Yoshimura et al.
ene chloride (500 mL) was added and the organic layer was
separated, washed with brine (150 mL), dried (MgSO4),
filtered, and concentrated under vacuum. This compound could
be used directly in the following step without further purifica-
tion; however, an analytical sample was obtained following
flash column chromatography with EtOAc in hexanes (30%)
to give (()-6 as a clear oil: IR (neat) 3466, 1719 cm-1; 1H NMR
(CDCl3) δ 7.69-7.80 (m, 4 H), 7.41-7.55 (m, 6 H), 4.63 (m, 1
H, converted to a t after D2O, J ≈ 8.6 Hz), 4.38 (td, 1 H, J )
8.0, 4.9 Hz), 4.18 (m, 2 H), 2.12-2.23 (m, 2 H, reduced to 1 H
after D2O exchange), 2.07 (m, 1 H), 1.74 (irregular t, 1 H, J ≈
5 Hz), 1.38-1.52 (m, 2 H), 1.29 (t, 3 H, J ) 7.1 Hz), 1.13 (s, 9
H); FAB MS m/z (relative intensity) 135 (92), 169 (40.1), 199
(100), 321 (10.6), 367 (13.4), 407 (25.4), 425 (5.5, MH+). Anal.
Calcd for C25H32O4Si: C, 70.72; H, 7.60. Found: C, 70.76; H,
7.70.
on top of a short silica gel column and eluted with EtOAc in
hexanes (40%). The fractions containing the inseparable
mixture were combined and rechromatographed with the same
solvent system (33%f40%) to give (+)-10 (82 mg, 64%) and
acetal 11 (11 mg, 8%) as separate diastereoisomers.
(+)-10: oil; [R]25 ) +71.3° (c 0.79, CHCl3); IR (neat) 3446,
D
1731, 1238 cm-1; 1H NMR (CDCl3) δ 5.26 (t, 1 H, J ) 8.3 Hz),
4.45-4.51 (m, 1 H), 4.24 (d, 1 H, J ) 11.9 Hz), 3.90 (d, 1H, J
) 11.9 Hz), 2.51 (td, 1H, J ) 13.5, 7.8 Hz), 2.06, 2.05 (s, each
3 H), 1.68 (td, 1H, J ) 8.3, 4.3 Hz), 1.58 (d, 1 H, J ) 6.0 Hz,
D2O exchanged), 1.25 (dd, 1H, J ) 5.6, 4.4, Hz), 1.17 (td, 1H,
J ) 13.5, 8.8 Hz), 0.71 (irregular t, 1H, J ≈ 6.9 Hz); FAB MS
m/ z (relative intensity) 91 (53.6), 109 (100), 169 (61.3), 211
(44.9, MH+ - H2O), 229 (11.1, MH+). Anal. Calcd for C11H16O5‚
0.2H2O: C, 56.99; H, 7.13. Found: C, 56.85; H, 7.23.
11: oil; IR (neat) 3451, 1738, 1258, 1024 cm-1 1H NMR
;
4-(2,2-Dim eth yl-1,1-diph en yl-1-silapr opoxy)-1-(h ydr oxy-
m eth yl)bicyclo[3.1.0]h exa n -2-ol [(()-7]. A stirred suspen-
sion of LAH (1.27 g, 33.6 mmol) in diethyl ether (250 mL) was
treated dropwise with a solution of crude (()-6 (ca. 22.4 mmol)
in diethyl ether (50 mL) at 0 °C After stirring for 10 min, water
(1.4 mL), 15% aqueous NaOH solution (1.4 mL), and water
(1.8 mL) were added dropwise successively at 0 °C. The
reaction mixture was filtered through a pad of Celite and the
filtrate was concentrated under vacuum. The residue was
purified by flash column chromatography using EtOAc in
hexanes (60%) to give (()-7 (6.42 g, 75%) as a clear oil: IR
(neat) 3348 cm-1; 1H NMR (CDCl3) δ 7.70-7.80 (m, 4 H), 7.40-
7.55 (m, 6 H), 4.31-4.44 (m, 2 H), 3.78 (d, 1 H, J ) 11.2 Hz),
3.56 (d, 1 H, J ) 11.2 Hz), 2.20 (m, 1 H), 2.01 (br s, 1 H, D2O
exchanged), 1.76 (br s, 1 H, D2O exchanged), 1.38-1.48 (m, 3
H), 1.13 (s, 9 H), 0.63 (dd, 1 H, J ) 8.8, 6.6 Hz); FAB MS m/z
(relative intensity) 109 (29.6), 127 (19.5), 135 (95.4), 199 (100),
325 (12), 365 (28.1), 381 (5.0, MH+ - H2). Anal. Calcd for
(major isomer, CDCl3) δ 4.68 (q, 1 H, J ) 5.3 Hz), 4.36-4.42
(m, 1 H), 4.36 (d, 1 H, J ) 12.0 Hz), 4.18 (t, 1 H, J ) 8.1 Hz),
3.89 (d, 1 H, J ) 12.0 Hz), 3.27 (s, 3 H), 2.35 (td, 1 H, J )
13.4, 7.5 Hz), 2.07 (s, 3 H), 1.60 (td, 1 H, J ) 8.2, 4.2 Hz), 1.51
(br s, 1 H, D2O exchanged), 1.30 (d, 3 H, J ) 5.3 Hz), 1.23-
1.27 (m, 2 H), 0.63 (iregular t, 1 H, J ) 7.6, 6.1 Hz); FAB MS
m/ z (relative intensity) 59 (100), 109 (20.8), 137 (5.2), 169
(23.1), 219 (7.9), 227 (4.5, MH+ - H2O). Anal. Calcd for
C
12H20O5‚0.5H2O: C, 56.90; H, 8.36. Found: C, 56.92; H, 8.30.
(1R,2S,4R,5S)-(2-Acetoxy-4-h ydr oxybicyclo[3.1.0]h exyl)-
m eth yl Aceta te [(+)-10] a n d (1S,2R,4S,5R)-(2,4-Dih y-
dr oxybicyclo[3.1.0]h exyl)m eth yl Acetate [(-)-12]. A stirred
solution of compound (+)-8 (contaminated with 8′) (1.10 g, 2.37
mmol) in DMF-H2O (10:1, 16.5 mL) was treated with am-
monium hydrogen fluoride (1.35 g, 23.7 mmol) at room
temperature. The mixture was then kept at 50 °C for 17 h.
After allowing the solution to reach room temperature, the
insoluble materials were removed by filtration, and the filtrate
was concentrated under reduced pressure. The residue was
coevaporated with toluene three times and then purified by
silica gel column chromatography [50%f66% EtOAc in hex-
anes (system A), followed by 2%f4% MeOH in EtOAc (system
B)]. The fractions obtained from system A were concentrated
to give compound (+)-10 as a clear oil (430 mg, 79%), whereas
the fractions obtained from system B provided compound (-)-
12. All the spectral data for compound (+)-10 matched exactly
with the material obtained before.
C
23H30O3Si: C, 72.21; H, 7.90. Found: C, 71.96; H, 8.13.
[(1R,2S,4R,5S)-[2-Acetoxy-4-(2,2-dim eth yl-1,2-diph en yl-
1-sila p r op oxy)bicyclo[3.1.0]h exyl]m eth yl Aceta te [(+)-8]
a n d [(1S,2R,4S,5R)-[4-(2,2-Dim eth yl-1,1-d ip h en yl-1-sila -
p r op oxy)-2-h yd r oxybicyclo[3.1.0]h exyl]m eth yl Aceta te
[(-)-9]. To a suspension of diol (()-7 (6.10 g, 15.9 mmol) and
Lipase PS-C “Amano” I (6.10 g) in tert-butyl methyl ether (250
mL) was added vinyl acetate (14.65 mL, 159 mmol). The
mixture was stirred at room temperature for 64 h. The enzyme
was removed by filtration through a pad of Celite and the solid
cake was washed with EtOAc (200 mL) and CH2Cl2 (200 mL).
The combined filtrate was concentrated under reduced pres-
sure and the residue was purified by silica gel column
chromatography with EtOAc in hexanes (5%f10%f20%). The
less polar fractions were collected and concentrated to give
diacetate (+)-8 as a clear oil (4.26 g, >57%) which was
contaminated with an inseparable byproduct (vide infra). The
more polar fractions were combined and concentrated to give
(-)-12: oil; [R]25 ) -41.9° (c 1.99, CHCl3); IR (neat) 3357,
D
1736, 1710, 1245, 1021 cm-1 1H NMR (CDCl3) δ 4.41 (m, 1
;
H), 4.34 (td, 1 H, J ) 8.3, 4.0 Hz), 4.28 (d, 1 H, J ) 11.9 Hz),
4.03 (d, 1 H, J ) 12.0 Hz), 2.33 (td, 1 H, J ) 13.3, 7.6 Hz),
2.10 (s, 3 H), 2.04 (d, 1 H, J ) 4.8 Hz, D2O exchanged), 1.64
(td, 1 H, J ) 8.2, 4.1 Hz), 1.52 (d, 1 H, J ) 5.4 Hz, D2O
exchanged), 1.22 (irregular t, 1 H, J ) 5.9, 4.0 Hz), 1.19 (td, 1
H, J ) 13.3, 8.9 Hz), 0.61 (t, 1 H, J ) 6.8 Hz); FAB MS m/ z
(relative intensity) 59 (100), 109 (63.2), 117 (18.2), 169 (73.6,
MH+ - H2O), 187 (17.4, MH+). Anal. Calcd for C9H14O4‚
0.4H2O: C, 55.89; H, 7.71. Found: C, 55.88; H, 7.77.
monoacetate (-)-9 (2.83 g, 42%) as an oil: [R]25 ) -35.0° (c
D
1.09, CHCl3); IR (neat) 3445, 1736, 1714, 1056 cm-1; 1H NMR
(CDCl3) δ 7.61-7.68 (m, 4 H), 7.32-7.42 (m, 6 H), 4.29 (td,
1H, J ) 8.1, 4.5 Hz), 4.10-4.15 (m, 2 H), 3.88 (d, 1H, J ) 12.0
Hz), 2.07 (td, 1H, J ) 13.3, 7.6 Hz), 2.00 (s, 3H), 1.26-1.38
(m, 3 H), 1.01 (s, 9 H), 0.53 (dd, 1H, J ) 7.9, 5.4 Hz); FAB MS
m/ z (relative intensity) 135 (65.6), 169 (100), 199 (70.4), 347
Syn th esis of (+)-8 fr om Com p ou n d (+)-10. A stirred
solution of (+)-10 (60 mg, 0.262 mmol) and imidazole (32 mg,
0.472 mmol) in CH2Cl2 (2 mL) was treated with TBDPSCl (81
µL, 0.314 mmol) at room temperature for 2 h. Additional CH2-
Cl2 (20 mL) was added and the organic solution was extracted
with water (15 mL), dried (MgSO4), and filtered. The filtrate
was concentrated under reduced pressure and the residue was
purified by silica gel column chromatography (5%f10% EtOAc
(5.0), 365 (9.6), 367 (4.8), 407 (8.9, M+-H2O), 423 (3.4, MH+
-
H2), 425 (0.7, MH+). Anal. Calcd for C25H32O4Si: C, 70.72; H,
7.60. Found: C, 70.43; H, 7.62.
(1R,2S,4R,5S)-(2-Acetoxy-4-h ydr oxybicyclo[3.1.0]h exyl)-
m eth yl Aceta te [(+)-10] a n d (1S,2R,4S,5R)-[4-Hyd r oxy-
2-(m eth oxyeth oxy)bicyclo[3.1.0]h exyl]m eth yl Acetate (11).
Compound (+)-8 (contaminated with 8′) (263 mg, 0.563 mmol)
was added to a stirred solution of ammonium fluoride in MeOH
(0.5 M, 11.26 mL) at room temperature. The temperature of
the bath was raised to 60 °C and stirring was continued
overnight. After cooling to room temperature, silica gel (ca 2
g) was added and the solvent was removed under reduced
pressure. The solid with the adsorbed compound was placed
in hexanes) to give (+)-8 (113 mg, 92%) as a clear oil: [R]25
)
D
1
+44.9° (c 0.82, CHCl3); IR (neat) 1738, 1241, 1021 cm-1; H
NMR (CDCl3) δ 7.62-7.71 (m, 4 H), 7.36-7.46 (m, 6 H), 5.09
(t, 1 H, J ) 8.3 Hz), 4.39 (td, 1 H, J ) 8.0, 4.6 Hz), 4.14 (d, 1
H, J ) 11.9 Hz), 3.78 (d, 1H, J ) 12.0 Hz), 2.33 (td, 1 H, J )
13.5, 7.8 Hz), 2.04, 1.98 (s, each 3 H), 1.41 (td, 1 H, J ) 8.3,
4.2 Hz), 1.29-1.37 (m, 2 H), 1.04 (s, 9 H), 0.67 (dd, 1H, J )
7.6, 5.9 Hz); FAB MS m/ z (relative intensity) 91 (61.5), 135
5944 J . Org. Chem., Vol. 67, No. 17, 2002