Synthetic studies toward the kempane diterpenes. Diels-Alder additions to bicyclic dienes

Article abstract of DOI:10.1039/b104924k

Diels-Alder additions of 2,6-dimethyl-p-benzoquinone to the bicyclic dienes 24, 30 and 32 took place with very high regio-, stereo- and facial selectivity. Reduction and then alkylation of a tetracyclic adduct with 1,3-dithienium tetrafluoroborate provided compound 56, which has the correct stereochemistry at three key carbons for elaboration to the kempane diterpenes. Exploratory reactions with tricyclic model compounds and with tetracyclic adducts have been used to assess the development of the desired stereochemistry about the decalin moiety. X-Ray structures for 52, 53 and 59 were determined.

Full text of DOI:10.1039/b104924k

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Synthetic studies toward the kempane diterpenes. Diels–Alder
additions to bicyclic dienes
Chunjian Liu, Guanglin Bao and D. Jean Burnell*
1
Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland,
Canada A1B 3X7. E-mail: jburnell@mun.ca; Fax: 709-737-3702; Tel: 709-737-8535
Received (in Cambridge, UK) 5th June 2001, Accepted 2nd August 2001
First published as an Advance Article on the web 24th September 2001
Diels–Alder additions of 2,6-dimethyl-p-benzoquinone to the bicyclic dienes 24, 30 and 32 took place with very
high regio-, stereo- and facial selectivity. Reduction and then alkylation of a tetracyclic adduct with 1,3-dithienium
tetrafluoroborate provided compound 56, which has the correct stereochemistry at three key carbons for elaboration
to the kempane diterpenes. Exploratory reactions with tricyclic model compounds and with tetracyclic adducts have
been used to assess the development of the desired stereochemistry about the decalin moiety. X-Ray structures for 52,
53 and 59 were determined.
which bears oxygen functionality at all of the necessary posi-
Introduction
tions, but 5 lacks the methyl group at C-2a.6 The initial stages of
The kempanes (1–3, Fig. 1) are a small class of tetracyclic diter-
penes that have been isolated in tiny amounts from the defen-
that work are described in detail here, also.
sive secretions of soldiers of the termite species Nasutitermes
kempae and Nasutitermes octopilis.1 An apparently rearranged
Results and discussion
Our initial retrosynthetic analysis is provided in Scheme 1. It is
congener, rippertane (4), has also been isolated from other
nasute termites.2
based on a conviction that establishing the correct relative
stereochemistry at C-10a, C-10b and C-10c early in the syn-
thetic sequence would allow for the development of the
rest of the stereochemistry in a predictable manner. All three
There has been only one successful total synthesis of 1,
by Dauben and co-workers.3 Unfortunately, an attempt by
Paquette’s group4 to synthesize 2 failed in the very last stage. In
both Dauben’s and Paquette’s routes, the decalin system was
used as the scaffold upon which first the five-, and then the
seven-membered rings, were constructed. The only approach to
4 used α-santonin as the starting compound,5 but the comple-
tion of this synthesis has not yet been published. In contrast
with the earlier efforts towards 1 and 2, we wanted to be able to
produce all three kempanes from a common tetracyclic com-
pound. This entailed a synthetic approach with intermediates
carrying more functionality than either of the previous
approaches. Herein are reported the results of exploratory reac-
tions for the development of such a synthesis of the kempane
diterpenes. This approach includes a number of options for the
introduction of the methyl group at C-2a, and some model
reactions to accomplish this are outlined. We previously com-
municated a route that produced the pentacyclic compound 5,
Fig. 1 Kempane diterpenes (1–3), rippertane (4) and the synthetic
pentacyclic compound 5.
Scheme 1 Initial retrosynthetic analysis. (Compound numbering in
this Scheme follows that of the kempanes.)
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This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104924k

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Scheme 2 Initial reactions in Dauben’s synthesis3 of 1. Reagents and
conditions: i, BF3ؒEt2O; ii, Zn, AcOH, reflux.
Scheme 4 Diels–Alder reactions of four bicyclic dienes. Reagents and
conditions: i, TBDMSOTf, Et3N; ii, 12, toluene, reflux, 3 days; iii, LDA,
TBDMSOTf, THF, Ϫ78 ЊC to RT; iv, LDA, TBDMSCl, THF–HMPA,
Ϫ78 ЊC to RT; v, isopropenyl acetate, ( )-CSA, reflux, 4 days; vi, 12,
toluene, reflux, 12 days.
give a compound with the relative stereochemistry of 8. This
apparently trivial process was of some concern because of the
low yield reported in the initial steps of Dauben’s synthesis of
1.3 These are shown in Scheme 2. The Lewis acid-catalysed
Diels–Alder reaction of 12 with isoprene, followed by reduction
and equilibration of the adduct 13 gave the bicyclic diketone 14
in a yield of only 13%.
Our work began with the construction of possible precursors
for a diene-lactone (Scheme 3). Enone-lactones 20 and 23
were prepared from 3-methylcyclohex-2-en-1-one by a process
reminiscent of Corey’s prostaglandin synthesis.7 Addition of
dichloroketene to diene 15 took place with complete chemo-
and regiochemical control to provide 16. Similar reactions have
been reported by Harding et al.8 Reductive removal of the
chlorine atoms of 16 gave the ketone 17, which in turn afforded
only lactone 18 by a Baeyer–Villiger reaction with peroxyacetic
acid. Ozonolysis of the double bond of 18 led to a rather
unstable compound 19, so aldol cyclization was carried out
immediately with dilute HCl to give 20. Our attempts to carry
out the aldol cyclization under basic conditions led to very
complex mixtures. The process outlined in Scheme 1 calls for a
methyl-bearing diene (11), therefore 18 was methylated to give
predominantly 21. Ozonolysis produced unstable 22, and aldol
cyclization yielded 23.
Scheme 3 Synthesis of the diene precursors. Reagents and conditions:
i, 1. TsNHNH2, HCl, THF, 2. 2.2 equiv. MeLi, Et2O, 0 ЊC; ii,
Cl2CHCOCl, Et3N, RT; iii, Zn, NH4Cl, MeOH; iv, H2O2, AcOH; v, 1.
O3, CH2Cl2, Ϫ78 ЊC, 2. Me2S; vi, 1 : 1 5% aqueous HCl–THF, reflux,
12 h; vii, LDA, MeI, THF–HMPA, Ϫ78 ЊC; viii, ( )-CSA, C6H6, reflux,
25 h.
kempanes (1–3) might be derived from 6, which would arise by
opening the acetal of 7 and aldol cyclization to establish the
C-7a–C-8 bond. The relative stereochemistry at C-4a and C-7
of 7 was expected to be established in 8 by equilibration follow-
ing reduction of 9. Methylation of the enol ether function on
the convex side of compound 10 would take place syn to the
methyl at C-10c. The rigid diene lactone 11 was adopted for the
key Diels–Alder step to provide rapid access to an adduct with
well-positioned functionality. In order to ascertain that these
transformations, and their order, might be feasible, three pro-
cesses needed to be examined. Firstly, and most importantly, it
was imperative that the Diels–Alder addition of 2,6-dimethyl-
p-benzoquinone (12) to a diene such as 11 be assessed. It was
not clear if the stereochemistry at C-10 would influence the
selectivity of the cycloaddition. Secondly, a process was needed
With enone-lactones 20 and 23 in hand, assessment could
begin of the relative importance in the Diels–Alder reaction of
two variables in the diene, i.e., i. the presence and the relative
stereochemistry of the methyl group at C-3, and ii. the identity
for the addition of the methyl group at C-2a (10
9). The third
objective was to examine the equilibration at C-4a and C-7 to
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of the enol protecting group (Scheme 4). Firstly, the unmethyl-
ated diene 24 was obtained by treatment of 20 with TBDMS-
triflate and triethylamine.9 A toluene solution of 24 and the
quinone 12 was heated under reflux for three days. Two adducts
were detected in the crude product, and these were isolated by
chromatography. The 1H NMR data for the major adduct (80%
yield) included nuclear Overhauser effect (NOE) enhancements
that placed the methyl group on C-10c in the proximity of the
hydrogens on C-10 and C-10b. These, and other NOE data,
showed that the major adduct was the desired isomer 25. The
minor adduct, which was isolated in only 6% yield, was identi-
fied as 26, the product of endo addition to the face of 24 anti to
the lactone ring, but with regiochemistry opposite to the path-
the effect of this difference on the reactivity of the diene. The
Diels–Alder reaction of 34 was very sluggish, giving a yield of
only 50% after heating it in toluene with an excess of 12 for
12 days. Furthermore, two inseparable Diels–Alder adducts, 35
and 36, were obtained, in a ratio of only 4 : 1. Because of the
poor reactivity of 34 and the modest regioselectivity, the use of
an acetoxy-diene was not pursued further.
Adducts 31 and 33 lack only two of the carbons required for
the kempanes. Each adduct would need a methyl group at C-2a
(kempane numbering) and a carbon that will become C-8 dur-
ing the cyclization of the final, seven-membered ring (7
6 in
Scheme 1). It was decided to try to introduce the latter carbon
much earlier in the reaction sequence than shown in Scheme 1.
Treatment of diene 30 with methyllithium afforded the hemi-
acetal 37 as a 2.2 : 1 mixture of epimers (Scheme 5). Diels–Alder
1
way that produced 25. In the H NMR spectrum of 26, the
resonances for the hydrogens on C-10b and C-10c were coupled
(J = 5.3 Hz). Furthermore, NOE enhancements established that
the methyl at C-4a was on the same side of the rings as the
hydrogens on C-10b and C-10c and that the hydrogen on C-10c
was close to a hydrogen on C-10. Whereas high endo selectivity
should be expected for Diels–Alder reactions of quinones,
it was gratifying that the regioselectivity was good† and the
facial selectivity was excellent. Indeed, the facial selectiv-
ity with diene 24 was much superior to the facial selectivity
reported by Overman and co-workers11 for Diels–Alder
reactions of 3-methyl-1-vinylcyclopentene, which might be con-
sidered a simple model for the facial alternatives in 24.
The excellent stereoselectivity in the methylation of 18 to 21
and the lack of epimerization in the formation of 23 were com-
promised in the formation of diene 30 from 23. A 6 : 1 mixture
of the epimeric dienes 30 and 32, respectively, was obtained
when one equivalent of LDA was used to deprotonate 23. Two
equivalents of LDA provided a 1 : 6 mixture, with 32 being the
major epimer. (This stereogenic centre would ultimately dis-
appear in the kempanes.) It was not clear that the Diels–Alder
additions of the epimeric dienes would have the same selectiv-
ity. The methyl group of diene 32 extends into the concave space
of molecule, and it seemed likely that this would engender con-
formational changes that might alter the selectivity. Diene 30
reacted with 12 to give only one adduct, 31, in 81% yield. The
Diels–Alder reaction of 32 was like that of 30, and an 82% yield
of the desired adduct 33 was obtained. NMR analysis did not
reveal any other Diels–Alder adducts. Thus, the methyl group
has no significant influence in the Diels–Alder reaction that is
the key for this approach to the kempanes. The acetoxy-
substituted diene 34 was prepared from 23 in order to examine
Scheme 5 Attempted opening and cyclization of hemiacetal. Reagents
and conditions: i, MeLi, Et2O; ii, 12, toluene, reflux, 2 days; iii, 5%
aqueous HCl–THF, RT, 24 h.
reaction of this mixture with the quinone 12 provided two
products in almost equal amounts. These were 38, still a mix-
ture of epimers, and 39, which was obviously derived from 38
by dehydration. The total yield of adduct was 68%. Cyclization
of the seven-membered ring was attempted by adding the mix-
ture of 38 and 39 to dilute acid. It was hoped that the methyl
ketone 40, unmasked by a reversible opening of the hemiacetal
moiety of 38, might undergo aldol closure with dehydration to
give a tetracyclic product such as 41. This approach was overly
optimistic. None of the cyclized product was detected in the
reaction mixture. Instead, the hydrolysed and oxidized epimeric
mixture 42 was obtained. Therefore, the early introduction of
C-8 and the immediate cyclization of the seven-membered ring
was abandoned in favour of the original sequence (Scheme 1).
Next, the question of introduction of the methyl at the
encumbered C-2a of the kempanes was addressed. Adding a
carbon onto the silyl enol ether moiety in adduct 25, 31 or
34 seemed like a way of ensuring that the carbon be added
only at the desired position. Furthermore, the shape of these
adducts, with cis ring junctions between the six-membered
rings, was expected to allow the carbon to be added only onto
the correct face. Attempts to methylate directly with, for
instance, iodomethane failed, so attention turned to methods
for indirect methylation. Most of these were failures as
well. Some methods, e.g. PhSCH2Cl with TiCl4,12 returned the
hydrolysed and oxidized compound, such as 43 from 31 (Fig. 2).
This was the same result as just adding HCl to 31.
† 1-Substituents on butadiene generally greatly dominate over
2-substituents in determining the regioselectivity of Diels–Alder
reactions with methyl-substituted p-benzoquinones, even when the
2-substituent is a stronger π-donor.10 It was therefore very surprising
that, in our hands, the reaction of quinone 12 with diene 27, for which a
1-alkyl substituent and the oxygen substituent on the butadiene moiety
should both direct the quinone to add in the same direction, gave 28
and 29 in ratio of only 2 : 1.
Further experimentation with indirect approaches to methyl-
ation was carried out with a simpler tricyclic model compound
44 (Scheme 6). Although there are not many examples of cyclo-
propanation of TBDMS-enol ethers in the literature,13 these
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Fig. 2 Product from attempted methylation at C-6a.
Fig. 3 X-Ray crystal structure of compound 53.
alkylated product 50. Methylation of 47b followed by reaction
with 1,3-dithienium tetrafluoroborate gave 52 as a single isomer
in 59% yield. The structure of 52 was confirmed by X-ray
crystallography.
As shown in Scheme 7, addition of 1,3-dithienium tetrafluoro-
Scheme 6 Model studies for the introduction of a methyl group at
C-2a of the kempanes. Reagents and conditions: i, CH2I2, Et2Zn; ii,
LiAl(OBut)3H, THF, 0 ЊC; iii, NaBH4, CeCl3; iv, with 47a, 1,3-
dithienium tetrafluoroborate, CH2Cl2–MeNO2, Ϫ78 ЊC; v, Ac2O, Et3N,
DMAP; vi, K2CO3, MeOH; vii, NaH, MeI.
silyloxycyclopropanes can be converted to α-methyl ketones
with base14 or acid.13 Treatment of 44 and a large excess of
CH2I2 with Et2Zn gave the cyclopropanated compound 45 that
had the desired stereochemistry at C-3a (from NOE experi-
ments). Furthermore, monoreduction of 45 with a bulky
hydride smoothly gave 46 with high chemo- and stereoselectiv-
ity.15 This result suggested that the construction of the seven-
membered ring via attack of a nucleophile onto the carbonyl
at C-9a could be carried out selectively. It was then very dis-
appointing when attempts to cyclopropanate the tetracyclic
adduct 31 under similar conditions failed completely.
1,3-Dithienium tetrafluoroborate has been used to alkylate a
trimethylsilyloxy alkene.16 We found that the TBDMS enol
ether derived from cyclohexanone was also alkylated with 1,3-
dithienium tetrafluoroborate, in a yield of 88%. The reaction of
this electrophile with 44 gave a complex mixture. In order to
limit side-reactions, the carbonyl at C-6 of 44 was reduced.
Monoreduction of enediones such as 44 with NaBH4 in the
presence of CeCl3 is known to be regioselective, but not facially
selective.17 Thus, it was not surprising that the product was
47a,b, a 1 : 1 mixture of epimers. Introduction of an excess of
1,3-dithienium tetrafluoroborate to 47a gave 48 in modest yield,
but it is important to note that the alkylation took place
exclusively on the desired face of the silyl enol ether, i.e., syn to
the methyl at C-9a. Protection of the alcohol function of 47a as
the acetate 49 led to a significant improvement in the yield of
Scheme 7 Alkylation of tetracyclic Diels–Alder adducts with 1,3-
dithienium tetrafluoroborate. Reagents and conditions: i, 1,3-dithienium
tetrafluoroborate. CH2Cl2–MeNO2, Ϫ78 ЊC; ii, NaBH4, CeCl3; iii,
Ac2O, Et3N, DMAP; iv, K2CO3, MeOH; v, NaBH4, MeOH–CH2Cl2.
borate to the adduct 33 gave no dithiane-containing product.
Instead, the product was the pentacyclic compound 53, for
which the structure was determined by X-ray analysis (Fig. 3).
The same compound could be obtained by simply adding
17
some HF to 33. Reduction of adduct 25 with NaBH4–CeCl3
gave the 1 : 1 epimeric mixture 54a,b, which was separated by
chromatography. One isomer (54a) was acetylated (55) and
treated with 1,3-dithienium tetrafluoroborate to give 56. None
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of the compound with the opposite stereochemistry at C-6a was
detected by NMR. Hydrolysis of the alkylated product could
be carried out easily to give the alcohol 57. Reduction of 56
with sodium borohydride took place from the convex face with
a high degree of selectivity to yield the hemiacetal 58.
Compound 43 had been produced in many unsuccessful
methylation experiments. This compound was therefore con-
venient to use to study the reduction and equilibration process
(9
8 in Scheme 1) to establish the stereochemistry at C-2
and C-4a (Scheme 8). A similar process had proven to be very
Fig. 4 X-Ray crystal structure for compound 59.
In a similar manner, 42 was reduced by zinc in hot acetic acid
to give a very complex mixture in which 61, now a cyclic ether,
was a major component.
Conclusions
While the route to the kempanes proposed in Scheme 1 contains
elements that are feasible, some adjustments to the synthetic
plan would be required. The key Diels–Alder reaction (11
10) was a selective and efficient reaction. Also, indirect intro-
duction of the kempanes’ C-2a methyl group (10
9)
appeared to be possible through the reaction of the silyl enol
ether with 1,3-dithienium tetrafluoroborate or via cyclo-
propanation, although the latter had failed with adduct 28. The
one attempt to cyclize the seven-membered ring (7
6) early in
the synthetic sequence had not been encouraging, although
reduction of a ketone function in the cyclopropanated model 42
and in the modified adduct 53 showed that this ketone was
sufficiently unhindered that cyclization of the seven-membered
ring onto this ketone might still be reasonably anticipated.
Finally, it was clear that establishing the correct stereochemistry
at C-4a and C-7 of the kempanes by equilibration would
not take place as originally planned. These conclusions were
instrumental in the design of a route, described in the following
paper, that was ultimately successful in preparing the chal-
lenging ring system of the kempanes.
Scheme 8 Reduction and equilibration study. Reagents and conditions:
i, Zn, AcOH, ∆; ii, TiCl3, H2O, RT.
inefficient in Dauben’s synthesis of 1 (Scheme 2).3 Reduction of
both double-bonds in 43 took place with zinc in hot acetic acid.
The lactone ring was unaffected under these conditions, and
two isomeric products were detected by NMR. The relative
amounts of these changed during prolonged heating such that
the initial minor product equilibrated to the major one, which
was shown to be compound 59. NOE data for this major
product included a 9% enhancement of the signal for the
hydrogen on C-10a and a 6% enhancement for the hydrogen on
C-2 on saturation of the signal for the hydrogen on C-4a. This
showed that the decalin ring-junction was trans, but the C-2
methyl was also trans to the C-4a hydrogen. The structure of 59
was corroborated by X-ray analysis, which showed that, at least
in the solid state, the diketone ring was in a twisted conform-
ation in which the C-2 methyl was pseudo-equatorial (Fig. 4).
This was not the desired isomer for the synthesis of the kem-
panes. Attention was turned to the initially major isomer. Both
double-bonds of 43 could be reduced quickly with TiCl3 in
water18 at room temperature to give mainly the product that
was identical with the initial major product from the reduction
with zinc and acetic acid. The NOE data for this isomer
included enhancements of the signals for both the C-2 and the
C-4a hydrogens on saturation of the C-10c methyl signal. Thus,
the compound was 60. The configuration at C-2 was the desired
one, but the decalin ring-junction was cis. Treatment of 60 with
hot acetic acid gave 59, but the desired isomer was never
observed.
Experimental
General
Uncorrected melting points were determined on a Fisher–Johns
apparatus. Infrared spectra were measured on a Mattson
Polaris FT instrument. A General Electric GE 300-NB spectro-
meter provided the 1H and 13C NMR spectra (300 MHz for 1H,
75 MHz for 13C). Unless otherwise noted, CDCl3 was the sol-
vent. Shifts are relative to internal tetramethylsilane. Nuclear
Overhauser effect (NOE) measurements were made using
difference spectra. The NOE data have this form: saturated
signal (enhanced signal, enhancement). 13C NMR signals are
followed in parentheses by the assignments (based on APT
spectra and heterocorrelated spectra) or the number of attached
hydrogens (e.g. 2 = CH2). Mass spectra (EI) were usually
obtained on a V. G. Micromass 7070HS instrument. The X-ray
diffractometer was a Rigaku AFC6S instrument. Unless
otherwise noted, solutions were “dried” by stirring with
anhydrous MgSO4 followed by filtration. “Chromatography”
refers to flash column chromatography on silica gel; elution
was generally with hexane containing an increasing proportion
of ethyl acetate.
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cis-8,8-Dichloro-3-methylbicyclo[4.2.0]oct-2-en-7-one 16
cis-3a,6,7,7a-Tetrahydro-5-methylbenzofuran-2(3H)-one 18
A mixture of 3-methylcyclohex-2-en-1-one (22.5 g, 200 mmol),
p-tolylsulfonylhydrazine (38.4 g, 200 mmol) and 1.5 ml of con-
centrated HCl in THF (280 ml) was stirred at RT for 15 h.
Three times, benzene (200 ml) was added to the red solution,
and the mixture was concentrated under reduced pressure.
The residue was solidified by trituration with diethyl ether
and dried in a desiccator over CaCl2 under vacuum for 24 h.
The p-tolylsulfonylhydrazone (57.8 g) was a 2 : 1 mixture of
stereoisomers by 1H NMR: δH (for the major isomer) 7.85 (2 H,
d, J 8.2), 7.31 (2 H, d, J 8.2), 5.94 (1 H, q, J 1.4), 2.42 (3 H, s),
2.24 (2 H, t, J 6.5), 2.05 (2 H, t, J 6.0), 1.81 (3 H, d, J 1.4)
and 1.75 (2 H, m); δH (for the minor isomer) 7.86 (2 H, d,
J 8.5), 7.31 (2 H, t, J 8.5), 6.13 (1 H, q, J 1.4), 2.42 (3 H, s), 2.32
(2 H, t, J 6.4), 2.15 (2 H, t, J 6.1), 1.87 (3 H, d, J 1.4) and 1.75
(2 H, m).
To a vigorously stirred suspension of the hydrazone mixture
(28.9 g, 100 mmol) in anhydrous diethyl ether (150 ml) was
added methyllithium (1.4 M in diethyl ether, 157 ml, 220 mmol)
at 0 ЊC over 3 h. After stirring for an additional 15 h, water
(200 ml) was cautiously added. The organic layer was extracted
with pentane (3 × 60 ml), and the pentane extracts were
combined with the diethyl ether solution. The combined
solutions were washed with 5% aqueous HCl (2 × 60 ml),
saturated aqueous NaHCO3 (60 ml) and brine (60 ml). This
solution of 15 was dried over anhydrous Na2SO4 then over solid
KOH.
To a solution of crude 17 (4.34 g, approximately 31.9 mmol) in
glacial acetic acid (30 ml) at 0 ЊC was added 30% hydrogen
peroxide (9.00 g, 79.4 mmol) over 10 min. The solution was
stirred at 0 ЊC for 15 h before it was poured into water (100 ml),
and dichloromethane (100 ml) was added. Solid Na2CO3 was
introduced until gas evolution ceased. The aqueous layer was
re-extracted with dichloromethane (3 × 40 ml). The combined
organic extracts were washed with saturated aqueous NaHCO3
solution (50 ml) and brine (50 ml). After drying over MgSO4,
the solution was concentrated under vacuum. Chromatography
of the residue afforded 18 (4.05 g, overall 27% from 3-
methylcyclohex-2-en-1-one) as a colourless oil: νmax(film)/cmϪ1
1779; δH 5.15 (1 H, broad s, 4-H), 4.72 (1 H, m, 7a-H), 2.97
(1 H, m, 3a-H), 2.75 (1 H, dd, J 17.1 and 8.5, 3-H syn to 3a-H),
2.27 (1 H, dd, J 17.1 and 2.9, 3-H anti to 3a-H), 2.18–2.07 (2 H,
m, 6-H and 7-H), 1.90–1.71 (2 H, m, 6-H and 7-H) and 1.69
(3 H, s, 5-methyl); NOE data 5.15 (2.97, 1.4%; 2.27, 1.4%),
4.72 (2.97, 1.6%) and 2.75 (2.97, 1.2%; 2.27, 7%); δC 177.1
(C-2), 136.1 (C-5), 119.7 (C-4), 77.6 (C-7a), 36.3 (C-3), 34.8
(C-3a), 24.9 (2), 23.9 (2) and 23.7 (5-methyl); m/z 152.0845
(Mϩ, 24%, C9H12O2 requires 152.0837), 141 (11), 110 (27),
95 (29), 93 (100), 86 (51), 81 (26), 79 (22), 77 (21), 68 (31), 67
(29) and 60 (34).
cis-5-Acetyl-3,3a,6,6a-tetrahydrocyclopenta[b]furan-2(2H)-one
20
Dry triethylamine (26.8 ml, 193 mmol) and dichloroacetyl
chloride (26.0 g, 175 mmol) in pentane were added at RT over
3 h. This was stirred for another 3.5 h. A precipitate was removed
by filtration. The filtrate was washed with water (200 ml),
saturated aqueous NaHCO3 solution (3 × 130 ml) and brine
(2 × 130 ml). The organic solution was dried and concentrated
under reduced pressure. Distillation (75–91 ЊC/3 mmHg) of the
residue provided crude 16 (11.4 g), which was used in the next
step. An analytical sample was obtained by chromatography as
a colourless oil: νmax(film)/cmϪ1 1804; δH 5.60 (1 H, m, 2-H),
4.05 (1 H, m, 6-H), 3.43 (1 H, m, 1-H), 2.15 (1 H, m, 5-H anti to
6-H), 1.99–1.92 (2 H, m, 4-H), 1.77 (3 H, s, 3-methyl), 1.65 (1 H,
m, 5-H syn to 6-H); NOE data 4.05 (3.43, 1.3%; 2.15, 0.8%;
1.65, 1.2%), 2.15 (4.05, 1.3%; 1.65, 6%) and 1.65 (4.05, 2%; 2.15,
6%); δC 197.0 (C-7), 140.4 (C-3), 117.1 (C-2), 87.1 (C-8), 52.4
(C-6), 44.8 (C-1), 25.9 (C-4), 24.6 (3-methyl) and 19.4 (C-5); m/z
206 (Mϩ ϩ 2, 3%), 204.0103 (Mϩ, 5, C9H1035Cl2O requires
204.0109), 105 (9), 94 (22), 91 (10), 79 (29), 77 (22) and 55 (100).
Ozone was introduced into a solution of 18 (12.0 g, 79.0 mmol)
in dichloromethane (750 ml) at Ϫ78 ЊC until a blue colour
persisted. The excess ozone was removed by bubbling
nitrogen through the solution until the blue colour disappeared.
Dimethyl sulfide (45 ml) was added. The mixture was allowed
to warm to RT as it was stirred overnight. The solvent and any
remaining dimethyl sulfide were evaporated under vacuum. The
residue (19) was immediately redissolved in THF (350 ml) and
5% aqueous HCl (350 ml) was added. The mixture was heated
under reflux for 17 h. Most of the THF was evaporated under
reduced pressure, and the remaining aqueous solution was
extracted with ethyl acetate (4 × 50 ml). The combined organic
extracts were washed with brine (2 × 50 ml), dried and concen-
trated under reduced pressure. Chromatography (silica gel,
eluted with 3% methanol in chloroform) of the residue
provided 20 (5.60 g, 42%) as a white solid: mp 109–111 ЊC;
νmax(CH2Cl2 solution)/cmϪ1 1751, 1662 and 1617; δH 6.46 (1 H,
d, J 1.3, 4-H), 5.18 (1 H, apparent t, J 5.5, 6a-H), 3.77 (1 H, m,
3a-H), 3.02–2.91 (2 H, m, 6-H), 2.88 (1 H, dd, J 18.0 and 10.2,
3-H syn to 3a-H), 2.56 (1 H, dd, J 18.0 and 2.0, 3-H anti to
3a-H) and 2.35 (3 H, s, COCH3); δC 195.8 (COCH3), 175.5
(C-2), 143.9 (C-5), 141.0 (C-4), 82.3 (C-6a), 46.6 (C-3a), 37.8
(C-6), 32.4 (C-3) and 26.8 (COCH3); m/z 166.0628 (Mϩ, 8%,
C9H10O3 requires 166.0629), 151 (25), 122 (11), 95 (20), 67 (29),
65 (10), 51 (11) and 43 (100).
cis-3-Methylbicyclo[4.2.0]oct-2-en-7-one 17
To a vigorously stirred mixture of crude 16 (11.4 g, approxi-
mately 55.4 mmol) and NH4Cl (23.5 g, 44.7 mmol) in methanol
(300 ml) at 0 ЊC was added zinc dust (47.9 g, 730 mmol) in
portions over 1 h. Stirring was continued at RT for 10 h. Diethyl
ether (150 ml) was added and solid material was removed by
filtration. The filtrate was concentrated under vacuum, and
water (200 ml) was added to the residue. This was extracted
with diethyl ether (4 × 50 ml). The combined organic extracts
were washed with water (40 ml) and brine (40 ml), then dried
and concentrated under vacuum. Distillation (70–80 ЊC/5
mmHg) provided 17 as a colourless oil. This was sufficiently
pure to be used in the next step, but an analytical sample was
obtained by chromatography: νmax (film)/cmϪ1 1778; δH 5.63
(1 H, q, J 1.3, 2-H), 3.49 (1 H, m, 6-H), 3.24 (1 H, ddd, J 16.8,
9.2 and 2.8, 8-H), 2.91 (1 H, m, 1-H), 2.54 (1 H, ddd, J 16.8, 3.7
and 2.6, 8-H), 2.05–1.94 (2 H, m, 4-H and 5-H), 1.80 (1 H, m,
4-H), 1.70 (3 H, s, 3-methyl) and 1.57 (1 H, m, 5-H); NOE
data 3.49 (2.91, 2.2%), 3.24 (2.91, 1.7%; 2.54, 5%) and 2.54
(3.49, 4%); δC 212.2 (C-7), 135.8 (C-3), 122.6 (C-2), 56.3 (C-6),
52.3 (C-8), 26.2 (C-4), 24.4 (3-methyl), 23.4 (C-1) and 19.9
(C-5); m/z 136.0892 (Mϩ, 0.3%, C9H12O requires 136.0888), 94
(84), 93 (16), 91 (14), 79 (100), 77 (22) and 55 (22).
(3ꢀ,3aꢀ,7aꢀ)-3a,6,7,7a-Tetrahydro-3,5-dimethylbenzofuran-
2(3H)-one 21
n-BuLi (7.72 ml of 2.5 M in hexane, 19.3 mmol) was added to a
solution of diisopropylamine (2.81 ml, 21.2 mmol) in dry THF
(26 ml) at 0 ЊC over 20 min. After stirring for 10 min, the solu-
tion was cooled to Ϫ78 ЊC. A solution of 18 (2.94 g, 19.3 mmol)
in dry THF (26 ml) was introduced over 30 min. This was
stirred for 30 min before iodomethane (3.04 g, 21.3 mmol) in
hexamethylphosphoramide (4.16 g, 23.2 mmol) was added over
20 min, and this was stirred at Ϫ78 ЊC for 3 h. The solution was
warmed to 0 ЊC, and dilute aqueous NH4Cl solution (100 ml)
was added at once followed by diethyl ether (300 ml). The
organic layer was washed with water (3 × 80 ml) and brine
(80 ml), dried (Na2SO4) and concentrated under vacuum.
Chromatography provided 21 (2.87 g, 89%) as a colourless oil:
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656
2649

View Article Online
νmax(film)/cmϪ1 1773; δH 5.32 (1 H, m, 4-H), 4.67 (1 H, ddd,
J 10.8, 6.8 and 4.1, 7a-H), 2.58 (1 H, m, 3a-H), 2.37 (1H, dq,
J 7.5 and 7.5, 3-H), 2.08–1.70 (4 H, m, 6-H and 7-H), 1.71 (3 H,
s, 5-methyl) and 1.31 (3 H, d, J 7.5, 3-methyl); NOE data 4.67
(2.58, 2%) and 1.31 (5.32, 1%; 2.58, 3%; 2.37, 4%); δC 179.7
(C-2), 136.0 (C-5), 119.4 (C-4), 75.9 (C-7a), 42.7 (C-3a), 41.7
(C-3), 26.1 (2), 25.6 (2), 23.5 (5-methyl) and 14.4 (3-methyl); m/z
166.0996 (Mϩ, 23%, C10H14O2 requires 166.0994), 121 (9), 110
(17), 107 (28), 96 (14), 95 (17), 93 (81), 91 (20), 86 (17), 81 (17),
79 (29) and 74 (100).
solvent was evaporated under reduced pressure, and chromato-
graphy of the residue gave 25 (1.96 g, 80%) and 26 (0.141 g,
6%).
For 25: pale yellow foam, νmax(CCl4)/cmϪ1 1776 and 1681;
δH 6.44 (1 H, t, J 1.5, 3-H), 5.06 (1 H, apparent dt, J 6.5
and 2.5, 7a-H), 3.61 (1 H, ddd, J 15.0, 8.2 and 2.5, 10a-H),
2.94 (1 H, broad t, J 8.4,10b-H), 2.93 (1 H, m, 7β-H), 2.79 (1 H,
dd, J 17.7 and 8.4, 10β-H), 2.60 (1 H, broad d, J 18.1, 7α-H),
2.39 (1 H, m, 5α-H), 2.37 (1 H, dd, J 17.7 and 2.0, 10α-H),
2.28 (1 H, m, 4a-H), 2.13 (1 H, m, 5β-H), 1.97 (3 H, d, J 1.4,
2-methyl), 1.42 (3 H, s, 10c-methyl), 0.89 (9 H, s, SiC(CH3)3),
0.07 (3H, s, SiCH3) and 0.05 (3H, s, SiCH3); NOE data 3.61
(5.06, 8%; 2.79, 3%), 2.28 (3.61, 1%; 2.94, 8%; 2.79, 4%) and
1.42 (3.61, 5%; 2.94, 8%; 2.37, 8%; 2.28, 11%); δC 202.0 (0),
199.4 (0), 176.6 (C-9), 148.2 (C-2), 139.5 (C-6), 133.8 (C-3),
117.4 (C-6a), 85.2 (C-7a), 56.7 (C-10b), 53.3 (C-4a), 50.8
(C-10c), 41.2 (C-10a), 36.9 (C-10), 34.4 (C-7), 31.5 (C-5),
25.5 (SiC(CH3)3), 24.4 (10c-methyl), 18.0 (SiC(CH3)3), 16.5
(2-methyl), Ϫ3.9 (SiCH3) and Ϫ4.0 (SiCH3); m/z 416.1990 (Mϩ,
2%, C23H32O5Si requires 416.2019), 360 (11), 359 (35), 224 (21),
223 (37), 195 (12), 181 (21), 117 (20), 103 (16), 75 (100) and 73
(85).
(3ꢀ,3aꢀ,7aꢀ)-5-Acetyl-3,3a,6,6a-tetrahydro-3-methyl-2H-cyclo-
penta[b]furan-2-one 23
Ozone was introduced into a solution of 21 (3.05 g, 18.4 mmol)
in dichloromethane (200 ml) at Ϫ78 ЊC until a blue colour
persisted. Excess ozone was removed by bubbling nitrogen
through the solution until the blue colour disappeared.
Dimethyl sulfide (15 ml, 205 mmol) was added. The mix-
ture attained RT while stirring overnight. Solvent and excess
dimethyl sulfide were evaporated under reduced pressure to give
a yellow oil (22), which was immediately redissolved in benzene
(350 ml). ( )-Camphorsulfonic acid (0.43 g, 1.8 mmol) was
added, and the mixture was heated under reflux in a Dean–
Stark apparatus for 25 h. The cooled solution was washed with
5% aqueous NaHCO3 solution (2 × 100 ml) and brine (2 × 100
ml), dried (Na2SO4) and concentrated under reduced pressure.
Chromatography provided 23 (1.59 g, 48% from 21) as a pale
yellow oil: νmax(film)/cmϪ1 1769, 1670 and 1616m; δH 6.51 (1 H,
d, J 1.7, 4-H), 5.20 (1 H, apparent dt, J 5.5 and 1.6, 6a-H), 3.41
(1 H, m, 3a-H), 2.98–2.82 (2 H, m, 6-H), 2.65 (1 H, qd, J 7.6
and 1.9, 3-H), 2.35 (3 H, s, COCH3) and 1.42 (3H, d, J 7.6,
3-methyl); NOE data 5.20 (3.41, 2%; 2.98–2.82, 1.6%), 3.41
(6.51, 1.6%; 5.20, 2%; 1.42, 1.3%) and 1.42 (5.20, 1.6%; 3.41,
4%, 2.65, 5%); δC 195.9 (COCH3), 178.8 (C-2), 143.6 (C-5),
140.7 (C-4), 80.7 (C-6a), 54.7 (C-3a), 39.3 (C-3), 37.6 (C-6), 26.7
(COCH3) and 17.4 (3-methyl); m/z 180.0781 (Mϩ, 19%,
C10H12O3 requires 180.0786), 165 (22), 136 (16), 121 (17), 109
(15) and 43 (100).
For 26: pale yellow foam, νmax(CCl4)/cmϪ1 1775 and 1684;
δH 6.49 (1 H, q, J 1.3, 2-H), 5.05 (1 H, td, J 6.5 and 1.9, 7a-H),
3.77 (1 H, m, 10a-H), 3.03 (1 H, d, J 5.3, 10c-H), 2.98 (1 H, m,
7β-H), 2.72 (1 H, dd, J 17.7 and 8.2, 10β-H), 2.59 (1 H, m,
7α-H), 2.52 (1 H, m, 10b-H), 2.36 (1 H, dd, J 17.7 and 2.1,
10α-H), 2.26 (1 H, dq, J 17.2 and 2.8, 5β-H), 1.99 (3 H, d, J 1.3,
3-methyl), 1.78 (1 H, dq, J 17.2 and 2.5, 5α-H), 1.37 (3 H, s,
4a-methyl), 0.90 (9 H, s, SiC(CH3)3), 0.08 (3H, s, SiCH3) and
0.06 (3H, s, SiCH3); NOE data 5.05 (3.77, 11%; 2.98, 6%; 2.72,
2%), 3.77 (5.05, 9%; 3.03, 1%; 2.72, 5%), 2.52 (3.77, 2%; 3.03,
11%; 1.37, 2%) and 1.37 (3.03, 14%; 2.52, 14%; 1.78, 7%);
δC 202.9 (0), 198.5 (0), 176.9 (C-9), 146.7 (C-3), 139.3 (C-6),
136.9 (C-2), 116.1 (C-6a), 85.2 (C-7a), 51.8 (C-10c), 50.6
(C-4a), 43.7 (C-10b), 40.9 (C-10a), 37.7 (C-5), 35.5 (C-10), 33.6
(C-7), 25.5 (SiC(CH3)3), 21.3 (4a-methyl), 17.9 (SiC(CH3)3),
16.4 (3-methyl), Ϫ3.9 (SiCH3) and Ϫ4.0 (SiCH3); m/z 416.2036
(Mϩ, 6%, C23H32O5Si requires 416.2019), 360 (30), 359 (96),
251 (70), 223 (21), 195 (15), 194 (20), 181 (17), 75 (98) and
73 (100).
cis-5-[1-(1,1-Dimethylethyl)dimethylsilyloxyethenyl]-3,3a,6,6a-
tetrahydro-2H-cyclopenta[b]furan-2-one 24
To a solution of 20 (0.548 g, 3.30 mmol) and tert-butyl-
dimethylsilyl triflate ‡ (0.83 ml, 3.61 mmol) in dichloromethane
(30 ml) at 0 ЊC was added triethylamine (0.60 ml, 4.30 mmol).
After stirring the solution for 10 min, the solvent was evapor-
ated under reduced pressure. Chromatography of the residue
provided 24 (0.682 g, 74%) as a colourless oil: νmax(film)/cmϪ1
1778; δH 5.77 (1 H, broad s, 4-H), 5.16 (1 H, m, 6a-H), 4.36
(3ꢀ,3aꢀ,6aꢀ)-5-[1-(1,1-Dimethylethyl)dimethylsilyloxyethenyl]-
3,3a,6,6a-tetrahydro-3-methyl-2H-cyclopenta[b]furan-2-one 30
and (3ꢀ,3aꢁ,6aꢁ)-5-[1-(1,1-dimethylethyl)dimethylsilyloxy-
ethenyl]-3,3a,6,6a-tetrahydro-3-methyl-2H-cyclopenta[b]furan-
2-one 32
Method A. To a solution of diisopropylamine (0.14 ml, 1.00
mmol) in dry THF (4.0 ml) at 0 ЊC was added n-BuLi (2.5 M
in hexane, 0.40 ml, 1.00 mmol) over 5 min. The solution was
stirred for 20 min before it was transferred over 15 min by
syringe to a solution of 23 (0.180 g, 1.00 mmol) and tert-
butyldimethylsilyl triflate (0.28 ml, 1.2 mmol) in dry THF (5.0
ml) at Ϫ78 ЊC. This mixture was stirred at Ϫ78 ЊC for 1 h before
it was allowed to warm to RT. Hexane (100 ml) was added. This
solution was washed with water (3 × 30 ml) and brine (30 ml),
dried (Na2SO4) and concentrated under reduced pressure.
Preparative thin-layer chromatography (silica gel, 0.5 mm
thickness, 25% ethyl acetate in hexane) provided 30 (214 mg,
73%) and a small amount of 32 (37 mg, 12%).
Method B. To a solution of diisopropylamine (0.23 ml, 1.75
mmol) in dry THF (5.0 ml) at 0 ЊC was added n-BuLi (2.5 M
in hexane, 0.63 ml, 1.57 mmol) over 5 min. The solution was
stirred for 10 min then cooled to Ϫ78 ЊC. A solution of 23
(0.128 g, 0.710 mmol) in dry THF (1.0 ml) was added over
10 min. This mixture was stirred at Ϫ78 ЊC for 30 min. Hexa-
methylphosphoramide (1.0 ml) was added followed by a solu-
tion of tert-butylchlorodimethylsilane (243 mg, 1.56 mmol) in
dry THF (1.0 ml). The mixture was allowed to warm to RT, and
(1 H, s, CH ᎐), 4.33 (1 H, s, CH ᎐), 3.61 (1 H, m, 3a-H), 2.83–
᎐
᎐
2
2
2.80 (2 H, m, 6-H), 2.76 (1 H, dd, J 18.0 and 9.6, 3-H syn to
3a-H), 2.46 (1 H, dd, J 18.0 and 1.5, 3-H anti to 3a-H), 0.95
(9 H, s, SiC(CH3)3) and 0.17 (6H, s, Si(CH3)2); NOE data 5.16
(3.61, 3%) and 2.76 (3.61, 2%; 2.46, 7%); δC 176.4 (C-2), 152.4
(0), 140.2 (0), 127.3 (C-4), 94.8 (CH ᎐), 83.4 (C-6a), 45.6 (C-3a),
᎐
2
39.0 (C-6), 33.5 (C-3), 25.7 (SiC(CH3)3), 18.2 (SiC(CH3)3) and
Ϫ4.7 (Si(CH3)2); m/z 280.1496 (Mϩ, 0.6%, C15H24O3Si requires
280.1495), 223 (11), 181 (10), 117 (12), 75 (100) and 73 (14).
(4aꢀ,7aꢁ,10aꢁ,10bꢀ,10cꢀ)-6-[(1,1-Dimethylethyl)dimethylsilyl-
oxy]-4a,5,7,7a,10,10a,10b,10c-octahydro-2,10c-dimethyl-1H-
benz[6,7]indeno[2,1-b]furan-1,4,9-trione 25 and (4aꢀ,7aꢁ,10aꢁ,
10bꢀ,10cꢀ)-6-[(1,1-dimethylethyl)dimethylsilyloxy]-4a,5,7,7a,
10,10a,10b,10c-octahydro-3,4a-dimethyl-1H-benz[6,7]indeno-
[2,1-b]furan-1,4,9-trione 26
A solution of 24 (1.65 g, 5.89 mmol) and 12 (1.60 g, 11.8 mmol)
in toluene (70 ml) was heated under reflux for 3 days. The
‡ The IUPAC name for triflate is trifluoromethanesulfonate.
2650
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656

View Article Online
it was stirred for 2 h before it was diluted with pentane (100 ml).
This solution was washed with water (2 × 30 ml) and brine
(30 ml), dried (Na2SO4) and concentrated under reduced
pressure. Preparative TLC (silica gel, 0.5 mm thickness, 25%
ethyl acetate in hexane) provided 32 (100 mg, 48%) and a small
amount of 30 (16 mg, 8%).
Signals attributable to only one adduct were detected in the 1H
NMR spectrum of the residue. Preparative TLC (silica gel,
0.5 mm thickness, 30% ethyl acetate in hexane) provided 33
(147 mg, 82%): colourless crystals, mp 131–133 ЊC; νmax(CCl4
solution)/cmϪ1 1770 and 1682; δH 6.45 (1 H, q, J 1.4, 3-H),
5.08 (1 H, m, 7a-H), 3.70 (1 H, m, 10a-H), 2.98–2.83
(3 H, m, 4a-H, 7β-H and 10-H), 2.57–2.47 (2 H, m, 5-H and
7α-H), 2.41 (1 H, m, 10b-H), 2.03 (1 H, m, 5-H), 1.95 (3 H,
d, J 1.4, 2-methyl), 1.37 (3 H, s, 10c-methyl), 1.25 (3H, d, J 7.6,
10-methyl), 0.88 (9 H, s, SiC(CH3)3), 0.05 (3 H, s, SiCH3)
and 0.04 (3 H, s, SiCH3); NOE data 5.08 (3.70, 5%), 2.41 (2.98–
2.83, 8%), 1.37 (3.70, 6%; 2.98–2.83, 8%) and 1.25 (2.98–2.83,
6%; 2.41, 7%); δC 202.2 (0), 199.7 (0), 179.4 (C-9), 147.9
(C-2), 140.0 (C-6), 133.9 (C-3), 119.4 (C-6a), 83.9 (C-7a), 57.1
(C-4a), 51.9 (C-10c), 46.7 (C-10b), 45.2 (C-10a), 38.6 (C-10),
35.5 (C-7), 31.7 (C-5), 25.5 (SiC(CH3)3), 25.5 (10c-methyl),
18.0 (SiC(CH3)3), 16.5 (2-methyl), 13.5 (10-methyl) and Ϫ4.0
(Si(CH3)2); m/z 430.2177 (Mϩ, 10%, C24H34O5Si requires
430.2176), 374 (17), 373 (48), 238 (25), 237 (22), 209 (29), 181
(17), 131 (26), 130 (28), 117 (34), 91 (21), 75 (96) and 73
(100).
For 30: colourless crystals, mp 75–76.5 ЊC; νmax(CH2Cl2
solution)/cmϪ1 1772 and 1590; δH 5.80 (1 H, d, J 1.4, 4-H),
5.19 (1 H, apparent td, J 5.5 and 1.7, 6a-H), 4.36 (1 H, s, CH ᎐),
᎐
2
4.33 (1 H, s, CH ᎐), 3.25 (1 H, m, 3a-H), 2.88–2.73 (2 H,
᎐
2
m, 6-H), 2.58 (1 H, qd, J 7.6 and 1.9, 3-H), 1.37 (3 H, d, J 7.6,
3-methyl), 0.96 (9 H, s, SiC(CH3)3) and 0.17 (6 H, s, Si(CH3)2);
NOE data 5.19 (3.25, 7%; 2.88–2.73, 3%), 3.25 (5.80,
7%; 5.19, 8%; 2.58, 2%) and 1.37 (5.19, 1.3%; 3.25, 10%;
2.58, 10%); δC 179.9 (C-2), 152.4 (0), 140.0 (0), 127.1 (C-4),
94.8 (CH ᎐), 81.7 (C-6a), 53.8 (C-3a), 40.2 (C-3), 38.9
᎐
2
(C-6), 25.7 (SiC(CH3)3), 18.2 (SiC(CH3)3), 17.4 (3-methyl),
Ϫ4.7 (Si(CH3)2); m/z 294.1646 (Mϩ, 1%, C16H26O3Si requires
294.1649), 279 (1), 238 (8), 237 (7), 209 (18), 181 (14), 130 (18),
117 (18), 75 (100) and 73 (18).
For 32: colourless oil, νmax(film)/cmϪ1 1772 and 1590; δH 5.86
(1 H, broad s, 4-H), 5.06 (1 H, m, 6a-H), 4.37 (1 H, s, CH ᎐),
᎐
2
4.34 (1 H, s, CH ᎐), 3.64 (1 H, apparent broad t, J 6.8, 3a-H),
(3ꢀ,3aꢀ,6aꢀ)-5-[(1-Acetoxy)ethenyl]-3,3a,6,6a-tetrahydro-3-
methyl-2H-cyclopenta[b]furan-2-one 34
᎐
2
2.89–2.75 (3 H, m, 3-H and 6-H), 1.27 (3 H, d, J 7.4, 3-methyl),
0.96 (9 H, s, SiC(CH3)3), 0.18 (3 H, s, SiCH3) and 0.16 (3 H, s,
SiCH3); NOE data 5.06 (3.64, 4%), 3.64 (5.06, 4%) and 1.27
(5.86, 6%); δC 178.7 (C-2), 152.5 (0), 141.1 (0), 123.7 (C-4), 94.8
A solution of 23 (180 mg, 1.00 mmol) and ( )-camphorsulfonic
acid (20 mg, 0.09 mmol) in isopropenyl acetate (5.0 ml,
45 mmol) was heated under reflux for 4 days. The excess
isopropenyl acetate was evaporated under reduced pressure.
Preparative TLC (silica gel, 0.5 mm thickness, 60% ethyl acetate
in hexane) provided 34 (130 mg, 58%) as a pale yellow oil:
νmax(film)/cmϪ1 1765, 1648 and 1602; δH 5.64 (1 H, d, J 1.1,
4-H), 5.20 (1 H, td, J 5.9 and 1.2, 6a-H), 5.00 (1 H, d, J 2.0,
(CH ᎐), 81.1 (C-6a), 50.6 (C-3a), 39.2 (C-6), 37.7 (C-3), 25.7
᎐
2
(SiC(CH3)3), 18.2 (SiC(CH3)3), 12.0 (3-methyl), Ϫ4.6 (SiCH3)
and Ϫ4.8 (SiCH3); m/z 294.1651 (Mϩ, 0.4%, C16H26O3Si
requires 294.1649), 238 (5), 237 (5), 209 (10), 181 (12), 130 (17),
117 (15), 75 (100) and 73 (15).
CH ᎐), 4.98 (1 H, d, J 2.0, CH ᎐), 3.27 (1 H, m, 3a-H), 2.93
᎐
᎐
2
2
(4aꢀ,7aꢁ,10ꢁ,10aꢁ,10bꢀ,10cꢀ)-6-[(1,1-Dimethylethyl)dimethyl-
silyloxy]-4a,5,7,7a,10,10a,10b,10c-octahydro-2,10,10c-tri-
methyl-1H-benz[6,7]indeno[2,1-b]furan-1,4,9-trione 31
(1 H, ddt, J 17.3, 5.9 and 1.7, 6-H), 2.83 (1 H, dd, J 17.3 and 1.2,
6-H), 2.57 (1 H, qd, J 7.6 and 2.1, 3-H), 2.22 (3 H, s, COCH3)
and 1.37 (3 H, d, J 7.6, 3-methyl); δC 179.4 (C-2), 168.7
(COCH ), 149.0 (0), 136.3 (0), 127.7 (C-4), 105.5 (CH ᎐), 81.1
᎐
2
3
A solution of diene 30 (295 mg, 1.00 mmol) and 12 (206 mg,
1.50 mmol) in dry toluene (10 ml) was heated under reflux for
3 days. The solvent was evaporated under reduced pressure.
Signals attributable to only one adduct were detected in the 1H
NMR spectrum of the residue. Preparative TLC (silica gel,
0.5 mm thickness, 30% ethyl acetate in hexane) provided 31
(347 mg, 81%): colourless crystals, mp 134–135 ЊC; νmax(CCl4
solution)/cmϪ1 1774 and 1682; δH 6.44 (1 H, q, J 1.4, 3-H), 5.14
(1 H, m, 7a-H), 3.14–3.00 (2 H, m, 7β-H and 10a-H), 2.94 (1 H,
m, 4a-H), 2.45–2.34 (3 H, m, 5β-H, 7α-H and 10-H), 2.32 (1 H,
m, 10b-H), 2.07 (1 H, m, 5α-H), 1.97 (3 H, d, J 1.4, 2-methyl),
1.41 (3 H, s, 10c-methyl), 1.31 (3H, d, J 7.3, 10-methyl), 0.89
(9H, s, SiC(CH3)3), 0.06 (3 H, s, SiCH3) and 0.05 (3 H, s,
SiCH3); NOE data 5.14 (3.14–3.00, 9%), 2.94 (2.45–2.34, 8%;
2.32, 15%; 1.41, 1%), 2.32 (3.14–3.00, 5%; 2.94, 9%; 2.07, 5%),
1.41 (6.44, 2%; 3.14–3.00, 5%; 2.94, 9%; 2.45–2.34, 2%; 2.32,
16%) and 1.31 (3.14–3.00, 4%; 2.45–2.34, 5%); δC 201.8 (0),
199.6 (0), 179.5 (C-9), 148.1 (C-2), 139.6 (C-6), 133.8 (C-3),
116.8 (C-6a), 82.0 (C-7a), 56.5 (C-4a), 52.8 (C-10b), 51.0
(C-10c), 49.1 (C-10a), 43.1 (C-10), 34.6 (C-7), 31.6 (C-5),
25.5 (SiC(CH3)3), 24.8 (10c-methyl), 18.0 (SiC(CH3)3), 16.5
(2-methyl), 15.2 (10-methyl), Ϫ3.9 (SiCH3) and Ϫ4.1 (SiCH3);
m/z 430.2157 (Mϩ, 10%, C24H34O5Si requires 430.2176), 415 (8),
373 (45), 238 (21), 237 (22), 209 (32), 181 (18), 131 (20), 130
(32), 117 (28), 75 (100) and 73 (81).
(C-6a), 54.0 (C-3a), 39.9 (C-3), 38.8 (C-6), 20.8 (COCH3) and
17.3 (3-methyl).
(4aꢀ,7aꢁ,10ꢁ,10aꢁ,10bꢀ,10cꢀ)-6-Acetoxy-4a,5,7,7a,10,10a,
10b,10c-octahydro-2,10,10c-trimethyl-1H-benz[6,7]indeno[2,1-
b]furan-1,4,9-trione 35 and (4aꢀ,7aꢁ,10ꢁ,10aꢁ,10bꢀ,10cꢀ)-6-
acetoxy-4a,5,7,7a,10,10a,10b,10c-octahydro-3,4a,10-trimethyl-
1H-benz[6,7]indeno[2,1-b]furan-1,4,9-trione 36
A solution of 34 (107 mg, 0.481 mmol) and 12 (73 mg,
0.53 mmol) in dry toluene (5.0 ml) was heated under reflux.
After 4 days another 110 mg (0.808 mmol) of 2,6-dimethyl-1,4-
benzoquinone was added and the solution was heated under
reflux for 8 days. The solvent was evaporated under reduced
pressure. Preparative TLC (silica gel, 0.5 mm thickness, 60%
ethyl acetate in hexane) gave a pale yellow foam (83 mg, 50%)
consisting of an inseparable 4 : 1 mixture of 35 and 36, respec-
tively. The following NMR data were obtained from the adduct
mixture.
For 35: δH 6.45 (1 H, apparent t, J 1.4, 3-H), 5.19 (1 H, m, 7a-
H), 3.18 (1 H, dd, J 13.2 and 5.8, 10a-H), 3.02 (1 H, m, 4a-H),
2.90 (1 H, m, 7β-H), 2.62 (1 H, m), 2.51–2.39 (3 H, m), 2.19
(1 H, m), 2.10 (3 H, s, COCH3), 1.99 (3 H, d, J 1.4, 2-methyl),
1.44 (3 H, s, 10c-methyl) and 1.32 (3 H, d, J 7.4, 10-methyl);
NOE data 6.45 (1.99, 1%), 5.19 (3.18, 5%; 2.90, 3%), 3.18 (5.19,
6%), 1.44 (3.02, 8%) and 1.32 (3.18, 7%); δC 201.4, 198.8, 179.1,
168.4, 148.1, 137.4, 133.8, 127.1, 81.8, 55.9, 52.8, 51.1, 48.9,
43.2, 34.4, 28.7, 24.4, 20.6, 16.5 and 15.3.
(4aꢀ,7aꢁ,10ꢀ,10aꢁ,10bꢀ,10cꢀ)-6-[(1,1-Dimethylethyl)dimethyl-
silyloxy]-4a,5,7,7a,10,10a,10b,10c-octahydro-2,10,10c-
trimethyl-1H-benz[6,7]indeno[2,1-b]furan-1,4,9-trione 33
Discernable signals for 36: δH 6.63 (1 H, q, J 1.4, 2-H), 4.94
(1 H, m, 7a-H), 2.17 (3 H, s, COCH3), 2.02 (3 H, d, J 1.4,
3-methyl), 1.40 (3 H, d, J 7.7, 10-methyl) and 1.25 (3 H, s,
10c-methyl); δC 137.3, 81.2, 57.1, 53.8, 42.2, 42.0, 35.1, 33.6,
21.7, 20.7, 17.7 and 16.4.
A solution of diene 32 (123 mg, 0.418 mmol) and 12 (85 mg,
0.63 mmol) in dry toluene (5.0 ml) was heated under reflux for
3 days. The solvent was evaporated under reduced pressure.
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656
2651

View Article Online
(2ꢀ,3ꢀ,3aꢀ,6aꢀ)- and (2ꢀ,3ꢁ,3aꢁ,6aꢁ)-5-[1-(1,1-Dimethylethyl)-
dimethylsilyloxyethenyl]-3,3a,6,6a-tetrahydro-2-hydroxy-2,3-
dimethyl-2H-cyclopenta[b]furan 37
the mixture was stirred at RT for 24 h. Ethyl acetate (160 ml)
was added and the organic solution was washed with water
(3 × 50 ml) and brine (50 ml). The solution was dried, concen-
trated under reduced pressure and subjected to chromato-
graphy, which provided 42 (472 mg, 52% from 37) as a mixture
composed mainly of two isomers (approximately 2 : 1). Selected
NMR data for 42: major isomer: δH 6.99 (1 H, broad s), 6.58
(1 H, s), 2.15 (3 H, broad s), 1.57 (3 H, s), 1.44 (3 H, s) and 0.78
(3 H, d, J 6.7); δC 200.3, 197.6, 185.5, 151.1, 149.7, 139.3, 138.6,
127.7, 109.5, 83.0, 81.8, 52.6, 52.5, 51.2, 48.8, 35.9, 30.6, 25.7,
17.1 and 13.8; minor isomer: δH 6.98 (1 H, broad s), 6.55 (1 H, s),
2.15 (3 H, broad s), 1.60 (3 H, s), 1.36 (3 H, s) and 0.72 (3 H, d,
J 7.2); δC 201.4, 197.3 and 186.0.
To a solution of 30 (458 mg, 1.56 mmol) in anhydrous diethyl
ether (20 ml) at Ϫ30 ЊC was added methyllithium (1.28 ml of a
1.4 M solution in diethyl ether, 1.79 mmol) over 6 min. The
mixture was allowed to warm to 0 ЊC over 2.5 h. Water (50 ml)
was added, and the aqueous layer was extracted with diethyl
ether (3 × 25 ml). The combined organic solutions were washed
with brine (2 × 30 ml), dried and concentrated under reduced
pressure. Chromatography afforded a white solid, 37 (403 mg,
83%), as a 2.2 : 1 mixture of epimers: νmax(CCl4)/cmϪ1 3404
(broad) and 1588; for the major epimer: δH 5.94 (1 H, d, J 2.0,
4-H), 4.87 (1 H, m, 6a-H), 4.29 (1 H, s, CH ᎐), 4.28 (1 H, s,
᎐
2
(6aꢀ,7aꢁ,10ꢁ,10aꢁ,10bꢀ,10cꢀ)-6a,7,7a,10a,10b,10c-Hexahydro-
2,10,10c-trimethyl-1H-benz[6,7]indeno[2,1-b]furan-1,4,6,
9(6aH)-tetraone 43
CH ᎐), 3.06 (1 H, m, 3a-H), 2.76–2.67 (2 H, m), 2.51 (1 H, m),
᎐
2
1.44 (3 H, s, 2-methyl), 1.13 (3 H, d, J 7.0, 3-methyl), 0.97 (9 H,
s, SiC(CH3)3), 0.18 (3 H, s, SiCH3) and 0.17 (3 H, s, SiCH3);
clearly discernable signals for the minor epimer: δH 6.04 (1 H, d,
J 1.3, 4-H), 1.36 (3 H, s, 2-methyl) and 1.04 (3 H, d, J 7.2,
3-methyl).
To a solution of 41 (335 mg, 0.778 mmol) in THF (16 ml) was
added 8 ml of 10% aqueous HCl. After stirring at RT for 24 h,
ethyl acetate (80 ml) was added. The organic layer was washed
with water (3 × 25 ml) and brine (25 ml), dried (Na2SO4) and
concentrated under reduced pressure. Chromatography of the
residue afforded 43 (150 mg, 61%) as yellow crystals: mp 180–
182 ЊC; νmax(CH2Cl2)/cmϪ1 1767, 1667 and 1624; δH (CDCl3)
7.00 (1 H, q, J 1.4), 6.61 (1 H, s), 4.72 (1 H, apparent q, J 9.2),
3.19–2.99 (3 H, m), 2.82 (1 H, m), 2.16 (3 H, d, J 1.4), 2.05 (1 H,
m), 1.86 (1 H, m), 1.64 (3 H, s) and 1.12 (3 H, d, J 7.5);
δH (CD3COCD3) 7.10 (1 H, q, J 1.4, 3-H), 6.40 (1 H, s,
5-H), 4.72 (1 H, apparent q, J 8.2, 7a-H), 3.34 (1 H, apparent
t, J 6.7, 6a-H), 3.23 (1 H, dd, J 8.8 and 6.1, 10b-H), 2.84 (1 H,
m, 7β-H), 2.75 (1 H, dq, J 7.5 and 4.8, 10-H), 2.33 (1 H,
apparent td, J 9.1 and 4.7, 10a-H), 2.15 (3 H, d, J 1.4,
2-methyl), 1.91 (1 H, m, 7α-H), 1.70 (3 H, s, 10c-methyl)
and 1.07 (3 H, d, J 7.5, 10-methyl); NOE data (CD3-
COCD3): 4.72 (2.84, 1.6%; 2.33, 7%), 3.23 (2.75, 12%; 1.91,
2%; 1.70, 1%), 1.91 (4.72, 2%; 3.34, 4%; 3.23, 2%; 2.84,
6%), 1.70 (7.10, 1.2%; 6.40, 2%; 3.34, 10%; 3.23, 9%) and
1.07 (2.33, 6%); δC (CDCl3) 198.4, 197.3, 185.1, 179.7, 150.7,
149.7, 139.0, 127.4, 80.9, 52.8, 50.6, 48.6, 47.9, 41.6, 36.5,
30.4, 18.0 and 17.1; δC (CD3COCD3) 199.6 (0), 198.9 (0),
186.3 (0), 180.3 (C-9), 152.1 (0), 150.5 (0), 139.9 (C-3),
127.6 (C-5), 81.8 (C-7a), 53.6 (C-10b), 51.5 (C-10c), 48.8
(C-6a), 48.8 (C-10a), 42.5 (C-10), 36.9 (C-7), 30.5 (10c-
methyl), 17.9 (10-methyl) and 17.1 (2-methyl); m/z 314.1162
(Mϩ, 45%, C18H18O5 requires 314.1154), 296 (16), 286 (22),
268 (22), 253 (15), 241 (28), 217 (21), 213 (24), 188 (22), 176
(100), 148 (42), 120 (23), 96 (18), 94 (45), 91 (53), 79 (42) and
77 (34).
(4aꢀ,7aꢁ,10ꢁ,10aꢁ,10bꢀ,10cꢀ)-6-[(1,1-Dimethylethyl)dimethyl-
silyloxy]-5,7,7a,9,10,10a,10b,10c-octahydro-9-hydroxy-2,9,10,
10c-tetramethyl-1H-benz[6,7]indeno[2,1-b]furan-1,4(4aH)-dione
38and(4aꢀ,7aꢁ,10aꢁ,10bꢀ,10cꢀ)-6-[(1,1-dimethylethyl)dimethyl-
silyloxy]-5,7,7a,10a,10b,10c-hexahydro-2,9,10,10c-tetramethyl-
1H-benz[6,7]-indeno[2,1-b]furan-1,4(4aH)-dione 39
A solution of 37 (2.2 : 1 epimeric mixture; 111 mg, 0.357 mmol)
and 12 (97.2 mg, 0.714 mmol) in toluene (5.0 ml) was heated
under reflux for 48 h. The solvent was evaporated under
reduced pressure. Preparative TLC (silica gel, 0.5 mm thickness,
30% ethyl acetate in hexane) gave 38 (50 mg, 31%), as an 8 : 1
mixture of epimers at C-9, and 39 (57 mg, 37%).
NMR data for 38: major epimer: δH 6.38 (1 H, narrow m,
3-H), 4.89 (1 H, apparent q, J 7.7, 7a-H), 3.05–2.83 (3 H, m),
2.33 (1 H, m), 2.18–2.01 (2 H, m), 1.94 (3 H, broad s, 2-methyl),
1.67 (1 H, m), 1.47 (3 H, s), 1.39 (3 H, s), 1.22 (1 H, m),
1.03 (3 H, d, J 6.8, 10-methyl), 0.87 (9 H, s), 0.04 (3 H, s)
and 0.02 (3 H, s); δC 201.5, 200.4, 148.4, 138.0, 133.3, 119.7,
108.0, 81.3, 56.9, 51.4, 49.8, 36.3, 31.7, 26.0, 25.6, 25.2, 18.0,
16.5, 12.4, Ϫ3.9 and Ϫ4.2; clearly discernable signals for
the minor epimer: δH 6.49 (1 H, s, 3-H), 5.07 (1 H, m, 7a-H),
0.97 (3 H, d, J 7.5, 10-H), 0.93 (9 H, s), 0.19 (3 H, s) and 0.14
(3 H, s).
For 39: pale yellow solid, mp 128–129.5 ЊC; νmax(CCl4)/cmϪ1
1681; δH 6.38 (1 H, s, 3-H), 5.06 (1 H, apparent q, J 7.5, 7a-H),
3.68 (1 H, d, J 8.3, 10a-H), 3.12 (1 H, dd, J 15.3 and 7.6, 7β-H),
2.94 (1 H, apparent t, J 8.9, 4a-H), 2.41–2.32 (2 H, m, 5-H and
10b-H), 2.19–2.00 (2 H, m, 7α-H and 5-H), 1.95 (3 H, d, J 1.3,
2-methyl), 1.72 (3 H, s, 9-methyl), 1.56 (3 H, s, 10-methyl), 1.43
(3 H, s, 10c-methyl), 0.88 (9H, s, SiC(CH3)3), 0.05 (3 H, s,
SiCH3) and 0.03 (3 H, s, SiCH3); NOE data 5.06 (3.68, 7%; 3.12,
3%) and 1.43 (3.68, 8%; 2.94, 6%; 2.41–2.32, 4%); δC 201.9 (0),
200.5 (0), 148.4 (0), 145.7 (0), 137.8 (0), 133.3 (1), 118.1 (0),
104.6 (0), 82.5 (1), 57.2 (1), 53.5 (1), 51.5 (0), 50.5 (1), 36.9 (2),
31.9 (2), 25.6 (3), 24.9 (3), 18.0 (0), 16.6 (3), 11.8 (3), 10.6 (3),
Ϫ3.9 (3) and Ϫ4.2 (3); m/z 428.2374 (Mϩ, 3%, C25H36O4Si
requires 428.2383), 332 (5), 291 (10), 275 (6), 247 (5), 179 (7),
109 (14), 75 (32) and 73 (100).
(5aꢀ,9aꢀ,9bꢀ)-4-[(1,1-Dimethylethyl)dimethylsilyloxy]-2,3,5,5a,
9a,9b-hexahydro-8,9a-dimethyl-1H-benz[e]indene-6,9-dione 44
A solution of 1-{[(1,1-dimethylethyl)dimethylsilyloxy]ethenyl}-
cyclopentene§ (3.64 g, 16.2 mmol) and 12 (4.46 g, 32.4 mmol) in
toluene (200 ml) was heated under reflux for 3 days. The solvent
was evaporated under reduced pressure. Chromatography of
the residue gave 44 (4.86 g, 83%) as a viscous oil: νmax(film)/cmϪ1
1683 and 1624; δH 6.41 (1 H, s, 7-H), 2.87 (1 H, t, J 8.0, 5a-H),
2.42–2.10 (5 H, m), 1.95 (3 H, d, J 0.8, 8-methyl), 1.39 (3 H, s,
9a-methyl), 0.89 (9 H, s, SiC(CH3)3), 0.05 (3 H, s, SiCH3) and
0.04 (3 H, s, SiCH3); NOE data: 1.39 (2.87, 4%); δC 202.4 (0),
200.5 (0), 148.7 (0), 137.3 (0), 133.5 (C-7), 120.8 (0), 57.1 (C-5a),
50.4 (C-9a), 49.4 (C-9b), 31.8 (2), 28.0 (2), 27.8 (2), 25.6
(SiC(CH3)3), 24.8 (9a-methyl), 24.5 (2), 17.9 (SiC(CH3)3), 16.5
(8-methyl) and Ϫ4.1 (Si(CH3)2); m/z 360.2134 (Mϩ, 2%,
C21H32O3Si requires 360.2119), 345 (1), 303 (3), 244 (2), 211 (3),
168 (8), 167 (7) and 75 (100).
(6aꢀ,7aꢁ,10aꢁ,10bꢀ,10cꢀ)-6a,7,7a,9,10,10a,10b,10c-Octahydro-
9-hydroxy-2,9,10,10c-tetramethyl-1H-benz[6,7]indeno[2,1-b]-
furan-1,4,6-trione 42
A solution of 37 (2.2 : 1 epimeric mixture; 845 mg, 2.72 mmol)
and 12 (680 mg, 5.00 mmol) in toluene (40 ml) was heated
under reflux for 70 h. The solvent was evaporated under
reduced pressure, and the residue (38 and 39) was redissolved in
THF (40 ml). To this was added 5% aqueous HCl (20 ml), and
§ The diene was produced by treatment of 1-acetylcyclopentene with
TBDMS-OTF and Et3N.
2652
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656

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[(3aꢀ,4ꢁ,5aꢀ,9aꢀ,9bꢀ)-4-[(1,1-Dimethylethyl)dimethylsilyloxy]-
2,3,3a,4,5,5a,9a,9b-octahydro-3a,4-methano-8,9a-dimethyl-1H-
benz[e]indene-6,9-dione 45
data: 4.93 (6.34, 4%; 1.28, 7%); δC 202.7 (C-9), 144.1 (C-7),
138.1 (0), 134.2 (0), 121.4 (0), 67.9 (C-6), 50.9 (1), 50.2 (1), 47.9
(C-9a), 28.9 (2), 28.0 (2), 25.7 (SiC(CH3)3), 25.0 (2), 22.0
(9b-methyl), 18.0 (SiC(CH3)3), 15.9 (2-methyl), Ϫ4.0 (SiCH3)
and Ϫ4.1 (SiCH3); m/z 317 (Mϩ Ϫ 45, 2%), 262 (4), 244 (8), 229
(6), 175 (11), 149 (100), 147 (26), 121 (30), 98 (68), 91 (23), 75
(27), 55 (28) and 43 (34).
To a solution of 44 (117 mg, 0.325 mmol) in dry toluene (5 ml)
was added diethylzinc (1.95 ml of a 1.0 M solution in hexane,
1.95 mmol), and diiodomethane (0.32 ml, 3.9 mmol) at RT. The
mixture was stirred at RT for 2 h. The mixture was poured
into an aqueous saturated NH4Cl solution (20 ml). This was
extracted with diethyl ether (4 × 30 ml). The combined extracts
were washed with water (20 ml), brine (20 ml), dried and con-
centrated under reduced pressure. Chromatography of the resi-
due provided 45 (68 mg, 56%) as an oil: νmax(film)/cmϪ1 1726,
1697 and 1622; δH 6.30 (1 H, m, 7-H), 2.38–2.13 (4 H, m), 1.97
(3 H, d, J 1.6, 8-methyl), 1.94 (1 H, m), 1.83 (1 H, dd, J 12.6 and
1.7), 1.77 (1 H, dd, J 3.8 and 1.2), 1.64 (1 H, m), 1.41 (2 H, m),
1.24 (3 H, s, 9a-methyl), 0.79 (9 H, s, SiC(CH3)3), 0.71 (1 H, d,
J 5.3, cyclopropyl), 0.36 (1 H, d, J 5.3, cyclopropyl), 0.010 (3 H,
s, SiCH3) and 0.009 (3 H, s, SiCH3); NOE data: 1.24 (0.36,
5%); δC 202.7 (0), 201.1 (0), 150.6 (C-8), 132.4 (C-7), 58.2 (C-4),
57.4 (1), 53.0 (1), 50.2 (0), 34.8 (2), 33.3 (2), 31.0 (0), 28.3 (2),
27.7 (C-1), 26.0 (2), 25.6 (SiC(CH3)3), 24.7 (9a-methyl), 17.7
(SiC(CH3)3), 16.6 (8-methyl), Ϫ3.2 (SiCH3) and Ϫ4.0 (SiCH3);
m/z 374.2273 (Mϩ, 2%, C22H34O3Si requires 374.2275), 317 (7),
181 (33), 149 (18), 75 (71) and 73 (100).
For 47b: pale yellow viscous oil; νmax(Nujol)/cmϪ1 3393
(broad) and 1712; δH 6.51 (1 H, d, J 2.1, 7-H), 4.32 (1 H,
m, 6-H), 2.46–2.23 (m), 2.16–1.98 (m), 1.79 (3 H, d, J 0.9,
8-methyl), 1.66 (1 H, dd, J 9.2 and 3.5), 1.55–1.41 (m), 1.34
(3 H, s, 9a-methyl), 1.24 (1 H, m), 0.93 (9 H, s, SiC(CH3)3),
0.12 (3 H, s, SiCH3) and 0.11 (3 H, s, SiCH3); δC 202.7 (C-9),
144.7 (C-7), 137.7 (0), 135.2 (0), 121.1 (0), 66.7 (C-6), 49.5 (1),
49.0 (1), 45.3 (C-9a), 30.2 (2), 29.9 (2), 25.7 (SiC(CH3)3),
25.2 (9a-methyl), 25.1 (2), 22.5 (2), 18.1 (SiC(CH3)3), 16.1
(8-methyl), Ϫ4.0 (SiCH3) and Ϫ4.2 (SiCH3); m/z 362 (Mϩ, 1%),
317 (2), 264 (16), 149 (10), 138 (14), 98 (13), 75 (100) and 73
(23).
(3aꢀ,5aꢀ,6ꢁ,9aꢀ,9ba)-3a-(1,3-Dithian-2-yl)-1,2,3,3a,4,5,5a,6,
9a,9b-decahydro-6-hydroxy-8,9a-dimethyl-9H-benz[e]indene-
4,9-dione 48
To a solution of 47a (101 mg, 0.279 mmol) in dry dichloro-
methane (3.0 ml) at Ϫ78 ЊC under argon was added over 5 min a
solution of 1,3-dithienium tetrafluoroborate (172 mg, 0.836
mmol) in dry nitromethane (1.0 ml). After the solution was
stirred for another 20 min at Ϫ78 ЊC, it was allowed to warm to
RT. The mixture was poured into saturated aqueous NaHCO3
solution (10 ml), and this was extracted with ethyl acetate
(3 × 20 ml). The combined organic extracts were washed with
brine (20 ml) and dried. The solution was concentrated under
reduced pressure, and chromatography of the residue provided
48 (34 mg, 40%) as a white solid: mp 171–172 ЊC; νmax(Nujol)/
cmϪ1 3407 (broad) and 1712; δH 6.34 (1 H, d, J 1.5, 7-H), 4.86
(1 H, apparent t, J 2.2, 6-H), 4.34 (1 H, s, 2-H of dithiane),
2.91–2.77 (m), 2.66 (1 H, dd, J 9.0 and 5.7), 2.29 (1 H,
dd, J 17.8 and 9.2), 2.14–2.05 (m), 1.97–1.79 (m), 1.75 (3 H,
s, 8-methyl), 1.68 (m) and 1.40 (3 H, s, 9a-methyl); δC 211.6
(C-4), 201.8 (C-9), 140.6 (C-7), 136.1 (C-8), 67.1 (C-6), 63.5
(C-3a), 58.1 (C-2 of dithiane), 53.0 (1), 48.5 (C-9a), 47.6 (1),
36.9 (2), 33.5 (2), 31.8 (2), 31.6 (2), 28.7 (2), 25.7 (2), 24.2 (2),
23.4 (9a-methyl) and 15.9 (8-methyl); m/z 366.1330 (Mϩ, 6%,
C19H26O3S2 requires 366.1322), 349 (7), 348 (21), 228 (17) and
119 (100).
(3aꢀ,4ꢁ,5aꢀ,9ꢁ,9aꢀ,9bꢀ)-4-[(1,1-Dimethylethyl)dimethylsilyl-
oxy]-1,2,3,3a,4,5,5a,9,9a,9b-decahydro-9-hydroxy-3a,4-
methano-8,9a-dimethyl-6H-benz[e]inden-6-one 46
LiAl(OBut)3H (0.22 ml of a 1.0 M solution in THF, 0.22 mmol)
was added to a solution of 45 (68 mg, 0.18 mmol) in dry THF
(5 ml) at 0 ЊC, and this solution was stirred at 0 ЊC for another
2 h. Water (2 ml) was added slowly followed by ethyl acetate
(100 ml) and brine (20 ml). The organic layer was dried and
concentrated under reduced pressure. Chromatography of the
residue gave 46 (45.5 mg, 67%) as a white solid: mp 144–146 ЊC;
νmax(Nujol)/cmϪ1 1712 and 1658; δH 5.77 (1 H, s, 7-H), 3.82
(1 H, d, J 8.8, 9-H), 2.33 (1 H, dd, J 13.3 and 5.6), 2.09 (3 H, d,
J 1.2, 8-methyl), 2.06–1.58 (m), 1.41 (1 H, dd, J 12.4 and 5.9),
1.11 (2 H, m), 0.87 (3 H, s, 9a-methyl), 0.82 (9 H, s, SiC(CH3)3),
0.82 (1 H, d, J 5.5, cyclopropyl), 0.46 (1 H, d, J 5.5, cyclo-
propyl), 0.06 (3 H, s, SiCH3) and 0.04 (3 H, s, SiCH3); δC 202.4
(C-6), 157.4 (C-8), 123.3 (C-7), 73.8 (C-9), 58.3 (C-4), 52.6 (1),
52.2 (1), 37.8 (C-9a), 35.4 (2), 34.0 (2), 30.8 (C-9b), 27.9 (cyclo-
propyl), 27.5 (2), 26.3 (9a-methyl), 26.0 (2), 25.6 (SiC(CH3)3),
22.1 (8-methyl), 17.7 (SiC(CH3)3), Ϫ3.2 (SiCH3) and Ϫ4.0
(SiCH3); m/z 376.2431 (Mϩ, 1%, C22H36O3Si requires 376.2434),
319 (4), 301 (4), 277 (3), 181 (15), 75 (67), 73 (100) and 41 (22).
(5aꢀ,6ꢁ,9aꢀ,9bꢀ)-6-Acetoxy-4-[(1,1-dimethylethyl)dimethyl-
silyloxy]-1,2,3,5,5a,6,9a,9b-octahydro-8,9a-dimethyl-9H-
benz[e]inden-9-one 49
(5aꢀ,6ꢁ,9aꢀ,9bꢀ)-4-[(1,1-Dimethylethyl)dimethylsilyloxy]-
1,2,3,5,5a,6,9a,9b-octahydro-6-hydroxy-8,9a-dimethyl-9H-
benz[e]inden-9-one 47a and (5aꢀ,6ꢀ,9aꢀ,9bꢀ)-4-[(1,1-dimethyl-
ethyl)dimethylsilyloxy]-1,2,3,5,5a,6,9a,9b-octahydro-6-hydroxy-
8,9a-dimethyl-9H-benz[e]inden-9-one 47b
To a solution of 47a (544 mg, 1.50 mmol) in dry dichloro-
methane at RT was added acetyl chloride (0.71 ml, 7.5 mmol),
triethylamine (1.05 ml, 7.50 mmol) and 4-(dimethylamino)-
pyridine (DMAP) (36.7 mg, 0.30 mmol). This solution was
stirred at RT for 24 h. The mixture was diluted with dichloro-
methane (100 ml) before it was washed with brine (2 × 20 ml),
dried and concentrated under reduced pressure. Chromato-
graphy of the residue provided 49 (478 mg, 74%) as a yellow
oil; νmax(film)/cmϪ1 1736 and 1674; δH 6.44 (1 H, s, 7-H), 5.92
(1 H, apparent t, J 2.5, 6-H), 2.98 (1 H, m), 2.90 (1 H, m), 2.73
(1 H, m), 2.57–2.53 (2 H, m), 2.40 (1 H, dd, J 17.3 and 12.9),
2.12 (3 H, s, CH3CO2), 2.08 (m), 1.94 (1 H, m), 1.84 (3 H,
8-methyl), 1.67 (1 H, m), 1.50 (3 H, 9a-methyl), 0.92 (9 H, s,
SiC(CH3)3) and 0.1 (6 H, s, Si(CH3)2); δC 198.5 (C-9), 170.1
(CH3CO2), 139.6 (C-7), 138.0 (0), 137.4 (0), 136.8 (0), 68.2 (C-8),
49.1 (C-9a), 46.5 (1), 36.0 (2), 35.7 (2), 29.3 (2), 25.7 (SiC-
(CH3)3), 21.7 (2), 21.4 (9a-methyl), 21.0 (CH3CO2), 18.1 (SiC-
(CH3)3), 15.9 (8-methyl) and Ϫ3.6 (Si(CH3)2); m/z 404.2372
(Mϩ, 2%, C23H36O4Si requires 404.2381), 303 (6), 285 (5), 191
(9), 149 (100), 147 (21), 121 (21), 98 (79), 75 (32) and 43 (85).
To a solution of 44 (360 mg, 1.00 mmol) and CeCl3ؒ7H2O (373
mg, 1.00 mmol) in methanol (10 ml) at 0 ЊC was added NaBH4
(26.6 mg, 0.70 mmol) over 5 min. The mixture was stirred for
2 min before 40 ml of a dilute aqueous NH4Cl solution was
added. This was extracted with ethyl acetate (4 × 25 ml). The
combined extracts were washed with water (2 × 25 ml) and
brine (25 ml), dried and concentrated under reduced pressure.
Chromatography of the residue gave 47a and 47b (347 mg, 96%)
as a 1 : 1 mixture. These epimers were ultimately separated by
repeated chromatography.
For 47a: colourless viscous oil; νmax(Nujol)/cmϪ1 3421
(broad) and 1713; δH 6.34 (1 H, d, J 1.2, 7-H), 4.93 (1 H, m,
6-H), 2.53–2.43 (m), 2.33–2.19 (m), 1.91–1.78 (m), 1.74 (3 H, s,
8-methyl), 1.43 (1 H, m), 1.28 (3 H, s, 9a-methyl), 0.90 (9 H, s,
SiC(CH3)3), 0.04 (3 H, s, SiCH3) and 0.02 (3 H, s, SiCH3); NOE
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656
2653

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(3aꢀ,5aꢀ,6ꢁ,9aꢀ,9ba)-6-Acetoxy-3a-(1,3-dithian-2-yl)-1,2,3,3a,
4,5,5a,6,9a,9b-decahydro-8,9a-dimethyl-9H-benz[e]indene-4,9-
dione 50
combined extracts were washed with brine (20 ml), dried and
concentrated under reduced pressure. Chromatography of the
residue gave 52 (83.5 mg, 59%) as a white solid: mp 226–228
ЊC; νmax(Nujol)/cmϪ1 1745, 1710 and 1661; δH 6.69 (1 H, s,
7-H), 4.84 (1 H, s, 2-H of dithiane), 3.65 (1 H, dt, J 10.1 and
2.0, 6-H), 3.49 (3 H, s, OCH3), 3.09 (1 H, dd, J 13.8 and 6.0),
2.95 (1 H, dd, J 7.8 and 3.1), 2.89 (1 H, dt, J 6.6 and 1.5),
2.84 (1 H, m), 2.70 (1 H, dd, J 13.6 and 2.5), 2.59 (1 H, dt,
J 14.1 and 8.7), 2.43 (1 H, m), 2.13 (2 H, dq, J 14.0 and 3.3),
1.88 (1 H, ddd, J 13.7, 10.3 and 3.1), 1.81 (3 H, t, J 1.6,
8-methyl), 1.70 (3 H, s, 9a-methyl), 1.56 (1 H, m), 1.43 (1 H,
dd, J 12.6 and 6.5), 1.29 (1 H, m) and 0.96 (1 H, m); NOE
data: 4.84 (3.09, 7%; 1.70, 9%), 1.70 (4.84, 11%; 3.09, 4%;
2.43, 5%); δC 210.0 (C-4), 201.0 (C-9), 142.3 (C-7), 135.7
(C-8), 75.3 (C-6), 63.3 (C-3a), 57.8 (OCH3), 56.5 (C-2 of
dithiane), 53.4 (1), 50.1 (1), 45.6 (C-9a), 36.4 (2), 31.8 (2), 31.1
(2, 2C), 27.9 (2), 26.2 (9a-methyl), 25.8 (2), 22.8 (2) and 16.3
(8-methyl); m/z 380.1484 (Mϩ, 1%, C20H28O3S2 requires
380.1478), 262 (4), 221 (8), 152 (18), 149 (13), 135 (15), 119
(100), 112 (29) and 69 (15).
To a solution of 49 (415 mg, 1.10 mmol) in dry dichloro-
methane (10 ml) at Ϫ78 ЊC under argon was added over 5 min
a solution of 1,3-dithienium tetrafluoroborate (600 mg, 2.91
mmol) in dry nitromethane (2.0 ml). After the solution was
stirred for another 20 min at Ϫ78 ЊC, it was allowed to warm to
RT. The mixture was poured into saturated aqueous NaHCO3
solution (20 ml), and this was extracted with ethyl acetate
(3 × 40 ml). The combined organic extracts were washed with
brine (20 ml) and dried. The solution was concentrated under
reduced pressure, and chromatography of the residue provided
50 (233 mg, 52%) as a yellow oil: δH 6.26 (1 H, s, 7-H), 5.83 (1 H,
apparent t, J 2.4, 6-H), 4.30 (1 H, s, 2-H of dithiane), 2.99 (1 H,
m), 2.92–2.82 (2 H, m), 2.71 (1 H, dd, J 14.6 and 8.0), 2.66 (1 H,
dd, J 5.9 and 3.6), 2.32 (1 H, dd, J 18.8 and 10.1), 2.26 (1 H, m),
2.17–2.08 (4 H, m), 2.05 (3H, s, CH3CO2), 1.95–1.79 (3 H, m),
1.76 (3 H, s, 8-methyl), 1.66 (1 H, s) and 1.46 (3 H, s, 9a-methyl);
NOE data: 4.30 (2.99, 3%; 2.71 and 2.66, 12%), 1.46 (5.83, 12%;
4.30, 2%; 2.99, 3%; 2.71 and 2.66, 17%); δC 210.5 (C-4), 201.2
(C-9), 170.2 (CH3CO2), 137.4 (C-8), 136.5 (C-7), 69.4 (C-6),
63.3 (C-3a), 57.8 (C-2 of dithiane), 52.6 (1), 48.5 (C-9a), 44.8
(1), 37.2 (2), 33.4 (2), 31.7 (2), 31.5 (2), 28.6 (2), 25.6 (2), 24.1
(2), 23.4 (9a-methyl), 20.9 (CH3CO2) and 15.9 (8-methyl).
X-Ray crystal structure determination for 52
A colourless irregular crystal of dimensions 0.35 × 0.10 × 0.40
mm was mounted on a glass fibre: C20H28O3S2, M = 380.56,
orthorhombic, a = 21.765(7), b = 14.725(6), c = 11.857(6) Å,
V = 3800(2) Å3, T = 299 K, space group Pbca (no. 61), Z = 8,
µ(Cu-Kα) 26.67 cmϪ1, 3219 reflections collected, 2257 observed
(I > 2.00σ(I )); R = 0.094, Rw = 0.092, goodness of fit = 6.93.
Hydrolysis of 50 to 48
To a solution of 50 (197 mg, 0.480 mmol) in methanol (10 ml)
at RT was added a solution of K2CO3 (335 mg, 2.40 mmol)
in water (2 ml). The mixture was stirred at RT for 2 h. A 1%
aqueous HCl solution (5 ml) was added to the mixture, and this
was extracted ethyl acetate (3 × 20 ml). The combined extracts
were washed with brine (20 ml) and dried. The solution was
concentrated under reduced pressure, and chromatography of
the residue afforded 48 (89%).
(1R*,4S*,5R*,9R*,10S*,11S*,12R*, 15S*)-5-Hydroxy-7,9,12-
trimethyl-14-oxapentacyclo[8.6.0.01,5.04,9.011,15]hexadec-6-ene-
2,8,13-trione 53
A solution of 1,3-dithienium tetrafluoroborate (24.0 mg, 0.116
mmol) in nitromethane (1.0 ml) was added to a solution of
33 (50.0 mg, 0.116 mmol) in dry dichloromethane (3.0 ml) at
Ϫ78 ЊC. The mixture was stirred at this temperature for 20 min
before it was allowed to warm to RT. Ethyl acetate (25 ml) was
added, and this solution was washed with a saturated aqueous
NaHCO3 solution (2 × 20 ml) and brine (2 × 20 ml). The solu-
tion was dried (Na2SO4) and concentrated under reduced pres-
sure. Preparative TLC provided 53 (18 mg, 48%) as colourless
crystals: mp >220 ЊC (dec.); νmax(Nujol)/cmϪ1 3405, 1748 and
1669; δH (CD3COCD3) 7.00 (1 H, s, 6-H), 5.20 (1 H, s, OH,
removed with D2O), 4.90 (1 H, t, J 5.7), 2.80 (1 H, m), 2.66–2.44
(3 H, m), 2.35 (1 H, d, J 16.2), 2.08–2.01 (3 H, m), 1.83 (3 H, d,
J 1.4, 7-methyl), 1.35 (3 H, s, 9-methyl) and 0.98 (3 H, d, J 7.2,
12-methyl); δC (CD3COCD3) 209.0, 200.8, 178.0, 149.4, 138.3,
88.6, 83.5, 76.1, 59.6, 55.9, 54.7, 48.1, 39.3, 37.2, 26.6, 18.1, 15.1
and 12.1; m/z 316.1306 (Mϩ, 62%, C18H20O5 requires 316.1310),
288 (10), 205 (18), 178 (17), 165 (36), 151 (100), 137 (14), 123
(12), 91 (13) and 79 (15).
(5aꢀ,6ꢀ,9aꢀ,9bꢀ)-4-[(1,1-Dimethylethyl)dimethylsilyloxy]-
1,2,3,5,5a,6,9a,9b-octahydro-6-methoxy-8,9a-dimethyl-9H-
benz[e]inden-9-one 51
To a solution of 47b (690 mg, 1.90 mmol) in THF (30 ml) at RT
was added sodium hydride (235 mg, 9.50 mmol) and iodo-
methane (1.2 ml, 19 mmol). This was stirred at RT for 12 h. Ice-
cold water (30 ml) was added, and this solution was extracted
with ethyl acetate (4 × 50 ml). The combined extracts were
washed with brine (2 × 40 ml), dried and concentrated under
reduced pressure. Chromatography provided 51 (614 mg, 86%)
as a pale yellow oil: νmax(film)/cmϪ1 1712, 1674 and 1625;
δH 6.58 (1 H, s, 7-H), 3.76 (1 H, m, 6-H), 3.43 (3 H, s, OCH3),
2.46–2.22 (m), 2.15–2.07 (m), 1.79 (3 H, s, 8-methyl), 1.73
(1 H, m), 1.56–1.41 (3 H, m), 1.34 (3 H, s, 9a-methyl), 0.93
(9 H, s, SiC(CH3)3) and 0.10 (6 H, s, Si(CH3)2); δC 203.0 (C-9),
139.8 (C-7), 137.8 (0), 135.4 (0), 120.8 (0), 76.1 (C-6), 57.0
(OCH3), 49.4 (1), 46.0 (1), 45.6 (C-9a), 30.8 (2), 29.9 (2), 25.7
(SiC(CH3)3), 25.2 (9a-methyl), 23.1 (2), 18.1 (SiC(CH3)3), 16.2
(8-methyl), Ϫ4.0 (SiCH3) and Ϫ4.1 (SiCH3); m/z 376.2444 (Mϩ,
<1%, C22H36O3Si requires 376.2432), 361 (1), 280 (3), 225 (13),
205 (11), 152 (100), 112 (26), 75 (46) and 73 (35).
X-Ray crystal structure determination for 53
A colourless irregular crystal of dimensions 0.40 × 0.30 × 0.15
mm was mounted on a glass fibre: C18H20O5, M = 316.35, tet-
ragonal, a = 9.055(3), c = 18.635(6) Å, V = 1527.8(7) Å3, T = 299
K, space group P43 (no. 78), Z = 4, µ(Mo-Kα) 1.0 cmϪ1, 1588
reflections collected, 1409 unique (Rint = 0.022); 1045 observed
(I > 1.50σ(I )); R = 0.033, Rw = 0.033, goodness of fit = 1.36.
(3aꢀ,5aꢀ,6ꢀ,9aꢀ,9ba)-3a-(1,3-Dithian-2-yl)-1,2,3,3a,4,5,5a,6,
9a,9b-decahydro-6-methoxy-8,9a-dimethyl-9H-benz[e]indene-
4,9-dione 52
(4ꢀ,4aꢁ,7aꢀ,10aꢀ,10bꢁ,10cꢁ)-6-[(1,1-Dimethylethyl)dimethyl-
silyloxy]-4,4a,5,7,7a,10,10b,10c-octahydro-4-hydroxy-2,10c-
dimethyl-1H-benz[6,7]indeno[2,1-b]furan-1,9(10aH)-dione 54a
and (4ꢀ,4aꢀ,7aꢁ,10aꢁ,10bꢀ,10cꢀ)-6-[(1,1-dimethylethyl)dimethyl-
silyloxy]-4,4a,5,7,7a,10,10b,10c-octahydro-4-hydroxy-2,10c-
dimethyl-1H-benz[6,7]indeno[2,1-b]furan-1,9(10aH)-dione 54b
A solution of 1,3-dithienium tetrafluoroborate (153 mg, 0.744
mmol) in dry nitromethane (1.0 ml) was added over 5 min to a
solution of 51 (140 mg, 0.372 mmol) in dry dichloromethane
(3.0 ml) at Ϫ78 ЊC under argon. The solution was stirred at
Ϫ78 ЊC for 20 min before it was allowed to warm to RT. The
mixture was added to a saturated aqueous NaHCO3 solution
(20 ml). This was extracted with ethyl acetate (3 × 40 ml). The
To a solution of 25 (858 mg, 2.06 mmol) and CeCl3ؒ7H2O
2654
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656

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(775 mg, 2.06 mmol) in methanol (20 ml) at 0 ЊC was added
sodium borohydride (55.7 mg, 1.44 mmol) in small portions
over 5 min. After stirring for another 2 min, dilute aqueous
NH4Cl solution (40 ml) was added. This was extracted with
ethyl acetate (4 × 40 ml). The combined extracts were washed
with water (2 × 40 ml) and brine (40 ml), dried and concen-
trated under reduced pressure. Chromatography of the residue
provided a 1 : 1 epimeric mixture of alcohols 54a and 54b
(712 mg, 83%). Further careful chromatography did separate
these isomers.
(4ꢀ,4aꢁ,6aꢁ,7aꢀ,10aꢀ,10bꢁ,10cꢁ)-6a-(1,3-Dithian-2-yl)-
4,4a,5,6a,7,7a,10,10a,10b,10c-decahydro-4-hydroxy-2,10c-
dimethyl-1H-benz[6,7]indeno[2,1-b]furan-1,6,9-trione 57
To a solution of 56 (35 mg, 0.075 mmol) in methanol (2.0 ml)
was added a solution of K2CO3 (105 mg, 0.753 mmol) in water
(1.0 ml). The mixture was stirred at RT for 2 h. Ethyl acetate
(100 ml) was added and the solution was washed with 1% aque-
ous HCl (10 ml) and brine (10 ml). The solution was dried and
concentrated under reduced pressure. Chromatography of the
product provided 57 (22.5 mg, 80%) as a white solid: mp 264–
267 ЊC; νmax(Nujol)/cmϪ1 1713 and 1674; δH (CD3SOCD3) 6.41
(1 H, s, 3-H), 4.99 (1 H, m, 7a-H), 4.66 (1 H, broad s, 4-H), 4.43
(1 H, s, 2-H of dithiane), 3.44 (1 H, m), 2.94–2.70 (m), 2.62
(1 H, d, J 5.1), 2.53 (1 H, dd, J 15.6 and 4.2), 2.48 (1 H, m), 2.38
(1 H, dd, J 18.0 and 1.8), 2.25 (1 H, d, J 15.0), 2.10 (1 H, dd,
J 17.1 and 7.8), 2.01 (1 H, m), 1.60 (3 H, s, 2-methyl) and 1.31
(3 H, s, 10c-methyl); NOE data 4.99 (3.44, 7%; 2.48, 2%), 4.43
(2.94–2.70, 6%; 2.62, 4%) and 1.31 (4.66, 7%; 3.44, 6%; 2.62,
6%); δC (CD3SOCD3) 208.5 (C-6), 202.5 (C-1), 177.0 (C-9),
144.7 (C-3), 133.7 (C-2), 85.0 (C-7a), 65.6 (C-4), 63.2 (C-6a),
60.5 (1), 56.0 (C-2 of dithiane), 48.7 (C-10c), 46.6 (1), 41.6 (1),
37.1 (2), 37.0 (2), 31.0 (2), 30.8 (2), 25.5 (2), 22.3 (10c-methyl)
and 15.6 (2-methyl); m/z 422.1229 (Mϩ, <1%, C21H26O5S2
requires 422.1229), 286 (1), 241 (4), 119 (100) and 57 (12).
For 54a: pale yellow solid, mp 100–102 ЊC; νmax(Nujol)/cmϪ1
3422 and 1712; δH 6.38 (1 H, s, 3-H), 5.05 (1 H, dt, J 6.2 and 2.6,
7a-H), 4.96 (1 H, m, 4-H), 3.89 (1 H, m), 2.90 (1 H, dd, J 6.3
and 2.7), 2.82 (1 H, dd, J 17.7 and 9.0), 2.64 (1 H, broad s),
2.57–2.45 (m), 2.41 (1 H, d, J 2.7), 2.35 (1 H, d, J 2.4), 2.31–2.21
(m), 2.05–1.97 (1 H, m), 1.75 (3 H, s, 2-methyl), 1.29 (3 H, s,
10c-methyl), 0.90 (9 H, s, SiC(CH3)3), 0.06 (3 H, s, SiCH3) and
0.04 (3 H, s, SiCH3); NOE data 3.89 (5.05, 7%; 2.82, 4%) and
1.29 (4.96, 12%; 3.89, 5%); δC 202.3 (C-1), 177.4 (C-9), 142.1
(C-3), 140.6 (0), 133.9 (0), 117.3 (0), 86.0 (C-7a), 67.5 (C-4),
54.9 (10), 49.7 (1), 48.3 (C-10c), 41.2 (1), 37.6 (2), 34.4 (2), 28.6
(2), 25.6 (SiC(CH3)3), 21.4 (10c-methyl), 17.9 (SiC(CH3)3), 15.8
(2-methyl), Ϫ3.8 (SiCH3) and Ϫ4.0 (SiCH3); m/z 418.2191 (Mϩ,
5%, C23H34O5Si requires 418.2174), 281 (8), 224 (15), 223 (25),
138 (100), 121 (20), 117 (18), 75 (95) and 73 (97).
For 54b: white solid, mp 128–130 ЊC; νmax(Nujol)/cmϪ1 3416,
1746, 1708 and 1665; δH 6.54 (1 H, t, J 1.7, 3-H), 4.91 (1 H, dt,
J 7.1 and 2.6, 7a-H), 4.25 (1 H, m, 4-H), 3.03 (1 H, dd, J 15.7
and 7.1, 10a-H), 2.86 (1 H, apparent q, J 8.6), 2.58 (1 H, dd,
J 18.2 and 8.3), 2.38–2.29 (m), 2.26–2.17 (m), 2.14–2.02 (m),
1.80 (3 H, s, 2-methyl), 1.41 (3 H, s, 10c-methyl), 0.93 (9 H, s,
SiC(CH3)3), 0.11 (3 H, s, SiCH3) and 0.10 (3 H, s, SiCH3); NOE
data: 4.91 (3.03, 4%; 2.86, 5%), 4.25 (2.86, 5%), 2.86 (4.91, 7%;
4.25, 5%) and 1.41 (2.14–2.02, 10%); δC 210.8 (C-1), 176.9 (C-9),
142.9 (C-3), 140.0 (0), 135.3 (0), 117.1 (0), 83.9 (C-7a), 67.0
(C-4), 51.9 (1), 48.8 (1), 45.6 (C-10c), 42.0 (1), 35.2 (2), 33.1 (2),
30.4 (2), 25.6 (SiC(CH3)3), 25.2 (10c-methyl), 18.0 (SiC(CH3)3),
16.1 (2-methyl), Ϫ4.0 (SiCH3) and Ϫ4.1 (SiCH3); m/z 418.2198
(Mϩ, 5%, C23H34O5Si requires 418.2174), 359 (9), 281 (13), 224
(7), 223 (15), 138 (100), 117 (10), 75 (61) and 73 (50).
(1R*,2R*,3R*,4R*,8S*,10S*,11S*,13S*,14R*)-14-Acetoxy-10-
(1,3-dithian-2-yl)-11-hydroxy-2,16-dimethyl-7,17-dioxapenta-
cyclo[9.5.1.02,13.03,10.04,8]heptadec-15-en-6-one 58
To a solution of 56 (34.5 mg, 0.074 mmol), in 1 : 1 methanol–
dichloromethane (4 ml) at 0 ЊC was added sodium borohydride
(4.3 mg, 0.11 mmol). The mixture was stirred at 0 ЊC for 10 min,
then at RT for 2 h. The mixture was poured into a dilute aque-
ous NH4Cl solution (10 ml), which was extracted with ethyl
acetate (4 × 20 ml). The combined extracts were washed with
brine (20 ml), dried and concentrated under reduced pressure.
Chromatography gave 58 (27.5 mg, 80%) as a white solid: mp
242–243.5 ЊC; νmax(Nujol)/cmϪ1 1765 and 1714; δH 5.42 (1 H, m,
14-H), 5.40 (1 H, s, 15-H), 5.06 (1 H, m, 8-H), 4.14 (1 H, s, 2-H
of dithiane), 3.62 (1 H, d, J 1.3, 1-H), 3.03–2.85 (3 H, m),
2.83–2.72 (3 H, m), 2.53–2.45 (2 H, m), 2.38 (1 H, m), 2.21–1.94
(4 H, m), 2.09 (3 H, s, CH3CO2), 1.86 (3 H, 16-methyl) and 0.93
(3 H, 2-methyl); NOE data: 2.38 (5.42, 8%; 4.14, 7%) and 0.93
(5.42, 12%; 3.62, 5%; 3.03–2.85, 5%; 2.53–2.45, 6%); δC 176.6
(0), 170.8 (0), 138.4 (C-16), 121.7 (C-15), 98.2 (C-11), 86.3
(C-8), 74.5 (C-1), 71.6 (C-14), 58.8 (C-10), 58.7 (1), 57.9 (C-2 of
dithiane), 41.1 (1), 37.3 (1), 36.2 (2), 35.3 (2), 31.8 (2), 31.3 (2),
25.5 (2), 21.5 (16-methyl), 21.2 (CH3CO2) and 18.2 (2-methyl);
m/z 466.1493 (Mϩ, 2%, C23H30O6S2 requires 466.1484), 243 (11),
119 (100) and 43 (21).
(4ꢀ,4aꢁ,6aꢁ,7aꢀ,10aꢀ,10bꢁ,10cꢁ)-4-Acetoxy-6a-(1,3-dithian-2-
yl)-4,4a,5,6a,7,7a,10,10a,10b,10c-decahydro-2,10c-dimethyl-
1H-benz[6,7]indeno[2,1-b]furan-1,6,9-trione 56
The formation of 55 followed the same procedure as for 49. 1,3-
Dithienium tetrafluoroborate (498 mg, 2.42 mmol) in dry
nitromethane (2.0 ml) was added over 5 min to a solution of
55 (371 mg, 0.805 mmol) in dry dichloromethane (10 ml) at
Ϫ78 ЊC. The solution was stirred at Ϫ78 ЊC for 20 min before it
was allowed to warm to RT. The mixture was poured into a satur-
ated aqueous NaHCO3 solution (20 ml). This was extracted
with ethyl acetate (3 × 40 ml). The combined organic extracts
were washed with brine (20 ml), dried and concentrated under
reduced pressure. Compound 56 (157 mg, 42%) was difficult
to separate by chromatography from the hydrolysis by-product.
For 56: mp 192–195 ЊC; νmax(Nujol)/cmϪ1 1708 and 1669;
δH 6.29 (1 H, s, 3-H), 5.87 (1 H, m, 4-H), 5.14 (1 H, t, J 6.4,
7a-H), 4.16 (1 H, s, 2-H of dithiane), 3.62 (1 H, m), 3.15 (1 H,
m), 2.98–2.82 (6 H, m), 2.50 (1 H, m), 2.38 (1 H, ddd, J 20.7,
18.7 and 1.4), 2.11 (3 H, s, CH3CO2), 2.07 (1 H, m), 1.78 (1 H,
m), 1.74 (3 H, d, J 2.6, 2-methyl) and 1.46 (3 H, s, 10c-methyl);
NOE data: 5.87 (3.15, 8%; 1.46, 10%) and 1.46 (5.87, 12%; 3.62,
8%; 2.77, 8%); δC 208.0 (C-6), 201.3 (C-1), 176.6 (C-9), 170.1
(CH3CO2), 137.9 (C-3), 136.9 (C-2), 86.0 (C-7a), 69.7 (C-4),
63.0 (C-6a), 59.9 (1), 56.2 (C-2 of dithiane), 49.3 (C-10c),
44.6 (1), 42.2 (1), 38.7 (2), 38.3 (2), 37.8 (2), 32.2 (2), 31.5 (2),
25.3 (2), 22.1 (10c-methyl), 20.9 (CH3CO2) and 15.7 (2-methyl);
m/z 464.1307 (Mϩ, <1%, C23H28O6S2 requires 464.1326), 241
(2), 119 (100) and 43 (22).
(2ꢀ,4aꢁ,6aꢀ,7aꢁ,10ꢁ,10aꢁ,10bꢀ,10cꢀ)-2,4a,5,6a,7,7a,10,10a,
10b,10c-Decahydro-2,10,10c-trimethyl-3H-benz[6,7]indeno-
[2,1-b]furan-1,4,6,9-tetraone 59
To a solution of 43 (80 mg, 0.25 mmol) in glacial acetic acid
(10 ml) heated under reflux was added zinc dust (0.98 g,
15 mmol) in portions until the solution was colourless and TLC
indicated that 43 was completely consumed. The mixture was
heated under reflux for an additional 7 h. The mixture was
filtered, and the filtrate was poured into ethyl acetate (100 ml)
and water (40 ml). Solid Na2CO3 was added until CO2-
evolution ceased. The aqueous layer was re-extracted with ethyl
acetate (2 × 15 ml). The combined organic layers were washed
with water (2 × 30 ml) and brine (30 ml), dried (Na2SO4) and
concentrated under reduced pressure. Chromatography of
the residue gave a 6 : 1 ratio of 59 and 60 (combined 62 mg,
76%). Crystallization from dichloromethane and ethyl acetate
gave a small sample of homogeneous 59 as a solid: mp >220 ЊC
(dec.); νmax(Nujol)/cmϪ1 1754 and 1705; δH (CD2Cl2) 4.80 (1 H,
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656
2655

View Article Online
apparent broad q, J 7.5, 7a-H), 3.42 (1 H, dd, J 9.9 and 7.1,
4a-H), 3.02–2.89 [3 H, m, 2-H (m), 6a-H (t) and 7β-H (dd)],
2.84 (1 H, dd, J 19.0 and 7.5, 3β-H), 2.82 (1 H, dd, J 9.5 and 7.0,
10b-H), 2.61–2.58 (2 H, m, 5-H2), 2.49 (1 H, qd, J 7.5 and 3.6,
10-H), 2.26 (1 H, dd, J 19.0 and 12.6, 3α-H), 1.98 (1 H, appar-
ent dt, J 9.5 and 3.6, 10a-H), 1.51 (1 H, m, 7α-H), 1.30 (3 H, s,
10c-methyl), 1.17 (3 H, d, J 6.2, 2-methyl) and 1.11 (3 H, d,
J 7.5, 10-methyl); NOE data: 4.80 (3.02–2.89 [7β-H], 3%; 1.98,
4%), 3.43 (3.02–2.89 [2-H], 6%; 2.61–2.58, 1%; 1.98, 9%), 1.98
(4.80, 5%; 3.43, 9%; 1.11, 1%), 1.30 (3.02–2.89 [6a-H], 5%; 2.82,
16%; 2.61–2.58, 5%; 2.26, 2%), 1.17 (3.02–2.89 [2-H], 6%; 2.26,
3%) and 1.11 (2.49, 4%; 1.98, 4%); δC (CD2Cl2) 212.8 (0), 208.7
(0), 206.7 (0), 179.9 (C-9), 81.7 (C-7a), 56.3 (C-10b), 50.5
(C-6a), 49.5 (C-4a), 48.0 (C-10c), 47.2 (C-10a), 42.5 (C-3), 42.3
(C-2), 42.2 (C-10), 36.7 (C-5), 32.5 (C-7), 21.8 (10c-methyl),
18.2 (10-methyl) and 13.8 (2-methyl); m/z 318.1446 (Mϩ, 22%,
C18H22O5 requires 318.1466), 221 (7), 207 (100), 179 (12), 161
(27), 152 (19), 121 (14), 112 (15), 109 (17), 93 (16), 55 (41), 42
(32) and 41 (45).
was heated for another 10 h. After cooling, the mixture was
filtered, and the filtrate was added to ethyl acetate (80 ml) and
water (80 ml). Solid Na2CO3 was added until CO2-evolution
ceased. The aqueous layer was re-extracted with ethyl acetate
(2 × 30 ml). The combined organic layers were washed with
water (30 ml) and brine (30 ml), dried and concentrated under
reduced pressure. Chromatography of the residue provided 61
(50 mg, 20%) as a colourless solid: mp 179–181 ЊC; νmax(Nujol)/
cmϪ1 1709; δH 4.36 (1 H, m, 7a-H), 3.52 (1 H, dd, J 10.4 and 6.5,
4a-H), 3.42 (1 H, dq, J 8.8 and 6.1, 9-H), 3.06 (1 H, m, 2-H),
3.05 (1 H, t, J 7.7, 6a-H), 2.86 (1 H, dd, J 9.6 and 7.0, 3β-H),
2.81 (1 H, dd, J 12.6 and 6.9, 10b-H), 2.74 (1 H, dd, J 13.6
and 7.7, 7β-H), 2.59 (2 H, m, 5-H2), 2.26 (1 H, dd, J 19.6 and
13.4, 3α -H), 1.70 (1 H, m, 10a-H), 1.57–1.49 (2 H, m, 7α -H
and 10-H), 1.30 (3 H, s, 10c-methyl), 1.23 (3 H, d, J 6.1,
9-methyl), 1.20 (3 H, d, J 6.4, 2-methyl) and 0.80 (3 H, d, J 6.7,
10-methyl); NOE data 4.36 (3.42, 4%; 2.74, 4%; 1.70, 3%), 3.52
(3.06, 7%; 1.70, 6%), 1.70 (4.36, 5%; 3.52, 10%; 0.80, 1%), 1.30
(3.05, 8%; 2.81, 6%, 2.59, 6%) and 0.80 (3.42, 4%; 3.06, 2%;
1.70, 3%; 1.57–1.49, 2%); δC 212.0 (0), 209.1 (0), 207.0 (0), 85.8
(C-9), 83.1 (C-7a), 55.7 (C-10b), 53.2 (C-10a), 53.1 (C-6a), 48.9
(C-4a), 47.5 (C-10c), 47.4 (C-10), 42.0 (C-3), 41.5 (C-2), 36.2
(C-5), 30.3 (C-7), 21.8 (10c-methyl), 18.7 (9-methyl), 17.0
(10-methyl) and 13.4 (2-methyl); m/z 318.1839 (Mϩ, 12%,
C19H26O4 requires 318.1831), 207 (9), 178 (10), 161 (23), 152
(11), 136 (10), 121 (14), 112 (100), 97 (68), 55 (37), 43 (52) and
41 (35).
X-Ray crystal structure determination for 59¶
A colourless irregular crystal of dimensions 0.40 × 0.20 × 0.20
mm was mounted on a glass fibre: C18H22O5, M = 318.37,
monoclinic, a = 6.942(7), b = 27.82(1), c = 7.998(4) Å, β
94.95(7)Њ, V = 1539(2) Å3, T = 299 K, space group P21/n
(no. 14), Z = 4, µ(Mo-Kα) 0.99 cmϪ1, 3045 reflections collected,
2809 unique (Rint = 0.121); 1331 observed (I > 2.00σ(I ));
R = 0.093, Rw = 0.094, goodness of fit = 3.21.
Acknowledgements
(2ꢀ,4aꢁ,6aꢁ,7aꢀ,10ꢀ,10aꢀ,10bꢁ,10cꢁ)-2,4a,5,6a,7,7a,10,10a,
10b,10c-Decahydro-2,10,10c-trimethyl-3H-benz[6,7]indeno-
[2,1-b]furan-1,4,6,9-tetraone 60
We are very grateful to Mr David O. Miller of this Department
for the X-ray crystal structures. This research was supported by
a grant from the Natural Sciences and Engineering Research
Council of Canada.
To a solution of 43 (28 mg, 0.089 mmol) in acetone (2.0 ml)
was added in small portions a 20% aqueous solution of TiCl3
(0.24 ml, 0.38 mmol) at RT. The solution was stirred for 20 min
before it was poured into 25 ml of brine. This was extracted
with ethyl acetate (3 × 15 ml). The combined organic solutions
were washed with water (20 ml) and brine (20 ml), dried and
concentrated under reduced pressure. Chromatography of the
residue provided 60 (14 mg, 50%) as a white solid: 178–180 ЊC;
νmax(Nujol)/cmϪ1 1770 and 1710; δH 4.78 (1 H, apparent q, J 7.2,
7a-H), 3.49 (1 H, m, 4a-H), 3.27 (1 H, m, 2-H), 3.05–2.92 (4 H,
m), 2.74 (1 H, dd, J 9.6 and 7.7, 10b-H), 2.53 (1 H, m, 5β-H),
2.49 (1 H, dq, J 9.5 and 5.0, 10-H), 2.26 (1 H, dd, J 19.6 and
13.4, 3α-H), 1.68 (3 H, s, 10c-methyl), 1.67 (1 H, m, 10a-H),
1.58 (1 H, m, 7β-H ), 1.20 (3 H, d, J 6.4, 2-methyl) and 1.13
(3 H, d, J 7.5, 10-methyl); NOE data: 3.49 (3.27, 6%; 2.53, 1%;
1.68, 1%) and 1.20 (3.27, 8%; 2.26, 2%); δC 211.9 (0), 207.0 (0),
206.2 (0), 179.3 (C-9), 81.6 (C-7a), 55.4 (C-10b), 54.1 (C-4a),
49.6 (C-6a), 47.92 (C-10c), 47.87 (C-10a), 42.3 (C-3), 41.9 (C-
10), 39.0 (C-2), 34.6 (C-5), 31.9 (C-7), 28.0 (10c-methyl), 17.6
(10-methyl) and 13.6 (2-methyl); m/z 318.1447 (Mϩ, 44%,
C18H22O5 requires 318.1466), 290 (11), 276 (17), 248 (12), 245
(11), 231 (22), 221 (18), 207 (100), 161 (22), 152 (46), 109 (36),
99 (32), 93 (37), 91 (32), 79 (42), 77 (32), 69 (51), 55 (91), 42 (77)
and 41 (84).
References
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(2ꢀ,4aꢁ,6aꢀ,7aꢁ,9ꢀ,10ꢁ,10aꢁ,10bꢀ,10cꢀ)-4a,5,6a,7,7a,9,10,10a,
10b,10c-Decahydro-2,9,10,10c-tetramethyl-3H-benz[6,7]indeno-
[2,1-b]furan-1(2H),4,6-trione 61
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A solution of 42 (0.258 g, 0.781 mmol) in glacial acetic acid
(40 ml) heated under reflux as zinc dust (1.45 g, 21.7 mmol) was
added in portions until the solution became colourless and
TLC indicated that 42 was completely consumed. The mixture
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¶ CCDC reference number(s) 164940–164942. See http://www.rsc.org/
suppdata/p1/b1/b104924k/ for crystallographic files in .cif or other
electronic format.
2656
J. Chem. Soc., Perkin Trans. 1, 2001, 2644–2656