Syntheses of a partially benzylated derivative of the anhydro-d-altro-heptulose found in Coriaria japonica A and of its analogs

Article abstract of DOI:10.1016/j.tet.2008.06.068

A partially benzylated derivative of anhydro-d-altro-heptulose found in Coriaria japonica A, which is a synthetically useful unit, was successfully synthesized from a d-mannose derivative by a novel synthetic approach involving the intramolecular O-ketopy

Full text of DOI:10.1016/j.tet.2008.06.068

Tetrahedron 64 (2008) 8082–8088
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Tetrahedron
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Syntheses of a partially benzylated derivative of the anhydro- -altro-heptulose
D
found in Coriaria japonica A and of its analogs
,
,
b
Sho Matsuda a b, Takashi Yamanoi a , Mikio Watanabe
*
a The Noguchi Institute, 1-8-1 Kaga, Itabashi-ku, Tokyo 173-0003, Japan
b Department of Chemistry, School of Science, Tokai University, Kitakaname 1117, Hiratsuka, Kanagawa 259-1292, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A partially benzylated derivative of anhydro-D-altro-heptulose found in Coriaria japonica A, which is
Received 25 January 2008
Received in revised form 18 June 2008
Accepted 18 June 2008
a synthetically useful unit, was successfully synthesized from a
D
-mannose derivative by a novel
synthetic approach involving the intramolecular O-ketopyranosylation reaction developed by us. This
synthetic approach was also applicable to the preparation of its four analogs.
Ó 2008 Elsevier Ltd. All rights reserved.
Available online 21 June 2008
Keywords:
Anhydrosugar
Anhydro-D-altro-heptulose
Anhydrohexose
Synthesis
Coriaria japonica A
1. Introduction
D
-mannopyranose derivative to a
introduction of a vinyl group into the C-1 position of the altro-
pyranose derivative to produce a 1-C-vinylated -altro-pyranose
derivative, (3) intramolecular O-glycosidation of the 1-C-vinylated
-altro-pyranose derivative to form the anhydroketopyranose
D-altro-pyranose derivative, (2)
Several
anhydroketopyranoses
having
6,8-dioxabicy-
D
clo[3.2.1]octane structures are found in natural products such as
Sedum spectabile,1 Smallanthus sonchifolius,2 and Coriaria japonica
D
A.3 Coriariin, found in C. japonica A, has an anhydro-
D-altro-hep-
structure, and (4) conversion of the vinyl group of the anhy-
droketopyranose into a hydroxymethyl group to produce the
desired compound 2. The third key reaction step is based on the
tulose 1 bound to a tannin via an ester linkage (Fig. 1). Its analogs
have biologically important antitumor and antivirus activities.3
Compound 1 is synthetically interesting because it has not only
a unique anhydroketopyranose structure but also a rare D-altro-
pyranose-ring configuration. Several synthetic approaches to 1
OH
OH
OH
have been reported, such as enzymatic transketolization reaction of
O
hydroxypyruvic acid with D
-ribose,4 molybdic acid treatment of
O
O
OH
C
O
2-C-hydroxymethyl-allofuranose,5 and radical intramolecular
cyclization of a C-altropyranoside derivative via intramolecular
hydrogen abstraction reaction.6 Unfortunately, these methods
require complicated processes or special compounds.
O
OH
OH
O
O
OH
HO
OH
HO
HO
Coriariin
1
HO
Our preliminary letter described the synthesis of a partially
benzylated anhydro-D
-altro-heptulose derivative 2.7 Compound 2 is
O
a useful unit for synthesizing coriariin because it has a free hydroxyl
function as a binding site with a tannin and its other hydroxyl
functions are protected by benzyl groups. Our approach to 2 starts
O
R6
R2
OH
OH
O
O
R3
OBn
R5
R1
BnO
from a D-mannopyranose derivative and consists of the following
BnO
R4
5 : R5 = OBn, R6 = H
key reaction steps: (1) steric inversion at the C-3 position from a
2 : R1 = OBn, R2 = H, R3 = OBn, R4 = H
3 : R1 = H, R2 = OBn, R3 = H, R4 = OBn
4 : R1 = H, R2 = OBn, R3 = OBn, R4 = H
6 : R5 = H, R6 = OBn
* Corresponding author. Tel./fax: þ81 3 5944 3213.
E-mail address: tyama@noguchi.or.jp (T. Yamanoi).
Figure 1.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.06.068

S. Matsuda et al. / Tetrahedron 64 (2008) 8082–8088
8083
OR2
OTBS
OTBS
OTBS
OBn
OBn
OBn
OBn
O
(g)
(c)
BnO
(f)
O
O
O
BnO
R1O
BnO
BnO
2
4
O
2
4
OH
R1O
BnO
O
O
BnO
7: R1= H, R2= H
10: R1= Ac
11: R1= H
12: R1= Bn
13
14
(h)
(a)
(b)
(d)
(e)
8: R1= H, R2= TBS
9: R1= Tf, R2= TBS
OTBS
O
O
5
OBn
OH
OBn
(i)
O
1
(j)
BnO
O
O
OBn
4
2
OBn
OBn
BnO
OH
BnO
BnO
2
16
15
Scheme 1. Reagents and conditions: (a) TBSCl (2 equiv), imidazole (2 equiv), CH2Cl2, rt, 2 h, 88%; (b) Tf2O (1.5 equiv), pyridine, ꢁ20 ꢀC to rt, 2.5 h, 93%; (c) CsOAc (2 equiv),
18-crown-6 (2 equiv), toluene, sonication, 30 ꢀC, 24 h, 62%; (d) NaOMe, MeOH (cat.), rt, overnight, 95%; (e) BnBr (1.7 equiv), NaH (4 equiv), DMF, 0 ꢀC to rt, overnight, 96%; (f) PdCl2
(3 equiv), AcOH–AcONa buffer, sonication, 30 ꢀC, 4 h, 87%; (g) DMSO, Ac2O, rt, overnight, 99%; (h) vinylMgCl (1.2 equiv), CeCl3 (1.2 equiv), toluene, ꢁ78 ꢀC, 1 h, 62%; (i) TfOH
(0.05 equiv), CH3CN, 0 ꢀC, 88%; (j) O3, Ph3P (5 equiv), CH2Cl2, ꢁ78 ꢀC, 45 min, then NaBH4 (8 equiv), THF, 0 ꢀC, 3 h, 72%.
intramolecular O-ketosylation reaction developed by us. It can ef-
ficiently convert ketopyranoses into anhydroketopyranoses having
the 6,8-dioxabicyclo[3.2.1]octane structures.8
The above-mentioned synthetic method was expected to be
applicable to the preparation of some analogs of 2. We then utilized
our method for the synthesis of the four compounds shown in
into C-1 of 14 to produce 15, which is the second key reaction step,
was successfully achieved in 62% yield using vinylmagnesium
chloride (1.2 equiv) in toluene in the presence of CeCl313 (1.2 equiv)
at ꢁ78 ꢀC for 1 h.
Intramolecular O-glycosidation of 15, which is the third key
reaction step, smoothly proceeded to afford the desired compound
16 in 88% yield using 5 mol % TfOH in the presence of CaSO4 in
CH3CN at 0 ꢀC for 2 h. These are the same reaction conditions as
those used in our previous study.8 It is unnecessary to deprotect the
TBS group at C-6 of 15 prior to the intramolecular O-glycosidation
because the TBS group is removed under acidic conditions during
the intramolecular O-glycosidation, as we reported previously.8
As the final key reaction step, the vinyl group of 16 was con-
verted into a hydroxymethyl group to give the desired 2. Compound
2 was obtained from 16 in 72% yield by ozone oxidation and
treatment with triphenylphosphine (5 equiv) at ꢁ78 ꢀC for 45 min,
Figure 1. The anhydro-
manno-heptulose 4 are stereoisomeric analogs of 2. The anhydro-
altro-octulose 5 and the anhydro-
D
-gluco-heptulose 3 and the anhydro-
D
-
-
D
D-manno-octulose 6 are analogs
of 2 having a hydroxyethyl group at C-5. This paper describes in
detail the synthetic approaches to 2 and its four analogs 3–6.
2. Results and discussion
Our synthetic approach to 2 from 79 is shown in Scheme 1. First,
the conversion of 7 into 9 was investigated. A tert-butyldime-
thylsilyl (TBS) group was introduced into C-6 of 7 using TBSCl and
imidazole in CH2Cl2. Introduction of a Tf group into C-3 was per-
formed using Tf2O in pyridine. Steric inversion at C-3 of 9 into 10,
which is the first key reaction step, was successfully accomplished
in 62% yield using AcOCs (2 equiv) in the presence of 18-crown-6
(2 equiv) in toluene at 30 ꢀC for 24 h under ultrasonic conditions.10
The altropyranoside structure of 10 was assigned by measurement
of the 1H NMR spectrum. The signal of H-3 of 10 was observed at
5.33 ppm with a triplet peak (J2,3¼3.4 Hz, J3,4¼3.4 Hz), and its spin
coupling constants indicated the dihedral angles of H-2eq–H-3eq
and H-3eq–H-4ax. These results supported the ring conformation of
the altropyranoside.
Next, the conversion of 10 into the lactone 14 was investigated.
Deprotection of the acetyl group of 10 using NaOMe in MeOH and
subsequent introduction of the benzyl group to C-3 using NaH and
benzyl bromide in DMF gave 12. The allyl group of 12 was removed
using PdCl2 in AcOH–AcONa at 30 ꢀC for 4 h under ultrasonic con-
ditions.11 Oxidation of 13 using dimethyl sulfoxide (DMSO) and
Ac2O12 produced the desired 14. Introduction of the vinyl group
14
and subsequent reduction using NaBH4 (8 equiv) at 0 ꢀC for 3 h.
Next, the stereoisomers 3 and 4 were synthesized by the same
synthetic approach, as shown in Scheme 2. The introduction of the
vinyl group to the lactone 17 or 20 was performed efficiently using
vinylmagnesium chloride. The intramolecular O-glycosidation of 18
or 21 to afford the ketopyranose 19 or 22 was accomplished in the
presence of 5 mol % TfOH. The conversion of 19 or 22 into the
desired 3 or 4 was successfully accomplished by ozone oxidation
and subsequent reduction using NaBH4.
The syntheses of the octulose analogs 5 and 6 were also
examined, as shown in Scheme 3. The syntheses of 5 and 6 were
successfully achieved from 14 or 25 by introduction of an allyl
group to C-1 using allylmagnesium bromide, intramolecular
O-glycosidation using 5 mol % TfOH, and conversion of terminal
olefins to the hydroxyethyl group.
In summary, a partially benzylated anhydro-
derivative 2, which is a synthetically useful unit for coriariin found
in C. japonica A, was successfully synthesized from a -mannose
D-altro-heptulose
D
derivative by
a
novel synthetic approach involving the
OTBS
OTBS
O
O
R2
O
5
R2
R2
O
OBn
O
OBn
OH
1
(a) or (b)
(c)
(d)
O
BnO
BnO
BnO
BnO
2
R2
2
4
O
4
R1
BnO
R1
BnO
R1
R1
OH
17: R1= OBn, R2= H
20: R1= H, R2= OBn
18: R1= OBn, R2= H
21: R1= H, R2= OBn
19: R1= OBn, R2= H
22: R1= H, R2= OBn
3: R1= OBn, R2= H
4: R1= H, R2= OBn
Scheme 2. Reagents and conditions: (a) vinylMgCl (1.2 equiv), THF, ꢁ78 ꢀC, 1 h, 80% (18); (b) vinylMgCl (1.5 equiv), CeCl3 (1.5 equiv), toluene, ꢁ78 ꢀC, 1 h, 64% (21); (c) TfOH
(0.05 equiv), CH3CN, 0 ꢀC, 89% (19), 89% (22); (d) O3, Ph3P (5 equiv), CH2Cl2, ꢁ78 ꢀC, 45 min, then NaBH4 (8 equiv), THF, 0 ꢀC, 3 h, 73% (3), 77% (4).

8084
S. Matsuda et al. / Tetrahedron 64 (2008) 8082–8088
OR3
OR3
O
O
R2
R2
OBn
O
OBn
O
5
1
(a) or (b)
(c)
(d)
O
O
BnO
R2
BnO
R2
OH
2
OBn
OBn
2
O
4
4
R1
BnO
R1
BnO
R1
R1
OH
14: R1= OBn, R2= H, R3= TBS
23: R1= OBn, R2= H, R3= TBS
24: R1= OBn, R2= H
5: R1= OBn, R2= H
25: R1= H, R2= OBn, R3= Ac
26: R1= H, R2= OBn, R3= H
27: R1= H, R2= OBn
6: R1= H, R2= OBn
Scheme 3. Reagents and conditions: (a) allylMgBr (1.2 equiv), THF, ꢁ78 ꢀC, 1.5 h, 92% (23); (b) allylMgCl (2.4 equiv), THF, ꢁ78 ꢀC, 2 h, 85% (26); (c) TfOH (0.05 equiv), CH3CN, 0 ꢀC,
99% (24), 87% (27); (d) O3, Ph3P (5 equiv), CH2Cl2, ꢁ78 ꢀC, 45 min, then NaBH4 (3 equiv), THF, 0 ꢀC, 3 h, 85% (5), 95% (6).
intramolecular O-ketopyranosylation reaction developed by us.
This approach was also found to be applicable to the syntheses of
washed with a solution of ~30% citric acid, water, and brine. After
the organic layer was dried over anhydrous Na2SO4, the organic
solvent was filtered and evaporated under reduced pressure. The
crude product was purified by flash silica gel column chromatog-
the four analogs: anhydro-
D
-gluco-heptulose 3, anhydro-
D
-manno-
-manno-
heptulose 4, anhydro-D-altro-octulose 5, and anhydro-
octulose 6.
D
raphy (ethyl acetate/hexane¼1:2) to give 9 (167.8 mg, 93% yield) as
23
a colorless oil. [
a
]
þ35 (c 2.6, CHCl3). 1H NMR (CDCl3):
d 0.069 (3H,
D
3. Experimental
3.1. General
s, (CH3)2Si), 0.073 (3H, s, (CH3)2Si), 0.89 (9H, s, (CH3)3C), 3.62 (1H,
dd, J¼2.8, 12.4 Hz, H-6), 3.49 (1H, d, J¼11.7 Hz, OCHaHbCH]CH2),
3.88–3.93 (2H, m, Ha-7, OCHaHbCH]CH2), 3.97 (1H, dd, J¼2.1,
2.7 Hz, H-3), 4.10 (1H, dd, J¼5.5, 13.1 Hz, Hb-7), 4.19 (1H, t, J¼9.6 Hz,
H-5), 4.86 (1H, s, H-2), 5.16–5.23 (2H, m, OCH2CH]CH2), 5.27 (1H,
dd, J¼3.4, 9.6 Hz, H-4), 5.81 (1H, m, OCH2CH]CH2). 13C NMR
1H NMR and 13C NMR spectra were recorded on JEOL EX-400
and ECA-600 spectrometers in CDCl3 using TMS as the internal
standard. IR spectra were registered on a JASCCO FT/IR-460Plus
spectrophotometer. Optical rotations were recorded on a JASCO
DIP-360 digital polarimeter. High-resolution mass spectra (HRMS)
were obtained on a Mariner spectrometer (PerSeptive Biosystems,
Inc.). Preparative thin-layer chromatography (TLC) was performed
on Merck silica gel 60GF254. Column chromatography was con-
(CDCl3):
d
ꢁ5.4 (Si(CH3)2), ꢁ5.2 (Si(CH3)2), 18.2 (C(CH3)3), 25.8
(C(CH3)3), 61.8 (OCH2CH]CH2), 67.9 (C-7), 72.5 (C-5), 73.1 (C-6),
73.2 (CH2Ph), 75.2 (CH2Ph), 76.8 (C-3), 88.3 (C-4), 96.3 (C-2), 117.8
(OCH2CH]CH2), 133.2 (OCH2CH]CH2). HRMS (ESI): m/z calcd for
C
30H41O8SSSi$Naþ: 669.2136; found: 669.2142.
ducted using silica gel 60 N (40–50
All anhydrous solvents were purified according to standard
methods.
m
m, Kanto Chemical Co., Inc.).
3.1.3. (2S,3S,4R,5R,6R)-2-Allyloxy-3,5-bisbenzyloxy-6-[(tert-butyl-
dimethylsilyl)oxy]methyl-tetrahydropyran-4-yl acetate (10)
A toluene solution (25 mL) of 9 (134 mg, 0.21 mmol), 18-crown-
6 (116 mg, 0.44 mmol), and cesium acetate (85 mg, 0.44 mmol) was
sonicated at 30 ꢀC for 24 h, and water (15 mL) was then added to
the mixture. The reaction mixture was extracted with AcOEt
(30 mL), and the organic layer was washed with water and brine.
After the organic layer was dried over anhydrous Na2SO4, the sol-
vent was filtered and evaporated under reduced pressure. The
crude mixture was separated by preparative TLC (silica gel ethyl
3.1.1. (2S,3S,4S,5R,6R)-2-Allyloxy-3,5-bisbenzyloxy-6-[(tert-
butyldimethylsilyl)oxy]methyl-tetrahydropyran-4-ol (8)
To a solution of 7 (365 mg, 0.91 mmol) and imidazole (148 mg,
2.2 mmol) in CH2Cl2 (10 mL) was added TBSCl (148 mg, 2.1 mmol)
at rt. After stirring for 2 h, the reaction was then quenched by ad-
dition of a solution of ~30% citric acid (5 mL). The reaction mixture
was extracted with CH2Cl2 (10 mL). After the organic layer was
dried over anhydrous Na2SO4, the solvent was filtered and evapo-
rated under reduced pressure. The crude mixture was separated by
acetate/hexane¼1:6) to give 10 (71.1 mg, 62% yield) as a colorless
22
oil. [a
]
þ63 (c 3.6, CHCl3). 1H NMR (CDCl3):
d 0.07 (3H, s, Si(CH3)2),
D
0.08 (3H, s, Si(CH3)2), 0.91 (9H, s, C(CH3)3), 2.01 (3H, s, CH3CO), 3.71
(1H, dd, J¼1.4, 3.4 Hz, H-3), 3.80 (1H, dd, J¼5.5, 11.0 Hz, Ha-7), 3.88
(1H, dd, J¼3.4, 8.9 Hz, H-5), 3.85–3.93 (2H, m, OCHaHbCH]CH2,
Hb-7), 4.03 (1H, m, H-6), 4.23 (1H, m, OCHaHbCH]CH2), 4.80 (1H,
d, J¼1.4 Hz, H-2), 5.13 (1H, ddd, J¼1.4, 3.4, 10.3 Hz, OCH2CH]
CHaHb), 5.13 (1H, ddd, J¼1.4, 2.1, 18.6 Hz, OCH2CH]CHaHb), 5.33
(1H, t, J¼3.4 Hz, H-4), 5.87 (1H, m, OCH2CH]CH2). 13C NMR
preparative TLC (silica gel ethyl acetate/hexane¼1:4) to give 8
23
(415.1 mg, 88% yield) as a colorless oil. [
a]
þ27 (c 2.7, CHCl3). 1H
D
NMR (CDCl3): d 0.07 (3H, s, Si(CH3)2), 0.08 (3H, s, Si(CH3)2), 0.91 (9H,
s, C(CH3)3), 2.35 (1H, d, J¼9.6 Hz, OH), 3.57–3.60 (1H, m, H-6), 3.65
(1H, t, J¼9.6 Hz, H-5), 3.74 (1H, dd, J¼1.4, 3.4 Hz, H-3), 3.83–3.88
(2H, m, H-7), 3.92 (1H, dt, J¼4.1, 9.6 Hz, H-4), 3.93 (1H, dd, J¼6.2,
13.1 Hz, OCHaHbCH]CH2), 4.01 (1H, ddd, J¼1.4, 5.5, 13.1 Hz,
OCHaHbCH]CH2), 4.93 (1H, d, J¼1.4 Hz, H-2), 5.16 (1H, dd, J¼1.4,
10.3 Hz, OCH2CH]CHaHb), 5.25 (1H, dd, J¼1.4, 17.2 Hz,
OCH2CH]CHaHb), 5.86 (1H, m, OCH2CH]CH2). 13C NMR (CDCl3):
(CDCl3):
d
ꢁ5.4 (Si(CH3)2), ꢁ5.2 (Si(CH3)2), 18.2 (C(CH3)3), 21.0
(CH3CO), 25.8 (C(CH3)3), 62.7 (C-7), 67.3 (C-4), 67.4 (OCH2CH]CH2),
68.9 (C-6), 70.7 (C-5), 71.5 (CH2Ph), 72.4 (CH2Ph), 75.6 (C-3),
97.5 (C-2, JC2–H2¼164.7 Hz), 116.3 (OCH2CH]CH2), 134.1
(OCH2CH]CH2), 170.7 (CH3CO). HRMS (ESI): m/z calcd for
d
ꢁ5.3 (Si(CH3)2), ꢁ5.1 (Si(CH3)2), 18.3 (C(CH3)3), 25.9 (C(CH3)3),
62.6 (C-7), 67.6 (OCH2CH]CH2), 71.8 (C-4), 72.3 (C-6), 72.7 (CH2Ph),
74.8 (CH2Ph), 76.6 (C-5), 78.6 (C-3), 95.7 (C-2, JC2–H2¼167.6 Hz),
117.2 (OCH2CH]CH2),133.8 (OCH2CH]CH2). HRMS (ESI): m/z calcd
for C29H42O6Si$Naþ: 537.2643; found: 537.2690.
C
31H44O7Si$Naþ: 579.2749; found: 579.2795.
3.1.4. (2S,3S,4R,5R,6R)-2-Allyloxy-3,5-bisbenzyloxy-6-[(tert-
butyldimethylsilyl)oxy]methyl-tetrahydropyran-4-ol (11)
To a solution of 10 (468 mg, 0.84 mmol) in MeOH (5 mL) was
added two drops of a 28% sodium methoxide methanol solution at
rt. After the reaction mixture was stirred overnight, the reaction
was quenched by addition of water (5 mL). The reaction mixture
was extracted with AcOEt (5 mL), and the organic layer was washed
with water and brine. After the organic layer was dried over an-
hydrous Na2SO4, the organic solvent was filtered and evaporated
under reduced pressure. The crude product was purified by flash
3.1.2. (2S,3S,4S,5R,6R)-2-Allyloxy-3,5-bisbenzyloxy-6-[(tert-
butyldimethylsilyl)oxy]methyl-4-trifuloromethanesulfonyloxy-
tetrahydropyran (9)
To a solution of 8 (110 mg, 0.21 mmol) in pyridine (2.5 mL), Tf2O
(0.053 mL, 0.32 mmol) was added dropwise at ꢁ20 ꢀC under Ar
atmosphere, and the reaction temperature was then allowed to
increase up to rt. After stirring for 2.5 h, the reaction was then
quenched by addition of a satd NaHCO3 solution. The reaction
mixture was extracted with AcOEt (5 mL), and the organic layer was
silica gel column chromatography (ethyl acetate/hexane¼1:4) to
23
give 11 (413 mg, 95% yield) as a colorless oil. [
a]
þ61 (c 3.0, CHCl3).
D

S. Matsuda et al. / Tetrahedron 64 (2008) 8082–8088
8085
1H NMR (CDCl3):
d
0.05 (3H, s, Si(CH3)2), 0.08 (3H, s, Si(CH3)2), 0.84
18.3 (C(CH3)3), 25.9 (C(CH3)3), 62.6 (C-7), 68.2 (C-6), 71.7 (CH2Ph),
71.9 (C-4), 72.4 (CH2Ph), 74.0 (CH2Ph), 75.5 (C-5), 77.3 (C-3), 92.8 (C-
2). HRMS (ESI): m/z calcd for C33H44O6Si$Naþ: 587.2799; found:
587.2775.
(9H, s, C(CH3)3), 3.61 (1H, dd, J¼1.4, 3.8 Hz, H-3), 3.71 (1H, dd, J¼3.3,
9.5 Hz, H-5), 3.76 (1H, dd, J¼5.7, 11.5 Hz, Ha-7), 3.83–3.85 (2H, m,
H-6, Hb-7), 3.93 (1H, dtd, J¼1.2, 6.2, 12.9 Hz, OCHaHbCH]CH2),
4.04–4.06 (1H, m, H-4), 4.16 (1H, dtd, J¼1.4, 5.3, 12.9 Hz,
OCHaHbCH]CH2), 4.82 (1H, d, J¼0.2 Hz, H-2), 5.11 (1H, ddd, J¼1.2,
2.6, 10.3 Hz, OCH2CH]CHaHb), 5.18 (1H, ddd, J¼1.5, 3.1, 17.2 Hz,
OCH2CH]CHaHb), 5.81 (1H, m, OCH2CH]CH2). 13C NMR (CDCl3):
3.1.7. (3S,4R,5R,6R)-6-[(tert-Butyldimethylsilyl)oxy]methyl-
3,4,5-trisbenzyloxy-tetrahydropyran-2-one (14)
To a solution of 13 (70.3 mg, 0.124 mmol) in DMSO (3 mL) was
added Ac2O (2 mL). After stirring overnight, cool water was added
to the reaction mixture. The reaction mixture was extracted with
AcOEt (5 mL), and the organic layer was washed with water and
brine. After the organic layer was dried over anhydrous Na2SO4, the
solvent was filtered and evaporated under reduced pressure. The
crude product was purified by a preparative flash silica gel column
d
ꢁ5.4 (Si(CH3)2), ꢁ5.2 (Si(CH3)2), 18.2 (C(CH3)3), 25.9 (C(CH3)3),
62.8 (C-7), 66.6 (C-4), 68.0 (OCH2CH]CH2), 68.2 (C-6), 71.2
(CH2Ph), 71.9 (C-5), 72.1 (CH2Ph), 76.6 (C-3), 97.3 (C-2, JC2–
¼168.3 Hz), 117.9 (OCH2CH]CH2), 133.3 (OCH2CH]CH2). HRMS
H2
(ESI): m/z calcd for C29H42O6Si$Naþ: 537.2643; found: 537.2657.
3.1.5. (2S,3S,4R,5R,6R)-2-Allyloxy-6-[(tert-butyldimethylsilyl)oxy]-
methyl-3,4,5-trisbenzyloxy-tetrahydropyran (12)
chromatography (ethyl acetate/hexane¼1:6) to give 14 (69.8 mg,
23
99%) as a colorless oil. [
a
]
ꢁ21 (c 1.4, CHCl3). IR (neat): 3088, 3063,
D
To a solution of 11 (177 mg, 0.34 mmol) in anhydrous DMF
(6 mL) was added NaH (33 mg, 1.4 mmol) at 0 ꢀC. After the sus-
pension was stirred for 40 min, benzyl bromide (0.07 mL,
0.58 mmol) was added dropwise over a 5-min period and stirred
for 30 min; the reaction temperature was then allowed to warm to
rt. The reaction mixture was stirred overnight, and 5 mL of MeOH
was then added slowly to react with the excess NaH, and water
(5 mL) was added to the reaction. The reaction mixture was
extracted with AcOEt (5 mL), and the organic layer was washed
with water and brine. After the organic layer was dried over an-
hydrous Na2SO4, the solvent was filtered and evaporated under
reduced pressure. The crude mixture was separated by preparative
3033, 2952, 2929, 2857, 1741, 1496, 1455, 1361, 1265, 1119, 1027, 837,
737, 699 cmꢁ1. 1H NMR (CDCl3):
d
0.08 (3H, s, Si(CH3)2), 0.09 (3H, s,
Si(CH3)2), 0.91 (9H, s, C(CH3)3), 3.86 (2H, d, J¼3.2 Hz, H-7), 4.06 (1H,
dd, J¼2.7, 6.3 Hz, H-4), 4.23 (1H, dd, J¼2.7, 6.3 Hz, H-5), 4.26 (1H, d,
J¼6.3 Hz, H-3), 4.57–4.59 (1H, m, H-6). 13C NMR (CDCl3):
d
ꢁ5.4
(Si(CH3)2), ꢁ5.2 (Si(CH3)2), 18.3 (C(CH3)3), 25.9 (C(CH3)3), 62.0 (C-7),
71.9 (C-5), 72.6 (CH2Ph), 72.7 (CH2Ph), 73.6 (CH2Ph), 74.9 (C-4), 75.7
(C-3), 79.0 (C-6), 168.7 (C-2). HRMS (ESI): m/z calcd for
C
33H42O6Si$Naþ: 585.2643; found: 585.2681.
3.1.8. (3S,4R,5R,6R)-6-[(tert-Butyldimethylsilyl)oxy]methyl-3,4,5-
tris(benzyloxy)-2-vinyl-tetrahydropyran-2-ol (15)
TLC (silica gel ethyl acetate/hexane¼1:6) to give 12 (199 mg, 96%
To a solution of 14 (54.5 mg, 0.097 mmol) in toluene (3 mL),
a 1.3 M THF solution of vinylmagnesium chloride (0.090 mL,
0.12 mmol) was added dropwise at ꢁ78 ꢀC in the presence of dry
CeCl3 (30.6 mg, 0.12 mmol) under Ar atmosphere. After the
resulting mixture was stirred at ꢁ78 ꢀC for 1 h, the reaction was
quenched by addition of water (5 mL). The reaction mixture was
extracted with AcOEt (5 mL), and the organic layer was washed
with water. After the organic layer was dried over anhydrous
Na2SO4, the solvent was filtered and evaporated under reduced
pressure. The crude mixture was separated by preparative TLC
(silica gel ethyl acetate/toluene¼1:19) to give 15 (35.1 mg, 62%
23
yield) as a colorless oil. [
a
]
þ55 (c 3.3, CHCl3). 1H NMR (CDCl3):
D
d
0.04 (6H, s, Si(CH3)2), 0.89 (9H, s, C(CH3)3), 3.74–3.83 (5H, m, H-3,
H-7, H-4, H-5, or H-6), 3.98 (1H, dd, J¼6.2, 13.1 Hz,
OCHaHbCH]CH2), 4.09–4.12 (2H, m, H-4, H-5, or H-6), 4.26 (1H,
dd, J¼4.8, 13.1 Hz, OCHaHbCH]CH2), 4.83 (1H, d, J¼0.7 Hz, H-2),
5.15 (1H, dd, J¼1.4, 10.3 Hz, OCH2CH]CHaHb), 5.29 (1H, dd, J¼1.4,
19.2 Hz, OCH2CH]CHaHb), 5.91 (1H, m, OCH2CH]CH2). 13C NMR
(CDCl3):
d
ꢁ5.4 (Si(CH3)2), ꢁ5.2 (Si(CH3)2), 18.3 (C(CH3)3), 25.9
(C(CH3)3), 63.0 (C-7), 6.7.8 (OCH2CH]CH2), 70.2, 71.7 (CH2Ph), 72.0
(CH2Ph), 72.6 (CH2Ph), 72.8, 74.3, 76.5, 98.6 (C-2, JC2–H2¼167.5 Hz),
116.7 (OCH2CH]CH2), 134.4 (OCH2CH]CH2). HRMS (ESI): m/z
calcd for C36H48O6Si$Naþ: 627.3112; found: 627.3154.
yield) as a colorless oil. 1H NMR (CDCl3):
d 0.08 (3H, s, Si(CH3)2),
0.09 (3H, s, Si(CH3)2), 0.91 (9H, s, C(CH3)3), 3.33 (1H, d, J¼3.4 Hz,
H-3), 3.80 (1H, dd, J¼2.1, 3.4 Hz, H-4), 3.89 (1H, d, J¼11.0 Hz, Ha-
7), 3.98–4.12 (3H, m, H-5, H-6, Hb-7), 5.22 (1H, dd, J¼2.1, 11.0 Hz,
CH]HaHb), 5.58 (1H, dd, J¼2.1, 17.9 Hz, CH]HaHb), 5.98 (1H, m,
3.1.6. (3S,4R,5R,6R)-6-[(tert-Butyldimethylsilyl)oxy]methyl-3,4,5-
trisbenzyloxy-tetrahydropyran-2-ol (13)
To a solution of AcOH (13.6 mL), water (0.68 mL), AcONa
(448 mg), and 12 (199 mg, 0.33 mmol) was added PdCl2 (180 mg,
1.01 mmol). After the reaction mixture was sonicated at 30 ꢀC for
4 h, the mixture was filtered on a bed of Celite, and NaHCO3 (5 g)
was added to the solution. The reaction mixture was extracted with
AcOEt, and the organic layer was washed with a satd NaHCO3 and
brine. After the organic layer was dried over anhydrous Na2SO4, the
solvent was filtered and evaporated under reduced pressure. The
crude mixture was separated by preparative TLC (silica gel ethyl
acetate/hexane¼1:4) to give 13 (162 mg, 87% yield) as a colorless
oil.
CH]CH2). 13C NMR (CDCl3):
d
ꢁ5.3 (Si(CH3)2), ꢁ5.0 (Si(CH3)2),
18.3 (C(CH3)3), 5.9 ((CH3)3C), 62.6 (C-7), 68.9 (C-5 or C-6), 71.2 (C-
5 or C-6), 72.6 (CH2Ph), 73.1 (CH2Ph), 73.9 (CH2Ph), 75.4 (C-
4), 78.4 (C-3), 96.5 (C-2), 116.3 (CH]CH2), 138.1 (CH]CH2).
HRMS (ESI): m/z calcd for C35H46O6Si$Naþ: 613.2950; found:
613.2968.
3.1.9. (1R,2R,3R,4S,5R)-2,3,4-Tris(benzyloxy)-5-vinyl-6,8-
dioxabicyclo[3.2.1]octane (16)
To a stirred solution of TfOH (0.25 mL, 0.0028 mmol) and dry
CaSO4 (35.3 mg) was added 15 (32.7 mg, 0.0554 mmol) in CH3CN
(2 mL) at 0 ꢀC under Ar atmosphere. After the resulting mixture was
stirred for 2 h, the reaction was then quenched by addition of a satd
NaHCO3 solution (5 mL). The reaction mixture was extracted with
AcOEt (5 mL), and the organic layer was washed with water and
a satd NaCl solution. After the organic layer was dried over anhy-
drous Na2SO4, the solvent was filtered and evaporated under
reduced pressure. The crude mixture was separated by preparative
a
Form. 1H NMR (CDCl3):
d 0.07 (3H, s, (CH3)2Si), 0.09 (3H, s,
(CH3)2Si), 0.91 (9H, s, (CH3)3C), 3.53 (1H, dd, J¼2.1, 12.4 Hz, H-3),
3.59 (1H, d, J¼4.1 Hz, H-5), 3.85–3.90 (2H, m, H-4, Ha-7), 3.99–4.03
(1H, m, H-6, Hb-7), 5.04–5.08 (1H, m, H-2). 13C NMR (CDCl3):
d
ꢁ5.3
(Si(CH3)2), ꢁ5.0 (Si(CH3)2), 18.3 (C(CH3)3), 25.9 (C(CH3)3), 62.8 (C-7),
68.2 (C-6), 72.2 (CH2Ph), 73.065 (CH2Ph), 73.074 (CH2Ph), 73.5 (C-
4), 75.2 (C-5), 77.3 (C-3), 91.6 (C-2).
b d 0.07
Form. 1H NMR (CDCl3):
(3H, s, (SiCH3)2), 0.09 (3H, s, Si(CH3)2), 0.91 (9H, s, C(CH3)3), 3.47
(1H, t, J¼2.1 Hz, H-3), 3.75 (1H, dd, J¼2.1, 2.8 Hz, H-4), 3.85–3.90
(2H, m, H-5, Ha-7), 3.99–4.03 (2H, m, H-6, Hb-7), 5.06 (1H, d,
TLC (silica gel ethyl acetate/benzene¼1:10) to give 16 (22.3 mg, 88%
23
yield) as amorphous crystals. [
a]
ꢁ66 (c 1.1, CHCl3). 1H NMR
D
(CDCl3):
d
3.62 (1H, dd, J¼0.7, 7.6 Hz, Ha-7), 3.66 (1H, dd, J¼2.4,
J¼2.1 Hz, H-2). 13C NMR (CDCl3):
d
ꢁ5.4 (Si(CH3)2), ꢁ5.1 (Si(CH3)2),
3.6 Hz, H-2), 3.78–3.82 (2H, m, H-3, H-4), 3.80 (1H, dd, J¼0.7, 6.9 Hz,

8086
S. Matsuda et al. / Tetrahedron 64 (2008) 8082–8088
Hb-7), 4.59–4.65 (1H, m, H-1), 5.33 (1H, dd, J¼2.1, 11.0 Hz,
CH]CHaHb), 5.70 (1H, dd, J¼2.1, 17.9 Hz, CH]CHaHb), 6.10 (1H, dd,
CH]CHaHb), 5.96 (1H, dd, J¼11.0, 17.2 Hz, CH]CH2). 13C NMR
(CDCl3):
d
ꢁ5.3 (Si(CH3)2), ꢁ5.0 (Si(CH3)2), 18.3 (SiC(CH3)3), 25.9
J¼11.0, 17.2 Hz, CH]CH2). 13C NMR (CDCl3):
d
66.1 (C-7), 72.1
(C(CH3)3), 61.8 (C-7), 72.7 (C-6), 75.0 (CH2Ph), 75.7 (CH2Ph), 75.8
(CH2Ph), 77.7 (C-5), 83.1 (C-3), 83.3 (C-4), 96.4 (C-2), 116.8
(CH]CH2), 138.9 (CH]CH2). ESI-MS m/z calcd for C29H42O6Si$Naþ:
613.2956; found: 613.2972.
(CH2Ph), 72.7 (CH2Ph), 74.7 (C-2), 75.2 (C-1), 75.3 (CH2Ph), 78.5 (C-
3), 82.9 (C-4), 106.7 (C-5), 118.3 (CH]CH2), 133.0 (CH]CH2). HRMS
(ESI): m/z calcd for C29H30O5$Naþ: 481.1985; found: 481.1999.
3.1.10. (1R,2R,3R,4S,5R)-2,3,4-Tris(benzyloxy)-6,8-
3.1.13. (1R,2R,3S,4R,5R)-2,3,4-Tris(benzyloxy)-5-vinyl-6,8-
dioxabicyclo[3.2.1]octane-5-methanol (2)
dioxabicyclo[3.2.1]octane (19)
Ozone was bubbled through a stirred solution of 16 (21.7 mg,
0.047 mmol) in CH2Cl2 (5 mL) at ꢁ78 ꢀC for 45 min. Ph3P (62.2 mg,
0.237 mmol) was added to the reaction mixture. The reaction
temperature was then allowed to increase to rt, and the solvent was
evaporated under reduced pressure. After the reaction mixture was
dissolved in THF (4 mL), NaBH4 (15.1 mg, 0.399 mmol) was added at
0 ꢀC and stirred for 3 h. The reaction was then quenched by addition
of a solution of ~30% citric acid (5 mL). The reaction mixture was
extracted with AcOEt (5 mL), and the organic layer was washed
with water and brine. After the organic layer was dried over
anhydrous Na2SO4, the solvent was filtered and evaporated under
reduced pressure. The crude mixture was separated by preparative
To a stirred solution of TfOH (1.0 mL, 0.0113 mmol) was added 18
(136.1 mg, 0.231 mmol) in CH3CN (2 mL) at 0 ꢀC in the presence of
dry CaSO4 (137.2 mg) under Ar atmosphere. The resulting mixture
was stirred for 2 h. The remaining procedure was the same as that
used for the preparation of 16. The crude mixture was separated by
preparative TLC (silica gel ethyl acetate/hexane¼1:4) to give 19
27
(94.1 mg, 89% yield) as a colorless oil. [
a
]
ꢁ12 (c 1.9, CHCl3). 1H
D
NMR (CDCl3): d 3.31 (1H, s, H-4), 3.33 (1H, s, H-2), 3.60 (1H, s, H-3),
3.79 (1H, dd, J¼6.2, 6.9 Hz, Ha-7), 4.03 (1H, d, J¼6.9 Hz, Hb-7), 4.67
(1H, br d, J¼5.5 Hz, H-1), 5.30 (1H, dd, J¼2.4, 10.8 Hz, CH]CHaHb),
5.66 (1H, dd, J¼1.8,17.4 Hz, CH]CHaHb), 6.23 (1H, m, CH]CH2). 13
C
NMR (CDCl3): d 65.5 (C-7), 71.0 (CH2Ph), 71.6 (CH2Ph), 72.6 (CH2Ph),
TLC (silica gel ethyl acetate/hexane¼3:1) to give 2 (16.1 mg, 72%
74.6 (C-2), 75.6 (C-3), 75.7 (C-1), 77.6 (C-4), 105.4 (C-5), 117.6
(CH]CH2), 134.0 (CH]CH2). ESI-MS m/z calcd for C29H30O5Si$Naþ:
481.1985; found: 481.1941.
23
yield) as amorphous crystals. [
a
]
ꢁ45 (c 0.8, CHCl3). IR (KBr) 3486,
D
3087, 3063, 3031, 2962, 2904, 2871, 1496, 1454, 1371, 1358, 1241,
1146, 1090, 1079, 1044, 1017, 860, 831, 803, 747, 696 cmꢁ1. 1H NMR
(CDCl3):
3.74–3.83 (4H, m, H-4, Hb-7, CH2OH), 3.93 (1H, d, J¼8.9 Hz, H-3),
4.57–4.63 (1H, m, H-1). 13C NMR (CDCl3):
62.0 (CH2OH), 66.6 (C-
d
3.63 (1H, dd, J¼0.7, 8.3 Hz, Ha-7), 3.67–3.68 (1H, m, H-2),
3.1.14. (1R,2R,3S,4R,5R)-2,3,4-Tris(benzyloxy)-6,8-
dioxabicyclo[3.2.1]octane-methanol (3)
d
Ozone was bubbled through a stirred solution of 19 (35.8 mg,
0.0781 mmol) in CH2Cl2 (5 mL) at ꢁ78 ꢀC for 40 min. Ph3P
(117.5 mg, 0.448 mmol) was added to the reaction mixture, and the
reaction temperature was then allowed to increase to rt. After the
solvent was evaporated under reduced pressure and tetrahydro-
furan (4 mL) was added, NaBH4 (25.2 mg, 0.666 mmol) was then
added to the solution at 0 ꢀC. The remaining procedure was the
same as that used for the preparation of 2. The crude mixture was
7), 72.1 (CH2Ph), 72.5 (CH2Ph), 74.6 (C-2), 75.2 (CH2Ph), 75.5 (C-1),
78.9 (C-4), 79.8 (C-3), 107.9 (C-5). HRMS (ESI): m/z calcd for
C
28H30O6$Naþ: 485.1935; found: 485.1950.
3.1.11. (3R,4S,5R,6R)-6-[(tert-Butyldimethylsilyl)oxy]methyl-3,4,5-
trisbenzyloxy-tetrahydropyran-2-one (17)
To a solution of (3R,4S,5R,6R)-6-[(tert-butyldimethylsilyl)oxy]-
methyl-3,4,5-trisbenzyloxy-tetrahydropyran-2-ol15
(197.2 mg,
separated by preparative TLC (silica gel ethyl acetate/hexane¼3:1)
27
0.349 mmol) in DMSO (3 mL) was added Ac2O (2 mL). The resulting
mixture was stirred overnight. The remaining procedure was the
same as that used for the preparation of 14. The crude product was
purified by preparative flash silica gel column chromatography
to give 3 (26.5 mg, 73% yield) as a colorless oil. [
a]
ꢁ28 (c 1.3,
D
CHCl3). IR (neat) 3476, 3087, 3062, 3031, 2898, 1496, 1454, 1392,
1370, 1328, 1266, 1207, 1074, 1028, 938, 860, 737, 699 cmꢁ1 1H
NMR (CDCl3):
.
d
3.35 (1H, d, J¼1.4 Hz, H-4), 3.42 (1H, s, H-2), 3.61
(ethyl acetate/hexane¼1:15) to give 17 (186.1 mg, 95% yield) as
(1H, d, J¼1.4 Hz, H-3), 3.71 (1H, dd, J¼6.9, 11.7 Hz, CHaHbOH), 3.76
(1H, dd, J¼5.5, 6.9 Hz, Ha-7), 3.89 (1H, dd, J¼6.2, 11.7 Hz, CHaH-
bOH), 4.03 (1H, d, J¼6.9 Hz, Hb-7), 4.67 (1H, br d, J¼5.5 Hz, H-1).
25
a colorless oil. [
a
]
þ70 (c 4.5, CHCl3). IR (neat) 3064, 3031, 2952,
D
2928, 2856, 1757, 1455, 1362, 1097, 1074, 1028, 1007, 837, 779, 737,
697 cmꢁ1 1H NMR (CDCl3):
.
d
0.06 (6H, s, Si(CH3)2), 0.88 (9H, s,
13C NMR (CDCl3):
d 62.8 (CH2OH), 65.9 (C-7), 71.1 (CH2Ph), 71.6
C(CH3)3), 3.79 (1H, dd, J¼2.8, 11.7 Hz, Ha-7), 3.87 (1H, dd, J¼2.1,
11.7 Hz, Hb-7), 3.93 (1H, dd, J¼6.9, 7.6 Hz, H-4), 3.97 (1H, dd, J¼7.6,
8.2 Hz, H-5), 4.08 (1H, d, J¼7.6 Hz, H-3), 4.30 (1H, m, H-6). 13C NMR
(CH2Ph), 72.2 (CH2Ph), 74.7 (C-2), 75.0 (C-4), 75.1 (C-3), 75.8 (C-1),
106.2 (C-5). ESI-MS m/z calcd for C28H30O6Si$Naþ: 485.1935;
found: 485.1952.
(CDCl3):
d
ꢁ5.5 (Si(CH3)2), ꢁ5.3 (Si(CH3)2), 18.2 (C(CH3)3), 25.8
(C(CH3)3), 61.6 (C-7), 73.9 (CH2Ph), 74.0 (CH2Ph), 74.2 (CH2Ph), 75.7
(C-5), 77.7 (C-3), 79.4 (C-6), 81.0 (C-4), 169.6 (C-2). HRMS (ESI): m/z
calcd for C33H42O6Si$Naþ: 585.2643; found: 585.2655.
3.1.15. (3S,4S,5R,6R)-6-[(tert-Butyldimethylsilyl)oxy]methyl-3,4,5-
trisbenzyloxy-tetrahydropyran-2-one (20)
To a solution of (3S,4S,5R,6R)-6-[(tert-butyldimethylsilyl)oxy]-
methyl-3,4,5-trisbenzyloxy-tetrahydropyran-2-ol
(497.4 mg,
3.1.12. (3R,4S,5R,6R)-6-tert-Butyldimethylsilyloxymethyl-3,4,5-
tris(benzyloxy)-2-vinyl-tetrahydropyran-2-ol (18)
881 mmol) in DMSO (3 mL) was added Ac2O (2 mL). The resulting
mixture was stirred overnight. The remaining procedure was the
To a stirred solution of 17 (86.3 mg, 0.153 mmol) in tetrahy-
drofuran (2 mL), a 1.4 M THF solution of vinylmagnesium chloride
(0.231 mL, 0.307 mmol) was added dropwise at ꢁ78 ꢀC under Ar
atmosphere. The resulting mixture was stirred at ꢁ78 ꢀC for 3 h.
The remaining procedure was the same as that used for the prep-
aration of 15. The crude mixture was separated by preparative TLC
(silica gel ethyl acetate/hexane¼1:4) to give 18 (72.7 mg, 80% yield)
same as that used for the preparation of 14 to afford 20 (489.8 mg,
27
93% yield) as a colorless oil. [
a
]
577 ꢁ9.6 (c 2.7, CHCl3). IR (neat) 2952,
2927, 2855, 1772, 1471, 1455, 1254, 1107, 1028, 837, 779, 737,
698 cmꢁ1 1H NMR (CDCl3):
.
d
0.50 (3H, s, Si(CH3)2), 0.52 (3H, s,
Si(CH3)2), 0.87 (9H, s, C(CH3)3), 3.75 (1H, dd, J¼4.8, 11.0 Hz, Ha-7),
3.78 (1H, dd, J¼4.1, 11.0 Hz, Hb-7), 3.87 (1H, dd, J¼2.1, 6.9 Hz, H-5),
4.05 (1H, dd, J¼2.1, 2.8 Hz, H-4), 4.12 (1H, m, H-6), 4.35 (1H, d,
as a colorless oil. 1H NMR (CDCl3):
d
0.07 (3H, s, Si(CH3)2), 0.08 (3H,
J¼2.1 Hz, H-3). 13C NMR (CDCl3):
d
ꢁ5.43 (Si(CH3)2), ꢁ5.42
s, Si(CH3)2), 0.85 (9H, s, C(CH3)3), 3.38 (1H, d, J¼8.9 Hz, H-3), 3.77
(1H, dd, J¼8.9, 9.6 Hz, H-5), 3.83 (1H, d, J¼11.0 Hz, Ha-7), 3.88–3.90
(1H, m, H-6), 3.98 (1H, dd, J¼8.9, 9.6 Hz, H-4), 3.98–4.00 (1H, m,
Hb-7), 5.28 (1H, d, J¼11.0 Hz, CH]CHaHb), 5.59 (1H, d, J¼17.2 Hz,
(Si(CH3)2), 18.2 (C(CH3)3), 25.8 (C(CH3)3), 62.5 (C-7), 71.8 (CH2Ph),
72.8 (CH2Ph), 72.8 (CH2Ph), 75.2 (C-5), 75.8 (C-3), 76.7 (C-4), 80.0
(C-6), 169.4 (C-2). ESI-MS m/z calcd for C33H42O6Si$Naþ: 585.2643;
found: 585.2648.

S. Matsuda et al. / Tetrahedron 64 (2008) 8082–8088
8087
3.1.16. (3S,4S,5R,6R)-6-tert-Butyldimethylsilyloxymethyl-3,4,5-
tris(benzyloxy)-2-vinyl-tetrahydropyran-2-ol (21)
preparation of 15. The crude mixture was separated by preparative
TLC (silica gel ethyl acetate/hexane¼1:6) to give 23 (81.1 mg, 92%
To a stirred solution of 20 (86.3 mg, 0.153 mmol) in toluene
(3 mL), a 1.3 M THF solution of vinylmagnesium chloride (0.231 mL,
0.307 mmol) was added dropwise at ꢁ78 ꢀC in the presence of dry
CeCl3 (61.7 mg, 0.250 mmol) under Ar atmosphere. The resulting
mixture was stirred at ꢁ78 ꢀC for 1 h. The remaining procedure was
the same as that used for the preparation of 15. The crude mixture
was separated by preparative TLC (silica gel ethyl acetate/
benzene¼1:9) to give 21 (70.5 mg, 64% yield) as a colorless oil. 1H
yield) as a colorless oil. 1H NMR (CDCl3):
d 0.05 (3H, s, Si(CH3)2),
0.06 (3H, s, Si(CH3)2), 0.88 (9H, s, C(CH3)3), 2.42–2.44 (2H, m,
CH2CH]CH2), 3.33 (1H, d, J¼3.6 Hz, H-3), 3.80 (1H, dd, J¼2.4,
4.0 Hz, H-4), 3.80 (1H, d, J¼11.3 Hz, Ha-7), 3.95–4.01 (3H, m, H-5, H-
6, Hb-7), 5.04–5.07 (2H, m, CH2CH]CH2), 5.88 (1H, m,
CH2CH]CH2). 13C NMR (CDCl3):
d
ꢁ5.31 (Si(CH3)2), ꢁ5.26
(Si(CH3)2), 18.3 (SiC(CH3)3), 25.9 (SiC(CH3)3), 41.6 (CH2CH]CH2),
62.5 (C-7), 68.7 (C-6), 71.3 (C-5), 72.4 (CH2Ph), 71.6 (CH2Ph), 73.3
(CH2Ph), 74.4 (C-4), 76.5 (C-3), 98.3 (C-2), 117.1 (CH2CH]CH2), 133.5
(CH2CH]CH2). ESI-MS m/z calcd for C36H48O6Si$Naþ: 627.3112;
found: 627.3147.
NMR (CDCl3): d 0.03 (3H, s, Si(CH3)2), 0.05 (3H, s, Si(CH3)2), 0.87 (9H,
s, C(CH3)3), 3.73 (1H, d, J¼2.8 Hz, H-3), 3.80–3.83 (2H, m, H-5, Ha-7),
3.93 (1H, dd, J¼4.8, 11.7 Hz, Hb-7), 4.09–4.12 (2H, m, H-2, H-6), 5.19
(1H, dd, J¼1.4, 11.0 Hz, CH]CHaHb), 5.47 (1H, dd, J¼1.4, 17.2 Hz,
CH]CHaHb), 6.12 (1H, m, CH]CH2). 13C NMR (CDCl3):
d
ꢁ5.4
3.1.20. (1R,2R,3R,4S,5R)-5-Allyl-2,3,4-tris(benzyloxy)-6,8-
dioxabicyclo[3.2.1]octane (24)
(Si(CH3)2), ꢁ5.1 (Si(CH3)2), 18.2 (C(CH3)3), 25.9 (C(CH3)3), 62.6 (C-7),
72.4 (CH2Ph), 73.9 (C-5), 74.58 (CH2Ph), 74.61 (C-4), 75.1 (CH2Ph),
79.2 (C-3), 81.2 (C-6), 97.4 (C-2), 115.6 (CH]CH2), 140.6 (CH]CH2).
ESI-MS m/z calcd for C29H42O6Si$Naþ: 613.2956; found: 613.2985.
To a stirred solution of TfOH (0.58 mL, 0.066 mmol) was added
23 (81.1 mg, 0.134 mmol) in CH3CN (2 mL) at 0 ꢀC in the presence of
dry CaSO4 (120.0 mg) under Ar atmosphere. The resulting mixture
was stirred for 2 h. The remaining procedure was the same as that
used for the preparation of 16. The crude mixture was separated by
3.1.17. (1R,2R,3S,4S,5R)-2,3,4-Tris(benzyloxy)-5-vinyl-6,8-
dioxabicyclo[3.2.1]octane (22)
preparative TLC (silica gel ethyl acetate/hexane¼1:4) to give 24
ꢁ66 (c 3.1, CHCl3). 1
H
28
To a stirred solution of TfOH (0.29
m
L, 0.00328 mmol) was added
(62.5 mg, 99% yield) as a colorless oil. [
a]
D
21 (38.1 mg, 0.0645 mmol) in CH3CN (2 mL) at 0 ꢀC in the presence
of dry CaSO4 (49.4 mg) under Ar atmosphere. The resulting mixture
was stirred for 1 h. The remaining procedure was the same as that
NMR (CDCl3):
d
2.59 (1H, dd, J¼8.2, 15.1 Hz, CHaHbCH]CH2), 2.72
(1H, dd, J¼6.2, 15.8 Hz, CHaHbCH]CH2), 3.58 (1H, d, J¼8.2 Hz,
Ha-7), 3.66 (1H, s, H-2), 3.73 (1H, dd, J¼6.2, 6.9 Hz, Hb-7), 3.78–3.81
(2H, m, H-4, H-3), 5.10–5.13 (2H, m, CHaHbCH]CH2), 5.86 (1H, m,
used for the preparation of 16 to afford 22 (26.2 mg, 89% yield) as
27
a colorless oil. [
a
]
D
ꢁ28 (c 0.68, CHCl3). 1H NMR (CDCl3):
d
3.49 (1H,
CH2CH]CH2). 13C NMR (CDCl3):
d 37.2 (CH2CH]CH2), 66.3 (C-7),
t, J¼2.1 Hz, H-2), 3.34 (1H, d, J¼5.5 Hz, H-4), 3.80 (1H, dt, J¼2.1,
5.5 Hz, H-3), 3.86 (1H, dd, J¼6.9, 6.2 Hz, Ha-7), 4.26 (1H, d, J¼6.9 Hz,
Hb-7), 4.54 (1H, br d, J¼6.2 Hz, H-1), 5.33 (1H, dd, J¼1.4, 11.0 Hz,
CH]CHaHb), 5.71 (1H, dd, J¼1.4, 17.2 Hz, CH]CHaHb), 3.17 (1H, m,
71.8 (CH2Ph), 72.3 (CH2Ph), 74.4 (C-2), 75.0 (C-1), 75.2 (CH2Ph), 79.0
(C-3 or C-4), 81.6 (C-3 or C-4), 108.8 (C-5), 118.4 (CH2CH]CH2),
131.8 (CH2CH]CH2). ESI-MS m/z calcd for C30H32O5$Naþ: 495.2142;
found: 495.2106.
CH]CH2). 13C NMR (CDCl3):
d 65.8 (C-7), 71.3 (CH2Ph), 72.3
(CH2Ph), 73.3 (CH2Ph), 74.9 (C-3), 75.3 (C-1), 76.6 (C-2), 77.2 (C-4),
105.9 (C-5), 117.7 (CH]CH2), 133.8 (CH]CH2). ESI-MS m/z calcd for
C
3.1.21. (1R,2R,3R,4S,5R)-2,3,4-Tris(benzyloxy)-6,8-
dioxabicyclo[3.2.1]octane-5-ethanol (5)
29H30O5SiNaþ: 481.1985; found: 481.1985.
Ozone was bubbled through a stirred solution of 24 (31.6 mg,
0.0669 mmol) in CH2Cl2 (5 mL) at ꢁ78 ꢀC for 30 min. Ph3P (93.0 mg,
0.355 mmol) was added to the reaction mixture, and the reaction
temperaturewas then allowed toincrease tort. Afterthe solvent was
evaporated under reduced pressure and tetrahydrofuran (4 mL) was
added, NaBH4 (6.8 mg, 0.180 mmol) was then added to the solution
at 0 ꢀC. The resulting mixture was stirred for 3 h. The remaining
3.1.18. (1R,2R,3S,4S,5R)-2,3,4-Tris(benzyloxy)-6,8-
dioxabicyclo[3.2.1]octane-5-methanol (4)
Ozone was bubbled through a stirred solution of 22 (13.6 mg,
0.0297 mmol) in CH2Cl2 (5 mL) at ꢁ78 ꢀC for 30 min. Ph3P (40.4 mg,
0.154 mmol) was added to the reaction mixture, and the reaction
temperature was then allowed to increase to rt. After the solvent
was evaporated under reduced pressure and tetrahydrofuran
(4 mL) was added, NaBH4 (11.1 mg, 0.293 mmol) was then added to
the solution at 0 ꢀC. The resulting mixture was stirred for 2.5 h. The
remaining procedure was the same as that used for the preparation
of 2. The crude mixture was separated by preparative TLC (silica gel
procedure was the same as that used for the preparation of 2 to af-
27
ford 5 (27.0 mg, 85% yield) as a colorless oil. [
a
]
ꢁ5.6 (c 1.4, CHCl3).
D
IR (neat) 3475, 3088, 3063, 3033, 3009, 2968, 2891,1497,1454,1398,
1370, 1361, 1265, 1208, 1142, 1098, 1048, 969, 941, 796, 734,
697 cmꢁ1. 1H NMR (CDCl3):
d 1.91 (1H, m, CHaHbCH2OH), 2.34 (1H,
m, CHaHbCH2OH), 3.61 (1H, dd, J¼0.7, 8.2 Hz, Ha-7), 3.67 (1H, dd,
ethyl acetate/hexane¼2:1) to give 4 (10.9 mg, 77% yield) as a col-
J¼2.7, 4.1 Hz, H-2), 3.74–3.79 (5H, m, H-3, H-4, Hb-7, CH2CH2OH),
orless oil. [
a
]
D
þ15 (c 0.55, CHCl3). IR (neat) 3476, 3063, 3032, 2921,
4.58–4.60 (1H, m, H-1). 13C NMR (CDCl3):
d 34.2 (CH2CH2OH), 55.7
27
1496, 1454, 1366, 1329, 1266, 1213, 1093, 1027, 737, 700 cmꢁ1
NMR (CDCl3):
.
1H
(CH2CH2OH), 66.4 (C-7), 72.1 (CH2Ph), 72.4 (CH2Ph), 74.4 (C-2), 75.1
(C-1), 75.5 (CH2Ph), 798.6 (C-3 or C-4), 82.0 (C-3 or C-4),109.9 (C-5).
ESI-MS m/z calcd for C29H32O6$Naþ: 499.2091; found: 499.2088.
d
3.51 (1H, t, J¼2.1 Hz, H-2), 3.73 (1H, d, J¼12.4 Hz, H-
4), 3.77 (1H, ddd, J¼0.7, 7.6 Hz, J¼12.4 Hz, Ha-7), 3.82–3.84 (2H, m,
CH2OH), 3.92 (1H, dd, J¼0.7, 3.4 Hz, H-3), 4.27 (1H, d, J¼7.6 Hz, Hb-
7), 4.54–4.56 (1H, m, H-1). 13C NMR (CDCl3):
d
62.4 (CH2OH), 66.4
3.1.22. (3S,4S,5R,6R)-2-Allyl-6-hydroxymethyl-3,4,5-
(C-7), 71.4 (CH2Ph), 71.6 (CH2Ph), 73.3 (CH2Ph), 74.2 (C-4), 74.3 (C-
3), 75.4 (C-1), 76.4 (C-2), 106.9 (C-5). ESI-MS m/z calcd for
C
tris(benzyloxy)-tetrahydropyran-2-ol (26) and (2R,3R,4S,5S)-6-
allyl-6-hydroxy-3,4,5-tris(benzyloxy)-tetrahydropyran-2-ylmethyl
acetate (6-O-acetyl-1-C-allyl-2,3,4-tri-O-benzyl-D-mannopyranose)
29H30O5Si$Naþ: 485.1935; found: 485.1972.
To a stirred solution of 2516 (36.1 mg, 0.0736 mmol) in THF
(2 mL), a 1.0 M diethyl ether solution of allylmagnesium bromide
(0.177 mL, 0.177 mmol) was added dropwise at ꢁ78 ꢀC under Ar
atmosphere. The resulting mixture was stirred at ꢁ78 ꢀC for 1 h.
The remaining procedure was the same as that used for the prep-
aration of 15. The crude mixture was separated by preparative TLC
(silica gel ethyl acetate/hexane¼1:1) to give 26 (30.6 mg, 85% yield)
as a colorless oil and the intermediate, (2R,3R,4S,5S)-6-allyl-6-
3.1.19. (3S,4R,5R,6R)-2-Allyl-[(6-tert-butyldimethylsilyl)oxy]-
methyl-3,4,5-tris(benzyloxy)-tetrahydropyran-2-ol (23)
To a stirred solution of 14 (81.9 mg, 0.146 mmol) in THF (3 mL),
a
1.0 M diethyl ether solution of allylmagnesium bromide
(0.175 mL, 0.175 mmol) was added dropwise at ꢁ78 ꢀC under Ar
atmosphere. The resulting mixture was stirred at ꢁ78 ꢀC for 1.5 h.
The remaining procedure was the same as that used for the

8088
S. Matsuda et al. / Tetrahedron 64 (2008) 8082–8088
hydroxy-3,4,5-tris(benzyloxy)-tetrahydropyran-2-ylmethyl acetate
3.1.24. (1R,2R,3S,4S,5R)-2,3,4-Tris(benzyloxy)-6,8-
dioxabicyclo[3.2.1]octane-5-ethanol (6)
(3.6 mg, 9% yield), as a colorless oil. Compound 26: 1H NMR
(CDCl3):
d
2.19 (1H, dd, J¼9.6, 13.8 Hz, CHaHbCH]CH2), 2.74 (1H,
Ozone was bubbled through a stirred solution of 27 (51.4 mg,
0.109 mmol) in CH2Cl2 (5 mL) at ꢁ78 ꢀC for 30 min. Ph3P (85.0 mg,
0.324 mmol) was added to the reaction mixture, and the reaction
temperature was then allowed to increase to rt. After the solvent
was evaporated under reduced pressure and tetrahydrofuran
(4 mL) was added, NaBH4 (12.1 mg, 0.320 mmol) was then added to
the solution at 0 ꢀC. The resulting mixture was stirred for 1 h. The
dd, J¼4.8, 13.8 Hz, CHaHbCH]CH2), 3.70–3.73 (1H, m, Ha-7), 3.74
(1H, d, J¼2.7 Hz, H-3), 3.77–3.81 (2H, m, H-6, Hb-7), 3.98 (1H, t,
J¼9.6 Hz, H-5), 4.15 (1H, dd, J¼1.4, 9.6 Hz, H-4), 5.15 (1H, d,
J¼17.2 Hz,
CH2CH]CHaHb),
5.47
(1H,
d,
J¼10.3 Hz,
CH2CH]CHaHb), 5.79 (1H, m, CH2CH]CH2). 13C NMR (CDCl3):
42.4 (CH2CH]CH2), 62.4 (C-7), 72.7 (CH2Ph), 72.8 (C-6), 74.7
d
(CH2Ph), 75.0 (C-5), 75.1 (CH2Ph), 78.7 (C-3), 81.7 (C-4), 97.9 (C-2),
121.3 (CH2CH]CH2), 131.4 (CH2CH]CH2). ESI-MS m/z calcd for
C
remaining procedure was the same as that used for the preparation
27
of 2 to afford 6 (49.2 mg, 95% yield) as a colorless oil. [
2.5, CHCl3). IR (neat) 3522, 3087, 3062, 3031, 2893,1496, 1454,1398,
a
]
ꢁ5.7 (c
D
30H34O6$Naþ: 513.2248; found: 513.2260.
1367, 1331, 1266, 1208, 1076, 1027, 735, 699 cmꢁ1. 1H NMR (CDCl3):
3.1.22.1. (2R,3R,4S,5S)-6-Allyl-6-hydroxy-3,4,5-tris(benzyloxy)-tetra-
hydropyran-2-ylmethyl acetate (6-O-acetyl-1-C-allyl-2,3,4-tri-O-
d
1.85 (1H, ddd, J¼2.7, 6.2, 15.1 Hz, CHaHbCH2OH), 2.47 (1H, ddd,
J¼2.8, 7.5, 15.1 Hz, CHaHbCH2OH), 3.51 (1H, s, H-2), 3.53 (1H, d, J¼
5.5 Hz, H-4), 3.77–3.83 (3H, m, Ha-7, CH2CH2OH), 3.82 (1H, d,
J¼6.2 Hz, H-3), 4.26 (1H, d, J¼7.6 Hz, Hb-7), 4.47–4.55 (1H, m, H-1).
benzyl-D-mannopyranose). 1H NMR (CDCl3):
d 2.03 (3H, s, COCH3),
2.18 (1H, dd, J¼9.6, 13.7 Hz, CHaHbCH]CH2), 2.77 (1H, dd, J¼4.8,
13.7 Hz, CHaHbCH]CH2), 3.75 (1H, d, J¼2.7 Hz, H-5), 3.91 (1H, t,
J¼9.6 Hz, H-3), 3.91–3.99 (1H, m, H-2), 4.15 (1H, dd, J¼2.9, 8.9 Hz,
H-4), 4.23 (1H, J¼4.8, 12.3 Hz, CHaHbOAc), 4.32 (1H, dd, J¼2.1,
11.7 Hz, CHaHbOAc), 5.15 (1H, d, J¼17.2 Hz, CH2CH]CHaHb), 5.25
13C NMR (CDCl3):
d 34.6 (CH2CH2OH), 57.7 (CH2CH2OH), 66.0 (C-7),
71.4 (CH2Ph), 71.6 (CH2Ph), 73.2 (CH2Ph), 73.8 (C-3), 75.0 (C-1), 76.1
(C-2), 76.5 (C-4), 108.9 (C-5). ESI-MS m/z calcd for C29H32O6$Naþ:
499.2091; found: 499.2091.
(1H, d, J¼10.3 Hz, CH2CH]CHaHb), 5.80 (1H, m, CH2CH]CH2). 13
C
NMR (CDCl3):
d 20.9 (COCH3), 42.4 (CH2CH]CH2), 63.9 (CH2OAc),
70.8 (C-2), 72.6 (CH2Ph), 74.5 (C-3), 74.9 (CH2Ph), 75.1 (CH2Ph), 77.5
(C-5), 81.8 (C-4), 97.8 (C-6), 121.2 (CH2CH]CH2), 132.0
(CH2CH]CH2), 171.0 (COCH3). ESI-MS m/z calcd for C32H36O7$Naþ:
555.2353; found: 555.2356.
References and notes
1. La Forge, F. B.; Hudson, C. S. J. Biol. Chem. 1917, 30, 61–77.
2. Takenaka, M.; Ono, H. Tetrahedron Lett. 2003, 44, 999–1002.
3. Hatano, T.; Yoshihara, R.; Hattori, S.; Yoshizaki, M.; Shingu, T.; Okuda, T. Chem.
Pharm. Bull. 1992, 40, 1703–1710.
4. Dalmas, V.; Demuynck, C. Tetrahedron: Asymmetry 1993, 4, 1169–1172.
5. Hricoviniova-Bilikova, Z.; Petrus, L. Carbohydr. Res. 1999, 320, 31–36.
6. Francisco, C. G.; Herrera, A. J.; Suarez, E. J. Org. Chem. 2002, 67, 7439–7445.
7. Matsuda, S.; Matsumura, K.; Watanabe, M.; Yamanoi, T. Tetrahedron Lett. 2007,
48, 5807–5810.
3.1.23. (1R,2R,3S,4S,5R)-5-Allyl-2,3,4-tris(benzyloxy)-6,8-
dioxabicyclo[3.2.1]octane (27)
To a stirred solution of TfOH (1.20 mL, 0.0126 mmol) was added
26 (123.7 mg, 0.252 mmol) in CH3CN (2 mL) at 0 ꢀC in the presence
of dry CaSO4 (158.1 mg) under Ar atmosphere. The resulting mix-
ture was stirred for 1.5 h. The remaining procedure was the same as
that used for the preparation of 16. The crude mixture was sepa-
8. Yamanoi, T.; Matsumura, K.; Matsuda, S.; Oda, Y. Synlett 2005, 2973–2977.
9. Ogawa, T.; Nukada, T. Carbohydr. Res. 1985, 136, 135–152.
10. Sato, K.; Yoshitomo, A. Chem. Lett. 1995, 39–40. A similar steric inversion has
been reported at the C-2 and C-4 positions of the
to form the -mannopyranose derivative.
D-galactopyranose derivative
rated by preparative TLC (silica gel ethyl acetate/hexane¼1:3) to
D
27
give 27 (103.8 mg, 87% yield) as a colorless oil. [
a
]
ꢁ13 (c 5.2,
11. Ogawa, T.; Nakabayashi, S.; Kitajima, T. Carbohydr. Res. 1983, 114, 225–236.
12. Kuzuhara, H.; Fletcher, H. G. J. Org. Chem. 1967, 32, 2531–2534.
13. Compound 15 was scarcely obtained from 14 under the reaction conditions
using vinylmagnesium chloride in THF at ꢁ78 ꢀC. It was reported that the ad-
dition of Grignard reagents to a ketone was enhanced by cerium chloride with
remarkable suppression of side reactions. Imamoto, T.; Takiyama, N.; Naka-
mura, K.; Hatajima, T.; Kamiya, Y. J. Am. Chem. Soc. 1989, 111, 4392–4398.
14. A similar conversion procedure of the 1-propenyl group of the fructofuranoside
derivative into a hydroxymethyl group has been reported Nicotra, F.; Panza, L.;
Russo, G. J. Org. Chem. 1987, 52, 5627–5630.
D
CHCl3). 1H NMR (CDCl3):
d
2.60 (1H, dd, J¼8.2, 14.4 Hz,
CHaHbCH]CH2), 2.79 (1H, dd, J¼6.2, 14.4 Hz, CHaHbCH]CH2),
3.49 (1H, s, H-2), 3.58 (1H, d, J¼4.8 Hz, H-4), 3.76 (1H, dd, J¼6.2,
6.9 Hz, Ha-7), 3.82 (1H, d, J¼4.8 Hz, H-3), 4.19 (1H, d, J¼6.9 Hz, Hb-
7), 4.50–4.52 (1H, m, H-1), 5.09 (1H, d, J¼10.3 Hz, CH2CH]CHaHb),
5.13 (1H, d, J¼17.2 Hz, CH2CH]CHaHb), 5.87 (1H, m, CH2CH]CH2).
13C NMR (CDCl3):
d 37.8 (CH2CH]CH2), 66.0 (C-7), 71.2 (CH2Ph),
15. Adinolfi, M.; Iadonisi, A.; Schiattarella, M. Tetrahedron Lett. 2003, 44, 6479–
6482.
16. El-Badri, M. H.; Willenbring, D.; Tantillo, D. J.; Gervay-Hague, J. J. Org. Chem.
2007, 72, 4663–4672.
71.4 (CH2Ph), 73.0 (CH2Ph), 74.2 (C-3), 75.0 (C-1), 76.1 (C-2), 76.2 (C-
4), 107.7 (C-5), 118.1 (CH2CH]CH2), 132.1 (CH2CH]CH2). ESI-MS
m/z calcd for C30H32O5$Naþ: 495.2142; found: 495.2182.