5778 J . Org. Chem., Vol. 65, No. 18, 2000
Ho et al.
The organic layer was separated and evaporated, and the
residue extracted with ether, dried, and evaporated to afford,
after chromatrography over silica (eluent: EtOAc/hexane 2.5:
97.5), methyl ketone 12c (1.24 g, 54%) as a colorless oil. IR
5-Isopr opyl-2-exo,7-exo-dim eth yltr icyclo[5.2.1.04,8]decan -
3-ol (17a ). To a stirred suspension of lithium aluminum
hydride (55.0 mg, 1.45 mmol) in THF (2 mL) was added a
solution of ketone 16 (0.16 g, 0.73 mmol) in THF (3 mL). After
stirring at room temperature for 15 min, the mixture was
refluxed overnight, cooled, and quenched with aqueous NH4-
Cl. Further treatment with 2 N HCl, filtration, drying over
MgSO4, and concentration in vacuo afforded the alcohol 17a
(neat) νmax 1668 cm-1 1H NMR δ 0.93 (3H, s), 0.96 (3H, s),
;
1.13 (1H, d, J ) 13.8 Hz), 1.53 (3H, s), 1.58-1.65 (2H, m),
1.67 (3H. s), 1.74 (1H, br s), 1.98 (3H, d, J ) 6.9 Hz), 2.11 (1H,
br s), 2.19 (3H, s), 2.38 (1H, d, J ) 6.3 Hz), 5.08 (1H, t, J ) 3.8
Hz), 6.91 (1H, d, J ) 6.9 Hz); 13C NMR δ 17.9 (q), 19.5 (q),
25.8 (q), 25.9 (q), 27.5 (q), 28.2 (t), 38.3 (t), 38.9 (d), 40.0 (d),
44.9 (d), 45.4 (t), 50.7 (s), 122.1 (d), 132.5 (s), 142.1 (s), 146.5
(d), 199.3 (s); HRMS 246.1981 (246.1985 calcd for C17H26O).
3-exo-6,6,8,13-exo-P e n t a m e n t h y l-7-o x a t e t r a c y c lo -
[7.3.1.03,11.05,10]tr id ec-8-en e (13). A solution of ketone 12c
(0.36 g, 1.46 mmol) in toluene (1 mL) was heated in a sealed
tube for 2 days at 225 °C. Evaporation of the solution gave
the cycloadduct, which was purified by chromatography over
silica (eluent EtOAC/hexane 2.5:97.5) to afford 13 (0.31 g, 86%)
as an oil. IR (neat) νmax 1652 cm-1; 1H NMR δ 0.97 (3H, d, J )
7.2 Hz), 0.98 (3H, s), 1.13 (3H, s), 1.16 (3H, s), 1.28-1.38 (1H,
m), 1.45-1.57 (3H, m), 1.67 (3H, s), 1.71-2.03 (5H, m), 2.25-
2.34 (2H, m); 13C NMR δ 16.8 (q), 18.1 (q), 26.5 (t), 27.4 (q),
28.6 (q), 30.2 (q), 37.8 (d), 38.0 (d), 42.1 (t), 42.5 (d), 45.0 (s),
48.1 (d), 49.7 (t), 54.2 (d), 73.5 (s), 103.9 (s), 143.7 (s); HRMS
246.1981 (246.1985 calcd for C17H26O).
(0.13 g, 82%) as a colorless oil. IR (neat) νmax 3479 (br) cm-1
;
1H NMR δ 0.81 (3H, d, J ) 6.5 Hz), 0.98 (3H, d, J ) 6.5 Hz),
1.03 (3H, d, J ) 6.4 Hz), 1.05 (3H, s), 1.23 (1H, d, J ) 5.0 Hz),
1.27 (1H, d, J ) 5.0 Hz), 1.43-1.56 (4H, m), 1.67 (1H, d, J )
12.0 Hz), 1.79-2.05 (4H, m), 2.58 (1H, q, J ) 12.0, 7.5 Hz),
3.51 (1H, dd, J ) 10.3, 8.0 Hz); 13C NMR δ 22.1 (q), 23.3 (q),
23.5 (q), 27.9 (t), 30.5 (d), 30.6 (q), 42.7 (d), 43.4 (d), 45.7 (d),
46.1 (s), 47.3 (t), 50.9 (t), 53.1 (d), 53.8 (d), 76.8 (d); HRMS
222.1989 (222.1985 calcd for C15H26O).
5-Isop r op yl-2-exo,7-exo-d im eth yltr icyclo[5.2.1.04,8]d ec-
3-yl Ben zoa te (17b). Pyridine (0.11 mL, 1.35 mmol) was
added to an ice-cooled stirred mixture of alcohol 17a (0.1 g,
0.45 mmol) and benzoyl chloride (0.1 mL, 0.68 mmol) in CH2-
Cl2 (3 mL) under nitrogen. After stirring for 10 min at 0 °C,
the resulting solution was warmed to room temperature, kept
overnight, and extracted with ether. The organic solution was
washed with water, dried, evaporated, and chromatographed
over silica gel (eluent: hexane/EtOAc 97.5:2.5) to afford
1-(2-exo,7-exo-d im et h yl-3-oxot r icyclo[5.2.1.04,8]d ec-5-
yl)-1-m eth yleth yl Aceta te (14). A solution of vinyl ether 13
(0.9 g, 3.66 mmol) in CH2Cl2 (120 mL) was treated with excess
ozone at -78 °C. After nitrogen purge, Me2S was added, and
allowed to warm to room temperature over 12 h. Evaporation
of the solvent followed by extraction of the residue with ether
and concentration of the dried extracts afforded the keto
acetate 14, which was purified by chromatography over silica
(eluent: EtOAc/hexane 5:95) to give a colorless oil (0.91 g,
benzoate 17b (0.17 g, 96%) as an oil. IR (neat) νmax 1699 cm-1
;
1H NMR δ 0.59 (3H, d, J ) 6.3 Hz), 0.76 (3H, d, J ) 6.5 Hz),
0.87 (3H, d, J ) 6.7 Hz), 1.09 (3H, s), 1.15-1.24 (1H, m), 1.29-
1.37 (2H, m), 1.53-1.63 (3H, m), 1.75-1.99 (3H, m), 2.04 (2H,
t, J ) 6.5 Hz), 2.78-2.85 (1H, m), 5.08 (1H, dd, J ) 11.1, 7.9
Hz), 7.38-7.44 (2H, m), 7.50-7.55 (1H, m), 8.02 (2H, d, J )
5.0 Hz); 13C NMR δ 21.4 (q), 22.6 (q), 23.3 (q), 28.1 (t), 20.9
(d), 30.5 (q), 39.6 (d), 43.3 (d), 43.7 (d), 46.2 (t), 47.5 (s), 50.9
(t), 53.2 (d), 53.3 (d), 78.3 (d), 128.3 (d), 129.5 (d), 130.7 (s),
132.6 (d), 166.8 (s); HRMS 326.2255 (326.2247 calcd for
1
89%). IR (neat) νmax 1737, 1697 cm-1; H NMR δ 1.03 (3H, d,
J ) 7.1 Hz), 1.19 (3H, s), 1.42 (3H, s), 1.62 (3H, s), 1.79 (3H,
s), 1.83-2.19 (9H, m), 2.32 (1H, q, J ) 14.2, 7.1 Hz), 2.95 (1H,
t, J ) 6.4 Hz); 13C NMR δ 16.9 (q), 21.7 (q), 24.3 (q), 25.4 (q),
30.5 (q), 31.2 (t), 42.8 (t), 43.6 (d), 46.3 (s), 50.4 (d), 52.2 (t),
53.7 (d), 55.2 (d), 59.0 (d), 81.2 (s), 169.8 (s), 215.5 (s); HRMS
278.1884 (278.1883 calcd for C17H26O3).
C
22H30O2).
5-Isop r op yl-2-exo,7-exo-d im eth yltr icyclo[5.2.1.04,8]d ec-
2-en e (18). A solution of keto benzoate 17b (0.1 g, 0.31 mmol)
in toluene (2 mL) was added dropwise by means of an addition
funnel into a vertically mounted Pyrex column (350 by 14 mm)
containing loosely packed glass wool and maintained at 410
°C, while a slow stream of nitrogen was passed through the
column. The pyrolysate was collected at the bottom in a flask
charged with aqueous NaHCO3 and ether and immersed in
ice/water. After the pyrolysis the column was rinsed two more
times with toluene then the combined solution was extracted
with ether. Solvent removal gave the alkene 18 (69.0 mg, 97%)
5-Isop r op en yl-2-exo, 7-exo-d im eth yltr icyclo[5.2.1.04,8]-
d eca n -3-on e (15). A solution of the keto acetate 14 (0.22 g,
0.79 mmol) in toluene (5 mL) was added dropwise by means
of an additional funnel into a vertically mounted Pyrex column
(350 × 14 mm) placed in a tubular furnace at 410 °C, while a
slow stream of nitrogen was passed through the column. The
pyrolysate was collected at the bottom in a flask charged with
aqueous NaHCO3 and ether and immersed in ice/water. At the
end of the pyrolysis the column was rinsed two more times
with toluene, and the combined solution was diluted with
ether, separated into layers, and dried over MgSO4. Solvent
removal gave the oily 15 (0.17 g, 99%). IR (neat) νmax 1698
1
as an oil. H NMR δ 0.78 (3H, d, J ) 6.2 Hz), 0.92 (3H, d, J )
6.2 Hz), 1.05 (3H, s), 1.39-1.47 (4H, m), 1.49-1.52 (2H, m),
1.57 (2H, m), 1.65 (3H, s), 1.89 (1H, br s), 2.09 (1H, br s), 2.64
(1H, br s), 5.01 (1H, br s); 13C NMR δ 22.1 (q), 22.2 (q), 23.1
(q), 29.7 (d), 30.5 (q), 33.6 (t), 41.8 (d), 45.7 (d), 46.4 (s), 47.4
(t), 52.1 (t), 53.2 (d), 53.2 (d), 117.4 (d), 143.6 (s); HRMS
204.1881 (204.1879 calcd for C15H25).
1
cm-1; H NMR δ 1.06 (3H, d, J ) 7.3 Hz), 1.18 (3H, s), 1.28-
1.31 (2H, m), 1.42-1.75 (4H, m), 1.85 (3H, s), 2.02 (1H, q, J )
7.3 Hz), 2.09 (1H, br s), 2.19 (1H, br s), 2.54-2.64 (1H, m),
2.91 (1H, t, J ) 6.2 Hz), 4.51 (1H, s), 4.75 (1H, s); 13C NMR δ
18.4 (q), 23.2 (q), 30.3 (q), 30.9 (t), 42.8 (d), 45.3 (t), 46.0 (s),
49.9 (d), 51.2 (d), 51.5 (t), 52.9 (d), 60.7 (d), 109.6 (t), 145.5 (s),
215.9 (s); HRMS 218.1663 (218.1671 calcd for C15H22O).
N-(5-Isop r op yl-2-exo,7-exo-d im eth yltr icyclo[5.2.1.04,8]-
d ec-2-yl)for m a m id e (19). A solution of alkene 18 (60.0 mg,
0.29 mmol) in acetic acid (2 mL) at 0 °C under N2 was treated,
in sequence, with NaCN (0.12 g, 2.35 mmol) and concentrated
sulfuric acid (0.13 mL, 2.35 mmol). After 5 min, the cold bath
was removed and the reaction was continued at ambient
temperature for 24 h. After several drops of H2O were
introduced to the mixture, the reaction mixture was poured
slowly into a stirred mixture of ice and Na2CO3. Addition of
10% NaOH was followed by extraction with ether. Drying the
extracts over MgSO4 and evaporation furnished a pale yellow
viscous oil which was chromatographed over silica gel using
hexane/EtOAc (70:30) as eluent to give the formamide 19 (50.0
mg, 70%). IR (neat) νmax 3283, 1662 cm-1; 1H NMR δ 0.77 (3H,
d, J ) 6.4 Hz), 0.81 (3H, d, J ) 6.2 Hz), 1.03 (3H, s), 1.22 (3H,
s), 1.29 (1H, br s), 1.45-1.54 (6H, m), 1.74-1.85 (3H, m), 2.01
(3H, m), 6.11 (1H, br s), 8.19 (1H, d, J ) 12.4 Hz); 13C NMR δ
21.9 (q), 22.0 (q), 27.8 (d), 28.2 (q), 29.8 (t), 30.1 (q), 33.2 (t),
5-Isopr opyl-2-exo,7-exo-dim eth yltr icyclo[5.2.1.04,8]decan -
3-on e (16). A platinum oxide (40 mg) catalyst suspended in
methanol (5 mL) was reduced under a hydrogen atmosphere
for 30 min and cooled to 0 °C, and keto alkene 15 (97 mg, 0.45
mmol) in methanol (5 mL) was added. After 3 h of stirring
under H2, the reaction mixture was filtered and concentrated
in vacuo to yield the ketone 16 (0.12 g, 99%) as an oil. IR (neat)
νmax 1696 cm-1; 1H NMR δ 0.74 (3H, d, J ) 6.3 Hz), 0.98 (3H,
d, J ) 6.3 Hz), 1.01 (3H, d, J ) 7.5 Hz), 1.10 (3H, s), 1.32-
1.66 (6H, m), 1.75-1.97 (2H, m), 1.98-2.10 (2H, m), 2.14-
2.21 (1H, m), 2.75 (1H, t, J ) 6.6 Hz); 13C NMR δ 18.3 (q),
21.9 (q), 22.2 (q), 30.5 (q), 30.5 (d), 31.0 (t), 42.9 (d), 46.3 (s),
48.1 (t), 51.5 (t), 52.1 (d), 53.1 (d), 60.2 (d), 217.6 (s). HRMS
220.1823 (220.1828 calcd for C15H24O).