8778 J . Org. Chem., Vol. 61, No. 25, 1996
An and Wiemer
replaced by a water condenser, and the NH3 was allowed to
evaporate. The reaction was quenched by addition of satu-
rated NH4Cl, and the aqueous layer was extracted three times
with ether (50 mL each). The combined organic layer was
dried over Na2SO4 and concentrated in vacuo. Flash column
chromatography (40% hexanes, 60% ethyl acetate) gave com-
pound 9 (1.19 g, 81%) as an oil: [R]D ) +24.6° (CHCl3, c )
1.0); 1H NMR δ 6.72-6.71 (m, 2), 6.50 (s, 1), 3.94-3.75 (m, 4),
3.73 (s, 3), 3.70 (s, 3), 2.90 (d, J ) 13.3 Hz, 1), 2.80 (d, J )
13.3 Hz, 1), 2.57-2.47 (m, 1), 2.36-2.22 (m, 2), 1.95-1.85 (m,
1), 1.77-1.44 (br, m, 7), 1.04 (s, 6); 13C NMR δ 217.0, 152.9,
152.3, 127.4, 117.8, 112.7, 112.3, 110.8, 65.0, 64.6, 55.6, 55.3,
51.8, 45.0, 42.1, 39.6, 35.2, 29.9, 28.3, 22.8, 22.7, 20.9, 17.2;
EIMS m/ z (rel intensity) 388 (M+, 8), 237 (6), 210 (6), 151
(100), 121 (19), 99 (58), 85 (12), 55(14); HRMS calcd for
119.0, 111.0, 110.8, 55.5, 55.3, 49.3, 47.6, 42.3, 37.5, 37.2, 35.6,
32.3, 26.8, 25.6, 21.9, 18.9, 18.0, 17.3.
(1S,2S,4a S)-(-)-tr a n s-Deca h yd r o-1r-[(2,5-d im et h ox-
yp h en yl)m eth yl]-5-m eth ylen e-1â,2â,4a â-tr im eth yln a p h -
th a len e (13). To a suspension of methyltriphenylphospho-
nium bromide (0.66 g, 1.84 mmol) in anhydrous 1,4-dioxane
(10 mL) was added n-BuLi (1.1 mL, 1.60 mmol, 1.6 M in
hexane) over 2 min. The resulting orange suspension was
stirred at rt for 1 h. Ketone 12 (0.11 g, 0.31 mmol) in 2 mL of
1,4-dioxane was then added to the phosphorane solution, and
the reaction was heated at reflux for 3 h. The reaction was
quenched by addition of water (5 mL) and concentrated in
vacuo. The residue was purified by flash column chromatog-
raphy (80% hexanes, 20% ethyl acetate) to give compound 13
(0.10 g, 97%) as a white solid: [R]D ) -34° (CHCl3 c ) 1.4);
1
mp 80 °C; H NMR δ 6.74-6.63 (m, 3), 4.40 (s, 1), 4.37 (s, 1),
C
23H32O5 388.2250, found 338.2271. Anal. Calcd for
3.74 (s, 3), 3.70 (s, 3), 2.66 (d, J ) 14.0 Hz, 1), 2.58 (d, J )
14.0 Hz, 1), 2.39-2.28 (m, 1), 2.10 (br, 1), 2.06 (br, 1), 1.93-
1.88 (br, m, 1), 1.60-1.27 (br, m, 7), 1.05 (s, 3), 1.05-0.95 (m,
1), 1.00 (d, J ) 5.8 Hz, 3), 0.84 (s, 3); 13C NMR δ 160.2, 152.9,
152.7, 128.6, 118.7, 111.2, 110.7, 102.6, 55.6, 55.3, 48.1, 42.1,
40.2, 37.1, 36.5, 36.2, 33.1, 28.3, 27.7, 23.1, 20.6, 17.7, 17.5;
EIMS m/ z (rel intensity) 342 (M+, 12), 191 (10), 177 (7), 152
(100), 121 (29), 109 (16), 95 (68), 55 (14); HRMS calcd for
C23H34O2 342.2559, found 342.2559.
(1S,2S,4a S)-(+)-tr a n s-1r-[(2,5-Dim eth oxyp h en yl)m eth -
yl]-1,2,3,4,4a ,8a ,7,8-oct a h yd r o-1â,2â,4a â,5-t et r a m et h yl-
n a p h th a len e (14, d im eth yl eth er a va r ol). A mixture of
compound 13 (76 mg, 0.22 mmol) and Rh3Cl‚H2O (5 mg) in 5
mL of ethanol was heated at reflux for 20 h. After concentra-
tion of the solution, the residue was purified by flash column
chromatography (80% hexanes, 20% ethyl acetate) to give
compound 14 (68 mg, 89%) as a white solid: [R]D ) +8.9°
(CHCl3, c ) 1.1); mp 78 °C (lit.3 mp 80-81 °C); both 1H NMR
and 13C NMR spectra were identical to literature data for
material derived from the natural product; EIMS m/ z (rel
intensity) 342 (M+, 2), 191 (2), 190 (2), 152 (57), 151 (44), 121
(11), 120 (14), 95 (81), 94 (100), 55 (8).
Ava r on e (2). A mixture of compound 14 (26 mg, 0.08
mmol) and (NH4)2Ce(NO3)6 (83 mg, 0.15 mmol) in CH3CN (4
mL) and water (2 mL) was stirred at rt for 3 days. The
reaction was then concentrated in vacuo and purified by flash
column chromatography (90% hexanes, 10% ethyl acetate) to
give compound 2 (12 mg, 49%) as a yellow oil with 1H NMR
data identical to that reported for natural product;2 13C NMR
δ 187.4, 187.3, 147.4, 144.1, 137.2, 136.2, 136.0, 120.5, 47.0,
42.7, 38.5, 37.0, 36.1, 35.4, 27.4, 26.4, 20.0, 19.3, 18.0, 17.7,
16.7.
Ava r ol (1). To a solution of avarone (2, 5 mg, 0.016 mmol)
in THF (2 mL) and water (0.7 mL) was added solid Na2S2O3
at rt, and the reaction mixture was stirred for 10 min. After
concentration of the solution, the residue was purified by flash
column chromatography (10% hexanes, 90% ethyl acetate) to
give avarol 1 (3 mg, 60%): 1H NMR, identical to that reported
for natural product;2 EIMS m/ z (rel intensity) 314 (M+, 0.5),
189 (2), 107 (43), 95 (100), 55 (24); HRMS calcd for C21H30O2
314.2245, found 314.2265.
Exo-a va r on e (15). A mixture of compound 13 (45 mg, 0.13
mmol) and (NH4)2Ce(NO3)6 (288 mg, 0.53 mmol) in CH3CN (6
mL) and water (2 mL) was stirred at rt for 3 days. The
reaction was then concentrated in vacuo and purified by flash
column chromatography (90% hexanes, 10% ethyl acetate) to
give compound 15 (20.3 mg, 50%) as a yellow oil: 1H NMR δ
6.77-6.68 (m, 2), 6.64 (br, 1), 4.46 (s, 1), 4.44 (s, 1), 2.58 (d, J
) 13.5 Hz, 1), 2.40 (d, J ) 13.5 Hz, 1), 2.32-2.25 (m, 1), 2.12-
2.06 (m, 1), 1.92-1.82 (m, 2), 1.57-1.40 (m, 6), 1.25-1.10 (m,
2), 1.05 (s, 3), 0.94 (d, J ) 6.5 Hz, 3), 0.86 (s, 3); 13C NMR δ
187.4, 187.2, 159.6, 147.2, 137.2, 136.1, 136.0, 103.2, 49.3, 43.1,
40.3, 37.2, 36.8, 35.3, 32.9, 28.1, 27.5, 22.7, 20.6, 17.7, 16.8;
EIMS m/ z (rel intensity) 312 (M+, 0.3), 192 (4), 191 (23), 175
(4), 135 (10), 121 (16), 109 (23), 95 (100), 79 (18), 67 (12), 55
(13); HRMS calcd for C21H28O2 312.2089, found 312.2095.
(4S)-(+)-4-Me t h yl-4-(2-m e t h yl-1,3-d ioxola n -2-yl)-2-
m eth ylen ecycloh exa n on e (21). A mixture of â-keto phos-
phonate 19 (0.79 g, 2.3 mmol), K2CO3 (0.32 g, 2.3 mmol), and
paraformaldehyde (0.21 g, 7.0 mmol) in 1,4-dioxane (10 mL)
C23H32O5: C, 71.11; H, 8.30. Found: C, 71.01; H, 8.31.
(1S,4a S)-(+)-tr a n s-1r-[(2,5-Dim eth oxyp h en yl)m eth yl]-
1â,4a â-d im eth yl-5-(2-m eth yl-1,3-d ioxola n -2-yl)-2-m eth yl-
en eocta h yd r o-5(6H)-n a p h th a len on e (10). To a suspension
of methyltriphenylphosphonium bromide (4.20 g, 12.0 mmol)
in anhydrous 1,4-dioxane (50 mL) was added n-BuLi (6.9 mL,
11.0 mmol, 1.6 M in hexane) over 5 min. The resulting orange
suspension was stirred at rt for 60 min, compound 9 (0.66 g,
1.7 mmol) in 5 mL of 1,4-dioxane was added, and the reaction
was heated at reflux for 24 h. After the reaction was quenched
by addition of water (20 mL) and concentrated in vacuo, the
residue was purified by flash column chromatography (90%
hexanes, 10% ethyl acetate) to give olefin 10 (0.46 g, 70%) as
1
an oil: [R]D ) +101° (CHCl3, c ) 1.04); H NMR δ 6.70-6.60
(m, 3), 4.74 (br, 1), 4.27(br, 1), 4.00-3.84 (m, 4), 3.73 (s, 3),
3.70 (s, 3), 2.77 (d, J ) 13.1 Hz, 1), 2.59 (d, J ) 13.1 Hz, 1),
2.35-2.27 (m, 1), 2.17-1.95 (m, 3), 1.74-1.40 (br, m, 6), 1.30-
1.15 (m, 1), 1.05 (s, 3), 0.91 (s, 3); 13C NMR δ 153.9, 152.8,
152.4, 128.4, 118.7, 113.6, 111.4, 110.6, 107.3, 64.9, 64.5, 55.7,
55.6, 46.3, 43.5, 42.9, 39.9, 32.0, 29.8, 26.9, 23.0, 22.9, 20.8,
20.3; EIMS m/ z (rel intensity) 386 (M+, 3), 324 (2), 235 (13),
189 (1), 151 (16), 121 (12), 99 (100), 91 (9), 55 (14); HRMS
calcd for C24H34O4 386.2457, found 386.2457. Anal. Calcd for
C24H34O4: C, 74.56; H, 8.87. Found: C, 74.41; H, 8.84.
(1S,2S,4a S)-(-)-tr a n s-1R-[(2,5-Dim eth oxyp h en yl)m eth -
yl]-5-(2-m et h yl-1,3-d ioxola n -2-yl)-oct a h yd r o-1â,2â,4a â-
tr im eth yl-5(6H)-n a p h th a len on e (11). Olefin 10 (0.41 g,
1.05 mmol), 10% Pd-C (0.68 g) in triethylamine (10 mL), and
methanol (2 drops) was stirred at rt under 1 atm of hydrogen
for 12 h. The reaction was filtered through Celite, and the
filtrate was concentrated in vacuo. The residue was purified
by flash column chromatography (90% hexanes, 10% ethyl
acetate) to give compound 11 (0.25 g, 62%): 1H NMR δ 6.77-
6.66 (m, 3), 3.87-3.67 (m, 4), 3.78 (s, 3), 3.73 (s, 3), 2.63 (s, 2),
1.94 (d, J ) 13.6 Hz, 1), 1.71-1.59 (m, 3), 1.51-1.43 (m, 2),
1.39-1.22 (br, m, 6), 1.05 (s, 3), 0.94 (d, J ) 5.6 Hz, 3), 0.8 (s,
3); 13C NMR δ 152.9, 152.7, 128.9, 118.3, 113.4, 111.9, 110.9,
65.1, 64.8, 55.8, 55.4, 43.7, 43.2, 41.5, 37.2, 36.1, 30.7, 29.6,
27.3, 22.8, 21.8, 17.5 (2), 16.8; EIMS m/ z (rel intensity) 388
(M+, 6), 237 (43), 175 (27), 152 (90), 99 (100), 55 (28); HRMS
calcd for C24H36O4 388.2613, found 388.2585. Anal. calcd for
C24H36O4: C, 74.18; H, 9.34. Found: C, 74.24; H, 9.29.
(1S,2S,4a S)-(-)-tr a n s-1r-[(2,5-Dim eth oxyp h en yl)m eth -
y l]-o c t a h y d r o -1â,2â,4a â-t r im e t h y l-5(6H )-n a p h t h a le -
n on e (12). Ketal 11 (400 mg, 10 mmol) in THF (8 mL) and
aqueous HCl (5%, 2 mL) was stirred at rt for 2 h. The reaction
was quenched by addition of solid Na2CO3, and THF was
removed in vacuo. The remaining aqueous layer was extracted
three times with ether (20 mL each). The combined organic
layer was dried over Na2SO4, and concentrated in vacuo. The
residue was purified by flash column chromatography (80%
hexanes, 20% ethyl acetate) to give compound 12 as a white
1
solid (350 mg, 99%) with H NMR data identical to the partial
spectrum reported for racemic material:11 [R]D ) -42.3°
(CHCl3, c ) 1.04); mp 105 °C; 1H NMR δ 6.74-6.61 (m, 3),
3.73 (s, 3), 3.70 (s, 3), 2.73 (d, J ) 14.0 Hz, 1), 2.63 (d, J )
14.0 Hz, 1), 2.63-2.51 (m, 1), 2.24-2.04 (br, m, 3), 1.81-1.67
(m, 1), 1.59-1.37 (m, 6), 1.14 (s, 3), 1.11 (m, 1), 1.05 (d, J )
5.8 Hz, 3), 0.90 (s, 3); 13C NMR δ 216.2, 152.7, 152.6, 127.9,