Practical synthesis of 1,3-O-Di-tert-butylsilylene-protected D- and L-erythritols as a four-carbon chiral building block

Full text of DOI:10.1021/jo0107103

8666
J . Org. Chem. 2001, 66, 8666-8668
Sch em e 1
P r a ctica l Syn th esis of
1,3-O-Di-ter t-bu tylsilylen e-P r otected D- a n d
L-Er yth r itols a s a F ou r -Ca r bon Ch ir a l
Bu ild in g Block
Yuji Mori* and Hisafumi Hayashi
Faculty of Pharmacy, Meijo University, 150 Yagotoyama,
Tempaku-ku, Nagoya 468-8503, J apan
mori@ccmfs.meijo-u.ac.jp
Received J uly 13, 2001
Marine polycyclic ether toxins consist of bioactive
agents whose skeletons incorporate regular oxygenated
heterocycles,1 and their unique ladder architectures and
potent biological activities have attracted the attention
of numerous synthetic chemists. The highly symmetrical
trans-fused polycyclic ether skeleton consisting of six-
membered rings has led researchers to believe that an
iterative or convergent approach might be the best way
to synthesize these molecules.2,3 As part of our program
toward these ring systems, we have developed a five-step
iterative approach to trans-fused polytetrahydropyrans
1 based on a combination strategy of alkylation of an
oxiranyl anion and a 6-endo cyclization.2b To apply this
strategy to the synthesis of natural toxins, we required
a four-carbon building block, erythritol (3), for the
preparation of a tetrasubstituted tetrahydropyran 2
(Scheme 1). Regioselective cyclic protection of the two
hydroxyl groups at the C(1)- and C(3)-positions or the
C(2)- and C(4)-positions of erythritol provides enantio-
meric 1,3-O-protected D- or L-erythritol, respectively.
However, as erythritol belongs to a meso-compound, its
use as a chiral four-carbon building block is very limited
compared to threitol and its derivatives.4
Sch em e 2
building blocks as well as their carboxaldehyde ana-
logues,9 and interestingly, a 2-butylidene derivative,
coruscol A, was recently isolated from a Penicillium sp.
as a natural product.10 Although acetals 4 can be easily
prepared from D-glucose, synthesis of its enantiomer
requires expensive L-glucose as reported in the synthesis
of glycosidase inhibitor salacinol.11 Furthermore, the
acetal functional group in 4 would not tolerate acidic
reaction conditions such as p-toluenesulfonic acid in
methanol, which may be employed for the synthesis of
2. In this paper, we report a simple and efficient synthe-
sis of both enantiomers of 1,3-O-silylene-protected D- and
L-erythritols (5 and 6) that are more acid stable than 1,3-
O-alkylidene derivatives.
1,3-O-Alkylidene-L-erythritols [2-substituted (2R,4S,5R)-
5-hydroxy-1,3-dioxane-4-methanols] 4 with R ) Me,5 Pr,6
Ph,7 or p-MeOPh8 have been employed as useful chiral
* To whom correspondence should be addressed. Phone: +81-52-
832-1781. Fax: +81-52-834-8090.
(1) (a) Shimizu, Y. Marine Natural Products; Academic Press: New
York, 1978; Vol. 1. (b) Shimizu, Y. Chem. Rev. 1993, 93, 1685. (c)
Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897.
(2) For examples of iterative approaches, see: (a) Mori, Y. Chem.
Eur. J . 1997, 3, 849. (b) Mori, Y.; Yaegashi, K.; Furukawa, H. J . Am.
Chem. Soc. 1996, 118, 8158. (c) Evans, P. A.; Roseman, J . D.; Garber,
L. T. J . Org. Chem. 1996, 61, 4880. (d) Clark, J . S.; Kettle, J . G.
Tetrahedron Lett. 1997, 38, 123. (e) Rainer, J . D.; Allwein, S. P.
Tetrahedron Lett. 1998, 39, 9601. (f) Bowman, J . L.; McDonald, F. E.
J . Org. Chem. 1998, 63, 3680. (g) Hori, N.; Matukura, H.; Matsuo, G.;
Nakata, T. Tetrahedron Lett. 1999, 40, 2811.
According to the reported procedure,7 1,3-O-benzylidene-
L-erythritol (8) was prepared from 4,6-O-benzylidene-D-
glucose (7) by NaIO4 oxidation in the presence of NaHCO3
followed by NaBH4 reduction (Scheme 2). Cyclic protec-
tion of the primary and secondary hydroxyl groups with
di-tert-butylsilyl bis(trifluoromethanesulfonate)12 gave
(3) For examples of convergent approaches, see: (a) Nicolaou, K.
C.; Postema, M. H. D.; Claiborne, C. F. J . Am. Chem. Soc. 1996, 118,
1565. (b) Alvarez, E.; Pe´rez, R.; Rico, M.; Rodr´ıguez, R. M.; Mart´ın, J .
D. J . Org. Chem. 1996, 61, 3003. (c) Sasaki, M.; Fuwa, H.; Inoue, M.;
Tachibana, K. Tetrahedron Lett. 1998, 39, 9027. (d) Fujiwara, K.; Saka,
K.; Takaoka, D.; Murai, A. Synlett 1999, 1037. (e) Maeda, K.; Oishi,
T.; Oguri, H.; Hirama, M. Chem. Commun. 1999, 1063. (f) Sasaki, M.;
Fuwa, H.; Ishikawa, M.; Tachibana, K. Org. Lett. 1999, 1, 1075. (g)
Fujiwara, K.; Morishita, H.; Saka, K.; Murai, A. Tetrahedron Lett.
2000, 41, 507. (h) Matsuo, G.; Hinou, H.; Koshino, H.; Suenaga, T.;
Nakata, T. Tetrahedron Lett. 2000, 41, 903. (i) Mori, Y.; Mitsuoka, S.;
Furukawa, H. Tetrahedron Lett. 2000, 41, 4161.
(6) Bonner, T. G.; Bourne, E. J .; Lewis, D. J . Chem. Soc. 1965, 7453.
(7) (a) Foster, A. B.; Haines, A. H.; Homer, J .; Lehmann, L.; Thomas,
L. F. J . Chem. Soc. 1961, 5005. (b) Marco, J . A.; Carda, M.; Gonzalez,
F.; Rodoriguez, S.; Murga, J . Liebigs Ann. 1996, 1801.
(8) Ishiwata, A.; Sakamoto, S.; Noda, T.; Hirama, M. Synlett 1999,
692.
(9) For recent examples, see: (a) Li, L.-S.; Wu, Y.-L.; Wu, Y. Org.
Lett. 2000, 2, 891. (b) Storz, T.; Bernet, B.; Vasella, A. Helv. Chim.
Acta 1999, 82, 2380. (c) Kuban, J .; Blanarikova, I.; Fisera, L.;
J aroskova, L.; Fengler-Veith, M.; J ager, V.; Kozisek, J .; Humpa, O.;
Pronayova, N.; Langer, V. Tetrahedron 1999, 55, 9501. (d) Yu, Q.; Wu,
Y.; Ding, H.; Wu, Y.-L. J . Chem. Soc., Perkin Trans. 1 1999, 1183. (e)
Zhu, Q.; Qiao, L.-X.; Wu, Y.; Wu, Y.-L. J . Org. Chem. 1999, 64, 2428.
(f) Garcia, F. S.; Cebrian, G. M. P.; Lopez, A. H.; Herrera, F. J . L.
Tetrahedron Lett. 1998, 54, 6867. (g) Baker, S. R.; Clissold, D. W.;
McKillop, A. Tetrahedron Lett. 1988, 29, 991. (h) Rapoport, H.; Hauske,
R. J . Org. Chem. 1979, 44, 2472.
(4) Gawronski, J .; Gawronska, K. Tartaric and Malic Acids in
Synthesis; J ohn Wiley & Sons: New York, 1999.
(5) (a) Baker, R.; MacDonald, D. L. J . Am. Chem. Soc. 1960, 82,
2301. (b) Marusawa, H.; Setoi, H.; Kuroda, A.; Seki, J .; Motoyama, Y.;
Tanaka, H. Bioorg. Med. Chem. 1999, 7, 2635. (c) Carda, M.; Casabo,
P.; Gonzalez, S.; Rodoriguez, S.; Domingo, L. R.; Marco, J . A. Tetra-
hedron: Asymmetry, 1997, 8, 559. (d) Calvo-Flores, F. G.; Garcia-
Mendoza, P.; Hernandez-Mateo, F.; Isae-Garcia, J .; Santoyo-Gonzalez,
F. J . Org. Chem. 1997, 62, 3944.
(10) Kagata, T.; Sigemori, H.; Mikami, Y.; Kobayashi, J . J . Nat.
Prod. 2000, 63, 886.
(11) Ghavami, A.; J ohnston, B. D.; Pinto, B. M. J . Org. Chem. 2001,
66, 2312.
10.1021/jo0107103 CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/20/2001

Notes
J . Org. Chem., Vol. 66, No. 25, 2001 8667
Sch em e 3
oxiranyllithium generated from the racemic trans-epoxy
sulfone 1313,14 in THF in the presence of HMPA at -100
°C gave the coupled product 14 in 91% yield.
As 14 is a diastereoisomeric mixture of R- and â-ep-
oxides, cyclization of 14 was carried out according to the
method we developed.13 Thus, detriethylsilylation with
p-toluenesulfonic acid in methanol followed by exposure
to MgBr2‚OEt2 in CH2Cl2 gave a mixture of hydroxy
bromoketones, which was treated with DBU to afford an
equilibrium mixture of cyclized products, from which the
desired cyclic ketone 15 was isolated in 79% overall yield
along with a 9% yield of its epimer. Finally, reduction of
the ketone to alcohol 16 with sodium borohydride and
debenzylation by hydrogenolysis gave the optically active
tetrahydropyran diol 17 in 95% yield, which serves as
useful starting material for marine polycyclic ether
synthesis.
Sch em e 4
In conclusion, an efficient and enantioselective method
to synthesize 1,3-O-silylene-protected D- and L-erythritols
from D-glucose derivatives has been established. Each
enantiomer would be useful as a four-carbon chiral
building block, and the utilization of the chiral building
blocks is very effective for the synthesis of dissymmetri-
cally protected tetrahydropyrans.
Exp er im en ta l Section
Gen er a l. IR spectra were recorded in CHCl3 solution on a
1
J ASCO FTIR-420 spectrometer. H and 13C NMR spectra were
recorded on a J EOL A-400 or A-600 spectrometer in CDCl3
solution using TMS and CDCl3 (77.00 ppm) as internal stan-
dards, respectively. Mass spectra were obtained on a J EOL J MS-
700 mass spectrometer. Optical rotations were determined on a
J ASCO DIP-370 digital polarimeter. Air- and moisture-sensitive
reactions were carried out under an argon atmosphere under
anhydrous conditions. Flash chromatography was carried out
with E. Merck silica gel 60 (230-400 mesh). The term “dried”
refers to the drying of an organic solution over MgSO4 followed
by filtration.
silylene acetal 9 in 95% yield. Selective deprotection of
benzylidene acetal by hydrogenolysis using palladium
hydroxide on carbon in ethyl acetate-acetic acid afforded
1,3-O-di-tert-butylsilylene-D-erythritol 5 [(4R,5S)-2-di-
tert-butyl-5-hydroxy-1,3-dioxa-2-silacyclohexane-4-metha-
nol] in 98% yield.
(1R,6S,8R)-3,3-Di-ter t-bu tyl-8-p h en yl-2,4,7,9-tetr a oxa -3-
sila b icyclo[4.4.0]d eca n e (9). To a solution of 1,3-O-ben-
zylidene-L-erythritol (8: (2R,4S,5R)-2-phenyl-5-hydroxy-1,3-
dioxane-4-methanol)7 (4.50 g, 21.43 mmol) and 2,6-lutidine (7.5
mL, 64.29 mmol) in DMF (30 mL) was added tert-Bu2Si(OTf)2
at 0 °C under argon, and the reaction mixture was stirred for 4
h. The mixture was extracted with Et2O, and the combined
extracts were washed with water and brine, dried, and evapo-
rated. Purification of the residue by flash chromatography (20%
Et2O/hexane) gave 9 (7.09 g, 95%) as a crystalline solid: mp
Its enantiomeric diol 6 was prepared from the com-
mercially available tri-O-acetyl-D-glucal (10) (Scheme 3).
Deacetylation and the following regioselective cyclic
silylation were performed in a one-pot procedure. Metha-
nolysis of 10 with a catalytic amount of K2CO3 followed
by removal of methanol gave D-glucal, which was then
dissolved in DMF and 2,6-lutidine and treated with di-
tert-butylsilyl bis(trifluoromethanesulfonate) at -20 °C
to give 4,6-O-silylene D-glucal 11 in 84% yield. Oxidative
ring cleavage with excess NaIO4 in the presence of a
catalytic amount of OsO4 and reduction of the resulting
aldehyde with NaBH4 gave 1,3-O-di-tert-butylsilylene-L-
erythritol 6 [(4S,5R)-2-di-tert-butyl-5-hydroxy-1,3-dioxa-
2-silacyclohexane-4-methanol] in 84% yield. The enan-
tiomeric isomer of 8 could be readily obtained from 6 by
benzylidene acetal formation followed by desilylation.
We next turned our attention to the synthesis of tetra-
hydropyran 2 utilizing a chiral four-carbon building block
6 (Scheme 4). Regioselective activation and protection of
two hydroxyl groups were carried out in a one-pot
process.2b Treatment of a solution of 6 and 2,6-lutidine
in CH2Cl2 with trifluoromethanesulfonic anhydride fol-
lowed by triethylsilyl trifluoromethanesulfonate gave 12
in 95% yield. The corresponding TES-protected triflate
prepared from 8 was found to be labile and decomposed
during purification. Reaction of the triflate 12 with the
124-125 °C; [R]24 +9.0 (c 0.33, CHCl3); IR (CHCl3) 1473, 1103
D
cm-1; 1H NMR (400 MHz) δ 1.02 (s, 9H), 1.07 (s, 9H), 3.65 (t, J
) 10.2 Hz, 1H), 3.83 (ddd, J ) 10.2, 10.2, 5.1 Hz, 1H), 4.01(t, J
) 9.5 Hz, 1H), 4.08 (ddd, J ) 10.2, 9.5, 4.4 Hz, 1H), 4.22 (dd, J
) 9.5, 5.1 Hz, 1H), 4.35 (dd, J ) 10.2, 4.4 Hz, 1H), 7.33-7.47
(m, 5H); 13C NMR (100 MHz) δ 20.10, 22.70, 27.05, 27.41, 66.50,
68.92, 71.39, 77.71, 101.63, 126.12, 128.34, 129.13; EIMS m/z
350 (M+). Anal. Calcd for C19H30O4Si: C, 65.11; H, 8.63. Found:
C, 65.34; H, 8.58.
(4R,5S)-2,2-Di-ter t-bu tyl-5-h yd r oxy-1,3-d ioxa -2-sila cyclo-
h exa n e-4-m eth a n ol (5). A mixture of 9 (6.00 g, 17.14 mmol)
and 20% Pd(OH)2/C (600 mg) in EtOAc (86 mL) and AcOH (8.6
mL) was stirred for 15 h at room temperature under H2
atmosphere. The reaction mixture was passed through a short
column of Celite and eluted with EtOAc. The filtrate was washed
with dilute NH4OH and brine, dried, and evaporated. Purifica-
tion by flash chromatography (50f60% EtOAc/hexane) gave 5
(4.4 g, 98%) as a crystalline solid: mp 106-107 °C; [R]20D +26.6
(c 1.0, CHCl3); IR (CHCl3) 3587, 3419 cm-1; 1H NMR (400 MHz)
δ 0.99 (s, 9H), 1.05 (s, 9H), 2.21 (br t, J ) 6.3 Hz, OH), 2.36 (br
d, J ) 4.9 Hz, OH), 3.77-3.85 (m, 4H), 3.90 (m, 1H), 4.11 (m,
(13) Mori, Y.; Yaegashi, K.; Furukawa, H. Tetrahedron Lett. 1999,
40, 7239.
(14) Ashwell, M.; Clegg, W.; J ackson, R. F. W. J . Chem. Soc., Perkin
Trans. 1 1991, 897.
(12) Corey, E. J .; Hopkins, P. B. Tetrahedron Lett. 1982, 23, 4871.

8668 J . Org. Chem., Vol. 66, No. 25, 2001
Notes
1H); 13C NMR (100 MHz) δ 20.05, 22.69, 27.08, 27.46, 64.87,
66.28, 77.61; EIMS m/z 262 (M+). Anal. Calcd for C12H26O4Si:
C, 54.93; H, 9.99. Found: C, 54.65; H, 10.27.
at room temperature for 2 h, the reaction was quenched with
Et3N (0.1 mL) and the solvent was evaporated. The residue was
purified by flash chromatography (30% EtOAc/hexane) to give
a 1:1 mixture of hydroxy epoxy sulfones (2.55 g, 98%).
(1S,6R,10R)-3,3-Di-ter t-bu tyl-10-h yd r oxy-2,4,7-tr ioxa -3-
sila bicyclo[4.4.0]d ec-8-en e (11). To a solution of tri-O-acetyl-
D-glucal (10: 15.5 g, 57.0 mmol) in MeOH (57 mL) was added
K2CO3 (79 mg, 0.57 mmol), and the mixture was stirred at room
temperature for 3 h. After the solvent was evaporated, the
resulting D-glucal was suspended in CHCl3 (50 mL) and then
concentrated under reduced pressure to remove the residual
MeOH. This operation was repeated three times. The D-glucal
obtained was dissolved in DMF (40 mL) and 2,6-lutidine (15.9
mL, 142.5 mmol), and to this solution was added tert-Bu2Si(OTf)2
(20.8 mL, 57.0 mmol) at -20 °C under argon. After stirring at
-20 °C for 30 min, the reaction mixture was warmed to 0 °C
over a period of 30 min and extracted with Et2O. The combined
extracts were washed with water and brine, dried, and evapo-
rated. The residue was purified by flash chromatography (15%
(iii) Bromoketone formation: To a stirred solution of the
hydroxy epoxy sulfones (2.55 g, 4.54 mmol) in CH2Cl2 (45 mL)
was added MgBr2‚OEt2 (1.41 g, 5.44 mmol) at 0 °C. After stirring
at room temperature for 1 h, the reaction mixture was poured
into water and extracted with CH2Cl2. The combined extracts
were washed with saturated aqueous NaHCO3 and brine, dried,
and evaporated. Purification by flash chromatography (25%
EtOAc/hexane) gave a 1:1 mixture of bromoketones (2.14 g, 97%).
(iv) Cyclization: To a stirred solution of the bromoketones
(2.14 g, 4.39 mmol) in CH2Cl2 (30 mL) at 0 °C was added DBU
(0.69 mL, 4.61 mmol). After the mixture was stirred at 0 °C for
1 h, the reaction was quenched with saturated aqueous NH4Cl
and the mixture was extracted with CH2Cl2. The combined
extracts were washed with water, dried, and evaporated.
Purification by flash chromatography (3f15% EtOAc/hexane)
gave 15 (1.49 g, 83%) as a solid and its C(8)-epimer (162 mg,
9%) as an oil. 15: mp 101-102 °C; [R]25D -12.08 (c 0.59, CHCl3);
EtOAc/hexane) to give 11 (13.7 g, 84%) as an oil: [R]24 -17.4
D
(c 0.58, CHCl3); IR (CHCl3) 3595, 1465, 1473 cm-1; 1H NMR (400
MHz) δ 1.00 (s, 9H), 1.07 (s, 9H), 2.44 (br s, OH), 3.84 (ddd, J )
10.3, 10.3, 4.9 Hz, 1H), 3.92 (dd, J ) 10.3, 7.3 Hz, 1H), 3.97 (t,
J ) 10.3 Hz, 1H), 4.18 (dd, J ) 10.3, 4.9 Hz, 1H), 4.30 (br d, J
) 6.8 Hz, 1H), 4.76 (dd, J ) 5.9, 2.0 Hz, 1H), 6.27 (dd, J ) 6.4,
2.0 Hz, 1H); 13C NMR (100 MHz) δ 19.84, 22.72, 26.90, 27.42,
65.71, 70.19, 72.26, 102.97, 143.62; HREIMS calcd for C14H26O4-
Si 286.1599, found 286.1571.
1
IR (CHCl3) 1725, 1473, 1114 cm-1; H NMR (400 MHz) δ 1.00
(s, 9H), 1.05 (s, 9H), 2.44 (dd, J ) 16.1, 10.7 Hz, 1H), 3.04 (dd,
J ) 16.1, 5.9 Hz, 1H), 3.63 (ddd, J ) 10.3, 10.3, 4.9 Hz, 1H),
3.66 (dd, J ) 10.7, 5.9 Hz, 1H), 3.87 (dd, J ) 10.7, 2.9 Hz, 1H),
3.95 (t, J ) 10.3 Hz, 1H), 4.06 (dd, J ) 6.3, 2.9 Hz, 1H), 4.18
(ddd, J ) 10.7, 10.3, 5.9 Hz, 1H), 4.31 (dd, J ) 10.3, 4.9 Hz,
1H), 4.53 and 4.57 (each d, J ) 12.1 Hz, 1H), 7.27-7.36 (m, 5H);
13C NMR (100 MHz) δ 19.90, 22.59, 26.98, 27.37, 48.22, 66.54,
68.33, 72.49, 73.71, 76.05, 82.61, 127.73, 127.76, 128.39, 137.83,
203.93; EIMS m/z 406 (M+). Anal. Calcd for C22H34O5Si: C,
64.99; H, 8.43. Found: C, 64.62; H, 8.69.
(4S,5R)-2,2-Di-ter t-bu tyl-5-h yd r oxy-1,3-d ioxa -2-sila cyclo-
h exa n e-4-m eth a n ol (6). To a stirred solution of 11 (12.9 g, 45.2
mmol) in MeOH (200 mL) were added a solution of NaIO4 (38.7
g, 180.9 mmol) in water (300 mL), NaHCO3 (7.60 g, 90.5 mmol),
and a catalytic amount of OsO4 (20 mg). The resulting suspen-
sion was stirred at room temperature for 24 h and then filtered
through a short pad of Celite with MeOH. The MeOH was
evaporated, and the residue was extracted with EtOAc. The
combined extracts were washed with water and brine, dried, and
evaporated to give a mixture of aldehyde and its dimeric
hemiacetal. The crude product was dissolved in MeOH (60 mL),
and NaBH4 (1.55 g, 40.9 mmol) was added at 0 °C. The solution
was stirred for 1 h, and then water (20 mL) was added. After
evaporation of the solvent, the residue was extracted with
EtOAc. The combined extracts were washed with water and
brine, dried, and evaporated to give a solid. Purification by flash
chromatography (35% EtOAc/hexane) gave 6 (9.92 g, 84%) as a
solid: mp 105-107 °C; [R]25D -26.0 (c 0.47, CHCl3). The 1H NMR
and 13C NMR spectra were identical with those of compound 5.
(1S,6R,8S,9R)-8-(Ben zyloxy)m eth yl-3,3-di-ter t-bu tyl-2,4,7-
tr ioxa -3-sila bicyclo[4.4.0]d eca n -9-ol (16). To a stirred solu-
tion of 15 (1.49 g, 3.67 mmol) in CH2Cl2 (15 mL) and MeOH (15
mL) at -78 °C was added NaBH4 (300 mg, 7.93 mmol), and the
reaction mixture was stirred at -78 °C for 30 min. The reaction
mixture was poured into water and extracted with EtOAc. The
combined extracts were washed with water and brine, dried, and
evaporated. Purification by flash chromatography (20% EtOAc/
hexane) gave 16 (1.42 g, 95%) as a crystalline solid: mp 77-79
°C; [R]25 -6.16 (c 0.53, CHCl3); IR (CHCl3) 3496, 1473, 1220,
D
1108 cm-1; 1H NMR (400 MHz) δ 0.98 (s, 9H), 1.03 (s, 9H), 1.50
(q, J ) 12.2 Hz, 1H), 2.47 (ddd, J ) 12.2, 4.4, 4.4 Hz, 1H), 2.71
(br s, OH), 3.30 (ddd, J ) 10.2, 9.3, 4.9 Hz, 1H), 3.36 (ddd, J )
9.3, 5.9, 4.9 Hz, 1H), 3.60 (dd, J ) 11.2, 5.9 Hz, 1H), 3.69 (ddd,
J ) 11.2, 9.3, 4.4 Hz, 1H), 3.71 (dd, J ) 11.2, 4.9 Hz, 1H), 3.77
(ddd, J ) 11.2, 9.3, 4.4 Hz, 1H), 3.78 (t, J ) 10.2 Hz, 1H), 4.12
(dd, J ) 10.2, 4.9 Hz, 1H), 4.53 and 4.58 (each d, J ) 11.7 Hz,
1H), 7.27-7.37 (m, 5H); 13C NMR (100 MHz) δ 19.93, 22.60,
27.04, 27.42, 40.96, 66.75, 68.38, 71.19, 72.01, 73.76, 77.05, 79.22,
127.84, 127.99, 128.55, 137.45; EIMS m/z 408 (M+). Anal. Calcd
for C22H36O5Si: C, 64.67; H, 8.89. Found: C, 64.39; H, 8.96.
(1S,6R,8S,9R)-8-(Ben zyloxy)m et h yl-3,3-d i-ter t-b u t yl-9-
h yd r oxy-2,4,7-t r ioxa -3-sila b icyclo[4.4.0]d eca n e-8-m et h a -
n ol (17). A mixture of 16 (800 mg, 1.96 mmol) and 20%
Pd(OH)2/C (160 mg) in EtOAc (14 mL) was stirred for 40 min at
room temperature under H2 atmosphere. The reaction mixture
was passed through a short column of Celite and eluted with
EtOAc. The filtrate was evaporated to give 17 (622 mg, 100%)
(4S,5R)-2,2-Di-ter t-bu tyl-5-tr ieth ylsiloxy-1,3-d ioxa -2-si-
la cycloh exa n e-4-m eth yl Tr iflu or om eth a n esu lfon a te (12).
To a stirred solution of diol 6 (1.40 g, 5.34 mmol) in dry CH2Cl2
(14 mL) at -78 °C under argon were added 2,6-lutidine (1.85
mL, 16.03 mmol) and triflic anhydride (0.94 mL, 5.61 mmol).
After the mixture was stirred at -78 °C for 30 min, TESOTf
(1.42 mL, 6.41 mmol) was added and stirring was continued for
another 30 min. The reaction mixture was poured into water
and extracted with EtOAc. The combined extracts were washed
with saturated aqueous NaHCO3, water, and brine, dried, and
evaporated. Purification by flash chromatography (3% EtOAc/
hexane) gave 12 (2.59 g, 95%) as a pale yellow oil: [R]25 -38.5
D
1
(c 0.22, CHCl3); IR (CHCl3) δ 1473, 1413, 1225, 1207 cm-1; H
NMR (600 MHz) δ 0.61 (q, J ) 8.1 Hz, 6H), 0.95 (t, J ) 8.1 Hz,
9H), 1.00 (s, 9H), 1.04 (s, 9H), 3.79 (m, 2H), 4.06 (m, 2H), 4.61
(dd, J ) 10.3, 4.4 Hz, 1H), 4.68 (dd, J ) 10.3, 2.2 Hz, 1H).
as a crystalline solid: mp 211-212 °C; [R]25 -37.4 (c 0.50,
D
CHCl3); IR (KBr) 3587, 3420 cm-1; 1H NMR (600 MHz, acetone-
d6) δ 0.98 (s, 9H), 1.02 (s, 9H), 1.51 (q, J ) 11.7 Hz, 1H), 2.40
(ddd, J ) 11.7, 4.4, 4.4 Hz, 1H), 3.20 (ddd, J ) 8.8, 5.9, 2.9 Hz,
1H), 3.31 (ddd, J ) 9.5, 9.5, 5.1 Hz, 1H), 3.53 (t, J ) 6.4 Hz,
OH), 3.55-3.62 (m, 2H), 3.74 (t, J ) 10.3 Hz, 1H), 3.77 (m, 2H),
4.07 (dd, J ) 10.3, 5.1 Hz, 1H), 4.10 (d, J ) 5.1 Hz, OH); 13C
NMR (150 MHz, acetone-d6) δ 20.43, 23.11, 27.47, 27.79, 42.74,
63.13, 66.58, 67.66, 73.43, 77.66, 83.68; EIMS m/z 318 (M+).
Anal. Calcd for C15H30O5Si: C, 56.57; H, 9.50. Found: C, 56.43;
H, 9.76.
(1S,6R,8S)-8-(Ben zyloxy)m et h yl-3,3-d i-ter t-b u t yl-2,4,7-
tr ioxa -3-sila bicyclo[4.4.0]d eca -9-on e (15). (i) Alkylation reac-
tion: A solution of triflate 12 (2.59 g, 5.09 mmol) and the racemic
trans-epoxy sulfone 13 (2.43 g 7.65 mmol) in HMPA (2.66 mL,
15.29 mmol) and dry THF (34 mL) under argon was cooled to
-100 °C and treated with n-BuLi (4.78 mL of 1.6 M solution in
hexane, 7.65 mmol). After the mixture was stirred at -100 °C
for 40 min, the reaction was quenched with saturated aqueous
NH4Cl. The mixture was warmed to 0 °C and extracted with
EtOAc. The combined extracts were washed with water and
brine, dried, and evaporated. Purification by flash chromatog-
raphy (6% EtOAc/hexane) gave 14 (3.15 g, 91%) as a 1:1 mixture
of two diastereoisomers.
Ack n ow led gm en t. This work was generously sup-
ported by a grant of the High-Tech Research Center
Project from J apanese Ministry of Education, Culture,
Sports, Science and Technology.
(ii) Detriethylsilylation: Product 14 (3.15 g 4.65 mmol)
obtained above was dissolved in MeOH (31 mL), and TsOH‚H2O
(18 mg, 0.093 mmol) was added. After the mixture was stirred
J O0107103