The synthesis of Ambrox-like compounds starting from (+)-larixol

Article abstract of DOI:10.1016/S0040-4020(01)00494-X

The oxidation of the (3-hydroxy-3-methyl-4-pentenyl)-side chain at C(9) of some labdanic diterpenoids with potassium permanganate was investigated. Triols, ketones, or cyclic enol ethers are the main reaction products, strongly influenced by the substituent at C(8). Further degradation of the methyl ketones by the Baeyer-Villiger reaction and modification of the exocyclic 8(17) double bond lead to suitable intermediates, which have been transformed into Ambrox-like compounds. Synthetic routes using palladium catalyzed elimination or isomerization of allylic acetates, followed by ozonolysis have been developed as well for shortening of the side chain of (+)-larixol. Products from both routes have been cyclized to 6α-hydroxy Ambrox. This compound was used as the key intermediate for the synthesis of several other Ambrox-like compounds of which some showed pleasant odour properties.

Full text of DOI:10.1016/S0040-4020(01)00494-X

TETRAHEDRON
Pergamon
Tetrahedron 57 $2001) 5663±5679
The synthesis of Ambroxw-like compounds
starting from ꢀ1)-larixol
Marjon G. Bolster, Ben J. M. Jansen and Aede de Grootp
Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, HB 6703 Wageningen, The Netherlands
Received 23 January 2001; revised 17 April 2001; accepted 3 May 2001
AbstractÐThe oxidation of the $3-hydroxy-3-methyl-4-pentenyl)-side chain at C$9) of some labdanic diterpenoids with potassium per-
manganate was investigated. Triols, ketones, or cyclic enol ethers are the main reaction products, strongly in¯uenced by the substituent at
C$8). Further degradation of the methyl ketones by the Baeyer±Villiger reaction and modi®cation of the exocyclic 8$17) double bond lead to
suitable intermediates, which have been transformed into Ambroxw-like compounds. Synthetic routes using palladium catalyzed elimination
or isomerization of allylic acetates, followed by ozonolysis have been developed as well for shortening of the side chain of $1)-larixol.
Products from both routes have been cyclized to 6a-hydroxy Ambroxw. This compound was used as the key intermediate for the synthesis of
several other Ambroxw-like compounds of which some showed pleasant odour properties. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
developed for sclareol $6),12±16 do not proceed in the same
way for larixol $1) due to differences in the functional
groups at C$8). The C$8) hydroxyl group of sclareol $6)
participates in reaction intermediates of the oxidation,
while such participation is not possible in larixol $1), its
acetate $2) and in epi-manool $3). Furthermore the presence
of an exocyclic double bond at C$8) in the latter three
compounds may cause selectivity problems, and this may
be also the case with the hydroxyl group at C$6) in 1 and 4.
Labdanes form a large group of diterpenes, characterized by
a 4,4,10-trimethyl substituted trans-decalin system, with a
b-orientated substituted side chain at C$9).1 Labdane diter-
penoids are easily available from Nature and they have been
used frequently as starting material for the synthesis of other
4,4,10-trimethyl substituted decalins.2 The synthesis of
$2)-Ambroxw and other ¯avour compounds from $2)-
sclareol3 has been studied extensively. Larixol $1) and
larixyl acetate are also easily available from Nature,4 but
have been used to a much lesser extent as starting materials
in synthesis. However, oxidation of the C$9) side chain of
these labdanes also may provide suitable synthons for the
synthesis of Ambroxw-like compounds. For this purpose the
side chain of larixol $1) has to be shortened to a two carbon
moiety and the exocyclic 8$17) methylene group has to be
modi®ed to enable the construction of the cyclic ether that is
characteristic for Ambroxw-type molecules.
So there is still a need for a general selective good yield
procedure for the degradation of the labdane side chain and
for this purpose a modi®cation of the method of Ogino et
al.17 using solid potassium permanganate18 in the presence
of a phase-transfer catalyst was investigated for the oxida-
tion of the labdanes 1±7, aiming at an optimum yield for
methyl ketones.9 An obvious way to achieve further break-
down of methyl ketones into a functionalized two carbon
moiety is the Baeyer±Villiger oxidation and this reaction
was investigated for methyl ketone 11 and for its C$6)
acetate 12 and tert-butyldimethylsilyl $TBDMS) ether 25.
Pd catalysed isomerization or elimination, followed by
ozonolysis can provide for a short route to break down the
side chain in labdanes as well. Both routes lead to inter-
mediates which are suitable for cyclization to 6a-hydroxy
Ambroxw 39. This compound can be considered as a key
intermediate in the syntheses of other Ambroxw-like
compounds as depicted in Scheme 1.
The side chain of labdanes may contain various functional
groups, but the labdanic terpenoids used in this research
all have the generally occuring $3-hydroxy-3-methyl-4-
pentenyl)-side chain at C$9) $Scheme 1). Several studies
to oxidize this side chain have been reported in literature
for larixol $1) and manool,5±11 but many use expensive,
environmentally suspect oxidants, are irreproducible, or
give rise to experimental dif®culties during work-up. Also
some special oxidation procedures, which have been
2. Results and discussion
Keywords: labdanes; larixol; potassium permanganate oxidation; Baeyer±
Villiger oxidation; 6a-hydroxy Ambroxw; Ambroxw-like compounds.
Corresponding author. Tel.: 131-317-482370; fax: 131-317-484914;
p
Besides the labdanes larixol $1) and C$13)-epi-manool $3),
the oleoresin of the larch turpentine mainly consists of
e-mail: aede.degroot@bio.oc.wag-ur.nl
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020$01)00494-X

5664
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
Scheme 1.
larixyl acetate $2).10,19,20 To facilitate puri®cation, the
acetate is hydrolyzed ®rst to larixol $1), which can be
obtained in pure form via crystallization from cyclohexane.
The most apolar compound in the residual mother liquor is
$1)-epi-manool $3),21,22 which can be isolated easily by
chromatography. Compound 4 was obtained from larixol
$1) in 64% overall yield after epoxidation of the exocyclic
double bond with oxone and reduction of the epoxide using
lithium aluminum hydride $LiAlH4) and its structure was
fully determined $vide infra in Scheme 5).23 The corre-
sponding acetate 5 was obtained after treatment of
compound 4 with acetic anhydride in pyridine. Compound
724 was synthesized from larixol $1) in 73% overall yield by
oxidation of the C$6)-hydroxyl group with pyridinium
chlorochromate $PCC) to the C$6)-ketone, which was trans-
formed into the conjugated ketone 7 via base catalyzed
isomerization of the exocyclic 8$17) double bond using
methanolic sodium methoxide. The same C$6)-ketone can
also be obtained by Swern oxidation of larixol $1), followed
by isomerization.
clear that generally good yields of the desired methyl
ketones could be obtained when 3.0 equiv. of potassium
permanganate were used. The ratio between the two
products was slightly pH dependent with alkaline conditions
giving higher yields of the triols.25,26 Longer reaction times,
higher temperature or more equivalents of oxidant gave no
improvement of the yield of methyl ketones and in the
labdanes 1±3 products rising from oxidation of the
exocyclic methylene group were found.10 For substrate 7
the use of 3 equiv. of potassium permanganate did not
show a signi®cant difference in product ratio, but when
this reaction was carried out at room temperature, the
methyl ketone 24 is obtained as main product in 68%
isolated yield.
The in¯uence of the substituent on C$8) is also clear. When
an exocyclic double bond is present at C$8) a reasonable
selective oxidation of the double bond in the side chain can
be achieved to give the methyl ketones 11±13 in good
yields. When a hydroxyl group is present at C$8), this
group has a strong tendency to react with the methyl ketone
in the side chain, and the cyclic enol ethers 20±22 are
isolated as the main products in high yield. A further break-
down in a separate reaction with another 3.0 equiv. of
KMnO4 could not be achieved. Decomposition of these
enol ethers was observed during longer chromatographic
The oxidation of compounds 1±7 was investigated using
two standard methods with 1.5 or 3.0 equiv. of potassium
permanganate respectively, at 08C, and the results are
summarized in Table 1. In all cases mixtures of triols and
methyl ketones were obtained $Scheme 2), but it became
Table 1. Potassium permanganate oxidation of labdanes using 1.5 and 3.0 equiv., respectively, at 08C
Substrate
Products on oxidation with 1.5 equiv. KMnO4
Products on oxidation with 3.0 equiv. KMnO4
Triol $%)a
Methyl ketone $%)a
Enol ether $%)a
Triol $%)a
Methyl ketone $%)a
Enol ether $%)a
1
2
310
4
8 $38)
9 $26)
$24)
11 $45)
12 $48)
13 $48)
17 $±)b
18 $±)b
19 $6)
8 $±)b
9 $±)b
11 $68)
12 $72)
13 $67)
17 $±)b
18 $±)b
19 $±)b
24 $11)
10 $±)b
14 $±)b
15 $±)b
16 $±)b
23 $56)
14 $±)b
15 $±)b
16 $25)
23 $56)
20 $47)
21 $48)
22 $51)
20 $74)
21 $90)
22 $86)
5
631
7
24 $8)
a
Isolated pure yields.
Not isolated, maximum yield ,5%.
b

M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
5665
Scheme 2. Reagents and conditions: $a) KMnO4, for details see Table 1; $b) Ac2O, CH2Cl2, py, DMAP, 91%.
procedures or upon standing, so in preparative procedures it
is advisable to use them immediately for further trans-
formations without puri®cation. Sonication27 accelerated
the oxidation appreciably, i.e. a shortening of the reaction
time from 14 to 2 h. However, the yield and product
composition was not affected. Presumably, sonication
promotes the decomposition of the cyclic manganate
ester which is responsible for the formation of the
products.28 The periodate±permanganate system for
the oxidation of ole®nic double bonds29,30 was also
investigated but it did not improve the yields of the methyl
ketones.
Further breakdown of the methyl ketones into a function-
alized two carbon moiety using the Baeyer±Villiger
oxidation32 was investigated for methyl ketone 11, its C$6)
acetate 12 and its C$6) TBDMS ether 25. When methyl
ketone 11 was treated with 10 equiv. of meta-chloroper-
benzoic acid $m-CPBA) during 10 days acetal 28 was
obtained in 50% yield and the expected epoxy acetate 26
Scheme 3. Reagents and conditions: $a) for RˆOH: m-CPBA $2 equiv.), CH2Cl2, 83%, 26:28:30ˆ3:4:1; for RˆOTBDMS: m-CPBA $2.5 equiv.), CH2Cl2,
85%, 27:29:31ˆ2:2:5; $b) TBDMSiCl, DMF, imidazole, 608C, 87%; $c) MMPP, CH2Cl2, 60%; $d) LiAlH4, THF, 08C to rt, 62%; $e) spontaneously upon
standing.

5666
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
Scheme 4. Reagents and conditions: $a) for RˆOAc: m-CPBA, CH2Cl2, 84%; for RˆH: see literature data34; $b) for RˆOH, OAc: LiAlH4, THF, 08C to rt,
95%, 36:35ˆ1:8.5; for RˆH: see literature data34; $c) for RˆOH: p-TsOH, CH3NO2, 64%.
was formed in only 35% yield. Treatment of 11 with just
2 equiv. of m-CPBA again gave rise to 28 and 26 in 30 and
40% yield, respectively and epoxide 30 was found as a
minor byproduct $12%) $Scheme 3).
tion of 31 in CDCl3, acetal 29 was formed and upon standing
a conversion of 31 into 29 was also observed.
In an attempt to obtain 27 in a better yield the oxidation was
also carried out with magnesium monoperoxyphthalate
hexahydrate33 $MMPP) in stead of m-CPBA, but this
reagent epoxidized only the exocyclic double bond to give
compound 31, and left the methyl ketone unaffected. On the
other hand when acetate 12 was treated with m-CPBA
compound 34 was obtained in a good yield of 84% together
with 11% of compound 33, in which only the exocyclic
double bond is epoxidized $Scheme 4).
1
The structure of compound 28 was elucidated by H,1H-
1
NOESY-NMR and H,1H-COSY-NMR, whereby no nOe
is observed between H$15) and the protons of the C$10)-
methyl group. Apparently epoxidation of the double bond is
faster than the Baeyer±Villiger oxidation of the methyl
ketone and a subsequent acid catalyzed reaction of the car-
bonyl group with the epoxide than gives the acetal 28.
Baeyer±Villiger oxidation of the TBDMS protected
compound 25 with m-CPBA gave again a mixture, with
the desired epoxy acetate 27 as the minor product. Epoxide
31 was obtained in almost 80% yield as the major product
after ¯ash column chromatography, as was established by
1H NMR. However already during the 13C NMR identi®ca-
The epoxy acetates 26, 27 and 34 were treated with lithium
aluminum hydride $LiAlH4) with the aim to introduce the
desired tertiairy hydroxyl group at C$8), and to reduce the
acetates to hydroxyl groups as well. However, the reduction
of the epoxy acetates 26 and 34 both gave the cyclic ether 36
Scheme 5. Reagents and conditions: $a) oxone, acetone, H2O, CH2Cl2, [18]crown-6, NaHCO3, 08C, 68%; $b) LiAlH4, THF, 08C to rt, 94%; $c) Ac2O, CH2Cl2,
py, DMAP, 91%; $d) KMnO4, BTEACl, CH2Cl2, 08C to rt, 70±85%; $e) Jones, acetone, 50%; $f) LiAlH4, THF, 08C to rt, 94%; $g) p-TsOH, CH3NO2, 64%; $h)
for RˆOH: cat. OsO4, NaIO4, THF, 80±90%, 45a,b:43ˆ1:2.2; for RˆOAc: cat. OsO4, NaIO4, THF, 72%.

M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
5667
as the main product and the desired triol 37 could be isolated
only as a minor product. Obviously the acetate group in the
side chain was reduced ®rst, followed by attack of the
alkoxide on the epoxide to give the cyclic ether 36. Its
con®guration was determined by 1H,1H-NOESY-NMR,
whereby a clear nOe was observed between H$13) and
H$9). Reduction of epoxy acetate 27 gave 32 as the sole
product in a reasonable 62% yield $Scheme 3). Cyclization
of 37 was achieved by stirring in nitromethane in the
presence of p-toluenesulfonic acid $p-TsOH) and gave 39
in 64% yield.
oxone $2KHSO5´KHSO4´K2SO4) which proved to be the
oxidant of choice compared with m-CPBA because its selec-
tivity for the 8$17) exocyclic double bond was much better.
Over-epoxidation to give the 8$17), 14$15)-diepoxide 41
was observed in 19%. Epoxide 42 was reduced with
LiAlH4 to give the triol 423 which proceeded in good yield
and without the competitive formation of cyclic ethers as
seen before in Scheme 4. The C$6)-hydroxyl group in 4
could be protected selectively as its acetate 5, and 4 and 5
were both oxidized with a catalytic amount of osmium
tetroxide $OsO4) and an excess of sodium metaperiodate
$NaIO4) $Scheme 5). This oxidation gave the aldehydes 43
and 44 respectively, as the major products along with some
side products, of which two were identi®ed as the epimers
45a and b. A high ratio of NaIO4/OsO4 favoured cleavage to
the aldehyde above rearrangement to methyl ketones 45a
and b.35
When the results depicted in Schemes 3 and 4 are compared
with each other and with a similar reaction sequence of
methyl ketone 13, derived from manool, it can be concluded
that the C$6) substituent in larixol $1) and its derivatives has
a de®nitive but rather unpredictable in¯uence on the course
and yields of the reactions involved. Treatment of methyl
ketone 13 with two equivalents of m-CPBA effected a clean
conversion into the epoxy acetate 35 by successive epoxida-
tion and Baeyer±Villiger reaction. Reduction of this epoxy
acetate with LiAlH4 afforded the diol 38 in 72% yield.34 The
related compounds 11 and 25 gave mixtures in the Baeyer±
Villiger reaction but the same reaction with acetate 12 gave
a high yield of the desired epoxy diacetate 34. However, the
reduction of epoxide 34 proceeded in the wrong way and
gave the desired triol 37 in only 10% yield. Although
incidental transformations proceeded in good yield, no over-
all high yield conversion of 11 into key intermediate 39
could be achieved and therefore other routes were
investigated.
Some other routes starting from 4 were also investigated
$Scheme 5). Oxidation of 4 or 5 with potassium perman-
ganate $KMnO4)17 has been mentioned before and leads to
formation of the enol ethers 20 and 21. Attempts to cleave
the double bond in these enol ethers by a second oxidation
with KMnO4 were unsuccesful, but Jones' oxidation36
immediately followed by reduction of the resulting mixture
of aldehydes and acids gave triol 37 in 50% yield, based on
the enol ethers. Various other oxidation procedures were
also applied to these enol ethers, but did not lead to
improvements.37 The aldehydes 43 and 44 isolated from
the osmylation reactions, both gave triol 37 in 94% yield
upon reduction with LiAlH4.
The major dif®culties in the former route were connected
with the lack of selectivity in the Baeyer±Villiger oxidation
of the 3-oxo-butyl side chain and in the reduction of the
resulting epoxy acetate. A new route was investigated in
which these transformations could be avoided and therefore
the exocyclic 8$17) double bond in larixol $1) was converted
®rst into a methyl group and a hydroxyl group at C$8). This
was performed by epoxidation of this double bond with
Elimination or rearrangement of allylic acetates in the side
chain of larixol or its derivatives followed by ozonolysis
also could provide for an easy access to compounds with
a two or four carbon moiety at C$9) and this approach was
investigated as well. The acetylation of the secondary and
both tertiary hydroxyl groups in 4 could be achieved with
acetyl chloride in N,N-dimethylaniline to give the triacetate
48 $Scheme 6). When 48 was treated with a catalytic amount
Scheme 6. Reagents and conditions: $a) AcCl, N,N-dimethylaniline, 80%; $b) Pd$OAc)2, CaCO3, PPh3, dioxane, D, 94%, 49a:b:cˆ4:2:3; $c) O3, MeOH/
CH2Cl2 3:1, 2788C; $d) NaBH4, 2788C; $e) NaOMe, MeOH, 67%; $f) LiAlH4, THF, 08C to rt, 87%; $g) PdCl2$CH3CN)2, THF, 98%; $h) O3, CH2Cl2/ MeOH
1:1, 2788C; $i) PPh3, 2788C, 95%; $j) m-CPBA, CH2Cl2, 83%; $k) LiAlH4, THF, 08C to rt, 85%; $l) NaOMe, MeOH, 85%.

5668
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
Scheme 7. Reagents and conditions: $a) H2Cr2O7, acetone, 91%; $b) Ac2O, CH2Cl2, py, DMAP, 94%; $c) NaH, MeI, DMF, 1008C, 95%; $d) p-TsOH, benzene,
D, 80%, 56:57:58ˆ2:1:1; $e) SOCl2, py, 08C to rt, 57%; $f) MsCl, 08C to rt, 92%; $g) LiBr, Li2CO3, DMF, 1208C, 71%; $h) MgI2, toluene, 67%.
$1 mol%) of palladium acetate3j,38c in the presence of tri-
phenylphosphine at 1008C, a mixture of unsaturated acetates
GC-MS apparatus and on a GC-sniff apparatus, and all three
compounds had a pleasant smell, with the D5-alkene 56 as
the most attractive one. The structure of alkene 56 was
deduced from the NMR spectrum and from its MS
spectrum, which showed a clear retro Diels±Alder reaction.
Moreover, its structure was proven by an independent
synthesis $vide infra). Compound 57 showed two vinylic
protons which coupled with each other, strongly indicating
the proposed structure, which is additionally supported by
the MS spectrum. The third product most likely has a
rearranged skeleton, but further investigations are required
to determine the precise structure.
1
49a, b and c in a ratio of 4:2:3, determined with H NMR,
was obtained in over 90% yield. Ozonolysis of this mixture
afforded aldehyde 44, which was reduced and saponi®ed to
give triol 37 in 67% yield starting from the mixture of
dienes.
In a second variant triacetate 48 was isomerized in
quantitative yield to the allylic acetate 5038 $Scheme 6).
Ozonolysis of the double bond gave the methyl ketone 51,
which was transformed into triacetate 52 by a Baeyer±
Villiger oxidation, now in good yield $83%). Exhaustive
reduction of 52 with LiAlH4 gave triol 37 in 85% yield.
This triol was also obtained in the same yield from the tria-
cetate by saponi®cation using sodium methoxide in methanol.
The D5-alkene 56 was produced in a more selective way in
57% yield by treating 39 with thionyl chloride in pyridine,
but this approach was not compatible with the preservation
of its pleasant odour. Conversion of 39 to mesylate 59 was
achieved by methanesulfonyl chloride in pyridine in a 92%
yield, and syn elimination of this mesylate by treatment
with magnesium iodide in toluene afforded the D5-alkene
56 in 67% yield, with preservation of its pleasant smell. This
compound also was obtained in 71% yield from the same
mesylate 59 by treatment with lithium bromide and lithium
carbonate in N,N-dimethyl formamide at 1208C. Several
attempts were undertaken to achieve a selective synthesis
of the D6-alkene, but all met with moderate success.
When the results of the different approaches for the conver-
sion of larixol $1) into 6a-hydroxy Ambroxw $39) are
compared, it can be seen that the best yield is obtained by
the route described in Scheme 5, using the poisonous OsO4.
Although the second route described in Scheme 6 needs two
steps more, the overall yield of 39 is comparable and
environmentally safe chemicals are used. Furthermore, the
intermediates are all formed in high yield, which avoids
dif®cult puri®cation procedures, so in our opinion this is
the route of choice.
None of the Ambroxw-like compounds 39, 5339,40±55
showed the typical ambergris fragrance properties, only
the D5- and the D6-alkenes 56 and 57, respectively, and 58
had a pleasant smell.
6a-Hydroxy Ambroxw $39) was used as the key inter-
mediate for the preparation of some Ambroxw-like
compounds $Scheme 7). Treatment of 39 with Jones'
reagent in acetone afforded ketone 53 in 91% yield. Con-
version of 39 into its acetate 54 was achieved by acetic
anhydride in 94% yield, and the reaction of the alkoxide
of 39 with methyl iodide gave the methyl ether 55 in 95%
yield. When 39 was treated with p-toluenesulfonic acid in
benzene under Dean Stark conditions a non-separable
mixture of three compounds 56, 57 and 58 was formed in
3. Experimental
3.1. General and instrumentation41
3.1.1. ꢀ1)-ꢀ1S,4S,4aR,8aS)-4-ꢀꢀ3S)-3-Hydroxy-3-methyl-
4-pentenyl)-4a,8,8-trimethyl-3-methylenedecahydro-1-
naphthalenol ꢀlarixol ꢀ1)). The oleoresin of the larch
1
a ratio of 2:1:1, determined with H NMR and GC experi-
ments. This pleasant smelling mixture was analysed on a

M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
5669
turpentine $250 g), purchased from Carl Roth GmbH and
Co. $Karlsruhe, Germany), was dissolved in ether
$600 mL), and washed with a 2% aqueous solution of
KOH $400 mL). The organic layer was evaporated and the
yellow residue was dissolved in EtOH $300 mL) and hydro-
lyzed with a 4 M aqueous solution of KOH $200 mL) by
re¯uxing it for 3 h. The mixture was cooled to room
temperature and acidi®ed with a 4 M aqueous solution of
HCl. Extraction with ether, followed by usual work up gave
the crude larixol as a dark yellow oil. Crystallization from
cyclohexane gave pure larixol $1) $108 g). Mp 102±1038C
$lit.10a: 103±1048C); [a]Dˆ153.0 $c 2.1) $lit.10a: 150.4); IR
$KBr) nmax 3466, 3083, 2928, 1741, 1727, 1374, 1249,
3086, 2931, 2868, 2851, 1767, 1737, 1668, 1369, 1245,
1
1172 cm21; H NMR d 0.70 $s, 3H), 0.83 $s, 3H), 0.97 $s,
3H), 1.21 $s, 3H), 1.02±1.81 $m, 15H), 1.99 $s, 3H), 2.64
$dd, Jˆ5.1, 12.2 Hz, 1H), 4.62 $d, Jˆ1.3 Hz, 1H), 4.90 $d,
Jˆ1.3 Hz, 1H), 5.01 $dd, Jˆ1.4, 10.7 Hz, 1H), 5.16 $dd,
Jˆ1.3, 17.4 Hz, 1H), 5.86 $dd, Jˆ10.7, 17.4 Hz, 1H); 13C
NMR d 16.0 $q), 18.0 $t), 19.0 $t), 22.0 $q), 22.4 $q), 27.7
$q), 33.5 $s), 36.2 $q), 39.1 $t), 39.8 $s), 41.3 $t), 43.5 $t), 44.2
$t), 56.4 $d), 57.5 $d), 73.3 $d), 73.5 $s) 109.5 $t), 111.7 $t),
144.3 $s), 145.2 $d), 170.1 $s); HRMS: $M1260), found
288.2451. C20H32O requires 288.2449; MS m/e $%) 288
[$M1260), 22], 270 $66), 255 $80), 187 $33), 153 $100),
123 $43), 105 $35), 95 $36), 73 $40), 43 $39); Anal. found
C, 75.38; H, 10.39%. C22H36O3 requires C, 75.81; H,
10.41%.
1
1047 cm21; H NMR d 0.64 $s, 3H), 0.91 $s, 3H), 1.12 $s,
3H), 1.22 $s, 3H), 1.09±1.84 $m, 14H), 1.98 $t, Jˆ11.6 Hz,
1H), 2.32 $dd, Jˆ4.8, 12.1 Hz, 1H), 3.76 $dt, Jˆ4.9,
10.7 Hz, 1H), 4.60 $d, Jˆ1.4 Hz, 1H), 4.89 $d, Jˆ1.4 Hz,
1H), 5.05 $dd, Jˆ2.7, 10.7 Hz, 1H), 5.20 $dd, Jˆ10.7,
17.4 Hz, 1H), 5.91 $dd, Jˆ10.7, 17.4 Hz, 1H); 13C NMR d
16.0 $q), 18.0 $t), 19.1 $t), 22.3 $q), 27.6 $q), 33.8 $s), 36.6
$q), 39.2 $t), 39.5 $s), 41.3 $t), 43.7 $t), 49.1 $t), 56.4 $d), 60.5
$d), 71.6 $d), 73.5 $s), 108.4 $t), 111.6 $t), 145.2 $d), 145.5
$s); HRMS: $M1218), found 288.2449. C20H32O requires
288.2449; MS m/e $%) 288 [$M1218), 79], 273 $59), 270
$58), 255 $70), 153 $100), 135 $100), 121 $41), 109 $78), 95
$45); Anal. found C, 78.10; H, 11.28%. C20H34O2 requires
C, 78.38; H, 11.18%.
3.1.3. ꢀ1)-ꢀ3R)-5-ꢀꢀ1S,4aS,8aS)-5,5,8a-Trimethyl-2-
methylenedecahydro-1-naphthalenyl)-3-methyl-1-
penten-3-ol ꢀepi-manool ꢀ3)). 13-Epi-manool $3) was
isolated from the mother liquor left after crystallization of
larixol $1a) by ¯ash column chromatography on silica gel
$eluent PE/EA 15:1) as a very thick light yellow oil, $lit.21a
:
mp 35±388C). [a]Dˆ144.6 $c 2.6) $lit.21a: 148.0); IR
$liquid ®lm) nmax 3444, 3082, 2925, 1715, 1645, 1386,
1
1367, 1120 cm21; H NMR d 0.61 $s, 3H), 0.73 $s, 3H),
0.80 $s, 3H), 1.20 $s, 3H), 0.85±2.20 $m, 16H), 2.31 $dd,
Jˆ4.2, 12.2 Hz, 1H), 4.44 $d, Jˆ1.5 Hz, 1H), 4.74 $d,
Jˆ1.5 Hz, 1H), 4.79 $dd, Jˆ1.4, 10.7 Hz, 1H), 5.13 $dd,
Jˆ1.3, 17.3 Hz, 1H), 5.84 $dd, Jˆ10.7, 17.3 Hz, 1H); 13C
NMR d 14.4 $q), 17.7 $t), 19.4 $t), 21.7 $q), 24.4 $t), 27.6 $q),
33.5 $s), 33.6 $q), 38.4 $t), 39.1 $t), 39.9 $s), 41.4 $t), 42.2 $t),
55.6 $d), 57.3 $d), 73.6 $s), 106.5 $t), 111.6 $t), 145.3 $d),
148.7 $s); HRMS: M1, found 290.2612. C20H34O requires
290.2610; MS m/e $%) 290 $M1, 1), 272 $42), 257 $63), 137
$100), 123 $36), 109 $33), 107 $30), 95 $51), 93 $35), 81 $56),
69 $37).
3.1.2. ꢀ1)-ꢀ1S,4S,4aR,8aS)-4-ꢀꢀ3S)-3-Hydroxy-3-methyl-
4-pentenyl)-4a,8,8-trimethyl-3-methylenedecahydro-1-
naphthalenyl acetate ꢀlarixyl acetate ꢀ2)). To a solution of
larixol $1a) $5.0 g; 16.34 mmol) in pyridine $150 mL) was
added acetic anhydride $5 mL; 5.44 g; 53.2 mmol) and
4-N,N-dimethylaminopyridine $50 mg; 0.40 mmol). The
reaction mixture was stirred for 1 h, then poured into an
ice cold aqueous 4 M solution of HCl, and worked up
with ethyl acetate, to give the crude larixyl acetate as a
yellow oil. Puri®cation by ¯ash column chromatography
on silica gel with PE/EA 4:1 as eluent gave ®rst ꢀ1)-ꢀ1S)-
1-ꢀ2-ꢀꢀ1S,4S,4aS,8aR)-4-ꢀacetyloxy)-5,5,8a-trimethyl-2-
methylenedecahydro-1-naphthalenyl)ethyl)-1-methyl-2-
propenyl acetate ꢀlarixyl diacetate) $0.58 g; 1.47 mmol;
9%) as a white solid. Mp 115±116.58C $lit.21a 1178C);
[a]Dˆ146.6 $c 2.2) $lit.21a: 136.0); IR $KBr) nmax 2937,
3.1.4. ꢀ1)-ꢀ1S,3R,4R,4aS,8aS)-4-ꢀꢀ3S)-3-Hydroxy-3-
methyl-4-pentenyl)-3,4a,8,8-tetramethyldecahydro-1,3-
naphthalenediol ꢀ4). Epoxide 42 $5.5 g; 17.08 mmol) was
added in small portions at 08C into a stirred suspension of
LiAlH4 $1.3 g; 34.21 mmol) in freshly distilled THF
$100 mL). After stirring overnight at room temperature the
mixture was treated carefully with ethyl acetate $50 mL),
and diluted with an 1 M aqueous solution of HCl
$200 mL). The aqueous layer was extracted with ethyl
acetate and worked up as usual. The residue was recrystal-
lized from EA/CH2Cl2 1:1 to give compound 4 as white
crystals $5.2 g; 16.05 mmol; 94%). Mp 158±1598C;
[a]Dˆ143.4 $c 1.3, EtOH); IR $KBr) nmax 3427, 2923,
1
2895, 1728, 1257, 1243, 1023 cm21; H NMR d 0.72 $s,
3H), 0.85 $s, 3H), 0.99 $s, 3H), 1.47 $s, 3H), 1.01±1.95
$m, 13H), 2.02 $s, 3H), 2.04 $s, 3H), 2.57 $dd, Jˆ5.1,
12.2 Hz, 1H), 4.61 $d, Jˆ1.3 Hz, 1H), 4.91 $d, Jˆ1.3 Hz,
1H), 4.97 $dd, Jˆ4.5, 11.0 Hz, 1H), 5.08 $s, 1H), 5.14 $d,
Jˆ5.1 Hz, 1H), 5.95 $d, Jˆ10.9, 17.7 Hz, 1H); 13C NMR d
15.9 $q), 17.6 $t), 19.0 $t), 21.9 $q), 22.2 $q), 22.4 $q), 23.5
$q), 33.5 $s), 36.1 $q), 39.0 $t), 39.1 $t), 39.8 $s), 43.4 $t), 44.3
$t), 56.2 $d), 57.5 $d), 73.1 $d), 83.2 $s), 109.4 $t), 113.1 $t),
141.8 $d), 144.2 $s), 169.9 $s) 170.1 $s); HRMS: $M111),
found 391.2833. C24H39O4 requires 391.2848; MS m/e $%)
391 [$M111), 1], 331 $5), 289 $4), 273 $6), 272 $21), 271
$100), 270 $4), 269 $5), 203 $3), 101 $3), 61 $12); Anal.
found C, 74.14; H, 9.88%. C24H38O4 requires C, 73.80; H,
9.81%.
1
2542, 2474, 1457, 1388 cm21; H NMR $CDCl3/CD3OD)
d 0.72 $s, 3H), 0.90 $s, 3H), 1.08 $s, 3H), 1.11 $s, 3H),
1.18 $s, 3H), 1.04±1.48 $m, 13H), 2.00 $dd, Jˆ3.8,
11.9 Hz, 1H), 3.26 $br s, 3H), 3.70 $dt, Jˆ3.8, 10.7 Hz,
1H), 4.99 $dd, Jˆ1.5, 10.7 Hz, 1H), 5.13 $dd, Jˆ1.5,
17.4 Hz, 1H), 5.77 $dd, Jˆ10.7, 17.4 Hz, 1H); 13C NMR
$CDCl3/CD3OD) d 15.9 $q), 17.8 $t), 18.7 $t), 21.5 $q),
24.7 $q), 28.6 $q), 33.3 $s), 35.9 $q), 39.2 $s), 39.4 $t),
43.5 $t), 44.3 $t), 51.1 $d), 53.3 $t), 60.7 $d), 68.3 $d),
73.9 $s), 74.0 $s), 111.6 $t), 144.1 $d); HRMS: $M1218),
found 306.2560. C20H34O2 requires 306.2559; MS m/e
$%) 306 [$M1218), 1], 292 $6), 191 $53), 187 $56), 150
$53), 123 $81), 109 $72), 87 $100), 43 $99); Anal. found C,
Further elution gave larixyl acetate $2) $5.07 g; 14.54 mmol;
89%) as a white solid. Mp 78±798C $lit.21a: 828C);
[a]Dˆ145.2 $c 2.4) $lit.21a: 167.0); IR $KBr) nmax 3526,

5670
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
73.71; H, 11.37%. C20H36O3 requires C, 74.02; H,
11.18%.
IR $liquid ®lm) nmax 3429, 3088, 2912, 1651 cm21; 1H NMR
d 0.77 $s, 3H), 1.05 $s, 3H), 1.08 $s, 3H), 1.25 $s, 3H), 1.12±
1.92 $m, 13H), 1.85 $s, 3H), 5.03 $dd, Jˆ1.2, 10.7 Hz, 1H),
5.17 $dd, Jˆ1.2, 17.3 Hz, 1H), 5.68 $t, Jˆ1.4 Hz, 1H), 5.86
$dd, Jˆ10.7, 17.3 Hz, 1H); 13C NMR d 14.6 $q), 18.2 $t),
21.4 $t), 21.5 $q), 22.1 $q), 27.8 $q), 32.3 $s), 33.4 $q), 38.7
$t), 43.2 $t), 43.4 $s), 44.6 $t), 56.6 $d), 63.6 $d), 73.4 $s),
112.3 $t), 128.4 $d), 144.6 $d), 159.0 $s), 200.4 $s); HRMS:
M1, found 304.2394. C20H32O2 requires 304.2402; MS m/e
$%) 286 [$M1218), 17], 219 $19), 218 $34), 135 $100), 109
$28), 95 $21), 73 $89), 43 $31).
3.1.5. ꢀ1)-ꢀ1S,3R,4R,4aS,8aS)-3-Hydroxy-4-ꢀꢀ3S)-3-
hydroxy-3-methyl-4-pentenyl)-3,4a,8,8-tetramethyl-
decahydro-1-naphthalenyl acetate ꢀ5). A solution of
6a-hydroxy 4 $1.5 g; 4.63 mmol) in CH2Cl2 $10 mL) and
pyridine $8 mL) was treated with acetic anhydride
$1.75 mL; 1.90 g; 18.6 mmol) and DMAP $25 mg;
0.20 mmol) and stirred at 08C. After stirring for 150 min
the mixture was poured into an ice cold aqueous 4 M solu-
tion of HCl, and worked up with ethyl acetate. Flash column
chromatography $eluent PE/EA 3:1) of the residue gave
compound 5 $1.54 g; 4.21 mmol; 91%) as white crystals.
Mp 126±1288C; [a]Dˆ152.9 $c 2.1); IR $KBr) nmax
3.2. General procedure for the oxidation with 1.5 equiv.
of potassium permanganate
1
3423, 2924, 2869, 1727, 1716, 1469, 1266, 1239 cm21; H
To an ice-cooled stirred solution of labdanes 1±7
$3.25 mmol) and N,N,N0-triethylbenzenemethanaminium
chloride $1.1 g; 4.91 mmol) in dichloromethane $40 mL)
was added solid KMnO4 $0.77 g; 4.91 mmol) in small
portions in 15 min and then the mixture was allowed to
warm up to room temperature and stirring was continued
until conversion of the starting material, which took about
14 h. The dark brown reaction mixture was treated with an
aqueous saturated Na2SO3 solution $75 mL) and with a 3%
aqueous solution of oxalic acid $75 mL). Extraction of the
now colourless reaction mixture with ethyl acetate was
followed by usual work-up and puri®cation was performed
by ¯ash column chromatography. Gradient eluation gave
®rst methyl ketones 11±13, 24 and enol ethers 20±22
$eluent PE/EA 3:1), followed by triols 8±10, 23 $eluent
EA/MeOH 9:1).
NMR d 0.85 $s, 3H), 0.86 $s, 3H), 1.02 $s, 3H), 1.26 $s, 6H),
1.30±1.84 $m, 14H), 2.04 $s, 3H), 2.07 $dd, Jˆ3.9, 11.7 Hz,
1H), 2.54 $br s, 2H), 5.07 $dd, Jˆ3.3, 10.8 Hz, 1H), 5.23
$dd, Jˆ1.4, 17.2 Hz, 1H), 5.87 $dd, Jˆ10.8, 17.2 Hz, 1H);
13C NMR d 16.2 $q), 18.0 $t), 19.0 $t), 22.0 $2£q), 25.6 $q),
29.2 $q), 33.3 $s), 36.1 $q), 39.5 $t), 39.7 $s), 43.5 $t), 44.3 $t),
50.0 $t), 58.4 $d), 61.0 $d), 70.9 $d), 74.1 $s), 74.2 $s), 112.0
$t), 144.9 $d), 170.3 $s); HRMS: $M1218), found 348.2669.
C22H36O3 requires 348.2664; MS m/e $%) 348 [$M1218),
2], 288 $44), 191 $48), 190 $81), 121 $43), 109 $50), 95 $50),
81 $50), 71 $44), 69 $48), 43 $100); Anal. found C, 72.44; H,
10.69%. C22H38O4 requires C, 72.09; H, 10.45%.
3.1.6. ꢀ1)-ꢀ4S,4aR,8aS)-4-ꢀꢀ3S)-3-Hydroxy-3-methyl-4-
pentenyl)-3,4a,8,8-tetramethyl-4a,5,6,7,8,8a-hexahydro-
1ꢀ4H)-naphthalenone ꢀ7). To a stirred solution of larixol
Ê
$1) $2.5 g; 8.18 mmol) in CH2Cl2 $60 mL) was added 3 A
3.2.1. ꢀ1)-ꢀ2z,3S)-5-ꢀꢀ1S,4S,4aS,8aR)-4-Hydroxy-5,5,8a-
trimethyl-2-methylenedecahydro-1-naphthalenyl)-3-
methyl-1,2,3-pentanetriol ꢀ8). Compound 8 was isolated as
a white crystalline solid in 38% yield. Mp 139±1418C;
[a]Dˆ133.2 $c 1.5, EtOH); IR $KBr) nmax 3389, 2939,
molecular sieves $2.0 g) followed by pyridinium chloro-
chromate $PCC) $2.63 g; 12.25 mmol) and 10 drops of
acetic acid. After 1 h the mixture was ®ltered over silica
gel 60H and ¯ushed with ethyl acetate. Puri®cation of the
crude product by ¯ash column chromatography $PE/EA 3:1)
1
1644, 1382, 1271 cm21; H NMR d 0.42 $s, 3H), 0.71 $s,
gave
ꢀ1)-ꢀ4S,4aR,8aS)-4-ꢀꢀ3S)-3-hydroxy-3-methyl-4-
3H), 0.85 $s, 3H), 0.87 $s, 3H), 1.02±1.84 $m, 17H), 2.34
$dd, Jˆ4.8, 12.2 Hz, 1H), 3.14±3.84 $m, 4H), 4.33 $br s,
1H), 4.58 $br s, 1H); 13C NMR d 15.3 $q), 16.9 $t), 18.6 $t),
21.2 $q), 21.5 $q), 33.3 $s), 35.8 $q), 37.3 $t), 38.8 $t), 38.9
$s), 43.3 $t), 48.2 $t), 56.2 $d), 59.6 $d), 62.4 $t), 70.5 $d),
73.7 $s), 76.1 $d), 107.3 $t), 145.4 $s); HRMS: M1, found
340.2597. C20H36O4 requires 340.2614; HRMS: $M1218),
found 322.2509. C20H34O3 requires 322.2508; MS m/e $%)
340 $M1, 3), 322 $11), 261 $49), 243 $58), 218 $58), 153
$71), 109 $87), 95 $66), 69 $100), 43 $75); Anal. found C,
70.24; H, 10.71%. C20H36O4 requires C, 70.55; H, 10.66%.
pentenyl)-4a,8,8-trimethyl-3-methyleneoctahydro-1ꢀ2H)-
naphthalenone $2.35 g; 7.75 mmol; 95%) as a colourless
oil. [a]Dˆ174.6 $c 3.0); IR $liquid ®lm) nmax 3467, 2930,
1715, 1652, 1464, 1293, 1233 cm21; H NMR d 0.63 $s,
1
3H), 0.96 $s, 3H), 1.17 $s, 3H), 1.28 $s, 3H), 1.14±1.86
$m, 15H), 4.68 $d, Jˆ1.1 Hz, 1H), 4.85 $d, Jˆ1.1 Hz, 1H),
5.06 $dd, Jˆ1.3, 10.7 Hz, 1H), 5.20 $dd, Jˆ1.3, 17.2 Hz,
1H), 5.91 $dd, Jˆ10.7, 17.2 Hz, 1H); 13C NMR d 15.8
$q), 18.2 $t), 18.9 $t), 21.6 $q), 27.9 $q), 32.6 $s), 32.8 $q),
38.9 $t), 41.1 $t), 41.4 $s), 42.7 $t), 55.9 $t), 57.3 $d), 66.4 $d),
73.4 $s), 110.1 $t), 111.9 $t), 143.4 $s), 145.1 $d), 208.2 $s);
HRMS: M1, found 304.2400. C20H32O2 requires 304.2402;
MS m/e $%) 304 $M1, 4), 287 $23), 286 $100), 258 $23), 206
$52), 151 $63), 135 $36), 109 $28), 68 $30).
3.2.2. ꢀ1)-ꢀ1S,4S,4aR,8aS)-4a,8,8-Trimethyl-3-methyl-
ene-4-ꢀꢀ3S,4z)-3,4,5-trihydroxy-3-methylpentyl)-deca-
hydro-1-naphthalenyl acetate ꢀ9). Compound 9 was
isolated as an oil in 26% yield. [a]Dˆ124.6 $c 1.9); IR
1
$liquid ®lm) nmax 3378, 2910, 1720, 1647, 1258 cm21; H
The above mentioned C$6)-ketone $2.0 g; 6.58 mmol) was
isomerized into the conjugated ketone 7 by treatment with
an 1 M solution of sodium methoxide $5 mL) in methanol
$35 mL) at room temperature during 2 h. The methanol was
evaporated and an 1 M aquous solution of HCl $200 mL)
was added. Extraction with ether followed by usual work up
gave the crude product which was puri®ed by ¯ash column
chromatography $PE/EA 2:1) to give compound 724 $1.96 g;
6.45 mmol; 98%) as a light yellow oil. [a]Dˆ143.5 $c 3.6);
NMR d 0.71 $s, 3H), 0.83 $s, 3H), 0.97 $s, 3H), 1.10 $s, 3H),
1.16±1.84 $m, 16H), 2.00 $s, 3H), 2.63 $dd, Jˆ5.1, 12.2 Hz,
1H), 3.43 $t, Jˆ4.3 Hz, 1H), 3.64 $d, Jˆ2.6 Hz, 2H), 4.62 $s,
1H), 4.88 $s, 1H), 4.97 $dt, Jˆ5.8, 11.0 Hz, 1H); 13C NMR d
16.0 $q), 17.5 $t), 19.0 $t), 22.0 $2£q), 22.1 $q), 33.5 $s), 36.2
$q), 38.3 $t), 39.1 $t), 39.6 $s), 43.5 $t), 44.2 $t), 56.5 $d), 57.5
$d), 63.3 $t), 73.3 $d), 74.6 $s), 75.9 $d), 109.4 $s), 144.3 $s),
170.3 $s); HRMS: $M1218), found 364.2609. C22H36O4

M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
5671
requires 364.2614; MS m/e $%) 382 $M1, 2), 364 $3), 322
$26), 243 $83), 189 $44), 188 $43), 153 $54), 123 $34), 109
$30), 105 $29), 95 $29), 81 $31), 43 $100).
PE/EA 15:1) gave acetate 12 $0.73 g; 2.29 mmol; 91%) as a
colourless oil. Spectral data of 12 were identical with the
above mentioned.
3.2.3. ꢀ1)-ꢀ2z,3R)-5-ꢀꢀ1S,4aS,8aS)-5,5,8a-Trimethyl-2-
methylenedecahydro-1-naphthalenyl)-3-methyl-1,2,3-
pentanetriol ꢀ10). Compound 10 was isolated as a white
crystalline solid in 24% yield, as its hydrate. Mp 129±
1318C; [a]Dˆ120.8 $c 0.53); IR $KBr) nmax 3418, 2943,
3.2.7. ꢀ1)-4-ꢀꢀ1S,4aS,8aS)-5,5,8a-Trimethyl-2-methylene-
decahydro-1-naphthalenyl)-2-butanone ꢀ13). Methyl
ketone 13 was isolated as a colourless oil in 48% yield.
[a]Dˆ135.5 $c 1.8); IR $liquid ®lm) nmax 3477, 2931,
1
3078, 1716, 1460, 1366, 1162 cm21; H NMR d 0.44 $s,
1
2476, 3082, 1639, 1458, 1387 cm21; H NMR d 0.62 $s,
3H), 0.55 $s, 3H), 0.62 $s, 3H), 1.02±1.79 $m, 15H), 1.85 $s,
3H), 2.29 $dd, Jˆ4.2, 12.1 Hz, 1H), 4.19 $d, Jˆ0.9 Hz, 1H),
4.57 $d, Jˆ0.9 Hz, 1H); 13C NMR d 14.3 $q), 17.5 $t), 19.3
$t), 21.7 $q), 24.4 $t), 30.1 $q), 33.6 $2£q), 38.3 $t), 39.0 $t),
39.8 $s), 42.1 $t), 42.9 $t), 55.5 $d), 56.2 $d), 106.3 $t), 148.3
$s), 209.6 $s); HRMS: M1, found 262.2300. C18H30O requires
262.2297; MS m/e $%) 262 $M1, 52), 244 $48), 204 $51), 177
$40), 137 $100), 123 $36), 107 $40), 95 $55), 81 $51), 43 $56).
3H), 0.73 $s, 3H), 0.81 $s, 3H), 1.06 $s, 3H), 1.10±1.96
$m, 16H), 2.28 $dd, Jˆ4.0, 12.1 Hz, 1H), 3.36±3.66 $m,
5H), 4.46 $br s, 1H), 4.73 $br s, 1H); 13C NMR d 14.3 $q),
17.1 $t), 19.2 $t), 21.5 $q), 21.7 $q), 24.3 $t), 33.3 $s), 33.4
$q), 36.0 $t), 36.2 $t), 36.9 $t), 39.7 $s), 42.0 $t), 55.4 $d), 57.3
$d), 62.9 $t), 74.3 $s), 75.9 $d), 106.2 $t), 146.6 $s); HRMS:
M1, found 324.2664. C20H36O3 requires 324.2664; MS m/e
$%) 324 $M1, 6), 306 $10), 275 $28), 245 $100), 204 $38),
137 $81), 121 $42), 109 $43), 95 $61), 69 $58), 43 $52); Anal.
found C, 70.45; H, 11.14%. C20H36O3´H2O requires C,
70.13; H, 11.18%.
3.2.8. ꢀ1)-ꢀ2z,3S)-5-ꢀꢀ1R,2R,4aS,8aS)-2-Hydroxy-2,5,5,8a-
tetramethyldecahydro-1-naphthalenyl)-3-methyl-1,2,3-
pentanetriol ꢀ16). Compound 16 was isolated as a colour-
less oil in 25% yield. [a]Dˆ10.9 $c 1.5); IR $KBr) nmax
1
3.2.4. ꢀ1)-4-ꢀꢀ1S,4S,4aS,8aR)-4-Hydroxy-5,5,8a-trimethyl-
2-methylenedecahydro-1-naphthalenyl)-2-butanone ꢀ11).
Methyl ketone 11 was isolated as a white crystalline solid
in 45% yield. Mp 77±798C; [a]Dˆ143.4 $c 2.0); IR $liquid
®lm) nmax 3467, 2926, 1713, 1644, 1361 cm21; 1H NMR d
0.69 $s, 3H), 0.99 $s, 3H), 1.15 $s, 3H), 1.07±2.06 $m, 14H),
2.10 $s, 3H), 2.66 $dd, Jˆ4.9, 12.1 Hz, 1H), 3.82 $dt, Jˆ4.9,
10.6 Hz, 1H), 4.49 $d, Jˆ1.2 Hz, 1H), 4.88 $d, Jˆ1.2 Hz,
1H); 13C NMR d 15.9 $q), 17.7 $t), 19.1 $t), 22.3 $q), 30.1
$q), 33.9 $s), 36.6 $q), 39.2 $t), 39.4 $s), 42.8 $t), 43.6 $t), 49.0
$t), 55.4 $d), 60.4 $d), 71.6 $d), 108.2 $t), 145.3 $s), 209.2 $s);
HRMS: $M1218), found 260.2131. C18H28O requires
260.2140; MS m/e $%) 260 [$M1218), 76], 202 $53), 153
$52), 109 $55), 95 $38), 93 $72), 43 $100); Anal. found C,
78.12; H, 11.28%. C18H30O2 requires C, 77.65; H, 10.86%.
3405, 2927, 2860, 1464, 1387, 1085 cm21; H NMR d
0.73±1.20 $5£s, 5£3H), 1.26±1.98 $m, 18H), 3.31±3.77
$m, 5H); 13C NMR d 15.5 $q), 18.1 $t), 18.4 $t), 20.4 $t),
21.2 $q), 21.4 $q), 23.9 $q), 33.2 $s), 33.9 $q), 39.2 $s), 39.5
$t), 41.3 $t), 42.0 $t), 43.6 $t), 56.1 $d), 61.8 $d), 63.0 $t), 74.4
$s), 78.1 $d), 78.7 $s); HRMS: M1, found 342.2764.
C20H38O4 requires 342.2770; MS m/e $%) 342 $M1, 2),
324 $9), 306 $13), 245 $100), 177 $39), 137 $37), 109 $46),
95 $49), 81 $41), 69 $50), 43 $64).
3.2.9. ꢀ1)-4-ꢀꢀ1R,2R,4aS,8aS)-2-Hydroxy-2,5,5,8a-tetra-
ꢀ19).
methyldecahydro-1-naphthalenyl)-2-butanone
Methyl ketone 19 was isolated as a colourless oil in 6%
yield. After its isolation this methyl ketone quickly cyclized
to sclareol oxide $22). [a]Dˆ17.3 $c 1.3) $lit.42: 16.7, c
1.0); IR $liquid ®lm) nmax 3439, 2924, 2866, 1731, 1683,
1459, 1376, 1248, 1048 cm21; 1H NMR d 0.75 $s, 3H), 0.78
$s, 3H), 0.83 $s, 3H), 1.12 $s, 3H), 1.50±2.05 $m, 15H), 2.10
$s, 3H), 2.48±2.60 $m, 1H), 2.60±2.70 $m, 1H); MS m/e $%)
280 $M1, 1), 262 $100), 191 $81), 177 $39), 123 $46), 109
$97), 95 $64), 43 $78).
3.2.5. ꢀ1)-ꢀ1S,4S,4aR,8aS)-4a,8,8-Trimethyl-3-methyl-
ene-4-ꢀ3-oxobutyl)-decahydro-1-naphthalenyl
acetate
ꢀ12). Methyl ketone 12 was isolated as a colourless oil in
48% yield. [a]Dˆ156.2 $c 1.8); IR $liquid ®lm) nmax 2929,
1733, 1717, 1647, 1243 cm21; 1H NMR d 0.71 $s, 3H), 0.83
$s, 3H), 0.91 $s, 3H), 2.02 $s, 3H), 2.07 $s, 3H), 1.01±2.42
$m, 13H), 2.64 $dd, Jˆ5.1, 12.2 Hz, 1H), 4.51 $d, Jˆ1.3 Hz,
1H), 4.89 $d, Jˆ1.3 Hz, 1H), 4.97 $dt, Jˆ5.1, 10.9 Hz, 1H);
13C NMR d 15.8 $q), 17.6 $t), 18.9 $t), 21.9 $q), 22.4 $q), 30.0
$q), 33.4 $s), 36.1 $q), 38.9 $t), 39.6 $s), 42.6 $t), 43.3 $t), 44.0
$t), 55.2 $d), 57.4 $d), 73.1 $d), 109.2 $t), 144.0 $s), 170.0 $s),
209.0 $s); HRMS: $M1260), found 260.2146. C18H28O
requires 260.2140; MS m/e $%) 260 [$M1260), 76], 202
$88), 189 $35), 187 $32), 159 $19), 153 $57), 135 $21), 133
$36), 123 $22), 43 $100).
3.2.10. ꢀ4aR,6S,6aS,10aS,10bR)-3,4a,7,7,10a-Pentamethyl-
4a,5,6,6a,7,8,9,10,10a,10b-decahydro-1H-benzo[f]chro-
men-6-ol ꢀ20). Compound 20 was isolated as a colourless
1
oil in 47% yield. [a]Dˆ124.9 $c 0.4); H NMR d 0.82 $s,
3H), 1.00 $s, 3H), 1.13 $s, 3H), 1.15 $s, 3H), 1.75 $s, 3H),
1.10±1.94 $m, 12H), 2.23 $dd, Jˆ3.9, 11.8 Hz, 1H), 3.89
$dt, Jˆ3.9, 11.2 Hz, 1H), 4.42 $br d, Jˆ2.9 Hz, 1H); 13C
NMR d 16.2 $q), 18.3 $t), 18.6 $t), 20.3 $q), 21.2 $q), 22.0
$q), 33.6 $s), 36.6 $q), 37.4 $s), 39.3 $t), 43.6 $t), 52.0 $d),
52.1 $t), 61.4 $d), 68.9 $d), 75.5 $s), 94.7 $d), 147.8 $s);
HRMS: M1, found 278.2241. C18H30O2 requires
278.2246; MS m/e $%) 278 $M1, 99), 245 $29), 217 $100),
215 $30), 191 $53), 189 $52), 175 $44), 119 $30), 109 $39).
3.2.6. ꢀ1)-ꢀ1S,4S,4aR,8aS)-4a,8,8-Trimethyl-3-methyl-
ene-4-ꢀ3-oxobutyl)-decahydro-1-naphthalenyl
acetate
ꢀ12). To solution of methyl ketone 11 $0.7 g;
a
2.52 mmol) in CH2Cl2 $20 mL) and pyridine $15 mL) was
added acetic anhydride $2.17 g; 21.3 mmol) and 4-N,N-
dimethylaminopyridine $25 mg; 0.20 mmol). The reaction
mixture was stirred for 1 h, then poured into a 4 M aqueous
solution of HCl, and worked up with ethyl acetate. Puri®ca-
tion by ¯ash column chromatography on silica gel $eluent
3.2.11. ꢀ4aR,6S,6aS,10aS,10bR)-3,4a,7,7,10a-Pentamethyl-
4a,5,6,6a,7,8,9,10,10a,10b-decahydro-1H-benzo[f]chro-
men-6-yl acetate ꢀ21). Compound 21 was isolated as a
colourless oil in 48% yield. H NMR d 0.87 $s, 3H), 0.89
$s, 3H), 1.02 $s, 3H), 1.21 $s, 3H), 1.23±1.89 $m, 14H), 2.04
1

5672
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
$s, 3H), 2.17 $dd, Jˆ4.1, 11.7 Hz, 1H), 4.41±4.44 $m, 1H),
5.12 $dt, Jˆ4.1, 11.3 Hz, 1H); 13C NMR d 16.1 $q), 18.2 $t),
18.5 $t), 20.2 $q), 21.0 $q), 21.9 $q), 22.1 $q), 33.2 $s), 36.2
$q), 37.5 $s), 39.1 $t), 43.3 $t), 47.5 $t), 51.9 $d), 58.4 $d),
70.5 $d), 75.1 $s), 94.6 $d), 147.8 $s), 170.2 $s); HRMS: M1,
found 320.2350. C20H32O3 requires 320.2351; MS m/e $%)
320 $M1, 5), 260 $37), 190 $34), 189 $90), 119 $100), 109
$36), 69 $33), 43 $95).
reaction mixture was treated with an aqueous saturated
Na2SO3 solution and a 3% aqueous solution of oxalic
acid. Extraction of the colourless reaction mixture with
ethyl acetate was followed by usual work-up. Puri®cation
by ¯ash column chromatography $eluent PE/EA 3:1) gave
methyl ketone 24 $0.68 g; 2.24 mmol; 68%) as a colourless
oil. The analytical data were as mentioned before.
3.3. ꢀ1)-4-ꢀꢀ1S,4S,4aS,8aR)-4-ꢀꢀtert-Butylꢀdimethyl)-
silyl)oxy)-5,5,8a-trimethyl-2-methylenedecahydro-1-
naphthalenyl)-2-butanone ꢀ25)
3.2.12. ꢀ1)-ꢀ4aR,6aS,10aS,10bR)-3,4a,7,7,10a-Pentamethyl-
4a,5,6,6a,7,8,9,10,10a,10b-decahydro-1H-benzo[f]chro-
mene, ꢀsclareol oxide ꢀ22)). Compound 22 was isolated as a
light yellow oil in 51% yield. [a]Dˆ14.9 $c 1.3) $lit.42:
[a]Dˆ15.7, c 1.6); IR $liquid ®lm) nmax 3055, 2950,
A mixture of methyl ketone 11 $0.30 g; 1.08 mmol), tert-
butyldimethylsilyl chloride $1.63 g; 10.79 mmol) and
imidazole $1.47 g; 21.58 mmol) in DMF $25 mL) was
stirred at 608C. After heating overnight the mixture was
cooled to room temperature, diluted with ether, washed
with H2O and worked up as usual. The crude yellow oil
was puri®ed by ¯ash column chromatography $eluent PE/
EA 10:1) to give silyl ether 25 as an oil $0.32 g; 0.91 mmol;
84%). [a]Dˆ140.7 $c 0.7); IR $liquid ®lm) nmax 2928,
1
2900, 2890, 1687, 1470, 1390, 1342, 1000 cm21; H NMR
d 0.74 $s, 6H), 0.81 $s, 3H), 1.25 $s, 3H), 1.61 $s, 3H), 1.76±
1.83 $m, 13H), 1.87 $dt, Jˆ.3, 14.6 Hz, 1H), 4.30 $br s, 1H);
13C NMR d 19.3 $q), 18.2 $q), 18.6 $t), 19.8 $t), 20.7 $q), 21.0
$q), 26.6 $q), 28.6 $q), 33.1 $s), 36.7 $s), 39.3 $t), 41.1 $t),
41.9 $t), 52.4 $d), 55.2 $d), 76.2 $s), 94.6 $d), 147.8 $s);
HRMS: M1, found 262.2294. C18H30O requires 262.2297;
MS m/e $%) 262 $M1, 100), 191 $81), 177 $39), 123 $46),
109 $97), 95 $64), 81 $72), 43 $78).
1
2856, 1720, 1471, 1463, 1361, 1233 cm21; H NMR d
0.11 $s, 3H), 0.13 $s, 3H), 0.71 $s, 3H), 0.90 $s, 9H), 0.96
$s, 3H), 1.13 $s, 3H), 2.12 $s, 3H), 1.16±2.42 $m, 12H), 2.57
$m, 2H), 3.85 $dt, Jˆ4.6, 10.4 Hz, 1H), 4.48 $br s, 1H), 4.85
$br s, 1H); 13C NMR d 23.7 $q), 23.5 $q), 16.0 $q), 17.7 $t),
18.1 $s), 19.0 $t), 22.3 $q), 26.1 $3£q), 30.1 $q), 33.7 $s), 36.5
$q), 39.3 $s), 39.6 $t), 42.9 $t), 44.1 $t), 49.6 $t), 55.5 $d), 60.0
$d), 72.6 $d), 107.8 $t), 145.9 $s), 209.4 $s); HRMS:
$M1215), found 377.2878. C23H41O2Si requires 377.2876;
MS m/e $%) 392 $M1, 2), 377 $3), 335 $49), 267 $36), 243
$100), 211 $63), 119 $26), 43 $21).
3.2.13. ꢀ1)-ꢀ4S,4aR,8aS)-3,4a,8,8-Tetramethyl-4-ꢀꢀ3S)-
3,4,5-trihydroxy-3-methylpentyl)-4a,5,6,7,8,8a-hexahydro-
1ꢀ4H)-naphthalenone ꢀ23). Compound 23 was isolated as a
white crystalline solid in 56% yield. Mp 108±1108C;
[a]Dˆ121.0 $c 1.1); IR $KBr) nmax 3422, 2928, 1669,
1
1384, 1293, 1234, 1087 cm21; H NMR d 0.77 $s, 3H),
1.04 $s, 3H), 1.06 $s, 3H), 1.12 $s, 3H), 1.90 $s, 3H),
1.12±1.94 $m, 15H), 3.48 $t, Jˆ4.2 Hz, 1H), 3.76 $d,
Jˆ4.2 Hz, 2H), 5.72 $br s, 1H); 13C NMR d 14.6 $q), 18.0
$t), 21.0 $t), 21.4 $q), 21.9 $q), 22.2 $q), 33.3 $q), 38.6 $t),
41.8 $t), 43.0 $t), 43.4 $s), 43.5 $s), 56.7 $d), 63.3 $t), 63.5 $d),
74.5 $s), 74.8 $d), 128.3 $d), 159.1 $s), 200.6 $s); HRMS:
M1, found 338.2449. C20H34O4 requires 338.2457; MS 338
$M1, 10), 320 $13), 277 $17), 219 $49), 218 $73), 203 $12),
148 $14), 135 $100), 109 $18), 73 $17), 69 $18), 43 $22);
Anal. found C, 70.82; H, 10.12%. C20H34O4 requires C,
70.97; H, 10.13%.
3.4. Baeyer±Villiger oxidation with m-chloroperbenzoic
acid of 11
A mixture of methyl ketone 11 $0.20 g; 0.72 mmol) and
m-CPBA $0.35 g; 1.51 mmol) in CH2Cl2 $15 mL) was stir-
red at room temperature for 13 days. Ether was added and
the mixture was washed with a 2% aqueous Na2S2O3 solu-
tion, saturated aqueous sodium bicarbonate, brine, dried and
evaporated. Flash column chromatography $eluent PE/EA
5:1) gave epoxy acetate 26 $0.07 g; 0.22 mmol; 31%), acetal
28 $0.085 g; 0.29 mmol; 40%), and epoxide 30 $0.025 g;
0.09 mmol; 12%), respectively.
3.2.14. ꢀ1)-ꢀ4S,4aR,8aS)-3,4a,8,8-Tetramethyl-4-ꢀ3-oxo-
butyl)-4a,5,6,7,8,8a-hexahydro-1ꢀ4H)-naphthalenon ꢀ24).
Methyl ketone 24 was isolated as a colourless oil in 8%
yield. [a]Dˆ134.0 $c 1.4); IR $liquid ®lm) nmax 2928,
1
1716, 1669, 1454, 1357, 1176 cm21; H NMR d 0.79 $s,
3.4.1. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-2-ꢀ4-Hydroxy-3,4,4a,5,6,7,
8,8a-octahydro-5,5,8a-trimethyl-spiro[naphtalene-2ꢀ1H),
20-oxiran]-yl-ethyl acetate ꢀ26). Colourless oil;
[a]Dˆ116.7 $c 1.1); IR $liquid ®lm) nmax 3480, 3002,
3H), 1.06 $s, 3H), 1.09 $s, 3H), 1.84 $s, 3H), 1.14±2.06
$m, 10H), 2.11 $s, 3H), 2.47±2.70 $m, 2H), 5.70 $dd,
Jˆ1.3, 2.7 Hz, 1H); 13C NMR d 14.6 $q), 18.1 $t), 20.5 $t),
21.4 $q), 22.1 $q), 30.0 $q), 32.2 $s), 33.4 $q), 38.9 $t), 43.0 $t),
43.4 $s), 45.4 $t), 55.5 $d), 63.5 $d), 128.8 $d), 158.0 $s), 200.3
$s), 207.9 $s); HRMS: M1, found 276.2082. C18H28O2
requires 276.2089; MS m/e $%) 276 $M1, 2), 219 $6), 135
$19), 109 $13), 95 $6), 73 $100), 69 $2), 43 $30), 41.
1
2930, 2869, 1738, 1714, 1248, 1034 cm21; H NMR d
0.83 $s, 3H), 0.99 $s, 3H), 1.19 $s, 3H), 1.05±1.98 $m,
13H), 2.05 $s, 3H), 2.59 $d, Jˆ4.1 Hz, 1H), 2.76 $dd,
Jˆ1.9, 4.1 Hz, 1H), 4.03 $dt, Jˆ3.8, 10.4 Hz, 1H), 3.95±
4.14 $m, 2H); 13C NMR d 15.8 $q), 18.2 $t), 21.0 $q), 21.5
$t), 22.2 $q), 33.7 $s), 36.5 $q), 39.6 $s), 43.6 $t), 46.7 $t), 49.6
$d), 50.8 $t), 57.0 $s), 60.1 $d), 65.2 $t), 69.7 $d), 171.6 $s);
HRMS: M1, found 310.2139. C18H30O4 requires 310.2144;
MS m/e $%) 310 $M1, 1), 250 $27), 153 $39), 126 $48), 109
$100), 98 $48), 69 $70), 43 $82).
3.2.15. ꢀ1)-ꢀ4S,4aR,8aS)-3,4a,8,8-Tetramethyl-4-ꢀ3-oxo-
butyl)-4a,5,6,7,8,8a-hexahydro-1ꢀ4H)-naphthalenon ꢀ24).
To a solution of 7 $1.0 g; 3.29 mmol) and benzyltriethyl-
ammonium chloride $2.21 g; 9.87 mmol) in dichloro-
methane $40 mL) was added solid KMnO4 $1.55 g;
9.87 mmol) at once at room temperature. The mixture was
stirred until completion of the reaction. The dark brown
3.4.2. ꢀ1)-ꢀ3S,4S,9S,10R)-5,5,9,13-Tetramethyl-14,16-dioxa-
tetracyclo[11.2.1.01,10.04,9]hexade-can-3-ol ꢀ28). Crystalline

M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
5673
1
solid; mp 126±1288C; [a]Dˆ117.1 $c 1.0); IR $KBr) nmax
3457, 2985, 2923, 2849, 1460, 1385, 1030 cm21; 1H NMR d
1.09 $s, 3H), 1.14 $s, 3H), 1.18 $s, 3H), 1.45 $s, 3H), 0.91±
1.85 $m, 14H), 2.10 $dd, Jˆ4.3, 13.4 Hz, 1H), 3.38 $d,
Jˆ6.8 Hz, 1H), 3.81 $d, Jˆ6.8 Hz, 1H), 4.19 $dt, Jˆ4.3,
11.0 Hz, 1H); 13C NMR d 16.9 $t), 17.8 $q), 18.3 $t), 22.5
$q), 24.9 $q), 33.6 $s), 33.6 $t), 37.2 $q), 40.3 $t), 40.4 $s), 43.9
$t), 45.6 $t), 49.6 $d), 59.8 $d), 68.2 $d), 75.8 $t), 82.4 $s),
108.6 $s); HRMS: M1, found 294.2198. C18H30O3 requires
294.2195; MS m/e $%) 294 $M1, 11), 234 $71), 206 $100),
191 $33), 188 $44), 173 $30), 109 $35), 95 $28), 69 $36), 43
$45); Anal. found C, 73.19; H, 10.47%. C18H30O3 requires C,
73.43; H, 10.27%.
1253, 1061 cm21; H NMR d 20.02 $s, 3H), 0.00 $s, 3H),
0.76 $s, 3H), 0.77 $s, 9H), 0.90 $s, 3H), 1.02 $s, 3H), 1.28 $s,
3H), 1.87 $dd, Jˆ4.2, 13.3 Hz, 1H), 0.95±1.80 $m, 13H),
3.23 $d, Jˆ6.7 Hz, 1H), 3.62 $d, Jˆ6.7 Hz, 1H), 4.06 $dt,
Jˆ4.2, 10.6 Hz, 1H); 13C NMR d 23.7 $q), 23.6 $q), 17.0
$t), 17.9 $q), 18.1 $s), 18.2 $t), 22.4 $q), 25.0 $q), 26.2 $3£q),
33.4 $s), 33.6 $t), 37.0 $q), 40.1 $s), 40.8 $t), 44.4 $t), 46.0 $t),
49.7 $d), 59.8 $d), 69.1 $d), 76.0 $t), 82.3 $s), 108.5 $s);
HRMS: M1, found 408.3050. C24H44O2Si requires
408.3060; MS m/e $%) 408 $M1, 2), 352 $27), 351 $100),
275 $14), 119 $9), 117 $11), 75 $26), 43 $10); Anal. found C,
70.68; H, 11.14%. C24H44O3Si requires C, 70.54; H,
10.85%.
3.4.3. ꢀ1)-ꢀ1S,4S,4aS,8aR)-4-ꢀ4-Hydroxy-octahydro-5,5,
8a-trimethyl-spiro[naphtalene-2ꢀ1H),20-oxiran]-yl)-2-
butanone ꢀ30). Colourless oil; [a]Dˆ119.1 $c 0.4); IR
$liquid ®lm) nmax 3479, 2928, 2870, 1714, 1462, 1386,
3.5.3. ꢀ1)-ꢀ1S,4S,4aS,8aR)-4-ꢀ4-[ꢀ1,1-Dimethylethyl)di-
methylsilyl]oxy-octahydro-5,5,8a-trimethyl-spiro[naph-
1
talene-2ꢀ1H),20-oxiran]-yl)-2-butanone ꢀ31). H NMR d
0.05 $s, 3H), 0.07 $s, 3H), 0.83 $s, 3H), 0.87 $s, 9H), 0.97
$s, 3H), 1.12 $s, 3H), 1.08±1.98 $m, 12H), 1.58 $dd, Jˆ3.8,
11.2 Hz, 1H), 2.09 $s, 3H), 2.32±2.65 $m, 2H), 2.82 $dd,
Jˆ2.1, 4.2 Hz, 1H), 4.03 $dt, Jˆ4.5, 10.7 Hz, 1H).
1
1362 cm21; H NMR d 0.81 $s, 3H), 0.97 $s, 3H), 1.15 $s,
3H), 1.04±2.02 $m, 15H), 2.07 $s, 3H), 2.48±2.55 $m, 1H),
2.80 $dd, Jˆ1.9, 4.3 Hz, 1H), 3.98 $dt, Jˆ4.5, 10.9 Hz, 1H);
13C NMR d 15.8 $q), 16.0 $t), 18.3 $t), 22.2 $q), 29.9 $q), 33.7
$s), 36.5 $q), 39.1 $t), 40.1 $s), 43.5 $t), 47.0 $t), 51.0 $t), 52.2
$d), 57.8 $s), 60.0 $d), 69.6 $d), 75.7 $t), 209.2 $s); HRMS:
M1, found 294.2200. C18H30O3 requires 294.2195; MS m/e
$%) 294 $M1, 6), 234 $44), 206 $61), 153 $32), 109 $81), 95
$48), 81 $45), 69 $67), 43 $100).
3.6. Baeyer±Villiger oxidation with m-chloroperbenzoic
acid of 12
A mixture of acetate 12 $0.20 g; 0.62 mmol) and m-CPBA
$0.38 g; 1.56 mmol) in CH2Cl2 $10 mL) was stirred at room
temperature for 10 days. Ether was added and the mixture
was washed with a 2% aqueous solution of Na2S2O3, satu-
rated aqueous sodium bicarbonate, and worked up as usual.
Flash column chromatography $eluent PE/EA 5:1) afforded
epoxy diacetate 34 $0.187 g; 0.53 mmol; 84%) as white
crystals. Further elution gave epoxy methyl ketone 33
$0.023 g; 0.069 mmol; 11%) as an oil.
3.5. Baeyer±Villiger oxidation with m-chloroperbenzoic
acid of 25
A mixture of silyl ether 25 $0.10 g; 0.25 mmol) and
m-CPBA $0.18 g; 0.71 mmol) in CH2Cl2 $8 mL) was stirred
at room temperature for 48 h. Ether was added and the
mixture was washed with a 2% aqueous solution of sodium
thiosulfate, saturated aqueous sodium bicarbonate, brine,
dried and evaporated. Flash column chromatography $eluent
PE/EA 15:1) of the crude product gave acetal 29 $0.023 g;
0.056 mmol; 20%), epoxy acetate 27 $0.020 g; 0.047 mmol;
17%), and epoxide 31 $0.050 g; 0.12 mmol; 48%), respec-
tively. During the identi®cation procedure epoxide 31 is
converted into acetal 29.
3.6.1. ꢀ1)-ꢀ1S,4S,4aS,8aR)-4-ꢀ4-Acetoxy-octahydro-5,5,
8a-trimethyl-spiro[naphtalene-2ꢀ1H),20-oxiran]-yl)-2-
butanone ꢀ33). IR $KBr) nmax 2929, 2869, 1731, 1714,
1
1366, 1244, 1027 cm21; H NMR d 0.85 $s, 3H), 0.88 $s,
3H), 0.99 $s, 3H), 1.03±1.99 $m, 12H), 2.04 $s, 3H), 2.09 $s,
3H), 2.27±2.85 $m, 3H), 2.82 $dd, Jˆ1.9, 4.2 Hz, 1H), 5.19
$dt, Jˆ5.0, 11.2 Hz, 1H); 13C NMR d 15.8 $q), 16.1 $t), 18.3
$t), 21.8 $q), 22.3 $q), 29.7 $s), 29.9 $q), 36.1 $q), 39.0 $t),
40.2 $s), 42.5 $t), 43.3 $t), 44.6 $t), 50.9 $t), 52.1 $d), 57.2 $d),
57.4 $s), 71.2 $d), 170.0 $s), 208.9 $s); HRMS: $M1260),
found 276.2085. C18H28O2 requires 276.2089; MS m/e $%)
336 $M1, 2), 292 $10), 276 $26), 203 $38), 189 $30), 188
$29), 187 $100), 109 $38), 95 $29), 69 $40), 43 $87).
3.5.1. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-2-ꢀ4-[ꢀ1,1-Dimethylethyl)-
dimethylsilyl]oxy-3,4,4a,5,6,7,8,8a-octahydro-5,5,8a-
trimethyl-spiro[naphtalene-2ꢀ1H),20-oxiran]-yl-ethyl
acetate ꢀ27). Oil; [a]Dˆ16.2 $c 1.1); IR $liquid ®lm) nmax
1
2927, 2854, 1724, 1224, 1208 cm21; H NMR d 20.01 $s,
3H), 0.00 $s, 3H), 0.73 $s, 3H), 0.78 $s, 9H), 0.89 $s, 3H),
1.08 $s, 3H), 1.07±1.72 $m, 12H), 1.95 $s, 3H), 2.44 $d,
Jˆ4.1 Hz, 1H), 2.66 $dd, Jˆ2.0, 4.1 Hz, 1H), 3.88±4.02
$m, 3H); 13C NMR d 24.0 $q), 23.5 $q), 16.0 $q), 18.1
$s), 18.2 $t), 21.1 $q), 21.5 $t), 22.2 $q), 26.0 $3£q), 33.6
$s), 36.4 $q), 39.5 $t), 39.6 $s), 44.0 $t), 47.2 $t), 49.5 $d), 50.8
$t), 57.1 $s), 59.7 $d), 65.3 $t), 70.5 $d), 171.1 $s); HRMS:
$M1215), found 409.2772. C23H41O4Si requires 409.2774;
MS m/e $%) 409 [$M1215), 1], 367 $21), 233 $71), 215 $78),
183 $57), 109 $44), 105 $43), 69 $49), 43 $41), 32 $100).
3.6.2. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-2-ꢀ4-Acetoxy-3,4,4a,5,6,7,
8,8a-octahydro-5,5,8a-trimethyl-spiro[naphtalene-2ꢀ1H),
20-oxiran]-1b-yl-ethyl acetate ꢀ34). Mp 86±888C;
[a]Dˆ18.4 $c 1.2); IR $KBr) nmax 2928, 1721, 1735,
1
1245 cm21; H NMR d 0.89 $s, 3H), 0.91 $s, 3H), 1.06 $s,
3H), 2.05 $s, 3H), 2.06 $s, 3H), 1.11±2.03 $m, 12H), 2.67 $d,
Jˆ4.1 Hz, 1H), 2.77 $dd, Jˆ2.0, 4.1 Hz, 1H), 4.03 $dt,
Jˆ1.5, 7.0 Hz, 2H), 5.21 $dt, Jˆ5.0, 11.2 Hz, 1H); 13C
NMR d 15.8 $q), 18.2 $t), 21.0 $q), 21.5 $t), 21.8 $q), 22.3
$q), 33.4 $s), 36.1 $q), 39.0 $t), 39.8 $s), 42.1 $t), 43.3 $t), 49.6
$d), 50.7 $t), 56.6 $s), 57.2 $d), 65.1 $t), 71.1 $d), 170.0 $s),
171.0 $s); HRMS: $M1260), found 292.2036. C18H28O3
requires 292.2038; MS m/e $%) 292 [$M1260), 35], 232
$96), 217 $65), 187 $24), 153 $24), 109 $33), 43 $100); Anal.
3.5.2. ꢀ1)-ꢀ1R,3S,4S,9S,10R)-tert-Butylꢀdimethyl)silyl-5,
5,9,13-tetramethyl-14,16-dioxatetracyclo[11.2.1.01,10.04,9]-
hexadec-3-yl ether ꢀ29). Crystals; mp 54±568C;
[a]Dˆ129.6 $c 0.7); IR $KBr) nmax 3442, 2929, 1385,

5674
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
found C, 68.08; H, 9.27%. C20H32O5 requires C, 68.15; H,
9.15%.
with ethyl acetate. The combined organic layers were
washed with brine and worked up as usual. The crude oil
was puri®ed by ¯ash column chromatography on silica gel
$eluent PE/EA 1:1) to give diol 36 $0.155 g; 0.58 mmol;
85%) and triol 37 $0.018 g; 0.068 mmol; 10%) both as
white crystalline materials.
3.7. ꢀ1)-ꢀ1S,4S,4aS,8aR)-4-ꢀ4-[ꢀ1,1-Dimethylethyl)-
dimethylsilyl]oxy-octahydro-5,5,8a-trimethyl-spiro-
[naphtalene-2ꢀ1H),20-oxiran]-yl)-2-butanone ꢀ31)
3.7.3. ꢀ1)-ꢀ3aS,5S,5aS,9aS,9bR)-3a-ꢀHydroxymethyl)-6,
6,9a-trimethyldodecahydronaphtho[2,1-b]furan-5-ol ꢀ36).
Mp 133±1358C; [a]Dˆ111.0 $c 0.5); IR $KBr) nmax 3395,
2918, 1472, 1344, 1212, 1015 cm21; 1H NMR $400 MHz) d
0.88 $s, 3H), 0.98 $s, 3H), 1.00 $s, 3H), 1.14±2.03 $m, 10H),
2.17 $dd, Jˆ5.6, 15.2 Hz, 1H), 2.87 $br s, 3H), 3.42 $dd,
Jˆ11.0, 17.8 Hz, 2H), 3.78±3.90 $m, 2H), 4.11 $dt, Jˆ1.9,
5.8 Hz, 1H); 13C NMR d 17.0 $q), 18.3 $t), 22.5 $q), 26.8 $t),
33.7 $s), 33.9 $q), 36.4 $s), 40.1 $t), 42.0 $t), 42.3 $t), 53.8 $d),
59.2 $d), 66.4 $t), 66.4 $d), 68.2 $t), 83.7 $s); HRMS:
$M1231), found 237.1854. C15H25O2 requires 237.1855;
MS m/e $%) 238 [$M1230), 16], 237 $100), 219 $12), 113
$16), 85 $16), 69 $24), 57 $12), 55 $13), 43 $14), 32 $12);
Anal. found C, 72.28; H, 10.81%. C16H28O3 requires C,
71.60; H, 10.52%.
Silyl ether 25 $0.10 g; 0.28 mmol) and MMPP $0.44 g;
0.71 mmol) were dissolved in CH2Cl2 $8 mL) and stirred
at room temperature for 3 days. Ether was added and the
mixture was treated with an aqueous 1 M solution of hydro-
chloric acid. The aqueous mixture was extracted with ethyl
acetate. The combined organic layers were washed with a
saturated aqueous sodium bicarbonate solution and worked
up as usual. Flash column chromatography $eluent PE/EA
6:1) gave epoxide 31 $0.07 g; 0.17 mmol; 60%) as a colour-
less oil. [a]Dˆ117.3 $c 0.6); IR $liquid ®lm) nmax 2931,
1
2868, 1721, 1209 cm21; H NMR d 0.05 $s, 3H), 0.07 $s,
3H), 0.83 $s, 3H), 0.87 $s, 9H), 0.97 $s, 3H), 1.12 $s, 3H),
1.08±1.98 $m, 12H), 1.58 $dd, Jˆ3.8, 11.2 Hz, 1H), 2.09 $s,
3H), 2.32±2.65 $m, 2H), 2.82 $dd, Jˆ2.1, 4.2 Hz, 1H), 4.03
$dt, Jˆ4.5, 10.7 Hz, 1H); 13C NMR d 24.0 $q), 23.5 $q),
16.0 $q), 16.1 $t), 18.1 $s), 18.2 $t), 22.2 $q), 26.0 $3£q), 26.2
$q), 33.6 $s), 36.5 $q), 39.6 $t), 39.8 $s), 44.0 $t), 44.9 $t), 47.6
$t), 51.0 $t), 52.2 $d), 59.8 $d), 70.5 $d), 82.3 $s), 209.1 $s);
MS m/e $%) 408 $M1, 2), 367 $2), 233 $44), 215 $100), 159
$32), 145 $34), 117 $38), 105 $33), 75 $64), 73 $44), 69 $39),
43 $36).
37; Mp 156±1588C; [a]Dˆ131.4 $c 0.8, EtOH); IR $KBr)
max 3462, 3287, 2925, 2872, 1463, 1378, 1247, 1051 cm21
;
n
1H NMR $DMSO-d6) d 0.73 $s, 3H), 0.87 $s, 3H), 1.02 $s,
3H), 1.10 $s, 3H), 1.05±1.56 $m, 10H), 1.90 $dd, Jˆ3.4,
11.9 Hz, 1H), 2.48 $d, Jˆ1.7 Hz, 1H), 3.33 $t, Jˆ7.7 Hz,
2H), 3.48±3.55 $m, 1H), 4.09 $br s/m, 3H); 13C NMR
$CDCl3/CD3OD) d 20.3 $q), 22.0 $t), 25.7 $q), 29.0 $q),
31.6 $t), 37.5 $s), 40.1 $q), 43.1 $s), 43.4 $t), 47.5 $t), 57.7
$t), 62.2 $d), 64.7 $d), 67.4 $t), 72.3 $d), 76.2 $s); HRMS:
$M1215), found 255.2071. C15H27O3 requires 255.1960;
HRMS: $M1215±18), found 237.1852. C15H25O2
requires 237.1855; MS m/e $%) 270 $M1, 2), 255 $1),
151 $6), 109 $7), 95 $6), 87 $100), 69 $9), 43 $11); Anal.
found C, 71.38; H, 11.35%. C16H30O3 requires C, 71.07; H,
11.18%.
3.7.1. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-4-ꢀꢀtert-Butylꢀdimethyl)-
silyl)oxy)-1-ꢀ2-hydroxyethyl)-2,5,5,8a-tetramethyldeca-
hydro-2-naphthalenol ꢀ32). Epoxy acetate 27 $0.016 g;
0.038 mmol) was dissolved in freshly distilled THF
$5 mL), cooled to 08C and LiAlH4 $0.01 g; 0.15 mmol)
was added. After stirring for 3 h at room temperature, the
mixture was carefully treated with ethyl acetate and diluted
with 4 M HCl. The aqueous mixture was extracted with
ethyl acetate, the combined organic layers were washed
with brine and worked up as usual. Puri®cation by ¯ash
column chromatography $eluent PE/EA 1:1) on silica gel
gave compound 32 $0.01 g; 0.023 mmol; 62%) as a sticky
colourless oil. [a]Dˆ133.6 $c 0.05); IR $liquid ®lm) nmax
3.7.4. ꢀ1)-ꢀ1S,3R,4R,4aS,8aS)-4-ꢀ2-Hydroxyethyl)-3,4a,
8,8-tetramethyldecahydro-1,3-naphthalenediol
ꢀ37).
Aldehyde 43 was treated with LiAlH4 as described
above. The triol 37 was obtained in 74% yield as white
crystals. For analytical data see foregoing experimental
procedure.
1
3344, 2929, 2858, 1373, 1027 cm21; H NMR d 0.12 $s,
3H), 0.14 $s, 3H), 0.85 $s, 3H), 0.89 $s, 9H), 0.94 $s, 3H),
1.14 $s, 3H), 1.23 $s, 3H), 1.10±1.98 $m, 11H), 2.13 $dd,
Jˆ3.6, 12.2 Hz, 1H), 2.46 $br s, 2H), 3.47±3.52 $m, 1H),
3.78±3.86 $m, 1H), 3.91 $dt, Jˆ3.4, 10.5 Hz, 1H); 13C NMR
d 23.9 $q), 23.5 $q), 16.6 $q), 18.1 $t), 22.0 $q), 25.7 $q),
26.1 $3£q), 27.7 $t), 29.7 $s), 33.6 $s), 36.3 $q), 39.2 $s), 39.8
$t), 43.9 $t), 54.7 $t), 58.4 $d), 60.9 $d), 64.0 $t), 69.7 $d), 72.8
$s); HRMS: $M1215±18), found 351.2722. C18H28O3
requires 351.2719; MS m/e $%) 351 [$M1215±18), 4],
309 $26), 237 $66), 217 $39), 191 $100), 119 $39), 109
$47), 95 $44), 75 $79), 73 $39), 69 $59), 43 $47).
An unpuri®ed mixture of aldehyde 44 and acid 47 was
reduced as described above. Puri®cation by ¯ash column
chromatography $eluent EA/MeOH 95:5) gave the same
pure triol 37 as white crystals as obtained before.
Aldehyde 44 was treated with LiAlH4 as above mentioned.
The triol 37 was obtained in 87% yield as white crystals.
The analytical data were as mentioned before.
Triacetate 52 was dissolved in freshly distilled THF, cooled
to 08C and treated with LiAlH4. Work up as usual and after
puri®cation crystalline triol 37 was obtained in 85% yield.
The analytical data were as mentioned before.
3.7.2. ꢀ1)-ꢀ1S,3R,4R,4aS,8aS)-4-ꢀ2-Hydroxyethyl)-3,4a,
8,8-tetramethyldecahydro-1,3-naphthalenediol
ꢀ37).
Epoxy acetate 34 $0.24 g; 0.68 mmol) was dissolved in
freshly distilled THF $8 mL), cooled to 08C and LiAlH4
$110 mg; 2.89 mmol) was added in small portions. After
stirring overnight, the mixture was carefully treated with
ethyl acetate, and then diluted with a 4 M aqueous solution
of hydrochloric acid. The aqueous mixture was extracted
Triacetate 52 was dissolved in MeOH and treated with
an 1 M solution of sodium methoxide in methanol. Usual
work up, followed by puri®cation by ¯ash column

M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
5675
chromatography gave triol 37 in 85% yield as white crystals,
identical with the product obtained before.
$100 mL), H2O $180 mL), [18]crown-6 $600 mg) and
sodium hydrogen carbonate $24 g) was added a solution of
oxone $18.08 g; 29.41 mmol) in H2O $100 mL) at 08C. After
stirring at 08C for 90 min the mixture was diluted with a
saturated aqueous sodium hydrogen carbonate solution. The
aqueous mixture was extracted with ethyl acetate and the
combined organic layers were washed with a 10% aqueous
solution of Na2S2O3, saturated aqueous sodium bicarbonate
and brine. Usual work up gave a crude oil which was puri-
®ed by ¯ash column chromatography $eluent PE/EA 1:1) to
give ®rst monoepoxide 42 $4.46 g; 13.33 mmol; 68%) as a
white crystalline solid. Further elution afforded the diepox-
ide 41 $1.26 g; 3.73 mmol; 19%) as white crystals.
3.7.5. ꢀ1)-ꢀ1S,3R,4R,4aS,8aS)-4-ꢀ2-Hydroxyethyl)-3,4a,
8,8-tetramethyldecahydro-1,3-naphthalenediol ꢀ37). A
mixture of CaCO3 $0.25 g; 2.50 mmol), PPh3 $0.65 g;
0.25 mmol), a catalytic amount of Pd$OAc)2 $5 mg) and
triacetate 48 $1.0 g; 2.20 mmol) in dioxane $25 mL) was
re¯uxed for 90 min. The mixture was cooled to room
temperature and diluted with ether. The ethereal solution
was washed with an aqueous saturated sodium bicarbonate
solution $2£), water, and brine and worked up as usual. The
residual light yellow oil was puri®ed by ¯ash column chro-
matography $eluent PE/EA 6:1) to yield an unseparable
mixture of dienes 49.
3.7.8. ꢀ1)-ꢀ1S,4S,4aR,8aS)-4ꢀꢀ3S)-3-Hydroxy-3-methyl-
4-spiro-20-oxiran)-4a,8,8-trimethyl-3-spiro-20-oxiran-
decahydro-1-naphtalenol ꢀ41). Mp 74±758C; [a]Dˆ
117.7 $c 1.9); IR $liquid ®lm) nmax 3445, 3051, 2930,
A solution of a mixture of dienes 49 $0.50 g; 1.28 mmol)
in a mixture of MeOH and CH2Cl2 3:1 $40 mL) was
ozonolyzed at 2788C. The excess ozone was expelled and
NaBH4 $0.10 g; 2.56 mmol) was added at 2788C. The
mixture was allowed to warm to room temperature. After
stirring overnight an 1 M aqueous solution of hydrochloric
acid was added. The aqueous mixture was extracted with
ethyl acetate. The combined organic layers were washed
with brine and worked up as usual.
1
2866, 1460, 1455, 1387, 1366 cm21; H NMR d 0.76 $s,
3H), 0.97 $s, 3H), 1.12 $s, 3H), 1.18 $s, 3H), 1.03±1.91
$m, 16H), 2.51±2.84 $m, 5H), 3.96 $dt, Jˆ3.5, 11.2 Hz,
1H); 13C NMR d 15.4 $t), 15.8 $q), 18.3 $t), 22.3 $q), 22.6
$q), 33.8 $s), 36.6 $q), 39.2 $s), 40.2 $s), 42.9 $t), 43.2 $t),
43.7 $t), 47.0 $t), 51.1 $t), 53.3 $d), 57.6 $s), 58.0 $d), 60.3
$d), 69.5 $s), 69.8 $d); HRMS: M1, found 338.2460.
C20H34O4 requires 338.2457; MS m/e $%) 338 $M1, 1),
307 $43), 213 $63), 153 $48), 109 $100), 95 $79), 93 $45),
81 $63), 69 $96), 55 $62), 43 $97), 41 $51); Anal. found C,
70.90; H, 10.12%. C20H34O4 requires C, 70.97; H, 10.12%.
The crude product was dissolved in MeOH $10 mL) and an
1 M solution of sodium methoxide in methanol $2 mL) was
added. After stirring overnight at room temperature the
MeOH was evaporated under reduced pressure. The residue
was acidi®ed with an 1 M aqueous solution of hydrochloric
acid and extracted with CH2Cl2. Work up as usual afforded a
residue which was ¯ash chromatographed $eluent ®rst EA,
then EA/MeOH 95:5) to yield triol 37 $0.27 g; 0.86 mmol;
67%) as a white crystalline solid, identical with the product
mentioned before.
42; Mp 114±1158C; [a]Dˆ116.3 $c 1.7); IR $KBr) nmax
1
3442, 3048, 2932, 2857, 1455, 1237 cm21; H NMR d
0.81 $s, 3H), 0.99 $s, 3H), 1.19 $s, 3H), 1.24 $s, 3H),
0.94±2.05 $m, 16H), 2.59 $d, Jˆ4.3 Hz, 1H), 2.79 $dd,
Jˆ1.8, 4.2 Hz, 1H), 4.01 $dt, Jˆ4.8, 10.9 Hz, 1H), 5.04
$dd, Jˆ1.3, 10.7 Hz, 1H), 5.20 $dd, Jˆ1.3, 17.2 Hz, 1H),
5.84 $dd, Jˆ10.7, 17.2 Hz, 1H); 13C NMR d 15.8 $q), 16.0
$t), 18.3 $t), 22.3 $q), 28.1 $q), 33.8 $s), 36.6 $q), 39.2 $t),
40.2 $s), 43.6 $t), 43.7 $t), 47.0 $t), 51.2 $t), 53.7 $d), 57.7 $s),
60.3 $d), 69.9 $d), 73.6 $s), 111.8 $t), 145.0 $d); HRMS:
$M1231), found 291.2323. C19H31O2 requires 291.2324;
MS m/e $%) 291 [$M1231), 8], 233 $60), 109 $91), 69
$90), 43 $59), 31 $100); Anal. found C, 74.19; H, 10.85%.
C20H34O3 requires C, 74.49; H, 10.63%.
3.7.6. ꢀ1)-ꢀ3aR,5S,5aS,9aS,9bR)-3a,6,6,9a-Tetramethyl-
dodecahydronaphtho[2,1-b]furan-5-ol ꢀ39). A solution
of triol 37 $1.0 g; 3.70 mmol) and p-toluenesulfonic acid
$0.10 g; 0.52 mmol) in nitromethane $50 mL) was stirred
at room temperature for 4 h. Ether was added and the
mixture was washed with saturated aqueous sodium bicar-
bonate and brine and worked up as usual. Flash column
chromatography on silica gel $eluent PE/EA 1:1) gave 6a-
hydroxy Ambroxw $39) $0.60 g; 2.37 mmol; 64%) as white
crystals. Mp 146±1488C; [a]Dˆ115.1 $c 1.1); IR $KBr)
nmax 3423, 2964, 2844, 1463, 1414, 1379, 1247,
3.7.9. ꢀ2)-ꢀ1R,2R,4S,4aS,8aS)-4-Hydroxy-2,5,5,8a-tetra-
methyl-1-ꢀ2-oxo-ethyl)decahydro-2-naphthalenyl acetate
ꢀ43). A solution of 6a-hydroxy 4 $0.30 g; 0.92 mmol) and
NaIO4 $1.28 g; 6.0 mmol) in THF $20 mL) and water $4 mL)
was treated with a 2.5 wt% OsO4 solution in tert-BuOH
$0.5 mL). The mixture was warmed to 458C and stirred
overnight. The reaction mixture was ®ltered and diluted
with a saturated aqueous Na2SO3 solution and extracted
with ethyl acetate. The combined organic layers were dried
and evaporated. Puri®cation was performed by ¯ash column
chromatography $eluent PE/EA 1:1) to yield aldehyde 43
$0.183 g; 0.58 mmol; 63%) as a colourless oil. Further elution
gave the acetyl compounds 45a $0.044 g; 0.15 mmol; 16%)
and 45b $0.033 g; 0.11 mmol; 12%) as liquids.
1
1051 cm21; H NMR d 0.86 $s, 3H), 1.00 $s, 3H), 1.12 $s,
3H), 1.15 $s, 3H), 1.02±1.74 $m, 12H), 2.27 $dd, Jˆ3.9,
11.1 Hz, 1H), 3.77±4.00 $m, 3H); 13C NMR d 16.7 $q),
18.6 $t), 22.1 $q), 22.9 $q), 23.0 $t), 34.1 $s), 35.8 $s), 36.7
$q), 40.3 $t), 44.4 $t), 51.7 $t), 60.3 $d), 62.8 $d), 65.7 $t), 70.9
$d), 79.1 $s); HRMS: $M121), found 251.2013. C16H27O2
requires 251.2011; MS m/e $%) 252 $M1, 1), 251 $1), 237
$100), 219 $10), 125 $7), 113 $11), 109 $10), 95 $6), 69 $15),
43 $8); Anal. found C, 76.14; H, 11.18%. C16H28O2 requires
C, 76.08; H, 11.34%.
3.7.7. ꢀ1)-ꢀ1S,4S,4aR,8aS)-4ꢀꢀ3S)-3-Hydroxy-3-methyl-
4-pentenyl)-4a,8,8-trimethyl-3-spiro-20-oxiran-decahy-
dro-1-naphtalenol ꢀ42). To a stirred solution of larixol $1)
$6.0 g; 19.61 mmol) in CH2Cl2 $100 mL), acetone
43; [a]Dˆ29.6 $c 0.2, EtOH); IR $KBr) nmax 3498, 2933,
1
1726, 1713, 1388, 1274, 1055 cm21; H NMR d 0.87 $s,
3H), 0.98 $s, 3H), 1.13 $s, 3H), 1.52 $s, 3H), 1.88 $s, 3H),

5676
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
1.17±1.93 $m, 12H), 3.02 $dd, Jˆ4.0, 12.2 Hz, 1H), 3.86
$dt, Jˆ4.0, 10.9 Hz, 1H), 9.65 $t, Jˆ2.2 Hz, 1H); 13C NMR
d 17.1 $q), 18.0 $t), 21.5 $q), 21.9 $q), 22.5 $q), 33.6 $s), 36.3
$q), 38.3 $s), 39.9 $t), 40.4 $t), 43.2 $t), 49.6 $t), 52.7 $d), 60.3
$d), 68.3 $d), 84.0 $s), 169.7 $s), 202.0 $d); HRMS:
$M1215), found 295.1902. C17H27O4 requires 295.1909;
MS m/e $%) 295 [$M1215), 46], 125 $8), 124 $40), 109
$100), 97 $37), 95 $44), 87 $32), 81 $39), 69 $78), 43 $87).
$3.2 g; max. 8.12 mmol) in acetone $80 mL) was treated
dropwise with Jones' reagent $20 mL; 53.44 mmol) at
08C. Stirring was continued for 1 h and water $300 mL)
was added. The aqueous mixture was extracted with ethyl
acetate. The combined organic layers were washed with
brine and worked up as usual to give a mixture of aldehyde
44 and acid 47 $2.73 g). A sample was puri®ed by ¯ash
column chromatography on silica gel $eluent EA) to give
crystalline 44 $26%) and oily 47 $24%). Spectral data of 44
were identical with the above mentioned.
3.7.10. 1-ꢀꢀ2z,3aR,5S,5aS,9aS,9bR)-5-Hydroxy-3a,6,6,9a-
tetramethyldodecahydronaphtho[2,1-b]furan-2-yl)etha-
none ꢀ45a). [a]Dˆ10.6 $c 0.5); IR $KBr) nmax 3483, 2924,
1711, 1459, 1245, 1047 cm21; 1H NMR d 0.80 $s, 3H), 0.93
$s, 3H), 1.09 $s, 3H), 1.14 $s, 3H), 0.98±2.03 $m, 12H), 2.14
$s, 3H), 2.28 $dd, Jˆ3.9, 11.1 Hz, 1H), 3.88 $dt, Jˆ3.9,
10.8 Hz, 1H), 4.34 $dd, Jˆ3.2, 9.8 Hz, 1H); 13C NMR d
16.2 $q), 18.1 $t), 21.6 $q), 22.8 $q), 26.8 $q), 26.9 $t), 33.7
$s), 35.3 $s), 36.2 $q), 39.8 $t), 43.9 $t), 51.1 $t), 59.1 $d), 62.1
$d), 70.2 $d), 81.2 $d), 81.8 $s), 210.8 $s); HRMS: $M1243),
found 251.2013. C16H27O2 requires 251.2011; MS m/e $%)
251 [$M1243), 30], 233 $79), 189 $67), 125 $34), 119 $38),
109 $45), 43 $48), 31 $100); Anal. found C, 73.06; H, 9.99%.
C18H30O3 requires C, 73.43; H, 10.27%.
47; [a]Dˆ145.5 $c 0.4); IR $KBr) nmax 3437, 2929, 1740,
1709, 1244, 1134, 1033 cm21; 1H NMR d 0.85 $s, 3H), 0.93
$s, 3H), 1.02 $s, 3H), 1.56 $s, 3H), 1.89 $s, 3H), 1.11±1.95
$m, 10H), 2.04 $s, 3H), 2.33±2.42 $m, 2H), 2.88 $dd, Jˆ4.0,
12.1 Hz, 1H), 5.11 $dt, Jˆ4.0, 11.1 Hz, 1H); 13C NMR d
16.7 $q), 17.9 $t), 21.2 $q), 21.8 $q), 22.0 $q), 22.4 $q), 30.4
$t), 33.1 $s), 35.9 $q), 38.6 $t), 38.9 $s), 43.0 $t), 45.0 $t), 54.3
$d), 57.5 $d), 69.7 $d), 84.3 $s), 169.8 $s), 170.1 $s), 180.2 $s);
HRMS: $M1260), found 308.1988. C18H28O4 requires
308.1988; MS m/e $%) 308 [$M1260), 2], 266 $26), 249
$26), 248 $100), 233 $22), 188 $43), 173 $23), 119 $31), 69
$27), 43 $54).
3.7.11. 1-ꢀꢀ2z,3aR,5S,5aS,9aS,9bR)-5-Hydroxy-3a,6,6,9a-
tetramethyldodecahydronaphtho[2,1-b]furan-2-yl)etha-
none ꢀ45b). [a]Dˆ25.0 $c 0.1); IR $KBr) nmax 3470, 2926,
1717, 1459, 1385, 1058 cm21; 1H NMR d 0.79 $s, 3H), 0.89
$s, 3H), 1.05 $s, 3H), 1.09 $s, 3H), 1.02±1.99 $m, 12H), 2.17
$s, 3H), 2.26 $dd, Jˆ3.9, 11.2 Hz, 1H), 3.87 $dt, Jˆ7.0,
10.8 Hz, 1H), 4.28 $t, Jˆ8.2 Hz, 1H); 13C NMR d 16.6
$q), 18.1 $t), 21.6 $q), 24.3 $q), 26.0 $t), 26.9 $q), 33.7 $s),
35.4 $s), 36.3 $q), 39.9 $t), 43.9 $t), 51.2 $t), 60.3 $d), 62.1
$d), 70.2 $d), 81.0 $s), 82.8 $d), 211.0 $s); HRMS: $M1215),
found 279.1959. C17H27O3 requires 279.1960; MS m/e $%)
279 [$M1215), 2], 233 $75), 189 $86), 125 $43), 119 $52),
109 $65), 69 $100), 43 $74); Anal. found C, 72.98; H, 9.96%.
C18H30O3 requires C, 73.43; H, 10.27%.
3.7.14. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-4-ꢀAcetyloxy)-1-ꢀꢀ3S)-3-
ꢀacetyloxy)-3-methyl-4-pentenyl)-2,5,5,8a-tetramethyl-
decahydro-2-naphthalenyl acetate ꢀ48). 6a-Hydroxy 4
$0.50 g; 1.54 mmol) was dissolved in N,N-dimethylaniline
$15 mL) and acetyl chloride $8.83 g; 112.5 mmol) was
added dropwise and stirred overnight. The reaction mixture
was acidi®ed cautiously by a 4 M aqueous solution of sul-
furic acid and worked up as usual. The residual yellow oil
was puri®ed by ¯ash column chromatography on silica gel
$eluent PE/EA 3:1) to yield triacetate 48 $0.57 g;
1.23 mmol; 80%) as white crystals. Mp 100±1028C;
[a]Dˆ138.8 $c 2.2); IR $KBr) nmax 3441, 2931, 1737,
1
1732, 1372, 1258, 1239, 1021 cm21; H NMR d 0.81 $s,
3H), 0.88 $s, 3H), 0.97 $s, 3H), 1.49 $s, 3H), 1.01±1.92
$m, 16H), 1.93 $s, 3H), 1.98 $s, 3H), 1.99 $s, 3H), 2.74
$dd, Jˆ4.1, 12.0 Hz, 1H), 5.03 $dt, Jˆ4.1, 11.0 Hz, 1H),
5.07 $dd, Jˆ0.9, 17.5 Hz, 1H), 5.15 $dd, Jˆ0.9, 10.7 Hz,
1H), 5.92 $dd, Jˆ10.9, 17.5 Hz, 1H); 13C NMR d 16.6
$q), 17.9 $t), 19.4 $t), 21.7 $q), 21.8 $q), 21.9 $q), 22.1 $q),
22.7 $q), 23.6 $q), 33.1 $s), 35.9 $q), 39.4 $t), 39.4 $s), 42.1
$t), 43.3 $t), 44.9 $t), 57.7 $d), 57.9 $d), 70.0 $d), 83.0 $s),
85.8 $s), 113.2 $t), 141.7 $d), 169.7 $s), 169.9 $s), 170.1 $s);
HRMS: M1, found 450.2977. C26H42O6 requires 450.2981;
MS m/e $%) 450 $M1, 1), 435 $1), 270 $68), 262 $63), 202
$69), 190 $88), 189 $100), 43 $83); Anal. found C, 69.07; H,
9.48%. C26H42O6 requires C, 69.30; H, 9.40%.
3.7.12. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-4-ꢀAcetyloxy)-2,5,5,8a-
tetramethyl-1-ꢀ2-oxo-ethyl)decahydro-2-naphthalenyl
acetate ꢀ44). This reaction was performed as described for
43. Puri®cation by ¯ash column chromatography $eluent
PE/EA 3:2) afforded aldehyde 44 $0.174 g; 0.49 mmol;
72%) as a white crystalline solid. Mp 114±1168C;
[a]Dˆ131.2 $c 0.5); IR $KBr) nmax 2929, 1719, 1710,
1
1239, 1045 cm21; H NMR d 0.87 $s, 3H), 0.95 $s, 3H),
1.04 $s, 3H), 1.57 $s, 3H), 1.07±1.89 $m, 11H), 1.90 $s,
3H), 2.05 $s, 3H), 2.94 $dd, Jˆ4.1, 12.2 Hz, 1H), 5.14 $dt,
Jˆ4.1, 11.2 Hz, 1H), 9.69 $t, Jˆ2.1 Hz, 1H); 13C NMR d
16.9 $q), 17.9 $t), 21.4 $q), 21.8 $q), 21.9 $q), 22.5 $q), 33.2
$s), 35.9 $q), 38.5 $s), 39.8 $t), 40.4 $t), 43.0 $t), 45.2 $t), 52.4
$d), 57.8 $d), 69.6 $d), 84.3 $s), 169.5 $s), 170.0 $s), 201.7
$d); HRMS: $M1215), found 337.2006. C19H29O5 requires
337.2015; MS m/e $%) 337 [$M1215), 1], 293 $4), 233 $64),
190 $70), 109 $29), 43 $100); Anal. found C, 67.95; H,
9.15%. C20H32O5 requires C, 68.15; H, 9.15%.
3.7.15. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-4-ꢀAcetyloxy)-1-ꢀꢀ3E)-5-
ꢀacetyloxy)-3-methyl-3-pentenyl)-2,5,5,8a-tetramethyl-
decahydro-2-naphthalenyl acetate ꢀ50). A mixture of tri-
acetate 48 $1.0 g; 2.22 mmol) and PdCl2$CH3CN)2 $25 mg;
0.10 mmol) in freshly distilled THF $25 mL) was stirred at
room temperature for 1 h. Ether was added and the mixture
was washed with brine and worked up as usual. Flash
column chromatography $eluent PE/EA 6:1) gave 50
$0.98 g; 2.18 mmol; 98%) as a sticky solid. Mp 58±618C;
[a]Dˆ138.2 $c 2.5); IR $KBr) nmax 3443, 2931, 1735, 1367,
3.7.13. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-4-ꢀAcetyloxy)-2,5,5,8a-
tetramethyl-1-ꢀ2-oxo-ethyl)decahydro-2-naphthalenyl
acetate ꢀ44) and ꢀ1)-ꢀꢀ1R,2R,4S,4aS,8aS)-2,4-Bisꢀacetyl-
oxy)-2,5,5,8a-tetramethyldecahydro-1-naphthalenyl)-
acetic acid ꢀ47). A stirred solution of the crude enol ether 21
1
1025 cm21; H NMR d 0.78 $s, 3H), 0.81 $s, 3H), 0.94 $s,
3H), 1.47 $s, 3H), 1.65 $s, 3H), 1.12±1.87 $m, 13H), 1.88 $s,

M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
5677
3H), 1.95 $s, 3H), 2.00 $s, 3H), 2.72 $dd, Jˆ4.1, 12.0 Hz,
1H), 4.52 $d, Jˆ7.1 Hz, 2H), 5.04 $dt, Jˆ4.1, 11.1 Hz, 1H),
5.27 $dt, Jˆ1.2, 7.2 Hz, 1H); 13C NMR d 16.0 $q), 16.5 $q),
17.9 $t), 21.0 $q), 21.7 $q), 21.8 $q), 21.9 $q), 22.7 $q), 24.2
$t), 33.5 $s), 35.9 $q), 38.2 $t), 39.1 $t), 39.6 $s), 43.4 $t), 44.1
$t), 55.2 $d), 57.5 $d), 61.3 $t), 73.2 $d), 118.2 $d), 142.6 $s),
144.1 $s), 169.9 $s), 170.0 $s), 171.0 $s); HRMS: $M1260),
found 390.2767. C24H38O4 requires 390.2770; MS m/e $%)
390 [$M1260), 1], 330 $6), 270 $12), 190 $100), 140 $34),
119 $19), 81 $11), 69 $10).
droxy Ambroxw $39) $0.30 g; 1.19 mmol) in acetone
$10 mL) was treated with Jones' reagent $2 mL;
5.34 mmol) at 08C. After 1 h the excess of Jones' reagent
was destroyed by adding i-PrOH $3 mL) and the mixture
was diluted with water $150 mL). Extraction with ethyl
acetate, followed by usual work up gave after ¯ash column
chromatography on silica gel $eluent PE/EA 5:1) ketone 53
$0.27 g; 1.08 mmol; 91%) as a crystalline solid. Mp 66±
688C; [a]Dˆ234.1 $c 1.3); IR $KBr) nmax 3412, 2927,
1
1705, 1451, 1388, 1361, 1267 cm21; H NMR d 0.88 $s,
3H), 0.96 $s, 3H), 1.06 $s, 3H), 1.13 $s, 3H), 1.09±1.94
$m, 8H), 2.13 $dd, Jˆ6.2, 13.0 Hz, 2H), 2.65 $dd, Jˆ6.2,
17.3 Hz, 2H), 3.95±4.07 $m, 2H); 13C NMR d 15.9 $q), 18.0
$t), 21.3 $q), 21.5 $q), 22.2 $t), 32.2 $s), 32.2 $q), 36.8 $s),
40.3 $t), 42.8 $t), 58.0 $t), 60.0 $d), 65.4 $t), 66.9 $d), 81.0 $s),
209.4 $s); HRMS: M1, found 250.1935. C16H26O2 requires
250.1933; MS m/e $%) 250 $M1, 12), 236 $14), 235 $100),
151 $15), 123 $16), 111 $23), 109 $16), 43 $12); Anal. found
C, 77.17; H, 10.74%. C16H26O2 requires C, 76.75; H,
10.47%.
3.7.16. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-4-ꢀAcetyloxy)-2,5,5,8a-
tetramethyl-1-ꢀ3-oxobutyl)decahydro-2-naphthalenyl
acetate ꢀ51). A solution of compound 50 $2.0 g; 4.44 mmol)
in a mixture of CH2Cl2 and MeOH 1:1 $60 mL) was ozono-
lyzed at 2788C. The excess ozone was expelled and PPh3
$2.33 g; 8.88 mmol) was added at 2788C. The mixture was
allowed to warm up to room temperature. After stirring
overnight the solvents were evaporated and the residue
was puri®ed by ¯ash column chromatography $eluent PE/
EA 3:1) to yield 51 $1.6 g; 4.22 mmol; 95%) as a white
solid. Mp 128±1298C; [a]Dˆ142.8 $c 1.1); IR $KBr) nmax
3433, 2931, 1722, 1708, 1369, 1248, 1025 cm21; 1H NMR d
0.81 $s, 3H), 0.90 $s, 3H), 0.97 $s, 3H), 1.51 $s, 3H), 1.21±
1.85 $m, 12H), 1.90 $s, 3H), 2.01 $s, 3H), 2.07 $s, 3H), 2.51
$dd, Jˆ7.0, 10.5 Hz, 1H), 2.74 $dd, Jˆ4.1, 12.1 Hz, 1H),
5.06 $dt, Jˆ4.1, 11.0 Hz, 1H); 13C NMR d 16.5 $q), 17.9 $t),
19.4 $t), 21.7 $q), 21.9 $q), 22.0 $q), 22.8 $q), 29.9 $q), 33.2
$s), 35.9 $q), 39.4 $s), 39.6 $t), 43.2 $t), 44.9 $t), 46.2 $t), 57.1
$d), 57.8 $d), 69.9 $d), 85.9 $s), 169.9 $s), 170.0 $s), 208.8 $s);
HRMS: $M1260), found 320.2334. C20H32O3 requires
320.2351; MS m/e $%) 320 [$M1260), 4], 260 $100), 242
$23), 202 $58), 189 $69), 187 $55), 153 $25), 119 $54), 43
$34); Anal. found C, 69.52; H, 9.68%. C22H36O5 requires C,
69.44; H, 9.54%.
3.7.19. ꢀ1)-ꢀ3aR,5S,5aS,9aS,9bR)-3a,6,6,9a-Tetramethyl-
dodecahydronaphtho[2,1-b]furan-5-yl acetate ꢀ54). A
solution of 6a-hydroxy Ambroxw $39) $0.30 g;
1.19 mmol) in dichloromethane $10 mL) and pyridine
$5 mL) was treated with acetic anhydride $0.5 mL; 0.54 g;
5.32 mmol) and DMAP $25 mg; 0.20 mmol). After 2 h the
reaction mixture was neutralized with a 4 M solution of
hydrochloric acid. Usual work up gave the crude product
which was puri®ed by ¯ash column chromatography $eluent
PE/EA 5:1) to give acetate 54 $0.33 g; 1.12 mmol; 94%) as
white crystals. Mp 73±748C; [a]Dˆ123.9 $c 1.2); IR
$liquid ®lm) nmax 2927, 2875, 1738, 1378, 1242,
1
1030 cm21; H NMR d 0.89 $s, 3H), 0.94 $s, 3H), 1.00 $s,
3H), 1.19 $s, 3H), 1.08±1.81 $m, 11H), 2.05 $s, 3H), 2.20
$dd, Jˆ4.1, 11.2 Hz, 1H), 3.79±4.00 $m, 2H), 5.19 $dt,
Jˆ4.1, 11.2 Hz, 1H); 13C NMR d 16.1 $q), 18.1 $t), 21.7
$q), 21.9 $q), 22.3 $q), 22.5 $t), 33.2 $s), 35.2 $s), 35.8 $q),
39.8 $t), 43.7 $t), 43.7 $t), 59.5 $d), 59.8 $d), 65.3 $t), 71.6 $d),
78.4 $s), 170.1 $s); HRMS: $M1215), found 279.1957.
C17H27O3 requires 279.1960; MS m/e $%) 294 $M1, 1),
279 $1), 220 $16), 219 $100), 123 $10), 69 $6), 43 $14);
Anal. found C, 73.11; H, 10.30%. C18H30O3 requires C,
73.43; H, 10.27%.
3.7.17. ꢀ1)-ꢀ1R,2R,4S,4aS,8aS)-4-ꢀAcetyloxy)-1-ꢀ2-ꢀacetyl-
oxy)ethyl)-2,5,5,8a-tetramethyldecahydro-2-naphthalenyl
acetate ꢀ52). Methyl ketone 51 $0.20 g; 0.52 mmol) and
m-CPBA $0.18 g; 1.04 mmol) in CH2Cl2 $25 mL) were
stirred at room temperature for 1 week. Ether was added
and the mixture was washed with a 2% aqueous solution
of Na2S2O3, saturated aqueous sodium bicarbonate and
brine, respectively, and worked up as usual. Flash column
chromatography $eluent PE/EA 6:1) of the residual oil gave
triacetate 52 $0.17 g; 0.42 mmol; 83%) as white crystals.
Mp 142±1448C; [a]Dˆ125.4 $c 0.9); IR $KBr) 3428,
3.7.20. ꢀ1)-ꢀ3aR,5S,5aS,9aS,9bR)-3a,6,6,9a-Tetramethyl-
dodecahydronaphtho[2,1-b]furan-5-yl methyl ether
ꢀ55). A 60% suspension of sodium hydride in mineral oil
$0.08 g; 2.0 mmol) and 6a-hydroxy Ambroxw $39) $0.10 g;
0.397 mmol) in dry DMF $15 mL) was heated at 1008C
under nitrogen for 1 h. Iodomethane $0.86 mL;
1.97 mmol) was added dropwise and the mixture was heated
overnight. The mixture was cooled, poured into water and
acidi®ed with a 4 M solution of hydrochloric acid and the
mixture was worked up as usual. Flash column chromato-
graphy with PE/EA 3:1 as the eluent gave ether 55 $0.10 g;
0.377 mmol; 95%) as a colourless oil. [a]Dˆ141.9 $c 0.2);
IR $liquid ®lm) nmax 3372, 2929, 2877, 1724, 1462, 1455,
1380, 1098 cm21; 1H NMR d 0.89 $s, 3H), 0.92 $s, 3H), 1.11
$s, 3H), 1.14 $s, 3H), 1.08±1.80 $m, 11H), 2.44 $dd, Jˆ3.8,
11.3 Hz, 1H), 3.35 $s, 3H), 3.87 $dt, Jˆ3.9, 10.7 Hz, 1H),
3.85±3.97 $m, 2H); 13C NMR d 16.5 $q), 18.2 $t), 22.0
$q), 22.6 $q), 22.7 $t), 33.6 $s), 35.2 $s), 36.1 $q), 39.9
1
2934, 1729, 1718, 1706, 1239, 1026 cm21; H NMR d
0.82 $s, 3H), 0.90 $s, 3H), 0.99 $s, 3H), 1.53 $s, 3H),
1.18±1.86 $m, 11H), 1.92 $s, 3H), 2.00 $s, 3H), 2.03 $s,
3H), 2.80 $dd, Jˆ4.1, 12.1 Hz, 1H), 3.94±4.18 $m, 2H),
5.08 $dt, Jˆ4.1, 11.2 Hz, 1H); 13C NMR d 16.7 $q), 17.9
$t), 21.6 $q), 21.9 $2£q), 22.0 $q), 22.8 $q), 24.8 $t), 33.2 $s),
35.9 $q), 39.0 $s), 39.4 $t), 43.2 $t), 44.9 $t), 54.0 $d), 57.8
$d), 65.6 $t), 69.8 $d), 85.2 $s), 169.9 $s), 170.0 $s), 171.0 $s);
HRMS: $M1260), found 336.2296. C20H32O4 requires
336.2301; MS m/e $%) 336 [$M1260), 1], 276 $30), 217
$19), 216 $68), 201 $35), 189 $21), 119 $20), 109 $20), 69
$25), 43 $100); Anal. found C, 66.99; H, 9.30%. C22H36O6
requires C, 66.64; H, 9.15%.
3.7.18. ꢀ2)-ꢀ3aR,5aS,9aR,9bR)-3a,6,6,9a-Tetramethylde-
cahydronaphtho[2,1-b]furan-5ꢀ2H)-one ꢀ53). 6a-Hy-

5678
M. G. Bolster et al. / Tetrahedron 57 ,2001) 5663±5679
$t), 43.8 $t), 45.0 $t), 56.2 $q), 59.9 $d), 60.7 $d), 65.3
$t), 78.6 $s), 79.8 $d); HRMS: $M1215), found 251.2014.
C16H27O2 requires 251.2011; MS m/e $%) 266 $M1, 3), 251
$33), 219 $11), 109 $7), 101 $20), 85 $10), 84 $100), 43 $12),
31 $9).
67%) as an odorous, colourless oil, with spectral data in
accordance with the above mentioned.
A mixture of mesylate 59 $0.025 g; 0.075 mmol), Li2CO3
$34 mg; 0.43 mmol) and LiBr $34 mg; 0.39 mmol) in dry
DMF $7 mL) was heated to 1208C under nitrogen for 4 h.
The mixture was cooled and water was added. The aqueous
mixture was extracted with light petroleum ether and
worked up as usual. The crude oil was puri®ed by ¯ash
column chromatography $eluent PE/EA 15:1) to give
fragrance compound 56 $0.013 g; 0.053 mmol; 71%) as an
odorous colourless oil with spectral data in agreement with
the above mentioned.
3.7.21. ꢀ2)-ꢀ3aR,9aR,9bR)-3a,6,6,9a-Tetramethyl-1,2,3a,
4,6,7,8,9,9a,9b-decahydronaphtho[2,1-b]furan ꢀ56). T o a
stirred mixture of 6a-hydroxy Ambroxw $39) $0.05 g;
0.20 mmol) in pyridine $5 mL) was added thionyl chloride
$5 mL; 8.16 g; 68.5 mmol) at 08C. The mixture was allowed
to come to room temperature and stirring was continued
overnight. The reaction mixture was quenched with ice-
water and the aqueous mixture was extracted with ethyl
acetate and usual work up afforded a yellow oil which
was puri®ed by ¯ash column chromatography on silica gel
$eluent PE/EA 15:1) to yield odorous compound 56
Acknowledgements
$0.027 g; 0.115 mmol; 57%) as
a
colourless oil.
This work was ®nanced by the European Union $Fair CT96-
1781). We thank A. van Veldhuizen for recording NMR
spectra, C. J. Teunis and H. Jongejan for mass spectral
data, and M. van Dijk and E. J. C. v. d. Klift for performing
the elemental analyses. The authors wish to thank Dr H.
Kooijman of the Department of Crystal & Structural
Chemistry, Bijvoet Center for Biomolecular Research,
Utrecht University, Faculty of Chemistry, for the X-ray
determinations. The authors also like to thank Dr J. P.
Roozen of the Department of Food Chemistry, Food Tech-
nology and Nutritional Sciences, Wageningen University,
for the opportunity to use the GC-sniff equipment and N.
Meert, Erasmus exchange student of the University of Gent,
for her help during the GC-sniff experiments.
[a]Dˆ270.0 $c 0.4); IR $KBr) nmax 3420, 2926, 1468,
1
1377, 1165, 1048 cm21; H NMR d 1.07 $s, 3H), 1.10 $s,
3H), 1.13 $s, 3H), 1.14 $s, 3H), 1.16±1.94 $m, 9H), 2.26 $d,
Jˆ4.0 Hz, 2H), 3.94 $m, 2H), 5.45 $t, Jˆ4.0 Hz, 1H); 13C
NMR d 18.3 $t), 19.5 $q), 21.8 $q), 23.4 $t), 28.9 $q), 33.2
$q), 36.2 $s), 38.3 $s), 41.4 $t), 41.9 $t), 42.2 $t), 57.2 $d), 65.4
$t), 78.3 $s), 117.5 $d), 149.8 $s); HRMS: M1, found
234.1981. C16H26O requires 234.1984; MS m/e $%) 234
$M1, 23), 219 $54), 151 $13), 150 $98), 135 $100), 105
$12), 91 $11), 43 $18).
3.7.22. ꢀ1)-ꢀ3aR,5S,5aS,9aS,9bR)-3a,6,6,9a-Tetramethyl-
dodecahydronaphtho[2,1-b]furan-5-yl methanesulfonate
ꢀ59). To a stirred solution of 6a-hydroxy Ambroxw $39)
$0.30 g; 1.19 mmol) in pyridine $10 mL) was added MsCl
$0.16 g; 0.11 mL; 1.42 mmol) at 08C. The mixture was
allowed to warm to room temperature and stirring was
continued for 1 h. The reaction mixture was neutralized
with a 4 M solution of hydrochloric acid and diluted with
ether. The organic layer was washed with saturated aqueous
sodium bicarbonate solution and worked up as usual. Puri-
®cation of the residue by ¯ash column chromatography
$eluent PE/EA 3:1) gave 59 $0.36 g; 1.09 mmol; 92%) as
a white crystalline solid. Mp 114±1158C; [a]Dˆ112.7 $c
References
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1967, 23, 509±514.
1.3); IR $KBr) nmax 3431, 2929, 1344, 1168, 954, 943 cm21
;
1H NMR d 0.95 $s, 3H), 1.05 $s, 3H), 1.10 $s, 3H), 1.20 $s,
3H), 1.24±1.92 $m, 11H), 2.61 $dd, Jˆ4.0, 11.0 Hz, 1H),
3.05 $s, 3H), 3.81±4.02 $m, 2H), 5.01 $dt, Jˆ4.1, 11.2 Hz,
1H); 13C NMR d 16.2 $q), 17.9 $t), 21.3 $q), 22.4 $q), 22.5
$t), 33.4 $s), 35.6 $q), 35.8 $s), 40.0 $q), 40.3 $t), 44.0 $t), 47.9
$t), 59.6 $q), 60.2 $d), 65.5 $t), 78.2 $s), 80.6 $d); HRMS: M1,
found 330.1869. C17H30O4S requires 330.1865; MS m/e $%)
330 $M1,1), 220 $16), 219 $100), 75 $21), 73 $19), 69 $16),
43 $16); Anal. found C, 61.45; H, 9.20%. C17H30O4S
requires C, 61.78; H, 9.15%.
3.7.23. ꢀ2)-ꢀ3aR,9aR,9bR)-3a,6,6,9a-Tetramethyl-1,2,3a,
4,6,7,8,9,9a,9b-decahydronaphtho[2,1-b]furan ꢀ56). The
above mentioned mesylate 59 $0.025 g; 0.075 mmol) in
toluene $5 mL) was purged through with nitrogen and
MgI2 $0.042 g; 0.15 mmol) was added quickly. After stir-
ring for 150 min the mixture was diluted with ether and
washed with a 2% aqueous solution of Na2S2O3 and brine
and worked up as usual. Flash column chromatography
$eluent PE/EA 15:1) yielded 56 $0.012 g; 0.050 mmol;
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39. We observed no strong typical ambergris smell for compound
53. However, according to literature, this compound is
supposed to show the typical ambergris smell.
È
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41 For a general description of the experimental procedures
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23. The structure of compound 4 was determined by 1H,1H-
COSY-NMR and by X-ray crystal structure. The X-ray crystal