Chiral synthons from carvone. Part 50. Enantiospecific approaches to both enantiomers of bicyclo[4.3.0]nonane-3,8-dione derivatives

Article abstract of DOI:10.1039/b104253j

Enantiospecific synthesis of both enantiomeric forms of bicyclo[4.3.0]nonane-3,8-dione derivatives has been described starting from (R)-carvone employing two different cyclopentannulation methodologies. Thus, in the first methodology, carveol (5) was converted into tricyclic ketone 4 employing a Claisen rearrangement and intramolecular diazo ketone cyclopropanation reactions. Degradation of the isopropenyl group followed by cyclopropane cleavage and cuprate addition generated the dione (-)-12a. Whereas, a Wacker mediated cyclopentannulation of (R)-carvone via the dione 15 furnished the, enone 17. Functional group manipulation including the degradation of isopropenyl group transformed the enone 17 into the dione (+)-12a, which on regioselective ketalisation generated the ketoketal (+)-2.

Full text of DOI:10.1039/b104253j

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Chiral synthons from carvone. Part 50.† Enantiospecific
approaches to both enantiomers of bicyclo[4.3.0]nonane-3,8-dione
derivatives
1
A. Srikrishna* and T. Jagadeeswar Reddy
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
E-mail: ask@orgchem.iisc.ernet.in; Fax: 91-80-3600683
Received (in Cambridge, UK) 15th May 2001, Accepted 2nd July 2001
First published as an Advance Article on the web 7th August 2001
Enantiospecific synthesis of both enantiomeric forms of bicyclo[4.3.0]nonane-3,8-dione derivatives has been
described starting from (R)-carvone employing two different cyclopentannulation methodologies. Thus, in the
first methodology, carveol (5) was converted into tricyclic ketone 4 employing a Claisen rearrangement and
intramolecular diazo ketone cyclopropanation reactions. Degradation of the isopropenyl group followed
by cyclopropane cleavage and cuprate addition generated the dione (Ϫ)-12a. Whereas, a Wacker mediated
cyclopentannulation of (R)-carvone via the dione 15 furnished the enone 17. Functional group manipulation
including the degradation of isopropenyl group transformed the enone 17 into the dione (ϩ)-12a, which on
regioselective ketalisation generated the ketoketal (ϩ)-2.
The creativity of Nature in devising varied molecular archi-
tectures is revealed through the isolation of a wide range of
natural products with remarkable skeletal build-up and multi-
farious functionality.1 Development of methodologies for the
total synthesis of natural products with diverse architecture and
varying degrees of complexity is an area that has inspired and
attracted several generations of organic chemists.2 Particularly
in the last three decades, dramatic advances were made in the
development of new synthetic methodologies with high regio-,
stereo- and enantiocontrol. Monoterpenes are being widely
used as chiral auxiliaries but their potential as chiral synthons
has not been properly exploited.3 The overwhelming emphasis
on carbohydrates as chirons4 in natural product synthesis has
somewhat marginalised the importance of the abundantly
available monoterpenes as chiral building blocks for the syn-
thesis of natural products in their optically active form. This
has come about despite the fact that monoterpenes are cheap,
readily available (in several cases, in both enantiomeric forms
unlike carbohydrates and amino acids) and are endowed with
only one or two chiral centres with modest functionality, which
means that it does not require recourse to wasteful manoeuvres
to dispense with excess chirality or functionality as in carbo-
hydrate based approaches. More interestingly, terpenes can
be readily restructured into cyclic and acyclic fragments that
can be directly incorporated into carbocyclic frameworks of
complex target molecules.
functionalised decalin systems5 and their conversion to a
variety of natural products. We have employed (R)-carvone as the
chiral starting material for the synthesis of a variety of bridged
systems and sesquiterpenoids.6,7 In continuation of our interest
in the development of enantiospecific methodologies for the
generation of both enantiomers of a particular carbon frame-
work, starting from a single enantiomer of carvone,6c,e,7 herein
we describe details of our investigation on the synthesis of both
enantiomers of the bicyclo[4.3.0]nonane based ketoketal 2
employing two different cyclopentannulation methodologies.8
Functionalised bicyclo[4.3.0]nonanes (hydrindane systems),
in particular with a substituent at one of the ring junction posi-
tions, or as part structures are present in many biologically
important natural products, e.g. picrotoxinin, bakkenolides,
homogynolides, palmosalide, zizaenes, neopupukenanes, etc.
Our interest in the synthesis of sesquiterpene natural products
containing a hydrindane framework led us to investigate new
approaches for the construction of bicyclo[4.3.0]nonanes
in optically active form. The readily available monoterpene
carvone (1) is an excellent chiral starting material in the
synthesis of natural products.3 (S)-Carvone has been exploited
by de Groot and coworkers for the construction of several
The isopropenyl group in carvone 1 was readily recognised
as a masked hydroxy group. To begin with, for the enantio-
specific synthesis of the (Ϫ)-ketoketal 2 an orthoester Claisen
rearrangement–intramolecular diazo ketone cyclopropanation
based approach was chosen starting from (R)-carvone 1. The
retrosynthetic pathway for the (Ϫ)-ketoketal 2 is depicted in
Scheme 1. It was anticipated that conjugate addition of a methyl
group followed by regio-selective ketalisation could transform
the enedione 3 into the ketoketal 2, and degradation of the
isopropenyl group followed by acid catalysed ring opening of
cyclopropane could transform the tricyclic ketone 4 into the
† For parts 49 and 48, see: references 6a and 6b, respectively.
2040
J. Chem. Soc., Perkin Trans. 1, 2001, 2040–2046
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104253j

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Lithium aluminium hydride (LAH) reduction of (R)-carvone
(1) in ether at Ϫ90 ЊC furnished carveol (5), the precursor for
the projected Claisen rearrangement, in quantitative yield with
a very high degree of stereoselectivity. The syn relationship
between the hydroxy and isopropenyl groups in carveol was well
established.9 An orthoester variant of the Claisen rearrange-
ment, developed10 by Johnson et al. was used for the stereo-
specific introduction of the acetate side chain. Thus, thermal
activation (180 ЊC) of a solution of carveol (5), triethyl ortho-
acetate and a catalytic amount of mercuric acetate in a sealed
tube furnished the γ,δ-unsaturated ester 6 in 70% yield, whose
structure was established from its spectral data. The stereo-
chemistry of the ester side chain was assigned based on the
well-established stereospecificity of the Claisen rearrangement.
The ester 6 was transformed into the tricyclic ketone 4 via an
intramolecular diazo ketone cyclopropanation11 strategy. Thus,
hydrolysis of the ester 6 using 15% aqueous sodium hydroxide
and methanol furnished the acid 7. Treatment of the acid 7 with
oxalyl chloride in benzene furnished the acid chloride, which on
addition to an excess of ethereal diazomethane furnished the
diazo ketone 8. Anhydrous copper sulfate catalyzed decom-
position of the diazo ketone 8 in refluxing cyclohexane
using a tungsten lamp led to the intramolecular insertion of
the intermediate ketocarbenoid into the ring olefin in a regio-
and stereospecific manner, resulting in the formation of the
cyclopropyl ketone 4 in 50% yield (from the acid 7). The cis
stereochemistry of the ring junction was a consequence of the
insertion of the intermediate ketocarbenoid from the preferred
syn face of the olefin.
With the successful synthesis of the cyclopropyl ketone 4,
attention was turned towards the degradation of the iso-
propenyl side chain into oxygen functionality, Scheme 3. Since
Scheme 1
enedione 3. A stereospecific Claisen rearrangement and intra-
molecular diazo ketone cyclopropanation could be exploited
for the conversion of carveol (5) into the tricyclic ketone 4.
Synthesis of the tricyclic ketone 4 is depicted in Scheme 2.
Scheme 3 (a) HCl; (b) DBU; (c) O3, Me2S; (d) pTSA.
a one-pot conversion of isopropenyl group into an acetoxy
group employing a Criegee rearrangement12 was found to be
inefficient, an alternative route was envisaged. Isomerisation of
the isopropenyl to the isopropylidene group by an addition–
elimination sequence and oxidative cleavage to generate the
ketone functionality was contemplated. Thus, treatment of
the cyclopropyl ketone 4 with an excess of freshly prepared
saturated solution of hydrogen chloride gas in ether gener-
ated the dichloride 9 via addition of hydrogen chloride to both
olefinic and cyclopropane moieties. Reaction of the dichloride
9 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in benzene
at 160 ЊC in a sealed tube led to double dehydrochlorination
to furnish the cyclopropyl ketone 10. Ozonolysis of the tri-
cyclic ketone 10 in methanol–methylene chloride followed
Scheme 2 (a) LAH; (b) MeC(OEt)3, Hg(OAc)2, ∆; (c) NaOH; (d)
(COCl)2, CH2N2; (e) CuSO4.
J. Chem. Soc., Perkin Trans. 1, 2001, 2040–2046
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by reductive work up of the ozonide with dimethyl sulfide
furnished the dione 11, which was found to undergo partial
isomerisation to enedione 3 on a silica gel column. Treatment
of the dione 11 with a catalytic amount of toluene-p-sulfonic
acid (pTSA) in methylene chloride brought about the complete
isomerisation via the cleavage of the cyclopropane ring
furnishing the enedione 3, whose structure rests secured from
its spectral data.
ation of the intermediate enolate was chosen. Thus, addition of
lithium dimethylcopper to (R)-carvone 1 followed by quenching
of the resultant enolate with allyl bromide in the presence of
HMPT provided a 9 : 1 epimeric mixture of the ketone 14. The
stereochemistry of the secondary methyl group in 14 was
assigned based on the preferred addition of the nucleophile
trans to the isopropenyl group, which has enough precedence
in the literature.13 Similarly, stereoselective alkylation of the
intermediate enolate generates the quaternary carbon as both
the secondary methyl at C-3 and the isopropenyl group at C-5
directs the approach of the electrophile trans to the secondary
methyl group. The regiospecificity of the Wacker reaction14 for
the oxidation of monosubstituted olefins was exploited for the
conversion of the allyl into an acetonyl group for the generation
of the 1,4-diketone necessary for cyclopentannulation. Thus,
reaction of the allyl compound 14 with palladium chloride and
cuprous chloride in a mixture of N,N-dimethylformamide and
water in an oxygen atmosphere furnished a 9 : 1 mixture of the
1,4-diketones 15 and 16, which were separated on a silica gel
column. Intramolecular aldol condensation of the major dione
15 using 10% aqueous potassium hydroxide in methanol cleanly
furnished the enone 17, whose structure was established from
its spectral data. The 13C NMR spectrum of the enone 17 exhib-
ited a singlet at δ 207.6 ppm due to the carbonyl carbon, two
olefinic carbon resonances at 187.3 and 127.4 typical for a
β-substituted cyclopentenone moiety,15 two olefinic signals at
Addition of lithium dimethylcopper to the enedione 3,
furnished a 3 : 2 epimeric mixture of hydrindanediones 12a,b
in 71% yield (Scheme 4). The structures of the diones 12a,b
146.0 and 111.7 ppm due to C᎐CH carbons in addition to
aliphatic carbon resonances, confirming the structure of the
enone 17.
᎐
2
Scheme 4
were established from the spectral data. It was anticipated that
protection of the 5-membered ring ketone in enedione 3 as its
cyclic ketal might increase the stereoselectivity in the cuprate
reaction. Accordingly, regioselective protection of the five
membered ketone in the enedione 3 with ethylene glycol in the
presence of a catalytic amount of pTSA using a Dean–Stark
water separator furnished the ketal 13 in 69% yield in a highly
regioselective manner. However, reaction of the ketoketal 13
with lithium dimethylcopper followed by hydrolysis of the ketal
moiety in the product generated a 2 : 1 mixture of the diones
12a,b with only marginal increase in stereoselectivity.
In the second approach, for the generation of enantiomeric
compounds, initial introduction of the secondary methyl
group and construction of a hydrindane by Wacker mediated
cyclopentannulation methodology was envisaged, as depicted
in Scheme 5. For the addition of methyl and allyl groups to
the enone at the β and α positions, respectively, in a trans
manner, a cuprate mediated 1,4-addition followed by allyl-
For further elaboration, regiospecific reduction of the endo
cyclic olefin was addressed first, employing electron transfer
methodology. Thus, regiospecific reduction of the enone 17
with lithium in liquid ammonia in the presence of tert-butanol
(2-methylpropan-2-ol) furnished a ≈2 : 1 mixture of the cis and
trans hydrindanones 18 and 19, which were separated by col-
umn chromatography on silver nitrate impregnated silica gel.
For the conversion of the isopropenyl moiety into ketone func-
tionality, as in the first approach, the three step sequence was
used. Thus, addition of hydrogen bromide followed by DBU
mediated dehydrobromination of the resultant tertiary bromide
20 transformed the hydrindanone 18 into the isomerised com-
pound 21 in near quantitative yield. Ozonolysis of the iso-
propylidene group in 21 followed by reductive work up with
triphenylphosphine furnished the dione 12a in 88% yield,
whose structure was established from its spectral data. Regio-
selective protection of the 6-membered ring ketone with 1.0
equivalent of ethylene glycol and pTSA using a Dean–Stark
Scheme 5 (a) Me2CuLi, CH2CH᎐CH2Br; (b) PdCl2, CuCl, DMF–H2O, O2; (c) KOH; (d) Li, liq. NH3; (e) HBr, (f ) DBU; (g) O3, Me2S;
᎐
(h) (CH2OH)2, pTSA.
2042
J. Chem. Soc., Perkin Trans. 1, 2001, 2040–2046

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water separator in refluxing benzene transformed the dione 12a
into the (ϩ)-ketoketal 2 in 68% yield, whose structure was
established from its spectral data.
In conclusion, employing two different cyclopentannulation
methodologies, (R)-carvone has been transformed, via several
useful chiral synthons, into both enantiomeric forms of
bicyclo[4.3.0]nonane-3,8-dione derivatives, potential precursors
in sesquiterpene synthesis.
(؊)-(1S,2S,4R,6R,9R)-4-Isopropenyl-1-methyltricyclo-
[4.3.0.02,9]nonan-8-one (4)
To a magnetically stirred solution of the acid 7 (3.0 g, 15.46
mmol) in dry benzene (6 ml) was slowly added oxalyl chloride
(3.0 ml, 34.9 mmol) and the reaction mixture was stirred for 2 h
at RT. Evaporation of benzene and excess oxalyl chloride under
reduced pressure furnished the acid chloride, which was taken
in dry ether (10 ml) and added dropwise to a cold magnetically
stirred ethereal solution of diazomethane (250 ml, prepared
from 30 g of N-nitroso-N-methylurea and 260 ml of 60% aq.
KOH solution). The reaction mixture was slowly warmed up to
RT, stirred for 2 h and the excess diazomethane and ether were
carefully evaporated on a water bath. Rapid purification by fil-
tration of the crude product through a silica gel column using
ethyl acetate–hexane (1 : 5) as eluent furnished the diazo ketone
8 (3.0 g) as a yellow oil. νmax (neat) 2080, 1640, 890 cmϪ1. δH (90
MHz, CDCl3) 6.50 (1 H, br s, olefinic H), 6.21 (1 H, s, CHN2),
Experimental
Melting points are recorded using a Tempo melting point
apparatus in capillary tubes and are uncorrected. IR spectra
1
were recorded on a Perkin-Elmer 781 spectrophotometer. H
(90, 200 and 270 MHz) and 13C NMR (22.5, 50 and 100 MHz)
spectra were recorded on JEOL FX-90Q, Bruker ACF-200,
WH-270 and AMX-400 spectrometers. The chemical shifts
(δ ppm) and the coupling constants (Hz) are reported in the
standard fashion with reference to either internal tetra-
4.65 (2 H, s, C᎐CH ), 2.50–2.80 (2 H, m, H-α), 1.80–2.30 (6 H,
᎐
2
m), 1.68 (6 H, s, 2 × olefinic CH3). To a magnetically stirred,
refluxing (by keeping two 100 W tungsten lamps near the flask)
suspension of anhydrous copper sulfate (14 g) in 400 ml dry
cyclohexane was added, dropwise, a solution of the diazo
ketone 8 (3.0 g) in cyclohexane (70 ml) over a period of 2 h and
refluxed for 4 h. The reaction mixture was then cooled and
copper sulfate was filtered off using a sintered funnel. Evapor-
ation of the solvent and purification of the product on a silica
gel column using ethyl acetate–hexane (1 : 20 to 1 : 5) as eluent
furnished the tricyclic ketone 4 (1.46 g, 50% from the acid 7) as
a yellow oil. [α]2D4: Ϫ100.5 (c 1.9, CHCl3). νmax (neat) 1720, 1640,
1
methylsilane (for H) or the central line (77.1 ppm) of CDCl3
(for 13C). In the 13C NMR spectra off-resonance multipli-
cities, when recorded are given in parentheses. Low and high
resolution mass measurements were carried out using a
JEOL JMS-DX 303 GC-MS instrument using a direct inlet
mode. Relative intensities of the ions are given in paren-
theses. Elemental analyses were carried out using a Carlo Erba
1106 CHN analyser. Optical rotations were measured using
a Jasco DIP-370 digital polarimeter and [α]D values are given
in the units of 10Ϫ1 deg cm2 gϪ1. Ozonolysis was carried out
using a Penwalt Wallace and Tierman ozonator. Acme’s silica
gel (100–200 mesh), approximately 15–20 g per 1 g of the crude
product, was used for column chromatography. All small-
scale dry reactions were carried out using a standard syringe-
septum technique. Dry THF was obtained by distillation over
sodium–benzophenone ketyl. HBr in ether was prepared by
bromination of tetralin with bromine according to the Vogel
procedure.
890 cmϪ1. δH (200 MHz, CDCl ) 4.70 (2 H, br s, C᎐CH ), 2.73
᎐
3
2
(1 H, dd, J 19.5 and 12 Hz), 2.50–2.70 (1 H, m), 2.30 (1 H, m),
1.90–2.20 (2 H, m), 1.50–1.80 (3 H, m), 1.68 (3 H, s, olefinic
CH3), 1.35 (3 H, s, tert-CH3), 1.25 (1 H, dd, J 14.2 and 8.8 Hz),
1.04 (1 H, d of t, J 14.2 and 6.6 Hz). δC (100 MHz, CDCl3)
213.2 (s, C᎐O), 148.6 (s, C᎐CH ), 108.6 (t, C᎐CH ), 47.6 (t,
᎐
᎐
᎐
2
2
CH C᎐O), 40.4 (d), 39.3 (d), 32.8 (d), 30.7 (s, C-1), 28.5 (t), 26.8
᎐
2
(t), 20.1 (d), 22.9 (q), 19.8 (q). Mass: m/z 190 (Mϩ, 5%), 162
(10), 147 (20), 133 (25), 107 (60), 93 (60), 79 (100). HRMS:
m/z Calcd. for C13H18O: M, 190.1358. Found: Mϩ, 190.1353.
(؉)-(1R,5R)-5-Isopropenyl-2-methylcyclohex-2-enylacetic acid
(7)
(؉)-(1S,2S,4R,6R)-2-Chloro-4-(2-chloro-2-propyl)-1-methyl-
bicyclo[4.3.0]nonan-8-one (9)
A solution of carveol 5 (4.0 g, 26.3 mmol), triethyl orthoacetate
(25 ml, 136.6 mmol) and mercuric acetate (25 mg) was placed
in a sealed tube and heated to 180 ЊC for 6 days in an oil bath.
The reaction mixture was cooled, diluted with ether (90 ml),
washed with 1 M HCl, saturated aq. NaHCO3 and brine, and
dried (Na2SO4). Evaporation of the solvent and purification of
the product on a silica gel column using ethyl acetate–hexane
(1 : 40) as eluent furnished the ester 6 (4.1 g, 70%): νmax (neat)
1735, 1640, 885 cmϪ1. δH (90 MHz, CDCl3) 5.28 (1 H, m,
A saturated solution of HCl gas in ether (150 ml) was added to
the tricyclic ketone 4 (658 mg, 3.46 mmol) and the reaction
mixture was stirred for 36 h under a closed system at RT. It was
then diluted with ether (20 ml), washed with water, saturated
NaHCO3 solution and brine, and dried (Na2SO4). Evaporation
of the solvent and purification of the residue on a silica gel
column using ethyl acetate–hexane (1 : 10 to 1 : 5) as eluent fur-
nished the dichloride 9 (760 mg, 84%), which was recrystallised
from a mixture of hexane and CH2Cl2. Mp: 93–95 ЊC. [α]2D4:
ϩ173 (c 1.2, CHCl3). νmax (Nujol) 1740 cmϪ1. δH (200 MHz,
CDCl3) 4.39 (1 H, t, J 2.9 Hz, CHCl), 2.63 (1 H, dd, J 18.7 and
7.1 Hz, H-7a), 2.43 (1 H, d, J 17.8 Hz, H-9a), 2.10–2.35 (3 H,
m), 1.85–2.05 (4 H, m), 1.58 (6 H, s, ClC(CH3)2), 1.24 (3 H, d,
J 1 Hz, C1-CH3), 1.03 (1 H, q, J 12 Hz). δC (50 MHz, CDCl3)
H-3), 4.55 (2 H, br s, C᎐CH ), 3.96 (2 H, q, J 7.2 Hz,
᎐
2
OCH2CH3), 1.40–2.70 (8 H, m), 1.66 (3 H, s) and 1.58 (3 H, s)
(2 × olefinic CH3), 1.20 (3 H, t, J 7.2 Hz, OCH2CH3). To
a solution of the ester 6 (4.0 g, 18 mmol) in 20 ml methanol
was added 15% aq. NaOH (30 ml). The reaction mixture
was refluxed for 8 h, cooled to RT and acidified with 3 M HCl.
It was then extracted with ether (3 × 25 ml). The ether extract
was washed with brine and dried (Na2SO4). Evaporation of
the solvent furnished the acid 7 (3.3 g, 95%) as a yellow oil.
[α]2D4: ϩ21.3 (c 4.0, CHCl3). νmax (neat) 3000, 1707, 1644,
885 cmϪ1. δH (90 MHz, CDCl3) 11.6 (1 H, br s, COOH), 5.50
216.7 (C᎐O), 73.2 (C-Cl), 66.6 (CH-Cl), 46.6 (CH C᎐O), 44.9
᎐
᎐
2
(CH C᎐O), 42.7 (C-1), 42.1 (CH), 37.8 (CH), 31.9 (CH ), 31.2
᎐
2
2
(CH2), 30.9 (CH3), 30.8 (CH3), 27.1 (CH3). Mass: m/z 262
(Mϩ, 25%), 264 (Mϩ ϩ 2, 15%), 227 (15), 191 (100), 183 (32),
149 (28), 121 (25), 109 (50), 107 (48). Anal. Calcd. for
C13H20Cl2O: C, 59.32; H, 7.66. Found: C, 59.06; H, 7.69%.
(1 H, br s, H-3), 4.64 (2 H, s, C᎐CH ), 2.50–2.80 (2 H, m,
H-α), 1.00–2.30 (6 H, m), 1.67 (3 H, s) and 1.63 (3 H, s)
᎐
2
(2 × olefinic CH3). δC (100 MHz, CDCl ) 179.9 (C᎐O), 149.6
᎐
3
(؊)-(1S,2S,6R,9R)-4-Isopropylidene-1-methyltricyclo-
[4.3.0.02,9]nonan-8-one (10)
(C᎐CH ), 134.3 (C-2), 123.9 (C-3), 108.8 (C᎐CH ), 41.3, 38.8,
᎐
᎐
2
2
37.1, 35.1, 31.1, 21.0, 20.7. Mass: m/z 194 (Mϩ, 25%), 151 (15),
134 (55), 126 (37), 119 (60), 105 (67), 93 (70), 84 (45), 81 (100).
HRMS: m/z Calcd. for C12H18O2: M 194.1307. Found: Mϩ,
194.1299.
A solution of the dichloride 9 (208 mg, 0.79 mmol) and DBU
(240 mg, 0.236 ml, 1.58 mmol) in dry benzene (2 ml) was heated
in a sealed tube at 160 ЊC for 30 min. The reaction mixture was
J. Chem. Soc., Perkin Trans. 1, 2001, 2040–2046
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then cooled to RT, diluted with ether (10 ml), washed with
water, 3 M HCl (5 ml), saturated aq. NaHCO3 solution and
brine, and dried (Na2SO4). Evaporation of the solvent and
purification of the residue over a silica gel column using ethyl
acetate–hexane (1 : 20 to 1 : 5) as eluent furnished the tricyclic
compound 10 (116 mg, 77.3%). [α]2D3: Ϫ150 (c 0.2, CHCl3). νmax
(neat) 1720 cmϪ1. δH (90 MHz, CDCl3) 1.50–2.60 (9 H, m), 1.60
(6 H, br s, 2 × olefinic CH3), 1.35 (3 H, s, tert-CH3). δC (100
of pTSA in 35 ml of dry benzene was refluxed using a Dean–
Stark water separator for 3.5 h. It was cooled, washed with
saturated aq. NaHCO3 and brine, and dried (Na2SO4). Evapor-
ation of the solvent under reduced pressure and purification of
the product on a silica gel column using ethyl acetate–hexane
(1 : 5 to 2 : 5) as eluent furnished the ketoketal 13 (124 mg, 54%,
63% based on consumed starting material). [α]2D5: Ϫ26.3 (c 3.8,
CHCl3). νmax (neat) 1675 cmϪ1. δH (270 MHz, CDCl3) 6.60 (1 H,
d, J 9.9 Hz, H-5), 5.92 (1 H, d, J 9.9 Hz, H-4), 3.86 (4 H, s,
OCH2CH2O), 2.62 (1 H, dd, J 17.9 and 6.0 Hz), 1.90–2.45 (5 H,
m), 1.83 (1 H, dd, J 13.6 and 10.7 Hz), 1.29 (3 H, s, tert-CH3). δC
(22.5 MHz, CDCl ) 197.7 (s, C᎐O), 156.3 (d, C-5), 126.5 (d, C-
4), 115.1 (s, O-C-O), 64.0 (t) and 63.7 (t) [OCH2CH2O], 50.8 (t),
42.4 (d, C-1), 41.7 (2 C, s and t), 37.2 (t), 24.9 (q, CH3). Mass:
m/z 208 (Mϩ, 5%), 164 (17), 112 (28), 99 (17), 95 (35), 86 (100).
Further elution of the column furnished the unreacted starting
material 3 (25 mg, 14%).
MHz, CDCl ) 215.1 (C, C᎐O), 126.7 (C) and 123.6 (C) (olefinic
᎐
3
C), 44.8 (CH2, C-7), 41.4 (CH), 35.1 (C, C-1), 34.8 (CH), 29.6
(CH2), 28.7 (CH), 24.1 (CH2), 20.6 (CH3), 20.2 (CH3), 20.0
(CH3). Mass: m/z 190 (Mϩ, 4%), 149 (15), 133 (25), 109 (85), 105
(60), 43 (100). HRMS: m/z Calcd. for C13H18O: M, 190.1358.
Found: Mϩ, 190.1357.
᎐
3
(؊)-(1S,6S)-6-Methylbicyclo[4.3.0]non-4-ene-3,8-dione (3)
Through a cold (Ϫ70 ЊC) solution of the compound 10 (400
mg, 2.1 mmol) in methanol (0.1 ml) and NaHCO3 (catalytic) in
12 ml of CH2Cl2 was passed a stream of pre-cooled ozone in
oxygen gas until the reaction mixture turned to blue in colour.
Excess ozone was flushed off by passing oxygen gas. Dimethyl
sulfide (1.1 g, 1.3 ml, 17.8 mmol) was added to the reaction
mixture, allowed to warm up to RT and stirred for 10 h. It was
then diluted with CH2Cl2, washed with brine and dried
(Na2SO4). Evaporation of the solvent furnished the dione 11,
which was taken in 5 ml CH2Cl2 and a catalytic amount pTSA
was added and stirred at RT for 8 h. Evaporation of the solvent
and purification of the product on a silica gel column using
ethyl acetate–hexane (1 : 5 to 2 : 5) as eluent furnished the
enedione 3 (307 mg, 89%) as an oil. [α]2D5: Ϫ55 (c 2.5, MeOH).
νmax (neat) 1745, 1675 cmϪ1. δH (90 MHz, CDCl3) 6.61 (1 H, d,
J 10.2 Hz, H-5), 6.00 (1 H, d, J 10.2 Hz, H-4), 2.00–2.80 (7 H,
m), 1.40 (3 H, s, tert-CH3). δC (22.5 MHz, CDCl3) 214.4 (s, C-8),
196.9 (s, C-3), 154.2 (d, C-5), 128.0 (d, C-4), 51.9 (t), 42.8 (t),
40.7 (d, C-1), 40.4 (s, C-6), 37.4 (t), 25.0 (q). Mass: m/z 164
(Mϩ, 48%), 122 (20), 95 (100), 79 (35), 67 (50), 41 (60). HRMS:
m/z Calcd. for C10H12O2: M, 164.0837. Found: Mϩ, 164.0818.
(1R,5S,6R) and (1R,5R,6R)-5,6-Dimethylbicyclo[4.3.0]nonan-
3,8-diones (12a,b)
Reaction of the ketal 13 (50 mg, 0.24 mmol) in 1 ml of ether
with lithium dimethylcopper [prepared from CuI (136 mg, 0.72
mmol) and MeLi (2 ml of a 0.7 M solution in ether, 1.4 mmol)],
as described earlier, for 3 h furnished 50 mg of the product,
which was taken up in 1.5 ml of THF and 3 M aq. HCl (1.0
ml) and stirred for 5 h at RT. It was then extracted with ether
(3 × 5 ml), washed with water, saturated NaHCO3 solution
and brine, and dried (Na2SO4). Evaporation of the solvent
and purification of the residue over a silica gel column using
ethyl acetate–hexane (1 : 5 to 2 : 5) as eluent furnished a 2 : 1
epimeric mixture of the diketones 12a,b (31 mg, 70%).
(2S,3R,5R) and (2R,3R,5R)-2-Allyl-5-isopropenyl-2,3-
dimethylcyclohexanones (14)
To a cold (Ϫ10 ЊC), magnetically stirred solution of lithium
dimethylcopper [prepared from cuprous iodide (1.9 g, 10 mmol)
and methyllithium in ether (20 mmol, 26 ml of a 0.765 M solu-
tion in ether)] was added a solution of (R)-carvone (1, 1.0 g,
6.66 mmol) in dry ether (15 ml) over a period of 15 min. The
reaction mixture was stirred for 30 min at RT, and a mixture of
allyl bromide (8.0 g, 5.6 ml, 66.1 mmol) and HMPT (1.43 g, 1.4
ml, 8 mmol) was added over 5 min. It was stirred for 24 h at RT,
quenched with 25% aq. NH4Cl solution and extracted with
ether (3 × 15 ml). The ether extract was washed with brine and
dried (Na2SO4). Evaporation of the solvent and purification of
the residue on a silica gel column, using ethyl acetate–hexane
(1 : 48) as eluent, furnished a 9 : 1 epimeric mixture of the
product 14 (1.22 g, 89%) as pale yellow oil. Partial purification
on a long silica gel column furnished a small amount of major
epimer of the product 14. [α]2D4: ϩ37 (c 1.2, CHCl3). νmax (neat)
1705, 1640, 910, 890 cmϪ1. δH (200 MHz, CDCl3) 5.63 (1 H, t of
dd, J 17.5, 9.5 and 7.3 Hz, H-2Ј), 5.08 (1 H, d, J 17.5 Hz) and
5.07 (1 H, d, J 9.5 Hz) [H-3Ј], 4.79 (1 H, s) and 4.72 (1 H, s)
(1R,5S,6R) and (1R,5R,6R)-5,6-Dimethylbicyclo[4.3.0]nonan-
3,8-diones (12a and b)
To a cold (Ϫ5 ЊC) magnetically stirred solution of lithium
dimethylcopper (0.92 mmol) in ether [prepared from CuI (174
mg, 0.913 mmol) and MeLi (1.97 ml of a 0.93 M solution in
ether, 1.83 mmol)] was slowly added a solution of the enedione
3 (50 mg, 0.305 mmol) in 1 ml of dry ether. The reaction mix-
ture was slowly warmed up to RT and stirred for 3 h. It was
then quenched with 5% aq. ammonia solution and extracted
with ether (3 × 5 ml). The ether extract was washed with brine
and dried (Na2SO4). Evaporation of the solvent and puri-
fication of the residue over a silica gel column using ethyl
acetate–hexane (1 : 5 to 2 : 5) as eluent furnished a 3 : 2 mixture
of epimers of the diketone 12a,b (39 mg, 71%) as an oil. νmax
(neat) 1740, 1710 cmϪ1. δH (270 MHz, CDCl3, 3 : 2 diastereo-
meric mixture) 1.80–2.80 (10 H, m), 1.27 and 1.18 (3 H, s, tert-
CH3), 0.97 and 1.02 (3 H, d, J 6.6 Hz, sec-CH3). δC (100 MHz,
CDCl3): For the major isomer 12a: 215.8 (C, C-8), 210.3 (C, C-
3), 51.9 (CH2), 45.5 (CH), 44.9 (CH2), 42.0 (CH2), 40.7 (2 C, C
and CH2), 35.7 (CH), 18.7 (CH3), 16.6 (CH3). For the minor
isomer 12b: 217.0 (C, C-8), 209.6 (C, C-3), 45.2 (CH2), 45.1
(CH2), 44.6 (CH), 42.3 (CH2), 40.8 (C), 26.2, 17.8. Mass: m/z
180 (Mϩ, 27 %), 137 (12), 111 (20), 109 (18), 96 (26), 69 (100).
HRMS: m/z Calcd. for C11H16O2: M, 180.1150. Found: Mϩ,
180.1140.
[C᎐CH ], 2.30–2.70 (5 H, m), 1.90–2.20 (2 H, m), 1.60–1.70
᎐
2
(1 H, m), 1.75 (3 H, s, olefinic CH3), 1.00 (3 H, s, tert-CH3), 0.91
(3 H, d, J 7.2 Hz, sec-CH3). δC (22.5 MHz, CDCl3) 213.4 (s,
C᎐O), 146.8 (s, C᎐CH ), 133.2 (d, CH᎐CH ), 117.0 (t, CH᎐
᎐
᎐
᎐
᎐
2
2
CH ), 109.7 (t, C᎐CH ), 51.1 (s, C-2), 42.2, 41.3, 39.9, 36.0 (d),
᎐
2
2
32.2 (t), 20.4 (q), 18.3 (q), 15.3 (q). Mass: m/z 206 (Mϩ, 10%),
191 (20), 163 (30), 123 (25), 109 (40), 95 (95), 41 (100). HRMS:
m/z Calcd. for C14H22O: M, 206.1671. Found: Mϩ, 206.1679.
(2S,3R,5R) and (2R,3R,5R)-5-Isopropenyl-2,3-dimethyl-2-
(2-oxopropyl)cyclohexanones (15) and (16)
(؊)-(1R,6S)-8,8-Ethylenedioxy-6-methylbicyclo[4.3.0]non-4-en-
3-one (13)
A suspension of palladium chloride (61 mg, 0.34 mmol) and
cuprous chloride (500 mg, 5 mmol) in DMF (2.5 ml) and water
(0.5 ml, 27.8 mmol) was magnetically stirred in an oxygen
atmosphere, created via evacuative displacement of air using an
A magnetically stirred solution of the enedione 3 (180 mg, 1.1
mmol), ethylene glycol (72 µl, 1.3 mmol) and a catalytic amount
2044
J. Chem. Soc., Perkin Trans. 1, 2001, 2040–2046

View Article Online
oxygen balloon, for 1 h at RT. A solution of the 9 : 1 mixture of
the allyl compound 14 (1.03 g, 5 mmol) in 1 ml of DMF was
then added, and the reaction mixture was stirred for 24 h at RT
in the oxygen atmosphere. 3 M HCl (5 ml) was added to the
reaction mixture and extracted with ether (3 × 10 ml). The ether
layer was washed with saturated aq. NaHCO3 solution followed
by brine and dried (Na2SO4). Evaporation of the solvent and
careful chromatography of the residue on a silica gel column
using ethyl acetate–hexane (1 : 20 to 1 : 10) as eluent, furnished
the diketone 16 (86 mg, 7.7%) as oil and 15 (775 mg, 70%) as a
white solid, which was recrystallised from hexane. For the minor
diketone 16: νmax (neat) 1700, 1640, 885 cmϪ1. δH (90 MHz,
H, s) [C᎐CH ], 2.43 (1 H, m, H-4), 1.50–2.20 (10 H, m), 1.76 (3
᎐
2
H, s, olefinic CH3), 0.83 (3 H, d, J 6.3 Hz, sec-CH3), 0.79 (3 H, s,
tert-CH3). δC (22.5 MHz, CDCl ) 215.6 (s, C᎐O), 146.6 (s, C᎐
᎐
᎐
3
CH ), 110.0 (t, C᎐CH ), 53.3 (t, CH C᎐O), 42.1 (s, C-1), 40.6
᎐
᎐
2
2
2
(d, C-4), 40.0 (d), 38.7 (d), 37.4 (t), 31.7 (t), 25.5 (t), 22.2 (q),
16.6 (q), 10.6 (q). Mass: m/z 206 (Mϩ, 15%), 178 (11), 163 (35),
149 (11), 135 (15), 123 (40), 121 (50), 109 (30), 107 (35), 96
(100). HRMS: m/z Calcd. for C14H22O: M, 206.1671. Found:
Mϩ, 206.1658. For the cis isomer 18: [α]2D6: Ϫ100.4 (c 2.5,
CHCl3). νmax (neat) 1740, 1640, 890 cmϪ1. δH (270 MHz, CDCl3)
4.69 (1 H, s) and 4.72 (1 H, s) [C᎐CH ], 2.54 (1 H, dd, J 18.7 and
᎐
2
8.5 Hz, H-7a), 1.95 and 2.52 (2 H, 2 × d, J 18.5 Hz, H-9), 1.40–
2.30 (8 H, m), 1.72 (3 H, s, olefinic CH3), 1.06 (3 H, d, J 7.1 Hz,
sec-CH3), 1.03 (3 H, s, tert-CH3). δC (22.5 MHz, CDCl3) 219.2
CDCl ) 4.77 (2 H, br s, C᎐CH ), 2.10–2.90 (5 H, m), 2.17 (3 H,
᎐
3
2
s, CH C᎐O), 1.74 (3 H, s, olefinic CH ), 1.60–1.85 (3 H, m), 1.41
᎐
3
3
(3 H, s, tert-CH3), 0.86 (3 H, d, J 7.0 Hz, sec-CH3). δC (22.5
MHz, CDCl ) 212.1 (s, ring C᎐O), 205.7 (s, MeC᎐O), 146.6 (s,
(s, C᎐O), 149.4 (s, C᎐CH ), 108.5 (t, C᎐CH ), 48.1 (t, C-9), 44.8
᎐ ᎐ ᎐
2 2
(t, C-7), 40.5 (s, C-1), 38.6 (d), 37.1 (d), 34.6 (t), 33.8 (2 C, d &
t), 25.4 (q), 21.0 (q), 16.0 (q). Mass: m/z 206 (Mϩ, 22%), 163
(35), 149 (25), 109 (55), 95 (55), 40 (100). HRMS: m/z Calcd. for
C14H22O: M, 206.1671. Found: Mϩ, 206.1688.
᎐
᎐
3
C᎐CH ), 109.2 (t, C᎐CH ), 49.9 (s, C-2), 45.1 (t, CH C᎐O),
᎐
᎐
᎐
2
2
2
41.1 (t, C-6), 40.2 (d), 37.3 (d), 32.1 (t), 30.7 (q), 21.7 (q), 19.9
(q), 15.5 (q). For the major diketone 15: mp: 53–54 ЊC. [α]2D3: ϩ6.1
(c 1.14, CHCl3). νmax (neat) 1710, 1700, 1650, 895 cmϪ1. δH (90
MHz, CDCl ) 4.83 (1 H, s) and 4.75 (1 H, s) (C᎐CH ), 2.78 (2
(؊)-(1S,2R,6S)-4-Isopropylidene-1,2-
dimethylbicyclo[4.3.0]nonan-8-one (21)
᎐
3
2
H, br s), 2.56 (2 H, br s), 2.20–2.50 (1 H, m), 2.12 (3 H, s,
COCH3), 1.65–1.85 (3 H, m), 1.72 (3 H, s, olefinic CH3), 1.02 (3
H, s, tert-CH3), 0.88 (3 H, d, J 7.2 Hz, sec-CH3). δC (22.5 MHz,
To an ice cold magnetically stirred saturated solution of HBr in
dry ether (50 ml) [by dissolving HBr gas, generated by bromin-
ation of tetralin, in ether] was added the hydrindanone 18
(400 mg, 1.94 mmol) in 2 ml of dry ether. The reaction mix-
ture was stirred at the same temp for 6 h, diluted with ether
(30 ml), washed with water, aq. NaHCO3 and brine, and dried
(Na2SO4). Evaporation of the solvent furnished the tertiary
bromide 20. A solution of the bromide 20 and DBU (0.347 ml,
2.3 mmol) in 5 ml of benzene was taken up in a sealed tube and
heated at 130 ЊC for 30 min. The reaction mixture was then
cooled to RT, diluted with water and extracted with ether
(3 × 10 ml). The ether extract was washed with 3 M HCl, satur-
ated NaHCO3 solution and brine, and dried (Na2SO4). Evapor-
ation of the solvent and purification of the residue over a
silica gel column using ethyl acetate–hexane (1 : 20) as eluent
furnished the isopropylidene compound 21 containing a trace
amount of the starting material 18 (390 mg, 97.5% in two
steps). [α]D26: ϩ79.1 (c 2.73, CHCl3). νmax (neat) 1740 cmϪ1. δH
CDCl ) 211.8 (s, ring C᎐O), 205.5 (s, MeC᎐O), 146.3 (s, C᎐
᎐
᎐
᎐
3
CH ), 109.6 (t, C᎐CH ), 49.4 (s, C-2), 49.1 (t, CH COCH ),
᎐
2
2
2
3
41.1 (t, C-6), 39.5 (d, C-5), 34.4 (d, C-3), 31.7 (t, C-4), 30.2 (q,
COCH3), 20.0 (q), 17.8 (q), 14.4 (q). Mass: m/z 222 (Mϩ, 5%),
165 (90), 109 (22), 95 (25), 43 (100). Anal. Calcd. for C14H22O2:
C, 75.63; H 9.97. Found: C, 75.74; H 10.19%.
(؉)-(1S,2R,4R)-4-Isopropenyl-1,2-dimethylbicyclo[4.3.0]non-6-
en-8-one (17)
To a solution of the diketone 15 (686 mg, 3.09 mmol) in 1 ml of
methanol was added 10% aq. KOH (1.73 ml, 3.71 mmol), and
the reaction mixture was refluxed for 3 h. It was cooled and
extracted with ether (3 × 10 ml). The ether extract was washed
with water followed by brine and dried (Na2SO4). Evaporation
of the solvent and purification of the residue on a silica gel
column, using ethyl acetate–hexane (1 : 6) as eluent furnished
the enone 17 (600 mg, 95%) as an oil. [α]2D5: ϩ44.2 (c 1.0,
CHCl3). νmax (neat) 1700, 1620, 888 cmϪ1. δH (200 MHz, CDCl3)
(90 MHz, CDCl ) 2.35 (1 H, d, J 18 Hz), 2.16 (2 H, s, CH C᎐
᎐
2
3
O), 1.93 (1 H, d, J 18 Hz), 1.60–2.60 (6 H, m), 1.68 (3 H, s), 1.63
(3 H, s), 1.10 (3 H, s, tert-CH3), 0.85 (3 H, d, J 6.3 Hz, sec-CH3).
5.80 (1 H, s, H-7), 4.73 (1 H, s) and 4.84 (1 H, s) [C᎐CH ], 2.50–
᎐
2
δC (22.5 MHz, CDCl ) 218.7 (s, C᎐O), 127.1 (s) and 123.9 (s)
᎐
3.10 (3 H, m), 2.20 (2 H, s, H-9), 1.50–1.80 (3 H, m), 1.70 (3 H,
s, olefinic CH3), 1.12 (3 H, s, tert-CH3), 0.91 (3 H, d, J 6.1 Hz,
3
[olefinic C], 52.4 (t, CH C᎐O), 45.0 (d), 40.8 (s, C-1), 40.4 (t),
᎐
2
35.3 (d), 33.8 (t), 28.3 (t), 19.7 (2 C, q), 18.7 (q), 16.1 (q). Mass:
m/z 206 (Mϩ, 80%), 163 (40), 149 (45), 121 (75), 110 (40), 109
(100), 107 (50). HRMS: m/z Calcd. for C14H22O: M, 206.1671.
Found: Mϩ, 206.1668.
sec-CH ). δ (50 MHz, CDCl ) 207.6 (C᎐O), 187.3 (C-6), 146.0
᎐
3
C
3
(C᎐CH ), 127.4 (C-7), 111.7 (C᎐CH ), 50.6 (C-9), 46.7 (C-1),
᎐
᎐
2
2
40.5, 36.4, 31.4, 30.0, 22.5, 18.5, 16.6. Mass: m/z 204 (Mϩ, 28%),
189 (20), 162 (100), 147 (31), 134 (62), 119 (40), 105 (33), 95
(29). HRMS: m/z Calcd. for C14H20O: M, 204.1514. Found:
Mϩ, 204.1514.
(؉)-(1S,5R,6S)-5,6-Dimethylbicyclo[4.3.0]nonan-3,8-dione
(12a)
(؊)-(1S,2R,4R,6S) and (؊)-(1S,2R,4R,6R)-4-Isopropenyl-1,2-
dimethylbicyclo[4.3.0]nonan-8-ones (18) and (19)
Ozonolysis of the enone 21 (390 mg, 1.89 mmol), in CH2Cl2 (10
ml) and methanol (0.4 ml), as described for the compound 10,
followed by reductive work up with triphenylphosphine (500
mg, 1.9 mmol) for 4 h at RT and purification of the product
over a silica gel column using ethyl acetate–hexane (1 : 5 to
2 : 5) as eluent furnished the dione 12a (300 mg, 88%). [α]2D4:
ϩ88.4 (c 1.9, CHCl3). νmax (neat) 1740, 1710 cmϪ1. δH (200 MHz,
CDCl3) 1.70–2.80 (10 H, m), 1.21 (3 H, s, tert-CH3), 0.90 (3 H,
d, J 6.6 Hz, sec-CH3). δC (100 MHz, CDCl3) 215.9 (C),
210.4 (C), 51.9 (CH2), 45.5 (CH), 45.0 (CH2), 42.0 (CH2), 40.7
(2 C, C & CH2), 35.7 (CH), 18.7 (CH3), 16.6 (CH3). Mass: m/z
180 (Mϩ, 25 %), 111 (10), 69 (100). HRMS: m/z Calcd. for
C11H16O2: M, 180.1150. Found: Mϩ, 180.1143.
To a dark blue coloured solution of lithium (190 mg, 27.3
mmol) in 400 ml of freshly distilled ammonia was added, drop-
wise, a solution of the enone 17 (1.5 g, 7.35 mmol) and tert-
butanol (0.6 ml, 6.4 mmol) in 20 ml of dry THF over a period
of 15 min. The reaction mixture was stirred for 50 min and then
quenched with ammonium chloride. Ammonia was evaporated,
it was diluted with water and extracted with ether (3 × 25 ml).
The ether extract was washed with brine and dried (Na2SO4).
Evaporation of the solvent and purification of the residue over
a silver nitrate impregnated silica gel column using ethyl
acetate–hexane (1 : 50 to 1 : 10) as eluent furnished the trans-
hydrindanone 19 (305 mg, 20%), cis-hydrindanone 18 (650 mg,
43%) and the unreacted starting material 17 (300 mg, 20%). For
the trans isomer 19: [α]D24: Ϫ186 (c 2.7, CHCl3). νmax (neat) 1745,
1640, 888 cmϪ1. δH (200 MHz, CDCl3) 4.93 (1 H, s) and 4.84 (1
(؉)-(1S,2R,6R)-4,4-Ethylenedioxy-1,2-
dimethylbicyclo[4.3.0]nonan-8-one (2)
Regioselective protection of the dione 12a (320 mg, 1.77 mmol)
J. Chem. Soc., Perkin Trans. 1, 2001, 2040–2046
2045

View Article Online
Wijnberg and A. de Groot, J. Org. Chem., 1996, 61, 4022; A. J.
Minnaard, G. A. Stork, J. B. P. A. Wijnberg and A. de Groot, J. Org.
Chem., 1997, 62, 2344; A. J. Minnaard, J. B. P. A. Wijnberg and A.
de Groot, J. Org. Chem., 1997, 62, 7336; A. J. Minnaard, J. B. P. A.
Wijnberg and A. de Groot, J. Org. Chem., 1997, 62, 7346, see also
T. M. Meulemans, G. A. Stork, F. Z. Macaev, B. J. M. Jansen and
A. de Groot, J. Org. Chem., 1999, 64, 9178.
6 (a) A. Srikrishna, T. J. Reddy, P. P. Kumar and S. J. Gharpure, Indian
J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 2001, 40, in the
press; (b) A. Srikrishna and S. J. Gharpure, J. Org. Chem., 2001, 66,
4379; (c) A. Srikrishna, P. R. Kumar and S. J. Gharpure, Tetrahedron
Lett., 2001, 42, 3929; (d ) A. Srikrishna, R. Viswajanani and C.
Dinesh, J. Chem. Soc., Perkin Trans. 1, 2000, 4321; (e) A. Srikrishna
and S. J. Gharpure, J. Chem. Soc., Perkin Trans. 1, 2000, 3191;
( f ) A. Srikrishna and D. Vijaykumar, J. Chem. Soc., Perkin Trans. 1,
2000, 2583 and references cited therein.
in 2 ml of dry benzene using ethylene glycol (98 µl, 108 mg, 1.75
mmol) and pTSA (catalytic) in 70 ml of dry benzene for 3 h, as
described for the ketoketal 13, and purification of the product
over a silica gel column using ethyl acetate–hexane (1 : 5) as
eluent furnished the ketoketal 2 (256 mg, 64.5%) as an oil. [α]2D5:
ϩ69.8 (c 1.64, CHCl3). νmax (neat) 1730 cmϪ1. δH (270 MHz,
CDCl3) 3.85–4.00 (4 H, m, OCH2CH2O), 2.93 (1 H, d of t,
J 16.0 and 7.0 Hz), 1.40–2.50 (9 H, m), 1.06 (3 H, s, tert-CH3),
0.85 (3 H, d, J 6.7 Hz, sec-CH3). δC (50 MHz, CHCl3 ϩ CDCl3)
219 (C᎐O), 109 (O-C-O), 64.4 and 63.5 (OCH CH O), 58.3,
᎐
2
2
52.2, 43.5, 41.5, 38.5, 31.8, 31.4, 18.4, 16.0. Mass: m/z 224
(Mϩ, 5%), 154 (35), 139 (10), 113 (100). HRMS: m/z Calcd. for
C13H20O3: M, 224.1412. Found: Mϩ, 224.1416.
7 (a) A. Srikrishna and P. Hemamalini, Indian J. Chem., Sect. B: Org.
Chem. Incl. Med. Chem., 1990, 29, 152; (b) A. Srikrishna and T. J.
Reddy, Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 1995,
34, 844; (c) A. Srikrishna and D. Vijaykumar, Tetrahedron Lett.,
1998, 39, 5833; (d ) A. Srikrishna and T. J. Reddy, J. Chem. Soc.,
Perkin Trans. 1, 1998, 2137; (e) A. Srikrishna, S. J. Gharpure and
P. P. Kumar, Tetrahedron Lett., 2000, 41, 3177.
Acknowledgements
We thank the Department of Science and Technology for the
financial support and the University Grants Commission for
the award of a research fellowship to TJR.
8 For a preliminary communication, see A. Srikrishna, T. J. Reddy and
S. Nagaraju, Tetrahedron Lett., 1996, 37, 1679.
9 (a) L. Garver, P. van Eikeren and J. E. Byrd, J. Org. Chem., 1976, 41,
2773; (b) Y.-D. Wu, K. N. Houk, J. Florez and B. M. Trost, J. Org.
Chem., 1991, 56, 3656.
10 W. S. Johnson, L. Werthemann, W. R. Bartlett, T. J. Brocksom,
T.-t. Li, D. J. Faulkner and M. R. Petersen, J. Am. Chem. Soc., 1970,
92, 741.
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