Stereocontrolled Synthesis of Tricyclo[m.n.0.0]alkenones
J . Org. Chem., Vol. 64, No. 20, 1999 7417
3-[(Tetr a h yd r o-2H-p yr a n -2-yl)oxy]-1-bu ta n ol 4-Meth -
ylben zen esu lfon a te (33).17 A stirred solution of 1,3-butane-
diol (6.92 g, 76.8 mmol) in pyridine (16.5 mL) was cooled to 0
°C, and p-toluenesulfonyl chloride (7.33 g, 38.4 mmol) was
added in one portion. After 2 d at 0 °C, the reaction mixture
was poured into water (50 mL) and extracted with ether (4 ×
100 mL). The extracts were combined, washed with 10%
aqueous HCl, saturated NaHCO3, and brine, dried (MgSO4),
and filtered, and volatiles were removed to give an oil (8.32
g). This oil was dissolved in CH2Cl2 (75 mL), and dihydropyran
(3.23 g, 38.4 mmol) and pyridinium p-toluenesulfonate (200
mg) were added. After 24 h, the reaction mixture was washed
with saturated NaHCO3, dried (MgSO4), and filtered, and
volatiles were removed to give an oil. This oil was subjected
to flash column chromatography on 230-400 mesh silica gel
(400 mL) eluted with 10 f 20% EtOAc/hexanes to give 8.84 g
(25.7 mmol, 67%) of 33 as a clear, colorless oil, Rf 0.41 (40%
EtOAc/hexanes).
(1S*,3R*,7R*)-3-Meth yl-3-[3-[(tetr a h yd r o-2H-p yr a n yl)-
oxy]bu tyl]bicyclo[5.1.0]octa n -2-on e (34). A solution of 25
(100 mg, 0.72 mmol), 33 (300 mg, 0.87 mmol), and NaH (70
mg, 2.88 mmol) in THF (10 mL) was heated at reflux for 12 h.
The reaction mixture was cooled to room temperature, water
(25 mL) was cautiously added, and the mixture was extracted
with CH2Cl2 (4 × 30 mL). The organic extracts were combined,
dried (MgSO4), and filtered, and volatiles were removed under
vacuum to give a yellow oil. This oil was subjected to flash
column chromatography on 230-400 mesh silica gel (200 mL)
eluted with 6% EtOAc/hexanes to give 73 mg (0.25 mmol, 35%)
of 34 as a clear, colorless oil, Rf 0.61 (40% EtOAc/hexanes).
(1S*,3R*,5R*)-3-Met h yl-3-(2-oxop r op yl)b icyclo[3.1.0]-
h exa n -2-on e (35). To a biphasic solution of 17 (133 mg, 0.81
mmol) and NaIO4 (728 mg, 3.40 mmol) in a 2:2:3 mixture of
CH3CN/CCl4/H2O (7 mL) was added 10-15 mg of RuCl3. The
reaction mixture was stirred for 15 min in a water bath at
room temperature. Water (10 mL) and CH2Cl2 (10 mL) were
then added, and the layers were separated. The water layer
was extracted with CH2Cl2 (4 × 15 mL), the organic phases
were combined, dried (MgSO4), and filtered, and volatiles were
removed under vacuum to give a brown oil. This oil was
subjected to flash column chromatography on 230-400 mesh
silica gel (100 mL) eluted with 30% EtOAc/hexanes to give 88
mg (0.53 mmol, 66%) of 35 as a clear, colorless oil, Rf 0.34 (40%
EtOAc/hexanes).
(1S*,3S*,5R*)-3-Met h yl-3-(2-oxop r op yl)b icyclo[3.1.0]-
h exa n -2-on e (36). By a similar method, 189 mg (1.15 mmol)
of 19 gave 172 mg (1.04 mmol, 90%) of 36 as a clear, colorless
oil, Rf 0.34 (40% EtOAc/hexanes).
(1S*,3R*,5R*)-3-Met h yl-3-(3-oxob u t yl)b icyclo[3.1.0]-
h ep ta n -2-on e (37). By a similar method, 168 mg (0.94 mmol)
of 18 gave 149 mg (0.83 mmol, 88%) of 37 as a clear, colorless
oil, Rf 0.29 (40% EtOAc/hexanes).
(1S*,3R*,6R*)-3-Met h yl-3-(2-oxop r op yl)b icyclo[4.1.0]-
h ep ta n -2-on e (38). By a similar method, 400 mg (2.24 mmol)
of 20 gave 357 mg (1.98 mmol, 88%) of 38 as a clear, colorless
oil, Rf 0.36 (40% EtOAc/hexanes).
(1S*,3S*,6R*)-3-Met h yl-3-(2-oxop r op yl)b icyclo[4.1.0]-
h ep ta n -2-on e (39). By a similar method, 300 mg (1.68 mmol)
of 22 gave 270 mg (1.50 mmol, 89%) of 39 as a clear, colorless
oil, Rf 0.35 (40% EtOAc/hexanes).
(1S*,3R*,6R*)-3-Met h yl-3-(3-oxob u t yl)b icyclo[4.1.0]-
h ep ta n -2-on e (40). By a similar method, 320 mg (1.66 mmol)
of 21 gave 297 mg (1.53 mmol, 92%) of 40 as a clear, colorless
oil, Rf 0.31 (40% EtOAc/hexanes).
(1S*,3S*,6R*)-3-Met h yl-3-(3-oxob u t yl)b icyclo[4.1.0]-
h ep ta n -2-on e (41). By a similar method, 381 mg (1.98 mmol)
of 23 gave 356 mg (1.83 mmol, 93%) of 41 as a clear, colorless
oil, Rf 0.35 (40% EtOAc/hexanes).
of 24 gave 82 mg (0.42 mmol, 75%) of 42 as a clear, colorless
oil, Rf 0.46 (40% EtOAc/hexanes).
(1S*,3S*,7R*)-3-Met h yl-1-(2-oxop r op yl)b icyclo[5.1.0]-
octa n -2-on e (43). By a similar method, 220 mg (1.14 mmol)
of 27 gave 133 mg (0.68 mmol, 60%) of 43 as a clear, colorless
oil, Rf 0.36 (40% EtOAc/hexanes).
(1S*,3R*,7R*)-3-Met h yl-3-(3-oxob u t yl)b icyclo[5.1.0]-
octa n -2-on e (44). THP ether 34 (153 mg, 0.52 mmol) was
taken up in 5% aqueous methanol (20 mL), and a catalytic
amount of p-toluenesulfonic acid was added. After 4 h,
saturated aqueous NaHCO3 (20 mL) and H2O (10 mL) were
added. The mixture was extracted with CH2Cl2 (5 × 40 mL),
the extracts were combined, dried (MgSO4), and filtered, and
volatiles were removed under vacuum to leave an oil. This oil
was dissolved in CH2Cl2 (20 mL), and PDC (255 mg, 0.67
mmol) was added. After being stirred for 8 h, additional PDC
(255 mg, 0.67 mmol) was added and stirring was continued
overnight. The reaction mixture was then filtered through
Celite, and volatiles were removed under vacuum. The residual
oil was subjected to chromatography on 230-400 mesh silica
gel (50 mL) eluted with 15% EtOAc/hexanes to give 76 mg
(0.36 mmol, 70%) of 44 as a clear, colorless oil, Rf 0.50 (40%
EtOAc/hexanes).
(2S*,3R*,6R*)-5-Meth yl-∆1,8-tr icyclo[3.3.0.02,3]n on en -7-
on e (2). Metallic sodium (approximately 20 mg) was added to
dry t-BuOH (20 mL). Diketone 35 (88 mg, 0.52 mmol) was
taken up in a 3 mL aliquot of this solution. After 10 min, the
reaction mixture was poured into water (10 mL), and the
mixture was extracted with hexanes (5 × 15 mL). The organic
extracts were combined, dried (MgSO4), and filtered, and
volatiles were removed under vacuum to afford 69 mg (0.46
mmol, 88%) of 2 as a pale yellow oil that was homogeneous by
TLC, Rf 0.42 (40% EtOAc/hexanes), and was not further
purified.
(2S*,3R*,6S*)-5-Meth yl-∆1,8-tr icyclo[3.3.0.02,3]n on en -7-
on e (3). Metallic sodium (approximately 10 mg) was added to
dry t-BuOH (10 mL). Diketone 36 (159 mg, 0.95 mmol) was
then taken up in a 5 mL aliquot of this solution. The reaction
mixture was stirred for 8 h at room temperature, during which
time aliquots of the t-BuONa/t-BuOH solution (3 × 1 mL) were
added. The reaction mixture was then poured into water (20
mL), and the mixture was extracted with hexanes (5 × 20 mL).
The organic extracts were combined, dried (MgSO4), and
filtered, and volatiles were removed under vacuum. The
residual yellow oil was subjected to chromatography on 230-
400 mesh silica gel (150 mL) eluted with 20% EtOAc/hexanes
to give 115 mg (0.78 mmol, 81%) of 3 as a clear, colorless oil,
Rf 0.47 (40% EtOAc/hexanes).
(6S*,8R*,9S*)-6-Meth yl-∆1,2-tr icyclo[4.3.0.08,9]d ecen -3-
on e (4). By a method similar to that described for the
preparation of 3, 131 mg (0.73 mmol) of diketone 37 gave 112
mg (0.69 mmol, 95%) of 4 as a clear, colorless oil, Rf 0.29 (40%
EtOAc/hexanes).
(2S*,3R*,6R*)-6-Meth yl-∆1,9-tr icyclo[4.3.0.02,3]d ecen -8-
on e (5). A solution of diketone 38 (133 mg, 0.74 mmol) and
KOH (12 pellets) in absolute EtOH (10 mL) was heated for 1
h at reflux under argon. The reaction mixture was cooled to
room temperature, H2O (50 mL) was added, and the mixture
was extracted with hexanes (8 × 50 mL). The organic extracts
were combined, dried (MgSO4), and filtered, and volatiles were
removed under vacuum. The residual yellow oil was subjected
to chromatography on 230-400 mesh silica gel (200 mL) eluted
with 20% EtOAc/hexanes to give 92 mg (0.56 mmol, 77%) of 5
as a clear, colorless oil, Rf 0.30 (40% EtOAc/hexanes).
(2S*,3R*,6S*)-6-Meth yl-∆1,9-tr icyclo[4.3.0.02,3]d ecen e-8-
on e (6). By a method similar to that described for the
preparation of 5, 270 mg (1.50 mmol) of diketone 39 gave 204
mg (1.26 mmol, 84%) of 6 as a colorless solid, mp 45-48 °C,
Rf 0.38 (40% EtOAc/hexanes).
(1S*,3S*,7R*)-3-Met h yl-3-(2-oxop r op yl)b icyclo[5.1.0]-
octa n -2-on e (42). By a similar method, 107 mg (0.56 mmol)
(2S*,3R*,6R*)-6-Meth yl-∆1,10-tr icyclo[4.4.0.02,3]u n d ecen -
9-on e (7). By a method similar to that described for the
preparation of 5, 280 mg (1.44 mmol) of diketone 40 gave 209
mg (1.19 mmol, 83%) of 7 as a clear, colorless oil, Rf 0.43 (40%
EtOAc/hexanes).
(17) While racemic 33 is apparently unknown, the 3R and 3S
enantiomers have been described; see: (a) Mori, K.; Watanabe, H.
Tetrahedron 1984, 40, 299-303. (b) Mori, K.; Tanida, K. Tetrahedron
1981, 37, 3221-3225. (c) Mori, K. Tetrahedron 1981, 37, 1341-1342.