Synthesis of the Pterosin Family of Sesquiterpenes
J . Org. Chem., Vol. 61, No. 1, 1996 79
to give 110 mg (80%) of the exo isomer of spiro[1,4,4-trimethyl-
10-oxatricyclo[5.2.1.02,6]decane-3,8-dione-9,1′-cyclopropane]
(8): mp 120-121 °C; IR (CDCl3) 2958, 1754, 1732, 1381, and
mmol) of potassium carbonate in 150 mL of DMSO was stirred
with a mechanical stirrer at rt overnight. The solution was
diluted with 150 mL of H2O, extracted with ether, and dried
over MgSO4, and the solvent was removed under reduced
pressure. The crude oil was purified to give 7.27 g (99%) of
1-acetyl-1-carbomethoxycyclopentane50 as a light yellow oil: IR
(neat) 2951, 1740, 1704, 1626, 1432, and 1353 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.60 (m, 4H), 2.10 (m, 4H), 2.17 (s, 3H),
and 3.72 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 25.6, 26.3, 32.9,
52.5, 66.7, 173.9, and 203.8; HRMS calcd for C9H15O3 (M + 1)
171.1021, found 171.1026.
1
980 cm-1; H NMR (300 MHz, CDCl3) δ 0.66 (m, 1H), 0.93-
1.14 (m, 2H), 0.99 (s, 3H), 1.03 (s, 3H), 1.26 (s, 3H), 1.28 (m,
1H), 1.76 (dd, 1H, J ) 13.2 and 7.8 Hz), 2.11 (dd, 1H, J ) 13.2
and 9.0 Hz), 2.65 (d, 1H, J ) 8.4 Hz), 2.82 (q, 1H, J ) 8.4 Hz),
and 4.23 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 11.8, 13.5, 14.4,
22.5, 25.8, 38.6, 39.5, 40.2, 47.6, 56.2, 85.4, 87.8, 212.3 and
219.3. Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found:
C, 71.75; H, 7.71.
A solution containing 7.0 g (60 mmol) of the above compound
and 75 mL of a 3.5 M aqueous KOH solution in 100 mL of
MeOH was stirred at rt overnight. The solution was concen-
trated under reduced pressure and washed with ether, and
the aqueous layer was acidified with 50% HCl to pH 2. The
acidified solution was extracted with ether, dried over MgSO4,
and concentrated under reduced pressure. The crude carboxy-
lic acid was not purified, but was immediately used in the next
step.
Rh od iu m (II)-Ca ta lyzed Rea ction of 1-Acetyl-1-(d ia zo-
a cetyl)cyclop r op a n e (16) w ith Cyclop en ten e. A solution
containing 106 mg (0.70 mmol) of R-diazo ketone 16 and 5 mL
(95 mmol) of cyclopentene was treated with 2 mg of rhodium-
(II) acetate. The reaction was complete after 2 h. The crude
oil was purified by silica gel chromatography to give 87 mg
(65%) of exo spiro[1-methyl-10-oxatricyclo[5.2.1.02,6]decan-8-
one-9,1′-cyclopropane] (26) as a clear oil: IR (neat) 1752, 1446,
1382, and 991 cm-1 1H NMR (300 MHz, CDCl3) δ 0.66 (m,
;
1H), 0.99 (m, 1H), 1.09 (m, 1H), 1.16 (s, 3H), 1.21 (m, 1H),
1.40 (m, 3H), 1.74 (m, 2H), 1.98 (m, 1H), 2.40 (m, 2H), and
4.12 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 11.5, 13.6, 13.9, 28.3,
28.8, 31.1, 37.8, 45.4, 51.0, 85.3, 86.1, and 213.8; HRMS calcd
for C12H16O2 192.1150, found 192.1150.
To a solution containing 7.0 g (45 mmol) of the above
compound in 150 mL of ether were successively added 5.9 mL
(76 mmol) of methyl chloroformate and 8.9 mL (76 mmol) of
triethylamine. The solution was stirred under argon at rt for
1 h, and the solid salts were removed by vacuum filtration.
This solution was immediately added to a solution containing
100 mmol of diazomethane in ether, and the mixture was
stirred at rt overnight. The crude oil was purified by silica
gel chromatography to give 4.9 g (50%) of 30 as a yellow oil:
IR (neat) 2109, 1713, 1634, 1357, and 1152 cm-1; 1H NMR (300
MHz, CDCl3) δ 1.55 (m, 4H), 2.02 (m, 4H), 2.07 (s, 3H), and
5.21 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 25.0, 25.3, 26.0, 31.4,
53.5, 72.5, 192.5, and 204.7; HRMS calcd for C9H13N2O2 (M +
1) 181.098, found 181.097.
Rh od iu m (II)-Ca ta lyzed Rea ction of Eth yl 3-(1-Acetyl-
cyclop r op yl)-2-d ia zo-3-oxop r op ion a te (17) w ith Cyclo-
p en ten e. To a solution containing 0.5 mL (5.69 mmol) of
cyclopentene and 2 mg of rhodium(II) acetate in 4 mL of
benzene was added a solution contaning 150 mg (0.67 mmol)
of R-diazo keto ester 17 in 4 mL of benzene, and the resulting
mixture was heated at reflux for 5 h. The product was purified
by silica gel chromatography to give 126 mg (71%) of exo spiro-
[7-carbethoxy-1-methyl-10-oxatricyclo[5.2.1.02,6]decan-8-one-
9,1′-cyclopropane] (27): mp 79-80 °C; IR (CDCl3) 2951, 1761,
1725, 1324, and 1130 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.68-
0.75 (m, 1H), 1.02-1.08 (m, 1H), 1.12-1.14 (m, 1H), 1.18 (s,
3H), 1.23-1.48 (m, 4H), 1.30 (t, 3H, J ) 7.2 Hz), 1.69-1.80
(m, 2H), 1.95 (m, 1H), 2.43 (q, 1H, J ) 8.1 Hz), 2.76 (q, 1H, J
) 8.1 Hz), and 4.33 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 12.2,
13.8, 14.3, 14.6, 27.9, 28.8, 29.3, 37.7, 48.3, 51.8, 61.6, 85.2,
91.4, 165.8, and 207.2. Anal. Calcd for C15H20O4: C, 68.16;
H, 7.63. Found: C, 68.12; H, 7.65.
Rh od iu m (II)-Ca ta lyzed Rea ction of 1-Acetyl-1-(d ia zo-
a cetyl)cyclop en ta n e (30) w ith 1,1-Dim eth oxyeth ylen e. A
solution containing 216 mg (1.2 mmol) of R-diazo ketone 30
and 0.40 mL (3.3 mmol) of 1,2-dimethoxyethylene was treated
with 2 mg of rhodium(II) acetate. The reaction was complete
in 4 h. The crude oil was purified by silica gel chromatography
to give 173 mg (60%) of 8,8-dimethoxy-7,10-epoxy-10-methyl-
6-oxospiro[4.5]decane (31) as a clear oil: IR (neat) 1757, 1456,
1
1120, and 1036 cm-1; H NMR (300 MHz, CDCl3) δ 1.30 (m,
1H), 1.42 (s, 3H), 1.50 (m, 3H), 1.7-1.9 (m, 5H), 2.10 (d, 1H,
J ) 13.2 Hz), 3.29 (s, 3H), 3.31 (s, 3H), and 4.25 (s, 1H); 13C
NMR (75 MHz, CDCl3) δ 17.5, 27.0, 27.1, 33.1, 33.9, 44.2, 49.3,
51.0, 59.7, 84.4, 88.8, 109.3, and 216.2; HRMS calcd for
C13H20O4 240.1361, found 240.1362.
Rh od iu m (II)-Ca ta lyzed Rea ction of 1-Acetyl-1-(d ia zo-
a cetyl)cyclop r op a n e (16) w ith Nor bor n en e. To a solution
containing 183 mg (2.0 mmol) of norbornene and 2 mg of
rhodium(II) acetate in 6 mL of benzene was added a solution
contaning 200 mg (1.3 mmol) of R-diazo ketone 16 in 6 mL of
benzene, and the resulting mixture was stirred for 6 h at rt.
The crude product was purified by silica gel chromatography
to give 193 mg (68%) of spiro[5,8-epoxy-1,4-methano-8-methyl-
6-oxooctahydronaphthalene-7,1′-cyclopropane] (28): mp 67-
Rh od iu m (II)-Ca ta lyzed Rea ction of 1-Acetyl-1-(d ia zo-
a cetyl)cyclop en ta n e (30) w ith Dim eth yl Ma lea te.
A
solution containing 201 mg (1.3 mmol) of R-diazo ketone 30
and 0.4 mL (3.3 mmol) of dimethyl maleate in 5 mL of CH2Cl2
was treated with 2 mg of rhodium(II) acetate. The reaction
was complete after 4 h. The crude oil was purified by silica
gel chromatography to give 119 mg (36%) of dimethyl 6,9-
epoxy-6-methyl-10-oxospiro[4.5]decane-7,8-dicarboxylate (32)
as a crystalline solid: mp 113-114 °C; IR (CDCl3) 2954, 1730,
1645, 1439, 1254, and 1005 cm-1; 1H NMR (300 MHz, CDCl3)
δ 1.39 (s, 3H), 1.44 (m, 1H), 1.52 (m, 2H), 1.76 (m, 4H), 1.99
(m, 1H), 3.03 (d, 1H, J ) 9.3 Hz), 3.33 (d, 1H, J ) 9.3 Hz),
3.69 (s, 3H), 3.70 (s, 3H), and 4.91 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 13.7, 26.8, 26.9, 32.2, 33.8, 49.0, 51.9, 52.1, 52.5, 62.2,
81.6, 91.1, 169.6, 170.7, and 217.3. Anal. Calcd for C15H20O6:
C, 60.80; H, 6.80. Found: C, 60.78; H, 6.79.
Rh od iu m (II)-Ca ta lyzed Rea ction of 1-Acetyl-1-(d ia zo-
a cetyl)cyclop en ta n e (30) w ith Dim eth yl Acetylen ed ica r -
boxyla te. A solution containing 256 mg (1.4 mmol) of R-diazo
ketone 30 and 0.70 mL (5.7 mmol) of DMAD in 5 mL of CH2-
Cl2 was treated with 2 mg of rhodium(II) acetate. The reaction
was complete after 5 h. The crude residue was purified to give
309 mg (80%) of dimethyl 6,9-epoxy-6-methyl-10-oxospiro[4.5]-
dec-7-ene-7,8-dicarboxylate (33) as a white crystalline solid:
mp 88-89 °C; IR (neat) 1752, 1738, 1720, 1645, 1432, and 1267
1
68 °C; IR (CDCl3) 1747, 1439, 1338, and 1102 cm-1; H NMR
(300 MHz, CDCl3) δ 0.53-0.62 (m, 1H), 0.82-0.89 (m, 2H),
1.00-1.18 (m, 4H), 1.13 (s, 3H), 1.41 (m, 2H), 1.80 (d, 1H, J )
6.9 Hz), 1.85 (d, 1H, J ) 6.9 Hz), 2.11 (d, 1H, J ) 9.6 Hz),
2.25 (bs, 1H), 2.31 (bs, 1H), and 4.21 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 11.5, 13.3, 13.4, 28.7, 29.2, 34.5, 36.8, 39.8,
40.3, 47.6, 53.5, 84.6, 85.8, and 212.6. Anal. Calcd for
C14H18O2: C, 77.03; H, 8.31. Found: C, 76.76; H, 8.29.
Rh od iu m (II)-Ca ta lyzed Rea ction of 1-Acetyl-1-(d ia zo-
a cetyl)cyclop r op a n e (16) w ith Cycloh exen e. A solution
containing 97 mg (0.64 mmol) of R-diazo ketone 16 and 5 mL
(49.4 mmol) of cyclohexene was treated with 2 mg of rhodium-
(II) acetate. The reaction was complete in 5 h. The crude oil
was purified to give 21 mg (16%) of spiro[1-methyl-11-
oxatricyclo[6.2.1.02,7]undecan-9-one-10,1′-cyclopropane] (29) as
a clear oil: IR (neat) 1752, 1460, 1382, 1332, and 812 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.62 (m, 1H), 0.98 (m, 1H), 1.10
(s, 3H), 1.2-1.7 (m, 10H), 1.90 (m, 1H), 2.10 (m, 1H), and 4.13
(s, 1H); 13C NMR (75 MHz, CDCl3) δ 11.6, 13.3, 13.6, 18.1, 18.3,
19.8, 21.8, 38.9, 39.2, 44.1, 85.7, 86.6, and 213.6; HRMS calcd
for C13H18O2 206.1307, found 206.1302.
P r ep a r a tion of 1-Acetyl-1-(d ia zoa cetyl)cyclop en ta n e
(30). A solution containing 5.0 g (43 mmol) of methyl acetoac-
etate, 15.9 g (52 mmol) of 1,4-diiodobutane, and 30 g (215
(50) (a) Bekhazi, M.; Smith, P. J .; Warkentin, J . Can. J . Chem. 1984,
62, 1646. (b) Warkentin, J . J . Org. Chem. 1984, 49. 343.