Synthesis and photoreaction of tricyclo[5.2.2.02,6]undecanes in the excited singlet (1S) state: A novel and stereospecific route to protoilludanoids

Article abstract of DOI:10.1039/a704817c

A novel and general approach to the synthesis of functionalised protoilludane skeletons having fused-four-, six- and five-membered rings is described. A photochemical sigmatropic 1,3-acyl shift in endotricyclo[5.2.2.0^2,6]undecanes having a β,γ-

Full text of DOI:10.1039/a704817c

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Synthesis and photoreaction of tricyclo[5.2.2.02,6]undecanes in the
excited singlet (1S ) state: a novel and stereospecific route to
protoilludanoids
Vishwakarma Singh* and Uday Sharma
Department of Chemistry, Indian Institute of Technology, Powai, Bombay 400 076, India
A novel and general approach to the synthesis of functionalised protoilludane skeletons having fused-
four-, six- and five-membered rings is described. A photochemical sigmatropic 1,3-acyl shift in endo-
tricyclo[5.2.2.02,6]undecanes having a â,ã-unsaturated carbonyl chromophore, and ð4s ϩ ð2s cycloaddition
of spiro[cyclohexa-2,4-diene-oxiran]-6-one are the key features of this approach. An efficient one-step
synthesis of the epoxy ketone 11 by ð4s ϩ ð2s cycloaddition of the in situ generated spiro[cyclohexa-2,4-
diene-oxiran]one is reported. Further transformation of 11 to a variety of endo-tricyclo[5.2.2.02,6]-
undecanes (20, 25, 28, 30 and 31) and their photochemical behaviour upon singlet (1S ) excitation is
described. Direct excitation of all the tricyclic chromophoric systems in benzene neatly furnished
the protoilludanoids 32–36.
A surge of interest in the sesquiterpenoids of protoilludane
family,1–2 is the result of the isolation of a large number of novel
secondary metabolites of types 1–6 from various strains of
[Eqn. (1)].5 Therefore, we designed a general strategy to syn-
thesize tricyclic skeletons of type 9 disposed with all the essen-
tial features of protoilludanes such as angular and geminal
methyl groups and functionalities in all the rings for further
manipulation. We thought that the intermediate 9 and its con-
geners could be readily obtained from the endo annulated
bicyclo[2.2.2]octenones having a β,γ-unsaturated carbonyl
chromophore such as 10 (Scheme 1). This would, in turn, we
R5
R3O
R4
OH
R2
O
O
H
R2O
Me
O
R1
1 R1 = CHO, R2 = OH
R1
O
2 R1 = CHO, R2 = R3 = R4 = R5 = H
3 R1= CHO, R2= R3 = R4 = H, R5 = OH
4 R1= CHO, R2 = Me, R3 = R4 = H, R5 = OH
5 R1 = CHO, R2 = R4 = H, R3 = Me, R5 = OH
6 R1 = CH2OH, R2 = R4 = H, R3 = Me, R5 = OH
O
Me
hν, 1
S
FG
FG
H
10
9
Basidiomycetes having a protoilludane skeleton, which exhibit
antitumour, antibiotic and antibacterial activity.1a,d Moreover,
some members of this family play an important role in the
biosynthesis3 of a host of biologically active sesquiterpenoids
such as lactaranes, illudalanes and marasmanes via the pro-
toilludyl cation. Further, the unique molecular architecture
composed of four-, six- and five-membered rings fused in an
angular cis:anti:cis fashion, together with the unusual func-
tionalities, the promising biological activities and the bio-
synthetic connections of these compounds have kindled interest
in their synthesis and chemistry.
O
OH
O
OH
12
11
Scheme 1
thought be readily available from the epoxy ketone 11 which
should itself be accessible from the appropriately substituted
phenol 12 after its oxidation and subsequent interception of the
resulting cyclohexa-2,4-dienone with cyclopentadiene.
We report herein a novel, efficient and stereospecific route to
functionalised protoilludanoids employing a photochemical
1,3-acyl shift upon singlet excitation of various tricyclo-
[5.2.2.02,6]undecenones as a key step. A general synthesis of a
variety of tricyclic chromophoric systems having β,γ-enone
chromophore by oxidation of a simple aromatic precursor such
as 4,6-dimethylsalicyl alcohol to a spiro[cyclohexa-2,4-diene-
oxiran]one, subsequent interception with cyclopentadiene and
manipulation of the resulting adduct is also reported.
No attempts have been made to synthesize recently isolated
protoilludanoids (e.g. 1–6 and related compounds) and, sur-
2a–e
prisingly, there are few routes
to earlier discovered
compounds.1f
In the context of our exploratory programme towards the
development of novel methodologies employing photochemical
reactions, we thought that a cyclobutane ring fused to a cis
hydrindane skeleton could be efficiently formed stereo-
selectively via a symmetry-allowed4 photochemical 1,3-sigma-
tropic acyl shift in an endo annulated tricyclic system such as 7
O
O
H
hν
H
(1)
Results and discussion
1S, 1,3-acyl shift
Synthesis of tricyclic chromophoric systems
Conceptually, the tricyclic systems of type 10 having a β,γ-
7
8
J. Chem. Soc., Perkin Trans. 1, 1998
305

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enone chromophore could be directly prepared by cyclo-
addition of 3,5-dimethylcyclohexa-2,4-dienone 16 and 4,4-
dimethylcyclopentene 17. However, while there are a few
basis of the general tendency of cyclohexa-2,4-dienones having
6-acetoxy functions during their cycloaddition, especially with
themselves,6 and comparison of the spectral features of 11 and
18 with similar adducts.
Towards the synthesis of the desired tricyclic chromophoric
systems it was necessary to remove the oxirane moiety present
at the bridge and introduce the geminal methyl groups in the
five-membered ring of the adduct 11; this was done as follows.
The keto epoxide 11 was reduced13 with zinc in MeOH–H2O
(7:1) to give the keto alcohol 19 as a major product (47%);
this was oxidised with Jones’ reagent and the resulting β-keto
acid was subsequently decarboxylated14 to give the tricyclic
compound 20 (Scheme 3). Oxidation of compound 20 with
OH
O
O
R1
R2
CHO
O
13
14
15 R1 = alkyl,
17
R2 = OAc
16 R1 = R2 = H
methods6,7 for the preparation of 6,6-disubstituted cyclohexa-
2,4-dienones, there are no methods for the cyclohexadienones
of type 16. Moreover, the dienone 16 (actually a keto tautomer
of the corresponding phenol) has been neither trapped, charac-
terised nor prepared. Therefore, we considered an alternate
indirect method for the synthesis of the desired chromophoric
system of type 10 from the keto-epoxide 11. The latter was
available from 4,6-dimethylsalicyl alcohol 12 by its oxidation to
the spiro[cyclohexa-2,4-diene-oxiran]one 13 and subsequent
interception with cyclopentadiene. In this connection, we have
recently developed a method for in situ generation of spiro-
[cyclohexa-2,4-diene-oxiran]one by two-phase periodate oxid-
ation of o-hydroxymethyl phenols.8
R
H
O
O
O
+
iv, ii
O
i
11
O
21b
21a
19 R = CH2OH (47%)
20 R = H (65%)
v
ii,iii
O
O
O
O
O
O
+
vi
X
O
Towards the preparation of the phenol 12, 4,6-dimethyl-
salicylaldehyde9 14 was reduced with sodium borohydride in
methanol–water (80:20). Although we observed that the reduc-
tion proceeded smoothly (TLC), attempts to isolate the corre-
sponding alcohol under a variety of conditions failed and led to
polymerisation. Therefore, we thought to oxidize the reaction
mixture containing 4,6-dimethylsalicyl alcohol 12 and intercept
the resulting spiro[cyclohexa-2,4-diene-oxiran]one 13 with
cyclopentadiene. Indeed, oxidation of the reaction mixture con-
taining 12 with sodium metaperiodate in the presence of freshly
cracked cyclopentadiene furnished the required adduct 11 in
excellent yield (75%) along with its stereoisomer 18 as a minor
product (~3%) in a single-pot reaction from the aldehyde 14
(Scheme 2). The adducts were obviously formed through gener-
O
23 X = –OH (98%)
vii
22a (51%)
22b (30%)
24 X =
=
O (90%)
Scheme 3 Reagents and conditions: i, Zn, NH4Cl, MeOH–H2O, RT; ii,
Jones’; iii, THF–H2O, heat; iv, SeO2, KH2PO4, dioxane–water, heat; v,
HOCH2CH2OH, PTSA, PhH, heat; vi, NaBH4, MeOH; vii, PCC,
CH2Cl2
selenium dioxide gave a regioisomeric mixture of allylic
alcohols which upon further oxidation with Jones’ reagent15
gave a mixture of the diene-diones 21a and 21b; these were
separated after ketalization of the carbonyl group at the ethano
bridge. Thus, the mixture of diene-diones 21a and 21b was
treated with ethylene glycol and toluene-p-sulfonic acid to give
the keto ketals 22a and 22b which were separated by a careful
chromatography (Scheme 3).
O
OH
OH
In order to introduce geminal dimethyl groups in the five-
membered ring, it was necessary to reduce the conjugated
carbon–carbon π bond in the five-membered ring. Therefore,
the ketal enone 22a was treated with sodium borohydride which
reduced both the double bond as well as carbonyl group (IR, 1H
NMR) and furnished the alcohol 23; subsequent oxidation of
this gave the keto ketal 24. Hydrolysis of the ketal 24 gave the
chromophoric system 25. The structure of all the compounds
are consistent with their spectral data.
Towards the introduction of the geminal methyl groups α to
the carbonyl group of cyclopentane ring, the keto ketal 24 was
first treated with methyl iodide in the presence of sodium
hydride in THF. This, unfortunately, furnished the undesired
trimethylated derivative 26. Such exhaustive alkylation was
avoided by selection of a bulky base. Thus, alkylation of the
keto ketal 24 with methyl iodide in the presence of potassium
tert-butoxide in dry tert-butyl alcohol smoothly furnished the
desired dimethylated keto ketal 27 whose structure was clearly
revealed from its spectral data.
The keto ketal 27 was reduced with sodium borohydride
in THF–H2O to give a stereoisomeric mixture of endo and
exo alcohols 29a,b which were separated by careful chrom-
atography. The stereochemical orientation of the hydroxy
groups was determined on the basis of the chemical shift and
coupling constants of the H᎐C᎐OH proton. Thus, H᎐C᎐OH in
the endo alcohol 29a resonated at δ 3.52 (dd, J 12 and 8) in its
1H NMR spectrum while H᎐C᎐OH in 29b appeared at δ 3.17 (d,
J 7), respectively. Hydrolysis of 29a gave the hydroxy ketone 30.
i
ii
O
14
13
12
O
O
9
O
O
8
1
10
11
2
+
7
3
6
4
5
18 (~3%)
11 (75%)
Scheme 2 Reagents and conditions: i, NaBH4, MeOH–H2O; ii, NaIO4,
MeCN
ation of 3,5-dimethylspiro[cyclohexa-2,4-diene-6,2Ј-oxiran]one
13 and its cycloaddition with cyclopentadiene wherein the
former species apparently behaved as a 4π and the latter as a 2π
partner. It is interesting to note the selectivity in the above
cycloaddition especially since there are various symmetry-
allowed pericyclic modes of addition between spiro[cyclohexa-
2,4-diene-oxiran]one 13 and cyclopentadiene.
The structures and stereochemistry of the adducts 11 and 18
were deduced from their highfield 1H NMR spectra, 13C NMR
spectra, and comparison with other data.10–12 The stereo-
chemical orientation of the oxirane moiety was deduced on the
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J. Chem. Soc., Perkin Trans. 1, 1998

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The alcohols 29a,b were also converted into their thio-
carbamates 29c,d whose reduction with tributyltin hydride
followed by hydrolysis furnished the chromophoric system 31
(Scheme 4).
potential of the photochemical 1,3-acyl shift in β,γ-enones has
not been realized until recently. 5
Although the photoreaction of β,γ-enones are characteristic
of excited states, a mixture of products may be obtained due to
unselective population of the excited states. Moreover, the
photoreactions of β,γ-enones are quite sensitive to the nature
of functional groups and substituent present on the chromo-
phoric systems.21 Considering the structural and functional
complexity of the above chromophoric systems many photo-
chemical reactions such as intramolecular cycloaddition,22
epimerization,23 photoreduction,24 decarbonylation25 and 1,3-
acyl shift can be expected.
In view of the above, we first explored the photoreaction of
compounds 20. Thus, a solution of 20 in benzene was irradiated
with a mercury vapour lamp (125 W, APP) in a quartz immer-
sion well; it gave a complex mixture of products. Therefore, a
benzene solution of 20 was irradiated in a Pyrex immersion well
(>300 nm) for ca. 1 h; this gave the 1,3-acyl shift product 32 in
reasonably good yield (31%) (Scheme 5) along with some
O
O
i
ii
O
24
O
O
O
iii
25
26
O
9
O
O
O
8
O
10
1
2
X
iv
i
O
7
11
3
4
6
5
28
27
29a X = endo OH(35%)
b X = exo OH(55%)
v
i
O
O
O
O
O
O
v i, i
OH
X
hν, quartz
hν, pyrex
H
Complex mixture
benzene
benzene
30
31
29c X = endo OCS2Me
d X = exo OCS2Me(80%)
32
20
Scheme 5
Scheme 4 Reagents and conditions: i, HCl–H2O; ii, NaH, THF, MeI,
V; iii, KOtBu, ButOH, MeI; iv, NaBH4, THF–H2O; v, NaH, THF, imi-
dazole, CS2, MeI; vi, TBTH, AIBN, Ph-Me, neat
unchanged starting material. The structure of compound 32
was deduced from its spectral data. It is interesting to note
the selectivity in the above photoreaction especially since
products of type 37 and/or 38 were not formed because of
Towards protoilludanes: photochemical reaction of the tricyclic
systems 20, 25, 28, 30 and 31 upon singlet (1S ) excitation
There has been a great deal of research on the photochemistry
of β,γ-enones,17 stimulated initially by spectroscopic studies17
and subsequently by observation of the then novel photo-
chemical equilibration of bicyclo[3.2.0]heptenones through a
process which was later termed a 1,3-sigmatropic acyl shift.18
Ever since, many types of photoreactions have been discovered
which are characteristic of alkenes and carbonyl chromophore.
However, it has been observed that rigid β,γ-enones undergo
two unusual molecular rearrangements upon electronic excit-
ation involving a 1,3-sigmatropic acyl shift and a oxa-di-π-
methane rearrangement.19,20 The direct irradiation (1S, π-π*) of
β,γ-enones causes a 1,3-acyl shift leading to the formation of
cyclobutanone derivatives while the triplet-sensitized irradi-
ation (3T, π-π*) leads to a 1,2-acyl shift or oxa-di-π-methane
rearrangement [Eqn. (2)], though a mixture of products may
O
O
37
38
intramolecular π2s ϩ π2s cycloaddition or oxa-di-π-methane
rearrangement.
Similar irradiation of compounds 30 and 31 under the
aforementioned conditions also gave the protoilludanoids 35
and 36, respectively. While the above photoreactions occurred
smoothly we were a little concerned about the photoreaction of
the diones 25 and 28 since these contain carbonyl groups in the
five-membered ring which are also reactive chromophores and
undergo α cleavage upon irradiation. It was a relief to find that
the dione 25 underwent a clean photoreaction upon direct
irradiation in benzene to furnish the desired 7-protoillu-
dendione 33. However, irradiation of the dione 28 gave a 1,3-
acyl shift product 34 contaminated with a minor product,
apparently formed due to α cleavage of the carbonyl group
present in the five-membered ring as revealed through its high-
O
O
O
hν, 1
S
hν, 3T
(2)
II
I
III
result because of indiscriminate population of the excited
states. We realized that a 1,3-acyl shift in an appropriately
designed tricyclic system having a β,γ-enone chromophore
would provide a general, efficient and stereospecific route to
protoilludanes, and hence this reaction was incorporated in the
strategy.
It is worth mentioning, however, that most of the investig-
ations on the photoreactions of β,γ-enones were directed to-
wards triplet-sensitized oxa-di-π-methane rearrangements;19,20
further, that most of the studies on excited singlet (1S ) state
photoreactions of β,γ-enones were carried out on simple
bicyclic systems in conjunction with oxa-di-π-methane
rearrangements in order to resolve the singlet–triplet dicho-
tomy.18 While the triplet excited state photochemistry of β,γ-
enones has been exploited in organic synthesis, the synthetic
1
field H NMR spectrum; this showed a signal at δ 9.46 for
an aldehydic proton. However, since the minor product could
not be separated on column chromatography, the mixture
of photoproducts was worked up with sodium bisulphite to
remove the minor aldehydic product and give the desired com-
pound 34 in pure form. The structure of the compound 34 is
consistent with its spectral data.
In summary we have described a novel and stereoselective
route to protoilludanes employing a photochemical sigmatropic
1,3-acyl shift in appropriately constructed endo-tricyclo-
[5.2.2.02,6]undecanes having
a
β,γ-unsaturated carbonyl
chromophore. There are several noteworthy features of the
present strategy. For example, it generates the angular cis:anti:
J. Chem. Soc., Perkin Trans. 1, 1998
307

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The combined extracts were washed with water (2 × 75 cm3)
O
O
and brine (1 × 75 cm3), dried and evaporated under reduced
pressure. The crude product was charged onto a column of
silica gel and eluted with LP to remove unchanged dicyclo-
pentadiene. Further elution with LP–ethyl acetate (98:2) gave
the adduct 11 (2.7 g, 75%) as a colourless solid which was
recrystallized from LP (bp 40–60 ЊC), mp 54–55 ЊC; νmax(film)/
cmϪ1 1735; λmax(MeOH)/nm 223.2 and 305.6; δH(300 MHz,
CDCl3) 5.72 (1H, m of d, J 6, olefinic H), 5.66 (1H, br m, γ-H
of β,γ-enone moiety), 5.42 (1H, m of d, J 6, olefinic H), 3.34
(1H, complex m of d, J 9, methine H), 3.12 (1H, m, J 2, methine
O
R1
R2
H
O
R1
R2
25 R1 = R2 = H
26 R1 = R2 = Me
33 R1 = R2 = H
34 R1 = R2 = Me
O
O
X
H
X
H), 3.04 (1H, part of an AB system, JAB 6, OCH2), 2.92 (1 H,
part of an AB system, JAB 6, OCH2), 2.71 (1H, dd of d, J 9, 10
and 5, methine H), 2.47 (1H, m of dd, J 17 and 10, methylene
H), 2.14 (1H, m of d, J 17, methylene H), 1.75 (3H, d, J 1.5,
CH3) and 1.04 (3H, s, CH3); δC(25 MHz, CDCl3) 205.6 (CO),
136.7, 133.1, 129.8, 128.9 (olefinic carbons), 59.9, 57.0, 50.8,
49.5, 41.9, 41.1, 36.5, 21.4, 14.9 (other methine, methylene
methyl and quaternary carbons); m/z 216 (Mϩ, 4%), 151 (71,
Mϩ Ϫ C5H5), 123 (100, Mϩ Ϫ C5H5 Ϫ CO), 91 (28) and 66 (41)
(Found: C, 77.54; H, 7.50. C14H16O2 requires C, 77.77; H,
7.40%).
Continued elution with the same solvent gave the minor
adduct 18 (0.1 g, ~3%) as a solid which was recrystallized from
LP (bp 40–60 ЊC), mp 76–77 ЊC; νmax(KBr)/cmϪ1 1735; δH(300
MHz, CDCl3) 5.72 (1H, m of d, J 6, olefinic H), 5.69 (1H, br m
merged with the signal at 5.72, olefinic proton of bicyclo-
[2.2.2]octene framework), 5.48 (1H, m of d, J 6, olefinic H),
3.30 (1H, complex m, methine H), 3.13 (1H, dd, J 3 and 2.5,
methine proton at the bridgehead), 3.0 (1H, part of an AB
system, JAB 6, OCH2), 2.89 (1 H, part of an AB system, JAB 6,
OCH2), 2.56 (1H, dd of d, J 10 and 6, methine H), 2.46 (1H, m
of dd, J 18 and 10, allylic methylene H), 2.20 (1H, m of d, J 18,
methylene H), 1.77 (3H, d, J 1.5, CH3) and 1.04 (3H, s, CH3);
m/z 216 (Mϩ, 10%), 151 (67), 123 (100), 91 (30) and 66 (38)
(Found: C, 77.71; H, 7.45. C14H16O2 requires C, 77.77; H,
7.40%).
30 X = OH
31 X = H
35 X = OH
36 X = H
cis tricyclic protoilludane framework in a single stereoselective
sequence from precursors in which most of the structural and
stereochemical features of protoilludanes are present in latent
form. Moreover, the penultimate precursors are easily derived
from the keto epoxide 11 which is prepared from the aromatic
compound 12 and cyclopentadiene in a single step. The present
strategy also illustrates the principle of generation of maximum
complexity26 rapidly and efficiently at the very beginning of
the synthetic route since 13 (out of 15) carbon atoms of
protoilludanes are assembled with appropriate connectivity
in just a single step. We have also presented a simple method-
ology for the synthesis of the desired tricyclic chromophoric
systems from aromatic precursors by cycloaddition of an in situ
generated spiro[cyclohexa-2,4-diene-oxiran]one and cyclopen-
tadiene. The route described in the present paper provides
opportunities for further investigation in the area of proto-
illudanes.
Experimental
Melting points were determined on a Veego apparatus of Buchi
type and are uncorrected. TLC analyses were carried out on
glass plates coated with TLC grade silica gel and spots were
visualized with iodine vapour. Silica gel (100–200 mesh) was
used for column chromatography. Laboratory solvents were
purified and pre-dried before use according to standard pro-
cedures. Light petroleum (LP; bp 60–80 ЊC) was used for
column chromatography. IR spectra were recorded on a Nicolet
Impact 400 FT-IR instrument. UV spectra were recorded on a
Shimadzu 260 instrument. NMR spectra were recorded on
either Varian VXR 300, or Bruker AMX 500 instruments using
CDCl3 as the solvent containing SiMe4 as an internal standard
with chemical shifts (δ) expressed as ppm downfield with
respect to SiMe4; J values are given in Hz. Elemental analysis
were performed on a CEST 1106 instrument. Mass spectra were
recorded on a HP GCD 1800A mass spectrometer. All organic
extracts were dried over anhydrous sodium sulfate.
1,11-Dimethyl-endo-tricyclo[5.2.2.02,6]undeca-4,10-dien-8-one
20
To a suspension of activated zinc (7.15 g, excess) in MeOH–
H2O (7:1; 100 cm3) was added a solution of compound 11 (4.7
g, 21.76 mmol) in methanol (25 cm3), followed by ammonium
chloride (2.7 g, excess). The reaction mixture was stirred at
room temperature (~30 ЊC) for ca. 6 h after which it was
filtered through a Celite pad and then concentrated in vacuo.
After dilution of the residue with water (50 cm3) it was
extracted with ethyl acetate (3 × 75 cm3). The combined
extracts were washed with water (2 × 30 cm3) and brine
(1 × 30 cm3), dried and evaporated under reduced pressure to
give a crude product. Chromatography of this over silica gel
with LP–ethyl acetate (90:10) as eluent furnished compound
19 (2.2 g, 47%) [νmax(film)/cmϪ1 3458 and 1711; m/z 218 (Mϩ,
8%), 153 (28), 131 (64) and 122 (100)]. This compound was
oxidized as follows.
To a stirred solution of the keto alcohol 19 (3 g, 13.76 mmol)
in acetone (80 cm3) at ~10 ЊC was added dropwise freshly pre-
pared Jones’ reagent. After the reaction was complete (TLC, ~2
h) the mixture was evaporated under reduced pressure and the
residue was diluted with water (100 cm3) and extracted with
ethyl acetate (3 × 50 cm3). The combined extracts were washed
with water (2 × 30 cm3) and brine (1 × 25 cm3), dried and evap-
orated to give the β-keto acid (3.1 g, 97%; νmax/cmϪ1 3500 and
1740) which was then directly subjected to decarboxylation as
follows. A mixture of the β-keto acid (3.1 g, 13.36 mmol) in
tetrahydrofuran–water (60:40; 50 cm3) was refluxed for ca. 12 h
after which the tetrahydrofuran was removed under reduced
pressure and the residue was diluted with water (50 cm3) and
extracted with diethyl ether (3 × 50 cm3). The combined
extracts were washed with saturated aqueous sodium hydrogen
1Ј,11Љ-Dimethylspiro[oxirane-2,9Ј-endo-tricyclo[5.2.2.02,6]-
undeca-4Ј,10Ј-dien]-8Ј-one 11
Methanol–water (80:20; 60 cm3) was added to the aldehyde 14
(2.5 g, 16.67 mmol) in a round bottom flask after which the
mixture was stirred while sodium borohydride (0.63 g, 16.57
mmol) was added to it all at once. The mixture was then further
stirred for 0.5 h at ambient temperature (~30 ЊC). After the
reduction was over (~1 h, TLC), acetonitrile (25 cm3), water
(100 cm3) and freshly cracked cyclopentadiene (10 cm3) were
added to the reaction mixture followed by finely powdered
sodium metaperiodate (15 g, 70 mmol), added over a period
of 0.5 h. After being stirred for 1 h the reaction mixture was
treated with additional cyclopentadiene (5 cm3) and then stirred
for 8 h at ambient temperature (~30 ЊC); it was then poured into
water (250 cm3) and extracted with diethyl ether (3 × 75 cm3).
308
J. Chem. Soc., Perkin Trans. 1, 1998

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carbonate (2 × 25 cm3), water (1 × 25 cm3) and brine (1 × 25
cm3), dried and evaporated. Chromatography of the residue
(LP–ethyl acetate, 95:5) gave the parent compound 20 which was
recrystallized from LP (bp 40–60 ЊC); it was obtained as a low
melting solid (1.62 g, 65%), mp 37–38 ЊC; νmax(film)/cmϪ1 1730;
λmax(MeOH)/nm 212 (s) and 294; δH(300 MHz, CDCl3) 5.67–
5.60 (2H, m merged with a br m, olefinic H), 5.42 (1H, m of d,
J 6, olefinic H), 3.24 (1H, m of d, J 7, methine H), 2.92 (1H, dd,
J 2.5 and 2.5, bridgehead H), 2.44–2.32 (2H, overlapped m,
methine and allylic methylene H), 2.06 (1H, m of d, J 16, allylic
methylene H), 1.94 (2H, AB system, JAB 18, methylene protons
α to ketone), 1.60 (3H, d, J 1.5, olefinic methyl) and 1.22 (3H, s,
CH3); δC(25 MHz, CDCl3) 212.0 (CO), 136.1 (s), 132.3 (d),
130.9 (d) and 129.5 (d) (olefinic carbons), 58.1 (d), 50.5 (d), 47.4
(d), 45.8 (t), 39.9 (s), 36.4 (t), 22.0 (q) and 21.1 (q); m/z 188 (Mϩ,
10%) and 123 (100, Mϩ Ϫ C5H5).
CH3], 118 (26) and 87 (64) (Found: C, 73.57; H, 7.66. C15H18O3
requires C, 73.17; H, 7.32%).
Continued elution with the same solvent furnished the minor
isomeric ketal 22b as a viscous liquid (1.02 g, 30%); νmax(film)/
cmϪ1 1703; λmax(MeOH)/nm 224.4; δH(300 MHz, CDCl3) 7.54
(1H, dd, J 6 and 1, β-H of the enone moiety), 6.20 (1H, d, J 6,
α-H of the enone group), 5.26 (1H, br m, olefinic proton), 3.96
[4H, m, (CH2O)2], 2.8 (3H, m, methine H), 1.76 (1H, part of an
AB system, JAB 15, methylene H), 1.7 (3H, d, J 1.5, olefinic
CH3), 1.65 (1H, part of an AB system, JAB 15, methylene H)
and 1.24 (3H, s, CH3); m/z 246 (Mϩ, 8%), 160 [25, Mϩ Ϫ
(CH O) ᎐CH ], 145 [100, Mϩ Ϫ {(CH O) ᎐CH } Ϫ CH ], 118
᎐
᎐
2
2
2
2
2
2
3
(27) and 87 (67).
1Ј,11Љ-Dimethyl-3Ј-hydroxyspiro[1,3-dioxolane-2,8Ј-endo-
tricyclo[5.2.2.02,6]undec-10Ј-en]-3Ј-one 24
Sodium borohydride (0.843 g, 22.18 mmol) was added as a
single portion to a solution of the ketal enone 22a (2.5 g, 10.16
mmol) in methanol (100 cm3) at room temperature (~30 ЊC).
After being stirred for 1 h the reaction mixture was concen-
trated in vacuo to ~20 cm3, diluted with water (100 cm3) and
extracted with dichloromethane (3 × 100 cm3). The combined
extracts were washed with water (2 × 75 cm3), dried and con-
centrated by removal of solvent. Column chromatography of
the residue (LP–ethyl acetate, 90:10) furnished the alcohol 23
(2.5 g, 98%); νmax(film)/cmϪ1 3535; δH(300 MHz, CDCl3) 5.83
(1H, br m, olefinic H), 4.20 (1H, complex m, HCOH), 3.91 [4H,
(CH2O)2], 2.62 (1H, complex m, methine H), 2.43 (1H, super-
imposed dd, J 2.5 and 2.5, methine H at the bridgehead), 1.99
(1H, dd, J 12 and 7, methine H), 1.88 (3H, d, J 1.5, CH3), 1.80–
1.60 (2H, merged multiplets, methylene H), 1.53 (2H, AB
system, JAB 15, methylene H), 1.44–1.38 (3H, complex m,
methylene H ϩ OH), 1.26 (3H, s, CH3) and 1.06–0.92 (1H,
complex m, methylene H); m/z 250 (Mϩ, 2%), 164 (48, Mϩ Ϫ
1,11-Dimethylspiro[1,3-dioxolane-2,8Ј-endo-tricyclo[5.2.2.02,6]-
undeca-4Ј,10Ј-dien]-3Ј-one 22a and 1,11-dimethylspiro-
[1,3-dioxolane-2,8Ј-endo-tricyclo[5.2.2.02,6]undeca-3Ј,10Ј-dien]-
5Ј-one 22b
To a stirred solution of selenium dioxide (10.32 g, 93 mmol) in
dioxane–water (75:25; 80 cm3) was added potassium dihydro-
gen orthophosphate (7.2 g, 53 mmol) followed by a solution of
compound 20 (5.0 g, 26.6 mmol) in dioxane (10 cm3), added
dropwise. The reaction mixture was heated at 100 ЊC for 10 h
after which it was filtered through a Celite pad; the pad was then
washed with diethyl ether (2 × 20 cm3). The combined filtrate
and washings were concentrated under reduced pressure and
then diluted with water (50 cm3) and extracted with ethyl acet-
ate (3 × 75 cm3). The combined extracts were washed with
water (2 × 50 cm3) and brine (1 × 50 cm3), dried and evaporated
in vacuo. The residue was chromatographed over silica gel with
LP–ethyl acetate (75:25) as eluent to yield a mixture of hydroxy
1
ketones (3 g, 55%) (IR and H NMR, 60 MHz) which was
(CH O) ᎐CH ), 120 (100), 107 (31) and 87 (17). The alcohol
᎐
2 2 2
subjected to further oxidation with Jones’ reagent as follows.
To a solution of the above mixture (3 g, 14.7 mmol) in acet-
one (100 cm3), was added freshly prepared Jones’ reagent drop-
wise at ca. 0–5 ЊC. After the reaction was over (TLC) the solvent
was removed in vacuo and the residue was diluted with water
and extracted with ethyl acetate (3 × 75 cm3). The combined
extracts were washed with water (2 × 75 cm3), aqueous sodium
hydrogen carbonate (1 × 75 cm3) and brine (1 × 50 cm3), dried
and evaporated. Column chromatography (LP–ethyl acetate,
75:25) of the residue over silica gel furnished a mixture of the
dienediones 21a and 21b (2.8 g, 94.26%) which was subjected to
ketalization.
23 was then oxidized as described below.
A suspension of PCC (3.54 g, 16.44 mmol) in dichloro-
methane (50 cm3) in a 250-cm3 flask equipped with addition
funnel was treated with a solution of the alcohol 23 in
dichloromethane (25 cm3), added dropwise with stirring over a
period of 30 min. After being stirred for 1 h (TLC) the reaction
mixture was diluted with ether (75 cm3), stirred for additional
30 min and then filtered through a short column of silica gel.
After removal of solvent, the brown residue was dissolved in
ether (150 cm3) and washed with 5% aqueous sodium hydroxide
(2 × 25 cm3), cold 5% aqueous hydrochloric acid (25 cm3), sat-
urated aqueous sodium hydrogen carbonate (1 × 25 cm3) and
brine (1 × 25 cm3) and then dried and evaporated in vacuo to
yield a yellow oil. This was chromatographed on silica gel to
furnish the ketone 24 as a colourless oil (2.23 g, 90%);
νmax(film)/cmϪ1 1730; λmax(MeOH)/nm 211s and 300w; δH(500
MHz, CDCl3) 5.52 (1H, br m, olefinic H), 3.9 [4H, m,
(CH2O)2], 3.0 (1H, complex m, methine H), 2.4 (1H, br m,
methine H), 2.08 (1H, d with str., J 8, methine H), 2.05–1.90
(3H, overlapped m), 1.85 (3H, d, J 1.5, CH3), 1.55 (1H, part of
an AB system, JAB 14, methylene H), 1.50 (1H, m), 1.42 (1H,
part of an AB system, JAB 14, methylene H) and 1.30 (3H, s,
CH3); δC(125 MHz, CDCl3) 220.9 (CO), 139.9, 129.9, 113.4,
64.3, 64.2, 55.5, 50.5, 48.6, 39.4, 39.2, 35.6, 24.9, 23.2 and 21.9;
A mixture of ethylene glycol (2 cm3, excess) and toluene-p-
sulfonic acid (10 mg) in dry benzene (50 cm3) was refluxed in a
Dean-Stark apparatus, in order to remove traces of water after
which the mixture of dienediones 21a and 21b (2.8 g, 13.9
mmol) was added to it; the reaction mixture was then refluxed
until completion of the reaction (TLC, ~4 h). The reaction mix-
ture was then cooled and washed with saturated aqueous
sodium hydrogen carbonate (2 × 25 cm3) and brine (1 × 25
cm3), dried and evaporated under reduced pressure to furnish a
mixture of compounds 22a and 22b (3.17 g). The crude product
was charged onto a column of silica gel and eluted with LP–
ethyl acetate (80:20) to give the ketal 22a (1.75 g, 51%), mp
92 ЊC; νmax(KBr)/cmϪ1 1699.9; λmax(MeOH)/nm 223.8; δH(300
MHz, CDCl3) 7.38 (1H, dd, J 5.8 and 3, β-H of the α,β-enone
moiety), 6.1 (1H, dd, J 5.8 and 1.8, α-H of α,β-enone moiety),
5.44 (1H, br s, olefinic H), 3.93 [4H, br s, (CH2O)2], 3.47 (1H, m,
methine H), 2.52 (1H, m, methine H), 2.1 (1H, d, J 5.7, methine
H, α to carbonyl), 1.67 (3H, s, CH3), 1.65 (1H, part of an AB
system, JAB 15, methylene H), 1.53 (1H, part of an AB system,
JAB 15, methylene H) and 1.4 (3H, s, CH3); δC(75 MHz, CDCl3)
210.3, 163.7, 136.8, 128.1, 113.2, 64.4, 64.3, 52.5, 48.4, 48.1,
43.3, 39.1, 29.7, 21.8 and 21.5; m/z 246 (Mϩ, 3%), 160 [33,
Mϩ Ϫ (CH O) ᎐CH ], 145 [100, Mϩ Ϫ {(CH O) ᎐CH } Ϫ
m/z 248 (Mϩ, 4%), 162 [100, Mϩ Ϫ (CH O) ᎐CH ], 134 (43),
106 (48), 91 (23), 87 (59) and 56 (22).
᎐
2
2
2
1,11-Dimethyl-endo-tricyclo[5.2.2.02,6]undeca-10-ene-3,8-dione
25
A solution of compound 24 (0.12 g, 0.48 mmol) in acetone–
water (90:10) (20 cm3) was treated with a few drops of con-
centrated hydrochloric acid and then stirred for 4 h at room
temperature (~30 ЊC) after which it was evaporated in vacuo.
The residue was diluted with ethyl acetate (1 × 50 cm3). The
organic layer was separated and washed with saturated aqueous
᎐
᎐
2
2
2
2
2
2
J. Chem. Soc., Perkin Trans. 1, 1998
309

View Article Online
sodium hydrogen carbonate (1 × 20 cm3), water (1 × 20 cm3)
and brine (1 × 25 cm3) and then dried and evaporated in vacuo.
Column chromatography (LP–ethyl acetate, 95:5) of the resi-
due furnished compound 25 (0.095 g, 96%); νmax(film)/cmϪ1
1730; λmax(MeOH)/nm 293.4 and 208.6; δH(300 MHz, CDCl3)
5.74 (1H, m, olefinic H), 3.08 (1H, dd, J 1.5 and 2.6), 2.95 (1H,
m), 2.31 (1H, d, J 9.3), 2.22–2.02 (3H, complex m), 1.96 (1H,
part of AB system, JAB 18.3, methylene H), 1.89 (3H, d, J 1.65,
CH3), 1.82 (1H, part of AB system, JAB 18.3, methylene
H), 1.72–1.64 (1H, m) and 1.46 (3H, s, CH3); m/z 204 (Mϩ, 6%),
162 (100, Mϩ Ϫ COCH2), 134 [34, Mϩ Ϫ {(COCH2) ϩ CO}],
119 [37, Mϩ Ϫ {(COCH2) ϩ CO ϩ CH3}], 106 [65, Mϩ Ϫ
{(COCH2) ϩ CO ϩ C2H6}], 91 (35) and 77 (14).
1,4,4,11-Tetramethyl-endo-tricyclo[5.2.2.02,6]undec-10-ene-3,8-
dione 28
Hydrolysis of compound 27 (0.1 g, 0.36 mmol) as described
above and chromatography of the crude product furnished
compound 28 (0.08 g, 95%); νmax(film)/cm Ϫ1 1730; λmax(MeOH)/
nm 207.8; δH(300 MHz, CDCl3) 5.81 (1H, m, olefinic H), 3.0–
2.9 (2H, m), (1H, d, J 10.4), 1.96 (1H, d, J 13.2), 1.93 (1H, part
of AB system, JAB 18.5, methylene H), 1.82 (1H, part of AB
system, JAB 18.5, methylene H), 1.79 (3H, d, J 1.65, CH3), 1.55
(3H, s, CH3), 1.21 (1H, m), 1.02 (3H, s, CH3) and 0.95 (3H, s,
CH3); m/z 232 (Mϩ, 4%), 190 [66, Mϩ Ϫ (COCH2)], 162 [20,
Mϩ Ϫ {(COCH2) ϩ CO}], 106 [100, Mϩ Ϫ {(COCH2) ϩ CO ϩ
C4H8}], 119 (45) and 91 (28).
1Ј,2Ј,4Ј,4Ј,11Ј-Pentamethylspiro[1,3-dioxolane-2,8Ј-endo-
tricyclo[5.2.2.02,6]undec-10Ј-en]-3Ј-one 26
1Ј,4Ј,4Ј,11Ј-Tetramethyl-3Ј-endo-hydroxy-spiro[1,3-dioxolane-
2,8Ј-endo-tricyclo-[5.2.2.02,6]undec-10-ene] 29a and 1Ј,4Ј,4Ј,11Ј-
tetramethyl-3Ј-exo-hydroxy-spiro[1,3-dioxolane-2,8Ј-endo-
tricyclo[5.2.2.02,6]undec-10Ј-ene] 29b
Sodium hydride (60% w/w suspension, 0.155 g; 3.2 mmol) in a
dry two-necked flask was washed with dry hexane after which
tetrahydrofuran (15 cm3) was added to it. A solution of the
ketone 24 (0.2 g, 0.8 mmol) in tetrahydrofuran (5 cm3) was
added to the reaction mixture followed by methyl iodide (2 cm3,
excess). The mixture was refluxed for ca. 0.5 h after which it was
quenched with cold water and the tetrahydrofuran then
removed in vacuo. The residue was extracted with ethyl acetate
(3 × 15 cm3), and the combined extracts were washed with
water (2 × 10 cm3) and brine (15 cm3), dried and evaporated.
Chromatography of the residue over silica gel (LP–ethyl acet-
ate, 95:5) furnished the alkylated product 26 as a colourless
liquid (0.14 g, 60%); νmax(film)/cmϪ1 1735; δH(500 MHz, CDCl3)
5.61 (1H, s, olefinic H), 3.92 [4H, m, (CH2O)2], 2.47 (1H, d of
dd, J 10.5, 5 and 2.5, ring junction H), 2.29 (1H, br s), 2.05 (1H,
dd, J 14 and 10, methylene H), 1.9 (1H, d, J 14, methylene H),
1.82 (3H, d, J 1.25, CH3), 1.31 (1H, d, J 14, methylene H), 1.25
(1H, d, J 14, methylene H), 1.28 (3H, s, CH3), 1.16 (3H, s, CH3),
1.04 (3H, s, CH3) and 0.89 (3H, s, CH3); m/z 290 (Mϩ, 3%), 204
(47), 178 (22) and 120 (100).
Sodium borohydride (0.5 g, 13.16 mmol) was added to a solu-
tion of the ketone 27 (1.2 g, 4.35 mmol) in tetrahydrofuran (50
cm3) and water (1 cm3) and the reaction mixture was stirred for
12 h at room temperature (~30 ЊC, TLC). After the mixture
had been concentrated by removal of the solvent under
reduced pressure, it was diluted with water (30 cm3) and
extracted with dichloromethane (3 × 50 cm3). The combined
extracts were washed with water (2 × 30 cm3) and brine (1 × 25
cm3) dried and evaporated in vacuo. Column chromatography
(LP–ethyl acetate, 90:10) of the crude product gave the alco-
hol 29a (0.43 g, 35%); νmax(film)/cmϪ1 3543; δH(300 MHz,
CDCl3) 5.82 (1H, br m, olefinic H), 3.93 [4H, m, (CH2O)2],
3.52 (1H, dd, J 12 and 8, HCOH), 2.78 (1H, complex m,
methine H), 2.35 (1H, br m, methine H), 2.28 (1H, dd, J 12
and 7, methine H), 1.87 (3H, d, J 1.5, CH3), 1.7 (1H, br s,
OH), 1.59 (1H, part of an AB system, JAB 14, methylene H),
1.49 (1H, part of an AB system, JAB 14, methylene H), 1.40
(1H, m, methylene H), 1.26 (3H, s, CH3), 0.98 (3H, s, CH3) and
0.90 (4H, s merged with m, CH3 ϩ 1H); m/z 278 (Mϩ, 1%), 192
[90, Mϩ Ϫ (CH2O)2᎐᎐CH2], 177 (21), 120 (100), 105 (22) and 87
(26).
1Ј,4Ј,4Ј,11Ј-Tetramethylspiro[1,3-dioxolane-2,8Ј-endo-tricyclo-
[5.2.2.02,6]undec-10Ј-en]-3Ј-one 27
tert-Butyl alcohol was added to potassium tert-butoxide (3.6 g,
32.2 mmol) in a flask (100 cm3) equipped with a reflux con-
denser, nitrogen inlet and addition funnel and after which the
flask was cooled to 10 ЊC. A solution of the ketone 24 (2.66
g, 10.72 mmol) in tert-butyl alcohol (20 cm3) was then added
rapidly with stirring to the flask followed by the immediate add-
ition of methyl iodide (5 cm3, 80.3 mmol). Once the initial
exothermic reaction had subsided, the reaction mixture was
refluxed for 5 h and then cooled and poured into cold water (50
cm3). After removal of the tert-butyl alcohol under reduced
pressure, the residue was extracted with ether (3 × 50 cm3). The
combined extracts were washed with water (2 × 30 cm3) and
brine (1 × 25 cm3), dried and evaporated in vacuo. Column
chromatography (LP–ethyl acetate, 90:10) of the crude product
furnished the alkylated compound 27 (1.33 g, 45%); νmax(film)/
cmϪ1 1734; λmax(MeOH)/nm 208.6 and 293.4; δH(300 MHz,
CDCl3) 5.62 (1H, br m, olefinic H), 3.93 [4H, m, (CH2O)2], 3.05
(1H, d of dd, J 10.4, 9 and 2.7, methine proton at C-2Ј), 2.40
(1H, br m, methine proton at C-1Ј), 2.36 (1H, d, J 10.4, methine
proton at C-6Ј), 1.86 (1H, dd, J 13 and 9, exo methylene proton
at C-3Ј), 1.80 (3H, d, J 1.5, CH3), 1.58 (1H, part of an AB
system, JAB 13.5, methylene proton at C-8Ј), 1.44 (1H, part of
an AB system, JAB 13.5, methylene proton at C-8Ј), 1.43 (3H, s,
CH3), 1.10 (1H, m of d, J 13, endo methylene proton at C-3Ј),
0.98 (3H, s, CH3) and 0.90 (3H, s, CH3); δC(125 MHz, CDCl3)
Further elution with LP–ethyl acetate (80:20) gave the alco-
hol 29b (0.67 g, 55%); νmax(film)/cmϪ1 3482; δH(300 MHz,
CDCl3) 5.60 (1H, br m, olefinic H), 3.91 [4H, m, (CH2O)2], 3.17
(1H, d, J 7, HCOH), 2.68 (1H, complex m, methine H), 2.20
(1H, br m, bridgehead H), 1.82 (3H, d, J 1.5, CH3), 1.72 (1H,
dd, J 12 and 9, methine H), 1.55–1.44 (3H, m), 1.24 (1H, br s),
1.18 (3H, s, CH3), 0.92 (3H, s, CH3), 0.88 (3H, s, CH3) and 0.80
(1H, superimposed dd, J 12 and 12, methylene H); m/z 278 (Mϩ,
1%), 192 [43, Mϩ Ϫ (CH O) ᎐CH ], 177 (8), 120 (100), 105 (16)
᎐
2
2
2
and 87 (12).
1,4,4,11-Tetramethyl-3-endo-hydroxy-endo-tricyclo[5.2.2.02,6]-
undec-10-en-8-one 30
Hydrolysis of compound 29a (0.1 g, 0.36 mmol) as described
above furnished the title compound 30 (0.080 g, 95%), mp
119 ЊC; νmax(KBr)/cmϪ1 3500 and 1722; λmax(MeOH)/nm 206,
296; δH(500 MHz, CDCl3) 5.99 (1H, br m, olefinic H), 3.60 (1H,
dd, J 10 and 6, HCOH), 2.91 (1H, superimposed dd, J 2.5 and
2.5, bridgehead H), 2.70 (1H, dd of dd, J 10.5, 6 and 3, ring
junction H), 2.44 (1H, dd, J 10 and 6, ring junction H), 1.88
(2H, AB system, JAB 18, methylene H), 1.84 (3H, d, J 2, CH3),
1.50 (1H, dd with str., J 13 and 8, methylene H), 1.36 (4H, s
overlapped with a signal, CH3 ϩ 1H), 1.60 (1H, d, J 3,
methylene H), 1.0 (3 H, br s, CH3) and 0.92 (3H, s, CH3);
δC(125 MHz, CDCl3) 212.6 (CO), 136.2, 134.8, 81.3, 58.1,
54.8, 48.0, 45.7, 42.6, 40.1, 39.3, 25.6, 22.6, 22.3 and 22.2 (all
222.3 (CO), 139.7, 130.4 (olefinic carbons), 113.5 [᎐C(OCH ) ],
᎐
2
2
64.3, 64.2, 53.1, 49.9, 49.2, 46.7, 39.9, 38.7, 32.6, 26.3, 23.5, 22.4
and 22.0 (all the carbons); m/z 276 (Mϩ, 2%), 190 [54,
Mϩ Ϫ (CH O) ᎐CH ], 162 [24, Mϩ Ϫ (CH O) ᎐CH ϩ CO],
the 15 carbons); m/z 234 (Mϩ, 5%), 192 [26, Mϩ Ϫ (CH ᎐C᎐O)],
2᎐ ᎐
120 [100, Mϩ Ϫ (CH ᎐C᎐O) Ϫ (C H )], 107 (25) and 91 (15)
᎐
᎐
᎐
2᎐ ᎐
2
2
2
2
2
2
5
12
106 [100, Mϩ Ϫ {(CH O) ᎐CH ϩ CO ϩ (Me) C᎐CH }], 119
(Found: C, 76.64; H, 9.35. C15H22O2 requires C, 76.92; H,
9.40%).
᎐
2
2
2
2
2
(49) and 87 (55).
310
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
1,4,4,11-Tetramethyl-endo-tricyclo-[5.2.2.02,6]undec-10-en-8-one
31
nm 207.2; δH(500 MHz, CDCl3) 5.85 (1H, m), 5.66 (1H, m),
5.25 (1H, br m), 3.16 (1H, br m, methine H), 3.10 (1H, dd, J 16
and 2, COCH2), 3.0 (1H, br m, methine H at the cyclobutanone
ring junction), 2.55 (1H, dd, J 16 and 4,5, COCH2), 2.45 (1H,
overlapped dd of d, J 9 and 10, methine H adjacent to the
allylic methylene), 2.28 (1H, m of dd, J 16 and 9, allylic
methylene), 1.95 (1H, m of d, J 16, allylic methylene), 1.68 (3H,
d, J 1.5, CH3) and 1.26 (3H, s, CH3); δC(125 MHz, CDCl3)
205.8, 133.4, 130.3, 125.4, 122.2, 66.7, 43.4, 42.7, 34.1, 30.4,
26.4, 22.2 and 21.3 (all the carbons); m/z 188 (Mϩ, 6%), 142 [10,
A mixture of the alcohol 29b (1.1 g, 3.96 mmol), sodium
hydride (50% suspension in oil; 0.57 g, 12 mmol) and imidazole
(0.005 g) in dry tetrahydrofuran (20 cm3) under nitrogen in a
three-necked flask (50 cm3) was refluxed and stirred for 3 h.
After this, carbon disulfide (2 cm3) in tetrahydrofuran (5 cm3)
was added to the reaction mixture and refluxing continued for a
further 45 min; methyl iodide (2 cm3, excess) was then added to
the mixture and refluxing continued for a further 0.5 h. After
the reaction mixture had been brought to room temperature
(~30 ЊC) it was treated with acetic acid (0.5 cm3) to quench the
reaction and then diluted with water (30 cm3) and extracted
with diethyl ether (3 × 50 cm3). The combined extracts were
washed with aqueous sodium hydrogen carbonate (2 × 10 cm3),
water (2 × 15 cm3) and brine (1 × 20 cm3), dried and evaporated
in vacuo. The crude product was charged onto a silica gel
column and eluted with LP to remove non-polar impurities;
further elution with LP–ethyl acetate (98:2) furnished the
S-methyl dithiocarbamate derivative 29c (1.16 g, 80%);
νmax(film)/cmϪ1 1461, 1220 and 1179; δH(500 MHz, CDCl3) 5.66
(1H, s, olefinic H), 5.55 (1H, d, J 8, HCCS2Me), 3.9 [4H, m,
(CH2O)2], 2.82 (1H, dd, J 10 and 8), 2.55 (3H, s, CS2CH3), 2.22
(2H, m), 1.86 (3H, s, CH3), 1.57–1.49 (4H, m), 1.03 (3H, s,
CH3), 0.97 (3H, s, CH3) and 0.95 (3H, s, CH3). The above thio-
carbamate was reduced with tributyltin hydride as described
below.
Mϩ Ϫ (CH ᎐C᎐O)], 131 (61), 123 (100), 94 (24) and 79 (19).
2᎐ ᎐
2,6-Dimethyltricyclo[6.3.0.02,5]undeca-6-ene-4,11-dione 33
Irradiation of compound 25 (0.056 g, 0.27 mmol) in dry ben-
zene (100 cm3) under nitrogen in a Pyrex immersion well as
described above for 1.5 h followed by chromatography (LP–
ethyl acetate, 95:5) of the photolysate gave compound 33
(0.017 g, 30%) followed by unchanged starting material (0.012
g); νmax(film)/cmϪ1 1777 and 1737; λmax(MeOH)/nm 260.0,
207.6; δH(500 MHz, CDCl3) 5.41 (1H, br m, olefinic H), 3.10–
2.90 (3H, overlapped m), 2.56 (1H, dd, J 16 and 5.5, methylene
H), 2.40 (1H, d, J 7, methine H), 2.20 (2H, m), 2.10 (1H, com-
plex m), 1.96 (1H, m), 1.71 (3H, d, J 1, CH3) and 1.63 (3H, s,
CH ); m/z 204 (Mϩ, 13), 162 [100, Mϩ Ϫ (CH ᎐C᎐O)], 91 (28)
2᎐ ᎐
3
and 79 (15).
2,6,10,10-Tetramethyltricyclo[6.3.0.02,5]undeca-6-ene-4,11-dione
34
A three-necked round-bottom flask (50 cm3) fitted with an
argon inlet, reflux condenser and septum was charged with
tributyltin hydride (1.8 g, 6.2 mmol) in dry toluene (25 cm3).
The reaction mixture was refluxed whilst a solution of the
S-methyl dithiocarbamate 29c (0.9 g, 2.45 mmol) in dry toluene
(10 cm3) was slowly injected into it. After the reaction mixture
had been refluxed for 12 h, toluene was removed under reduced
pressure and the residue was charged onto a silica gel column.
Elution with LP removed the organotin impurities whilst
further elution with LP–ethyl acetate (98:2) furnished the ketal
(0.66 g). This was taken up in acetone–water (90:10, 40 cm3)
and treated with a drop of concentrated hydrochloric acid. The
reaction mixture was stirred at ambient temperature (~30 ЊC)
for 3 h after which the acetone was removed under reduced
pressure and the residue dissolved in ethyl acetate (50 cm3). The
solution was then washed with saturated aqueous sodium
hydrogen carbonate (1 × 20 cm3), water (1 × 20 cm3) and brine
(1 × 20 cm3) and then dried and evaporated in vacuo. Column
chromatography of the crude material on silica gel and elution
with LP–ethyl acetate (95:5) furnished the desired compound
31 (0.28 g, 52%); νmax(film)/cmϪ1 1726; λmax(MeOH)/nm 208s
and 296w; δH(300 MHz, CDCl3) 5.71 (1H, br m, olefinic H),
2.82 (1H, superimposed dd, J 3 and 3, methine H at C-1), 2.62
(1H, m of dd, J 18 and 9, methylene H), 2.20 (1H, dd with str.,
J 18 and 9, methylene H), 1.86 (2H, AB system, JAB 16, methyl-
ene protons α to CO), 1.80 (3H, d, J 1.5, CH3), 1.50 (2H, dd
with str., J 20 and 9, methylene H), 1.12 (3H, s, CH3), 0.98
(3H, s, CH3), 0.94 (2H, m merged between the methyl signals,
methylene H) and 0.92 (3H, s, CH3); δC(75 MHz, CDCl3) 213.6
(CO), 136.3 (s), 133.0 (d), 58.6 (d), 49.4 (d), 47.5 (q), 44.3, 44.1,
41.8, 39.6, 39.5, 39.0, 28.5 (q), 27.4 (q) and 22.2; m/z 218 (Mϩ,
9%), 176 [100, Mϩ Ϫ (CH ᎐C᎐O)], 161 [69, Mϩ Ϫ (CH ᎐C᎐O ϩ
Irradiation of compound 28 (0.060 g, 0.26 mmol) in dry ben-
zene (100 cm3) under nitrogen in a Pyrex immersion well as
described above for 1 h followed by chromatography (LP–ethyl
acetate, 95:5) of the photolysate gave compound 34 (0.017 g,
28%) followed by unchanged starting compound (0.008 g);
νmax(film)/cmϪ1 1779 and 1735; λmax(MeOH)/nm 302.2w and
213.2s; δH(300 MHz, CDCl3) 5.43 (1H, m, olefinic H), 3.15
(1H, m), 3.04–2.88 (2H, m), 2.64 (1H, d, J 7.3), 2.56 (1H, dd,
J 16.5 and 5.8), 2.09 (1H, dd, J 13.2 and 1.1), 1.9 (1H, d with
fine str., J 13.2), 1.7 (3H, m, CH3), 1.64 (3H, d, J 0.6, CH3),
1.07 (3H, s, CH3) and 1.02 (3H, s, CH3); m/z 190 [60%,
Mϩ Ϫ O᎐C᎐CH )], 162 [17, Mϩ Ϫ {(COCH ) ϩ CO}], 119
᎐ ᎐
2
2
[46, Mϩ Ϫ {(COCH2) ϩ CO ϩ C3H7}], 106 [100, Mϩ Ϫ {(CO-
CH2) ϩ CO ϩ C4H8}] and 91 [31, 106 Ϫ CH3].
2,6,10,10-Tetramethyl-11-endo-hydroxytricyclo[6.3.0.02,5]-
undeca-6-en-4-one 35
Irradiation of compound 30 (0.070 g, 0.3 mmol) in dry benzene
(100 cm3) under nitrogen in a Pyrex immersion well as described
above for 1.5 h followed by chromatography (LP–ethyl acetate,
95:5) of the photolysate gave compound 35 (0.031 g, 44%) fol-
lowed by unchanged starting compound (0.022 g); νmax(film)/
cmϪ1 3427 and 1774; λmax(MeOH)/nm 207s, 305w; δH(500 MHz,
CDCl3) 5.53 (1H, s, olefinic H), 3.52 (1H, dd, J 10 and 4,
HCOH), 3.10 (1H, m, methine H), 3.02 (1H, dd, J 16.5 and 2.5,
methylene H), 2.78 (1H, m, methine H), 2.61 (1H, dd, J 16.5
and 6, methylene H), 2.41 (1H, dd, J 10 and 5, methine H), 2.02
(1H, dd, J 12.5 and 10, methylene H), 1.71 (3H, br s, CH3), 1.46
(1H, dd, J 12.5 and 4, methylene H), 1.44 (3H, s, CH3), 1.18
(1H, d, J 10.2), 1.06 (3H, s, CH3) and 1.01 (3H, s, CH3); δC(125
MHz, CDCl3) 206.3, 130.1, 127.3, 83.4, 68.1, 57.2, 45.6, 45.0,
43.2, 35.4, 29.9, 29.2, 25.4, 24.6 and 22.2; m/z 234 (Mϩ, 1%), 192
[22, Mϩ Ϫ O᎐C᎐CH ], 120 [100, Mϩ Ϫ (CH ᎐C᎐O ϩ C H )],
2᎐ ᎐
2᎐ ᎐
CH3)], 120 (31), 105 (36) and 91 (14).
᎐ ᎐
2᎐ ᎐
2
5
12
2,6-Dimethyltricyclo[6.3.0.02,5]undeca-6,9-dien-4-one 32
105 (29) and 91 (15).
A solution of compound 20 (0.086 g, 0.46 mmol) in benzene
(100 cm3) was irradiated under nitrogen with a mercury vapour
lamp (125 W; Applied Photophysics) in a Pyrex immersion well
for ca. 1.5 h after which the solvent was removed in vacuo. The
photolysate was then chromatographed over silica gel with LP–
ethyl acetate (98:2) as eluent to furnish compound 32 (0.027 g,
31%). Continued elution with the same solvent gave unchanged
starting material (0.018 g); νmax(film)/cmϪ1 1777; λmax(MeOH)/
2,6,10,10-Tetramethyltricyclo[6.3.0.02,5]undeca-6-en-4-one 36
Irradiation of compound 31 (0.120 g, 0.55 mmol) in dry ben-
zene (100 cm3) under nitrogen in a Pyrex immersion well as
described above for 1 h followed by chromatography (LP–ethyl
acetate, 95:5) of the photolysate gave compound 36 (0.041 g,
34%) followed by unchanged starting compound (0.027 g);
νmax(film)/cmϪ1 1778; δH(300 MHz, CDCl3) 5.30 (1H, br m), 3.0
J. Chem. Soc., Perkin Trans. 1, 1998
311

View Article Online
6 A. J. Waring, Advances in Alicyclic Chemistry, eds. H. Hart,
(1H, d with str. overlapped onto another m, J 18, COCH2), 2.99
(1H, m, methine H at cyclobutanone ring junction), 2.63 (1H,
br m, methine H at the allylic ring junction), 2.50 (1H, dd, J 18
and 5, COCH2), 2.26 (1H, d of dd, J 12 and 9, methine H at the
ring junction), 1.86 (1H, dd, J 12 and 7.5, methylene H), 1.69
(3H, br m, CH3), 1.52–1.42 (2H, complex m, methylene H), 1.23
(3H, s, CH3), 1.1 (1H, superimposed dd, J 12 and 12, methylene
H), 1.02 (3H, s, CH3) and 1.00 (3H, s, CH3); δC(75 MHz,
CDCl3) 206.0 (s), 127.8 (d), 125.4 (s), 66.5 (d), 55.5 (t), 47.9
(t), 43.3 (t), 42.9 (d), 39.2 (d), 37.9 (s), 32.2 (q), 32.1 (q), 30.8
(s), 26.4 (q) and 22.1 (q); m/z 218 (Mϩ, 2%), 176 [94,
Mϩ Ϫ O᎐C᎐CH ], 161 [100, Mϩ Ϫ (CH ᎐C᎐O ϩ CH )], 120
G. Karabatsos, Academic Press, New York, 1966, vol. 1, p. 131.
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᎐ ᎐
(44), 105 (68), 91 (21) and 77 (11).
2᎐ ᎐
2
3
Acknowledgements
We thank the R.S.I.C., I.I.T. Bombay and T.I.F.R. Bombay
1
for highfield H NMR and 13C NMR and mass spectra. U. S.
thanks C.S.I.R., New Delhi for a research fellowship. Financial
support to V. S. from DST, New Delhi is gratefully
acknowledged.
13 V. K. Singh and P. T. Deota, J. Chem. Res., 1989, (S), 390.
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Paper 7/04817C
Received 7th July 1997
Accepted 1st October 1997
312
J. Chem. Soc., Perkin Trans. 1, 1998