Notes
J . Org. Chem., Vol. 64, No. 5, 1999 1743
H each, each d, J ) 17.4 Hz), 1.08 (3 H, s), 1.03 (3 H, s),
0.85 (3 H, s); HRMS calcd for C17H25O2 (M+ + 1) 261.1855,
found 261.1849.
stirred at room temperature for 30 min. The reaction
mixture was cooled in an ice bath and quenched by the
addition of saturated aqueous NH4Cl solution, and the
product was isolated by extraction with CH2Cl2. The
combined organic extracts were washed with water and
brine, dried, and evaporated. The residue was purified
by chromatography on silica gel using pentane/ether 8:2
as eluent to give compound 13 (225 mg, 83%) as a 1:1
mixture of epimers at C1 (1H NMR analysis): IR (film)
1628, 1593, 926, 883 cm-1; 1H NMR (300 MHz, CDCl3) δ
7.4-7.2 (5H, m), 6.21 and 6.11 (total 1 H, two s), 4.83 (2
H, m), 4.58 (1 H, d, J ) 10.9 Hz), 4.42 and 4.41 (total 1
H, two d, J ) 10.9 Hz), 4.08 and 4.04 (total 1 H, two m),
1.15 and 1.09 (total 3 H, two s), 0.99 and 0.96 (total 3 H,
two s), 0.77 and 0.76 (total 3 H, two s); HRMS calcd for
C22H30O 310.2297, found 310.2305.
2-Ben zyloxy-1-[(1S)-1,2,2-t r im et h ylcyclop en t yl]-
h exa n e-1,5-d ion e (10). To a stirred solution of Na-
HMDS in THF (1.04 mL of a 1 M solution, 1.04 mmol)
was added dropwise a solution of the R-benzyloxyketone
8 (266 mg, 1.02 mmol) in THF (2 mL) at -78 °C. The
mixture was stirred for 30 min, 3-trimethylsilyl-3-buten-
2-one (174 µL, 1.05 mmol) was then added dropwise, and
the resulting solution was allowed to warm slowly to
room temperature over 3 h. The stirring was continued
at the same temperature for 1 h, and saturated aqueous
NH4Cl solution was added. The mixture was poured into
water and extracted with ethyl acetate. Work-up as usual
gave a residue, which was dissolved in a mixture of
methanol (3.5 mL) and 4% aqueous potassium hydroxide
(0.5 mL). After being stirred at room temperature for 6
h, the reaction mixture was poured into water and
extracted with ether. The combined organic layers were
washed with brine and dried. Chromatography of the
residue left after evaporation of the solvent, using hex-
ane/ethyl acetate 4:1 as eluent, afforded diketone 10 (269
mg, 80%) as a 1:1 mixture of epimers at C2 as shown by
1H NMR analysis. Both diastereomers could be partially
separated by MPLC using hexane/ethyl acetate 5:1 as
eluent, and their spectroscopic data were determined
1-Met h yl-3-[(1S)-1,2,2-t r im et h ylcyclop en t yl]ben -
zen e [(-)-Her ber ten e (3)]. A solution of diastereomeric
benzylic ethers 13 (71.6 mg, 0.23 mmol) and camphor-
sulfonic acid monohydrate (60 mg, 0.24 mmol) in CH2-
Cl2 (2 mL) was stirred at room temperature for 2 h.
Chromatography of the residue left after evaporation of
solvent under reduced pressure, using pentane as eluent,
afforded (-)-herbertene (3) (37.3 mg, 80%) as a colorless
and relatively volatile oil: [R]19 -56 (c 1.4, CHCl3) (lit.2
D
[R]D -48.3); IR (film) 1604, 1462, 784, 707 cm-1; 1H NMR
(300 MHz, CDCl3) δ 7.16 (3 H, m), 7.0 (1 H, m), 2.6-2.4
(1 H, m), 2.35 (3 H, s), 1.8-1.6 (4 H), 1.6-1.5 (1 H), 1.26
(3 H, s), 1.07 (3 H, s), 0.56 (3 H, s); HRMS calcd for C15H22
202.1722, found 202.1716.
independently. Less polar diastereoisomer: [R]19 -51 (c
D
2.9, CHCl3); IR (film) 1709 cm-1; H NMR (400 MHz,
1
CDCl3) δ 7.4-7.2 (5 H, m), 4.49 and 4.29 (1 H each, each
d, J ) 11.2 Hz), 4.26 (1 H, dd, J ) 7.2 and 4.1 Hz), 2.09
(3 H, s), 1.14 (3 H, s), 1.13 (3 H, s), 0.87 (3 H, s); HRMS
calcd for C21H31O3 (M+ + 1) 331.2281, found 331.2277.
More polar diastereoisomer: IR (film) 1708 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.4-7.2 (5 H, m), 4.49 and 4.29 (1 H
each, each d, J ) 11.2 Hz), 4.37 (1 H, dd, J ) 6.8 and 4.4
Hz), 2.08 (3 H, s), 1.12 (3 H, s), 1.11 (3 H, s), 0.91 (3 H,
s); HRMS calcd for C21H31O3 (M+ + 1) 331.2281, found
331.2279.
4-Meth yl-2-[(1S)-1,2,2-tr im eth ylcyclop en tyl]-2-cy-
cloh exen -1-on e (15). A mixture of 13 (518 mg, 1.67
mmol) and 10% palladium on carbon (77 mg) in ethyl
acetate (60 mL) was shaken at room temperature under
an H2 atmosphere for 1 h. After removal of the catalyst
by filtration through a pad of silica gel, the filtrate was
concentrated in vacuo. A mixture of the residual oil
obtained, Pd(OH)2 on carbon (20%, 779 mg), and pal-
ladium on calcium carbonate (5%, 779 mg) in absolute
EtOH (46 mL) was stirred at room temperature under 1
atm of H2 for 30 min. Removal of the palladium catalysts
by filtration through Celite, followed by evaporation of
the filtrate under reduced pressure, afforded a diaster-
eomeric mixture of allylic alcohols 14 (337 mg).
To a stirred mixture of the crude product obtained
above (337 mg, 1.52 mmol), NMO (267 mg, 2.28 mmol),
and powdered 4 Å molecular sieves (783 mg) in CH2Cl2
(3 mL) was added solid TPAP (31 mg, 0.09 mmol) in one
portion at room temperature. After 25 min of stirring at
the same temperature, the mixture was filtered through
a short pad of Celite, eluting with acetone. Chromatog-
raphy of the residue left after evaporation of the solvent,
using pentane/ether 8:2 as eluent, afforded methyl enone
15 (305 mg, 84% overall yield from 13) as a 1:1 mixture
of epimers at C4: IR (film) 1680 cm-1; 1H NMR (300 MHz,
CDCl3) δ 6.53 (1 H, br s), 1.20 and 1.19 (total 3 H, two
s), 1.12 (total 3 H, overlapping d, J ) 7 Hz), 1.07 and
1.05 (total 3 H, two s), 0.69 (3 H, s); HRMS calcd for
C15H24O 220.1827, found 220.1827.
4-Ben zyloxy-3[(1S)-1,2,2-tr im eth ylcyclop en tyl]-2-
cycloh exen -1-on e (11). A solution of epimeric diketones
10 (735 mg, 2.23 mmol) in a mixture of methanol (63 mL)
and 20% aqueous potassium hydroxide (12 mL) was
heated at 120 °C in a sealed tube under argon for 6 h.
The mixture was poured into water and extracted with
CH2Cl2. Work-up as usual afforded an oily residue, which
was purified by chromatography using pentane/ether 8:2
as eluent to afford the cyclohexenone 11 (542 mg, 78%)
as an equimolecular mixture of epimers at C4: IR (film)
1
1673, 1610 cm-1; H NMR (400 MHz, CDCl3) δ 7.4-7.2
(5 H, m), 6.02 and 5.94 (total 1 H, two s), 4.62 and 4.61
(total 1 H, overlapping d, J ) 11 Hz), 4.482 and 4.478
(total 1 H, overlapping d, J ) 11 Hz), 4.25 and 4.20 (total
1 H, two br s), 2.72 (1 H, m), 2.41 (1 H, m), 2.3 (1 H, m),
1.17 and 1.11 (total 3 H, two s), 1.02 and 0.96 (total 3 H,
two s), 0.802 and 0.799 (total 3 H, two s); HRMS calcd
for C21H29O2 313.2168, found 313.2165.
Ben zyl 4-Meth ylen e-2-[(1S)-1,2,2-tr im eth ylcyclo-
p en tyl]-2-cycloh exen y1-eth er (13). A solution of meth-
yl triphenylphosphonium bromide (942 mg, 2.64 mmol)
in DMSO (3 mL) was added to a solution of NaCH2-
SOCH3, prepared from sodium hydride (102 mg of 60%
dispersion in oil, 2.54 mmol) and DMSO (2 mL), at room
temperature. After 15 min of stirring, a solution of the
unsaturated ketone 11 (274 mg, 0.44 mmol) in DMSO
(1.5 mL) was added, and the resulting mixture was
4-Meth yl-2-[(1S)-1,2,2-tr im eth ylcyclop en tyl]p h e-
n ol [(-)-r-Her ber ten ol (4)]. An intimate mixture of
epimeric methyl ketones 15 (43.8 mg, 0.21 mmol) and
sulfur (8.1 mg, 0.24 mmol) was heated in a sealed tube
at 200 °C under argon for 1.5 h. The reaction mixture
was dissolved into CH2Cl2 and filtered through a short
pad of silica gel. Chromatography of the residue left after