Reaction Forming the Tricyclo[4.3.1.03,7] System
J . Org. Chem., Vol. 67, No. 9, 2002 2883
Kanto Chemical Co., Inc. Toluene, ClCH2CH2Cl, and NEt3
were distilled from CaH2. HMDS and DMSO were distilled
from CaH2 under reduced pressure. Unless otherwise de-
scribed, the materials were obtained from commercial suppli-
ers and used without further purification. Organic extracts
were dried over MgSO4, filtered, and concentrated under
reduced pressure using an evaporator. The 1H and 13C NMR
spectra were recorded at 300 and 75 MHz, respectively, and
were reported in ppm downfield from TMS (δ 0) for the 1H
NMR and relative to the central CDCl3 resonance (δ 77.00)
for the 13C NMR.
CN (30 mL) was added a solution of the above silyl enol ether
in CH3CN (10 mL) at ambient temperature and the stirring
continued for 4.5 h. After dilution with Et2O, the reaction
mixture was filtered through Celite. Evaporation of the filtrate
gave a residue, which was purified by column chromatography
on silica gel (29:78:3 v/v/v AcOEt/hexane/NEt3) to give 3 (1.35
g, 91% for two steps) as a colorless oil: 1H NMR (CDCl3) δ
6.98 (1H, dt, J ) 15.7, 6.9 Hz), 6.83 (1H, ddd, J ) 10.2, 2.7,
1.4 Hz), 6.01 (1H, dd, J ) 10.2, 2.5 Hz), 5.88 (1H, dt, J ) 15.7,
1.6 Hz), 3.74 (3H, s), 2.57-2.28 (5H, m), 2.19-2.08 (1H, m),
1.79-1.53 (3H, m); 13C NMR (CDCl3) δ 199.3, 166.6, 153.8,
147.9, 129.1, 121.5, 51.1, 36.4, 35.0, 32.4, 29.0, 28.0; LRMS
m/z 208 (M+). Anal. Calcd for C12H16O3: C, 69.21; H, 7.74.
Found: C, 69.08; H, 7.76.
8-[(3E a n d 3Z)-4-(Met h oxyca r b on yl)-3-b u t en yl]-1,4-
d ioxa sp ir o[4.5]d eca n e (6). To a solution of alcohol 58 (614
mg, 3.06 mmol) in DMSO (20 mL) was added NEt3 (4.27 mL,
30.6 mmol), and the mixture was stirred at ambient temper-
ature for 15 min. To the resulting mixture was added SO3-
pyridine complex (1.46 g, 9.19 mmol), and the mixture was
stirred for 1.5 h at the same temperature. The mixture was
diluted with saturated NaHCO3, extracted with Et2O, and
washed with brine. The removal of the solvent afforded the
corresponding crude aldehyde, which was used in the next
reaction without further purification. To a solution of the above
aldehyde in CH3CN (20 mL) was added methyl (triphenylphos-
phoranylidene)acetate (2.05 g, 6.13 mmol), and the mixture
was stirred for 23 h at ambient temperature. After the
concentration of the mixture, the resulting residue was puri-
fied by column chromatography on silica gel (1:4 v/v AcOEt/
hexane) to give a 13:1 mixture of (E)- and (Z)-6 (782 mg, >99%
for two steps) as a colorless oil: 1H NMR (CDCl3) δ 6.97 (0.93H,
dt, J ) 15.7, 6.9 Hz), 6.23 (0.07H, dt, J ) 11.5, 7.7 Hz), 5.82
(0.93H, dt, J ) 15.7, 1.4 Hz), 5.76 (0.07H, dt, J ) 11.5, 1.6
Hz), 3.94 (4H, s), 3.73 (2.79H, s), 3.71 (0.21H, s), 2.67 (0.14H,
tt, J ) 7.7, 1.6 Hz), 2.22 (1.86H, tt, J ) 6.9, 1.4 Hz), 1.79-
(1R*,2R*,5S*)- an d (1R*,2S*,5S*)-2-((Meth oxycar bon yl)-
m eth yl)bicyclo[3.3.1]n on -6-en -8-on e (8). Ru n 1 in Ta ble
1. To a solution of HMDS (55 mL, 0.26 mmol) in Et2O (1.5
mL) at 0 °C was added BuLi (1.52 M in hexane, 128 mL. 0.20
mmol). The solution was stirred at 0 °C for 2 h and then cooled
to -78 °C. To this was added a solution of 3 (27.1 mg, 0.13
mmol) in Et2O (1.5 mL) dropwise at -78 °C. The resulting
mixture was stirred for 2 h at -78 °C and for a further 2 h at
ambient temperature. After dilution with Et2O, the mixture
was washed with 10% HCl and brine. The organic layer was
dried and concentrated. Column chromatography on silica gel
(3:7 v/v AcOEt/hexane) afforded 8 (5.0 mg, 18%) as a colorless
oil (1.4:1 diastereomeric mixture): 1H NMR (CDCl3) δ 6.99-
6.91 (1H, m), 6.17 (1H, d, J ) 9.9 Hz), 3.68 (1.75 H, s), 3.67
(1.25 H, s), 2.68-1.17 (11H, m); IR (neat) 1730, 1665 cm-1
;
LRMS m/z 208 (M+); HRMS calcd for C12H16O3 (M+) 208.1100,
found 208.1105.
Ru n 2 in Ta ble 1. To a solution of 3 (31 mg, 0.15 mmol)
and NEt3 (0.20 mL, 1.5 mmol) in ClCH2CH2Cl (3 mL) was
added dropwise TBDMSOTf (57 mL, 0.40 mmol) at 0 °C.
Stirring of the mixture for 1 h at the same temperature,
followed by a workup and purification procedure similar to that
above, yielded a 1.4:1 diastereomeric mixture of 8 (2.0 mg, 7%)
as a colorless oil, which was identical with the above product
in all respects.
1.66 (4H, m), 1.58-1.15 (7H, m); IR (neat) 1715, 1659 cm-1
;
LRMS m/z 254 (M+). Anal. Calcd for C14H22O4: C, 66.12; H,
8.72. Found: C, 66.10; H, 8.79.
4-[(3E)-4-(Met h oxyca r b on yl)-3-b u t en yl]-1-cycloh exa -
n on e ((E)-7). To a solution of 6 (164 mg, 0.645 mmol) in THF
(2.2 mL) was added a 10% aqueous solution of HClO4 (4.4 mL)
at ambient temperature, and the resulting mixture was stirred
for 15 h at the same temperature. After dilution with Et2O,
the mixture was neutralized with NaHCO3 and then extracted
with Et2O. The organic layer was washed with brine. The
organic layer was dried and concentrated. Column chroma-
tography on silica gel (1:4 v/v AcOEt/hexane) afforded (E)-7
(121 mg, 89%) as a colorless oil and the Z isomer (8.7 mg, 6%)
as a colorless oil. (E)-7: 1H NMR (CDCl3) δ 6.98 (1H, dt, J )
15.7, 6.9 Hz), 5.86 (1H, dt, J ) 15.7, 1.6 Hz), 3.74 (3H, s), 2.44-
2.23 (6H, m), 2.11-2.00 (2H, m), 1.83-1.67 (1H, m), 1.54-
1.33 (4H, m); 13C NMR (CDCl3) δ 211.8, 166.9, 148.9, 121.1,
51.2, 40.4, 35.1, 33.5, 32.2, 29.5; IR 1710, 1650 cm-1; LRMS
m/z 210 (M+). Anal. Calcd for C12H18O3: C, 68.55; H, 8.63.
Found: C, 68.65; H, 8.85.
(1R*,2S*,3R*,6R*,7S*)-2-(Met h oxyca r b on yl)t r icyclo-
[4.3.1.03,7]d eca n -9-on e (9). Ru n 4 in Ta ble 1. A mixture of
3 (30 mg, 0.15 mmol), ZnBr2 (0.33 g, 1.5 mmol), NEt3 (1.49
mL, 11 mmol), and TMSCl (0.90 mL, 7.1 mmol) in toluene (3
mL) was heated for 20 h at 180 °C in a sealed tube. After
dilution with AcOEt, the mixture was washed with 10% HCl
and brine. The organic layer was dried and concentrated.
Column chromatography on silica gel (3:7 v/v AcOEt/hexane)
afforded 9 (18.8 mg, 62%) as a colorless oil: 1H NMR (CDCl3)
δ 3.67 (3H, s), 2.58-2.47 (3H, m), 2.44-2.33 (2H, m), 2.25-
1.92 (5H, m), 1.72-1.44 (3H, m); 13C NMR (CDCl3) δ 213.7,
174.9, 51.9, 51.5, 43.5, 39.1, 37.8, 36.2, 33.9, 33.0, 32.6; IR
(neat) 1730, 1695 cm-1; LRMS m/z 208 (M+); HRMS calcd for
C
12H16O3 (M+) 208.1100, found 208.1138.
(1R*,2S*,3R*,6R*,7S*)-9-Oxotr icyclo[4.3.1.03,7]d eca n e-
4-[(3Z)-4-(Met h oxyca r b on yl)-3-b u t en yl]-1-cycloh exa -
1
2-ca r boxylic Acid (10). To a solution of 9 (157 mg, 0.75 mmol)
in MeOH (4 mL) was added 63% aqueous KOH at ambient
temperature. After it was left for 2 min, the mixture was
concentrated to remove MeOH and then diluted with H2O. The
aqueous layer was washed with Et2O and acidified with 10%
HCl. After extraction with CHCl3, the extract was dried and
concentrated. The residue was purified by recrystallization
n on e ((Z)-7): H NMR (CDCl3) δ 6.25 (1H, dt, J ) 11.5, 7.4
Hz), 5.81 (1H, dt, J ) 11.5, 1.6 Hz), 3.72 (3H, s), 2.74 (2H, tt,
J ) 7.4, 1.6 Hz), 2.44-2.25 (4H, m), 2.16-2.04 (2H, m), 1.84-
1.68 (1H, m), 1.52-1.34 (4H, m); 13C NMR (CDCl3) δ 212.0,
166.6, 150.1, 119.4, 50.7, 40.4, 35.4, 34.3, 32.2, 26.4; LRMS
m/z 210 (M+); HRMS calcd for C12H18O3 (M+) 210.1256, found
210.1239.
i
from Pr2O to give 10 (147 mg, >99%) as colorless prisms: mp
4-[(3E)-4-(Meth oxyca r bon yl)-3-bu ten yl]-2-cycloh exen -
1-on e (3). To a solution of (E)-7 (1.49 g, 7.10 mmol) and NEt3
(4.95 mL, 35.5 mmol) in CH2Cl2 (35 mL) was added TMSOTf
(3.85 mL, 21.3 mmol) at -78 °C, and the mixture was stirred
for 3 h. After dilution with saturated NaHCO3, the mixture
was extracted with Et2O. The organic layer was dried and
concentrated to give the corresponding crude silyl enol ether,
which was used in the next reaction without further purifica-
tion. To a suspension of Pd(OAc)2 (1.91 g, 8.52 mmol) in CH3-
123-124 °C; 1H NMR (CDCl3) δ 8.72 (1H, br s), 2.59-1.91
(10H, m), 1.68-1.42 (3H, m); 13C NMR (CDCl3) δ 214.6, 179.8,
51.4, 43.2, 39.2, 38.0, 36.2, 34.0, 33.0, 32.9, 32.7; IR (CHCl3)
1715, 1705 cm-1; LRMS m/z 194 (M+). Anal. Calcd for
C
11H14O3: C, 68.02; H, 7.26. Found: C, 68.05; H, 7.19.
X-r a y Cr ysta llogr a p h y. Crystallographic data were col-
lected at 20.0 °C on a Rigaku AFC5R diffractometer with
graphite-monochromated Mo KR (λ ) 0.71 Å) radiation and a
rotating anode generator. The structure was solved using the
programs in teXsan. Prismatic crystals of 10 (0.20 × 0.20 ×
0.30 mm) suitable for X-ray crystallography were grown by
slow crystallization from i-Pr2O. The compound 10 belongs to
the monoclinic space group P21/c with a ) 12.023(2) Å, b )
(13) (a) J ohannes, R. E. Veliger 1963, 5, 104-105. (b) Burreson, B.
J .; Scheuer, P. J .; Finer, J .; Clardy, J . J . Am. Chem. Soc. 1975, 97,
4763-4764. (c) Hagadone, M. R.; Burreson, B. J .; Scheuer, P. J .; Finer,
J . S.; Clardy, J . Helv. Chim. Acta 1979, 62, 2484-2494.