d, JZ5.1 Hz, 1H,
H-1), 7.24–7.42 (m, 15H, Ar-H), 11.0 (br, 1H, NH); 13C
NMR (126 MHz, CDCl3) d 10.5, 26.9, 58.2, 68.2, 70.8,
72.5, 72.7, 73.6, 75.0, 78.8, 79.0, 95.9, 127.85, 127.91,
128.0, 128.1, 128.2, 128.4, 128.5, 128.6, 136.8, 137.4,
137.9, 174.4, 180.1; ESI-HRMS m/z calcd for C32H34N5-
O5Cl3Na (MCNa)C 696.1523, found 696.1537.
Data for N-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-D-gluco-
pyranosyl)-N-(2,2,2-trichloro-1-iminoethyl)propionamide
(42): TLC RfZ0.50 (2:1 hexane/AcOEt); [a]2D2ZK11.48 (c
1.61, CHCl3); IR (CHCl3) 3020, 2926, 2868, 2118, 1635,
1
1577, 1221, 1070 cmK1; H NMR (500 MHz, CDCl3) d
1.25 (dd, JZ7.4, 7.5 Hz, 3H, CH2CH3), 2.61 (m, 2H,
CH2CH3), 3.61 (brd, JZ10.8 Hz, 1H, H-6a), 3.66 (m, 1H,
H-5), 3.76 (dd, JZ3.4, 10.8 Hz, 1H, H-6b), 3.79 (dd, JZ
8.2, 9.4 Hz, 1H, H-4), 3.82 (dd, JZ8.2, 9.5 Hz, 1H, H-3),
3.89 (dd, JZ4.9, 9.5 Hz, 1H, H-2), 4.47 (d, JZ12.0 Hz, 1H,
OCHPh), 4.54 (d, JZ10.9 Hz, 1H, OCHPh), 4.59 (d, JZ
12.0 Hz, 1H, OCHPh), 4.80 (d, JZ10.9 Hz, 1H, OCHPh),
4.92 (d, JZ10.3 Hz, 1H, OCHPh), 4.94 (d, JZ10.3 Hz, 1H,
OCHPh), 5.46 (d, JZ4.9 Hz, 1H, H-1), 7.16 (m, 2H, Ar-H),
7.26–7.36 (m, 13H, Ar-H), 11.0 (br, 1H, NH); 13C NMR
(126 MHz, CDCl3) d 10.6, 26.9, 62.0, 68.0, 72.0, 73.6, 75.1,
76.1, 77.6, 78.8, 81.3, 95.8, 127.7, 127.86, 127.91, 128.0,
128.1, 128.2, 128.45, 128.50, 128.6, 137.2, 137.4, 137.5,
174.5, 179.8; FAB-HRMS m/z calcd for C32H35N5O5Cl3
(MCH)C 674.1704, found 674.1691; Anal. calcd for:
C32H34N5O5Cl3: C, 56.94; H, 5.08; N, 10.39; Cl, 15.76,
found: C, 57.34; H, 5.18; N, 10.31; Cl, 15.41.
Acknowledgements
This research was supported in part by a Grant-in-Aid for
Scientific Research on Priority Areas (A) ‘Exploitation
of Multi-Element Cyclic Molecules’ from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
T.T. is grateful to JSPS for a graduate fellowship. We thank
4.7.3. TMSOTf-promoted glycosidation of 2-azido-2-

10736
T. Tsuda et al. / Tetrahedron 60 (2004) 10711–10737
694–696. In this paper it was demonstrated that b-selectivities
are practically independent of the anomeric configuration of
the starting trichloroacetimidates.
Ms. H. Matsumoto, A. Maeda, S. Oka, and M. Kiuchi of the
Center for Instrumental Analysis, Hokkaido University, for
technical assistance in MS and elemental analysis.
9. Marra, A.; Gauffeny, F.; Sinay¨, P. Tetrahedron 1991, 47,
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