A radical cyclisation based cyclopentenone annulation of allyl alcohols

Article abstract of DOI:10.1016/S0957-4166(03)00535-4

A four-step cyclopentenone annulation reaction of allylic alcohols employing a 5-exo-trig radical cyclisation reaction of mixed allyl methyl ketals of bromoacetone as the key step is described. The annulated product 12b obtained from 2,3-dimethylcyclohexenol has been further elaborated into (±)-epibakkenolides employing a 5-exo-dig radical cylisation reaction based α-spiro-β-methylene-γ-butyrolactone annulation methodology.

Full text of DOI:10.1016/S0957-4166(03)00535-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2975–2983
A radical cyclisation based cyclopentenone annulation
of allyl alcohols
A. Srikrishna,* R. Viswajanani and J. A. Sattigeri
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 29 April 2003; accepted 15 May 2003
Abstract—A four-step cyclopentenone annulation reaction of allylic alcohols employing a 5-exo-trig radical cyclisation reaction
of mixed allyl methyl ketals of bromoacetone as the key step is described. The annulated product 12b obtained from
2,3-dimethylcyclohexenol has been further elaborated into ( )-epibakkenolides employing a 5-exo-dig radical cylisation reaction
based a-spiro-b-methylene-g-butyrolactone annulation methodology.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
cally over the last two decades. At the beginning of the
eighties, the place of radical reactions in organic syn-
thesis was limited to a few important functional group
transformations. However, during the past two
decades, radical carbonꢀcarbon bond forming reac-
tions, particularly, the intramolecular version leading to
cyclic compounds, i.e. radical cyclisation reactions,
have grown in importance to the present status where
they are now routinely considered at the strategy level
planning of complex target molecules.3 For the
cyclopentenone annulation of allyl alcohols, we envis-
aged a four step, radical cyclisation based methodol-
ogy, which is depicted in Scheme 1 in a retrosynthetic
mannner.4 The 5-exo-trig radical cyclisation reaction of
the bromo ketal 1 generates the cyclic ketal 2. A one
step hydrolysis and oxidation sequence converts the
Although cyclopentanes have been known for over a
century and are ubiquitous in nature, interest in their
synthesis and reactions remained low until mid-seven-
ties. This can be traced to the fact that until 1960,
relatively few cyclopentanoid natural products of rea-
sonable complexity were known that could constitute
challenging targets.1 However, discoveries and develop-
ments in the chemistry of natural and unnatural prod-
ucts rekindled interest in the synthetic design of
cyclopentanoids and a flurry of activity has been ini-
tiated in this area. The methodology of annulating a
functionalised cyclopentane ring onto an existing ring
residue, a cyclopentannulation, would have the poten-
tial to be useful if one could control the chemo-, regio-
and stereoselectivity of the reactions involved.2 The use
of radicals in organic chemistry has increased dramati-
cyclic ketal
2 into a 1,4-diketone 3 which on
intramolecular aldol condensation completes the annu-
Scheme 1.
* Corresponding author. E-mail: ask@orgchem.iisc.ernet.in
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00535-4

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A. Srikrishna et al. / Tetrahedron: Asymmetry 14 (2003) 2975–2983
lation of the cyclopentenone moiety to the C1ꢀC2 bond
of the allyl alcohol to generate the enone 4. The requi-
site radical precursor, bromo ketal 1, can be obtained
by a bromoketalisation reaction of the allyl alcohol 5.
ketal 9a into the diketone 10a was achieved employing
sonochemically accelerated reaction with Jones
a
reagent7 via a one pot hydrolysis and oxidation of the
resulting hydroxy ketone 11a (or hemi ketal). Thus,
sonochemical irradiation of a solution of the cyclic
ketal 9a and a freshly prepared 1.6 M Jones reagent in
acetone furnished, cleanly, the diketone 10a in 72%
yield. The IR spectrum showed absorption bands at
1700 and 890 cm−1 due to the C=O and RR%C=CH2
groups, respectively, and in the mass spectrum the
molecular ion appeared at m/z 208 establishing the
2. Results and discussion
To begin with, the sequence was carried out with
carveol 6a, which was obtained by regio- and stereose-
lective reduction of (R)-carvone 7a (Scheme 2).5 Brom-
ination of an enol ether in the presence of an alcohol
generates a bromo acetal via the nucleophilic addition
of the alcohol to the intermediate bromonium ion, and
generally referred as a bromoacetalisation reaction.6 In
the present investigations for the conversion of allyl
alcohols to allyl methyl mixed ketals of bromoacetone,
N-bromosuccinimide (NBS) was chosen as the source
of bromonium ion and 2-methoxypropene as the enol
ether component. Thus, reaction of 2-methoxypropene
with NBS in the presence of carveol 6a in methylene
chloride at −50°C furnished the radical precursor, the
bromo ketal 8a, as a mixture of epimers in 66% yield,
1
structure of the diketone 10a. In the H NMR spec-
trum, the presence of the resonances, broad singlets at
l 4.79 and 4.71 due to C=CH2, an AB quartet at 2.83
and 2.65 due to CH2-CO-CH3, a singlet at 2.13 due to
the acetyl methyl, a singlet at 1.72 due to the olefinic
methyl and a singlet at 1.12 due to the tert-methyl
group; and in the 13C NMR spectrum resonances at
213.4 and 206.8 due to two keto carbons, 147.2 and
110.4 due to two olefinic carbons, 50.6 due to CH2-CO-
CH3, 47.0 due to the quaternary carbon, 45.6 due to the
allylic CH, 42.9 due to the ring CH2-C=O, 37.1 and
25.6 due to two ring methylenes, 31.6, 22.9 and 20.9
ppm due to three methyl carbons confirmed the struc-
ture of the diketone 10a. Finally, intramolecular aldol
condensation of the diketone 10a using 10% aqueous
potassium hydroxide in methanol in a Carius tube at
100–110°C furnished the cyclopentenone 12a in 79%
yield. The presence of the molecular ion at m/z 190 in
the mass spectrum and the presence of absorption
bands at 1700, 1630, 1615 and 890 cm−1 due to the
cyclopentenone and C=CH2 moieties, respectively, in
the IR spectrum established the structure of the enone
1
whose structure was established from its H and 13C
NMR spectra. The 5-exo-trig radical cyclisation reac-
tion was achieved by refluxing a 0.02 M benzene solu-
tion of the bromo ketal 8a with 1.1 equivalents of
tri-n-butyltin hydride in the presence of a catalytic
amount of AIBN to furnish an epimeric mixture (at the
ketal carbon) of the cyclic ketal 9a in 72% yield in a
highly regio- and stereoselective manner. In the 1H
NMR spectrum, the absence of resonances due to the
ring olefinic proton and bromomethylene moiety and
the presence of signals, a multiplet at l 3.40–3.90 due to
the ring junction O-CH, two singlets at 3.32 and 3.26
due to O-CH3, a singlet at 1.76 due to olefinic methyl,
two singlets at 1.52 and 1.44 due to CH3-C-OCH3, two
singlets at 1.22 and 1.12 ppm due to bridgehead methyl
group, for the two epimers confirmed the structure of
the cyclic ketal 9a. The cis ring junction was a conse-
quence of the addition of the radical to the double
bond from the preferred syn face of the olefin, which
also fixes the b-stereochemistry of the bridgehead
methyl group. No attempt was made to separate the
methoxy epimers as they will converge into a single
diketone in the next step. The conversion of the cyclic
1
12a. The H NMR spectrum of the enone 12a revealed
the presence of a singlet at l 5.82 due to the ring
olefinic proton, three singlets at 4.87, 4.74 and 1.72 due
to the isopropenyl moiety, an AB quartet at 2.30 and
2.19 due to CH2C=O and a singlet at 1.28 ppm due to
tert-methyl group, which was further confirmed by the
13 lines 13C NMR spectrum.
After successful cyclopentenone ring annulation at the
C1ꢀC2 carbons of carveol 6a, to test the generality of
the methodology, the sequence was carried out with the
allyl alcohols 6b–e and the results are summarised in
Table 1. The allyl alcohols 6b–e were obtained by a
Scheme 2. Reagents and conditions: (a) LiAlH4, Et2O; (b) NBS, CH2=C(CH3)OCH3, CH2Cl2; (c) nBu3SnH, AIBN, C6H6; (d)
Jones reagent, acetone, ))); (e) KOH, MeOH, THF.

A. Srikrishna et al. / Tetrahedron: Asymmetry 14 (2003) 2975–2983
Table 1. Cyclopentenone annulation of allyl alcohols
2977
Entry
Allyl alcohol (% yield)
Bromo ketal (% yield)
Cyclic ketal (% yield)
Diketone (% yield)
Enone (% yield)
A
B
C
D
E
6a (95)
6b (92)
6c (89)
6d (94)
6e (91)
8a (66)
8b (59)
8c (83)
8d (79)
8e (83)
9a (72)
9b (74)
9c (75)
9d (72)
9e (73)
10a (72)
10b (72)
10c (73)
10d (89)
10e (80)
12a (79)
12b (94)
12c (92)
12d (68)
12e (85)
regioselective reduction of the corresponding enones
7b–e in ether with LAH at −70°C. Low temperature
bromination of 2-methoxypropene with NBS in the
presence of the allyl alcohols 6b–e in methylene chloride
furnished the bromo ketals 8b–e, respectively, as a
mixture of epimers. The key radical cyclisation reaction
was carried out by refluxing a 0.02 M benzene solution
of the bromo ketals 8b–e with 1.1 equivalents of tri-n-
butyltin hydride and a catalytic amount of AIBN to
furnish the cyclic ketals 9b–e as a mixture of methoxy
epimers in a stereoselective manner. The stereochem-
istry of the newly formed sec-methyl group in the ketals
9b and 9e during the radical cyclisation reaction was
assigned as endo based on the preferred approach of the
hydrogen from the less hindered side of the molecule,
by analogy with earlier reports.8 Sonochemically accel-
erated reaction with Jones reagent in acetone trans-
formed the cyclic ketals 9b–e into the corresponding
1,4-diketones 10b–e. Finally, intramolecular aldol con-
densation of the diketones 10b–e in methanol using
10% aqueous potassium hydroxide at 100–110°C in a
Carius tube furnished the cyclopentenone annulated
products 12b–e,9 whose structures rest secured from
their spectral data. The stereochemical integrity of the
enone 12b was found to be very good (>95%), obvi-
ously due to the very good stereoselectivity in the
radical cyclisation reaction 8b“9b.
furnished a :10:1 epimeric mixture of the diketone
10e, which on intramolecular aldol condensation gener-
ated a 6:1 mixture of the enone 12e. After successfully
establishing the generality of the four step, regiospecific
cyclopentenone annulation methodology, using a 5-
exo-trig radical cyclisation reaction as the key step, as
an application, the cyclopentenone 12b has been further
elaborated to 4-epibakkenolide-A and its spiro epimer.
Bakkanes are an interesting class of tricyclic sesquiter-
penes, containing an unusual a-spiro-b-methylene-g-
butyrolactone moiety fused to
a
hydrindane
framework. The simplest member of this class,
bakkenolide-A 13 was isolated in 1967 by Kitahara et
al. from the buds of Petasites japonicus subsp. gigantus
Maxim., found in the northern parts of Japan, along
with three other higher oxygenated analogues, and
named them bakkenolides A–D after the local name of
the species (Bakke). Simultaneously, Hayashi et al.
have also reported the isolation of the same set of
compounds and named them fukinanes after the
Japanese name (Fuki ) of the plant. Subsequently a few
other bakkanes were isolated10 from various sources
and some of the examples are depicted in Chart 1. The
presence of an unusual b-methylene-a-spiro-g-butyro-
lactone part structure and the associated biological
activities made the bakkenolides attractive and chal-
lenging synthetic targets.11
The sequence with 2-substituted allyl alcohol 6b (Table
1, entry B), similar to carveol 6a generated the annu-
lated product in a highly regio- and stereoselective
manner. However, when there is no substituent at the
2-position of the starting allyl alcohol (Table 1, entries
E), even though the radical cyclisation reaction pro-
ceeded in a stereoselective manner, the annulated
product was found to be a mixture of ring junction
epimers, because of the equilibration of the diketone
10e prior to the intramolecular aldol condensation in
the last step of the sequence, which was further estab-
lished by equilibrating the diketone 10e. The dione 10e
on equilibration with potassium carbonate in methanol
The bicyclic enone 12b obtained by cyclopentenone
annulation of 2,3-dimethylcyclohexenol 6b, was readily
identified as the key intermediate for the synthesis of
4-epibakkenolide-A 14 (Scheme 3). For the construc-
tion of the spiro lactone moiety, a 5-exo-dig radical
cyclisation
reaction
based
spiroannulation
methodology12 was employed. Thus, catalytic hydro-
genation of the enone 12b using 10%Pd/C in methanol
at one atmosphere pressure of hydrogen (balloon) fur-
nished the saturated bicyclic ketone 15. Wittig reaction
of the ketone 15 with methoxymethylenetriphenylphos-
phorane furnished the enol ether 16. The regiospecific

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A. Srikrishna et al. / Tetrahedron: Asymmetry 14 (2003) 2975–2983
Chart 1.
Scheme 3. Reagents and conditions: (a) H2, 10%Pd/C; MeOH; (b) Ph3P=CHOMe, C6H6; (c) NBS, HCꢀCCH2OH, CH2Cl2; (d)
nBu3SnCl, NaCNBH3, AIBN, t-BuOH; (e) Aq. HCl, THF; (f) PCC, silica gel, CH2Cl2.
bromoalkoxylation of the enol ether 16 was achieved by
treatment with NBS in methylene chloride in the pres-
ence of an excess of propargyl alcohol, to furnish the
bromo acetal 17 as a mixture of epimers. The key
radical cyclisation reaction was achieved by using an in
situ generated catalytic tri-n-butyltin hydride.13 Thus,
refluxing a 0.1 M tert-butanol solution of the bromo
acetal 17 with 0.15 equivalents of tri-n-butyltin chloride
and 1.7 equivalents of sodium cyanoborohydride in the
presence of a catalytic amount of AIBN for 1.5 h
furnished the 5-exo-dig radical cyclised product, the
spiro acetal 18 as a mixture of spiro and methoxy
epimers. Treatment of the spiro acetal 18 with 2.2N
aqueous HCl in THF under sonic irradiation for 4 h
furnished the lactol 19. Oxidation of the lactol 19 using
PCC and silica gel furnished a 1:1 mixture of 4-
epibakkenolide-A 14 and its spiroepimer 20, whose
structures were assigned from the spectroscopic data.
3. Experimental
3.1. (1R,4R)-4-Isopropenyl-1-methylbicyclo[4.3.0]non-6-
en-8-one 12a
To a cold (−50°C), magnetically stirred solution of
carveol 6a (500 mg, 3.2 mmol) and 2-methoxypropene
(0.62 ml, 6.4 mmol) in CH2Cl2 (10 ml) was added a
solution of NBS (570 mg, 3.2 mmol) in CH2Cl2 (20 ml)
over a period of 15 min. The reaction mixture was
allowed to warm up to room temperature over a period
of 1.5 h, and then diluted with CH2Cl2 (15 ml), washed
with 2% aq. NaOH, water and brine, and dried
(Na2SO4). Evaporation of the solvent and purification
of the product on a neutral alumina column using ethyl
acetate–hexane (1:40) as eluent furnished the bromo
ketal 8a (660 mg, 66%) as a colourless oil. IR (neat):
1
wmax 1635, 885 cm−1. H NMR (90 MHz, CDCl3, 1:1
mixture of epimers): l 5.55 (1H, br s, C=CH), 4.72
(2H, s, C=CH2), 4.38 (1H, br s, O-CH), 3.57 and 3.39
(AB q, J=6.3 Hz) and 3.47 (s) [2H, CH2-Br], 3.36 and
3.32 (3H, s, O-CH3), 1.80–2.45 (5H, m), 1.74 (6H, s,
2×olefinic CH3), 1.54 and 1.58 (3H, s, tert-CH3). 13C
NMR (22.5 MHz, CDCl3, 1:1 mixture of epimers): l
148.7 (s, C=CH2), 135.0 (s, C=CH), 125.3 and 125.0
(d, C=CH), 109.0 (t, C=CH2), 100.7 (s, O-C-O), 72.2
and 71.8 (d, O-CH), 50.0 and 49.0 (q, O-CH3), 40.7 (d,
In conclusion, we have developed a four-step methodol-
ogy for cyclopentenone annulation of allyl alcohols
employing a 5-exo-trig radical cyclisation reaction as
the key step. As an application of the methodology, one
of the products has been further elaborated into 4-epi
and 4,7-diepi-bakkenolides employing a 5-exo-dig radi-
cal cyclisation based a-spiro-b-methylene-g-butyrolac-
tone annulation strategy.

A. Srikrishna et al. / Tetrahedron: Asymmetry 14 (2003) 2975–2983
2979
C-5), 36.9 and 36.7 (t, CH2-Br), 35.9 and 35.7 (t, C-6),
30.7 (t, C-4), 22.4 and 21.9 (q), 20.3 (q) and 19.9 (q).
Mass: m/z 223 (M-Br, 1%), 191 (40), 153 (100), 155
(100), 135 (100), 119 (60), 107 (100), 93 (100). HRMS:
m/z for C13H19O (M-Br,CH3OH), calcd: 191.1436.
Found: 191.1424. A magnetically stirred solution of the
112.4 (C=CH2), 52.5 (C-9), 51.7 (C-1), 43.3, 40.9, 34.8,
30.6, 25.1, 23.7, 22.8. Mass: m/z 190 (M+, 62%), 148
(30), 147 (50), 133 (40), 125 (35), 119 (40), 109 (30), 107
(40), 105 (42). HRMS: m/z for C13H18O, calcd:
190.1358. Found: 190.1341.
n
bromo ketal 8a (304 mg, 1.0 mmol), Bu3SnH (0.3 ml,
3.2. (1b,2a)-1,2-Dimethylbicyclo[4.3.0]non-6-en-8-one
12b
1.1 mmol) and catalytic amount of AIBN in benzene
(56 ml) was refluxed for 2.5 h. The reaction mixture was
cooled, washed with 1% aqueous ammonia and brine,
and dried (Na2SO4). Evaporation of the solvent and
purification of the product on a neutral alumina
column using ethyl acetate–hexane (1:40) as eluent fur-
nished an epimeric mixture of the cyclic ketal 9a (163
To a cold (−78°C), magnetically stirred solution of the
enone 7b (980 mg, 8.9 mmol) in ether (20 ml) was
added LiAlH4 (167 mg, 4.5 mmol) and the reaction
mixture was stirred for 1.5 h. Ethyl acetate (0.5 ml) was
added to the reaction mixture to consume the excess
reagent. The reaction was then quenched with water
and extracted with ether (2×10 ml). Evaporation of the
solvent and purification of the product on a silica gel
column with CH2Cl2 as eluent furnished the allyl alco-
hol 6b (920 mg, 92%) as an oil. IR (neat): wmax 3330
1
mg, 72%) as an oil. IR (neat): wmax 1640, 885 cm−1. H
NMR (90 MHz, CDCl3, :1:1 mixture of methoxy
epimers): l 4.72 (2H, s, C=CH2), 3.40–3.90 (1H, m,
O-CH), 3.32 and 3.26 (3H, s, O-CH3), 1.30–2.50 (9H,
m), 1.76 (3H, s, olefinic CH3), 1.52 and 1.44 (3H, s,
CH3-C-OCH3) 1.22 and 1.12 (3H, s, tert-CH3). To a
solution of the cyclic ketal 9a (50 mg, 0.22 mmol) in
acetone (0.3 ml) was added freshly prepared Jones
reagent (1.6 M, 0.3 ml, 0.48 mmol) and the reaction
mixture was sonicated for 5 min in an ultrasonic clean-
ing bath. Isopropyl alcohol (0.2 ml) was added to
consume the excess reagent and the solvent was evapo-
rated under reduced pressure. The residue was taken in
ether and washed with 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 (1:10) as eluent furnished
the diketone 10a (33 mg, 72%) as an oil. IR (neat): wmax
1
cm−1. H NMR (90 MHz, CDCl3): l 3.95 (1H, br s,
O-CH), 1.40–2.10 (7H, m), 1.76 (3H, s) and 1.65 (3H, s)
[2×olefinic CH3]. The bromoacetalisation reaction of
the allyl alcohol 6b (500 mg, 3.97 mmol) at −50°C with
2-methoxypropene (0.7 ml, 7.94 mmol) and NBS (1.41
g, 7.94 mmol) in CH2Cl2 (30 ml) for 1.5 h as described
for the bromo ketal 8a, and purification of the product
on a neutral alumina column with ethyl acetate–hexane
(1:40) as eluent furnished the bromo ketal 8b (638 mg,
1
59%) as a colourless oil. IR (neat): wmax 1110 cm−1. H
NMR (90 MHz, CDCl3, 3:2 mixture of epimers): l 4.13
(1H, br s), 3.46 (2H, AB q, J=5.4 Hz), 3.32 and 3.36
(3H, s), 1.40–2.20 (6H, m), 1.69 (3H, s), 1.61 (3H, s),
1.59 and 1.57 (3H, s, tert-CH3). 13C NMR (22.5 MHz,
CDCl3, 3:2 mixture of epimers): l 132.5 and 132.3,
126.1, 100.5, 71.6 and 70.9, 49.6 and 48.8, 36.3, 31.9,
30.6 and 30.1, 22.3 and 22.0, 19.7, 18.7 and 18.2, 17.2
and 16.6. Mass: m/z 276 and 278 (M+ and M++2,
0.2%), 165 (21), 151 (100), 153 (100), 125 (20), 109
(100). The 5-exo-trig radical cyclisation reaction of the
bromo ketal 8b (138 mg, 0.5 mmol) in benzene (28 ml)
with nBu3SnH (0.15 ml, 0.55 mmol) and a catalytic
amount of AIBN for 2.5 h as described for the cyclic
ketal 9a, and purification of the product on a neutral
alumina column using ethyl acetate–hexane (1:40) as
eluent furnished the cyclic ketal 9b (72 mg, 74%) as an
oil. IR (neat): wmax 1375, 1065 cm−1. 1H NMR (90
MHz, CDCl3, :1:1 mixture of methoxy epimers): l
3.10–3.56 (1H, m), 3.32 and 3.25 (3H, s), 1.10–2.20 (8H,
m), 1.46 (3H, s) 1.20 and 1.18 (3H, s, tert-CH3), 0.88
and 0.84 (3H, overlapping d, sec-CH3). Sonochemically
accelerated reaction of the cyclic ketal 9b (60 mg, 0.3
mmol) in acetone (0.5 ml) with Jones reagent (1.6 M,
0.2 ml, 0.32 mmol) for 5 min as described for the
diketone 10a and purification of the product on a silica
gel column using ethyl acetate–hexane (1:10) as eluent
furnished the diketone9 10b (40 mg, 72%) as an oil. IR
1
1700, 1630, 890 cm−1. H NMR (270 MHz, CDCl3): l
4.79 (1H, br s) and 4.71 (1H, br s) [C=CH2], 2.83 and
2.65 (2H, AB q, J=16.2 Hz, CH2COCH3), 2.30–2.60
(2H, m), 2.13 (3H, s, CH3-C=O), 1.98 (1H, t of d,
J=13.3 and 4.0 Hz), 1.60–1.90 (3H, m), 1.72 (3H, s,
olefinic CH3), 1.52 (1H, t of t, J=9.8 and 4.3 Hz), 1.12
(3H, s, tert-CH3). 13C NMR (100 MHz, CDCl3, SEFT):
l 213.4 (C, ring C=O), 206.8 (C, CH3-C=O), 147.2 (C,
C=CH2), 110.4 (CH2, C=CH2), 50.6 (CH2,
CH2COCH3), 47.0 (C, C-2), 45.6 (CH, C-5), 42.9 (CH2,
C-6), 37.1 (CH2, C-3), 31.6 (CH3, CH3-C=O), 25.6
(CH2, C-4), 22.9 (CH3, olefinic CH3), 20.9 (CH3, tert-
CH3). Mass: m/z 208 (M+, 16%), 151 (36), 152 (44), 123
(16), 111 (20), 110 (24), 109 (34), 95 (42), 43 (100). To
a solution of the diketone 10a (25 mg, 0.12 mmol) in
methanol (0.3 ml), placed in a Carius tube, was added
10% aq. KOH (0.1 ml, 0.15 mmol) and heated the
reaction mixture at 100–110°C for 2.5 h. The reaction
mixture was cooled, diluted with ether (5 ml), washed
with 0.5N aq. HCl and brine, and dried (Na2SO4).
Evaporation of the solvent and purification of the
product on a silica gel column using ethyl acetate–hex-
ane (1:10) as eluent furnished the enone 12a (18 mg,
79%) as an oil. [h]D26: +23.5 (c 2, CHCl3). IR (neat): wmax
1700, 1630, 1615, 890 cm−1. 1H NMR (270 MHz,
CDCl3): l 5.82 (1H, s, olefinic H), 4.87 (1H, s) and 4.74
(1H, s) [C=CH2], 2.94 (1H, d, J=11.2 Hz), 2.60–2.75
(2H, m), 2.30 and 2.19 (2H, AB q, J=18.3 Hz, CH2-
C=O), 1.40–2.00 (4H, m), 1.72 (3H, s, olefinic CH3),
1.28 (3H, s, tert-CH3). 13C NMR (100 MHz, CDCl3): l
207.9 (C-8), 186.7 (C-6), 145.8 (C=CH2), 128.0 (C-7),
1
(neat): wmax 1710 cm−1. H NMR (90 MHz, CDCl3): l
2.93 and 2.68 (2H, AB q, J=17 Hz, CH2-CO-CH3),
2.42 (2H, m), 2.14 (3H, s, CH3-C=O), 1.35–2.10 (6H,
m), 1.22 (3H, s, tert-CH3), 0.91 (3H, d, J=7.2 Hz,
sec-CH3). 13C NMR (100 MHz, CDCl3): l 214.4 (ring
C=O), 207.1 (CH3-C=O), 51.1, 46.2, 43.2, 38.1, 31.7,
29.0, 26.0, 20.9, 16.1. Mass: m/z 182 (M+, 5%), 139

2980
A. Srikrishna et al. / Tetrahedron: Asymmetry 14 (2003) 2975–2983
(20), 125 (100). HRMS: m/z for C11H18O2, calcd:
182.1307. Found: 182.1295. The intramolecular aldol
condensation of the diketone 10b (40 mg, 0.22 mmol) in
methanol (0.5 ml) with 10% aq. KOH (0.15 ml, 0.26
mmol) at 100–110°C for 2.5 h as described for the
enone 12a, and purification of the product on a silica
gel (0.5 g) column using ethyl acetate–hexane (1:10) as
eluent furnished the enone 12b9 (34 mg, 94%) as an oil.
tone 10c (42 mg, 73%) as an oil. IR (neat): wmax 1710
1
cm−1. H NMR (270 MHz, CDCl3): l 3.00–3.20 (1H,
m), 2.92 (1H, dd, J=17.3 and 7.7 Hz) and 2.08 (1H,
dd, J=17.4 and 4.7 Hz) [CH2COCH3], 2.40–2.60 (1H,
m) and 2.20–2.30 (1H, m), 2.20 (3H, s, CH3-C=O),
1.00–1.80 (4H, m), 1.25 (3H, s), 0.99 (3H, s). 13C NMR
(50 MHz, CHCl3+CDCl3): l 211.9 (ring C=O), 207.2
(CH3-C=O), 46.2, 42.9, 42.0, 39.8, 37.7, 31.1, 30.3,
27.5, 24.1. The intramolecular aldol condensation of
the diketone 10c (120 mg, 0.66 mmol) in methanol (0.5
ml) with 10% aq. KOH (0.55 ml, 0.99 mmol) at 100–
110°C for 2.5 h as described for the enone 12a, and
purification of the product on a silica gel column using
ethyl acetate–hexane (1:10) as eluent furnished the
enone 12c (100 mg, 92%) as an oil. IR (neat): wmax 1705,
1
IR (neat): wmax 1700, 1615 cm−1. H NMR (270 MHz,
CDCl3): l 5.85 (1H, d, J=1.3 Hz, olefinic H), 0.9–2.70
(7H, m), 2.52 and 2.02 (2H, AB q, J=18.1 Hz, CH2-
C=O), 1.38 (3H, s, tert-CH3) and 0.86 (3H, d, J=7.2
Hz, sec-CH3). 13C NMR (67.5 MHz, CDCl3): l 209.6
(C-9), 187.1 (C-6), 128.6 (C-7), 48.7 (C-9), 48.4 (C-1),
39.2, 29.1, 28.3, 27.4, 22.3 (tert-CH3), 15.5 (sec-CH3).
Mass: m/z 164 (M+, 65%), 149 (20), 136 (70), 122 (35),
121 (100), 108 (40), 107 (65), 93 (50). HRMS: m/z for
C11H16O, Calcd.: 164.1201. Found: 164.1190.
1
1620 cm−1. H NMR (90 MHz, CDCl3): l 5.85 (1H, s,
olefinic H), 2.40–2.80 (3H, m), 1.90–2.30 (3H, m), 1.40–
1.80 (3H, m), 1.09 (3H, s) and 0.83 (3H, s) [2×tert-
CH3]. Mass: m/z 164 (M+, 100), 149 (25), 119 (25), 109
(27), 108 (53), 107 (25), 97 (28), 96 (30), 95 (25), 91 (25).
HRMS: m/z for C11H16O, calcd: 164.1201. Found:
164.1217.
3.3. 3,3-Dimethylbicyclo[4.3.0]non-6-en-8-one 12c
The regioselective reduction of the enone 7c (500 mg,
4.03 mmol) in ether (15 ml) at −78°C with LiAlH4 (90
mg, 2.4 mmol) for 1.5 h as described for the allyl
alcohol 6b, and purification of the product on a silica
gel column with CH2Cl2 as eluent furnished the allyl
alcohol 6c (450 mg, 89%) as an oil. IR (neat): wmax 3330
3.4. Bicyclo[4.3.0]non-6-en-8-one 12d
The bromoacetalisation reaction of cyclohexenol 6d
(400 mg, 4.54 mmol) at −50°C with 2-methoxypropene
(0.85 ml, 9.1 mmol) and NBS (1.42 g, 8.0 mmol) in
CH2Cl2 (30 ml) for 1.5 h as described for the bromo
ketal 8a, and purification of the product on a neutral
alumina column with ethyl acetate–hexane (1:40) as
eluent furnished the bromo ketal 8d (795 mg, 79%) as a
colourless oil. IR (neat): wmax 1650, 1210, 1110, 1075,
1
cm−1. H NMR (90 MHz, CDCl3): l 5.54 (2H, m), 4.13
(1H, br s), 1.30–2.10 (5H, m), 1.02 (3H, s), 0.98 (3H, s).
The bromoacetalisation reaction of the allyl alcohol 6c
(385 mg, 3.06 mmol) at −50°C with 2-methoxypropene
(0.58 ml, 6.1 mmol) and NBS (1.09 g, 6.1 mmol) in
CH2Cl2 (30 ml) for 1.5 h as described for the bromo
ketal 8a, and purification of the product on a neutral
alumina column using ethyl acetate–hexane (1:40) as
eluent furnished the bromo ketal 8c (700 mg, 83%) as a
colourless oil. IR (neat): wmax 1215, 1115, 1080, 1035
cm−1. 1H NMR (90 MHz, CDCl3, :1:1 mixture of
epimers): l 5.56 and 5.48 (2H, s), 4.25 (1H, m), 3.50
and 3.34 (2H, AB q, J=11 Hz, CH2-Br), 3.28 and 3.26
(3H, s, O-CH3), 1.16–2.00 (4H, m), 1.50 and 1.38 (3H,
s), 1.01 (3H, s), 0.97 (3H, s). 13C NMR (50 MHz,
CHCl3+CDCl3): l 140.5 and 140.4, 126.6 and 126.3,
100.4, 66.3 and 66.2, 49.0, 35.6, 34.3 and 34.1, 31.5,
29.5 and 29.3, 28.5, 27.6, 22.1. Mass: m/z 261 (M−CH3,
0.5%), 165 (50), 153 (100), 151 (100), 140 (20), 125 (80),
110 (60), 109 (100), 93 (20). The 5-exo-trig radical
cyclisation reaction of the bromo ketal 8c (138 mg, 0.5
1
1040 cm−1. H NMR (90 MHz, CDCl3, :1:1 mixture
of epimers): l 5.40–5.90 (2H, m), 4.26 (1H, m), 3.38
and 3.34 (2H, s), 2.68 (3H, s), 1.30–2.10 (6H, m), 1.54
and 1.48 (3H, s). 13C NMR (22.5 MHz, CDCl3): l
129.8 and 128.8 (d) and 129.1 and 128.6 (d), 100.0 (s),
65.2 and 63.9 (d), 48.5 and 48.2 (q), 35.2 (t), 30.2 (t),
24.9 (t), 24.5 (t), 21.7 and 19.3 (q). Mass: m/z 217 and
219 (M−OCH3, 1%), 151 (55), 153 (55), 112 (10), 81
(100). The 5-exo-trig radical cyclisation reaction of the
bromo ketal 8d (375 mg, 1.5 mmol) in benzene (80 ml)
with nBu3SnH (0.45 ml, 1.65 mmol) and a catalytic
amount of AIBN for 2.5 h as described for the cyclic
ketal 9a, and purification of the product on a neutral
alumina column using ethyl acetate–hexane (1:40) as
eluent furnished the cyclic ketal 9d (184 mg, 72%) as an
oil. IR (neat): wmax 1210, 1185, 1155, 1115, 1080, 1065,
n
mmol) in benzene (28 ml) with Bu3SnH (0.15 ml, 0.55
1
mmol) and a catalytic amount of AIBN for 2.5 h as
described for the cyclic ketal 9a, and purification of the
product on a neutral alumina column using ethyl ace-
tate–hexane (1:40) as eluent furnished the cyclic ketal 9c
(73.3 mg, 75%) as an oil. IR (neat): wmax 1105, 1025
cm−1. 1H NMR (90 MHz, CDCl3, :1:1 mixture of
methoxy epimers): l 3.90–4.20 (1H, m), 3.25 and 3.20
(3H, s), 1.00–2.20 (9H, m), 1.42 and 1.36 (3H, s), 0.88
(3H, s), 0.84 (3H, s). Sonochemically accelerated reac-
tion of the cyclic ketal 9c (62 mg, 0.32 mmol) in acetone
(0.5 ml) with Jones reagent (1.6 M, 0.45 ml, 0.7 mmol)
for 5 min as described for the diketone 10a, and
purification of the product on a silica gel column using
ethyl acetate–hexane (1:10) as eluent furnished the dike-
1040 cm−1. H NMR (90 MHz, CDCl3, :1:1 mixture
of methoxy epimers): l 3.80–4.35 (1H, m), 3.22 and
3.20 (3H, s), 1.20–2.20 (11H, m), 1.35 and 1.36 (3H, s).
Sonochemically accelerated reaction of the cyclic ketal
9d (184 mg, 1.1 mmol) in acetone (1.5 ml) with Jones
reagent (1.6 M, 1.5 ml, 2.4 mmol) for 5 min as
described for the diketone 10a, and purification of the
product on a silica gel column using ethyl acetate–hex-
ane (1:10) as eluent furnished the diketone9 10d (150
mg, 89%) as an oil. IR (neat): wmax 1710 cm−1. 1H NMR
(90 MHz, CDCl3): l 2.75–3.20 (3H, m, CH-C=O and
CH2COCH3), 2.17 (3H, s, CH3-C=O), 1.10–2.60 (8H,
m). The intramolecular aldol condensation of the dike-
tone 10d (10 mg, 0.07 mmol) in ethanol (0.2 ml) with

A. Srikrishna et al. / Tetrahedron: Asymmetry 14 (2003) 2975–2983
2981
10% aq. KOH (0.04 ml, 0.08 mmol) at 100–110°C for
2.5 h as described for the enone 12a, and purification of
the product on a silica gel column using ethyl acetate–
hexane (1:10) as eluent furnished the enone9 12d (6 mg,
(69 mg, 84%) as oil. IR (neat): wmax 1705 cm−1. 1H
NMR (270 MHz, CDCl3, peaks due to the major
isomer): l 3.01 (1H, m, CH-C=O), 2.70 (1H, dd,
J=16.7 and 9.0 Hz) and 2.41 (1H, dd, J=16.8 and 5.1
Hz) [CH2COCH3], 2.10–2.36 (2H, m), 2.19 (3H, s,
CH3-C=O), 1.45–1.70 (3H, m), 1.02 (3H, s) and 0.99
(3H, s) [2×tert-CH3], 0.92 (3H, d, J=7.2 Hz, sec-CH3).
13C NMR (100 MHz, CDCl3, SEFT, peaks due to the
major isomer): l 212.4 (C, ring C=O), 206.8 (C, CH3-
C=O), 52.6 (CH2, CH2COCH3), 49.4 (CH, CH-C=O),
43.6 (CH2, ring CH2-C=O), 40.3 (CH2, C-4), 36.6 (C,
C-5), 33.3 (CH3, CH3-C=O), 30.6 (CH, C-5), 29.9
(CH3), 28.3 (CH3), 17.8 (CH3). Mass: m/z 181 (M+−
CH3, 100), 149 (22), 123 (82), 109 (15), 97 (15), 95 (16).
The intramolecular aldol condensation of the diketone
10e (60 mg, 0.31 mmol) in methanol (0.5 ml) with 10%
aq. KOH (0.4 ml, 0.36 mmol) at 100–110°C for 2.5 h as
described for the enone 12a, and purification of the
product on a silica gel column using ethyl acetate–hex-
ane (1:10) as eluent furnished a 6:1 epimeric mixture of
the enones 12e (46 mg, 85%) as an oil. IR (neat): wmax
1700, 1615 cm−1. 1H NMR (400 MHz, CDCl3, 6:1
mixture of epimers, peaks due to major isomer): l 5.82
(1H, s, olefinic H), 2.54 (1H, dd, J=18.5 and 6.4 Hz)
and 2.04 (1H, dd, J=18.4 and 1.6 Hz) [H-9], 2.45 (1H,
dd, J=13.2 and 2.1 Hz) and 2.10 (1H, d, J=14.3 Hz)
[H-5], 2.10–2.20 (1H, m, H-1), 1.75–1.90 (1H, m, H-2),
1.35–1.55 (2H, m), 1.06 (3H, s) and 0.82 (3H, s) [2×tert-
CH3], 0.98 (3H, d, J=6.3 Hz, sec-CH3). peaks due to
the minor isomer: l 5.80 (s, olefinic H), 1.14 (d, J=6.4
Hz, sec-CH3), 1.09 (s) and 0.94 (s) [2×tert-CH3]. 13C
NMR (100 MHz, CDCl3, 6:1 mixture of epimers, peaks
due to the major isomer): l 207.8 (C-8), 182.0 (C-6),
127.2 (C-7), 47.3, 46.1, 42.6, 39.6, 35.1, 31.0, 30.8, 24.1,
19.6. peaks due to the minor isomer: l 207.8 (C-8),
188.3 (C-6), 123.6 (C-7), 46.5, 46.1, 41.0, 37.0, 33.1,
30.6, 28.4, 23.4, 16.7. Mass: m/z 178 (M+, 51%), 163
(30), 135 (15), 121 (35), 107 (15), 96 (40), 83 (100).
HRMS: m/z for C12H18O, calcd: 178.1358. Found:
178.1345.
1
68%) as an oil. IR (neat): wmax 1705, 1620 cm−1. H
NMR (270 MHz, CDCl3): l 5.83 (1H, s, olefinic H),
2.82 (1H, d, J=13.7 Hz), 2.40–2.70 (2H, m), 1.00–2.40
(8H, m).
3.5. (1a and 1b,2a)-2,4,4-Trimethylbicyclo[4.3.0]non-6-
en-8-one 12e
Regioselective reduction of isophorone (7e, 2.0 g, 14.5
mmol) in ether (30 ml) at −78°C with LiAlH4 (270 mg,
7.25 mmol) for 1.5 h as described for the allyl alcohol
6b, and purification of the product on a silica gel
column with CH2Cl2 as eluent furnished the allyl alco-
hol 6e (1.85 g, 91%) as an oil. IR (neat): wmax 3300, 1660
1
cm−1. H NMR (90 MHz, CDCl3): l 5.36 (1H, br s,
olefinic H), 3.80–4.14 (1H, m, O-CH), 2.88 (1H, s, OH),
1.00–2.20 (4H, m), 1.66 (3H, s, olefinic CH3), 1.00 (3H,
s) and 0.90 (3H, s) [2×tert-CH3]. The bromoacetalisa-
tion reaction of the allyl alcohol 6e (500 mg, 3.57
mmol) at −50°C with 2-methoxypropene (0.68 ml, 7.14
mmol) and NBS (712 mg, 4.0 mmol) in CH2Cl2 (30 ml)
for 1.5 h as described for the bromo ketal 8a, and
purification of the product on a neutral alumina
column using ethyl acetate–hexane (1:40) as eluent fur-
nished the bromo ketal 8e (865 mg, 83%) as a colourless
oil. IR (neat): wmax 1660, 1210, 1110, 1075, 1050, 1010
1
cm−1. H NMR (90 MHz, CDCl3): l 5.34 (1H, br s,
olefinic H), 4.34 (1H, br s, O-CH), 3.50 and 3.35 (AB q,
J=10 Hz) and 3.40 (s) [2H, CH2-Br], 3.30 and 3.26
(3H, s, O-CH3), 1.30–2.00 (4H, m), 1.68 (3H, s, olefinic
CH3), 1.52 and 1.38 (3H, s), 1.00 (3H, s), 0.91 (3H, s).
13C NMR (22.5 MHz, CDCl3): l 136.3 and 135.5 (s,
C=CH), 122.5 and 122.3 (d, C=CH), 100.5 (s, O-C-
O), 67.1 and 71.8 (d, O-CH), 49.1 and 50.0 (q, O-CH3),
43.9 and 44.2 (t), 43.7 and 43.5 (s), 42.3 and 35.8 (t),
31.4 (2 C, q and t), 26.3 (q), 23.8 (q), 22.4 (q). Mass:
m/z 179 [(M−CH3OH,Br), 22%], 151 and 153 (100), 139
(22), 123 (90). HRMS: m/z for C12H19O (M−
CH3OH,Br), calcd: 179.1436. Found: 179.1427. The
5-exo-trig radical cyclisation reaction of the bromo
ketal 8e (220 mg, 0.75 mmol) in benzene (40 ml) with
nBu3SnH (0.25 ml, 0.92 mmol) and a catalytic amount
of AIBN for 2.5 h as described for the cyclic ketal 9a,
and purification of the product on a neutral alumina
column using ethyl acetate–hexane (1:40) as eluent fur-
nished the cyclic ketal 9e (117 mg, 73%) as an oil. IR
(neat): wmax 1210, 1100, 1070, 1040, 1015 cm−1. 1H
NMR (90 MHz, CDCl3, :1:1 mixture of methoxy
epimers): l 4.00–4.40 (1H, m, O-CH), 3.29 and 3.26
(3H, s, O-CH3), 1.20–2.80 (8H, m), 1.47 and 1.41 (3H,
s, tert-CH3), 0.91 (3H, d, J=7.2 Hz, sec-CH3), 0.95
(3H, s) and 0.88 (3H, s) [2×tert-CH3]. Sonochemically
accelerated reaction of the cyclic ketal 9e (89 mg, 0.42
mmol) in acetone (0.5 ml) with Jones reagent (1.6 M,
0.5 ml, 0.9 mmol) for 5 min as described for the
diketone 10a, and purification of the product on a silica
gel column using ethyl acetate–hexane (1:10) as eluent
furnished a :3:1 epimeric mixture of the diketone 10e
3.6. (1b,2a)-1,2-Dimethylbicyclo[4.3.0]nonan-8-one 15
To a solution of the enone 12b (30 mg, 0.18 mmol) in
methanol (0.5 ml) was added 10%Pd/C (catalytic, :3
mg). The flask was filled with hydrogen via evacuative
displacement and the reaction mixture was magnetically
stirred under hydrogen (balloon) atmosphere for 5 h.
The catalyst was filtered off and the solvent was evapo-
rated under reduced pressure. Purification of the
product on a silica gel column using ethyl acetate–hex-
ane (1:10) as eluent furnished the saturated ketone 15
(30 mg, 99%) as oil. IR (neat): wmax 1745 cm−1. 1H
NMR (200 MHz, CDCl3): l 2.62 (1H, dd, J=18.8 and
7.4 Hz, H-7A), 2.29 and 1.86 (2H, AB q, J=18.3 Hz,
H-9), 1.00–2.00 (9H, m), 1.09 (3H, s, tert-CH3), 0.87
(3H, d, J=6.6 Hz, sec-CH3). 13C NMR (100 MHz,
CDCl3): l 44.9, 42.7, 42.5, 42.2, 39.2, 31.4, 30.9, 26.9,
25.2, 17.4 (ketone carbon not seen). Mass: m/z 166
(M+, 58%), 151 (20), 123 (32), 110 (25), 109 (100), 108
(37), 97 (25), 96 (35), 95 (40). HRMS: m/z for C11H18O,
calcd: 166.1358. Found: 166.1351.

2982
A. Srikrishna et al. / Tetrahedron: Asymmetry 14 (2003) 2975–2983
NaHCO3 and brine, and dried (Na2SO4). Evaporation
of the solvent and purification of the product on a silica
gel column using ethyl acetate–hexane (1:10) as eluent
furnished the hemi acetal 19 (5.6 mg, 76%) as a colour-
less oil. To a magnetically stirred solution of the hemi
acetal 19 (5.6 mg, 0.024 mmol) in CH2Cl2 (1 ml) was
added PCC (20 mg, 0.093 mmol) and silica gel (20 mg).
The reaction mixture was stirred at room temperature
for 2 h and filtered through a silica gel column using
CH2Cl2 as eluent. Evaporation of the solvent and fur-
ther purification of the product on a silica gel column
using ethyl acetate–hexane (1:40) as eluent furnished a
1:1 epimeric mixture of epibakkenolides-A 14 and 20
(5.3 mg, 95%) as a colourless oil. IR (neat): wmax 1775,
3.7. 1,2-Dimethylbicyclo[4.3.0]nonane-8,3%spiro-[4%-
methylenedihydrofuran-2%(3%H)-one] [4-epi-bakkenolide-A
14 and 4,7-diepibakkenolide-A 20]
To a magnetically stirred solution of potassium tert-
amylate [prepared from 51 mg (1.32 mmol) of potas-
sium in tert-amyl alcohol (1.5 ml] in dry THF (2 ml) at
room temperature was added (methoxymethyl)-
triphenylphosphonium chloride (480 mg, 1.4 mmol) and
the resulting red coloured solution was stirred at room
temperature for 15 min. To the ylide thus formed, was
added the ketone 15 (100 mg, 0.6 mmol) and stirred at
room temperature for 2 h. The reaction mixture was
then diluted with ether (5 ml), washed with brine and
dried (Na2SO4). Evaporation of the solvent and purifi-
cation of the product on a neutral alumina column
using ethyl acetate–hexane (1:40) as eluent furnished
the enol ether 16 (105 mg, 62%) as oil. IR (neat): wmax
1690 cm−1. To a cold (−40°C), magnetically stirred
solution of NBS (50 mg, 0.28 mmol) and propargyl
alcohol (0.05 ml, 0.86 mmol) in CH2Cl2 (4 ml) was
added a solution of the enol ether 16 (46 mg, 0.24
mmol) in CH2Cl2 (1 ml) over a period of 15 min. The
reaction mixture was stirred for 45 min at the same
temperature, diluted with CH2Cl2 (5 ml), washed with
1% aq. NaOH and brine, and dried (Na2SO4). Evapora-
tion of the solvent and purification of the product on a
neutral alumina column using ethyl acetate–hexane
(1:40) as eluent furnished the bromo acetal 17 (58 mg,
1
1670, 895 cm−1. H NMR (400 MHz, CDCl3): l 5.20
and 5.18 (1H, s) and 5.04 and 5.02 (1H, s) [C=CH2],
4.75 and 4.68 (2H, AB q, J=12 Hz, O-CH2), 2.65
(0.5H, dd, J=13.6 and 6.8 Hz), 2.39 (0.5H, d, J=13.4
Hz), 2.27 (0.5H, dd, J=13.6 and 6.4 Hz), 1.40–2.00
(10.5H, m), 1.24 and 1.13 (3H, s, tert-CH3), 0.89 and
0.86 (3H, d, J=6.8 Hz, sec-CH3). Mass: m/z 234 (M+,
36%), 219 (21, M−CH3), 175 (21), 149 (50), 147 (35),
133 (25), 124 (100), 123 (43), 111 (55), 109 (70). HRMS:
m/z for C15H22O2, calcd: 234.1620. Found: 234.1612.
Acknowledgements
1
75%) as oil. IR (neat): wmax 3300 cm−1. H NMR (90
We thank the University Grants Commission, New
Delhi and Indian Institute of Science for providing
senior research fellowships to R.V. and J.A.S. We are
grateful to DST and CSIR for supporting our research.
MHz, CDCl3, 3:1 mixture of epimers): l 4.51 and 4.48
(1H, s), 4.46 and 4.41 (2H, s), 3.64 and 3.62 (3H, s),
1.0–2.80 (13H, m), 1.32 and 0.98 (3H, s), 0.82 and 0.80
(3H, d, J=7.2 Hz). Mass: m/z 297 and 299 [(M−
OCH3), 1%], 249 (22), 217 (20), 193 (30), 161 (42), 149
(25), 109 (42), 100 (60), 99 (100), 93 (40). A magneti-
cally stirred suspension of the bromo acetal 17 (116 mg,
0.36 mmol), nBu3SnCl (0.015 ml, 0.056 mmol),
NaCNBH3 (40 mg, 0.64 mmol) and AIBN (catalytic) in
tert-butanol (3 ml) was refluxed for 1.5 h. The solvent
was then evaporated under reduced pressure and the
residue taken in water (5 ml) and extracted with ether
(3×5 ml). The combined ether extract was washed with
1% aqueous ammonia and brine, and dried (Na2SO4).
Evaporation of the solvent and purification of the
product on a silica gel column using ethyl acetate–hex-
ane (1:40) as eluent furnished the spiro acetal 18 (72
References
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3. (a) Giese, B.; Kopping, B.; Gobel, T.; Dickhaut, G.;
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5. Garver, L.; van Eikeren, P.; Byrd, J. E. J. Org. Chem.
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1
mg, 83%) as colourless oil. IR (neat): wmax 880 cm−1. H
NMR (90 MHz, CDCl3, :1:1 mixture of spiro
epimers): l 5.05 (1H, br s) and 4.95 and 4.85 (1H, br s)
[C=CH2], 4.7 and 4.65 (1H, s, O-CH-OCH3), 4.47 and
4.28 (2H, t of AB q, J=12 and 2 Hz, O-CH2), 3.32 and
3.34 (3H, s, O-CH3), 1.00–2.60 (12H, m), 1.03 and 1.01
(3H, s, tert-CH3), 0.90 and 0.80 (3H, d, J=7.2 Hz,
sec-CH3). Mass: m/z 219 (M−OCH3, 20%), 190 (55),
175 (65), 147 (100), 133 (40), 119 (35), 105 (35), 95 (35),
93 (35). HRMS: m/z for C16H26O2, calcd: 250.1933.
Found: 250.1920. To a solution of the spiro acetal 18 (7
mg, 0.028 mmol) in THF (0.5 ml) at room temperature
was added 2.2N aq. HCl (1 ml) and sonicated for 4 h in
an ultrasonic cleaning bath. The reaction mixture was
diluted with ether (5 ml), washed with saturated aq.
6. Rodriguez, J.; Dulcere, J.-P. Synthesis 1993, 1177.
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