Synthesis based on cyclohexadienes. Part 34. A tandem cationic rearrangement-ene cyclisation route to 2-pupukeanone

Article abstract of DOI:10.1039/b003409f

A tandom cationic rearrangement-ene cyclisation route to 2-pupukeanone was discussed. The synthesis of 2-pupukeanone was done using a one-pot tandom acid-catalysed rearrangement. Results showed that 2-pupukeanone could be obtained from the tricyclic keton

Full text of DOI:10.1039/b003409f

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Synthesis based on cyclohexadienes. Part 34.1 A tandem cationic
rearrangement–ene cyclisation route to 2-pupukeanone
P. John Biju, Krishna Kaliappan, M. S. Laxmisha and G. S. R. Subba Rao*
1
Department of Organic Chemistry, Indian Institute of Science, Bangalore-560012, India
Received (in Cambridge, UK) 27th April 2000, Accepted 4th September 2000
First published as an Advance Article on the web 19th October 2000
A new strategy for the construction of the isotwistane skeleton is reported from easily available cyclohexadienes,
which involves a one-pot cationic skeletal rearrangement and ene cyclisation of a bicyclo[2.2.2]octenone derivative
and a cationic rearrangement of a tricyclo[5.3.0.04,8]decane to a [4.3.1.03,7]decane skeleton as the key steps in the
synthesis of 2-pupukeanone.
Introduction
A number of marine organisms secrete some toxic or very
strongly smelling compounds from their skin glands as a part
of their self-defence mechanism in order to protect themselves
from their predators. Johannes2 observed that the nudibranch
Phyllidia varicosa Lamarck, 1801 secretes from its skin glands
a strong and (usually) smelly, heat-stable, volatile substance,
which is lethal to fish and crustaceans, to protect the delicate,
shell-less, brightly coloured opisthobranch mollusk from
its predators. In 1975, Scheuer and co-workers3 reported the
isolation of a metabolite, 9-isocyanopupukeanane 1, the first
member of the isotwistane carbon framework, from P. varicosa
and also from its prey, a sponge, Hymeniacidon sp. In 1979,
an isomeric substance, 2-isocyanopupukeanane 2 was also
isolated4 from the same source by the same group. These
compounds were named as pupukeananes after the place where
the mollusk and sponge were collected.
subunit with a bridgehead methyl group, we report herein a
formal synthesis of 2-pupukeanone 5, a degradation product
of 2-isocyanopupukeanane 2, employing a tandem cationic re-
arrangement and ene cyclisation as the key step. A preliminary
account of this work has been reported.10
Results and discussion
The synthesis of 2-pupukeanone 5 was devised employing
a one-pot tandem acid-catalysed rearrangement and an ene
cyclisation as depicted in Scheme 1. Our retrosynthetic analysis
indicated that 2-pupukeanone 5 could be obtained from the
tricyclic ketone 10, which in turn could be prepared from
the ketone 12 by employing a skeletal rearrangement. The
hydroxy ketone 12 can be obtained from the bicyclic ketone
11 by making use of a one-pot tandem rearrangement–ene
cyclisation reaction. The bicyclic ketone 11 can in turn be
prepared from the known bicyclic ketone 9.11
The structure of the metabolites incorporating the novel
isotwistane carbon framework 3 was established by chemical
degradation to the corresponding ketones 4 and 5 respectively
and confirmed by a single-crystal X-ray analysis; the absolute
configuration of the two compounds was also established in the
latter study. Since then several other pupukeananes have been
isolated from various other sources. These include thiocyanato-
neopupukeananes 7a and 7b from the sponges Phycopsis terpnis
and an unidentified species; and 9-isocyanoneopupukeanane 8
from the sponge Ciocalypta species.5,6
Synthesis of the bicyclic ketone 11
The total synthesis of these sesquiterpenes is challenging
since they possess i) a new rearranged isoprenoid skeleton with
a unique tricyclo[4.3.1.03,7]decane framework having a bicyclo-
[2.2.2]octane subunit with a methyl group at the bridgehead
position and ii) an isopropyl group in a thermodynamically
unfavourable position. Owing to their unique molecular
architecture, several syntheses of these tricyclic sesquiterpenes
have been reported.7,8 In continuation of our interest9 in the
total synthesis of sesquiterpenes having a bicyclo[2.2.2]octane
The bicyclic ketone 9 upon alkylation with lithium diisopropyl-
amide (LDA) and MeI afforded the ketone 13 having the methyl
group in the endo position (Scheme 2), as evidenced by the
spectral data. Stereoselective alkylation12 with prenyl bromide
(prenyl = 3-methylbut-2-enyl) was achieved by treating the
ketone 13 with LDA at Ϫ78 ЊC and quenching of the resultant
enolate with prenyl bromide in tetrahydrofuran (THF)–
hexamethylphosphonic triamide (HMPA). The structure of
the ketone 11 was established from its spectral characteristics,
3714
J. Chem. Soc., Perkin Trans. 1, 2000, 3714–3718
This journal is © The Royal Society of Chemistry 2000
DOI: 10.1039/b003409f

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Scheme 1
Scheme 3 Reagents and conditions (and yields): i) HClO4 (catalytic),
CH2Cl2, room temp. (57%); ii) PTSA, benzene, reflux, 1 h (95%).
15 was isomerised to the tetrasubstituted position by refluxing
the ketone 15 with PTSA in benzene to afford the ketone 12.
The formation of 15 from 11 presumably involves i) acid-
catalysed rearrangement13 of 11 having a bicyclo[2.2.2]octenone
subunit to the hydroxy enone 14, possessing the bicyclo[3.2.1]-
octenone framework and ii) an intramolecular ene reaction of
14 to afford the hydroxy ketone 15.
Scheme 2 Reagents and conditions (and yields): i) LDA, MeI, THF
(80%); ii) LDA, prenyl bromide, THF, HMPA, Ϫ78 ЊC (75%).
especially from its 1H NMR spectrum, which showed signals at
δ 1.08 (s, Me), 1.59 and 1.73 (two s, allylic Me) and 5.12 (prenyl
olefinic H).
Having succeeded in the tandem rearrangement–ene cyclis-
ation of the bicyclic ketone 11 having a prenyl subunit, we next
investigated a similar reaction on the corresponding alkyne
system 16. The literature is replete with reports15 which have
employed alkynes as the ene component in ene reactions.
Thus, alkylation of the lithium enolate of the ketone 13,
generated from LDA, with 1-bromobut-2-yne in the presence
of HMPA afforded the endo-alkylated product 16 exclusively12
(Scheme 4). The structure of 16 was established from its
spectral data. The IR spectrum showed absorptions at νmax 2240
and 1730 cmϪ1 due to the alkyne and carbonyl functionalities,
Having obtained the bicyclic ketone 11 in good yield, a
one-pot tandem acid-catalysed rearrangement–ene cyclisation
reaction was next investigated. It is known that bicyclo[2.2.2]-
octenones having a bridgehead methoxy group undergo a
skeletal rearrangement to give bicyclo[3.2.1]octenones.13 It
was anticipated that the bicyclic ketone 11 upon a similar
rearrangement would furnish the enone 14, which has both the
ene and the enophile properly oriented for an intramolecular
ene reaction. Thus, a tandem acid-catalysed rearrangement
and an ene reaction would furnish the tricyclic ketone 12. The
tricyclic ketone 12 is convertible into 2-pupukeanone 5.
With this background, we investigated a one-pot tandem
acid-catalysed rearrangement and ene cyclisation of the bicyclic
ketone 11. Thus, treatment of the bicyclic ketone 11 with Lewis
acid BF3ؒMeOH at room temperature gave only the starting
material, whilst for reactions at higher temperatures the
product decomposed. Treatment of the ketone 11 with SnCl4,
BF3ؒOEt2 and HCO2H failed to produce the desired com-
pound, as did heating it with toluene-p-sulfonic acid (PTSA) in
refluxing benzene.
1
respectively. The H NMR spectrum showed a triplet at δ 1.81
(J = 2.4 Hz) due to the methyl group attached to the alkyne, and
two quartets of doublets at δ 2.08 and 2.34 (J = 13.8 and 2.7 Hz)
due to the methylene protons on the carbon attached to the
acetylenic moiety.
The ketone 16, having been obtained in good yield, was
subjected to the tandem rearrangement–ene cyclisation con-
ditions. All attempts to bring about this transformation
employing reagents used in similar transformations15 were
unsuccessful. However, when the ketone 16 was stirred with a
14
However, when the ketone 11 was treated with HClO4 in
CH2Cl2,14 it underwent a smooth rearrangement followed by an
ene cyclisation to afford the tricyclic ketone 15 in good yield
(Scheme 3). The structure of 15 was delineated from its spectral
characteristics. The IR spectrum showed absorptions at νmax
3460 and 1700 cmϪ1 due to the hydroxy and the carbonyl groups,
catalytic amount of HClO4 in dichloromethane, it smoothly
underwent a tandem rearrangement followed by an ene cyclis-
ation, resulting in the dione 17. The structure of the dione 17
was established from its spectral data. The IR spectrum showed
the absence of absorptions due to the acetylenic moiety, and the
carbonyl absorptions appeared at νmax 1710 and 1700 cmϪ1. The
1H NMR spectrum showed a signal at δ 2.18 due to the protons
of the acetyl group. The structure of 17 was further confirmed
from its 13C NMR spectrum, which showed a 13-line spectrum,
with characteristic peaks at δC 203.8 and 209.7 due to the two
carbonyl carbons.
1
respectively. The H NMR showed the absence of methoxylic
protons at δ 3.52, and the exocyclic olefinic protons appeared
at δ 4.68 and 4.90. The stereochemistry of the isopropenyl
side chain was not confirmed since it is inconsequential for
the synthesis of 2-pupukeanone. The exocyclic double bond in
J. Chem. Soc., Perkin Trans. 1, 2000, 3714–3718
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The diene 19, on treatment with catalytic BF3ؒOEt2 in dry
dichloromethane, underwent the expected skeletal rearrange-
ment9 to furnish the isotwistane ketone 10, whose spectral
characteristics were identical with those reported earlier.8f The
ketone 10 has been converted into 2-pupukeanone 5 earlier in
our laboratory,8f and thus the present synthesis constitutes a
formal synthesis of 2-pupukeanone 5.
The same sequence of reactions was attempted on the dione
17. Thus, Wittig methylenation of the dione 17 furnished the
diene 20 (Scheme 6), whose structure was deduced from its
Scheme 6 Reagents and conditions (and yields): i) Ph3PMeI, penttOK,
PhH, reflux, 12 h (73%); ii) BF3ؒOEt2 (cat.), CH2Cl2.
spectral data. The IR spectrum showed the absence of carbonyl
absorptions. The 1H NMR spectrum showed four olefinic
protons at δ 4.67, 4.80, 4.83 and 4.93 due to the four exocyclic
olefinic protons. The diene 20 was expected to furnish the
isotwistane 21 upon acid-catalysed skeletal rearrangement,
similar to the aforementioned rearrangement. Thus, treatment
of 20 with catalytic BF3ؒOEt2 in dry dichloromethane furnished
a complex mixture of products, from which the isotwistane 21
could not, however, be isolated. Changing the acid catalyst
also did not alter the outcome of the reaction. The failure of
this rearrangement was surprising considering the structural
similarity between the dienes 19 and 20.
In conclusion, an efficient method for the construction of the
isotwistane skeleton present in pupukeananes is reported from
readily available cyclohexadienes, which involved a tandem
acid-catalysed rearrangement–ene cyclisation of a bicyclo-
[2.2.2]octenone to a tricyclo[5.3.0.04,8]decane skeleton as the
key step. This methodology was successful on the correspond-
ing alkyne system also. An acid-catalysed rearrangement to
the tricyclo[4.3.1.03,7]decane skeleton culminated in the formal
synthesis of 2-pupukeanone 5.
Scheme 4 Reagents and conditions (and yields): i) LDA, 1-bromobut-
2-yne, THF, HMPA, Ϫ78 ЊC (84%); ii) HClO4 (catalytic), CH2Cl2,
30 min (42%).
The formation of the dione 17 from the bicyclic ketone 16
presumably involves a similar type of rearrangement and an
ene cyclisation as described for compound 11, except that the
vinyl cation 18, formed after the ene cyclisation,15 undergoes
hydration under the reaction conditions to furnish the diketone
17 as shown in Scheme 4.
The next task in the synthetic sequence was to convert
the tricyclic intermediates 12 and 17 into 2-pupukeanone. An
acid-catalysed rearrangement9 was contemplated for the con-
version of the tricyclo[5.3.0.04,8]decane framework to the tri-
cyclo[4.3.1.03,7]decane framework. Thus, Wittig olefination
of the ketone 12 with (triphenyl)methylphosphonium iodide
and potassium tert-amylate in refluxing benzene furnished the
diene-alcohol 19 (Scheme 5). Although other bases such as
Experimental
All mps and bps are uncorrected. Mps were recorded on a
Mettler FP1 instrument. IR spectra were recorded on Perkin-
Elmer 78 and JASCO FT/IR-410 spectrophotometers. NMR
spectra were recorded on a JEOL FX-90Q, a Bruker ACF-200,
or a JEOL JNM LA-300 spectrometer. The chemical shifts
(δ/ppm) and coupling constants (J/Hz) are reported for
standard tetramethylsilane (for 1H) or the central line of CDCl3
(for 13C). Mass spectra were recorded on a JEOL MS-DX 303
with inbuilt direct-inlet system, and relative intensities of the
ions are given in parentheses. Microanalysis was carried out
using a Carlo Erba 1106 instrument. Analytical and preparative
TLC were performed on glass plates coated with Acme’s silica
gel G containing 13% calcium sulfate as binder. Visualisation
of the spot was accomplished by exposure to iodine vapour.
Acme’s silica gel (60–120 mesh) was used for column chroma-
tography. ‘Hexane’ refers to petroleum spirit fraction boiling
at 60–80 ЊC, and ether refers to diethyl ether. All dry solvents
were prepared by standard procedures. Liquid ammonia
was distilled over sodamide before use. All reactions involving
air- and moisture-sensitive reagents were performed under
either a blanket of nitrogen or argon-filled balloons. Wherever
it is mentioned, ‘the usual work-up’ means the reaction mixture
was washed successively with water and brine, dried over
anhydrous Na2SO4, and concentrated in a rotary evaporator
Scheme 5 Reagents and conditions (and yields): i) Ph3PMeI, penttOK,
PhH, reflux (83%); ii) BF3ؒOEt2 (catalytic), CH2Cl2 (80%).
n-BuLi, KOtBu and NaH have been used in the Wittig reaction
of the tricyclic ketone 12, consistent yields of the product were
obtained only with KOC5H11t, which may perhaps be due to its
solubility in the organic solvent.
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J. Chem. Soc., Perkin Trans. 1, 2000, 3714–3718

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at aspirator pressure for the isolation of the product mixture.
Unless otherwise stated, all starting materials were obtained
from commercial suppliers and were used without further
purification.
1-Hydroxy-5-isopropylidene-7-methyltricyclo[5.3.0.04,8]decan-2-
one 12
A solution of the hydroxy olefin 15 (0.25 g, 1.14 mmol) and
PTSA (catalytic) in dry benzene (5 ml) was refluxed for 1 h.
The reaction mixture was cooled, washed successively with
saturated aq. NaHCO3 (10 ml) and brine, and dried over
anhydrous Na2SO4. The solvent was evaporated under reduced
pressure and the residue was purified on a silica gel column
[ethyl acetate–‘hexane’ (1:30)] to yield the hydroxy ketone 12
(0.24 g, 95%) as a solid, which was recrystallised from
methylene dichloride; mp 77 ЊC; νmax/cmϪ1 3460, 2910 and 1700;
δH (300 MHz) 1.24 (3H, s, Me), 1.53 (3H, s, vinylic Me), 1.63
(3H, s, vinylic Me), 1.50–2.00 (6H, m), 2.11 and 2.16 (1H, dt,
J 15.9 and 2.1, H-8), 2.29 (1H, dd, J 12.6 and 9.3 Hz, H-3), 2.42
(1H, d, J 16.2, H-6) and 3.03 (1H, dd, J 9 and 5.4, H-4); δC (75
MHz) 17.6 (t), 18.1 (q), 20.6 (q), 20.7 (q), 32.3 (t), 38.0 (t), 41.0
(d), 42.3 (t), 44.8 (d), 53.7 (s), 74.4 (s), 123.6 (s), 136.1 (s) and
221.0 (s); m/z 220 (Mϩ, 100%), 202 (7), 192 (37), 177 (48), 159
(16), 134 (66), 119 (39) and 107 (22) (Found: Mϩ, 220.1452;
C, 76.13; H, 9.04. C14H20O2 requires M, 220.1453; C, 76.33;
H, 9.15%).
1-Methoxy-3-endo-methylbicyclo[2.2.2]oct-5-en-2-one 13
To a freshly prepared LDA solution [prepared from 1 M solu-
tion of n-BuLi (14.4 ml, 14.4 mmol) and diisopropylamine
(2 ml, 15.8 mmol) in 40 ml of THF] at Ϫ78 ЊC under argon was
added a solution of the ketone 9 (2.38 g, 13.14 mmol) in 40 ml
of THF dropwise. After stirring of the reaction mixture at
Ϫ78 ЊC for 1 h, methyl iodide (2 ml, 30 mmol) as a solution in
10 ml of THF was added and the mixture was stirred for 1 h.
The reaction mixture was poured into saturated aq. ammonium
chloride and extracted with ether. The ether layer was washed
successively with water, aq. sodium thiosulfate, water and brine,
and dried over anhydrous Na2SO4. Removal of the solvent fol-
lowed by column chromatography over silica gel [ether–pentane
(1:49)] as eluent afforded the ketone 13 as a colourless oil (2.1 g,
80%); νmax/cmϪ1 3005, 2925, 1715 and 1640; δH (90 MHz) 1.09
(3H, d, J 7.2, CHMe), 1.6–2.2 (5H, m), 2.73 (1H, m, bridgehead
H), 3.52 (3H, s, OMe) and 6.1–6.5 (2H, m, olefinic); δC (22.5
MHz) 16.7, 24.4, 25.0, 37.6, 43.4, 52.3, 83.6, 129, 134.2 and
210.3; m/z 166 (Mϩ, 55%), 138 (100), 122 (100) and 110 (60)
(Found: Mϩ, 166.0994. C10H14O2 requires M, 166.0994).
3-(But-2-ynyl)-1-methoxy-3-methylbicyclo[2.2.2]oct-5-en-2-one
16
To a solution of LDA [generated from 7 ml of 1.4 M BuLi
(10 mmol) and diisopropylamine (1.58 ml, 11.3 mmol) in 40 ml
of dry THF] at Ϫ78 ЊC under argon was added a solution of
the ketone 13 (1.1 g, 6.6 mmol) in dry THF (20 ml) dropwise.
After being stirred at the same temperature for 1 h, the mixture
was treated with 1-bromobut-2-yne (1.7 g, 13.2 mmol) and dry
HMPA (2 ml) and was stirred at Ϫ78 ЊC for another 30 min and
at room temperature for 2 h. Water was added and the product
was extracted with ether. The ether layer was washed succes-
sively with dil. HCl, water, and brine, and dried over anhydrous
Na2SO4. Removal of the solvent followed by chromatography
[ethyl acetate–‘hexane’ (1:25)] furnished the ketone 16 (1.22 g,
84%) as a colourless oil; νmax/cmϪ1 2240 and 1730; δH (300
MHz) 1.2 (3H, s, Me), 1.28–2.02 (4H, m), 1.81 (3H, t, J 2.4,
1-Methoxy-3-methyl-3-endo-(3-methylbut-2-enyl)bicyclo[2.2.2]-
oct-5-en-2-one 11
To a freshly prepared LDA solution [prepared from 1 M solu-
tion of n-BuLi (8 ml, 8 mmol) and diisopropylamine (1.04 ml,
7.4 mmol) in 20 ml of THF] at Ϫ78 ЊC under argon was added
a solution of the ketone 13 (0.66 g, 2.0 mmol) in THF (10 ml)
dropwise. The resultant solution was stirred for 1 h at Ϫ78 ЊC
and quenched with prenyl bromide (1.48 g, 10 mmol) followed
by the addition of HMPA (0.7 ml, 4 mmol). The reaction
mixture was stirred overnight, poured into ice-cold water, and
extracted with ether (4 × 25 ml). The combined organic layer
was washed successively with 2 M HCl, water and brine and
dried over anhydrous Na2SO4. Removal of the solvent followed
by column chromatography on silica gel [ethyl acetate–‘hexane’
(1:24)] afforded the ketone 11 (0.7 g, 75%) as an oil; νmax/cmϪ1
3020, 2940, 1720 and 1640; δH (90 MHz) 1.08 (3H, s, Me), 0.85–
2.18 (6H, m), 1.59 (3H, s, Me), 1.73 (3H, s, Me), 2.61 (1H, m,
bridgehead H), 3.52 (3H, s, OMe), 5.12 (1H, t, J 7.1, olefinic),
6.17 (1H, dd, J 6.7 and 1.7, olefinic) and 6.45 (1H, dd, J 8.2
and 6.7, olefinic); δC (22.5 MHz) 17.6, 21.0, 21.1, 25.7, 26.2,
36.5, 39.5, 47.0, 52.8, 84.2, 118.7, 127.4, 134.6, 136.5 and 213.1;
m/z 234 (Mϩ, 90%), 206 (25), 175 (26), 150 (75), 136 (100)
and 110 (100) (Found: Mϩ, 234.1616. C15H22O2 requires M,
234.1620).
acetylenic Me), 2.08 and 2.34 (2H, q of d, J 13.8 and 2.7,
᎐
C᎐CCH ), 2.93 (1H, br s, bridgehead proton), 3.51 (3H, s,
᎐
2
OMe), 6.15 (1H, d, J 8.4, olefinic) and 6.54 (1H, dd, J 8.4 and 6,
olefinic); δC (75 MHz) 3.4, 19.4, 26.3, 27.6, 30.3, 42.2, 48.9, 52.8,
76.1, 79.2, 83.9, 125.4, 142.2 and 211.4; m/z 218 (Mϩ, 14%), 190
(49), 110 (100) and 82 (33) (Found: Mϩ, 218.1842. C14H18O2
requires M, 218.1831).
5-Acetyl-1-hydroxy-7-methyltricyclo[5.3.0.04,8]decan-2-one 17
A solution of the ketone 16 (0.5 g, 2.3 mmol) in CH2Cl2 (20 ml)
was stirred with HClO4 (0.1 ml) at room temperature. After
30 min, the reaction mixture was washed successively with
water, saturated aq. NaHCO3, and brine, and dried over
anhydrous Na2SO4. Removal of the solvent followed by column
chromatography over silica gel [ethyl acetate–‘hexane’ (1:5)]
gave the hydroxy dione 17 (0.21 g, 42%) as a viscous oil;
νmax/cmϪ1 3460, 1710 and 1700; δH (300 MHz) 1.13 (3H, s, Me),
1.6–2.15 (8H, m), 2.18 (3H, s, COCH3) and 2.34–2.59 (3H, m);
δC (75 MHz) 16.4, 21.7, 27.2, 33.4, 33.6, 36.4, 38.0, 44.3, 47.8,
48.6, 85.0, 203.8 and 209.7; m/z 222 (Mϩ, 6%), 180 (43), 149
(50), 91 (62) and 41 (100) (Found: Mϩ, 222.1413. C13H18O3
requires M, 222.1419.
1-Hydroxy-5-isopropenyl-7-methyltricyclo[5.3.0.04,8]decan-2-one
15
A solution of the ketone 11 (0.5 g, 2.13 mmol) in CH2Cl2 (50 ml)
was stirred with HClO4 (70%; 0.1 ml) at room temperature.
After 30 min, the reaction mixture was diluted with CH2Cl2,
washed successively with water, saturated aq. NaHCO3 and
brine, and dried over Na2SO4. Evaporation of the solvent
followed by chromatography of the crude product over silica
gel [ethyl acetate–‘hexane’ (1:30)] gave the hydroxy ketone 15
(0.272 mg, 57%) as a viscous oil; νmax/cmϪ1 3460, 2920, 1700
and 1640; δH (300 MHz) 1.22 (3H, s, Me), 1.67 (3H, s,
Me), 1.30–2.50 (10H, m), 2.68–2.75 (1H, m, H-4), 4.68 (1H, s,
olefinic) and 4.90 (1H, s, olefinic); m/z 220 (Mϩ, 61.5%),
202 (11), 192 (73), 177 (41), 134 (97.5), 123 (100), 109 (67)
and 95 (86) (Found: Mϩ, 220.1466. C14H20O2 requires M,
220.1465).
5-Isopropylidene-7-methyl-2-methylenetricyclo[5.3.0.04,8]decan-
1-ol 19
A solution of potssium tert-amylate [prepared from potassium
(0.11 g, 2.727 mmol) and tert-amyl alcohol (0.5 ml)] was
added to a suspension of methyl(triphenyl)phosphonium iodide
(1.1 g, 2.727 mmol) in benzene (5 ml) under nitrogen via
cannula, and the resulting pale yellow solution was stirred
J. Chem. Soc., Perkin Trans. 1, 2000, 3714–3718
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for 20 min at room temperature. A solution of the ketone 12
(100 mg, 0.45 mmol) in dry benzene (5 ml) was added and the
mixture was refluxed for 24 h. After cooling of the reaction
mixture, water was added and the product was extracted with
ether. The extract was subjected to the usual work-up followed
by chromatography of the crude mixture over silica gel [ethyl
acetate–‘hexane’ (1:30)] to furnish the hydroxy olefin 19 (83 mg,
83%) as a colourless oil; νmax/cmϪ1 3350 and 1420; δH (90
MHz) 1.10 (3H, s, Me), 1.58 (3H, s, vinylic Me), 1.64 (3H, s,
vinylic Me), 1.70–2.80 (10H, m), 4.54 (1H, t, J 2.5, olefinic) and
4.80 (1H, t, J 2.5, olefinic); δC (22.5 MHz) 19.7, 20.2, 20.5, 21.1,
35.1, 37.2, 37.9, 45.5, 52.6, 52.8, 84.5, 103.4, 120.2, 138.3 and
152.4; m/z 218 (Mϩ, 21%), 203 (4), 185 (5), 175 (6), 134 (100),
119 (36), 105 (21) and 91 (24) (Found: Mϩ, 218.1673. C15H22O
requires M, 218.1672).
Acknowledgements
We thank the UGC, New Delhi for the award of a fellowship to
M. S. L. We thank CSIR, New Delhi for a fellowship to K. K.
and for financial assistance (Emeritus Scientist to G. S. R. S. R.).
References
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G. S. R. Subba Rao, Tetrahedron Lett., 2000, 41, 3759.
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4 M. R. Hegadone, B. J. Burreson, P. J. Scheuer, J. S. Finer and
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5 N. Fusetani, H. J. Wolstenholme and S. Matsunaga, Tetrahedron
Lett., 1990, 31, 5623.
5-Isopropenyl-7-methyl-2-methylenetricyclo[5.3.0.04,8]decan-1-ol
20
A solution of potassium tert-amylate [prepared from potassium
(0.21 g, 5 mmol) and tert-amyl alcohol (1 ml)] was added to
a suspension of methyl(triphenyl)phosphonium iodide (2.1 g,
5.4 mmol) in benzene (10 ml) under nitrogen via cannula,
and the resulting yellow solution was stirred for 20 min at room
temperature. The dione 17 (0.2g, 0.9 mmol) as a solution in dry
benzene (5 ml) was added and the mixture was refluxed for 12 h.
After cooling of the reaction mixture, water was added and the
product was extracted with ether. The extract was subjected to
the usual work-up followed by column chromatography of the
crude product over silica gel [ethyl acetate–‘hexane’ (1:30)] to
furnish the hydroxy diene 20 (0.15 g, 73%) as a colourless oil;
νmax/cmϪ1 3350, 1640 and 890; δH (300 MHz) 0.81 (3H, s, Me),
1.62 (3H, s, vinylic Me), 1.23–2.66 (11H, m), 4.67 (1H, t, J 1.5,
olefinic), 4.80 (1H, br s, olefinic), 4.83 (1H, t, J 1.5, olefinic) and
4.93 (1H, t, J 2.1, olefinic); m/z 218 (Mϩ, 56%), 203 (58), 175
(100), 91 (78) and 77 (50) (Found: Mϩ, 218.1782. C15H22O
requires M, 218.1672).
6 (a) A. T. Pham, T. Ichiba, W. Y. Yoshida, P. J. Scheuer, T. Uchida,
J. I. Tanaka and T. Higa, Tetrahedron Lett., 1991, 32, 4843;
(b) P. Karuso, A. Poiner and P. J. Scheuer, J. Org. Chem., 1989, 54,
2095.
7 (a) E. J. Corey, M. Behforouz and M. Ishiguro, J. Am. Chem. Soc.,
1979, 101, 1608; (b) S. L. Hseih, C. T. Chiu and N. C. Chang, J. Org.
Chem., 1989, 54, 3820; (c) H. Yamamoto and H. L. Sham, J. Am.
Chem. Soc., 1979, 101, 1609; (d) E. Piers and M. Winter, Justus
Liebigs Ann. Chem., 1982, 973; (e) G. A. Schiesher and J. D. White,
J. Org. Chem., 1980, 45, 1864.
8 (a) E. J. Corey and M. Ishiguro, Tetrahedron Lett., 1979, 2745;
(b) G. Frater and J. Wenger, Helv. Chim. Acta, 1984, 67, 1702;
(c) N. C. Chang and C. K. Chang, J. Org. Chem., 1996, 61, 4967;
(d) K. Kaliappan and G. S. R. Subba Rao, Tetrahedron Lett., 1997,
38, 2185; (e) K. Kaliappan and G. S. R. Subba Rao, J. Chem. Soc.,
Perkin Trans. 1, 1997, 3387; ( f ) K. Kaliappan and G. S. R. Subba
Rao, J. Chem. Soc., Perkin Trans. 1, 1997, 3393; (g) A. Srikrishna
and T. J. Reddy, J. Chem. Soc., Perkin Trans. 1, 1997, 3293; (h) A.
Srikrishna, D. Vijayakumar and G. V. R. Sharma, Tetrahedron Lett.,
1997, 38, 2003.
9 P. Sathya Shanker and G. S. R. Subba Rao, J. Chem. Soc., Perkin
Trans. 1, 1998, 539.
10 P. J. Biju and G. S. R. Subba Rao, Tetrahedron Lett., 1999, 40, 181.
11 D. A. Evans, W. L. Scott and L. K. Truesdale, Tetrahedron Lett.,
1972, 121.
12 G. Stork and N. H. Baine, Tetrahedron Lett., 1985, 26, 5927.
13 (a) I. Alfaro, W. Ashton, K. L. Rabone and N. A. J. Rogers,
Tetrahedron, 1974, 30, 559; (b) T. Uyehara, K. Osanai,
M. Sugimoto, I. Suzuku and Y. Yamamoto, J. Am. Chem. Soc.,
1989, 111, 7264.
14 (a) F. H. Koster and H. Wolf, Tetrahedron Lett., 1981, 22,
3937; (b) J. A. Marshall and P. G. Wuts, J. Org. Chem., 1977,
42, 1794.
5-Isopropylidene-1,3-dimethyltricyclo[4.3.1.03,7]decan-2-one 10
To a solution of the diene 19 (50 mg, 0.23 mmol) in dry CH2Cl2
(1 ml) was added catalytic BF3ؒOEt2 (one drop) and the
solution was stirred for 24 h at room temperature. Saturated
aq. Na2CO3 was added and the product was extracted with
ether. The extract was submitted to the usual work-up followed
by chromatography over silica gel [ethyl acetate–‘hexane’
(1:24)] to furnish the ketone 10 (40 mg, 80%); νmax/cmϪ1
2920 and 1712; δH (400 MHz) 0.89 (3H, s, Me), 1.17 (3H, s, Me),
0.9–2.4 (9H, m), 1.52 (3H, s, Me), 1.62 (3H, s, Me) and 2.9
(1H, m); δC (100 MHz) 17.0, 18.71, 19.88, 20.42, 20.61, 23.25,
27.57, 32.74, 38.39, 40.67, 41.88, 50.6, 122.69, 137.43 and
222.74; m/z 218 (Mϩ, 100%), 162 (50) and 134 (80) (Found:
Mϩ, 218.1681. C15H22O requires M, 218.1671).
15 (a) J. A. Amupitan, E. G. Scovell and J. K. Sutherland, J. Chem.
Soc., Perkin. Trans. 1, 1983, 755; (b) E. E. Tamelen and J. R. Hwu,
J. Am. Chem. Soc., 1983, 105, 2490; (c) B. E. McCarry, R. L.
Markezich and W. S. Johnson, J. Am. Chem. Soc., 1973, 95, 4416;
(d) B. M. Trost, Comprehensive Organic Synthesis, 1991, vol. 3,
pp. 341–377.
3718
J. Chem. Soc., Perkin Trans. 1, 2000, 3714–3718