Trimethylsilyl trifluoromethanesulfonate catalyzed nucleophilic substitution to give C- and N-glucopyranosides derived from d-glucopyranose

Article abstract of DOI:10.1055/s-2007-983882

This paper describes the synthesis of C- and N-glucopyranosides via trimethylsilyl trifluoromethanesulfonate catalyzed nucleophilic substitution of glucopyranosides, derived from D-glucopyranose, with methyl, ethyl, n-butyl, allyl, benzyl, and phenyl grou

Full text of DOI:10.1055/s-2007-983882

PAPER
3021
Trimethylsilyl Trifluoromethanesulfonate Catalyzed Nucleophilic Substitu-
tion To Give C- and N-Glucopyranosides Derived from D-Glucopyranose
T
rifluoromethanes
o
ulfonate-Cat
s
alyzed Nu
h
cleophilic Su
i
bstitut
k
ion To Give
iC- and N-Glu
O
c
opyranosides da, Takashi Yamanoi*
The Noguchi Institute, 1-8-1 Kaga, Itabashi-ku, Tokyo 173-0003, Japan
E-mail: tyama@noguchi.or.jp
Received 10 May 2007; revised 12 July 2007
Among these glucopyranose derivatives, the glucopy-
ranosyl acetates, which could be effectively activated by
catalytic scandium trifluoromethanesulfonate, worked as
highly reactive glucopyranosyl donors.
Abstract: This paper describes the synthesis of C- and N-glucopy-
ranosides via trimethylsilyl trifluoromethanesulfonate catalyzed
nucleophilic substitution of glucopyranosides, derived from D-glu-
copyranose, with methyl, ethyl, n-butyl, allyl, benzyl, and phenyl
groups at the anomeric carbon centers. Generally, the reactions us-
ing allyltrimethylsilane, trimethylsilyl azide, trimethylsilyl cyanide,
and 1-phenyl-1-(trimethylsiloxy)ethene as the nucleophiles in the
presence of 20 mol% trimethylsilyl trifluoromethanesulfonate in
acetonitrile at –40 °C smoothly proceeded with a-stereoselectivity
to afford various C- and N-glucopyranosides in 78–99% yield. Al-
though a decrease in the synthetic yields was observed for some re-
actions using glucopyranoses with allyl and benzyl groups at the
anomeric carbon, the yields could be improved using glucopyrano-
syl acetates in the presence of 20 mol% trimethylsilyl trifluoro-
methanesulfonate in acetonitrile–dichloromethane (1:1) at –78 °C.
For C-glycosidation, our preliminary letter described the
synthesis of C-glucopyranosides by the C-allylation of the
corresponding glucopyranoses.6 The reaction performed
with allyltrimethylsilane as nucleophile in the presence of
trimethylsilyl trifluoromethanesulfonate (TMSOTf) in
acetonitrile afforded the C-allylated glucopyranosides. To
the best of our knowledge, this is the first synthetic ap-
proach to give various kinds of C-allylated glucopyrano-
sides (C,C-dialkyl-D-glucopyranosides). After our C-
allylation method was published, Gomez et al. reported a
similar glycosidation of ketoses derived from D-glucopy-
ranose using several C- and N-nucleophiles.4b
Key words: glycosides, nucleophilic substitutions, D-glucopyran-
ose, trifluoromethanesulfonate catalysis, trimethylsilylated nucleo-
philes
During our investigation into the C-allylation, we found
that glucopyranoses with b,g-unsaturated allyl or benzyl
groups at the anomeric center showed different reactivity
from those derivatives containing other alkyl groups.7 The
C-allylation of the allyl or benzyl derivatives did not pro-
duce the glucopyranosides in satisfactory yields and
byproducts were observed. Therefore, it was necessary to
further investigate the glycosidation of these glucopy-
ranoses with various nucleophiles and to develop a more
useful C-glycosidation method. Such a development has
great significance because it can contribute to the synthe-
sis of various kinds of glucopyranosides, which are not
only useful chiral building blocks for constructing natural
products, but also attractive precursors for designing and
synthesizing novel glycosidase inhibitors.
The study of glycosides has become very significant in the
fields of carbohydrate chemistry and biochemistry.1 Gly-
cosides containing a C-glycosidic bond exist in some sub-
units of naturally occurring products, and are also
potentially useful as chiral intermediates in organic chem-
istry.2 Therefore, considerable effort is currently devoted
to the development of effective synthetic methods for C-
glycosides which involve carbon–carbon bond formation
at the anomeric centers of the carbohydrates.
The addition of an organometallic reagent (e.g., RLi or
RMgX) to sugar lactones readily produces a novel class of
various artificial ketoses.3 The effective C- or O-glycosi-
dations of the artificial ketoses to synthesize biologically
and chemically important glycosides have been studied by
some research groups.4
Therefore, we studied the glycosidation methods for syn-
thesizing various C- and N-glucopyranosides. In this
paper, we describe the C- and N-glycosidations of gluco-
pyranoses, derived from D-glucopyranose, with methyl,
ethyl, n-butyl, allyl, benzyl, and phenyl groups at the ano-
meric carbon using several trimethylsilylated nucleo-
philes in the presence of TMSOTf.
Our recent studies showed the O-glycosidation of benzyl-
protected glucopyranoses, derived from D-glucopyranose,
containing different alkyl groups (e.g., methyl, ethyl, n-
butyl, and benzyl groups) at the anomeric carbon position.
We also reported O-glycosidation methods for producing
various kinds of glucopyranosides from the correspond-
ing glucopyranose derivatives with dimethylphosphi-
nothioyloxy, acetoxy, or hydroxy functions as the leaving
groups in the presence of a Lewis or Brønsted acid.5
2,3,4,6-Tetra-O-benzyl-1-C-methyl-a-D-glucopyranose
(1a), 2,3,4,6-tetra-O-benzyl-1-C-ethyl-a-D-glucopyran-
ose (1b),8 2,3,4,6-tetra-O-benzyl-1-C-n-butyl-a-D-glu-
copyranose (1c), 1-C-allyl-2,3,4,6-tetra-O-benzyl-a-D-
glucopyranose (1d),9 1-C-benzyl-2,3,4,6-tetra-O-benzyl-
a-D-glucopyranose (1e),9 and 2,3,4,6-tetra-O-benzyl-1-C-
phenyl-a-D-glucopyranose (1f)10 were used as the D-glu-
copyranose derivatives (Figure 1). The glucopyranoses
could be prepared in 86–98% yield by the addition of the
SYNTHESIS 2007, No. 19, pp 3021–3031
x
x.
x
x
.
2
0
0
7
Advanced online publication: 11.09.2007
DOI: 10.1055/s-2007-983882; Art ID: F08307SS
© Georg Thieme Verlag Stuttgart · New York

3022
Y. Oda, T. Yamanoi
PAPER
organometallic reagent (RLi or RMgX) to 2,3,4,6-tetra-O- also effective for the C-allylation of 1b, 1c, and 1f, con-
benzyl-D-glucono-1,5-lactone.
taining normal alkyl and phenyl groups at the anomeric
center, to afford the C-allylated glucopyranosides 3b, 3c,
and 3f in 88–95% yield (entries 8, 9, and 12, respectively).
Under the same reaction conditions, however, glucopyra-
noses 1d and 1e did not produce the corresponding C-glu-
copyranosides 3d and 3e in satisfactory yields and the
benzyl glycosides 4d and 4e (Figure 2), respectively, were
still produced as major byproducts. It appeared that the
electronic or steric effects of the functional groups at the
anomeric centers of 1d and 1e influenced the leaving abil-
ity of the hemiacetal hydroxy group and the production of
4d and 4e.
BnO
BnO
R1
OH
O
BnO
BnO
R1 = Me; 1a
Et; 1b
n-Bu; 1c
All; 1d
Bn; 1e
Ph; 1f
Figure 1
BnO
BnO
BnO
BnO
R1
OBn
O
O
As previously reported, the C-allylation of 1a with allyl-
trimethylsilane in the presence of TMSOTf produced ben-
zyl 2,3,4,6-tetra-O-benzyl-1-C-methyl-a-D-glucopyran-
oside (2a)11 (Figure 2) as a major byproduct along with
the desired C-allylated glucopyranoside 3a (Scheme 1).
This was attributed to benzyl alcohol, produced with the
degradation of 1a under the given reaction conditions, act-
ing as a glycosyl acceptor of 1a to afford the glycoside 2a.
Therefore, we investigated the effects of different sol-
vents, temperatures, and amounts of reagents on the C-al-
lylation reaction using 1a in the presence of the drying
agent, calcium sulfate. We found that the reaction condi-
tions using three equivalents of allyltrimethylsilane in ace-
tonitrile at –40 °C in the presence of 20 mol% TMSOTf
smoothly produced 3a in 88% yield with almost no forma-
tion of 2a (Table 1, entry 7). The reaction conditions were
BnO
BnO
BnO
BnO
R1 = Me; 2a
8
All; 4d
Bn; 4e
Figure 2
We then investigated the reactions of glucopyranoses 1a–f
with various kinds of trimethylsilylated nucleophiles, i.e.
trimethylsilyl azide, trimethylsilyl cyanide, and 1-phenyl-
1-(trimethylsiloxy)ethene, under similar reaction condi-
tions in order to demonstrate the synthesis of various
kinds of C- and N-glucopyranosides (Scheme 1, Table 1).
All the reactions of 1a–c and 1f with these nucleophiles (3
BnO
BnO
BnO
R1
R1
O
O
BnO
BnO
BnO
cat. TMSOTf
BnO
+
C- or N-nucleophile
solvent, CaSO4
2
BnO
Nu
OR
1a–f; R2 = H
9d,e; R2 = Ac
C- or N-glucopyranoside (3, 5–7)
OTMS
Ph
,
TMSN3,
TMSCN,
C- or N-nucleophile =
TMS
BnO
BnO
BnO
BnO
BnO
BnO
BnO
R1
N3
R1
R1
BnO
BnO
O
R1
O
O
O
BnO
glucopyranoside =
BnO
BnO
BnO
BnO
BnO
BnO
CN
O
Ph
R1 = Me; 3a
Et; 3b
R1 = Me; 5a
Et; 5b
R1 = Me; 6a
Et; 6b
R1 = Me; 7a
Et; 7b
n-Bu; 7c
All; 7d
n-Bu; 3c
All; 3d
n-Bu; 5c
All; 5d
n-Bu; 6c
All; 6d
Bn; 3e
Bn; 5e
Bn; 6e
Bn; 7e
Ph; 3f
Ph; 5f
Ph; 7f
Scheme 1
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

PAPER
Trifluoromethanesulfonate-Catalyzed Nucleophilic Substitution To Give C- and N-Glucopyranosides
3023
equiv) in acetonitrile at –40 °C in the presence of 20 mol% 7d and 7e, respectively, in 53–73% yields. The differ-
TMSOTf successfully produced the desired glucopyrano- ences in the nucleophilic species significantly influenced
sides (i.e., 5a–c and 5f, 6a–c, and 7a–c and 7f) in 78–99% the yields of these glucopyranosides. In general, the yields
yields. For the corresponding reactions of 1d and 1e, us- of the C- and N-glucopyranosides were lower for the reac-
ing trimethylsilyl azide afforded 5d and 5e both in 80% tions using 1d and 1e than for those using 1a–c and 1f.
yield, while the reactions using trimethylsilyl cyanide and This was a similar result to that obtained for the reactions
1-phenyl-1-(trimethylsiloxy)ethene gave 6d and 6e and using allyltrimethylsilane, as mentioned above.
Table 1 Reactions of Glucopyranoses 1 or Glucopyranosyl Acetates 9 with Various C- or N-Nucleophiles in the Presence of Trimethylsilyl
Trifluoromethanesulfonate
Entrya
1b
Substrate
1a
1a
1a
1a
1a
1a
1a
1b
1c
Nucleophile
Solvent
CH2Cl2
Et2O
Temp (°C)
–10
–10
–10
–10
–20
–40
–40
–40
–40
–40
–40
–40
–78
–78
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
Product
3a
3a
3a
3a
3a
3a
3a
3b
3c
Yield (%)
49 (30)c
trace (25)c
67 (15)c
76 (9)c
79 (7)c
84 (3)c
88
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSN3
2b
3b
MeCN
4d
MeCN
5d
MeCN
6d
MeCN
7
MeCN
8
MeCN
88
9
MeCN
88
10
11
12
13f
14h
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
1d
1e
MeCN
3d
3e
31 (17)e
18
MeCN
1f
MeCN
3f
95
1d
1e
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
MeCN
3d
3e
53 (16)g
78
1a
1b
1c
5a
5b
5c
99
TMSN3
MeCN
96
TMSN3
MeCN
94
1d
1e
TMSN3
MeCN
5d
5e
80
TMSN3
MeCN
80
1f
TMSN3
MeCN
5f
96
1a
1b
1c
TMSCN
MeCN
6a
6b
6c
95
TMSCN
MeCN
90
TMSCN
MeCN
92
1d
1e
TMSCN
MeCN
6d
6e
65
TMSCN
MeCN
73
1a
1b
1c
H2C=C(OTMS)Ph
H2C=C(OTMS)Ph
H2C=C(OTMS)Ph
H2C=C(OTMS)Ph
H2C=C(OTMS)Ph
MeCN
7a
7b
7c
98
MeCN
91
MeCN
87
1d
1e
MeCN
7d
7e
53
MeCN
61
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

3024
Y. Oda, T. Yamanoi
PAPER
Table 1 Reactions of Glucopyranoses 1 or Glucopyranosyl Acetates 9 with Various C- or N-Nucleophiles in the Presence of Trimethylsilyl
Trifluoromethanesulfonate (continued)
Entrya
31
Substrate
Nucleophile
Solvent
Temp (°C)
–40
Product
7f
Yield (%)
1f
H2C=C(OTMS)Ph
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSCH2CH=CH2
TMSN3
MeCN
78
32
9e
9e
9d
9d
9e
9d
9e
9d
9e
MeCN
–40
3e
66 (10)i
80
33
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
MeCN–CH2Cl2 (1:1)
–78
3e
34
–78
3d
72
35
–78
5d
94
36
TMSN3
–78
5e
91
37
TMSCN
–78
6d
95
38
TMSCN
–78
6e
86
39
H2C=C(OTMS)Ph
H2C=C(OTMS)Ph
–78
7d
93
40
–78
7e
91
a Conditions: molar ratio (glucopyranose derivative/nucleophile/TMSOTf) 1:3:0.2, 2–3 h.
b Molar ratio (glucopyranose/allyltrimethylsilane/TMSOTf) 1:2:0.1.
c The yield in parenthesis is that of byproduct 2a.
d Molar ratio (glucopyranose/allyltrimethylsilane/TMSOTf) 1:2:0.2.
e The yield in parenthesis is that of byproduct 4d.
f Molar ratio (glucopyranose/allyltrimethylsilane/TMSOTf) 1:6:0.2.
g The yield in parenthesis is that of byproduct 8.
h Molar ratio (glucopyranose/allyltrimethylsilane/TMSOTf) 1:6:0.4.
i The yield in parenthesis is that of byproduct 4e.
Our next effort was directed at improving in the yields for All the glucopyranosides were produced as single iso-
the reactions of 1d and 1e with allyltrimethylsilane mers, and their NMR spectra indicated that there were nu-
(Scheme 1). First, we attempted changing the reaction clear Overhauser effect (NOE) interactions between the
temperatures and amounts of the reagents. Although for H-1¢ (or aromatic H) and H-3 protons as shown in
the reactions using excess amounts of the reagents, the Figure 3. These observations indicated that the nucleo-
yields of 3d and 3e increased to 53 and 78% (Table 1, en- philic attack took place stereoselectively at the a-side of
tries 13 and 14), respectively, they were not satisfactory the oxocarbenium cation intermediates generated from
yields. In addition, the production of exo-glycal derivative 1a–f. The axial attack was advantageous for the direct for-
89 as a novel byproduct was observed in 16% yield for the mation of the chair conformation from the oxocarbenium
reaction of 1d (Figure 2).
cation intermediates, and it forced the original anomeric
functional groups of 1a–f to take an equatorial orientation,
which would contribute to the stabilization of the 4C1 con-
formation (Scheme 2).
In order to increase the reactivities of 1d and 1e, we trans-
formed them into the corresponding glucopyranosyl ace-
tates. Acetates 9d and 9e4c,d were obtained in 82 and 94%
yield, respectively, from the reactions of 1d and 1e with In summary, we have investigated the synthesis of various
acetic anhydride using n-butyllithium in tetrahydrofuran. kinds of C- and N-glucopyranosides by TMSOTf-cata-
Compounds 9d and 9e were expected to be highly reactive
as glycosyl donors based on our findings that glucopy-
NOE
NOE
ranose derivatives with an acetoxy leaving group were
H
BnO
BnO
BnO
H
H
H
good glycosyl donors in our O-glycosidation method. The
C-allylation of 9e with allyltrimethylsilane in the presence
of 20 mol% TMSOTf in acetonitrile at –40 °C afforded 3e
in 66% yield (Table 1, entry 32), and the reaction in ace-
tonitrile–dichloromethane (1:1) at –78 °C successfully
gave 3e in good yield (80%, entry 33). Under similar con-
ditions using the latter solvent mixture, all the reactions of
9d and 9e with allyltrimethylsilane, trimethylsilyl azide,
trimethylsilyl cyanide, and 1-phenyl-1-(trimethylsil-
oxy)ethene produced the corresponding glucopyranosides
3d and 3e, 5d and 5e, 6d and 6e, and 7d and 7e in excel-
lent yields (entries 33–40) (Scheme 1).
R'
1'
C
O
O
BnO
BnO
BnO
3
3
H
BnO
BnO
Nu
Nu
Figure 3
BnO
OBn
+
BnO
OBn
O
O
Req
OBn
BnO
R
BnO
OBn
Nu
Nu–
Scheme 2
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

PAPER
Trifluoromethanesulfonate-Catalyzed Nucleophilic Substitution To Give C- and N-Glucopyranosides
3025
1 H, H-4), 4.53–4.93 (m, 8 H, CH2Ph), 5.08–5.12 (m, 2 H,
CH2CH=CH2), 5.80–5.91 (m, 1 H, CH2CH=CH2), 7.19–7.35 (m, 20
H, Ph).
13C NMR (100 MHz, CDCl3): d = 7.2 (CH2CH3), 28.5 (CH2CH3),
34.8 (CH2CH=CH2), 69.4 (C-7), 72.4 (C-6), 73.3 (CH2Ph), 75.0
(CH2Ph), 75.6 (2 CH2Ph), 78.1 (C-2), 79.2 (C-5), 80.7 (C-3), 84.4
(C-4), 117.7 (CH2CH=CH2), 127.3–128.3 (Ph), 133.0
(CH2CH=CH2), 138.1–138.5 (Ph).
lyzed nucleophilic substitutions to glucopyranoses 1a–f
using several trimethylsilylated nucleophiles. Generally,
the C- and N-glycosidations performed in the presence of
20 mol% TMSOTf in acetonitrile at –40 °C proceeded
smoothly with a-stereoselectivity to afford the glucopyra-
nosides in excellent yields. For those reactions using 1d
and 1e, the yields of the produced glucopyranosides de-
creased. The yields of these glucopyranosides were re-
markably improved by using glucopyranosyl acetates 9d
and 9e as the substrates in the presence of 20 mol%
TMSOTf in acetonitrile–dichloromethane (1:1) at –78 °C.
HRMS (ESI): m/z [M + Na+] calcd for C39H44O5: 615.3086; found:
615.3081.
(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-butyltetrahydropyran (3c) (Table 1, Entry 9)
TMSOTf (6.9 mL, 0.038 mmol) was added to a solution of 1c (112.7
mg, 0.19 mmol) and allyltrimethylsilane (94.9 mL, 0.6 mmol) in
MeCN (2 mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The
resulting mixture was stirred for 2 h, and then the same procedure
was followed as for the remaining preparation of 3a, giving 3c as a
white oil. Yield: 103.2 mg (88%).
1H and 13C NMR spectra were recorded on JEOL EX-400 and ECA-
600 spectrometers (JEOL) in CDCl3 using TMS as the internal stan-
dard. Optical rotations were recorded on a JASCO DIP-360 digital
polarimeter. HRMS were obtained using a Mariner spectrometer
(PerSeptive Biosystems Inc.). Preparative TLC was performed on
Merck silica gel 60GF254. Column chromatography was conducted
using silica gel 60N (40–50 mm, Kanto Chemical Co., Inc.) All dry
solvents were purified according to the standard methods. The spec-
tral data of 2a, 3a, 5a, 6a, 7a and 8a are reported in the litera-
ture.4b,9,11
[a]D23 +32.1 (c 5.16, CHCl3).
1H NMR (400 MHz, CDCl3): d = 0.86 (t, J = 6.9 Hz, 3 H,
CH2CH2CH2CH3), 1.17–1.29 (m, 3 H, CH2CHaHbCH2CH3), 1.50–
1.57 (m, 2 H, CHaHbCHaHbCH2CH3), 1.67–1.72 (m, 1 H,
CHaHbCH2CH2CH3), 2.37 (dd, J = 7.8, 15.4 Hz, 1 H, CHaH-
bCH=CH2), 2.68 (dd, J = 6.3, 15.4 Hz, 1 H, CHaHbCH=CH2), 3.59
(t, J = 9.3 Hz, 1 H, H-5), 3.60 (d, J = 9.3 Hz, 1 H, H-3), 3.63–3.65
(m, 1 H, H-6), 3.65–3.68 (m, 1 H, Ha-7), 3.74 (dd, J = 4.1, 11.1 Hz,
1 H, Hb-7), 3.92 (t, J = 9.0 Hz, 1 H, H-4), 4.53–4.92 (m, 8 H,
CH2Ph), 5.08–5.12 (m, 2 H, CH2CH=CH2), 5.81–5.91 (m, 1 H,
CH2CH=CH2), 7.18–7.36 (m, 20 H, Ph).
13C NMR (100 MHz, CDCl3): d = 14.3 (CH2CH2CH2CH3), 23.2
(CH2CH2CH2CH3), 25.0 (CH2CH2CH2CH3), 34.8 (CH2CH=CH2),
35.8 (CH2CH2CH2CH3), 69.3 (C-7), 72.4 (C-6), 73.2 (CH2Ph), 75.0
(CH2Ph), 75.1 (CH2Ph), 75.5 (CH2Ph), 78.2 (C-2), 79.2 (C-5), 81.3
(C-3), 84.5 (C-4), 117.7 (CH2CH=CH2), 127.3–128.3 (Ph), 133.0
(CH2CH=CH2), 138.1–138.5 (Ph).
(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-methyltetrahydropyran (3a) (Table 1, Entry 7)
TMSOTf (7.2 mL, 0.04 mmol) was added to a solution of 1a (110.0
mg, 0.2 mmol) and allyltrimethylsilane (94.7 mL, 0.6 mmol) in
MeCN (3 mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The
resulting mixture was stirred for 3 h. The reaction was then
quenched by the addition of sat. NaHCO3 soln (5 mL). The mixture
was extracted with CHCl3, and the organic layer was washed with
H2O and sat. NaCl soln. After the organic layer was dried (Na2SO4),
the solvent was evaporated under reduced pressure. The crude prod-
uct was purified by preparative TLC (silica gel, EtOAc–hexane,
1:4) to give 3a4b as a white oil. Yield: 101 mg (88%).
HRMS (ESI): m/z [M + Na+] calcd for C41H48O5: 643.3399; found:
643.3416.
(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-methyltetrahydropyran (3a) and
(2S,3R,4S,5R,6R)-2,3,4,5-Tetrakis(benzyloxy)-6-(benzyl-
oxy)methyl-2-methyltetrahydropyran (2a) (Table 1, Entry 4)
TMSOTf (7.2 mL, 0.04 mmol) was added to a solution of 1a (110.9
mg, 0.2 mmol) and allyltrimethylsilane (63.5 mL, 0.4 mmol) in
MeCN (3 mL) at –10 °C in the presence of CaSO4 (ca. 100 mg). The
resulting mixture was stirred for 3 h, and then the same procedure
was followed as for the remaining preparation of 3a. The crude mix-
ture was separated by preparative TLC (silica gel, EtOAc–hexane,
1:4) to give 3a and 2a11 as white oils; Yield of 3a: 88.2 mg (76%);
yield of 2a: 11.8 mg (9%).
(3R,4S,5R,6R)-2,2-Diallyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran (3d) (Table 1, Entry 34)
TMSOTf (8.4 mL, 0.046 mmol) was added to a solution of 9d (143.5
mg, 0.23 mmol) and allyltrimethylsilane (220 mL, 1.38 mmol) in
MeCN–CH2Cl2 (1:1, 3 mL) at –78 °C in the presence of CaSO4 (ca.
100 mg). The resulting mixture was stirred for 3 h, and then the
same procedure was followed as for the remaining preparation of
3a, giving 3d as a white oil. Yield: 139.4 mg (72%).
[a]D23 +72.6 (c 1.90, CHCl3).
1H NMR (400 MHz, CDCl3): d = 2.24 (dd, J = 9.4, 14.8 Hz, 1 H, b-
CHaHbCH=CH2), 2.31 (dd, J = 8.1, 15.4 Hz, 1 H, a-CHaH-
bCH=CH2), 2.51 (dd, J = 4.6, 14.6 Hz, 1 H, b-CHaHbCH=CH2),
2.63 (dd, J = 6.1, 15.4 Hz, 1 H, a-CHaHbCH=CH2), 3.50 (t, J = 9.5
Hz, 1 H, H-5), 3.53 (d, J = 9.5 Hz, 1 H, H-3), 3.57–3.61 (m, 1 H, H-
6), 3.62–3.69 (m, 2 H, H-7), 3.83 (t, J = 9.3 Hz, 1 H, H-4), 4.47–
4.84 (m, 8 H, CH2Ph), 4.94–5.06 (m, 4 H, CH2CH=CH2), 5.74–5.94
(m, 2 H, CH2CH=CH2), 7.20–7.34 (m, 20 H, Ph).
(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-ethyltetrahydropyran (3b) (Table 1, Entry 8)
TMSOTf (7.3 mL, 0.04 mmol) was added to a solution of 1b (113.2
mg, 0.2 mmol) and allyltrimethylsilane (94.9 mL, 0.6 mmol) in
MeCN (3 mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The
resulting mixture was stirred for 3 h, and then the same procedure
was followed as for the remaining preparation of 3a, giving 3b as a
white oil. Yield: 104.4 mg (88%).
13C NMR (100 MHz, CDCl3): d = 34.3 (a-CH2CH=CH2), 40.7 (b-
CH2CH=CH2), 69.3 (C-7), 72.6 (C-6), 73.3 (CH2Ph), 74.7 (CH2Ph),
75.1 (CH2Ph), 75.5 (CH2Ph), 78.7 (C-2), 79.1 (C-5), 81.3 (C-3),
84.4 (C-4), 117.9 (a-CH2CH=CH2), 118.1 (b-CH2CH=CH2),
127.0–128.3 (Ph), 132.5 (a-CH2CH=CH2), 134.4 (b-CH2CH=CH2),
138.0–138.8 (Ph).
[a]D23 +47.3 (c 4.31, CHCl3).
1H NMR (400 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H, CH2CH3),
1.52–1.61 (m, 1 H, CHaHbCH3), 1.76–1.85 (m, 1 H, CHaHbCH3),
2.38 (dd, J = 7.8, 15.4 Hz, 1 H, CHaHbCH=CH2), 2.69 (dd, J = 6.3,
15.4 Hz, 1 H, CHaHbCH=CH2), 3.59 (d, J = 9.5 Hz, 1 H, H-3), 3.60
(t, J = 9.5 Hz, 1 H, H-5), 3.64–3.67 (m, 1 H, H-6), 3.68–3.69 (m, 1
H, Ha-7), 3.75 (dd, J = 4.2, 11.2 Hz, 1 H, Hb-7), 3.93 (t, J = 9.5 Hz,
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

3026
Y. Oda, T. Yamanoi
PAPER
HRMS (ESI): m/z [M + Na+] calcd for C40H44O5: 627.3086; found:
627.3031.
1H NMR (400 MHz, CDCl3): d = 2.53 (dd, J = 8.0, 15.3 Hz, 1 H,
CHaHbCH=CH2), 2.79 (d, J = 14.4 Hz, 1 H, CCHaHbPh), 2.81 (dd,
J = 7.3, 14.8 Hz, 1 H, CHaHbCH=CH2), 3.19 (d, J = 14.4 Hz, 1 H,
CCHaHbPh), 3.35 (d, J = 9.5 Hz, 1 H, H-3), 3.49 (t, J = 9.5 Hz, 1 H,
H-5), 3.68–3.74 (m, 1 H, H-6), 3.75–3.82 (m, 2 H, H-7), 3.92 (t, 1
H, J = 9.2 Hz, H-4), 4.22–4.90 (m, 8 H, CH2Ph), 5.15–5.19 (m, 2 H,
CH2CH=CH2), 5.90–5.98 (m, 1 H, CH2CH=CH2), 7.13–7.37 (m, 25
H, Ph).
13C NMR (100 MHz, CDCl3): d = 35.1 (CH2CH=CH2), 42.3
(CCH2Ph), 69.5 (C-7), 72.5 (C-6), 73.3 (CH2Ph), 74.3 (CH2Ph),
75.1 (CH2Ph), 75.6 (CH2Ph), 79.0 (C-5), 79.5 (C-2), 80.3 (C-3),
84.7 (C-4), 118.1 (CH2CH=CH2), 126.1–131.1 (Ph), 132.7
(CH2CH=CH2), 137.4–139.1 (Ph).
(3R,4S,5R,6R)-2,2-Diallyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran (3d) and (2S,3R,4S,5R,6R)-2-Allyl-
2,3,4,5-tetrakis(benzyloxy)-6-(benzyloxy)methyltetrahydro-
pyran (4d) (Table 1, Entry 10)
TMSOTf (7.2 mL, 0.04 mmol) was added to a solution of 1d (114.9
mg, 0.2 mmol) and allyltrimethylsilane (94.3 mL, 0.59 mmol) in
MeCN (3 mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The
resulting mixture was stirred for 3 h, and then the same procedure
was followed as for the remaining preparation of 3a. The crude mix-
ture was separated by preparative TLC (silica gel, EtOAc–hexane
1:4) to give 3d and 4d as white oils. Yield of 3d: 37.3 mg (31%);
yield of 4d: 22.3 mg (17%).
HRMS (ESI): m/z [M + Na+] calcd for C44H46O5: 677.3237; found:
677.3176.
4d
[a]D23 +66.7 (c 0.3, CHCl3).
(2S,3R,4S,5R,6R)-2-Allyl-2-benzyl-3,4,5-tris(benzyloxy)-6-
(benzyloxy)methyltetrahydropyran (3e) and (2S,3R,4S,5R,6R)-
2-Benzyl-2,3,4,5-tetrakis(benzyloxy)-6-(benzyloxy)methyltet-
rahydropyran (4e) (Table 1, Entry 32)
TMSOTf (5.0 mL, 0.027 mmol) was added to a solution of 9e (91.8
mg, 0.14 mmol) and allyltrimethylsilane (65 mL, 0.41 mmol) in
MeCN (2 mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The
resulting mixture was stirred for 2 h, and then the same procedure
was followed as for the remaining preparation of 3a. The crude mix-
ture was separated by preparative TLC (silica gel, EtOAc–hexane,
1:4) to give 3e and 4e as white oils. Yield of 3e: 59.3 mg (66%);
yield of 4e: 10 mg (10%).
1H NMR (600 MHz, CDCl3): d = 2.65 (dd, J = 9.0, 13.7 Hz, 1 H,
CHaHbCH=CH2), 2.69–2.73 (m, 1 H, CHaHbCH=CH2), 3.56 (d, J =
9.6 Hz, 1 H, H-3), 3.61 (t, J = 9.6 Hz, 1 H, H-5), 3.67 (d, J = 11.0
Hz, 1 H, Ha-7), 3.74 (dd, J = 4.1, 11.0 Hz, 1 H, Hb-7), 3.77–3.79 (m,
1 H, H-6), 4.13 (t, J = 9.6 Hz, 1 H, H-4), 4.52–4.96 (m, 10 H,
CH2Ph), 5.01–5.07 (m, 2 H, CH2CH=CH2), 5.83–5.90 (m, 1 H,
CH2CH=CH2), 7.08–7.47 (m, 25 H, Ph).
13C NMR (150 MHz, CDCl3): d = 38.3 (CH2CH=CH2), 62.3
(CH2Ph), 68.9 (C-7), 72.1 (C-6), 73.3 (CH2Ph), 74.7 (CH2Ph), 75.0
(CH2Ph), 75.4 (CH2Ph), 78.8 (C-5), 81.3 (C-3), 83.4 (C-4), 102.1 (C-
2), 118.1 (CH2CH=CH2), 127.0–128.3 (Ph), 133.6 (CH2CH=CH2),
138.2–138.9 (Ph).
4e
[a]D23 +48.7 (c 1.03, CHCl3).
HRMS (ESI): m/z [M + Na+] calcd for C44H46O6: 693.3192; found:
693.3167.
1H NMR (600 MHz, CDCl3): d = 3.05 (d, J = 13.8 Hz, 1 H, CCHaH-
bPh), 3.24 (d, J = 9.0 Hz, 1 H, H-3), 3.29 (d, J = 13.8 Hz, 1 H,
CCHaHbPh), 3.47 (t, J = 9.6 Hz, 1 H, H-5), 3.68–3.76 (m, 3 H, H-6,
H-7), 4.10 (t, J = 9.6 Hz, 1 H, H-4), 4.32–4.85 (m, 8 H, CH2Ph),
7.13–7.37 (m, 30 H, Ph).
13C NMR (150 MHz, CDCl3): d = 40.0 (CCH2Ph), 62.3 (OCH2Ph),
69.1 (C-7), 72.2 (C-6), 73.2 (CH2Ph), 74.0 (CH2Ph), 75.1 (CH2Ph),
75.4 (CH2Ph), 78.7 (C-5), 80.0 (C-3), 83.5 (C-4), 102.9 (C-2),
126.9–130.5 (Ph).
(3R,4S,5R,6R)-2,2-Diallyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran (3d) and (Z)-(3R,4S,5R,6R)-2-Al-
lylidene-3,4,5-tris(benzyloxy)-6-(benzyloxy)methyltetrahydro-
pyran (8) (Table 1, Entry 13)
TMSOTf (7.5 mL, 0.041 mmol) was added to a solution of 1d (119.9
mg, 0.21 mmol) and allyltrimethylsilane (196.9 mL, 1.24 mmol) in
MeCN–CH2Cl2 (1:1, 3 mL) at –78 °C in the presence of CaSO4 (ca.
100 mg). The resulting mixture was stirred for 3 h, and then the
same procedure was followed as for the remaining preparation of
3a. The crude mixture was separated by preparative TLC (silica gel,
EtOAc–hexane 1:4) to give 3d and 89 as white oils. Yield of 3d:
(66.3 mg, 53%); yield of 8: 18.2 mg (16%).
HRMS (ESI): m/z [M + Na+] calcd for C48H48O6: 743.3349; found:
743.3385.
(2S,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-phenyltetrahydropyran (3f) (Table 1, Entry 12)
TMSOTf (8.1 mL, 0.044 mmol) was added to a solution of 1f (136.6
mg, 0.22 mmol) and allyltrimethylsilane (105.6 mL, 0.66 mmol) in
MeCN (3.0 mL) at –40 °C in the presence of CaSO4 (ca. 100 mg).
The resulting mixture was stirred for 3 h, and then the same proce-
dure was followed as for the remaining preparation of 3a, giving 3f
as a white oil. Yield: 134.1 mg (95%).
(2S,3R,4S,5R,6R)-2-Allyl-2-benzyl-3,4,5-tris(benzyloxy)-6-
(benzyloxy)methyltetrahydropyran (3e) (Table 1, Entry 14)
TMSOTf (14.8 mL, 0.081 mmol) was added to a solution of 1e
(128.5 mg, 0.20 mmol) and allyltrimethylsilane (194.2 mL, 1.22
mmol) in MeCN–CH2Cl2 (1:1, 2 mL) at –78 °C in the presence of
CaSO4 (ca. 100 mg). The resulting mixture was stirred for 2 h, and
then the same procedure was followed as for the remaining prepa-
ration of 3a, giving 3e as a white oil. Yield: 103.5 mg (78%).
[a]D23 +12.4 (c 6.31, CHCl3).
1H NMR (600 MHz, CDCl3): d = 2.92 (dd, J = 7.6, 16.5 Hz, 1 H,
CHaHbCH=CH2), 3.19 (dd, J = 6.2, 16.5 Hz, 1 H, CHaHbCH=CH2),
3.41 (d, J = 9.6 Hz, 1 H, H-3), 3.77 (d, J = 11.0 Hz, 1 H, Ha-7),
3.82–3.86 (m, 3 H, H-5, H-6, CHaHbPh), 3.88 (dd, J = 2.8, 10.3 Hz,
1 H, Hb-7), 3.98–4.01 (m, 1 H, H-4), 4.54–4.91 (m, 7 H, CH2Ph,
CHaHbPh), 4.96 (d, J = 10.3 Hz, 1 H, CH2CH=CHaHb), 5.08 (d, J =
17.2 Hz, 1 H, CH2CH=CHaHb), 5.50–5.67 (m, 1 H, CH2CH=CH2),
7.14–7.40 (m, 23 H, Ph), 7.65 (d, J = 7.5Hz, 2 H, CPh).
13C NMR (150 MHz, CDCl3): d = 31.9 (CH2CH=CH2), 69.5 (C-7),
72.3 (C-6), 73.4 (CH2Ph), 75.1 (CH2Ph), 75.5 (2 CH2Ph), 79.0 (C-
5), 79.8 (C-2), 84.2 (C-4), 86.8 (C-3), 117.7 (CH2CH=CH2), 126.5–
128.4 (Ph), 132.6 (CH2CH=CH2), 138.2–143.2 (Ph).
(2S,3R,4S,5R,6R)-2-Allyl-2-benzyl-3,4,5-tris(benzyloxy)-6-
(benzyloxy)methyltetrahydropyran (3e) (Table 1, Entry 33)
TMSOTf (4.5 mL, 0.024 mmol) was added to a solution of 9e (83.7
mg, 0.12 mmol) and allyltrimethylsilane (59.3 mL, 0.37 mmol) in
MeCN–CH2Cl2 (1:1, 2 mL) at –78 °C in the presence of CaSO4 (ca.
100 mg). The resulting mixture was stirred for 2 h, and then the
same procedure was followed as for the remaining preparation of
3a, giving 3e as a white oil. Yield: 64.8 mg (80%).
[a]D23 +27.4 (c 5.18, CHCl3).
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

PAPER
Trifluoromethanesulfonate-Catalyzed Nucleophilic Substitution To Give C- and N-Glucopyranosides
3027
HRMS (ESI): m/z [M + Na+] calcd for C43H44O5: 663.3081; found:
as for the remaining preparation of 3a, giving 5d as a white oil.
663.3128.
Yield: 71.3 mg (80%).
(2S,3R,4S,5R,6R)-2-Azido-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-methyltetrahydropyran (5a) (Table 1, Entry 15)
TMSOTf (9.3 mL, 0.051 mmol) was added to a solution of 1a (141.6
mg, 0.26 mmol) and TMSN3 (101.7 mL, 0.77 mmol) in MeCN (3
mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting
mixture was stirred for 3 h, and then the same procedure was fol-
lowed as for the remaining preparation of 3a, giving 5a4b as a white
oil. Yield: 147.1 mg (99%).
(2S,3R,4S,5R,6R)-2-Allyl-2-azido-3,4,5-tris(benzyloxy)-6-(ben-
zyloxy)methyltetrahydropyran (5d) (Table 1, Entry 35)
TMSOTf (4.7 mL, 0.026 mmol) was added to a solution of 9d (80.3
mg, 0.13 mmol) and TMSN3 (51.3 mL, 0.39 mmol) in MeCN–
CH2Cl2 (1:1, 2 mL) at –78 °C in the presence of CaSO4 (ca. 100
mg). The resulting mixture was stirred for 2 h, and then the same
procedure was followed as for the remaining preparation of 3a, giv-
ing 5d as a white oil. Yield: 73.1 mg (94%).
[a]D23 +68.8 (c 3.3, CHCl3).
(2S,3R,4S,5R,6R)-2-Azido-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-ethyltetrahydropyran (5b) (Table 1, Entry 16)
TMSOTf (7.6 mL, 0.042 mmol) was added to a solution of 1b (118.4
mg, 0.21 mmol) and TMSN3 (82.9 mL, 0.62 mmol) in MeCN (3 mL)
at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting mix-
ture was stirred for 3 h, and then the same procedure was followed
as for the remaining preparation of 3a, giving 5b as a white oil.
Yield: 119.1 mg (96%).
1H NMR (600 MHz, CDCl3): d = 2.69 (dd, J = 7.8, 14.4 Hz, 1 H,
CHaHbCH=CH2), 2.78 (dd, J = 6.1, 14.2 Hz, 1 H, CHaHbCH=CH2),
3.52 (d, J = 9.2 Hz, 1 H, H-3), 3.64–3.69 (m, 2 H, H-5, Ha-7), 3.78
(dd, J = 3.6, 11.2 Hz, 1 H, Hb-7), 3.87–3.89 (m, 1 H, H-6), 3.98 (t,
J = 9.3 Hz, 1 H, H-4), 4.51–4.94 (m, 8 H, CH2Ph), 5.16 (t, J = 17.1
Hz, 2 H, CH2CH=CH2), 5.85–5.88 (m, 1 H, CH2CH=CH2), 7.19–
7.35 (m, 20 H, Ph).
13C NMR (150 MHz, CDCl3): d = 40.0 (CH2CH=CH2), 68.4 (C-7),
73.3 (CH2Ph), 73.8 (C-6), 75.0 (CH2Ph), 75.3 (CH2Ph), 75.7
(CH2Ph), 77.7 (C-5), 81.4 (C-3), 83.7 (C-4), 93.7 (C-2), 119.7
(CH2CH=CH2), 127.5–128.4 (Ph), 131.3 (CH2CH=CH2), 138.0–
138.4 (Ph).
HRMS (ESI): m/z [M + Na+] calcd for C37H39N3O5: 628.2787;
found: 628.2737.
[a]D23 +58.9 (c 5.96, CHCl3).
1H NMR (600 MHz, CDCl3): d = 0.94 (t, J = 7.4 Hz, 3 H, CH2CH3),
1.86–1.91 (m, 1 H, CHaHbCH3), 2.03–2.08 (m, 1 H, CHaHbCH3),
3.49 (d, J = 9.3 Hz, 1 H, H-3), 3.64–3.69 (m, 2 H, H-5, Ha-7), 3.76
(dd, J = 3.5, 14.9 Hz, 1 H, Hb-7), 3.85–3.87 (m, 1 H, H-6), 4.00 (t,
J = 9.3 Hz, 1 H, H-4), 4.49–4.93 (m, 8 H, CH2Ph), 7.19–7.32 (m,
20 H, Ph).
13C NMR (150 MHz, CDCl3): d = 7.3 (CH2CH3), 28.4 (CH2CH3),
68.4 (C-7), 73.3 (CH2Ph), 73.5 (C-6), 74.9 (CH2Ph), 75.3 (CH2Ph),
75.7 (CH2Ph), 77.7 (C-5), 81.3 (C-3), 83.7 (C-4), 94.3 (C-2), 127.4–
138.3 (Ph).
HRMS (ESI): m/z [M + Na+] calcd for C36H39N3O5: 616.2787;
found: 616.2749.
(2S,3R,4S,5R,6R)-2-Azido-2-benzyl-3,4,5-tris(benzyloxy)-6-
(benzyloxy)methyltetrahydropyran (5e) (Table 1, Entry 19)
TMSOTf (4.2 mL, 0.023 mmol) was added to a solution of 1e (72.2
mg, 0.11 mmol) and TMSN3 (45.6 mL, 0.34 mmol) in MeCN (2 mL)
at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting mix-
ture was stirred for 2 h, and then the same procedure was followed
as for the remaining preparation of 3a, giving 5e as a white oil.
Yield: 60.9 mg (80%).
(2S,3R,4S,5R,6R)-2-Azido-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-butyltetrahydropyran (5c) (Table 1, Entry 17)
TMSOTf (3.3 mL, 0.018 mmol) was added to a solution of 1c (53.6
mg, 0.09 mmol) and TMSN3 (35.8 mL, 0.27 mmol) in MeCN (2 mL)
at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting mix-
ture was stirred for 2 h, and then the same procedure was followed
as for the remaining preparation of 3a, giving 5c as a white oil.
Yield: 52.6 mg (94%).
(2S,3R,4S,5R,6R)-2-Azido-2-benzyl-3,4,5-tris(benzyloxy)-6-
(benzyloxy)methyltetrahydropyran (5e) (Table 1, Entry 36)
TMSOTf (4.5 mL, 0.025 mmol) was added to a solution of 9e (81.3
mg, 0.12 mmol) and TMSN3 (49.2 mL, 0.37 mmol) in MeCN–
CH2Cl2 (1:1, 2 mL) at –78 °C in the presence of CaSO4 (ca. 100
mg). The resulting mixture was stirred for 2 h, and then the same
procedure was followed as for the remaining preparation of 3a, giv-
ing 5e as a white oil. Yield: 74.7 mg (91%).
[a]D23 +52.5 (c 2.63, CHCl3).
1H NMR (600 MHz, CDCl3): d = 0.86 (t, J = 6.9 Hz, 3 H,
CH2CH2CH2CH3), 1.22–1.54 (m, 4 H, CH2CH2CH2CH3), 1.78–
1.93 (m, 2 H, CH2CH2CH2CH3), 3.49 (d, J = 9.2 Hz, 1 H, H-3),
3.63–3.67 (m, 2 H, H-5, Ha-7), 3.75 (dd, J = 3.7, 11.1 Hz, 1 H, Hb-
7), 3.84–3.86 (m, 1 H, H-6), 3.99 (t, J = 9.2 Hz, 1 H, H-4), 4.51–
4.94 (m, 8 H, CH2Ph), 7.19–7.33 (m, 20 H, Ph).
[a]D23 +58.6 (c 3.24, CHCl3).
1H NMR (600 MHz, CDCl3): d = 3.17 (d, J = 13.9 Hz, 1 H, CCHaH-
bPh), 3.32 (d, J = 13.9 Hz, 1 H, CCHaHbPh), 3.40 (d, J = 9.3 Hz, 1
H, H-3), 3.64 (t, J = 9.0 Hz, 1 H, H-5), 3.71 (dd, J = 1.7, 11.0 Hz,
1 H, Ha-7), 3.80 (dd, J = 3.4, 11.0 Hz, 1 H, Hb-7), 3.85–3.88 (m, 1
H, H-6), 4.01 (t, J = 9.2 Hz, 1 H, H-4), 4.52–4.95 (m, 8 H, CH2Ph),
7.17–7.38 (m, 25 H, Ph).
13C NMR (150 MHz, CDCl3): d = 41.7 (CCH2Ph), 68.4 (C-7), 73.2
(CH2Ph), 73.7 (C-6), 75.0 (CH2Ph), 75.1 (CH2Ph), 75.7 (CH2Ph),
77.7 (C-5), 81.0 (C-3), 83.9 (C-4), 94.3 (C-2), 127.0–138.2 (Ph).
13C NMR (150 MHz, CDCl3): d = 14.1 (CH2CH2CH2CH3), 22.7
(CH2CH2CH2CH3),
25.0
(CH2CH2CH2CH3),
35.1
(CH2CH2CH2CH3), 68.4 (C-7), 73.2 (CH2Ph), 73.5 (C-6), 75.0
(CH2Ph), 75.3 (CH2Ph), 75.7 (CH2Ph), 77.8 (C-5), 81.4 (C-3), 83.8
(C-4), 94.2 (C-2), 127.5–138.3 (Ph).
HRMS (ESI): m/z [M + Na+] calcd for C38H43N3O5: 644.3100;
HRMS (ESI): m/z [M + Na+] calcd for C41H41N3O5: 678.2944;
found: 644.3062.
found: 678.2951.
(2S,3R,4S,5R,6R)-2-Allyl-2-azido-3,4,5-tris(benzyloxy)-6-(ben-
zyloxy)methyltetrahydropyran (5d) (Table 1, Entry 18)
TMSOTf (5.3 mL, 0.029 mmol) was added to a solution of 1d (84.9
mg, 0.15 mmol) and TMSN3 (58.2 mL, 0.44 mmol) in MeCN (2 mL)
at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting mix-
ture was stirred for 2 h, and then the same procedure was followed
(2S,3R,4S,5R,6R)-2-Azido-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-phenyltetrahydropyran (5f) (Table 1, Entry 20)
TMSOTf (7.5 mL, 0.041 mmol) was added to a solution of 1f (126
mg, 0.20 mmol) and TMSN3 (81.4 mL, 0.61 mmol) in MeCN (3 mL)
at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting mix-
ture was stirred for 3 h, and then the same procedure was followed
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

3028
Y. Oda, T. Yamanoi
PAPER
as for the remaining preparation of 3a, giving 5f as a white oil.
Yield: 125.6 mg (96%).
(CH2Ph), 75.9 (CH2Ph), 76.7 (C-5), 77.0 (C-6), 78.6 (C-2), 81.0 (C-
3), 84.6 (C-4), 117.3 (CN), 127.5–138.0 (Ph).
[a]D23 +11.1 (c 4.02, CHCl3).
HRMS (ESI): m/z [M + Na+] calcd for C39H43NO5: 628.3039;
found: 628.3005.
1H NMR (600 MHz, CDCl3): d = 3.43 (d, J = 9.6 Hz, 1 H, H-3), 3.81
(d, J = 11.0 Hz, 2 H, Ha-7, CH2Ph), 3.89 (t, J = 9.6 Hz, 1 H, H-5),
3.91 (dd, J = 3.5, 11.0 Hz, 1 H, Hb-7), 4.06 (t, J = 9.6 Hz, 1 H, H-
4), 4.09–4.10 (m, 1 H, H-6), 4.41–4.92 (m, 7 H, CH2Ph), 7.02–7.43
(m, 23 H, Ph), 7.67 (d, 2 H, CPh).
13C NMR (150 MHz, CDCl3): d = 68.7 (C-7), 73.4 (CH2Ph), 74.1
(C-6), 75.1 (CH2Ph), 75.7 (CH2Ph), 75.8 (CH2Ph), 77.9 (C-5), 83.2
(C-4), 84.8 (C-3), 95.7 (C-2), 126.9–138.6 (Ph).
(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-carbonitrile (6d) (Table 1,
Entry 24)
TMSOTf (4.5 mL, 0.025 mmol) was added to a solution of 1d (71.8
mg, 0.12 mmol) and TMSCN (49.5 mL, 0.37 mmol) in MeCN (2
mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting
mixture was stirred for 2 h, and then the same procedure was fol-
lowed as for the remaining preparation of 3a, giving 6d as a white
oil. Yield: 47.4 mg (65%).
HRMS (ESI): m/z [M + Na+] calcd for C40H39N3O5: 664.2787;
found: 664.2750.
(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-carbonitrile (6d) (Table 1,
Entry 37)
(2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-(benzyloxy)methyl-
2-methyltetrahydropyran-2-carbonitrile (6a) (Table 1, Entry
21)
TMSOTf (5.2 mL, 0.029 mmol) was added to a solution of 9d (89.2
mg, 0.14 mmol) and TMSCN (57.3 mL, 0.43 mmol) in MeCN–
CH2Cl2 (1:1, 2 mL) at –78 °C in the presence of CaSO4 (ca. 100
mg). The resulting mixture was stirred for 2 h, and then the same
procedure was followed as for the remaining preparation of 3a, giv-
ing 6d as a white oil. Yield: 80.6 mg (95%).
TMSOTf (4.9 mL, 0.027 mmol) was added to a solution of 1a (75.9
mg, 0.14 mmol) and TMSCN (54.7 mL, 0.41 mmol) in MeCN (2
mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting
mixture was stirred for 3 h, and then the same procedure was fol-
lowed as for the remaining preparation of 3a, giving 6a4b as a white
oil. Yield: 73.4 mg (95%).
[a]D23 +48.5 (c 2.21, CHCl3).
(2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-(benzyloxy)methyl-
2-ethyltetrahydropyran-2-carbonitrile (6b) (Table 1, Entry 22)
TMSOTf (6.8 mL, 0.037 mmol) was added to a solution of 1b (105.7
mg, 0.19 mmol) and TMSCN (74.4 mL, 0.56 mmol) in MeCN (3
mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting
mixture was stirred for 3 h, and then the same procedure was fol-
lowed as for the remaining preparation of 3a, giving 6b as a white
oil. Yield: 96.1 mg (90%).
1H NMR (600 MHz, CDCl3): d = 2.47–2.51 (m, 1 H, CHaHb-
CH=CH2), 2.72–2.76 (m, 1 H, CHaHbCH=CH2), 3.41 (d, J = 9.0 Hz,
1 H, H-3), 3.69–3.73 (m, 2 H, H-5, Ha-7), 3.80 (dd, J = 3.4, 11.0 Hz,
1 H, Hb-7), 3.85–3.86 (m, 1 H, H-6), 3.96 (t, J = 10.0 Hz, 1 H, H-
4), 4.51–4.97 (m, 8 H, CH2Ph), 5.15 (d, J = 17.1 Hz, 1 H,
CH2CH=CHaHb), 5.21 (d, J = 11.6 Hz, 1 H, CH2CH=CHaHb), 5.82–
5.89 (m, 1 H, CH2CH=CH2), 7.15–7.35 (m, 20 H, Ph).
13C NMR (150 MHz, CDCl3): d = 40.6 (CH2CH=CH2), 68.0 (C-7),
73.3 (CH2Ph), 75.0 (CH2Ph), 75.2 (CH2Ph), 75.8 (CH2Ph), 76.7 (C-
6), 76.8 (C-5), 78.3 (C-2), 80.3 (C-3), 84.7 (C-4), 117.1 (CN), 120.5
(CH2CH=CH2), 127.5–128.4 (Ph), 130.3 (CH2CH=CH2), 137.5–
138.1 (Ph).
[a]D23 +42.2 (c 4.72, CHCl3).
1H NMR (600 MHz, CDCl3): d = 1.05 (t, J = 7.4 Hz, 3 H, CH2CH3),
1.62–1.71 (m, 1 H, CHaHbCH3), 2.03–2.12 (m, 1 H, CHaHbCH3),
3.35 (d, J = 9.3 Hz, 1 H, H-3), 3.68–3.86 (m, 4 H, H-5, H-6, H-7),
3.96 (t, J = 9.7 Hz, 1 H, H-4), 4.49–4.96 (m, 8 H, CH2Ph), 7.17–
7.35 (m, 20 H, Ph).
13C NMR (150 MHz, CDCl3): d = 7.8 (CH2CH3), 29.9 (CH2CH3),
68.0 (C-7), 73.3 (CH2Ph), 75.0 (CH2Ph), 75.4 (CH2Ph), 75.8
(CH2Ph), 76.5 (C-6), 77.0 (C-5), 79.1 (C-2), 81.0 (C-3), 84.6 (C-4),
117.2 (CN), 127.5–138.0 (Ph).
HRMS (ESI): m/z [M + Na+] calcd for C38H39NO5: 612.2726;
found: 612.2690.
(2R,3R,4S,5R,6R)-2-Benzyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-carbonitrile (6e) (Table 1,
Entry 25)
TMSOTf (5.7 mL, 0.031 mmol) was added to a solution of 1e (99.5
mg, 0.16 mmol) and TMSCN (63.1 mL, 0.47 mmol) in MeCN (2
mL) at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting
mixture was stirred for 2 h, and then the same procedure was fol-
lowed as for the remaining preparation of 3a, giving 6e as a white
oil. Yield: 74.1 mg (73%).
HRMS (ESI): m/z [M + Na+] calcd for C37H39NO5: 600.2726;
found: 600.2679.
(2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-(benzyloxy)methyl-
2-butyltetrahydropyran-2-carbonitrile (6c) (Table 1, Entry 23)
TMSOTf (7.8 mL, 0.043 mmol) was added to a solution of 1c (128.3
mg, 0.21 mmol) and TMSCN (86 mL, 0.64 mmol) in MeCN (3 mL)
at –40 °C in the presence of CaSO4 (ca. 100 mg). The resulting mix-
ture was stirred for 3 h, and then the same procedure was followed
as for the remaining preparation of 3a, giving 6c as a white oil.
Yield: 119.9 mg (92%).
(2R,3R,4S,5R,6R)-2-Benzyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-carbonitrile (6e) (Table 1,
Entry 38)
TMSOTf (4.1 mL, 0.023 mmol) was added to a solution of 9e (75.9
mg, 0.11 mmol) and TMSCN (45.1 mL, 0.34 mmol) in MeCN–
CH2Cl2 (1:1, 2 mL) at –78 °C in the presence of CaSO4 (ca. 100
mg). The resulting mixture was stirred for 2 h, and then the same
procedure was followed as for the remaining preparation of 3a, giv-
ing 6e as a white oil. Yield: 61.8 mg (86%).
[a]D23 +52.5 (c 2.63, CHCl3).
1H NMR (600 MHz, CDCl3): d = 0.86 (t, J = 7.2 Hz, 3 H,
CH2CH2CH2CH3), 1.27 (m, 2 H, CH2CH2CH2CH3), 1.48–1.58 (m,
3 H, CHaHbCH2CH2CH3), 1.90–1.97 (m, 1 H, CHaHbCH2CH2CH3),
3.34 (d, J = 9.3 Hz, 1 H, H-3), 3.67–3.82 (m, 4 H, H-5, H-6, H-7),
3.95 (t, J = 9.2 Hz, 1 H, H-4), 4.48–4.96 (m, 8 H, CH2Ph), 7.18–
7.32 (m, 20 H, Ph).
[a]D23 +34.7 (c 1.2, CHCl3).
1H NMR (600 MHz, CDCl3): d = 2.95 (d, J = 14.2 Hz, 1 H, CCHaHb-
Ph), 3.25 (d, J = 14.1 Hz, 1 H, CCHaHbPh), 3.39 (d, J = 9.6 Hz, 1
H, H-3), 3.65–3.78 (m, 4 H, H-5, H-6, H-7), 3.99 (t, J = 9.1 Hz, 1
H, H-4), 4.53–5.03 (m, 8 H, CH2Ph), 7.22–7.37 (m, 25 H, Ph).
13C NMR (150 MHz, CDCl3): d = 22.4 (CH2CH2CH2CH3), 24.5
(CH2CH2CH2CH3),
25.4
(CH2CH2CH2CH3),
36.2
(CH2CH2CH2CH3), 68.0 (C-7), 73.2 (CH2Ph), 75.4 (CH2Ph), 75.8
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

PAPER
Trifluoromethanesulfonate-Catalyzed Nucleophilic Substitution To Give C- and N-Glucopyranosides
3029
13C NMR (150 MHz, CDCl3): d = 42.2 (CCH2Ph), 68.0 (C-7), 73.3
(CH2Ph), 75.0 (CH2Ph), 75.2 (CH2Ph), 75.9 (CH2Ph), 76.5 (C-6),
77.0 (C-5), 79.0 (C-2), 80.3 (C-3), 84.8 (C-4), 116.8 (CN), 127.4–
138.0 (Ph).
(CH2Ph), 75.2 (CH2Ph), 75.3 (CH2Ph), 78.8 (C-5), 79.8 (C-2), 81.3
(C-3), 84.0 (C-4), 127.2–138.9 (Ph), 198.3 (CH2COPh).
HRMS (ESI): m/z [M + Na+] calcd for C46H50O6: 721.3505; found:
721.3552.
HRMS (ESI): m/z [M + Na+] calcd for C42H41NO5: 662.2882;
found: 662.2913.
2-[(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-yl]-1-phenylethanone (7d)
(Table 1, Entry 29)
TMSOTf (7.3 mL, 0.04 mmol) was added to a solution of 1d (117.1
mg, 0.2 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (124 mL, 0.6
mmol) in MeCN (3 mL) at –40 °C in the presence of CaSO4 (ca. 100
mg). The resulting mixture was stirred for 2 h, and then the same
procedure was followed as for the remaining preparation of 3a, giv-
ing 7d as a white oil. Yield: 72.7 mg (53%).
1-Phenyl-2-[(2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-methyltetrahydropyran-2-yl]ethanone (7a)
(Table 1, Entry 26)
TMSOTf (6.8 mL, 0.037 mmol) was added to a solution of 1a (119
mg, 0.21 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (132 mL,
0.64 mmol) in MeCN (3 mL) at –40 °C in the presence of CaSO4
(ca. 100 mg). The resulting mixture was stirred for 3 h, and then the
same procedure was followed as for the remaining preparation of
3a, giving 7a4b as a white oil. Yield: 137.4 mg (98%).
2-[(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-yl]-1-phenylethanone (7d)
(Table 1, Entry 39)
TMSOTf (5.8 mL, 0.032 mmol) was added to a solution of 9d (99.2
mg, 0.16 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (98 mL,
0.47 mmol) in MeCN–CH2Cl2 (1:1, 2 mL) at –78 °C in the presence
of CaSO4 (ca. 100 mg). The resulting mixture was stirred for 2 h,
and then the same procedure was followed as for the remaining
preparation of 3a, giving 7d as a white oil. Yield: 100.5 mg (93%).
1-Phenyl-2-[(2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-ethyltetrahydropyran-2-yl]ethanone (7b)
(Table 1, Entry 27)
TMSOTf (6.8 mL, 0.037 mmol) was added to a solution of 1b (105.9
mg, 0.19 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (114.5 mL,
0.56 mmol) in MeCN (3 mL) at –40 °C in the presence of CaSO4
(ca. 100 mg). The resulting mixture was stirred for 3 h, and then the
same procedure was followed as for the remaining preparation of
3a, giving 7b as a white oil. Yield: 112.0 mg (91%).
[a]D23 +43.1 (c 3.48, CHCl3).
1H NMR (400 MHz, CDCl3): d = 2.38 (dd, J = 9.3, 14.4 Hz, 1 H,
CHaHbCH=CH2), 2.52 (dd, J = 9.3, 14.6 Hz, 1 H, CHaHbCH=CH2),
3.02 (d, J = 14.6 Hz, 1 H, CHaHbCOPh), 3.40 (d, J = 14.4 Hz, 1 H,
CHaHbCOPh), 3.46–3.49 (m, 1 H, Ha-7), 3.50 (d, J = 9.0 Hz, 1 H,
H-3), 3.53 (t, J = 9.3 Hz, 1 H, H-5), 3.62 (dd, J = 3.4, 11.3 Hz, 1 H,
Hb-7), 3.70–3.73 (m, 1 H, H-6), 3.73 (t, J = 9.0 Hz, 1 H, H-4), 4.33–
4.73 (m, 8 H, CH2Ph), 4.84–4.92 (m, 2 H, CH2CH=CH2), 5.74–5.85
(m, 1 H, CH2CH=CH2), 7.01–7.77 (m, 25 H, Ph).
13C NMR (100 MHz, CDCl3): d = 36.9 (CH2COPh), 41.6
(CH2CH=CH2), 68.9 (C-7), 73.0 (C-6), 73.3 (CH2Ph), 74.8
(CH2Ph), 74.9 (CH2Ph), 75.3 (CH2Ph), 78.7 (C-5), 79.9 (C-2), 81.3
(C-3), 83.8 (C-4), 118.4 (CH2CH=CH2), 127.2–132.9 (Ph), 133.8
(CH2CH=CH2), 136.9–138.7 (Ph), 198.2 (CH2COPh).
[a]D23 +35.7 (c 3.47, CHCl3).
1H NMR (400 MHz, CDCl3): d = 0.90 (t, J = 7.3 Hz, 3 H, CH2CH3),
1.76–1.80 (m, 1 H, CHaHbCH3), 1.84–1.88 (m, 1 H, CHaHbCH3),
3.09 (d, J = 14.4 Hz, 1 H, CHaHbCOPh), 3.61 (d, J = 14.4 Hz, 1 H,
CHaHbCOPh), 3.64 (d, J = 9.3 Hz, 1 H, H-3), 3.66–3.69 (m, 1 H,
Ha-7), 3.72 (t, J = 9.3 Hz, 1 H, H-5), 3.82 (dd, J = 3.6, 11.3 Hz, 1
H, Hb-7), 3.88–3.92 (m, 1 H, H-6), 3.92 (t, J = 9.1 Hz, 1 H, H-4),
4.50–4.90 (m, 8 H, CH2Ph), 7.19–7.96 (m, 25 H, Ph).
13C NMR (100 MHz, CDCl3): d = 7.5 (CH2CH3), 29.7 (CH2CH3),
36.9 (CH2COPh), 69.0 (C-7), 72.9 (C-6), 73.3 (CH2Ph), 75.0
(CH2Ph), 75.2 (CH2Ph), 75.4 (CH2Ph), 78.8 (C-5), 79.8 (C-2), 80.7
(C-3), 84.0 (C-4), 127.3–138.8 (Ph), 198.4 (CH2COPh).
HRMS (ESI): m/z [M + Na+] calcd for C44H46O6: 693.3192; found:
693.3144.
Anal. Calcd for C45H46O6: C, 79.15; H, 6.79. Found: C, 78.79; H,
6.74.
1-Phenyl-2-[(2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-butyltetrahydropyran-2-yl]ethanone (7c)
(Table 1, Entry 28)
TMSOTf (7.4 mL, 0.041 mmol) was added to a solution of 1c (121
mg, 0.20 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (124.7 mL,
0.61 mmol) in MeCN (3 mL) at –40 °C in the presence of CaSO4
(ca. 100 mg). The resulting mixture was stirred for 3 h, and then the
same procedure was followed as for the remaining preparation of
3a, giving 7c as a white oil. Yield: 123.6 mg (87%).
2-[(2R,3R,4S,5R,6R)-2-Benzyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-yl]-1-phenylethanone (7e)
(Table 1, Entry 30)
TMSOTf (6.8 mL, 0.037 mmol) was added to a solution of 1e (117.9
mg, 0.19 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (115 mL,
0.56 mmol) in MeCN (3.0 mL) at –40 °C in the presence of CaSO4
(ca. 100 mg). The resulting mixture was stirred for 2 h, and then the
same procedure was followed as for the remaining preparation of
3a, giving 7e as a white oil. Yield: 83.7 mg (61%).
[a]D23 +23.3 (c 3.47, CHCl3).
1H NMR (400 MHz, CDCl3): d = 0.80 (t, J = 6.9 Hz, 3 H,
CH2CH2CH2CH3), 1.18–1.28 (m, 3 H, CH2CHaHbCH2CH3), 1.43–
2-[(2R,3R,4S,5R,6R)-2-Benzyl-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyltetrahydropyran-2-yl]-1-phenylethanone (7e)
(Table 1, Entry 40)
TMSOTf (2.7 mL, 0.015 mmol) was added to a solution of 9e (50.4
mg, 0.075 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (46.1 mL,
0.22 mmol) in MeCN–CH2Cl2 (1:1, 2 mL) at –78 °C in the presence
of CaSO4 (ca. 100 mg). The resulting mixture was stirred for 2 h,
and then the same procedure was followed as for the remaining
preparation of 3a, giving 7e as a white oil. Yield: 46.4 mg (91%).
1.53 (m,
1 H, CH2CHaHbCH2CH3), 1.68–1.84 (m, 2 H,
CH2CH2CH2CH3), 3.10 (d, J = 14.4 Hz, 1 H, CHaHbCOPh), 3.59 (d,
J = 14.4 Hz, 1 H, CHaHbCOPh), 3.64 (d, J = 9.3 Hz, 1 H, H-3), 3.65
(d, J = 11.0 Hz, 1 H, Ha-7), 3.70 (t, J = 9.6 Hz, 1 H, H-5), 3.80 (dd,
J = 3.6, 11.1 Hz, 1 H, Hb-7), 3.84–3.89 (m, 1 H, H-6), 3.91 (t, J =
9.3 Hz, 1 H, H-4), 4.51–4.90 (m, 8 H, CH2Ph), 7.19–7.88 (m, 25 H,
Ph).
13C NMR (100 MHz, CDCl3): d = 14.2 (CH2CH2CH2CH3), 23.0
(CH2CH2CH2CH3), 25.2 (CH2CH2CH2CH3), 36.9 (CH2COPh), 37.1
(CH2CH2CH2CH3), 69.0 (C-7), 72.9 (C-6), 73.3 (CH2Ph), 75.0
[a]D23 +34.2 (c 2.85, CHCl3).
1H NMR (400 MHz, CDCl3): d = 3.05 (d, J = 14.4 Hz, 1 H, CCHaHb-
Ph), 3.22 (d, J = 14.4 Hz, 1 H, CHaHbCOPh), 3.30 (d, J = 14.1 Hz,
1 H, CCHaHbPh), 3.47 (d, J = 9.0 Hz, 1 H, H-3), 3.63 (d, J = 9.3 Hz,
1 H, H-5), 3.69 (d, J = 14.4 Hz, 1 H, CHaHbCOPh), 3.71–3.73 (m,
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

3030
Y. Oda, T. Yamanoi
PAPER
(2R,3R,4S,5R,6R)-2-Acetoxy-2-allyl-3,4,5-tris(benzyloxy)-6-
1 H, Ha-7), 3.82 (dd, J = 3.1, 10.8 Hz, 1 H, Hb-7), 3.89–3.93 (m, 2
H, H-4, H-6), 4.51–4.86 (m, 8 H, CH2Ph), 7.09–7.96 (m, 30 H, Ph).
(benzyloxy)methyltetrahydropyran (9d)
To a solution of 1d (417.3 mg, 0.72 mmol) in dry THF (5 mL) at
–78 °C was added 1.6 M n-BuLi in n-hexane (0.54 mL, 0.86 mmol)
under an Ar atmosphere, and the mixture was stirred for 1 h. The
temperature was gradually raised to –20 °C, and Ac2O (1.2 mL, 12.7
mmol) was added to the solution. The resulting mixture was stirred
for 1 h. The reaction was then quenched with sat. NaHCO3 soln (15
mL). The mixture was extracted with EtOAc, and the organic layer
was washed with H2O and sat. NaCl soln. After the organic layer
was dried (Na2SO4), the solvent was evaporated under reduced pres-
sure. The crude product was purified by preparative TLC (silica gel,
EtOAc–hexane, 1:4) to give 9d as a white oil. Yield: 367.7 mg
(82%).
13C NMR (100 MHz, CDCl3): d = 37.6 (CH2COPh), 43.1
(CCH2Ph), 69.2 (C-7), 72.8 (C-6), 73.2 (CH2Ph), 74.4 (CH2Ph),
74.8 (CH2Ph), 75.2 (CH2Ph), 78.6 (C-5), 80.4 (C-3), 80.7 (C-2),
84.0 (C-4), 126.3–138.8 (Ph), 198.5 (CH2COPh).
HRMS (ESI): m/z [M + Na+] calcd for C49H48O6: 755.3349; found:
755.3376.
1-Phenyl-2-[(2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyl-
oxy)methyl-2-phenyltetrahydropyran-2-yl]ethanone (7f)
(Table 1, Entry 31)
TMSOTf (6.9 mL, 0.038 mmol) was added to a solution of 1f (116.8
mg, 0.19 mmol) and 1-phenyl-1-(trimethylsiloxy)ethene (109.3 mL,
0.53 mmol) in MeCN (3 mL) at –40 °C in the presence of CaSO4
(ca. 100 mg). The resulting mixture was stirred for 3 h, and then the
same procedure was followed as for the remaining preparation of
3a, giving 7f as a white oil. Yield: 105.5 mg (78%).
[a]D23 +78.2 (c 2.61, CHCl3).
1H NMR (600 MHz, CDCl3): d = 2.07 (s, 3 H, CH3), 2.89 (dd, J =
9.0, 15.0 Hz, 1 H, CHaHbCH=CH2), 3.42 (dd, J = 5.0, 15.0 Hz, 1 H,
CHaHbCH=CH2), 3.52 (d, J = 9.0 Hz, 1 H, H-3), 3.64 (d, J = 9.0 Hz,
1 H, H-6), 3.71 (d, J = 11.0 Hz, 1 H, Ha-7), 3.80 (t, J = 9.0 Hz, 1 H,
H-5), 3.83 (dd, J = 2.8, 11.0 Hz, 1 H, Hb-7), 4.01 (t, J = 9.0 Hz, 1
H, H-4), 4.53–4.92 (m, 8 H, CH2Ph), 5.07–5.10 (m, 2 H,
CH2CH=CH2), 5.86–5.88 (m, 1 H, CH2CH=CH2), 7.17–7.36 (m, 20
H, Ph).
13C NMR (150 MHz, CDCl3): d = 22.2 (CH3), 38.4 (CH2CH=CH2),
68.2 (C-7), 73.4 (CH2Ph), 73.5 (C-6), 75.1 (2 CH2Ph), 75.4
(CH2Ph), 77.6 (C-5), 80.8 (C-3), 83.0 (C-4), 105.7 (C-2), 118.7
(CH2CH=CH2), 127.5–128.4 (Ph), 132.6 (CH2CH=CH2), 137.9–
138.4 (Ph), 168.6 (C=O).
[a]D23 +33.9 (c 4.39, CHCl3).
1H NMR (400 MHz, CDCl3): d = 3.47 (d, J = 8.9 Hz, 1 H, H-3), 3.71
(d, J = 17.2 Hz, 1 H, CHaHbCOPh), 3.77 (dd, J = 1.4, 11.0 Hz, 1 H,
Ha-7), 3.85–3.87 (m, 1 H, H-6), 3.89 (dd, J = 2.8, 10.3 Hz, 1 H,
Hb-7), 3.91 (d, J = 10.3 Hz, 1 H, CH2Ph), 3.92 (d, J = 9.6 Hz, 1 H,
H-5), 4.00 (t, J = 9.6 Hz, 1 H, H-4), 4.14 (d, J = 17.2 Hz, 1 H,
CHaHbCOPh), 4.59–4.95 (m, 7 H, CH2Ph), 7.17–7.44 (m, 26 H, Ph),
7.61 (d, J = 6.9 Hz, 2 H, CPh), 7.77 (d, J = 6.9 Hz, 2 H, Ph).
13C NMR (100 MHz, CDCl3): d = 36.0 (CH2COPh), 69.1 (C-7),
73.1 (C-6), 73.5 (CH2Ph), 75.1 (CH2Ph), 75.5 (CH2Ph), 75.7
(CH2Ph), 78.6 (C-5), 79.5 (C-2), 84.2 (C-4), 86.8 (C-3), 125.7–
143.4 (Ph), 196.3 (CH2COPh).
HRMS (ESI): m/z [M + Na+] calcd for C39H42O7: 645.2828; found:
645.2811.
HRMS (ESI): m/z [M + Na+] calcd for C48H46O6: 741.3192; found:
741.3188.
(2R,3R,4S,5R,6R)-2-Acetoxy-2-benzyl-3,4,5-tris(benzyloxy)-6-
(benzyloxy)methyltetrahydropyran (9e)
To a solution of 1e (362.2 mg, 0.57 mmol) in THF (6 mL) at –78 °C
was added 1.6 M n-BuLi in n-hexane (0.43 mL, 0.68 mmol) under
an Ar atmosphere, and the mixture was stirred for 1 h. The temper-
ature was gradually raised to –20 °C, and Ac2O (0.6 mL, 6.3 mmol)
was added to the solution. The resulting mixture was stirred for 1 h,
and then the same procedure was followed as for the remaining
preparation of 9d, giving 9e as a white oil. Yield: 364.1 mg (94%).
(2S,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-(benzyloxy)methyl-
2-butyltetrahydropyran-2-ol (1c)
To a solution of 2,3,4,6-tetra-O-benzyl-D-glucono-1,5-lactone
(1.0037 g, 1.86 mmol) in THF (10 mL) at –78 °C was added 1.5 M
n-BuLi in n-hexane (1.46 mL, 2.23 mmol) under an Ar atmosphere,
and the mixture was stirred for 2 h. The reaction was then quenched
with H2O (15 mL). The mixture was extracted with CHCl3, and the
organic layer was washed with H2O and sat. NaCl soln. After the or-
ganic layer was dried (Na2SO4), the solvent was evaporated under
reduced pressure. The crude product was purified by flash column
chromatography (silica gel, EtOAc–hexane, 1:8) to give 1c as a
white oil. Yield: 1.0562 g (95%).
[a]D23 +46.1 (c 1.40, CHCl3).
1H NMR (600 MHz, CDCl3): d = 2.14 (s, 3 H, CH3), 3.25 (d, J =
13.7 Hz, 1 H, CCHaHbPh), 3.30 (d, J = 8.9 Hz, 1 H, H-3), 3.67–3.70
(m, 1 H, H-6), 3.73 (t, J = 9.0 Hz, 1 H, H-5), 3.80 (dd, J = 2.0, 11.0
Hz, 1 H, Ha-7), 3.87 (dd, J = 2.8, 11.0 Hz, 1 H, Hb-7), 4.03 (t, J =
8.9 Hz, 1 H, H-4), 4.20 (d, J = 13.8 Hz, 1 H, CCHaHbPh), 4.40–4.90
(m, 8 H, CH2Ph), 7.15–7.37 (m, 25 H, Ph).
13C NMR (150 MHz, CDCl3): d = 22.4 (CH3), 39.9 (CCH2Ph), 68.5
(C-7), 73.3 (CH2Ph), 73.6 (C-6), 74.5 (CH2Ph), 75.2 (CH2Ph), 75.4
(CH2Ph), 77.6 (C-5), 79.5 (C-3), 83.3 (C-4), 106.8 (C-2), 126.6–
138.8 (Ph), 168.9 (C=O).
1H NMR (600 MHz, CDCl3): d = 0.86 (t, J = 6.9 Hz, 3 H,
CH2CH2CH2CH3), 1.24–1.25 (m, 3 H, CH2CHaHbCH2CH3), 1.33–
1.40 (m,
1
H, CH2CHaHbCH2CH3), 1.63–1.66 (m,
2
H,
CH2CH2CH2CH3), 2.68 (s, 1 H, OH), 3.43 (d, J = 8.9 Hz, 1 H, H-
3), 3.64 (t, J = 9.6 Hz, 1 H, H-5), 3.66 (dd, J = 3.4, 9.6 Hz, 1 H, Ha-
7), 3.74 (dd, J = 4.1, 11.0 Hz, 1 H, Hb-7), 3.99 (dd, J = 2.0, 12.2 Hz,
1 H, H-6), 4.01 (t, J = 8.9 Hz, 1 H, H-4), 4.52–4.93 (m, 8 H, CH2Ph),
7.19–7.34 (m, 20 H, Ph).
HRMS (ESI): m/z [M + Na+] calcd for C43H44O7: 695.2985; found:
695.2944.
13C NMR (150 MHz, CDCl3): d = 14.0 (CH2CH2CH2CH3), 22.8
(CH2CH2CH2CH3),
24.7
(CH2CH2CH2CH3),
38.3
References
(CH2CH2CH2CH3), 68.8 (C-7), 71.5 (C-6), 73.2 (CH2Ph), 74.8
(CH2Ph), 75.3 (CH2Ph), 75.5 (CH2Ph), 78.5 (C-5), 81.3 (C-3), 83.8
(C-4), 98.4 (C-2), 126.9–138.6 (Ph).
HRMS (ESI): m/z [M + Na+] calcd for C38H44O6: 619.3030; found:
(1) Levy, D. E.; Tang, C. The Chemistry of C-Glycosides;
Pergamon: Oxford, 1995.
(2) For examples, see: (a) Suh, H.; Wilcox, C. S. J. Am. Chem.
Soc. 1998, 110, 470. (b) Nicolaou, K. C.; Bunnage, M. K.;
McGarry, D. G.; Shi, S.; Somers, P. K.; Wallace, P. A.; Chu,
619.3036.
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York

PAPER
Trifluoromethanesulfonate-Catalyzed Nucleophilic Substitution To Give C- and N-Glucopyranosides
3031
X.-J.; Agrios, K. A.; Gunzner, J. L.; Yang, Z. Chem. Eur. J.
(5) (a) See reference 4c. (b) Yamanoi, T.; Matsuda, S.;
Yamazaki, I.; Inoue, R.; Hamasaki, K.; Watanabe, M.
1999, 5, 599. (c) Nicolaou, K. C.; Reddy, K. R.; Skokotas,
G.; Sato, F.; Xiao, X.-Y.; Hwang, C.-K. J. Am. Chem. Soc.
1993, 115, 3558. (d) Gomez, A. M.; Casillas, M.; Valverde,
S.; Lopez, J. C. Tetrahedron: Asymmetry 2001, 12, 2175.
(3) For examples, see: (a) Kraus, G. A.; Molina, M. T. J. Org.
Chem. 1988, 53, 752. (b) Czernecki, S.; Ville, G. J. Org.
Chem. 1989, 54, 610.
Heterocycles 2006, 68, 673. (c) Yamanoi, T.; Inoue, R.;
Matsuda, S.; Katsuraya, K.; Hamasaki, K. Tetrahedron:
Asymmetry 2006, 17, 2914. (d) Yamanoi, T.; Matsumura,
K.; Matsuda, S.; Oda, Y. Synlett 2005, 2973. (e) Yamanoi,
T.; Oda, Y.; Yamazaki, I.; Shinbara, M.; Morimoto, K.;
Matsuda, S. Lett. Org. Chem. 2005, 2, 242.
(4) For examples of reported C-glycosidation methods, see:
(a) Chen, G.-R.; Fei, Z. B.; Huang, X.-T.; Xie, Y.-Y.; Xu, J.-
L.; Gola, J.; Steng, M.; Praly, J.-P. Eur. J. Org. Chem. 2001,
2939. (b) Gomez, A. M.; Uriel, C.; Jarosz, S.; Valverde, S.;
Lopez, J. C. Eur. J. Org. Chem. 2003, 4830; and references
cited therein. For the reported O-glycosidation methods,
see: (c) Yamanoi, T.; Oda, Y.; Matsuda, S.; Yamazaki, I.;
Matsumura, K.; Katsuraya, K.; Watanabe, M.; Inazu, T.
Tetrahedron 2006, 62, 10383. (d) See also references cited
in reference 4c.
(6) Yamanoi, T.; Oda, Y. Heterocycles 2002, 57, 229.
(7) We also found that glucopyranoses carrying vinyl groups at
the anomeric centers showed quite different reactivity with
nucleophiles such as allyltrimethylsilane and silyl enol
ethers. The reactions of the glucopyranoses with these
nucleophiles in the presence of TMSOTf afforded the exo-
glycals via an SN1¢-type reaction mechanism, see: Yamanoi,
T.; Nara, Y.; Matsuda, S.; Oda, Y.; Yoshida, A.; Katsuraya,
K.; Watanabe, M. Synlett 2007, 785.
(8) Wenger, W.; Vasella, A. Helv. Chim. Acta 2000, 1542.
(9) Yang, W.-B.; Yang, Y.-Y.; Gu, Y.-F.; Wang, S.-H.; Chang,
C.-C.; Lin, C.-H. J. Org. Chem. 2002, 67, 3773.
(10) Ellsworth, B. A.; Doyle, A. G.; Patel, M.; Caceres-Cortes, J.;
Meng, W.; Deshpande, P. P.; Pullockaran, A.; Washburn, W.
N. Tetrahedron: Asymmetry 2003, 14, 3243.
(11) Li, X.; Ohtake, H.; Takahashi, H.; Ikegami, S. Tetrahedron
2001, 57, 4283.
Synthesis 2007, No. 19, 3021–3031 © Thieme Stuttgart · New York