Synthesis of drimanes from (+)-larixol

Article abstract of DOI:10.1055/s-2000-8225

The selective transformation of the side chain of larixol 1 to a functionalized one-carbon moiety leads to 6,8-diacetoxydrimenal 13, which was converted to the drimanes (-)-albrassitriol (2), (-)-drimenol (3), (-)-uvidin C (4) and (-)-epi-albrassitriol (5).

Full text of DOI:10.1055/s-2000-8225

SPECIAL TOPIC
1907
Synthesis of Drimanes from (+)-Larixol
a, b
b
a*
Béatrice M. F. Lagnel, Christophe Morin, Aede de Groot
a
Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands
b
Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité, UMR CNRS 5616 - Université Joseph Fourier - BP 53 - 38041
Grenoble, France
Fax +31 317484914; E-mail: Aede.deGroot@Bio.oc.wag-ur.nl
Received 24 July 2000
OH
OH
OH
Abstract: The selective transformation of the side chain of larixol
1
to a functionalized one-carbon moiety leads to 6,8-diacetoxydri-
menal 13, which was converted to the drimanes (-)-albrassitriol (2),
-)-drimenol (3), (-)-uvidin C (4) and (-)-epi-albrassitriol (5).
OH
(
Key words: drimane sesquiterpenoids, natural product synthesis,
+)-larixol, (-)-albrassitriol, (-)-uvidin C, (-)-epi-albrassitriol
OH
OH
(
1
2
3
OH
OH
OH
The biological activities of some drimane sesquiterpe-
noids have greatly stimulated the development of new
synthetic routes to this class of compounds, and many
syntheses of drimanes have appeared in the last twenty
O
OH
OH
1
-3
4
5
years.
The oleoresin of larch (Larix decidua, L. europea)4,5 con-
tains large amounts of the labdane diterpene larixol 1 (>10
Figure 1
weight%), which can be easily isolated from larix turpen-
tine in pure form. In view of its availability and its chem- ary alcohol with acetic anhydride in pyridine, the oxida-
5
24
19-21
ical structure, larixol seems to be a suitable starting tion of 8 with osmium tetroxide-sodium periodate
material for the synthesis of isoprenoids possessing a yielded acetoxyaldehyde 9 in one step (84%) (Scheme 1).
,4,10-trimethyldecalin skeleton. The higher functional-
4
ized drimane sesquiterpenoids are especially attractive
target molecules for syntheses starting from larixol. Since
larixol has a hydroxyl group at C-6 as a characteristic
structural element, it is particularly suited as chiral start-
ing material for the syntheses of drimanes that have a
functional group at the same position.
OH
OH
O
i
ii
OH
OH
OH
1
7
6
In this paper we report the first semisynthesis of (-)-al-
6
brassitriol (2) and the enantioselective synthesis of (-)-
7
OH
OH
OH
drimenol (3), which is an intermediate in the synthesis of
8
OH
the well-known drimanes (-)-polygodial and (-)-
iii
iv
9
warburganal (Figure 1). These drimanes have generated
considerable interest because of their potent antifeedant
OAc
8
1
0-12
OAc
OAc
and molluscicidal activities.
Moreover, (-)-uvidin C
OR
1
3-17
18
CHO
(
4)
and (-)-epi-albrassitriol (5), which exhibits
weak antiviral activity in in vitro tests against influenza
A- and myxovirus (MIC 44.4 mg/mL; dosis tolerata max-
ima 133.3 mg/mL) were prepared (Figure 1).
OAc
OAc
OAc
+
v or vi
For the conversion of larixol 1 into drimanes, first a selec-
tive oxidative degradation of the side chain has to take
place. The methodology developed for sclareol1
seemed appropriate and when applied to larixol acetate,
the diacetate 9 was obtained in high yield. Thus, the exo-
cyclic double bond of larixol 1 was selectively
OAc
OAc
OAc
9
R= Ac, 10a-10b, E/Z 2:1 (69%)
R= TBDMS, 11a-11b, E/Z 3:1
12 (20%)
9-21
Reagents and conditions: (i) oxone, CH Cl , acetone, H O, NaHCO ,
8-crown-6, 0-3 ºC, 81%; (ii) LiAlH , THF, r.t., 94%; (iii) Ac O, py-
ridine, r.t., 99%; (iv) OsO , NaIO , THF, H O, 45 ºC, 84%; (v) Ac O,
2
2
2
3
1
4
2
2
2
4
4
2
2
epoxidized to the epoxide 6, which was subsequently re-
duced to 6a-hydroxysclareol 7 with lithium aluminium
Et N, 4-DMAP, THF, reflux, 89% or (vi) TBDMSCl, NaH, THF, r.t.,
3
9
6%.
2
3
hydride. After selective protection of the (C-6)-second-
Scheme 1
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

1
908
B. M. F. Lagnel et al.
SPECIAL TOPIC
A further breakdown of the side chain of 9 can be per- For the synthesis of albrassitriol (2), we first tried to im-
formed by the oxidative degradation of the corresponding prove the selectivity of the elimination of the (C-8)-ace-
enol derivatives 10 or 11. The enol acetates 10a, 10b (ra- tate in 13 and to optimize the yield of aldehyde 14. Some
tio E/Z 2:1) and the tetraacetate 12 were prepared from 7 reaction sequences were investigated in which the leaving
with acetic anhydride in the presence of triethylamine.20 group capability of the substituent at C-6 was diminished
To avoid the formation of byproducts such as 12, it proved by protection as its t-butyldimethylsilyl derivative or by
to be more convenient to convert the acetoxyaldehyde 9 just maintaining it as an unprotected hydroxy group.
2
0,25
into its silyl enol ether
and a mixture of 11a and 11b
The secondary alcohol of 1 was first protected as the t-bu-
tyldimethylsilyl ether 16. Its epoxidation with oxone
was obtained in 96% yield (Scheme 1). Next, an ozonoly-
sis of these silyl enol ethers with dimethyl sulfide2 as
reducing agent was carried out to give aldehyde 13, as key
intermediate for the synthesis of these drimanes. The ace-
toxyaldehyde 13 underwent a regioselective elimination
of the (C-8)-acetate by heating with collidine to give a
moderate yield of 14. The diene 15 was obtained as a sec-
ond product (vide infra). The elimination of both acetates
26
22
0,25
gave the requisite epoxide 17 but now in a moderate 30%
yield, and epoxidation of the 14,-15 double bond was a
competing side reaction (29%). The reduction of the ep-
23
oxide 17 with lithium aluminium hydride furnished the
2
5
diol 18 (Scheme 4).
Because of the poor selectivity and yield of the epoxida-
tion of 16, the utility of triol 7 as starting material was in-
from aldehyde 13 could be achieved in high yield in a
more concentrated collidine solution (Scheme 2).25
vestigated as well. Exposure of 7 to osmium tetroxide and
sodium periodate1
9-21
readily afforded the acetoxyalde-
hyde 19 but also in a moderate yield (40-45%). Treat-
ment of 19 with t-butyldimethylsilyl chloride gave
unexpectedly 20 together with the silyl enol ether 21. In
both compounds, the acetate had moved to the undesired
C-6 position, thus promoting the wrong hydroxy group to
the better leaving group (Scheme 4).
CHO
OTBDMS
ii
CHO
OAc
OAc
14
OAc
i
OAc
iii
CHO
OAc
1a-11b
OH
OH
OH
1
13
1
O
i, ii
iii
OTBDMS
OTBDMS
18
15
17
OTBDMS
Reagents and conditions: (i) O , CH Cl -MeOH (3:2), -78 ºC; Me S,
3
2
2
2
OH
CHO
r.t., 78%; (ii) collidine, 200 ºC, 15 min, 41%; (iii) collidine, 200 ºC,
h 30, 77%.
1
OAc
O
OH
Scheme 2
7
+
iv
v
OH
OAc
OAc
21 (31%)
The reduction of the obtained diene aldehyde 15 with so-
19
20 (42%)
25
dium borohydride proceeded smoothly and unexpected-
ly yielded (-)-drimenol (3) in high yield. (-)-Drimenol
has been used before as a starting material in the synthesis
vi
COCH3
CHO
8
9
of (-)-polygodial and (-)-warburganal (Scheme 3).
O
18
OAc
+
vii
OH
OTBDMS
2 (46%)
OTBDMS
23 (23%)
CHO
CHO
R
2
CHO
Reagents and conditions: (i) TBDMSCl, imidazole, DMF, 60 ºC,
1%; (ii) oxone, CH Cl , acetone, H O, NaHCO , 18-crown-6, 0-3
a
9
2
2
2
3
ºC, 30%; (iii) LiAlH , THF, r.t., 68%; (iv) OsO , NaIO , THF, H O,
4
4
4
2
3
15
R= H, polygodial
R= OH, warburganal
45 ºC, 40-45%; (v) TBDMSCl, NaH, THF, r.t., 73%; (vi) TBDMSCl,
imidazole, DMF, 60 ºC, 79%; (vii) OsO , NaIO , THF, H O, 45 ºC,
4
4
2
6
9%.
Reagents and conditions: (i) NaBH , EtOH, 0 ºC to r.t., 89%.
4
Scheme 4
Scheme 3
Since the oxidation of 7 with osmium tetroxide gave a low
yield of 19, we decided to also test compound 18, obtained
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Drimanes from (+)-Larixol
1909
after conversion of 7 into its silyl enol ether. However,
OR
OTBDMS
treatment of 18 with osmium tetroxide1
9-21
gave com-
CHO
OAc
OAc
i
OH
iii
OH
iv
pound 22 as the major compound in a moderate yield to-
gether with 23 (Scheme 4). It became clear that seemingly
small changes of the functional groups in the molecule at
the C-6 position could have a profound and unpredictable
influence on the course and results of the reactions.
OH
O
13
28
R= H, 26
R= TBDMS, 27
ii
Therefore the moderate yield of 14 was accepted and its
conversion into (-)-albrassitriol (2) was investigated.
OR
OH
OH
2
5
Treatment of 14 with sodium borohydride afforded the
2
7
allylic alcohol 24, which was epoxidized to the a-ep-
oxide 25 in 95% yield. This epoxide was then converted
into (-)-albrassitriol (2) by treatment with lithium
O
vi
vii
O
OH
OH
31
4
2
8,29
diethylamide
(Scheme 5).
R= TBDMS, 29
R= H, 30
v
Reagents and conditions: (i) LiAlH , THF, r.t., 70%; (ii) TBDMSCl,
4
OH
CHO
imidazole, r.t., 1h, 94%; (iii) PCC, CH Cl , 3Å molecular sieves,
2 2
AcOH, r.t., 1h, 78%; (iv) SOCl , pyridine, 0 ºC to r.t., 71%; (v) TB-
2
AF, r.t., 60%, (vi) Dibal-H, dry THF, N , 0 ºC to r.t., 1h, 94%; (vii)
2
i
ii
m-CPBA, CH Cl , r.t., 1h, 95%.
2
2
Scheme 6
OAc
OAc
14
24
OH
O
OH
OH
An efficient route to (-)-epi-albrassitriol (5) has been de-
veloped via acetylation of 30 with acetic anhydride in
pyridine24 to afford compound 32 (Scheme 7). For the
synthesis of (-)-epi-albrassitriol (5), our plan was to intro-
duce the 9-a hydroxy group before the reduction of the ke-
tone at the C-6 position to the corresponding 6b-hydroxyl.
iii
OAc
OH
25
2
Exposure of 32 to DBU readily afforded the known di-
enone 33, which was submitted to osmylation. This re-
Reagents and conditions:(i) NaBH , EtOH, -8 ºC to r.t., 94%; (ii) m-
4
34
CPBA, CH Cl , r.t., 95%; (iii) Et NLi, anhyd Et O, 0 ºC to r.t., N ,
2
2
2
2
2
action proceeded smoothly, and as expected at the most
nucleophilic 9,-11 double bond from the less hindered a
side. The stereochemistry at C-9 is supported by the shift
of the proton H-5 (d 2.9) in comparison with the corre-
sponding signal for the enone 32. This downfield shift can
be attributed to the cis-1,3-diaxial interaction of H-5 with
the free C-9 hydroxyl group. Reduction of 34 with Dibal-
H afforded the 6b-alcohol 5 again arising from hydride
delivery from the least hindered a face of the carbonyl
group (Scheme 7).
4
3%.
Scheme 5
Another important and attractive target to synthesize is
-)-uvidin C (4), which was obtained from the 6,8-diacet-
oxydrimenal 13 in seven steps. Reduction of 13 with lith-
(
3
4
2
3
ium aluminium hydride gave the triol 26 as the only
product. After monoprotection of 26 with t-butyldimeth-
ylsilyl chloride, the oxidation with PCC
2
6
30,31
yielded ke-
tone 28, which underwent a regioselective elimination of
In conclusion, the utility of larixol as natural chiral start-
ing material3
5-37
for the synthesis of highly functionalized
the (C-8)-alcohol by treatment with thionyl chloride in
3
2
pyridine to give the expected unsaturated ketone 29 in a
slow reaction. Compound 30 could be obtained in pure
form after deprotection of the primary alcohol in 60%
drimane sesquiterpenoids was demonstrated by the first
semisynthesis of (-)-albrassitriol (2) and (-)-epi-albras-
sitriol (5) and by its conversion into (-)-drimenol (3) and
3
3
yield, by stirring the mixture with TBAF (Scheme 6).
(
-)-uvidin C (4).
Reduction of 30 with Dibal-H34 gave the 6b-alcohol 31
(
J5-6 = 4.2 Hz) in high yield. The high stereoselectivity in
Optical rotations were determined on a Perkin-Elmer 241 polari-
the reduction of the oxo function can be readily explained
meter with a 1 dm microcell, using CHCl as solvent (concentration
3
by the steric hindrance of the b-face of this ketone by the
expressed in g/ 100 mL). IR spectra were obtained on a BIORAD
1
axial methyl substituent, favouring hydride delivery from FTS-7 spectrometer with samples between NaCl. H NMR spectra
the bottom face of the carbonyl group. Treatment with m- were recorded on a Bruker AC 200 spectrometer. Chemical shifts
2
7
are given in ppm values with CHCl as reference (set at d 7.24 ppm),
chloroperbenzoic acid in dichloromethane afforded ex-
3
unless otherwise stated, and coupling constants in Hz. Abbrevia-
tions: s, singlet, d, doublet, t, triplet, dd, doublet of doublets, dt, dou-
clusively the b-epoxide, thus completing the synthesis of
(
-)-uvidin C (4) (Scheme 6).
1
3
blet of triplets, m, multiplet. C NMR spectra were measured in
CDCl or C D and recorded on a Bruker AC 200. Mass spectra
3
6
6
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

1
910
B. M. F. Lagnel et al.
SPECIAL TOPIC
1
3
C NMR (CDCl , 50 MHz): d = 145.6 (s), 145.2 (d), 111.7 (t),
OH
OAc
3
1
08.4 (t), 73.6 (s), 71.7 (d), 60.6 (d), 56.5 (d), 49.2 (t), 43.8 (t), 41.3
(
1
t), 39.6 (s), 39.3 (t), 36.7 (q), 33.9 (s), 27.8 (q), 22.4 (q), 19.1 (t),
8.0 (t), 16.1 (q).
i
ii
Epoxidation of (1S,4S,4aR,8aS)-4-[(3S)-3-Hydroxy-3-methyl-
pent-4-enyl]-4a,8,8-trimethyl-3-methylenedecahydronaphtha-
len-1-ol (1)
O
O
O
30
32
33
OH
OH
OH
OH
To a stirred solution of larixol 1 (6.08 g, 19.85 mmol) in CH Cl
2
2
(100 mL) at 0-3 °C were added acetone (100 mL), H O (100 mL),
2
1
8-crown-6 (605 mg), NaHCO (24.2 g) and a solution of oxone (18
3
g in 100 mL of H O). The mixture was stirred for 2.5 h, and sat.
2
iii
iv
NaHCO was added. The mixture was extracted with EtOAc/Et O
3
2
(
2¥). The combined organic solutions were dried (MgSO ) and con-
O
OH
4
34
5
centrated to yield the crude product (8.93 g) as a yellow oil. The oil
was purified by chromatography over silica gel (eluent: petroleum
ether-EtOAc 1:1) to afford white crystals of 6 (5.19 g, 81%); mp
100 °C.
Reagents and conditions: (i) Ac O, pyridine, r.t., 85%; (ii) DBU, an-
2
hyd benzene, reflux, 66%; (iii) OsO , pyridine, r.t., N , 88%; (iv) Di-
4
2
bal-H, anhyd THF, N , 0 ºC to r.t., 1h, 83%.
2
25
[
a]D +19.5 (c = 0.19, CHCl3).
Scheme 7
+
HRMS: m/z calcd for C H O (M ) 322.2508 and 304.2402 for
2
0
34
3
+
(
M-H O) , found 304.2403.
2
-
1
IR (film): n = 3417, 2931, 2867, 1649, 1218, 921 cm .
1
H NMR (CDCl , 200 MHz): d = 5.8 (X part of an ABX system,
(
MS) data were obtained on an AEI MS 902 spectrometer. Melting
3
Jcis = 10.8 Hz, J = 17.4 Hz, 1H), 5.2, 5.0 (AB part of an ABX sys-
tem, Jcis = 10.8 Hz, Jtrans = 17.4 Hz, J = 1.4 Hz, 2H), 3.9 (dt, J = 4.8
Hz, 1H), 2.8 (dd, J = 4.2 Hz, 1H), 2.5 (d, J = 4.2 Hz, 1H), 2.1-0.77
(
1
points (mp) were determined in capillary tubes. For analytical TLC,
Merck silica gel 60G in 0.25 mm-thick layers was used. Chromato-
graphic separations were carried out on Merck silica gel 60 using
petroleum ether (boiling range 40-60 °C)-EtOAc mixtures of in-
creasing polarity. Ozonization reactions were carried out with a
mixture of ozone-oxygen provided by an oxygen-feed Fischer ap-
paratus. All solvents were purified and dried by standard techniques
just before use. Aqueous solutions were usually extracted with an
organic solvent. The combined organic extracts were washed with
trans
m), 1.2 (s, 3H), 1.15 (s, 3H), 1.0 (s, 3H), 0.8 (s, 3H).
3
C NMR (CDCl , 50 MHz): d = 144.9 (d), 111.7 (t), 73.5 (s), 69.8
3
(d), 60.3 (d), 57.7 (s), 53.6 (d), 51.2 (t), 46.9 (t), 43.7 (t), 43.6 (t),
40.2 (s), 39.1 (t), 36.6 (q), 33.7 (s), 28.1 (q), 22.2 (q), 18.3 (t), 15.9
(t), 15.7 (q).
brine and dried (MgSO ), and the volatiles were evaporated under
4
(1S,3R,4R,4aR,8aS)-4-[(3S)-3-Hydroxy-3-methylpent-4-enyl]-
reduced pressure. Compound 1 was isolated from the oleoresin of
3
,4a,8,8-tetramethyldecahydronaphthalene-1,3-diol (7)
Larix decidua.4
To a stirred solution of LiAlH (694 mg, 18.26 mmol, 2 equiv) in an-
4
hyd THF (28 mL) under N was added 6 (2.94 g, 9.12 mmol). After
2
(
4
1S,4S,4aR,8aS)-4-[(3S)-3-Hydroxy-3-methylpent-4-enyl]-
a,8,8-trimethyl-3-methylenedecahydronaphthalen-1-ol (1)
stirring overnight, the excess of LiAlH was quenched with Et O
4
2
and a solution of 1M HCl. The mixture was then extracted with
The oleoresin of Larix decidua (25 g) was dissolved in hexane (100
mL) and a solution of 1M KOH (50 mL) was added. A precipitate
appeared and the mixture was filtered on Celite. The organic solu-
tion was separated and washed with a solution of 1N NaOH. The or-
EtOAc/Et O. The organic solution was washed with brine, dried
2
(MgSO ) and concentrated to afford white crystals of 7 (3.0 g),
4
which were recrystallized from EtOAc/CH Cl (2.77 g, 94%); mp
2
2
176 °C.
ganic solution was dried (MgSO ) and concentrated to yield the
4
25
[
a]D +48.9 (c = 0.09, CHCl3).
crude product as a yellow oil which was dissolved in a solution of
+
0
3
.1N KOH in EtOH (300 mL). The solution was heated at reflux for
h. After cooling, the solution was concentrated to 150 mL. Water
HRMS: m/z calcd for C20H O (M ) 324.2664, found 291.2325.
36 3
IR (film): n = 3355, 2939, 914 cm-1.
was added (100 mL) and the solution was concentrated to yield an
1
H NMR (CDCl +DMSO, 200 MHz): d = 5.8 (X part of an ABX
3
insoluble product, which was dissolved in Et O (100 mL). The
2
system, Jcis = 10.6 Hz, Jtrans = 17.4 Hz, 1H), 5.1, 5.0 (AB part of an
ABX system, Jcis = 10.6 Hz, Jtrans = 17.4 Hz, J = 2.0 Hz, 2H), 3.7 (dt,
J = 10.8 Hz, J = 3.8 Hz, 1H), 2.0 (dd, J = 12.0 Hz, J = 3.8 Hz, 1H),
1.65-0.7 (m), 1.2 (s, 3H), 1.1 (s, 3H), 1.0 (s, 3H), 0.9 (s, 3H), 0.7 (s,
3H).
aqueous solution was extracted with Et O and the combined organic
2
solutions were dried (MgSO ) and the solvent was evaporated. The
4
yellow oil was crystallized in cyclohexane (30 mL) to yield 1
3
8
(
°
3.47g, 14% w/w) as white crystals; mp 100 °C (lit.: 102 °C, 101
C ).
2
4
1
3
25
C NMR (CDCl +DMSO, 50 MHz): d = 144.4 (d), 111.9 (t), 74.0
3
[
a]D +52.9 (c = 0.59, CHCl3).
(
2 ¥ s), 68.7 (d), 61.0 (2 ¥ d), 53.6 (t), 44.4 (t), 43.7 (t), 39.7 (t), 39.4
+
HRMS: m/z calcd for C H O (M ) 306.2559, found 306.2848.
2
0
34
2
(s), 36.2 (q), 33.6 (s), 29.1 (q), 25.2 (q), 21.8 (q), 18.9 (t), 18.2 (t),
16.2 (q).
-
1
IR (film): n = 3590, 1644, 925, 890 cm .
1
H NMR (CDCl , 200 MHz): d = 5.9 (X part of an ABX system,
3
1
-(1S,3R,4R,4aS,8aS)-3-Hydroxy-4-[(3S)-3-hydroxy-3-methyl-
Jcis = 10.9 Hz, J = 16.4 Hz, 1H), 5.2, 5.05 (AB part of an ABX
trans
pent-4-enyl]-3,4a,8,8-tetramethyldecahydronaphthalen-1-yl
Acetate (8)
To a solution of 7 (1.01 g, 3.1 mmol) in pyridine (4.3 mL, 30.8
system, Jcis = 10.9 Hz, Jtrans = 16.4 Hz, J = 1.3 Hz, 2H), 4.9, 4.6 (2s,
2
H), 3.8 (dt, J = 10.7 Hz, J = 5.4 Hz, 1H), 2.65 (dd, J = 5.4 Hz,
J = 10.7 Hz, 1H), 2.0 (t, J = 10.9 Hz, 1H), 1.8-0.6 (m), 1.2 (s, 3H),
.1 (s, 3H), 1.0 (s, 3H), 0.7 (s, 3H).
mmol, 9.9 equiv) was added Ac O (1.4 mL, 15.1 mmol, 4.8 equiv).
2
1
The mixture was stirred overnight and then it was diluted with wa-
ter. The mixture was extracted with CH Cl and the organic solution
2
2
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Drimanes from (+)-Larixol
1911
was dried (MgSO ) and concentrated to yield the crude product
0.97 (s, 3H); 10b: d = 7.1 (d, J = 6.8 Hz, 1H), 4.8 (dd, J = 6.8 Hz,
J = 11.2 Hz, 1H), 3.15 (d, J = 11.0 Hz, 1H), 2.1 (s, 3H), 1.7 (s, 3H),
4
(
1.58 g) as a yellow oil. The oil was purified by chromatography
over silica gel (eluent: petroleum ether-EtOAc 2:1) to afford white
1.0 (s, 3H).
crystals of 8 (1.13 g, 99%); mp 120 °C.
13
C NMR (CDCl , 50 MHz): 10a: d = 170.2 (s), 170.1 (s), 168.0 (s),
3
25
[
a]D +46.0 (c = 0.35, CH Cl).
138.1 (d), 109.8 (d), 83.5 (s), 69.9 (d), 56.95 (d), 56.3 (d), 43.6 (t),
43.2 (t), 40.1 (t), 37.8 (s), 35.8 (q), 33.3 (s), 22.8 (q), 22.7 (q), 22.2
(q), 22.1 (q), 20.8 (q), 18.0 (t), 17.0 (q); 10b: d = 170.2 (s), 170.1
3
+
HRMS: m/z calcd for C H O (M ) 336.2770 and 348.2664 for
2
2
38
4
+
(
M-18) , found 348.2655.
(
(
s), 168.1 (s), 137.0 (d), 109.8 (d), 83.9 (s), 70.1 (d), 56.95 (d), 52.1
d), 43.6 (t), 43.2 (t), 40.5 (t), 38.3 (s), 35.8 (q), 33.3 (s), 22.8 (q),
-
1
IR (film): n = 3499, 2929, 1724, 1711, 1369, 1247, 1028, 919 cm .
1
22.7 (q), 22.2(q), 22.1 (q), 20.8 (q), 18.0 (t), 16.6 (q).
H NMR (CDCl , 200 MHz): d = 5.8 (X part of an ABX system,
3
Jcis = 10.6 Hz, Jtrans = 17.2 Hz, 1H), 5.2, 5.0 (AB part of an ABX sys-
tem, Jcis = 10.8 Hz, Jtrans = 17.2 Hz, J = 1.2 Hz, 2H), 5.0 (dt, J = 4.0
Hz, 1H), 2.1-0.8 (m), 2.0 (s, 3H), 1.2 (s, 2 ¥ 3H), 1.0 (s, 3H), 0.83
25
12: oil, [a]D
+64 (c = 0.05, CHCl3).
+
HRMS: m/z calcd for C H O (M ) 454.2567, 394.2355 and
2
4
38
8
3
34.2144, found 394.2146, 394.2361.
(
s, 3H), 0.8 (s, 3H).
-
1
1
3
IR (film): n = 1770, 1725, 1250 cm .
C NMR (CDCl , 50 MHz): d = 170.2 (s), 145.1 (d), 112.0 (t), 74.3
3
1
(
s), 74.1 (s), 70.9 (d), 60.9 (d), 58.4 (d), 50.0 (t), 44.2 (t), 43.5 (t),
H NMR (CDCl , 200 MHz): d = 6.9 (t, J = 6.2 Hz, 1H), 5.05 (dt,
3
3
9.7 (s), 39.5 (t), 36.1 (q), 33.3 (s), 29.1 (q), 25.7 (q), 22.0 (q), 21.9
J = 11.2 Hz, J = 4.0 Hz, 1H), 2.5 (dd, J = 12.0 Hz, J = 4.0 Hz, 1H),
(
q), 19.0 (t), 18.05 (t), 16.2 (q).
2.1 (s, 3H), 2.08 (s, 3H), 2.06 (s, 3H), 1.9 (s, 3H), 1.4 (s, 3H), 0.9 (s,
3
H), 0.8 (s, 3H), 0.7 (s, 3H).
(
1S,3R,4R,8aS)-4-(Acetyloxy)-2,5,5,8a-tetramethyl-1-(2-oxo-
ethyl)decahydronaphthalen-1-yl Acetate (9)
To a solution of 8 (630 mg, 1.72 mmol) in THF (51 mL) and H O
(1S,3R,4R,8aS)-3-(Acetyloxy)-4-{(E/Z)-2-[[tert-butyl(dimeth-
yl)silyl]oxy)ethenyl}-3,4a,8,8-tetramethyldecahydronaphtha-
len-1-yl Acetate (11a and 11b)
2
(
13 mL) were added NaIO (13.9 g, 65 mmol, 37.8 equiv) and OsO4
4
(
0.26 mL of a 2.5% wt solution in t-BuOH). The mixture was stirred
To a solution of 9 (900 mg, 2.55 mmol) in anhyd THF (25 mL) at
at 45 °C overnight. Then it was cooled and diluted with EtOAc. The
0-3 °C under N were added TBDMSCl (461 mg, 3.06 mmol, 1.2
2
organic solution was washed with aq Na SO , dried (MgSO ) and
equiv) and NaH (477 mg of 60% reagent in mineral oil, 19.9 mmol,
7.8 equiv). The mixture was allowed to warm to r.t. and stirred for
4 h. Then it was filtered through silica gel (eluent: THF) and the sol-
vent was evaporated to give a mixture of 11a and 11b (1.1 g, 96%,
E/Z 3:1) as an oil, which was not further purified.
2
3
4
concentrated, to yield the crude product (850 mg) as an orange oil.
The oil was chromatographed on silica gel (eluent: petroleum
ether-EtOAc acetate 3:2) to afford 9 (510 mg, 84%) as white crys-
tals; mp 100-110 °C.
25
25
[
a]D +37.4 (c = 1.47, CHCl3).
11a and 11b: [a]D +34.8 (c = 0.135, CHCl3).
+
+
+
HRMS: m/z calcd for C H O (M ) 337.2015 for (M-15) , found
HRMS: m/z calcd for C H O (M ) 450.3345, found 346.2691.
2
0
32
5
27 46
5
3
37.2017.
IR (film): n = 2961, 1730, 1661, 1365, 1244, 839 cm-1.
1
H NMR (C D , 200 MHz): d = 9.4 (t, J = 1.8 Hz, 1H), 5.2 (dt,
J = 11.2 Hz, J = 3.8 Hz, 1H), 3.15 (dd, J = 12.2 Hz, J = 4.0 Hz, 1H),
.15-0.5 (m), 1.62 (s, 3H), 1.6 (s, 3H), 1.4 (s, 3H), 1.0 (s, 3H), 0.8
1
6
6
H NMR (C D , 200 MHz): signals assigned to 11a d = 6.25 (d,
6
6
J = 11.6 Hz, 1H), 5.3 (dt, J = 10.8 Hz, J = 4.4 Hz, 1H), 5.0 (t,
J = 11.0 Hz, 1H), 2.8 (dd, J = 12.2 Hz, J = 4.2 Hz, 1H), 2.4 (t,
J = 10.8 Hz, 1H), 2.38 (d, J = 10.8 Hz, 1H), 2.1-0.0 (m), 1.7 (s,
3H), 1.65 (s, 3H), 1.5 (s, 3H), 1.1 (s, 3H), 0.95 (s, 3 ¥ 3H), 0.9 (s,
3H), 0.7 (s, 3H), 0.1 (s, 2 ¥ 3H).
2
(
s, 3H), 0.5 (s, 3H).
1
3
C NMR (C D , 50 MHz): d = 199.9 (d), 169.1 (s), 168.6 (s), 83.8
s), 69.2 (d), 57.4 (d), 52.0 (d), 45.4 (t), 43.0 (t), 40.1 (t), 39.3 (t),
8.2 (s), 35.8 (q), 33.0 (s), 21.8 (q), 21.7 (q), 21.1 (q), 21.0 (q), 17.8
6
6
(
3
13
C NMR (C D , 50 MHz): d = 169.1 (2 ¥ s), 143.3 (d), 106.5 (d),
4.0 (s), 69.8 (d), 57.1 (d), 56.0 (d), 44.0 (t), 43.4 (t), 41.1 (t), 37.9
6
6
(
t), 16.5 (q).
8
(
(
s), 35.9 (q), 33.2 (s), 25.5 (3 ¥ q), 22.8 (q), 22.3 (q), 22.0 (q), 21.1
q), 18.1 (t), 16.8 (q), -5.3 (2 ¥ q).
(
3
1S,3R,4R,8aS)-4-(Acetyloxy)-4-[(E/Z)-2-(acetyloxy)ethenyl]-
,4a,8,8-tetramethyldecahydronaphthalen-1-yl Acetate (10a
and 10b)
(
1S,3R,4R,4aS,8aS)-3-(Acetyloxy)-4-formyl-3,4a,8,8-tetrameth-
To a stirred solution of 9 (40 mg, 0.11mmol) in THF (0.6 mL) were
added Et N (55 mL, 0.4 mmol, 3.6 equiv), Ac O (77 mL, 0.82 mmol,
yldecahydronaphthalen-1-yl Acetate (13)
3
2
To a stirred solution of 11a and 11b (30 mg, 0.07 mmol) in anhyd
CH Cl -MeOH (3:2) (2 mL) was slowly added an O / O mixture
for 10 min at -78 °C. Then, Me S (0.9 mL) was added and the mix-
ture was stirred overnight at r.t. The solvent was evaporated afford-
ing the crude product (30 mg) as an oil. The oil was purified by
chromatography over silica gel (eluent: petroleum ether-ethyl-
acetate 3:1) to afford 13 (18 mg, 78%); mp 105 °C.
7
.45 equiv) and 4-DMAP (1 mg). The mixture was refluxed for 1
2
2
3
2
day under N . Then, the solvent was evaporated and the residue was
dissolved in Et O. The organic solution was washed with sat.
2
2
2
NaHCO and H O, dried (MgSO ) and concentrated to yield the
3
2
4
crude product (60 mg) as a yellow oil. The oil was purified by chro-
matography over silica gel (eluent: petroleum ether-EtOAc 6:1) to
afford a mixture of 10a and 10b (30 mg, 69%, E/Z 2:1) and 12 (10
mg, 20%).
[
a
]
2
5
+
5
3
.
3
(
c
=
0
.
0
7
5
,
C
H
C
l
)
.
D
3
+
2
5
HRMS: m/z calcd for C H O (M ) 338.4385, found 236.1747 and
19 30 5
2
1
0a and 10b: oil, [a]D +70 (c = 0.025, CHCl3).
52.1729.
+
HRMS: m/z calcd for C H O (M ) 394.2355, found 334.2143 and
2
2
34
6
-
1
IR (film): n = 2936, 1720, 1250 cm .
2
74.1930.
1
-
1
H NMR (C D , 200 MHz): d = 9.7 (d, J = 4.0 Hz, 1H), 5.2 (dt,
IR (film): n = 2929, 1765, 1730, 1664, 1250, 929 cm .
6
6
J = 9.6 Hz, J = 4.4 Hz, 1H), 2.6 (dd, J = 12.8 Hz, J = 4.4 Hz, 1H),
1
H NMR (CDCl , 200 MHz): signals assigned to 10a and 10b
3
2
3
.45 (d, J = 4 Hz, 1H), 2.0 (t, J = 9.6 Hz, 1H), 1.9-0.5 (m), 1.7 (s,
H), 1.6 (s, 2 ¥ 3H), 0.93 (s, 3H), 0.9 (s, 3H), 0.8 (s, 3H).
d = 5.1 (dt, 1H), 2.55 (dd, 1H), 2.0 (s, 3H), 1.4 (s, 3H), 0.94 (s, 3H),
0
.8 (s, 3H); 10a: d = 7.0 (d, J = 12.2 Hz, 1H), 5.3 (t, J = 11.2 Hz,
J = 12.2 Hz, 1H), 2.3 (d, J = 11.0 Hz, 1H), 2.06 (s, 3H), 1.9 (s, 3H),
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

1
912
B. M. F. Lagnel et al.
SPECIAL TOPIC
1
3
C NMR (C D , 50 MHz): d = 202.0 (d), 169.05 (2 x s), 81.9 (s),
(2S)-2-(2[(1S,4S,4aS,8aR)-4-({[tert-Butyl(dimethyl)silyl]oxy}-
5,5,8a-trimethyl-2-methylenedecahydronaphthalen-1-yl)eth-
yl]but-3-en-2-ol (16)
6
6
6
(
9.1 (d), 67.4 (d), 56.3 (d), 45.6 (t), 43.3 (t), 39.7 (t), 38.15 (s), 35.5
q), 33.0 (s), 22.9 (q), 21.8 (q), 21.7 (q), 20.95 (q), 17.6 (q), 17.6 (t).
To a stirred solution of 1 (130 mg, 0.42 mmol) in DMF (3 mL) were
added TBDMSCl (633 mg, 4.2 mmol, 10 equiv) and imidazole (572
mg, 8.4 mmol, 20 equiv). The mixture was stirred at 60 °C for 3
(
1R,4aS)-4-Formyl-3,4a,8,8-tetramethyl-1,2,4a,5,6,7,8,8a-oc-
tahydronaphthalen-1-yl Acetate (14)
A stirred solution of 13 (350 mg, 1.03 mmol) in 2,4,6-collidine (2
mL, 15 mmol, 14 equiv) was heated at 200 °C for 15 min. After
days, and sat. NaHCO was added. The mixture was extracted with
3
Et O. The organic solution was washed with brine, dried (MgSO )
2
4
cooling, the mixture was diluted with Et O. The organic solution
and concentrated to yield the crude product which was purified by
chromatography over silica gel (eluent: petroleum ether-EtOAc
4:1) to give 16 (160 mg, 91%) as white crystals.
IR (film): n = 3400, 2951, 1476, 1395, 1388, 834 cm-1.
2
was washed with 1M HCl and brine, dried (MgSO ) and the solvent
4
removed in vacuo to afford the crude product (160 mg) as a yellow
oil. The oil was purified by chromatography over silica gel (eluent:
petroleum ether-EtOAc 1:1) to afford 14 (120 mg, 41%) as an oil.
1
H NMR (CDCl , 200 MHz): d = 5.8 (X part of an ABX system,
3
[
a
]
2
5
+
8
0
(
c
=
0
.
0
0
5
,
C
H
C
l
)
.
D
3
Jcis = 10.8 Hz, Jtrans = 17.4 Hz, 1H), 5.05, 5.0 (AB part of an ABX
system, Jcis = 10.8 Hz, Jtrans = 17.4 Hz, J = 1.2 Hz, 2H), 4.7, 4.4 (2s,
+
HRMS: m/z calcd for C H O (M ) 278.1882, found 249.1848 and
1
7
26
3
2
H), 4.4 (s, 1H), 3.8 (dt, J = 10.4 Hz, J = 5.6 Hz, 1H), 2.5 (dd,
J = 4.8 Hz, J = 12.4 Hz, 1H), 1.9 (t, J = 11.2 Hz, 1H), 1.6-0.1 (m),
.15 (s, 3H), 1.0 (s, 3H), 0.88 (s, 3 ¥ 3H), 0.7 (s, 3H), 0.6 (s, 3H),
0.06 (s, 2 ¥ 3H).
2
34.1616.
-
1
IR (film): n = 2931, 1780, 1720, 1590, 1365, 1244 cm .
1
1
H NMR (C D , 200 MHz): d = 9.8 (s, 1H), 5.3 (m, 1H), 2.4 (dd,
6
6
J = 19.0 Hz, J = 6.4 Hz, 1H), 1.9-0.7 (m), 1.7 (s, 3H), 1.4 (s, 3H),
1
1
3
C NMR (CDCl , 50 MHz): d = 146.1 (s), 145.1 (d), 111.6 (t),
3
.2 (s, 3H), 1.1 (s, 3H), 0.9 (s, 3H).
1
08.0 (t), 73.6 (s), 72.6 (d), 60.0 (d), 56.5 (d), 49.7 (t), 44.1 (t), 41.3
1
3
C NMR (C D , 50 MHz): d = 190.7 (d), 169.3 (s), 147.7 (s), 142.9
(t), 39.6 (t), 39.4 (s), 36.5 (q), 33.6 (s), 27.7 (q), 26.1 (3 ¥ q), 22.3
(q), 19.0 (t), 18.1 (s), 17.9 (t), 16.1 (q), -3.6 (2 ¥ q).
6
6
(
s), 69.2 (d), 53.2 (d), 42.9 (t), 42.3 (t), 40.1 (s), 36.0 (q, t), 33.1 (s),
2
2.1 (q), 21.15 (q), 21.0 (q), 18.6 (t), 17.7 (q).
Epoxidation of (2S)-2-(2[(1S,4S,4aS,8aR)-4-{[tert-butyl(dime-
thyl)silyl]oxy}-5,5,8a-trimethyl-2-methylenedecahydronaph-
thalen-1-yl)-ethyl]but-3-en-2-ol (16)
(
4aS,8aS)-2,5,5,8a-Tetramethyl-4a,5,6,7,8,8a-hexahydronaph-
thalene-1-carbaldehyde (15)
A stirred solution of 13 (60 mg, 0.18 mmol) in 2,4,6-collidine (1
mL, 7.6 mmol, 42 equiv) was heated at 200 °C for 1.5 h. After cool-
To a stirred solution of 16 (160 mg, 0.38 mmol), in CH Cl (5 mL)
2
2
at 0-3°C were added acetone (5 mL), H O (5 mL), 18-crown-6 (12
2
ing, the mixture was diluted with Et O. The organic solution was
mg), NaHCO (463 mg) and a solution of oxone (627 mg in 3.5 mL
2
3
washed with 1M HCl and brine, dried (MgSO ) and the solvent re-
of H O). The mixture was stirred for 1.5 h, and sat. NaHCO was
4
2
3
moved in vacuo to afford the crude product (70 mg) as a yellow oil.
The oil was chromatographed on silica gel (eluent: petroleum
ether-EtOAc 8:1) to give 15 (30 mg, 77%) as a yellow oil.
added. The mixture was extracted with EtOAc/ Et O. The organic
2
solution was dried (MgSO ) and concentrated to yield the crude
4
product (100 mg) as a yellow oil, which was purified by chromatog-
-
1
raphy over silica gel (eluent: petroleum ether-EtOAc 1:1) to afford
IR (film): n = 3011, 2954, 2873, 1730, 1680, 1244, 757 cm .
2
5
white crystals of 17 (50 mg, 30%), mp 110 °C. [a] + 22.7 (c =
D
1
H NMR (C D , 200 MHz): d = 10.0 (s, 1H), 5.9 (dd, J = 9.6 Hz,
6
6
0.075, CHCl ).
3
J = 3.2 Hz, 1H), 5.6 (dd, J = 9.4 Hz, J = 3.0 Hz, 1H), 1.9 (t, J = 3.0
Hz, 1H), 1.7-0.75 (m), 1.7 (s, 3H), 1.1 (s, 3H), 0.8 (s, 3H), 0.8 (s,
-
1
IR (film): n = 3463, 2967, 2851, 1470, 1391, 1254, 1084, 879 cm .
1
3
H).
H NMR (CDCl , 200 MHz): d = 5.8 (X part of an ABX system,
3
1
3
Jcis = 10.6 Hz, J = 17.2 Hz, 1H), 5.1, 5.0 (AB part of an ABX sys-
C NMR (C D , 50 MHz): d = 190.8 (d), 144.2 (s), 142.9 (s), 136.5
trans
6
6
tem, Jcis = 10.6 Hz, Jtrans = 17.2 Hz, J = 1.4 Hz, 2H), 4.0 (dt, J = 10.8
Hz, J = 4.6 Hz, 1H), 2.8 (dd, J = 2.0 Hz, J = 4.0 Hz, 1H), 2.5 (d,
J = 4.2 Hz, 1H), 2.0 (t, J = 9.4 Hz, 1H), 1.9-0.04 (m), 1.2 (s, 3H),
(
d), 130.2 (d), 52.6 (d), 40.7 (t), 39.1 (s), 35.1 (t), 32.4 (q), 31.9 (s),
2
2.45 (2 ¥ q), 18.8 (t), 15.8 (q).
1
.1 (s, 3H), 1.0 (s, 3H), 0.9 (s, 3 ¥ 3H), 0.8 (s, 3H), -0.06 (s, 2 ¥ 3H).
(
-)-Drimenol (3)
13C NMR (CDCl
, 50 MHz): d = 144.9 (d), 111.7 (t), 73.6 (s), 70.5
3
To a stirred solution of 15 (10 mg, 0.046 mmol) in EtOH (0.4 mL)
was added NaBH (3 mg, 0.082mmol, 1.8 equiv) at -8 °C. After 15
(d), 59.8 (d), 57.8 (s), 53.5 (d), 51.2 (t), 47.3(t), 44.1 (t), 43.6 (t),
40.0 (s), 39.5 (t), 36.4 (q), 33.5 (s), 28.1 (q), 26.0 (3 ¥ q), 22.1 (q),
18.2 (t), 18.2 (s), 15.9 (q, t), -3.6 (q), -4.0 (q).
4
min, the mixture was stirred at r.t. for an additional 2 h, diluted with
H O and extracted with Et O. The organic solution was washed
2
2
with H O and brine, dried (MgSO ) and the solvent removed to af-
2
4
ford the crude product (10 mg) as an oil. The oil was purified by
(1R,2R,4S,4aS,8aR)-4-{[tert-Butyl(dimethyl)silyl]oxy}-1-[(3S)-
3-hydroxy-3-methylpent-4-enyl]-2,5,5,8a-tetramethyldecahy-
dronaphthalen-2-ol (18)
chromatography over silica gel (eluent: petroleum ether-EtOAc
7
8
9
:1) to afford (3) (9 mg, 89%) as white crystals; mp 98 °C (lit.: 96-
7 °C).
To a stirred solution of LiAlH (129 mg, 3.4 mmol, 2 equiv) in an-
4
+
hyd THF (16 mL) under N was added 17 (740 mg, 1.7 mmol). After
HRMS: m/z calcd for C H O (M ) 222.1984, found 204.1513.
2
1
5
26
stirring overnight, the excess of LiAlH was quenched with Et O
4
2
-
1
IR (film): n = 3400, 2929, 1715, 1154 cm .
and a solution of 1M HCl and the mixture was extracted with
EtOAc/ Et O. The organic solution was washed with brine, dried
(MgSO ) and concentrated to afford the crude product (700 mg) as
1
H NMR (CDCl , 200 MHz): d = 5.8 (m, 1H), 4.2 (m, J = 11.6 Hz,
H), 2.1-0.7 (m), 1.8 (s, 3H), 0.9 (s, 3H), 0.85 (s, 3H), 0.8 (s, 3H).
2
3
2
4
white crystals. The crude product was purified by chromatography
over silica gel (eluent: petroleum ether-EtOAc 4:1) to afford white
crystals of 18 (510 mg, 68%); mp 160-162 °C.
1
3
C NMR (CDCl , 50 MHz): d = 140.0 (s), 129.3 (d), 58.0 (t), 55.2
d), 53.0 (d), 41.0 (t), 38.6 (t), 38.2 (s), 35.2 (t), 32.9 (s), 32.5 (q),
2.1 (q), 22.8 (q), 18.9 (t), 16.5 (q).
3
(
3
2
5
[
a]D +49.1 (c = 0.11, CHCl3).
+
HRMS: m/z calcd for C H O Si (M ) 438.3424, found 363.2716.
2
6
50
3
-
1
IR (film): n = 3437, 2957, 1724, 1454, 945, 779 cm .
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Drimanes from (+)-Larixol
1913
1
13
H NMR (CDCl , 200 MHz): d = 5.9 (X part of an ABX system,
C NMR (C D , 50 MHz): d = 169.2 (s), 143.9 (d), 106.3 (d), 70.5
3
6
6
Jcis = 10.8 Hz, J = 17,4 Hz, 1H), 5.1, 5.0 (AB part of an ABX sys-
(s), 70.4 (d), 60.8 (d), 58.3 (d), 48.7 (t), 43.5 (t), 40.9 (t), 37.9 (s),
36.2 (q), 33.3 (s), 26.0 (q), 25.6 (3 ¥ q), 22.0 (q), 21.2 (q), 18.3 (t),
16.5 (q), -5.4 (2 ¥ q).
trans
tem, Jcis = 10.6 Hz, Jtrans = 17.2 Hz, J = 1.2 Hz, 2H), 3.9 (dt, J = 10.4
Hz, J = 3.6 Hz, 1H), 2.0 (dd, J = 12.0 Hz, J = 3.4 Hz, 1H), 1.7-0.07
(
0
1
m), 1.3 (s, 3H), 1.2 (s, 3H), 1.1 (s, 3H), 0.93 (s, 3H), 0.9 (s, 3 ¥ 3H),
.8 (s, 3H), 0.1 (2s, 2 ¥ 3H).
(1R,2R,4S,4aS,8aR)-4-{[tert-Butyl(dimethyl)silyl]oxy}-1-[(3S)-
3-hydroxy-3-methylpent-4-enyl]-2,5,5,8a-tetramethyldecahy-
dronaphthalen-2-ol (18)
To a stirred solution of 7 (189 mg, 0.58 mmol) in DMF (15 mL)
were added TBDMSCl (879 mg, 5.8 mmol, 10 equiv) and imidazole
3
C NMR (CDCl , 50 Hz): d = 144.9 (d), 112.0 (t), 74.3 (s), 74.2 (s),
3
6
(
(
9.8 (d), 61.7 (d), 60.9 (d), 54.5 (t), 44.6 (t), 44.2 (t), 40.1 (s), 39.4
t), 36.3 (q), 33.5 (s), 29.3 (q), 26.1 (3 ¥ q), 25.5 (q), 21.9 (q), 19.0
t), 18.1 (t, s), 16.4 (q), -3.5 (q), -3.9 (q).
(
1
790 mg, 11.6 mmol, 20 equiv). The mixture was stirred at 60 °C for
day, and sat. NaHCO was added. The mixture was extracted with
3
(
1R,2R,4S,4aS,8aS)-4-Hydroxy-2,5,5,8a-tetramethyl-1-(2-oxo-
Et O. The organic solution was washed with brine, dried (MgSO )
2
4
ethyl)decahydronaphthalen-2-yl Acetate (19)
To a solution of 7 (300 mg, 0.92 mmol) in THF (27 mL) and H O
(
OsO (140 mL of a 2.5% wt solution in t-BuOH). The mixture was
stirred at 45 °C overnight, and then it was cooled and diluted with
EtOAc. The organic solution was washed with aq Na SO , dried
(
an orange oil. The oil was purified by chromatography over silica
gel (eluent: petroleum ether-EtOAc 3:1) to afford 19 (129 mg,
4
and concentrated to yield the crude product. The residue was puri-
fied by chromatography over silica gel (eluent: petroleum ether-
EtOAc 1:1) to afford 18 (200 mg, 79%) as white crystals.
2
6.8 mL) were added NaIO (7.98 g, 37.3 mmol, 40.5 equiv) and
4
4
1
3
-((3aR,5S,5aS,9aR,9bR)-5-{[tert-Butyl(dimethyl)silyl]oxy}-
a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan-2-
2
3
MgSO ) and concentrated to yield the crude product (310 mg) as
4
yl)ethanone (22)
To a solution of 18 (150 mg, 0.34 mmol) in THF (10 mL) and H O
2
(2 mL) were added NaIO (2.74 g, 12.8 mmol, 37.6 equiv) and OsO
5%) as white crystals; mp 100 °C.
4
4
(
50 mL of a 2.5% wt solution in t-BuOH). The mixture was stirred
25
[
a]D -6.1 (c = 0.065, CHCl3).
at 45 °C for 5 h. Then it was cooled and diluted with EtOAc and
+
HRMS: m/z calcd for C H O (M ) 310.4284 and 232.1827, found
washed with aq Na SO . The organic solution was dried (MgSO )
1
8
30
4
2
3
4
3
04.2403 and 232.1825.
and concentrated to yield the crude product (100 mg) as a brown oil.
1
The oil was purified by chromatography over silica gel (eluent: pe-
troleum ether-EtOAc 5:1) to afford 22 (66 mg, 46%) and 23 (33
mg, 23%).
H NMR (C D , 200 MHz): d = 9.4 (m, 1H), 3.5 (dt, J = 10.8 Hz,
6
6
1
3
H), 3.0 (dd, J = 12.2 Hz, J = 4.0 Hz, 1H), 2.1-0.4 (m), 1.65 (s,
H), 1.35 (s, 3H), 1.3 (s, 3H), 1.0 (s, 3H), 0.5 (s, 3H).
+
1
3
22: oil, HRMS: m/z calcd for C24
65.2873 and 393.2825.
H
44
O
3
Si (M ) 408.3060, found
C NMR (C D , 50 MHz): d = 200.4 (d), 168.9 (s), 84.4 (s), 67.5
6
6
3
(
3
d), 59.5 (d), 52.5(d), 49.7 (t), 43.3 (t), 40.25 (t), 39.5 (t), 37.9 (s),
-
1
6.3 (q), 33.5 (s), 21.9 (2 ¥ q), 21.1 (q), 18.1 (t), 16.7 (q).
IR (film): n = 2930, 1724, 1244 cm .
1
H NMR (CDCl , 200 MHz): d = 4.4 (dd, J = 10.0 Hz, J = 2.8 Hz,
3
(
1S,3R,4R,4aR,8aS)-4-((E)-2-{[tert-Butyl(dimethyl)silyl]oxy}-
ethenyl)-3-hydroxy-3,4a,8,8-tetramethyldecahydronaphthalen-
-yl Acetate (21)
1
2
3
H), 4.0 (dt, J = 10.8 Hz, J = 4.0 Hz, 1H), 2.2 (dd, J = 12.8 Hz, 1H),
.2 (s, 3H), 2.3-0.8 (m), 1.2 (s, 3H), 1.1 (s, 3H), 1.0 (s, 3H), 0.93 (s,
¥ 3H), 0.9 (s, 3H), 0.16 (s, 3H), 0.14 (s, 3H).
1
To a solution of 19 (70 mg, 0.23 mmol) in anhyd THF (4.8 mL) un-
der N were added TBDMSCl (43 mg, 0.28 mmol, 1.2 equiv) and
NaH (62 mg of 60% reagent in mineral oil, 2.58 mmol, 11.2 equiv).
The mixture was allowed to warm to r.t. and stirred for an additional
4
1
3
C NMR (CDCl , 50 MHz): d 211.2 (s), 81.7 (s, d), 71.4 (d), 62.2
3
2
(
d), 59.6 (d), 51.4 (t), 44.7 (t), 40.7 (t), 36.5 (q), 35.6 (s), 33.9 (s),
2
-
7.5 (t), 27.2 (q), 26.5 (3 ¥ q), 23.1 (q), 21.9 (q), 18.4 (t), 16.5 (q),
3.0 (q), -3.6 (q).
h. Then it was filtered through silica gel (eluent: THF) and the sol-
+
vent was evaporated to give the crude product (80 mg) as an oil. The
oil was purified by chromatography over silica gel (eluent: petro-
leum ether-EtOAc 3:1) to afford 20 (30 mg, 42%) and 21 (31 mg,
23: oil, HRMS, m/z calcd for C H O Si (M ) 424.3009, 365.2545
24 44 4
and 393.2825, found 365.2545 and 393.2764.
IR (film): n = 2930, 1720, 1398, 1366, 1244 cm-1.
3
1%).
1
H NMR (CDCl , 200 MHz): d = 9.5 (t, J = 2.4 Hz, 1H), 3.8 (dt,
3
2
0: oil.
J = 11.0 Hz, 1H), 2.9 (dd, J = 12.4 Hz, J = 3.6 Hz, 1H), 2.4-0.7
+
HRMS: m/z calcd for C H O (M ) 310.2144, found 349.2558 and
2
(m), 1.8 (s, 3H), 1.4 (s, 3H), 1.0 (s, 3H), 0.8 (s, 3H), 0.78 (s, 4 ¥ 3H),
1
8
30
4
50.1932.
0.04 (s, 3H), 0.0 (s, 3H).
-
1
13
IR (film): n = 3595, 1072, 1024, 943 cm .
C NMR (CDCl , 50 MHz): d = 202.2 (d), 169.5 (s), 84.7 (s), 69.0
3
1
(d), 60.2 (d), 53.0 (d), 49.8 (t), 43.7 (t), 40.5 (2 ¥ t), 38.2 (s), 36.2
H NMR (C D , 200 MHz): d = 5.3 (t, J = 5.0 Hz, 1H), 5.1 (dt,
J = 11.2 Hz, J = 3.6 Hz, 1H), 2.1-0.7 (m), 1.95 (s, 3H), 1.2 (s, 3H),
6
6
(
(
q), 33.4 (s), 26.1 (3 ¥ q), 22.5 (q), 21.8 (q), 21.2 (q), 18.1 (s), 17.9
t), 17.2 (q), -3.6 (q), -4.0 (q).
0
.9 (s, 3H), 0.8 (s, 3H), 0.74 (s, 3H).
1
3
C NMR (C D , 50 MHz): d = 170.2 (s), 101.8 (d), 79.6 (s), 71.4
6
6
(
1S,4aS,8aS)-4-(Hydroxymethyl)-3,4a,8,8-tetramethyl-
(
d), 59.85 (d), 59.4 (d), 47.0 (t), 43.7 (t), 39.7 (t), 39.6 (s), 35.8 (q),
1
,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl Acetate (24)
3
2
3
3.3 (s), 30.7 (t), 25.7 (q), 22.0 (q), 21.75 (q), 18.0 (t), 16.3 (q)
To a stirred solution of 14 (40 mg, 0.14 mmol) in EtOH (8 mL) was
added solid NaBH (9 mg, 0.24 mmol, 1.7 equiv) at -8 °C. After 20
min, the mixture was warmed to r.t. and stirred for an additional 45
min, and then diluted with H O. The solvent was evaporated and the
mixture was extracted with EtOAc. The organic solution was
washed with H O and brine, dried (MgSO ) and the solvent was re-
+
1: oil, HRMS: m/z calcd for C H O Si (M ) 424.3009, found
2
4
44
4
4
64.2800.
-
1
IR (film): n = 3580, 2940, 1725, 1650, 1370, 1253, 974 cm .
2
1
H NMR (C D , 200 MHz): d = 6.25 (d, J = 11.6 Hz, 1H), 5.3 (dt,
6
6
2
4
J = 11.2 Hz, J = 4.0 Hz, 1H), 5.0 (t, J = 9.4 Hz, 1H), 2.35 (dd,
J = 12.0 Hz, J = 3.8 Hz, 1H), 1.8-0.7 (m), 1.7 (s, 3H), 1.1 (s, 3H),
moved in vacuo to afford the crude product (40 mg) as a yellow oil.
The oil was purified by chromatography over silica gel (eluent: pe-
troleum ether-EtOAc 4:1) to afford white crystals of 24 (37 mg,
1
.0 (s, 3H), 0.9 (s, 3 ¥ 3H), 0.9 (s, 3H), 0.75 (s, 3H), 0.1 (s, 2 ¥ 3H).
2
5
9
4%).[a]D +106.7 (c = 0.015, CHCl ).
3
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

1
914
B. M. F. Lagnel et al.
SPECIAL TOPIC
IR (film): n = 3397, 2957, 1711, 1454, 1209, 748 cm-1.
+
HRMS: m/z calcd for C H O (M ) 280.2038, found 249.1854.
1
7
28
3
-
1
1
IR (film): n = 3701, 1720, 1650, 1540, 1260, 1015 cm .
H NMR (CDCl , 200 MHz): d = 3.9 (m, 2H), 3.8 (dt, J = 4.0 Hz,
3
1
J = 10.4 Hz, 1H), 2.1 (dd, J = 3.8 Hz, J = 12.2 Hz, 1H), 2.0-0.7
(
H NMR (C D , 200 MHz): d = 5.5 (m, 1H), 3.95 (AB system,
6
6
m), 1.4 (s, 3H), 1.1 (s, 3H), 1.0 (s, 3H), 0.8 (s, 3H).
J = 11.6 Hz, 2H), 2.6 (dd, J = 6.6 Hz, J = 17.6 Hz, 1H), 2.2-0.8
1
3
(
m), 1.9 (s, 3H), 1.5 (s, 3H), 1.2 (s, 3H), 1.04 (s, 3H), 1.02 (s, 3H).
C NMR (CDCl , 50 MHz): d = 74.5(s), 68.6 (d), 61.1 (d), 59.8 (d),
3
1
3
53.9 (t), 43.1 (t), 40.2 (t), 38.2 (s), 36.3 (t), 33.7 (q, s), 25.7 (q), 22.3
(
C NMR (C D , 50 MHz): d = 169.7 (s), 140.9 (s), 129.15 (s), 70.5
d), 57.8 (t), 54.0 (d), 43.5 (t), 40.7 (t), 36.9 (t, s), 36.2 (q), 33.4 (s),
6
6
q), 18.4 (t), 18.2 (q).
(
2
2.3 (q), 21.9 (q), 21.4 (q), 18.9 (t), 18.7 (q).
(
1S,3R,4S,4aS,8aS)-4-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-
3
,4a,8,8-tetramethyldecahydronaphthalene-1,3-diol (27)
Epoxidation of (1S,4aS,8aS)-4-(Hydroxymethyl)-3,4a,8,8-tet-
ramethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl Acetate
To a stirred solution of 26 (260 mg, 1.01 mmol) in DMF (26 mL)
were added TBDMSCl (182 mg, 1.2 mmol, 1.2 equiv) and imida-
zole (202 mg, 2.9 mmol, 2.9 equiv). The mixture was stirred at r.t.
for 1 h, and H O was added. The mixture was extracted with Et O.
The organic solution was washed with brine, dried (MgSO ) and
concentrated to yield the crude product. The product was purified
(
24)
To a stirred solution of 24 (20 mg, 0.071 mmol) in CH Cl (4 mL)
2
2
2
2
was added m-CPBA (31 mg, 0.18 mmol, 2.5 equiv). The mixture
4
was stirred for 2 h, and H O was added. The mixture was extracted
2
with EtOAc/ Et O. The organic solution was dried (MgSO ) and
2
4
by chromatography over silica gel (eluent: petroleum ether-EtOAc
1
concentrated to yield the crude product (30 mg) as a yellow oil. The
oil was purified by chromatography over silica gel (eluent: petro-
leum ether-EtOAc 2:1) to afford 25 (20 mg, 95%) as an oil.
:1) to afford 27 (350 mg, 94%) as white crystals; mp 114-115 °C.
2
5
[a]D +58.9 (c = 0.09, CHCl3).
HRMS: m/z calcd for C H O Si (M ) 370.2903 and 295.2093,
found 295.2095 and 262.1933.
25
[
a]D +60.0 (c = 0.005, CHCl ).
+
3
2
1
42
3
+
HRMS: m/z calcd for C H O (M ) 296.1988 and 236.1776, found
1
7
28
4
2
36.1771.
IR (film): n = 3383, 2950, 1736, 1470, 1049 cm-1.
-
1
IR (film): n = 3600, 1720, 1250, 900, 805 cm .
1
H NMR (CDCl , 200 MHz): d = 3.8 (dt, 1H), 3.6 (m, 2H), 2.0 (dd,
3
1
H NMR (C D , 200 MHz): d = 5.1 (m, 1H), 3.6 (AB system,
J = 3.6 Hz, J = 12.4 Hz, 1H), 1.6-0.7 (m), 1.2 (s, 3H), 1.0 (s, 3H),
0.9 (s, 3H), 0.8 (s, 3 ¥ 3H), 0.7 (s, 3H), -0.4 (s, 6H).
6
6
J = 11.6 Hz, 2H), 2.3 (dd, J = 7.4 Hz, J = 6.0 Hz, 1H), 2.05 (d,
J = 10.2 Hz, 1H), 1.85 (dd, J = 16.0 Hz, J = 5.0 Hz, 1H), 1.8-0.8
(
13
C NMR (CDCl , 50 MHz): d = 73.0 (s), 67.9 (d), 62.0 (t), 60.6 (d),
3
m), 1.7 (s, 3H), 1.04 (s, 3H), 1.0 (s, 3H), 0.9 (s, 3H), 0.8 (s, 3H).
5
8.5 (d), 52.9 (t), 43.1 (t), 40.3 (t), 37.8 (s), 36.5 (q), 33.45 (s), 26.0
1
3
C NMR (C D , 50 MHz): d = 169.8 (s), 69.6 (s), 68.6 (d), 62.4 (s),
8.1 (t), 47.6 (d), 42.7 (t), 38.05 (s), 37.4 (t), 35.3 (t), 35.0 (q), 33.5
(q), 25.7 (3 ¥ q), 22.2 (q), 17.9 (t), 17.86 (s), 16.95 (q), -5.7 (2 ¥ q).
6
6
5
(
s), 22.4 (q), 21.3 (q), 20.1 (q), 18.4 (t), 18.2 (q).
(3R,4S,4aR,8aS)-4-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-3-
hydroxy-3,4a,8,8-tetramethyloctahydronaphthalen-1(2H)-one
(28)
(
-)-Albrassitriol (2)
To an ice-cold solution of lithium diethylamide (20 mg, 0.25 mmol,
To a solution of 27 (350 mg, 0.94 mmol) in CH Cl (7.5 mL), with
2
2
2
.5 equiv) in anhyd Et O (2 mL) was added 25 (30 mg, 0.1 mmol)
3Å molecular sieves was added PCC (304 mg, 1.42 mmol, 1.5
2
in anhyd Et O (2 mL). The mixture was stirred at r.t. for 3 h. Then
equiv). After 40 min, the mixture was diluted with Et O and filtered
2
2
it was poured into H O and the mixture was extracted with EtOAc/
through silica gel (eluent: Et O). After evaporation of the solvents,
2
2
Et O. The organic solution was washed successively with 1M HCl,
the green oil (280 mg) was purified by chromatography over silica
2
sat. NaHCO and H O. The solution was dried (MgSO ) and con-
gel (eluent: petroleum ether-EtOAc 4:1) to afford 28 (270 mg,
3
2
4
2
5
centrated to yield the crude product (30 mg) as a yellow oil. The oil
was purified by chromatography over silica gel (eluent: petroleum
ether-EtOAc 2:1) to afford (2) (11 mg, 43%) as an oil.
78%) as white crystals; mp 108-109 °C. [a] +54.5 (c = 0.055,
D
CHCl ).
3
+
HRMS: m/z calcd for C H O Si (M ) 368.2747 and 311.2032,
2
1
40
3
+
HRMS: m/z calcd for C H O (M ) 254.1882, found 254.1878.
found 311.2032.
1
5
26
3
1
IR (film): n = 3488, 2936, 1715, 1475, 1140, 829 cm-1.
H NMR (CDCl , 200 MHz): d = 5.3 (m, 1H), 4.0 (dd, J = 11.4 Hz,
3
1
(
H), 3.6 (dd, J = 11.6 Hz, 1H), 3.5 (dd, 1 H), 2.5 (s, 1H), 2.2-1.5
1
H NMR (CDCl , 200 MHz): 3.9 (m, 2H), 2.6 (m, 2H), 2.3 (s, 1H),
3
m), 1.3 (s, 3H), 1.05 (s, 3H), 0.8 (s, 3H), 0.6 (s, 3H).
2
.2-0.8 (m), 1.3 (s, 3H), 1.2 (s, 3H), 0.92 (s, 3H), 0.9 (s, 3 ¥ 3H),
1
3
C NMR (C D , 50 MHz): d = 128.9 (s), 124.3 (d), 76.0 (s), 68.4
0.8 (s, 3H), 0.1 (s, 2 ¥ 3H).
6
6
(
2
d), 59.0 (t), 50.3 (d), 42.6 (t), 42.4 (t), 38.05 (s), 34.6 (s), 32.4 (q),
13
C NMR (CDCl , 50 MHz): d = 208.9 (s), 76.0 (s), 65.5 (d), 61.8
3
2.4 (q), 20.1 (q), 18.4 (t), 18.2 (q).
(
t), 59.2 (d), 59.1 (t), 42.1 (t), 40.1 (t), 39.9 (s), 32.5 (q), 32.1 (s),
2
q).
6.0 (q), 25.7 (3 ¥ q), 21.7 (q), 18.2 (t), 17.9 (s), 16.7 (q), -5.7 (2 ¥
(
1S,3R,4S,4aS,8aS)-4-(Hydroxymethyl)-3,4a,8,8-tetramethyl-
decahydronaphthalene-1,3-diol (26)
To a stirred solution of LiAlH (425 mg, 11.18 mmol, 6 equiv) in an-
4
(
3
1
4S,4aR,8aS)-4-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-
,4a,8,8-tetramethyl-4a,5,6,7,8,8a-hexahydronaphthalen-
(4H)-one (29)
hyd THF (17 mL) under N was added 13 (630 mg, 1.86 mmol). Af-
2
ter stirring overnight, the excess of LiAlH was quenched with Et O
4
2
and a solution of 1M HCl. The mixture was then extracted with
To a solution of 28 (270 mg, 0.73 mmol) in pyridine (4.3 mL, 53
mmol, 73 equiv) was added 4-DMAP (88 mg) and SOCl (250 mL,
3
dine was evaporated in vacuo. The mixture was extracted with Et O
(
sat. NaHCO and brine. The organic solution was dried (MgSO )
and concentrated to yield the crude product (300 mg) as a yellow
oil. The oil was purified by chromatography over silica gel (eluent:
EtOAc/Et O. The organic solution was washed with brine, dried
2
2
(
MgSO ) and concentrated to afford white crystals (400 mg). The
4
.4 mmol, 4.7 equiv). After 5 h at r.t., ice was added and the pyri-
crude product was purified by chromatography over silica gel (elu-
2
ent: EtOAc) to afford 26 (332 mg, 70%) as white crystals; mp 150
2¥) and the organic solution was washed successively with H O,
2
5
2
°
C. [a]D +26.2 (c = 0.08, EtOH).
3
4
+
HRMS: m/z calcd for C H O (M ) 256.2038 and 220.1827, found
1
5
28
3
2
41.1803 and 220.1829.
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Drimanes from (+)-Larixol
1915
1
3
petroleum ether-EtOAc 9.5:0.5) to afford 29 (182 mg, 71%) as an
C NMR (C D , 50 MHz): d = 65.2 (d), 63.2 (s, d), 60.8 (t), 55.2
6
6
oil.
(d), 54.3 (d), 44.5 (t), 43.2 (t), 35.7 (s), 34.3 (s), 33.3 (q), 24.7 (q),
22.85 (q), 19.0 (q), 18.8 (t).
25
[
a]D -17.1 (c = 0.035, CHCl3).
+
HRMS: m/z calcd for C H O Si (M ) 350.2641 and 263.1467,
2
1
38
2
(
(1S,4aS,8aR)-2,5,5,8a-Tetramethyl-4-oxo-1,4,4a,5,6,7,8,8a-oc-
found 263.1829.
tahydronaphthalen-1-yl)methyl Acetate (32)
To a solution of 30 (15 mg, 0.13 mmol) in pyridine (2.1 mL) was
added Ac
at r.t. Then it was diluted with H O and extracted with CH Cl . The
organic solution was dried (MgSO ) and concentrated to yield the
crude product (50 mg) as a yellow oil. The oil was purified by
chromatography over silica gel (eluent: petroleum ether-EtOAc
2
[
-
1
IR (film): n = 3301, 2930, 1455, 1010 cm .
1
2
O (850 mL, 9.05 mmol). The mixture was stirred for 3 h
H NMR (CDCl , 200 MHz): d = 5,8 (s, 1H), 3.8 (m, 2H), 2.25 (m,
3
2
2
2
1
0
H), 2.0 (s, 1H), 1.9-0.8 (m), 1.2 (s, 3H), 1.15 (s, 3H), 1.1 (s, 3H),
4
.9 (s, 3H), 0.85 (s, 3 ¥ 3H), 0.02 (s, 2 ¥ 3H).
1
3
C NMR (CDCl , 50 MHz): d = 200.5 (s), 158.2 (s), 129.1 (d), 63.2
3
(
d), 59.8 (t), 58.1 (d), 43.3 (t), 42.4 (s), 39.4 (t), 33.6 (q), 32.3 (s),
:1) to afford white crystals of 32 (30 mg, 85%); mp 55-60 °C.
2
¥
5.8 (3 ¥ q), 22.0 (q), 21.7 (q), 18.3 (t), 18.2 (s), 16.05 (q), -5.5 (2
25
a]D +31.4 (c = 0.035, CHCl ).
3
q).
+
HRMS: m/z calcd for C H O (M ) 278.1882, found 278.1886.
1
7
26
3
-
1
IR (film): n = 3428, 2932, 1705, 1010 cm .
(
4
4S,4aR,8aS)-4-(Hydroxymethyl)-3,4a,8,8-tetramethyl-
a,5,6,7,8,8a-hexahydronaphthalen-1(4H)-one (30)
1
H NMR (CDCl , 200 MHz): d = 5.8 (m, 1H), 4.35, 4.3 (m, 2H),
.45 (br s, 1H), 2.05 (s, 1H), 2.0 (s, 3H), 1.9-0.9 (m), 1.9 (s, 3H),
3
To a solution of 29 (150 mg, 0.43 mmol) in THF (5.4 mL) was add-
ed TBAF (124 mL, 0.43 mmol). After 1 h, the mixture was diluted
with H O and extracted with CH Cl . The organic solution was
washed with brine, dried (MgSO ) and concentrated to yield the
crude product (180 mg) as a yellow oil. The oil was purified by
2
1
.15 (s, 3H), 1.1 (s, 3H), 0.9 (s, 3H).
2
2
2
13
C NMR (CDCl , 50 MHz): d = 199.6 (s), 170.8 (s), 155.4 (s),
29.4 (d), 63.0 (d), 61.7 (t), 54.6 (d), 42.85 (t), 42.2 (s), 39.1 (t), 33.5
q), 32.2 (s), 21.7 (q), 21.55 (q), 21.1 (q), 18.1 (t), 15.6 (q).
3
4
1
(
chromatography over silica gel (eluent: EtOAc) to afford 30 (62 mg,
6
0%) as an oil.
(
4aS)-3,4a,8,8-Tetramethyl-4-methylene-4a,5,6,7,8,8a-hexahy-
25
[
a]D +60.0 (c = 0.005, CHCl3).
dronaphthalen-1(4H)-one (33)
To a solution of 32 (40 mg, 0.14 mmol) in anhyd benzene (2 mL)
was added DBU (128 ml, 0.86 mmol). The mixture was stirred for
+
HRMS: m/z calcd for C H O (M ) 236.1776, found 236.1775.
1
5
24
2
1
H NMR (CDCl , 200 MHz): d = 5.8 (m, 1H), 3.95 (m, 2H), 2.2 (m,
3
3
.5 h at reflux under N . After evaporation of the solvent, the
2
1
0
H), 2.05 (s, 1H), 2.0-0.9 (m), 2.0 (s, 3H), 1.1 (s, 3H), 1.1 (s, 3H),
.9 (s, 3H).
residue was purified by chromatography over silica gel (eluent: pe-
troleum ether-EtOAc 3:1) to afford 33 (20 mg, 66%) as an oil.
[a]D -101.3° (c = 0.075, CHCl3).
1
3
C NMR (CDCl , 50 MHz): d = 200.3 (s), 157.5 (s), 129.0 (d), 63.0
25
3
(
d), 59.9 (t), 58.2 (d), 43.0 (t), 42.1 (s), 39.3 (t), 33.6 (q), 32.3 (s),
-
1
IR (film): n = 3428, 2932, 1705, 1010 cm .
2
2.0 (q), 21.7 (q), 18.2 (t), 15.9 (q).
1
H NMR (CDCl , 200 MHz): d = 5.8 (s, 1H), 5.2 (d, J = 12.0 Hz,
3
2
3
H), 2.2 (s, 1H), 2.0-0.75 (m), 2.0 (s, 3H), 1.15 (s, 3H), 1.1 (s, 2 ¥
H).
(
1
1R,4S,4aR,8aS)-4-(hydroxymethyl)-3,4a,8,8-tetramethyl-
,4,4a,5,6,7,8,8a-octahydronaphthalen-1-ol (31)
To a solution of 30 (30 mg, 0.13 mmol) in anhyd THF (1.2 mL) at
°C under N was added Dibal-H (0.42 mL of a 1.5M solution in
13
C NMR (CDCl , 50 MHz): d = 199.6 (s), 156.2 (s), 150.0 (s),
3
0
2
128.0 (d), 111.8 (t), 61.1 (d), 43.1 (t), 42.9 (s), 37.8 (t), 33.3 (q),
2.75 (s), 23.3 (q), 21.75 (q), 20.4 (t), 18.4 (q).
toluene, 0.6 mmol, 4.6 equiv). After stirring for 1 h, the excess of
Dibal-H was quenched with EtOAc and a solution of 5% H SO .
3
2
4
The mixture was then extracted with EtOAc/ Et O. The organic so-
2
(
4R,4aS,8aS)-4-Hydroxy-4-(hydroxymethyl)-3,4a,8,8-tetrame-
lution was washed with brine, dried (MgSO ) and concentrated to
4
thyl-4a,5,6,7,8,8a-hexahydronaphthalen-1(4H)-one (34)
To a solution of 33 (20 mg, 0.09 mmol) in anhyd pyridine (0.6 mL)
under N was added OsO (1.07 g of a 2.5% wt solution in t-BuOH,
0.1 mmol). The mixture was stirred at r.t. overnight. Then it was di-
luted with aq. 10% Na and stirred for 1 h. The mixture was ex-
tracted with Et O. The organic solution was washed with brine,
dried (MgSO ) and concentrated to yield the crude product (60 mg)
as a black oil. The oil was chromatographed on silica gel (eluent:
afford 31 (29 mg, 94%) as white crystals. The residue was not puri-
fied, but directly converted into 4.
2
4
-
1
IR (film): n = 3301, 2930, 1455, 1010 cm .
1
S O
2 2 3
H NMR (CDCl , 200 MHz): d = 5.7 (m, 1H), 4.4 (m, 1H), 3.8 (m,
3
2
2
H), 1.8-0.85 (m), 1.8 (s, 3H), 1.1 (s, 3H), 1.0 (s, 3H), 0.85 (s, 3H).
4
(
-)-Uvidin C (4)
EtOAc-MeOH 9:1) to afford 34 (20 mg, 88%) as white crystals; mp
To a solution of 31 (20 mg, 0.08 mmol) in CH Cl (5 mL) was added
m-CPBA (36 mg, 0.21 mmol, 2.5 equiv). The mixture was stirred
2
2
1
42 °C.
for 25 min, and H O was added. The mixture was extracted with
+
2
HRMS: m/z calcd for C H O (M ) 252.1725, found 191.1434.
15 24 3
EtOAc/ Et O. The organic solution was washed with 10% Na S O ,
2
2
2
3
IR (film): n = 3500, 2969, 2947, 1676, 1450, 970, 833 cm-1.
sat. NaHCO and brine. The organic solution was dried (MgSO )
3
4
1
and concentrated to yield the crude product (30 mg) as an oil. The
oil was purified by chromatography over silica gel (eluent: petro-
leum ether-EtOAc 2:1) to afford 4 (20 mg, 95%) as an oil.
H NMR (CDCl , 200 MHz): d = 5.6 (m, 1H), 4.7 (AB system,
3
J = 11.2 Hz, 2H), 3.2 (s, 1H), 2.0-0.8 (m), 2.0 (s, 3H), 1.15 (s, 3H),
1.12 (s, 3H), 1.1 (s, 3H).
-
1
13
IR (film): n = 3428, 2932, 1705, 1010 cm .
C NMR (CDCl , 50 MHz): d = 201.1 (s), 157.0 (s), 128.0 (d), 92.2
3
1
(s), 84.5 (t), 55.0 (d), 46.5 (s), 43.2 (t), 33.6 (q), 32.2 (s), 31.45 (t),
H NMR (C D , 200 MHz): d = 4.3 (dd, J = 5.4 Hz, J = 4.6 Hz, 1H),
6
6
2
1.8 (q), 20.9 (q), 18.1 (t), 14.2 (q).
3
0
.7 (d, J = 3.4 Hz, 2H), 2.9 (d, J = 5.8 Hz, 1H), 2.05 (s, 1H), 2.0-
.4 (m), 1.5 (s, 3H), 1.35 (s, 3H), 1.15 (s, 3H), 1.1 (s, 3H), 0.5 (d,
(
-)-epi-Albrassitriol (5)
To a solution of 34 (15 mg, 0.06 mmol) in anhyd THF (0.6 mL) at
°C under N was added Dibal-H (0.21 mL of a 1.5M solution in
J = 4.0 Hz, 1H).
0
2
Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York

1
916
B. M. F. Lagnel et al.
SPECIAL TOPIC
(15) de Bernardi, M.; Mellerio, G.; Vidari, G.; Vita-Finzi, P.;
toluene, 0.31 mmol, 5.1 equiv). After stirring 1h, the excess of
Dibal-H was quenched with aq NH Cl. The mixture was then ex-
Fronza, G. J. Chem. Soc., Perkin Trans. I 1983, 2739.
(16) Ziegler, F. E.; Jaynes, B. B. Tetrahedron Lett. 1985, 26, 5875.
(17) Lopez, J.; Sierra, J.; Cortés, M. Chem. Lett. 1986, 2073.
(18) Grabley, S.; Thiericke, R.; Zerlin, M. J. Antibiot. 1996, 49,
593.
4
tracted with EtOAc/ Et O. The organic solution was washed with
2
sat. NaHCO , dried (MgSO ) and concentrated to yield the crude
3
4
product as an oil. The oil was purified by chromatography over sil-
ica gel (eluent: EtOAc-MeOH 9:1) to afford (5) (14 mg, 83%) as an
oil.
(19) Barrero, A. F.; Alvarez-Manzaneda, E. J.; Altarejos, J.;
Salido, S.; Ramos, J. M. Tetrahedron 1993, 49, 10405.
1
H NMR (acetone-d , 200 MHz): d = 5.35 (m, 1H), 4.7 (m, 2H),
6
(
20) Barrero, A. F.; Manzaneda, E. A.; Altarejos, J.; Salido, S.;
Ramos, J. M.; Simmonds, M. S. J.; Blaney, W. M.
Tetrahedron 1995, 51, 7435.
4
.16 (t, 1H), 2.0-1.0 (m), 1.35 (s, 3H), 1.06 (s, 3H), 1.05 (s, 3H).
1
3
C NMR (acetone-d , 50 MHz): d = 141.0 (s), 127.4 (d), 74.5 (s),
6
6
7.2 (t), 63.3 (d), 48.3 (d), 46.3 (t), 41.0 (s), 33.8 (s), 33.1 (q), 33.0
(
(
21) Jung, M.; Lee, S.; Yoon, B. Tetrahedron Lett. 1997, 38, 2871.
22) Gijsen, H. J. M. (+)-Aromadendrene as Chiral Starting
Material for the Synthesis of Sesquiterpenes, Thesis,
Agricultural University, Wageningen (The Netherlands);
(
t), 25.1 (q), 20.4 (q), 19.3 (t), 18.2 (q).
Acknowledgement
1993.
(
(
(
(
(
(
23) Leite, M. A. F.; Sarragiotto, M. H.; Imamura, P. M.;
Marsaioli, A. J. J. Org. Chem. 1986, 51, 5409.
24) Norin, T.; Ohloff, G.; Willhalm, B. Tetrahedron Lett. 1965,
Support of this research, awarded by the Rhone-Alpes region
(France), International Agricultural Centre of Wageningen (The
Netherlands) and INTAS, are gratefully acknowledged. The authors
thank A. van Veldhuizen for NMR spectroscopic data, C. J. Teunis
and H. Jongegan for mass spectroscopic data.
3523.
25) Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.
Tetrahedron 1998, 54, 5635.
26) Verstegen-Haaksma, A. A.; Swarts, H. J.; Jansen, B. J. M.; de
Groot, A. Tetrahedron 1994, 50, 10095.
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Synthesis 2000, No. 13, 1907–1916 ISSN 0039-7881 © Thieme Stuttgart · New York