962
M. B. Villecco et al. / Tetrahedron 59 (2003) 959–963
m/z(rel. int.): 185 (2), 184 (Mþ, 1), 166 (55), 149 (30), 133
(25), 121 (49), 105 (20), 93 (32), 81 (19), 71 (36), 43 (100);
HREIMS m/z 185.1548 [MþH]þ (calcd for C11H21O2
185.1542).
4 mL) during 5 min and then allowed to reach the room
temperature. The reaction was quenched with a saturated
NH4Cl solution (1.5 mL) and diluted with EtOAc (12 mL).
The organic layer was decanted, washed with a saturated
NH4Cl solution (2£2.5 mL), dried over anhydrous Na2SO4
and the solvent removed under reduced pressure. TLC
analysis of the residue showed two spots with Rf 0.58 and
0.42 (hexane/EtOAc, 4:1). Column chromatography (19:1
hexane/EtOAc) of the mixture provided 43 mg of 13a (34%,
Rf 0.58) and 56 mg of 13b (44%, Rf 0.42) as colorless oils.
3.2.4. 11-Hydroxyhomocineole (11). A solution of 10
(750 mg, 4.08 mmol) in anhydrous THF (25 mL) was
treated with mercuric acetate (3 g, 9.42 mmol) and the
resulting suspension was stirred at 558C for 30 h. A solution
of NaOH (10 mL, 5 M), followed by a solution of NaBH4
(270 mg) in NaOH (10 mL, 5 M) were added, and stirring
continued for 1 h. The suspension was concentrated, diluted
with EtOAc (50 mL) and saturated with NaCl. The organic
layer was decanted, washed with brine (3£5 mL) and dried
over anhydrous Na2SO4. The solvent was removed under
reduced pressure and the residue purified by column
chromatography (9:1 to 41:9 hexane/EtOAc) to give 11
(510 mg, 68%) as a colorless oil. IR nmax 3440, 2970, 1380,
Compound 13a shows IR nmax 3416, 3076, 1648, 1128,
1
1020 cm21; H NMR d 4.79 (1H, br d, J¼1.6 Hz, H-14a),
4.76 (1H, br d, J¼1.1 Hz, H-14b), 4.26 (1H, dtd, J¼11.0,
6.7, 1.4 Hz, H-11), 2.32 (1H, dd, J¼13.5, 6.7 Hz, H-12a),
2.06 (1H, dd, J¼13.5, 6.7 Hz, H-12b), 1.94 (1H, dd, J¼14.3,
11.0 Hz, H-10a), 1.78 (3H, br s, H-15), 1.32 (3H, s, H-9),
1.23 (1H, dd, J¼14.3, 1.4 Hz, H-10b), 1.03 (3H, s, H-7); 13C
NMR d 143.0 (C-13), 112.3 (C-14), 77.3 (C-8), 70.6 (C-1),
66.9 (C-11), 46.5 (C-12), 44.2 (C-10), 32.8 (C-4), 31.4
(C-6), 31.1 (C-2), 27.2 (C-7), 24.8 (C-9), 22.6 (C-5), 22.6
(C-15), 22.3 (C-3); EIMS 70 eV m/z (rel. int.): 239 (20), 238
(Mþ, 6), 203 (3), 183 (13), 165 (16), 147 (17), 140 (13), 139
(100), 138 (9), 121 (14), 108 (6), 107 (6), 105 (8), 95 (4), 43
(19); HREIMS m/z 239.2006 [MþH]þ (calcd for C15H27O2
239.2011).
1
1220, 1210, 1080, 1050, 980, 950 cm21; H NMR d 4.04
(1H, td, J¼11.0, 3.5 Hz, H-11a), 3.71 (1H, dt, J¼11.0,
4.5 Hz, H-11b), 2.25 (1H, ddd, J¼14.0, 11.0, 4.5 Hz,
H-10a), 1.34 (1H, ddd, J¼14.0, 4.5, 3.5 Hz, H-10b), 2.09,
1.53 (2H, m, H-3a,b), 2.06, 1.51 (2H, m, H-5a,b), 1.71, 1.53
(2H, m, H-2a,b), 1.68, 1.51 (2H, m, H-6a,b), 1.41 (1H, m,
H-4), 1.29 (3H, br s, Me-9), 1.03 (3H, s, Me-7); 13C NMR d
77.2 (C-8), 70.3 (C-1), 60.2 (C-11), 40.2 (C-10), 32.5 (C-4),
31.4 (C-6), 31.2 (C-2), 27.4 (C-7), 24.6 (C-9), 22.7 (C-5),
22.3 (C-3); EIMS 20 eV m/z (rel. int.): 185 (16), 184 (Mþ,
4), 167 (15), 149 (21), 139 (100), 108 (22), 95 (15), 81 (13),
67 (10), 43 (33); HREIMS m/z 185.1547 [MþH]þ (calcd for
C11H21O2 185.1542).
Compound 13b shows IR nmax 3558, 3486, 3076, 3022,
1
1644, 1144, 1006, 920 cm21; H NMR d 4.87 (1H, br q,
J¼1.3 Hz, H-14a), 4.78 (1H, br q, J¼1.1 Hz, H-14b), 3.95
(1H, br quintet, J¼6 Hz, H-11), 2.20 (2H, d, J¼6 Hz, H-12),
1.76 (3H, br s, H-15), 1.72 (2H, d, J¼5.6 Hz, H-10), 1.32
(3H, s, H-9), 1.04 (3H, s, H-7); 13C NMR d 142.8 (C-13),
113.4 (C-14), 75.6 (C-8), 69.8 (C-1), 66.6 (C-11), 47.7
(C-10), 47.5 (C-12), 32.4 (C-4), 31.8 (C-6), 31.6 (C-2), 27.5
(C-9), 27.5 (C-7), 22.8 (C-5), 22.7 (C-3), 22.4 (C-15); EIMS
70 eV m/z (rel. int.): 238 (Mþ, 0.2), 220 (0.2), 205 (1), 183
(1), 165 (4), 147 (5), 140 (10), 139 (100), 121 (9), 108 (8),
107 (7), 105 (4), 95 (15), 93 (11), 81 (7), 67 (8), 43 (35);
HRDCIMS (NH3) m/z 239.2014 [MþH]þ (calcd for
C15H27O2 239.2011).
3.2.5. Aldehyde 12. To a solution of chromium trioxide
(652 mg, 6.52 mmol) in pyridine (1.1 mL) and dichloro-
methane (16 mL) was added dropwise a solution of 11
(197 mg, 1.07 mmol) in dichloromethane (1.2 mL), the
resulting suspension stirred for 5 min and then filtered
through a short pad of silica gel, using dichloromethane
as the eluting solvent. The organic layer was washed
successively with 10% HCl (10 mL), brine (15 mL), a
saturated solution of NaHCO3 (10 mL), and brine (15 mL),
dried over anhydrous Na2SO4 and evaporated to dryness.
The residue was purified by column chromatography (19:1
to 8:1 hexane/Et2O) to give 12 (162 mg, 83%) as a colorless
3.2.7. Isoheterocurvistone (14). A solution of chromium
trioxide (34 mg) in water (0.1 mL) was diluted with AcOH
(1.5 mL), cooled to 128C and added dropwise to a stirred
solution of 13a (32 mg, 0.134 mmol) in glacial acetic acid
(1.7 mL) at 128C. The reaction mixture was kept at room
temperature during 1 h, diluted with cold brine (6 mL) and
extracted with EtOAc (3£12 mL). The organic layer
was washed successively with brine (10 mL), a satured
solution of NaHCO3 (10 mL) and brine (12 mL), dried over
anhydrous Na2SO4 and evaporated. The residue was
purified by column chromatography (97:3 hexane/EtOAc)
to give 14 (26 mg, 82%) as a colorless oil. Compound 13b
(80 mg, 0.336 mmol) was oxidized as above to also give 14
(60 mg, 76%) as a colorless oil. IR nmax 3080, 3026, 3018,
1
oil. IR nmax 2928, 2700, 1750, 1716, 1048, 968 cm21; H
NMR d 9.83 (1H, dd, J¼3.8, 2.0 Hz, H-11), 2.74 (1H, dd,
J¼14.9, 2.0 Hz, H-10a), 2.54 (1H, dd, J¼14.9, 3.8 Hz,
H-10b), 1.38 (3H, s, Me-9), 1.07 (3H, s, Me-7); 13C NMR d
202.8 (C-11), 74.7 (C-8), 70.0 (C-1), 55.0 (C-10), 31.6
(C-6), 31.5 (C-4), 31.3 (C-2), 27.2 (C-7), 27.1 (C-9), 22.6
(C-5), 22.2 (C-3); EIMS 20 eV m/z (rel. int.): 182 (Mþ, 2),
181 (Mþ21, 1), 165 (4), 147 (6), 139 (100), 136 (23), 121
(19), 111 (10), 107 (18), 95 (28), 94 (19), 93 (36), 81 (16),
67 (13), 43 (50); HREIMS m/z 181.1228 [M21]þ (calcd for
C11H17O2 181.1229).
1
3.2.6. erythro- (13a) and threo-Isoheterocurvistol (13b).
Grignard reagent, prepared from 3-bromo-2-methylpropene
(361 mg, 2.67 mmol) and excess Mg turnings (289 mg) in
anhydrous Et2O (1.5 mL) and 1,2-dibromoethane (25 mL),
under an argon atmosphere at room temperature, was added
dropwise to a cooled (2208C) and vigorously stirred
solution of 12 (98 mg, 0.54 mmol) in THF/Et2O (1:3,
2972, 1706, 1648, 1224, 1050, 968, 900 cm21; H NMR d
4.94 (1H, br s, H-15a), 4.82 (1H, br s, H-15b), 3.18 (1H, d,
J¼14.8 Hz, H-12a), 3.16 (1H, d, J¼14.8 Hz, H-12b), 2.86
(1H, d, J¼15.4 Hz, H-10a), 2.64 (1H, d, J¼15.4 Hz,
H-10b), 1.74 (3H, br s, Me-14), 1.31 (3H, s, Me-9), 1.06
(3H, s, Me-7); 13C NMR d 207.9 (C-11), 139.4 (C-13),
115.0 (C-14), 75.2 (C-8), 69.9 (C-1), 53.9 (C-12), 52.7