Ozonolysis of alkenes and study of reactions of polyfunctional compounds: LXIV. Synthesis of ambreinolide and 8α,13-Epoxy-14,15,16-trisnorlabd-12-ene proceeding from isoabienol ozonolysis

Article abstract of DOI:10.1023/A:1012331013282

The ozonolysis of isoabienol in MeOH followed by hydrogenation of the peroxide ozonolysis products on Lindlar catalyst afforded ambreinolide that under treatment with diisobutylaluminum hydride furnished 8α, 13-epoxy-14,15,16-trisnorlabd-12-ene.

Full text of DOI:10.1023/A:1012331013282

Russian Journal of Organic Chemistry, Vol. 37, No. 2, 2001, pp. 235 237. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 2, 2001,
pp. 248 250.
Original Russian Text Copyright
2001 by Kukovinets, Zainullin, Odinokov, Kislitsyn, Roshchin, Galin, Tolstikov.
Ozonolysis of Alkenes and Study of Reactions of Polyfunctional
*
Compounds: LXIV. Synthesis of Ambreinolide
and 8 ,13-Epoxy-14,15,16-trisnorlabd-12-ene Proceeding
from Isoabienol Ozonolysis
O. S. Kukovinets, R. A. Zainullin, V. N. Odinokov, M. I. Kislitsyn, V. I. Roshchin,
F. Z. Galin, and G. A. Tolstikov
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, Bashkortostan, 450054 Russia
Received March 16, 1999
Abstract The ozonolysis of isoabienol in MeOH followed by hydrogenation of the peroxide ozonolysis
products on Lindlar catalyst afforded ambreinolide that under treatment with diisobutylaluminum hydride
furnished 8 ,13-epoxy-14,15,16-trisnorlabd-12-ene.
The ambreinolide is an important intermediate
compound in the synthesis of perfumes with amber
odor [3]. The most convenient among the known
procedures for its synthesis is oxidation with
potassium permanganate of the isoabienol. The latter
substance became available when it was found in
large amounts in the needles of an ordinary pine
into lactone II. In the course of its hydride reduction
arises an intermediate semiacetal G that under acid
treatment of the reaction mixture suffers dehydration
and transforms into ambroxide III.
The alternative path may consist in an attack of a
hydroxy group directly on the primary zwitterion A,
and then after the ozonolysis of the remaining double
bond in the intermediate compound H and the
reduction of the ozonolysis peroxy products should
form compound I. The decarbonylation of the latter
to afford lactone II is dubious under the given reac-
tion conditions.
(Pinus silvestris L.) [3]. We established that
ambreinolide (II) formed in over 90% yield at iso-
abienol (I) ozonolysis in methanol at 78 C followed
by catalytic hydrogenation of the peroxide ozonolysis
products.
The reduction of -lactone II with lithium
aluminum hydride is known [4] to afford the cor-
responding diol, ambreinolol. We developed a
method for quantitative conversion of compound II
into unsaturated epoxide 8 ,13-epoxy-14,15,16-
trisnorlabd-12-ene (III) with a strong amber odor [5].
This conversion is attained by treating lactone II with
diisobutylaluminum hydride at low temperature.
The simultaneous attack of ozone of both double
bonds in isoabienol (I) cannot explain the facts
observed since in the reaction products were neither
detected ketoaldehyde (J) nor compound (K) originat-
ing from intermolecular reaction between hydroxy
and keto groups.
The most probable reaction mechanism via inter-
mediates A G is in agreement with the published data
We presume that the most probable path of ozono-
lytic conversion of diene I into trisnorlabdane lactone
II is as follows. The prevailing initial attack of ozone
[
7]. The reduction of ambreinolide (II) by diisobutyl-
aluminum hydride accompanied with dehydration
results in high yield of 8 ,13-epoxy-14,15,16-tris-
norlabd-12-ene (III), ambroxide with a strong amber
odor.
1
3
occurs at C -methylene group, more substituted than
vinyl group (cf. [6]); as a result arises zwitterion A,
mesomeric to ion B. The subsequent addition of
MeOH to zwitterion B affords vinyl hydroperoxide C
that at further ozonization is either converted in
peracid D or in zwitterion E which is stabilized by its
own hydroxy group providing -bishydroperoxide F.
The peroxy compounds D and F are hydrogenated
EXPERIMENTAL
IR spectra were recorded on UR-20 spectrophoto-
1
meter from thin film. H NMR spectra were run on
spectrometer Tesla BS-576 (100 MHz), solvent
*
Communication LXIII see [1].
CDCl , internal reference TMS. GLC was performed
3
1
070-4280/01/3702-0235$25.00 2001 MAIK Nauka/Interperiodica

2
36
KUKOVINETS et al.
on Chrom-5 chromatograph (column 1200 4 mm,
stationary phase 5% SE-30 on Chromaton N-AW-
DMCS), oven temperature 50 300 C, carrier gas
helium. Mass spectrum was measured on MKh-1320
instrument at ionizing electrons energy 70 eV.
(8R)-14,15,16-Trisnorlabdan-13,8-olide
(II).
Through a solution of 1 g (3.4 mmol) of isoabienol
(I) in 40 ml of anhydrous MeOH was passed at 78 C
a stream of ozone-oxygen mixture (5.5 wt% of O3)
till the solution became blue. Then the reaction mix-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 2 2001

OZONOLYSIS OF ALKENES AND STUDY OF REACTIONS. LXIV.
237
1
ture was flushed with argon, warmed to 20 C, and
.1 g of Lindlar catalyst was added. Then the reaction
2.6, C H OH). IR spectrum ( , cm ): 1080, 1120,
2
5
1
0
1650. H NMR spectrum (CDCl , , ppm): 0.64
2.53 m (14H, CH, CH ), 0.78 s (3H, CH C ), 0.84
2 3
s (3H, -CH C ), 0.97 s (3H, -CH C ), 1.20 s (3H,
CH C ), 4.62 m (1H, HC = C ), 6.12 m (1H,
HC = C ). Mass spectrum, m/z (I , %): 248
[M] (30), 233 [M CH3] (1.5), 230 [M H2O]
1.2), 215 [M CH H O] (1.4), 191 [M C H ]
3
1
0
mixture was stirred under hydrogen atmosphere till
the negative test for peroxides with acid water solu-
tion of KI. The catalyst was filtered off, the filtrate
was evaporated in vacuo, and the residue crystallized.
We obtained 0.85 g (93%) of compound II, mp
4
4
3
3
8
12
13
3
1
3
12
rel
+
+
+
+
(
(
+
1
38.5 140 C (from hexane). Published data for
3
2
4
9
7), 95 [C H O]
+
(100).
ambreinolide (II) [8]: mp 140 141 C (from
6
7
1
petroleum ether). IR spectrum ( , cm ): 970, 1130,
1
REFERENCES
1
(
725. H NMR spectrum (CDCl , , ppm): 0.78 s
3
1
4
2H, H C ), 0.82 s (3H, CH C ), 0.89 s (3H,
2 3
1. Odinokov, V.N., Akhmetova, V.R., Savchenko, R.G.,
Bazunova, M.V., Paramonov, E.A., and Khali-
lov, L.M., Zh. Org. Khim., 2000, vol. 36, no. 10,
pp. 1474 1482.
1
0
4
CH C ), 0.94 s (3H, -CH C ), 1.31 2.77 m (12H,
3
3
8
CH, CH ), 1.32 s (3H, CH C ), 2.48 m (2H,
CH CO ). Mass spectrum, m/z, (I , %): 264 [M]
2
3
+
2
2
rel
+
+
(
2
4.6), 249 [M CH ] (23), 235 [M CHO] (1.3),
2. Vlad, P.F. and Koltsa, M.N., Sintez i primenenie du-
3
20 [M CO2]+ (8.8), 192 [M C H O ]
(100), 177
+
shistykh veshchestv iz labdanovykh diterpenoidov (Syn-
thesis and Application Scent Compounds), Lazur ev-
3
4
2
,
(
48), 149 (11.5), 137 (28.8).
skii, G.V., Ed., Kishinev: Shtiintsa, 1988, pp. 38 48.
8
,13-Epoxy-14,15,16-trisnorlabd-12-ene (III).
3
4
5
. Ekman, R., Sjoholm, R., and Hannus, K., Acta Chem.
Scand., B, 1977, vol. 31, no. 10, pp. 921 922.
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and Tolstikov, G.A., Zh. Org. Khim., 1993, vol. 29,
no. 1, pp. 39 43.
To a solution of 0.32 g (1.21 mmol) of ambreinolide
II in 20 ml of anhydrous ethyl ether at 70 C within
.5 h was added a solution of i-Bu AlH (1.2 ml,
0%) in 10 ml of ether. The reaction mixture was
3
7
2
poured into 300 ml of water, was added 0.7 ml of
CH COOH and 10 ml of CHCl , and the mixture was
3
3
stirred for 30 min, and again was added 50 ml of
CHCl . The organic layer was separated, washed
with saturated aqueous NaHCO , and dried on
3
3
MgSO . The drying agent was filtered off, the solvent
was distilled off. We obtained 0.3 g (99%) of com-
7. De Ninno, M.P., J. Am. Chem. Soc., 1995, vol. 117,
no. 39, pp. 9927 9928.
4
pound III mp 87 89 C, published data for ambroxide
8. Vlad, P.F., Russo, A.G., and Chan-Kuang, Fan, Zh.
Obshch. Khim., 1969, vol. 39, no. 2, pp. 451 457.
2
0
(III) [5]: mp 84 85 C (from ethanol). [ ]
5.1 (c
D
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 2 2001