5946
J. M. Castro et al. / Tetrahedron 58 (2002) 5941±5949
(1H, br s, H-14); 13C NMR d 39.72 (C-1), 18.40 (C-2), 41.89
(C-3), 33.22 (C-4), 56.07(C-5), 20.57(C-6), 44.33 (C-7),
reduced pressure to yield a residue (1.91 g, 5.25 mmol,
93%) formed by a mixture of 7a and b in a 55:45 ratio,
p
74.18 (C-8), 61.37 (C-9), 39.16 (C-10), 23.53 (C-11), 44.71p
(C-12), 161.35 (C-13), 114.70 (C-14), 167.35 (C-15), 19.09
(C-16), 23.98 (C-17), 33.36 (C-18), 21.46 (C-19), 15.40
(C-20), 50.76 (OMe) (p these signals may be interchanged);
MS m/z 304 (M12OH±Me, 0.6%), 303 (M12H2O±Me,
0.6), 289 (30412Me, 0.4), 276 (M12HCOOMe, 1), 266
(3), 243 (27612H2O±Me, 1), 205 (3), 191 (9), 177 (12),
163 (2), 149 (5), 135 (7), 123 (10), 114 (21), 109 (19), 95
(34), 82 (59), 69 (56), 55 (70), 43 (100).
1
according to the H NMR spectrum. An aliquot sample
(453 mg) of this residue was puri®ed by ¯ash chromato-
graphy (eluent: H/E 8:2) to afford pure 7a (161 mg) and
7b (131 mg).
3.4.1. Methyl 8a-formyloxy-labd-13Z-en-15-oate (7a).
Colorless crystals; mp 58.0±59.68C (hexane); [a]D
212.78 (c 1.02); IR (KBr) n 1728, 1193 (OOCH), 1705,
1241, 1171 (COOMe), 1649, 875 (CvC); 1H NMR d
0.77 (3H, s, Meb-4), 0.82 (3H, s, Me-10), 0.86 (3H, s,
Mea-4), 1.49 (3H, s, Me-8), 1.88 (3H, d, J1.4 Hz,
Me-13), 2.53 (1H, dt, J12.5, 3.3 Hz, Hb-7), 2.59±2.76
(2H, m, H-12), 3.65 (3H, s, OMe), 5.60 (1H, br s, H-14),
8.04 (1H, s, OOCH); 13C NMR d 39.36p (C-1), 18.35 (C-2),
41.80 (C-3), 33.13 (C-4), 55.52 (C-5), 20.01 (C-6), 39.32p
(C-7), 89.08 (C-8), 58.91 (C-9), 39.53 (C-10), 24.10 (C-11),
36.13 (C-12), 160.49 (C-13), 115.44 (C-14), 166.53 (C-15),
25.16 (C-16), 21.24 (C-17), 33.29 (C-18), 21.42 (C-19),
15.69 (C-20), 50.78 (OMe), 160.65 (OOCH) (p these signals
may be interchanged); MS m/z 364 (M1, 0.1%), 349
(M12Me, 0.2), 319 (M12OOCH, 12), 318 (M12HCOOH,
4), 304 (M12HCOOMe, 1), 303 (31812Me, 4), 287
(M12HCOOH±OMe, 4), 259 (31812COOMe, 4), 205
(12), 192 (21), 177 (19), 149 (11), 136 (21), 121 (23), 109
(27), 95 (39), 81 (41), 69 (55), 55 (70), 41 (100). HRMS (M1),
found 364.2615, C22H36O4 requires 364.2614.
3.3. 8a,13-Epoxy-14,15-dinorlabd-12-ene (6)
To a stirred solution of crude 4a/b (205 mg, 0.60 mmol,
55:45 ratio) in acetone (15 mL) was added a mixture of
KMnO4 (333 mg, 2.20 mmol) and anhydrous MgSO4
(290 mg) at room temperature. After stirring for 0.5 h the
reaction mixture was ®ltered over Celite and the solvent
evaporated under reduced pressure at room temperature.
The residue was solved in Et2O (20 mL) and washed with
H2O (3£10 mL). After drying the organic layer with anhy-
drous Na2SO4 and evaporation of the solvent under reduced
pressure at room temperature, a residue (164 mg) was
obtained which was composed of 5 and 6 in a 5:2 ratio,
according to the 1H NMR spectrum (GC analysis only
showed a single peak at Rt 15.08). 1H NMR data correspond-
ing to 5 (lit.22): d 0.79 (3H, s, Meb-4), 0.80 (3H, s, Me-10),
0.86 (3H, s, Mea-4), 1.15 (3H, s, Me-8), 1.87(1H, dt,
J12.2, 3.1 Hz, Hb-7), 2.13 (3H, s, Me-13), 2.57 (1H,
ddd, J17.8, 7.8, 5.7 Hz, H-12), 2.68 (1H, dt, J17.8,
7.8 Hz, H0-12).
3.4.2. Methyl 8a-formyloxy-labd-13E-en-15-oate (7b).
(hexane);
Colorless
crystals;
mp
89.1±91.08C
[a]D218.98 (c 1.06); IR (KBr) n 1716, 1184 (OOCH),
1
1716, 1218, 1148 (COOMe), 1651, 854 (CvC); H NMR
d 0.79 (3H, s, Meb-4), 0.84 (3H, s, Me-10), 0.88 (3H, s,
Mea-4), 1.50 (3H, s, Me-8), 2.17(3H, s, Me-13), 2.60 (1H,
dt, J12.1, 3.1 Hz, Hb-7), 3.69 (3H, s, OMe), 5.67 (1H, br s,
H-14), 8.01 (1H, s, OOCH); 13C NMR d 39.50 (C-1), 18.21
(C-2), 41.72 (C-3), 33.07 (C-4), 55.52 (C-5), 19.95 (C-6),
39.37(C-7), 89.00 (C-8), 58.46 (C-9), 39.50 (C-10), 23.87
(C-11), 43.62 (C-12), 160.77 (C-13), 114.83 (C-14), 167.23
(C-15), 19.02 (C-16), 21.03 (C-17), 33.22 (C-18), 21.36
(C-19), 15.60 (C-20), 50.74 (OMe), 160.28 (OOCH); MS
m/z 364 (M1, 0.5%), 349 (M12Me, 0.7), 319 (M12OOCH,
5), 318 (M12HCOOH, 4), 304 (M12HCOOMe, 1), 303
(31812Me, 7), 287 (M12HCOOH±OMe, 5), 259
(31812COOMe, 3), 205 (17), 192 (62), 177 (40), 149
(17), 137 (24), 123 (38), 109 (41), 95 (57), 81 (67), 69
(77), 55 (84), 41 (100). HRMS (M1), found 364.2606,
C22H36O4 requires 364.2614.
That residue was ¯ash chromatographied (eluent: H/E 8:2)
to yield pure 6 (107mg, 0.41 mmol, 68%) as a pale yellow
oil (lit.22); Rt 15.08; mp 34.0±36.08C (MeOH); [a]D11.28
1
(c 0.95); IR (neat) n 3054, 1683 (CvC), 1127(C±O±C); H
NMR d 0.82 (6H, s, Meb-4, Me-10), 0.88 (3H, s, Mea-4),
1.16 (3H, s, Me-8), 1.68 (3H, br s, Me-13), 1.94 (1H, dt,
J12.3, 3.2 Hz, Hb-7), 4.43 (1H, br s, H-12); 13C NMR d
39.29 (C-1), 18.56 (C-2), 41.91 (C-3), 33.14 (C-4), 56.17
(C-5), 19.74 (C-6), 41.12 (C-7), 76.17 (C-8), 52.43 (C-9),
36.66 (C-10), 18.26 (C-11), 94.54 (C-12), 147.83 (C-13),
20.43 (C-16), 20.07(C-17), 33.43 (C-18), 21.55 (C-19),
15.00 (C-20); MS m/z 263 (M111, 7%), 262 (M1, 35),
247(M 12Me, 8), 244 (7), 229 (M12Me±H2O, 16), 219
(3), 204 (4), 201 (5), 191 (42), 177 (25), 163 (5), 149 (9),
135 (16), 123 (29), 109 (73), 95 (50), 81 (55), 69 (32), 55
(40), 43 (100).
3.4. Reaction of 4a/b with FAM to give formate esters 7a
and b
3.5. 8a-Formyloxy-14,15-dinorlabdan-13-one (8)
To a stirred solution of crude 7a/7b (286 mg, 0.78 mmol,
55:45 ratio) in acetone (18 mL) was added a mixture of
KMnO4 (632 mg, 4.00 mmol) and anhydrous MgSO4
(600 mg) at room temperature. After stirring for 0.75 h the
reaction mixture was worked-up, as for compound 6, to
afford crude 8 (214 mg, 0.68 mmol, 88%). An aliquot
sample (107mg) of crude 8 was puri®ed by ¯ash chromato-
graphy (eluent: H/E 4:6) to give pure 8 (89 mg) as a color-
less solid; mp 66.0±67.48C (hexane); [a]D222.38 (c
1.01); IR (KBr) n 1722, 1198, 1165 (OOCH), 1696 (CO);
1H NMR d 0.79 (3H, s, Meb-4), 0.86 (3H, s, Me-10), 0.88
A sample (3.8 mL, 29.00 mmol) of formic acid±acetic
anhydride mixture (FAM), prepared from Ac2O and formic
acid as described in the literature,46 was slowly added for
15 min to a mixture of 4a and b (1.90 g, 5.65 mmol, 55:45
ratio) at 108C. After stirring for 48 h at room temperature,
water (50 mL) was added and the mixture extracted with
Et2O (3£50 mL). The combined organic layers were
washed with 2N HCl (50 mL), saturated aq. Na2CO3
(50 mL) and brine (50 mL). The organic phase was dried
over anhydrous Na2SO4 and the solvent evaporated under