A stereoselective total synthesis of (±)-pseudoclovene-B

Article abstract of DOI:10.1016/S0040-4020(02)00618-X

A stereocontrolled approach to the construction of the tricyclo[6.3.1.0^1,6]dodecane ring system related to the sesquiterpene pseudoclovene-B (3) is delineated. Starting from the indanone 4, the bromophenol 5 was prepared in a straightforward manner. An aryl participated intramolecular cyclisation of 5 afforded the tricyclic dienone 6 which was stereoselectively converted into the A/B cis-fused ketone 7 through the intermediates 13 and 14 or through the intermediate 15. The tosylhydrazone derivative of 7 was treated with methyl lithium to furnish (±)-pseudoclovene-B in high yield.

Full text of DOI:10.1016/S0040-4020(02)00618-X

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 6179±6184
A stereoselective total synthesis of (^)-pseudoclovene-B
p
Manuka Ghosal, Lokesh Chandra Pati, Arnab Roy and Debabrata Mukherjee
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 22 February 2002; revised 20 May 2002; accepted 13 June 2002
1
,6
AbstractÐA stereocontrolled approach to the construction of the tricyclo[6.3.1.0 ]dodecane ring system related to the sesquiterpene
pseudoclovene-B (3) is delineated. Starting from the indanone 4, the bromophenol 5 was prepared in a straightforward manner. An aryl
participated intramolecular cyclisation of 5 afforded the tricyclic dienone 6 which was stereoselectively converted into the A/B cis-fused
ketone 7 through the intermediates 13 and 14 or through the intermediate 15. The tosylhydrazone derivative of 7 was treated with methyl
lithium to furnish (^)-pseudoclovene-B in high yield. q 2002 Elsevier Science Ltd. All rights reserved.
Tricyclic sesquiterpenes derived from acid treatment of
tricyclic dienone 6 involving an aryl participated intra-
molecular cyclisation (Ar -6 cyclisation) of 5 in the
1
±3
caryophyllene and caryolan-1-ol possess novel skeletal
features and have been the subject of considerable synthetic
1
presence of base. A stereoselective conversion of the
dienone 6 into the A/B cis-fused ketone 7 was achieved in
high yield using the functional groups in the ring A of 6. The
transformation of 7 into (^)-pseudoclovene-B (3) was then
ef®ciently accomplished through Shapiro reaction. Aryl
participated intramolecular cyclisation of indane derivatives
to generate speci®cally functionalised bridged ring systems
related to tricyclic sesquiterpenes has been relatively
unexplored.
1
activity. Clovene (1), an acid-induced rearrangement
,2
2
,4
product of caryophyllene and isoclovene (2), a product
of dehydration of caryolan-1-ol with polyphosphoric acid,
incorporate tricyclo[6.3.1.0 ]dodecane and tricyclo-
1
,5
5,12
6.2.2.0 ]dodecane frameworks (Fig. 1), respectively,
[
and have attracted considerable attention
5
±12
as challenging
synthetic targets. The total syntheses of the sesquiterpenes
5
±9
10±12
1
of times. Pseudoclovene-B (3), another sesquiterpene hydro-
and 2
have been reported in the literature a number
1
carbon possessing a tricyclo[6.3.1.0 ]dodecane skeleton
,6
2
was isolated along with 2 and several other sesquiterpenes
1. Results and discussion
when caryolan-1-ol was treated with polyphosphoric acid.
On the basis of chemical and spectroscopic studies, the struc-
Our synthesis of (^)-pseudoclovene-B 3 from m-cresol is
outlined in Scheme 2. Reaction of m-cresol with metha-
cryloyl chloride provided the phenolic ester 8 which on
1
3,14
ture 3 (Fig. 1) was proposed
for pseudoclovene-B and
1
4
this structure was conclusively established through X-ray
crystallographic analysis of the corresponding dibromide.
The possible mode of fomation of 3 from caryolan-1-ol
was investigated by Parker and co-workers and a plausible
1
6
Fries rearrangement and concomitant intramolecular
cyclisation furnished the hydroxy-indanone 9 in 60%
yield. The ketone 9 was easily puri®ed by steam distillation
and converted into the corresponding methyl ether 4.
Having a convenient route to 4, we turned our attention to
convert 4 into the bromophenol 5. Michael reaction of 4
with methyl acrylate in the presence of NaOMe afforded
the keto-ester 10 in 76% yield. Reduction of 10 with
1
5
mechanistic scheme was proposed. A successful total
synthesis of pseudoclovene-B must address the following
1
,6
problems: (i) construction of the tricyclo[6.3.1.0 ]dodecane
framework with appropriate substituents at C-4 and C-8, (ii)
control of the stereochemistry of the A/B ring junction, and
LiAlH followed by hydrogenolysis of the resulting crude
4
(
iii) introduction of the isolated double bond in ring A. We
1
diol with Li in liquid ammonia afforded the primary
7
describe herein a short, ef®cient and highly stereocontrolled
total synthesis of (^)-pseudoclovene-B (3) and our basic
strategy for the desired synthesis from an easily accessible
indane derivative has been shown in Scheme 1. The bromo-
phenol 5, easily prepared from 2,5-dimethyl-7-methoxy-
indan-1-one (4), was smoothly converted into the bridged
alcohol 11 in high overall yield. Treatment of 11 with
PBr furnished the bromoether 12. The spectral character-
3
1
istics of the compounds 10±12 as revealed through their H
1
and C NMR spectra were fully in accord with their struc-
3
tures. Demethylation of 12 with BBr in CH Cl afforded the
2
3
2
desired bromophenol 5 in excellent yield.
Keywords: terpenes; cyclisation; hydrogenation; conjugate addition;
Shapiro reaction.
Corresponding author. Fax: 191-33-4732805;
e-mail: ocdm@mahendra.iacs.res.in
In order to effect an aryl participated intramolecular
cyclisation of the bromophenol 5, a dilute solution of 5
in dry t-BuOH was heated with t-BuOK (1 equiv.) at 808C
1
8
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00618-X

6180
M. Ghosal et al. / Tetrahedron 58 (2002) 6179±6184
Scheme 1.
Figure 1.
Scheme 2. Reagents and conditions: (i) NaCl±AlCl
3
melt, 180±1908C, 5 min, 60%; (ii) MeI, K
, NH Cl, 85%; (v) PBr
, 10% Pd±C, EtOH, 96.5% (6!13) and 90% (15!7); (ix) Br
O, 08C, 2 h, 83.5% (6!15) and 87% (14!7); (xi) NH NHSO Me, MeOH, HCl (trace), re¯ux, 2 h then
2
CO
, benzene, 708C, 4 h, 75%; (vi) BBr
, AcOH, 158C then LiBr, Li
3
, Me
2
CO, re¯ux, 10 h, 90%; (iii) CH
2
vCHCO
Cl , 08C to rt,
CO
2
Me,
NaOMe, MeOH, re¯ux, 6 h, 76%; (iv) LiAlH
4
, Et
2
O, re¯ux, 4 h then Li, liq. NH
3
4
3
3
, CH
2
2
18 h, 88%; (vii) t-BuOK, t-BuOH, 808C, 10 h, 78%; (viii) H
2
2
2
3
,
DMF, 120±1258C, 6 h, 75%; (x) LiMe
2
Cu, Et
2
2
2 6 4
C H
2
MeLi, Et O, 208C, 8 h, 73%.

M. Ghosal et al. / Tetrahedron 58 (2002) 6179±6184
6181
for 10 h. The dienone 6 was isolated as the only neutral
C
All solvent extracts were dried over anhydrous Na SO .
2 4
1
product of the reaction in 78% yield. The IR, H and
13
Product purities were routinely checked by TLC. Ether
refers to diethyl ether and light petroleum refers to the frac-
tion of petroleum ether in the boiling point range 40±608C.
NMR spectra of the dienone were in full accord with struc-
ture 6. Catalytic hydrogenation of the dienone 6 proceeded
stereoselectively with rapid uptake of two moles of hydro-
gen to furnish the A/B cis-fused ketone 13 as the sole
product in near quantitative yield. The construction of the
basic tricarbocyclic framework of pseudoclovene-B 3 was
thus accomplished in a stereocontrolled manner. cis-Stereo-
chemistry has been assigned to 13 since catalytic hydro-
2.1.1. m-Cresyl methacrylate (8). A solution of m-cresol
(10.8 g, 0.1 mol) in dry benzene (10 mL) was added drop-
wise with shaking to methacryloyl chloride (10.7 g,
0.102 mol) in benzene (20 mL) at 58C. The mixture was
re¯uxed for 6 h, cooled, diluted with water (25 mL), and
extracted with ether (3£30 mL). The organic extract was
washed successively with water (25 mL), cold 5% aqueous
KOH (2£20 mL) and water (2£25 mL), and dried. Evapora-
tion of the solvent followed by distillation of the residue at
98±1008C/10 mm Hg furnished the unsaturated ester
(14.8 g, 84%) as a colourless oil; (Found: C, 74.75; H,
5
,19±21
genation of closely related systems had generated
exclusively cis-stereochemistry at 6/5 ring junctures. The
assignment of cis-stereochemistry to 13 was con®rmed by
subsequent transformation of 13 into pseudoclovene-B
possessing cis-stereochemistry at the A/B ring junction.
Bromination of the ketone 13 in glacial AcOH and subse-
quent dehydrobromination of the resulting a-bromoketone
with LiBr and Li CO in DMF furnished the enone 14 in
6.98. C H O requires C, 74.98; H, 6.86%); n (®lm)
max
1
1
12
2
2
1738, 1637, 1614, 1589 cm ; d (300 MHz, CDCl ) 7.23
1
2
3
H
3
7
0
5% overall yield. Conjugate addition of LiMe Cu to 14 at
2
8C provided the saturated ketone 7 as a crystalline
(1H, t, Jˆ7.7 Hz, ArH), 7.00 (1H, d, Jˆ7.7 Hz, ArH), 6.92
(1H, s, ArH), 6.90 (1H, d, Jˆ7.7 Hz, ArH), 6.31 (1H, bs,
vinyl proton), 5.70 (1H, bs, vinyl proton), 2.33 (3H, s,
ArMe), 2.03 (3H, s, vCMe); d (75 MHz, CDCl ) 165.7,
compound in high yield. The saturated ketone 7 was also
prepared by an alternative route. Conjugate addition of
2
2
C
3
LiMe Cu to the dienone 6 at 08C was highly regioselective
2
150.7, 139.3, 135.8, 128.9, 126.8, 126.3, 122.0, 118.4, 21.1,
18.2.
providing the enone 15 in 87% yield. The spectral and
analytical data of the compound 15 agree with the assigned
structure. Catalytic hydrogenation of 15 yielded the satu-
rated ketone 7 as the sole product.
2.1.2. 2,5-Dimethyl-7-hydroxyindan-1-one (9). An
intimate mixture of anhydrous AlCl3 (25 g) and NaCl
(5 g) was stirred over a free ¯ame until molten. The ester
In order to complete the desired synthesis of pseudoclovene-
B (3), the last stepto be carried out was the introduction of
the required double bond in ring A and a Shapiro reaction
proved successful. The tosylhydrazone derivative of 7 was
8 (5 g) was added to this melt at 1408C with stirring. The
temperature was rapidly raised to 1808C and maintained at
180±1908C for 5 min. After cooling, the reaction mixture
was decomposed with cold dil. HCl (6N, 150 mL) and the
product was isolated by steam distillation. The steam
volatile part was extracted with ether (3£30 mL). The
ether extract was washed with water (2£20 mL), dried and
concentrated. The residue was evaporatively distilled at
136±1388C/1 mm Hg to afford the indanone 9 (3 g, 60%)
as a colourless oil; (Found: C, 75.15; H, 7.08. C H O
2
2
3
treated with MeLi (2.5 equiv.) in Et O at room tempera-
2
ture for 8 h. Chromatography of the crude product over
neutral alumina and elution with hexane afforded the tri-
cyclic hydrocarbon 3 in 73% yield from 7. The identity of
1
13
the present compound was secured through H, C NMR,
IR and microanalytical data. The spectral data of 3 also
agreed very well with those reported in the literature.
1
1
12
requires C, 74.98; H, 6.86%); n
1
(®lm) 3337, 1672,
626, 1597 cm ; d (300 MHz, CDCl ) 8.91 (1H, s,
max
2
1
H 3
In conclusion, in the present work a stereocontrolled total
synthesis of the bridged tricyclic sesquiterpene (^)-pseudo-
clovene-B has been successfully accomplished involving an
aryl participated intramolecular cyclisation of an
appropriate indane derivative as a key step.
ArOH), 6.70 (1H, s, ArH), 6.54 (1H, s, ArH), 3.32±3.24
(1H, m), 2.76±2.58 (2H, m), 2.35 (3H, s, ArMe), 1.31
(3H, d, Jˆ6.5 Hz, CHMe); dC (75 MHz, CDCl ) 211.4,
3
157.1, 153.6, 149.3, 119.6, 118.0, 113.9, 41.8, 34.7, 22.2,
16.0.
2
.1.3. 2,5-Dimethyl-7-methoxyindan-1-one (4). A mixture
of the hydroxy-indanone 9 (5 g, 28.4 mmol), dry acetone
30 mL), anhydrous K CO (4 g) and MeI (10 g,
2
. Experimental
(
2
3
2
.1. General
70.5 mmol) was re¯uxed with stirring under nitrogen for
0 h. It was then cooled, diluted with water (30 mL), and
1
The compounds described and having asymmetric centres
are all racemates. Melting points and boiling points are
uncorrected. IR spectra were recorded on Perkin±Elmer
extracted with ether (3£30 mL). The ether extract was
washed with cold 5% aqueous KOH (15 mL) and water
(2£20 mL), dried, and concentrated. Evaporative distilla-
tion of the crude product at 140±1428C/2 mm Hg furnished
the indanone 4 as a colourless oil (4.86 g, 90%); (Found: C,
model PE 2918 and Shimadzu FTIR-8300 spectro-
13
photometers.
H
75 MHz) spectra were recorded in CDCl on a Bruker
NMR (300 MHz) and
C NMR
(
DPX-300 spectrometer with SiMe as internal standard.
75.65; H, 7.23. C12
(®lm) 1699, 1608, 1587 cm ; d (300 MHz, CDCl ) 6.79
H 3
H O requires C, 75.76; H, 7.42%); nmax
14 2
1
3
2
4
The chemical shifts (d ppm) are reported relative to
SiMe (dH 0.00) for H and the central line of residual
CHCl3 (dC 77.0) for C. Moisture sensitive reactions
were carried out using standard syringe±septum technique.
Anhydrous solvents were obtained by standard procedures.
(1H, s, ArH), 6.58 (1H, s, ArH), 3.93 (3H, s, ArOMe), 3.32±
3.23 (1H, m), 2.70±2.57 (2H, m), 2.41 (3H, s, ArMe), 1.27
1
4
1
3
(3H, d, Jˆ7 Hz, CHMe); d
(75 MHz, CDCl ) 206.7, 157.9,
C 3
156.4, 147.9, 122.1, 118.9, 109.9, 55.5, 42.2, 34.5, 22.3,
16.8.

6182
M. Ghosal et al. / Tetrahedron 58 (2002) 6179±6184
2
.1.4. 2,5-Dimethyl-2-(2-methoxycarbonylethyl)-7-meth-
oxyindan-1-one (10). A solution of the indanone 4 (4.4 g,
3 mmol) in MeOH (10 mL) was added with stirring under
nitrogen to a solution of NaOMe (prepared from Na (0.24 g,
the bromide 12 (3.12 g, 75%) as a colourless oil; (Found: C,
60.74; H, 7.35. C H BrO requires C, 60.61; H, 7.12%);
1
5
21
2
1
2
nmax (®lm) 1614, 1591, 1493, 1462, 1315 cm
(300 MHz, CDCl ) 6.61 (1H, s, ArH), 6.48 (1H, s, ArH),
dH
3
1
4
0.4 g-at.)) in MeOH (25 mL). Methyl acrylate (4 g,
6.5 mmol) was then added dropwise at room temperature
3.79 (3H, s. ArOMe), 3.39 (2H, t, Jˆ6.8 Hz, CH Br), 2.79±
2
2.58 (4H, m, 2£ArCH ), 2.32 (3H, s, ArMe), 1.94±1.84 (2H,
2
and the resulting mixture was re¯uxed for 6 h. It was then
cooled, diluted with water (40 mL), and extracted repeat-
edly with ether (3£60 mL). The combined ether extract was
washed with water (2£30 mL), dried and concentrated. The
residue was distilled at 164±1668C/0.5 mm Hg to afford the
keto-ester 10 (4.86 g, 76%) as a colourless oil; (Found: C,
m), 1.63±1.56 (2H, m), 1.09 (3H, s, Me); dC (75 MHz,
CDCl ) 155.9, 144.7, 137.6, 127.1, 117.8, 108.9, 55.1,
46.5, 42.6, 42.3, 40.8, 34.5, 29.1, 26.6, 21.6.
3
2.1.7. 2-(3-Bromopropyl)-2,6-dimethyl-4-hydroxyindane
(5). To a stirred solution of 12 (3 g, 10.1 mmol) in CH Cl
2
2
6
(
9.80; H, 7.39. C H O requires C, 69.55; H, 7.30%); n
max
(15 mL) at 08C was added dropwise BBr3 (2.6 g,
10.38 mmol) in CH Cl (5 mL). The mixture was stirred
1
6
20
4
2
1
®lm) 1736, 1699, 1607, 1587 cm ; d (300 MHz, CDCl )
H
3
2
2
6
.78 (1H, s, ArH), 6.59 (1H, s, ArH), 3.92 (3H, s, ArOMe),
.63 (3H, s, CO Me), 2.95, 2.81 (2H, 2£d, Jˆ17.3 Hz,
at 08C for 2 h and at room temperature for 16 h. It was
then poured into ice and extracted with CH Cl
2
3
ArCH ), 2.41 (3H, s, ArMe), 2.31±2.24 (2H, m), 1.97±
2
2
(2£20 mL). The organic extract was washed with saturated
2
1.88 (2H, m), 1.20 (3H, s, Me); dC (75 MHz, CDCl3)
207.0, 173.7, 158.2, 154.9, 148.2, 121.9, 118.9, 110.1,
55.5, 51.4, 48.3, 39.8, 33.1, 29.5, 23.8, 22.3.
aqueous NaHCO (15 mL), water (2£15 mL), and dried.
3
Evaporation of the solvent followed by chromatography of
the residue on a silica gel column (70 g) using ether±light
petroleum (1:19) as eluent furnished the bromophenol 5
(2.52 g, 88%) as a colourless oil which solidi®ed on stand-
ing to furnish colourless crystals, mp50±51 8C; (Found: C,
59.20; H, 6.89. C H BrO requires C, 59.37; H, 6.76%);
2
.1.5.
2,6-Dimethyl-2-(3-hydroxypropyl)-4-methoxy-
indane (11). A solution of the keto-ester 10 (4.7 g,
7 mmol) in dry ether (25 mL) was added dropwise at
room temperature to a stirred suspension of LiAlH (1.2 g,
1
1
4
19
2
1
nmax (®lm) 3393, 1626, 1591 cm ; d (300 MHz, CDCl )
3
4
H
3
1.6 mmol) in ether (50 mL). After the addition, the mixture
6.59 (1H, s, ArH), 6.43 (1H, s, ArH), 4.75 (1H, bs, ArOH),
3.39 (2H, t, Jˆ6.8 Hz, CH Br), 2.80±2.55 (4H, m,
was stirred and re¯uxed for 4 h and then cooled. Excess of
hydride was carefully destroyed by addition of saturated
aqueous Na SO and the mixture was ®ltered through celite.
2
2£ArCH ), 2.26 (3H, s, ArMe), 1.94±1.84 (2H, m), 1.63±
2
1.58 (2H, m), 1.09 (3H, s, Me); d (75 MHz, CDCl ) 151.7,
C
2
4
3
The residue was washed thoroughly with ether (3£25 mL).
145.2, 137.9, 124.8, 118.0, 113.5, 46.4, 43.0, 41.6, 40.7,
34.5, 29.1, 26.5, 21.2.
The combined ®ltrate was washed with brine (30 mL), dried
and concentrated. The crude product (4.13 g, n
(®lm)
400±3300 cm ) was dissolved in dry ether (30 mL) and
max
2
1
1,6
2.1.8. 4,8-Dimethyltricyclo[6.3.1.0 ]dodeca-3,5-dien-2-
3
added under nitrogen to distilled liquid ammonia (200 mL).
To this mixture was added Li metal (0.9 g, 130 g-at.) with
stirring during 5 min. After stirring for another 15 min, an
one (6). To a stirred solution of t-BuOK (prepared from K
(0.34 g, 8.72 g-at.)) in t-BuOH (650 mL) at 808C was added
dropwise under nitrogen a solution of the bromophenol 5
(2.4 g, 8.47 mmol) in t-BuOH (10 mL). The mixture was
stirred at 808C for 10 h and then ca. 500 mL of t-BuOH
was removed under reduced pressure. The residue was
diluted with water (150 mL) and extracted repeatedly with
ether (3£150 mL). The combined ether extract was washed
with water (2£80 mL), dried and concentrated. The residue
was evaporatively distilled at 114±1168C/0.5 mm Hg to
afford the dienone 6 as a colourless oil (1.34 g, 78%);
excess of NH Cl was added and ammonia was allowed to
4
evaporate. The residue was diluted with water (30 mL) and
extracted with ether (3£50 mL). The ether extract was
washed with water (2£25 mL), dried and concentrated.
The residue was distilled to afford the alcohol 11 (3.4 g,
8
5%) as a colourless oil, bp(bath tem ep rature) 130±
1
requires C, 76.88; H, 9.46%); n
328C/0.5 mm Hg; (Found: C, 76.64; H, 9.55. C H O
2
1
5
22
(®lm) 3364, 1614,
591 cm ; d (300 MHz, CDCl ) 6.61 (1H, s, ArH), 6.47
max
2
1
1
(Found: C, 83.03; H, 8.79. C H O requires C, 83.12; H,
14 18
H
3
2
8.97%); nmax (®lm) 1666, 1647 cm ; d (300 MHz,
1
(
1H, s, ArH), 3.79 (3H, s, ArOMe), 3.61 (2H, t, Jˆ6 Hz,
H
CH OH), 2.76, 2.61 (2H, 2£d, Jˆ15.5 Hz, ArCH ), 2.68,
CDCl ) 5.83 (1H, bs, vinyl proton), 5.65 (1H, bs, vinyl
3
2
2
2
1
1
1
3
.61 (2H, 2£d, Jˆ15.6 Hz, ArCH ), 2.31 (3H, s, ArMe),
proton), 2.50, 2.21 (2H, 2£d, Jˆ18.6 Hz, vCCH ), 2.02
2
2
.78 (1H, bs, OH), 1.63±1.47 (4H, m, CH CH CH OH),
2
(3H, d, Jˆ0.9 Hz, vinyl methyl), 1.83±1.45 (8H, m), 1.10
2
2
.08 (3H, s, Me); dC (75 MHz, CDCl ) 155.8, 144.9,
3
37.5, 127.2, 117.8, 108.8, 63.6, 55.0, 46.4, 42.7, 42.3,
8.1, 28.7, 26.5, 21.6.
(3H, s, Me); dC (75 MHz, CDCl ) 206.7, 163.3, 154.6,
3
120.1, 117.2, 60.2, 44.9, 43.0, 38.4, 37.5, 37.2, 27.0, 22.7,
21.7.
2
.1.6.
2-(3-Bromopropyl)-2,6-dimethyl-4-methoxy-
2.1.9.
(1SR,4RS,6RS,8RS)-4,8-Dimethyltricyclo-
1
,6
indane (12). Phosphorous tribromide (2 g, 7.4 mmol) in
benzene (3 mL) was added dropwise at 08C to a stirred
solution of 11 (3.28 g, 14 mmol) in benzene (15 mL). The
mixture was stirred at 708C for 4 h, cooled, and poured into
crushed ice. The product was extracted with benzene
[6.3.1.0 ]dodecan-2-one (13). A solution of the dienone
6 (0.65 g, 3.2 mmol) in EtOH (10 mL) was hydrogenated
over Pd±C (10%, 0.3 g) at room temperature and
atmospheric pressure. Uptake of hydrogen (170 mL) ceased
after 15 min. The mixture was ®ltered from the catalyst.
Evaporation of the solvent furnished the saturated ketone
13 (0.64 g, 96.5%) as a colourless oil, bp(bath temperature)
108±1108C/0.6 mm Hg; (Found: C, 81.57; H, 10.55.
(
3£20 mL). The organic extract was washed with saturated
aqueous NaHCO (15 mL), water (2£20 mL), and dried.
3
The residue remaining upon removal of the solvent was
evaporatively distilled at 130±1328C/0.5 mm Hg to afford
C H O requires C, 81.50; H, 10.75%); n
1
(®lm)
max
4
22

M. Ghosal et al. / Tetrahedron 58 (2002) 6179±6184
6183
2
700 cm ; d (300 MHz, CDCl ) 2.36±1.10 (16H, m),
1
1
15 min and diluted with water (10 mL). The product was
extracted with ether (3£20 mL). The ether extract was
washed with water (2£15 mL), dried, and concentrated.
The solid residue was crystallised from light petroleum to
furnish the ketone 7 (0.28 g, 87%) as colourless needles, mp
57±588C; (Found: C, 81.68; H, 11.20. C H O requires C,
H
3
1
.03 (3H, s, Me), 0.96 (3H, d, Jˆ6.5 Hz, CHMe); d
C
(
4
75 MHz, CDCl ) 216.1, 55.5, 47.7, 46.9, 45.5, 44.4, 42.5,
3
0.3, 38.8, 33.0, 31.4, 27.4, 22.1, 19.6.
1
,6
.1.10. (1SR,6SR,8RS)-4,8-Dimethyltricyclo[6.3.1.0 ]-
2
dodec-3-en-2-one (14). A solution of bromine (0.4 g,
1
5
2
24
1
81.76; H, 10.98%); nmax (CHCl ) 1700 cm ; d (300 MHz,
3 H
2
1
2
.5 mmol) in AcOH (2 mL) was added dropwise during
0 min to a stirred solution of the ketone 13 (0.5 g,
.4 mmol) in AcOH (12 mL) at 158C, allowing each drop
CDCl ) 2.30±1.10 (15H, m), 1.03 (3H, s, Me), 0.98 (3H, s,
3
Me), 0.82 (3H, s, Me); dC (75 MHz, CDCl ) 216.4, 55.2,
3
51.7, 47.8, 47.0, 45.5, 41.8, 40.8, 38.9, 34.9, 32.6, 31.4,
27.5, 25.1, 19.7.
of bromine to decolourise before more was added. After the
addition, the mixture was stirred at room temperature for
2
h, diluted with water (20 mL) and extracted with CHCl3
(b) A solution of the enone 15 (0.35 g, 1.6 mmol) in EtOH
(10 mL) was hydrogenated over Pd±C (10%, 0.2 g) at room
temperature and atmospheric pressure. Uptake of hydrogen
(45 mL) ceased after 30 min. The mixture was ®ltered from
the catalyst. Evaporation of the solvent followed by crystal-
lisation of the residue from light petroleum furnished the
ketone 7 (0.32 g, 90%), mp57±58 8C. H and C NMR
spectra of 7, prepared by the methods (a) and (b), were
identical.
(
3£25 mL). The organic extract was washed with saturated
aqueous NaHCO (15 mL), water (2£15 mL), and dried.
3
Evaporation of the solvent furnished the crude bromoketone
(0.67 g) as a gummy material which was dissolved in dry
DMF (10 mL). LiBr (0.4 g, 4.6 mmol) and Li CO (0.3 g,
2
3
1
13
4
1
mmol) were added and the mixture was stirred at 120±
258C for 6 h under nitrogen. The reaction mixture was
cooled, poured into dil. HCl (2N, 10 mL) and extracted
with ether (3£25 mL). The ether extract was washed with
aqueous NaHCO (15 mL), water (2£15 mL), and dried.
2.1.13. (^)-Pseudoclovene-B (3). To a solution of the
ketone 7 (0.4 g, 1.81 mmol) in EtOH (4 mL) were added
p-toluenesulfonhydrazide (0.35 g, 1.88 mmol) and conc.
HCl (one drop) and the mixture was re¯uxed for 2 h. It
was then cooled in an ice-bath and the crystalline tosyl-
hydrazone derivative was collected by suction ®ltration
and dried, mp167±168 8C (700 mg). To a stirred suspension
of this material in anhydrous ether (10 mL) at 208C was
added under nitrogen MeLi (1.6 M in ether, 2.5 mL,
4 mmol) during 10 min and the mixture was stirred at
room temperature for 8 h. It was then diluted with water
3
Evaporation of the solvent and puri®cation of the product
on a silica gel column using ether±light petroleum (1:24) as
eluent furnished the enone 14 (0.37 g, 75%) as a colourless
oil, bp(bath tem pe rature) 108±110 8C/0.4 mm Hg; (Found:
C, 82.49; H, 9.78. C H O requires C, 82.30; H, 9.87%);
1
4
20
2
1
nmax (®lm) 1655 cm ; d (300 MHz, CDCl ) 5.84 (1H, bs,
H
COCHvC), 2.39±1.09 (13H, m), 1.91 (3H, s, vinyl
methyl), 1.03 (3H, s, Me); dC (75 MHz, CDCl ) 203.0,
3
3
1
2
59.7, 125.8, 52.7, 45.5, 45.0, 40.5, 40.0, 38.7, 38.2, 34.6,
7.5, 24.1, 19.8.
(
10 mL) and extracted with ether (3£20 mL). The ether
1
.1.11. 4,4,8-Trimethyltricyclo[6.3.1.0 ]dodec-5-en-2-
,6
2
one (15). A solution of LiMe Cu was prepared under
argon by dropwise addition of MeLi (1.6 M in ether,
6
4
extract was washed with water (2£15 mL), dried and
concentrated. The residue was chromatographed on neutral
alumina (15 g). Elution with hexane afforded (^)-pseudo-
clovene-B (3) (270 mg, 73%) as a colourless oil, bp(bath
temperature) 95±978C/3 mm Hg; (Found: C, 88.02; H,
2
.2 mL, 9.92 mmol) to a stirred suspension of CuI (0.95 g,
.99 mmol) in anhydrous ether (15 mL) at 08C. A solution
of the dienone 6 (0.5 g, 2.47 mmol) in ether (15 mL) was
then added over a period of 10 min and the resultant mixture
was stirred at 08C for 2 h. It was then treated with saturated
12.08. C15
3010, 1456, 1373, 1360, 750 cm ; d
5.35 (2H, s, vinyl protons), 1.91±1.00 (13H, m), 0.96 (3H, s,
H24 requires C, 88.16; H, 11.84%); nmax (®lm)
2
1
(300 MHz, CDCl )
3
H
aqueous NH Cl (16 mL), stirred for 20 min, diluted with
4
Me), 0.95 (3H, s, Me), 0.91 (3H, s, Me); d
CDCl
38.7, 38.0, 32.6, 31.1, 28.0, 27.7, 20.6. (Lit.,
ca. 1640 vw, 1375, 1360, and 750 cm ; t 4.66 (2H, s), 9.03
(6H) and 9.08 (3H)).
C
(75 MHz,
water (15 mL) and extracted with ether (3£25 mL). The
ether extract was washed with water (2£15 mL), dried and
concentrated. The residue was evaporatively distilled at
) 135.4, 132.7, 49.6, 45.6, 45.3, 44.8, 40.0, 38.9,
3
1
4
n
max 3010,
2
1
1
8
8
08±1108C/0.4 mm Hg to afford the enone 15 (0.45 g,
3.5%); (Found: C, 82.32; H, 10.18. C H O requires C,
1
5
22
2
2.52; H, 10.16%); nmax (®lm) 1711 cm ; d (300 MHz,
1
H
CDCl ) 5.29 (1H, bs, CHvC), 2.64, 2.09 (2H, 2£d,
Acknowledgements
3
Jˆ14.2 Hz), 2.27, 2.04 (2H, 2£d, Jˆ16.9 Hz), 1.78±1.59
(
4H, m), 1.52±1.34 (4H, m), 1.13 (3H, s, Me), 1.03 (3H,
s, Me), 0.99 (3H, s, Me); d (75 MHz, CDCl ) 214.6, 141.9,
We are grateful to the CSIR, New Delhi, for ®nancial
support (Grant No. 01(1742)/02/EMR-II). One of us
(L. C. P.) thanks the CSIR for fellowship.
C
3
1
3
28.6, 56.8, 50.0, 46.4, 41.8, 39.1, 38.9, 37.5, 37.2, 30.8,
0.6, 27.0, 20.4.
2
.1.12. 1
6.3.1.0 ]dodecan-2-one (7). (a) To a stirred solution of
(1SR,6RS,8RS)-4,4,8-Trimethyltricyclo-
References
,6
[
LiMe Cu (2.94 mmol) in dry ether (15 mL) at 08C was
added under argon, over a period of 10 min, a solution of
the enone 14 (0.3 g, 1.47 mmol) in ether (10 mL) and the
resultant mixture was stirred at 08C for 2 h. It was then
2
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