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diol 20 as a white amorphous solid, which was used without
any further purification. For a complete characterization,
flash chromatography (50–90% diethyl ether in petroleum
ether) of a small aliquot of crude gave pure 20.
ESIMS: m/z 387 [M+Na]+. Anal. Calcd for C21H36O3Si:
C, 69.18; H, 9.95. Found: C, 69.29; H, 9.81.
5.13. (1R,4aS,8R,8aS)-8-Hydroxy-5,5,8a-trimethyl-
1,4,4a,5,6,7,8,8a-octahydro-naphthalene-1,2-dicarb-
aldehyde [1-(R)-hydroxypolygodial] (2)
Compound 20: Rf¼0.20 (40% diethyl ether in petroleum
ether). 1H NMR (CDCl3, 400 MHz): d 0.11 (6H, s,
(CH3)2Si), 0.84 (3H, s, CH3), 0.85 (3H, s, CH3), 0.87 (3H,
s, CH3), 0.92 (9H, s, (CH3)3CSi), 1.15 (1H, dd, J¼4.8,
11.2 Hz, H-5), 1.28 (1H, ddd, J¼3.6, 13.6, 13.6 Hz, H-3),
1.39 (1H, ddd, J¼3.2, 3.2, 13.6 Hz, H-30), 1.51 (1H, dddd,
J¼3.2, 3.6, 4.0, 13.6 Hz, H-2), 1.65 (1H, dddd, J¼3.2,
11.2, 13.6, 13.6 Hz, H-20), 1.91–2.04 (2H, m, H-6 and H-60
overlapped), 2.26 (1H, m, H-9), 2.89 (2H, br s, 2ꢂOH),
3.55 (1H, dd, J¼4.0, 11.2 Hz, H-1), 3.72 (1H, dd, J¼7.2,
10.4 Hz, H-11), 3.92 (1H, d, J¼12 Hz, H-12), 4.30 (1H, d,
J¼12 Hz, H-120), 4.55 (1H, dd, J¼2.4, 10.4 Hz, H-110),
5.80 (1H, m, H-7). 13C NMR (CDCl3, 100 MHz): d ꢁ4.1
(CH3), ꢁ3.6 (CH3), 9.1 (CH3), 18.2 (C), 22.3 (CH3), 23.2
(CH2), 26.1 (ꢂ3) (CH3), 29.1 (CH2), 32.8 (C), 33.1 (CH3),
40.0 (CH2), 41.7 (C), 49.4 (CH), 53.3 (CH), 62.9 (CH2),
67.1 (CH2), 82.9 (CH), 127.0 (CH), 137.9 (C). [a]2D5 ꢁ20.4
(c 1.0, CHCl3). IR (CHC13): n¼3474 (br) cmꢁ1. ESIMS:
m/z 369 [M+H]+. Anal. Calcd for C21H40O3Si: C, 68.42;
H, 10.94. Found: C, 68.54; H, 10.89.
To a solution of 21 (60.0 mg, 0.165 mmol) in acetonitrile
(5.60 mL), in a silicon vessel, 48% aqueous hydrofluoric
acid (1.7 mL) was added at room temperature. The mixture
was stirred at room temperature overnight and then NaHCO3
was carefullyadded untilthe mixturewas neutralized. The or-
ganic solvent was removed in vacuo and the residual aqueous
layer was extracted with ethyl acetate (3ꢂ4 mL). The com-
binedorganicextractsweredried(Na2SO4),filteredandevapo-
rated in vacuo. Flash chromatography of the crude (30–60%
ethyl acetate in petroleum ether) under N2 afforded pure 2
(32.6 mg, 0.130 mmol, 79%) as a white amorphous solid.
Compound 2: Rf¼0.50 (50% ethyl acetate in petroleum
1
ether). H NMR (CDCl3, 400 MHz): d 0.88 (3H, s, CH3),
0.91 (3H, s, CH3), 0.94 (3H, s, CH3), 1.25 (1H, dd, J¼4.9,
11.4 Hz, H-5), 1.36 (1H, m, H-3), 1.51 (1H, ddd, J¼3.2,
3.2, 13.5 Hz, H-30), 1.56–1.66 (2H, m, H-2 and H-20), 2.37
(1H, dddd, J¼2.4, 3.8, 11.4, 20.0 Hz, H-6), 2.45 (1H, m,
H-60), 3.20 (1H, br s, H-9), 3.62 (1H, dd, J¼7.6, 8.2 Hz,
H-1), 7.09 (1H, m, H-7), 9.37 (1H, s, OHCC-8), 9.82 (1H,
d, J¼3.2 Hz, OHCC-9). 13C NMR (CDCl3, 62.5 MHz):
d 9.3 (CH3), 22.0 (CH3), 24.8 (CH2), 27.8 (CH2), 32.7
(CH3), 32.8 (C), 39.6 (CH2), 43.5 (C), 48.5 (CH), 59.8
(CH), 79.8 (CH), 139.5 (C), 153.1 (CH), 192.9 (CH),
203.9 (CH). [a]D25 ꢁ8.2 (c 1.0, CHCl3). IR (CC14):
n¼3513 (br), 2960, 2928, 2873, 2855, 2739, 1722,
1690 cmꢁ1. ESIMS: m/z 273 [M+Na]+. Anal. Calcd for
C15H22O3: C, 71.97; H, 8.86. Found: C, 71.77; H, 8.91.
5.12. (1R,4aS,8R,8aS)-8-(tert-Butyl-dimethyl-silanyl-
oxy)-5,5,8a-trimethyl-1,4,4a,5,6,7,8,8a-octahydro-
naphthalene-1,2-dicarbaldehyde (21)
To a stirring solution of oxalyl chloride (377.7 mg,
2.98 mmol, 0.260 mL) in 7 mL of dry CH2C12 cooled to
ꢁ78 ꢀC was added dropwise 464.9 mg (5.95 mmol,
0.549 mL) of DMSO under a nitrogen atmosphere. After
5 min, a solution of 137.0 mg (0.372 mmol) of 20 in
2.5 mL of CH2C12/DMSO (3/1) was added via cannula. Af-
ter 1 h, 1.40 g (13.8 mmol, 1.93 mL) of freshly distilled tri-
ethylamine was added and the resulting mixture was allowed
to stir at ꢁ78 ꢀC for 5 min and then warmed to room temper-
ature. Then it was passed through a short pad of silica gel
(particle size 0.040–0.263 mm) eluting with ethyl acetate,
under N2, and the eluent was concentrated to give a yellow
oil. The oil was purified by flash chromatography (40–
60% diethyl ether in petroleum ether) under N2 to give
118.0 mg (0.324 mmol, 87% for two steps) of 21 as a white
amorphous solid.
5.14. (1S,4aS,8R,8aS)-8-Hydroxy-5,5,8a-trimethyl-
1,4,4a,5,6,7,8,8a-octahydro-naphthalene-1,2-dicarb-
aldehyde [1-(R)-hydroxyisotadeonal] (3)
To a solution of 2 (5.5 mg, 0.022 mmol) in CH2Cl2 (2.5 mL)
basic Al2O3 (10.0 mg) was added at room temperature. The
mixture was stirred for 20 h and then filtered on a short pad
of silica gel. The pad was thoroughly washed with ethyl ace-
tate, under N2, and the filtrate was concentrated in vacuo to
afford a crude mixture containing 3 and 2 in a ratio of 4.4:1
1
(determined by H NMR). The crude was purified by flash
Compound 21: Rf¼0.50 (50% diethyl ether in petroleum
ether). 1H NMR (CDCl3, 400 MHz): d 0.12 (3H, s,
CH3Si), 0.14 (3H, s, CH3Si), 0.83 (3H, s, CH3), 0.90 (9H,
s, (CH3)3CSi), 0.91 (3H, s, CH3), 0.95 (3H, s, CH3), 1.26
(1H, dd, J¼4.9, 11.1 Hz, H-5), 1.33 (1H, ddd, J¼4.2, 13.2,
13.2 Hz, H-3), 1.50 (1H, ddd, J¼3.2, 3.2, 13.2 Hz, H-30),
1.56–1.71 (2H, m, H-2 and H-20 overlapped), 2.26–2.42
(2H, m, H-6 and H-60 overlapped), 3.30 (1H, br s, H-9),
3.65 (1H, dd, J¼4.5, 10.8 Hz, H-1), 7.03 (1H, m, H-7),
9.32 (1H, s, OHCC-8), 10.0 (1H, d, J¼3.6 Hz, OHCC-9).
13C NMR (CDCl3, 100 MHz): d ꢁ3.7 (CH3), ꢁ3.1 (CH3),
9.9 (CH3), 18.3 (C), 22.4 (CH3), 24.6 (CH2), 26.1 (ꢂ3)
(CH3), 28.0 (CH2), 32.6 (C), 32.8 (CH3), 39.8 (CH2), 44.8
(C), 49.0 (CH), 59.4 (CH), 81.7 (CH), 141.2 (C), 152.0
(CH), 192.7 (CH), 201.0 (CH). [a]2D5 +45.3 (c 1.0, CHCl3).
chromatography (30–70% ethyl acetate in petroleum ether)
under N2 to give 4.5 mg (0.018 mmol, 82%) of 3, as white
amorphous solid, and 1.0 mg (0.004 mmol, 18%) of 2.
Compound 3: Rf¼0.57 (50% ethyl acetate in petroleum
1
ether). H NMR (CDCl3, 400 MHz): d 0.91 (3H, s, CH3),
0.93 (3H, s, CH3), 0.95 (3H, s, CH3), 1.20–1.33 (2H, m,
H-3 and H-30 overlapped), 1.49 (1H, dd, J¼5.0, 11.7 Hz,
H-5), 1.62 (1H, dddd, J¼4.0, 4.0, 4.0, 13.0 Hz, H-2), 1.73
(1H, dddd, J¼3.3, 11.2, 11.2, 13.0 Hz, H-20), 2.28 (1H,
dddd, J¼2.4, 2.4, 11.7, 20.5 Hz, H-6), 2.56 (1H, ddd,
J¼5.0, 5.0, 20.5 Hz, H-60), 3.53 (1H, dd, J¼4.0, 11.2 Hz,
H-1), 3.66 (1H, br s, H-9), 7.11 (1H, dd, J¼2.4, 5.0 Hz, H-
7), 9.44 (1H, s, OHCC-8), 9.89 (1H, d, J¼2.5 Hz, OHCC-
9). 13C NMR (CDCl3, 100 MHz): d 14.8 (CH3), 22.1
(CH3), 25.3 (CH2), 27.5 (CH2), 32.3 (CH3), 32.7 (C), 39.6
IR (CHC13): n¼2929, 2856, 1715, 1682, 1255 cmꢁ1
.