Rearrangement approaches to sesquiterpenes containing multiple contiguous quaternary carbon atoms. Total synthesis of (±)-myltayl-8(12)-ene and (±)-6-epijunicedranol

Article abstract of DOI:10.1039/a906706j

Details of the first total syntheses of the sesquiterpenes myltayl-8(12)-ene and 6-epijunicedran-8-ol are described. The aldehyde 13, obtained by Claisen rearrangement of cyclogeraniol, was transformed into the dienones 12 and 18. Boron trifluoride-diethy

Full text of DOI:10.1039/a906706j

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Rearrangement approaches to sesquiterpenes containing multiple
contiguous quaternary carbon atoms. Total synthesis of ( )-myltayl-
8(12)-ene and ( )-6-epijunicedranol
A. Srikrishna,* C. V. Yelamaggad and P. Praveen Kumar
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received (in Cambridge, UK) 18th August 1999, Accepted 31st August 1999
Details of the first total syntheses of the sesquiterpenes myltayl-8(12)-ene and 6-epijunicedran-8-ol are described.
The aldehyde 13, obtained by Claisen rearrangement of cyclogeraniol, was transformed into the dienones 12 and 18.
Boron trifluoride–diethyl ether mediated cyclization and rearrangement transformed the dienones 12 and 18 into
the tricyclic ketones 16 and 17, efficiently creating three and four contiguous quaternary carbon atoms, respectively.
Wittig methylenation of 16 furnished ( )-myltayl-8(12)-ene (11), whereas reduction of the ketone 17 furnished ( )-6-
epijunicedranol (23).
The creativity of Nature in devising varied molecular archi-
tecture is revealed through the isolation of a wide range of
natural products with remarkable skeletal build-up and multi-
farious functionalities. Among the natural products, terpenoids
occupy a special position on account of their widespread
occurrence and the bewildering array of carbocyclic skeleta
that they embody. Sesquiterpenes, biogenetically derived from
farnesyl pyrophosphate, are assembled in acyclic, monocyclic,
bicyclic, tricyclic and even tetracyclic structures containing
small, medium and large rings and a wide range of function-
alities.1 Because of this phenomenal structural diversity, this
class of natural products holds special appeal to synthetic
chemists and provides a fertile ground for developing and
testing new synthetic strategies, particularly those directed
towards the carbocyclic ring construction. As a result, synthetic
activity in this area continues to flourish.2 Even though there
are several methods developed for the creation of a quaternary
carbon atom, the presence of two or more quaternary carbon
atoms in contiguous manner in sesquiterpenes makes them
challenging synthetic targets.
isolation of cyclomyltaylene 4a from the Taiwanese liverwort
Bazzania tridens and cyclomyltaylenol 4b from Reboulia
hemisphaerica. In 1996, Asakawa and co-workers reported6 the
isolation of myltaylenol 5 from the French liverwort Bazzania
trilobata. A characteristic of the structure of the myltaylane
and cyclomyltaylanes is the presence of a 2,2,6,8-tetramethyl-
tricyclo[5.2.2.01,6]undecane carbon framework comprising
three contiguous quaternary carbon atoms. Recently, Barrero
and co-workers reported7 the isolation of the crystalline
sesquiterpene, junicedranol 6 from the essential oil of the wood
of Juniperus oxycedrus sp. macrocarpa, comprising a 2,2,6,7-
tetramethyltricyclo[5.2.2.01,6]undecane carbon framework
incorporating four contiguous quaternary carbon atoms (C-1,
2, 6 and 7). The relative stereostructure of junicedranol (6) was
established by using various 2D NMR correlation techniques
on junicedranol (6) and its acetate 7. Biosynthetically junice-
dranol (6) is very interesting. A possible biosynthetic pathway
to junicedranol (6) was proposed7 by Barrero and co-workers as
depicted in Scheme 1. The chamigrenyl cation 8 was postulated
as the precursor of the junicedrane carbon skeleton. The
chamigrenyl cation 8 might be formed from either the cuparenyl
cation 9, or the widdrenyl cation 10. Cyclization of the
chamigrenyl cation 8 via an intramolecular anti-Markovnikov
addition leads to the junicedrane framework.
Interesting structural features, particularly the presence
of the tricyclo[5.2.2.01,6]undecane carbon framework com-
prising three and four contiguous quaternary carbon atoms
in myltaylane and junicedranes, respectively, made them
challenging synthetic targets. As part of our ongoing efforts on
the synthesis of sesquiterpenes containing multiple contiguous
carbon atoms,8 we have developed a novel approach to myltay-
lane and junicedranes.9,10 Subsequent to our report on the first
total synthesis9 of myltaylene 11, Winterfeldt and co-workers
reported11 an enatioselective synthesis of (Ϫ)-myltaylenol 1
by employing an intramolecular Diels–Alder cycloaddition
reaction based strategy. Herein we describe the details of our
first total synthesis9 of myltayl-8(12)-ene12 11 and its extension
to the first total synthesis10 of a junicedrane.
A biogenetically patterned cation mediated cyclization
and rearrangement of the dienone 12 was explored for the syn-
thesis of myltaylene 11. The synthetic sequence is depicted
in Scheme 2. It was conceived that the dienone 12 could be
prepared from the aldehyde 13, which in turn could be obtained
from cyclogeraniol 14 via the Claisen rearrangement. The
requisite starting material, cyclogeraniol 14 was obtained from
Matsuo and co-workers in 1985 and 1988 reported3 the
isolation of novel, irregular sesquiterpene alcohols, myltaylenol
1 and cyclomyltaylenol 2 from the liverwort Mylia taylorii
(Hook, S. Gray) and identified the new carbon frameworks
present in them as myltaylane and cyclomyltayalanes. In
1991, Asakawa and co-workers reported4 the isolation of
cyclomyltaylenol 3a and its caffeate ester 3b from the liverwort
Bazzania japonica. Later, Wu and co-workers reported5 the
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crystal X-ray analysis9 of 20 unambiguously established the
structure of normyltaylanone 16. Finally, Wittig methylenation
of normyltaylanone 16 with methylenetriphenylphosphorane
furnished myltayl-8(12)-ene 11. Formation of normyltaylanone
16 from the dienone 12 can be explained as depicted in Scheme
3. First, acid catalyzed cyclization of the dienone 12 generates
Scheme 3
Scheme 1
the bicyclic tertiary carbonium ion 21, which rearranges to the
spiro system 22. Reketonization of 22 via cyclization from the
α-face of the carbonium ion centre furnishes normyltaylanone
16 with methyl group at C-6 and the ketone anti to each other.
The remarkable similarity of the mechanism depicted in
Scheme 3 for the formation of normyltaylanone 16 to the
proposed7 biosynthesis of junicedranol (cf. Scheme 1) is worth
noting. A close perusal of the two schemes, particularly the last
step, indicates that the cyclization of the chamigrenyl cation 8
could lead to an isomeric junicedranyl carbonium ion 30 as
the cyclization places the C-6 methyl group and the cationic
centre anti to each other, analogous to 16. This prompted us to
investigate the synthesis of junicedranol employing the same
strategy as that used for myltaylene 11, which led to the first
total synthesis of 6-epijunicedranol (or 11-junicedranol) 23.
For the synthesis of epijunicedranol 23, based on the synthesis
of myltylene 11, it was anticipated that epijunicedran-8-one 17
could be obtained via a Lewis acid mediated cyclization of the
dienone 18, Scheme 2. Thus, reaction of the aldehyde 13 with
isopropenylmagnesium bromide in THF at room temperature
generated a 3:1 epimeric mixture of the corresponding allylic
alcohol. Oxidation of this secondary alcohol with pyridinium
chlorochromate,15
Scheme
2
Reagents and conditions: (a) O3/O2, MeOH; NaBH4;
(b) CH2᎐᎐CH–OEt, Hg(OAc)2; ∆; (c) CH2᎐᎐C(R)–MgBr; (d) PCC,
NaOAc; (e) BF3ؒOEt2; (f) Ph3P᎐CH2.
᎐
the commercially available β-ionone 15. Thus, controlled ozo-
nation8c,13 of β-ionone 15 followed by reduction of the ozonide
with sodium borohydride furnished cyclogeraniol 14. One-pot
Claisen rearrangement of cyclogeraniol 14 using ethyl vinyl
ether and mercuric acetate at 170 ЊC in a sealed tube furnished
the aldehyde14 13 in 65% yield. Addition of vinylmagnesium
bromide to the aldehyde 13 furnished an epimeric mixture
of the corresponding allyl alcohol, which on oxidation with
pyridinium chlorochromate (PCC)15 and sodium acetate
generated the key intermediate of the sequence, the dienone 12,
in 65% overall yield. Treatment of the dienone 12 with a
catalytic amount of boron trifluoride–diethyl ether in methy-
lene chloride furnished normyltaylanone 16, in 60% yield,
whose structure was established from its spectral data. To
confirm the structure of normyltaylanone 16, the ketone in
16 was reduced to the alcohol 19, and was converted into the
p-nitrobenzoate derivative 20, mp 156–157 ЊC. The single
sodium acetate and 4 Å molecular sieves
powder in methylene chloride at room temperature furnished
the dienone 18 in 82% yield. Treatment of the dienone 18
in methylene chloride with a catalytic amount of boron
trifluoride–diethyl ether for 30 min at 0 ЊC, as expected,
furnished 6-epijunicedran-8-one 17 in 60% yield. The
structure of 17 was established by comparison of the 1H and 13
C
NMR spectral data with those of normyltaylanone 16. Finally,
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treatment of the ketone 17 with lithium in liquid ammonia and
THF furnished 6-epijunicedranol (23), which on acetylation
with acetic anhydride and pyridine in the presence of a catalytic
amount of DMAP furnished the corresponding acetate 24.
Very recently,16 Frater and co-workers have reported the
formation of the 6-epijunicedran-8-yl formate 28 as a minor
product in the acid catalyzed formolysis reaction of either β-
monocyclofarnesol 25 or the tertiary alcohol 26 or chamigrene
27 via the carbonium ion 29 and junicedranyl carbonium
ion 30, Scheme 4. The formate 28 was converted into 6-
of chamigranyl cation 8 generates tricyclic cation 29, which
rearranges to the junicedranyl cation 30 (cf. Scheme 4). A
1,3-hydride shift16,17 in the cation 30 generates the isomeric
cation 31 leading to junicedranol 6. The second possibility is
the formation of the cyclopropane ring from the cation 30 to
form cyclojunicedrane 32, which reopens to generate the
junicedranyl cation 31 leading to junicedranol 6. The concept
of cyclojunicedrane is supported by the existense of myltaylane
and cyclomyltaylenes;5,6 seychellene and cycloseychellenes;
etc.1 type of sesquiterpenes in Nature.
In conclusion, we have achieved the first total synthesis of
( )-myltaylene (11) and ( )-6-epijunicedranol (23) starting
from the readily available cyclogeraniol (14), employing bio-
genetically patterned acid catalyzed carbonium ion mediated
cyclization and rearrangement of the dienones 12 and 18, in
which three and four contiguous quaternary carbon atoms were
efficiently generated, respectively.
Experimental
2-(1,3,3-Trimethyl-2-methylenecyclohexyl)acetaldehyde (13)
A solution of cyclogeraniol (14, 800 mg, 5.2 mmol), ethyl vinyl
ether (2.4 mL, 26.0 mmol) and a catalytic amount (40 mg) of
mercuric acetate was placed in a Carius tube and heated to
170 ЊC for 24 h in an oil bath. The reaction mixture was cooled,
diluted with ether (15 mL), washed with brine and dried
(Na2SO4). Evaporation of the solvent and purification of the
product on a silica gel (8 g) column using ethyl acetate–hexane
(1:20 to 1:10) as eluent furnished the aldehyde14 13 (600 mg,
1
64%) as an oil. IR (neat): νmax 2720, 1715, 1620, 900 cmϪ1. H
NMR (300 MHz, CDCl3 ϩ CCl4): δ 9.67 (1 H, t, J = 3.0 Hz),
5.10 (1 H, s), 4.90 (1 H, s), 2.64 (1 H, dd, J = 15 and 3 Hz), 2.30
(1 H, dd, J = 15.0 and 3.0 Hz), 1.70–1.40 (6 H, m), 1.26 (3 H, s),
1.16 (6 H, s). 13C NMR (75 MHz, DEPT, CDCl3 ϩ CCl4):
δ 203.4 (CH), 159.5 (C), 109.7 (CH2), 53.1 (CH2), 40.9 (CH2),
40.3 (CH2), 38.5 (C), 36.5 (C), 32.3 (CH3), 30.6 (CH3), 30.3
(CH3), 18.6 (CH2). Mass: m/z 180 (Mϩ, 1%), 153 (30), 137 (25),
123 (33), 107 (25), 95 (25), 73 (100).
1-(1,3,3-Trimethyl-2-methylenecyclohexyl)but-3-en-2-one (12)
To a cold (0 ЊC), magnetically stirred solution of vinylmagne-
sium bromide [prepared from magnesium (186 mg, 7.6 mmol)
and vinyl bromide (0.72 mL, 10.2 mmol) and a catalytic
amount of iodine in 4 mL of dry THF] was added dropwise
a solution of the aldehyde 13 (640 mg, 3.6 mmol) in 3 mL of
dry THF. The reaction mixture was slowly warmed up to room
temp. and stirred for 2 h. It was then poured into saturated
aq. NH4Cl solution and extracted with ether (2 × 10 mL).
The ether extract was washed with brine and dried (Na2SO4).
Evaporation of the solvent furnished an epimeric mixture of
the intermediate secondary alcohol (480 mg, 65%) as an oil. IR
(neat): νmax 3430, 1625, 900 cmϪ1. 1H NMR (300 MHz, CDCl3,
peaks due to the major isomer): δ 5.90–5.80 (1 H, m), 5.25–5.00
(2 H, m), 5.11 (1 H, s), 5.01 (1 H, s), 4.16 (1 H, t, J = 7.7 Hz),
2.30–1.25 (9 H, m), 1.23 (3 H, s), 1.14 (3 H, s), 1.09 (3 H, s).
Peaks due to the minor isomer: δ 5.90–5.80 (1 H, m), 4.30 (1 H,
t, J = 7.7 Hz), 1.21 (3 H, s), 1.18 (3 H, s), 1.15 (3 H, s). 13C
NMR (75 MHz, CDCl3, peaks due to the major isomer):
δ 160.5 (C), 142.7 (CH), 113.0 (CH2), 109.7 (CH2), 71.3 (CH),
46.6 (CH), 41.3 (CH2), 41.2 (CH2), 39.6 (CH2), 36.5 (C), 32.8
(C), 30.4 (CH3), 29.8 (CH3), 18.6 (CH3).
Scheme 4
epijunicedran-8-one 17 via hydrolysis and oxidation. Formation
of 6-epijunicedranone 17 from the dienone 18 in our synthesis,
and formation16 of the formate 28 from 26 and 27 is worth
noting in comparison to the biogenetic formation of junice-
dranol (cf. Scheme 1) from the same chamigrenyl carbonium
ion 8 (difference in stereochemistry at C-6). Alternatively one
can consider two possibilities for the biogenetic transformation
of the chamigranyl cation 8 into junicedranol (6) via the forma-
tion of the junicedranyl cation 30, Scheme 5. First, cyclization
To a magnetically stirred solution of the alcohol (440 mg,
2.11 mmol) in 5 mL of dry CH2Cl2 was added a homogeneous
mixture of PCC (910 mg, 4.2 mmol) and NaOAc (420 mg,
2.02 mmol) and the mixture was stirred vigorously for 30 min
at room temp. It was then filtered through a small silica gel
column and eluted with excess CH2Cl2. Evaporation of the
solvent and purification of the residue on a silica gel column
using ethyl acetate–hexane (1:4) as eluent furnished the
Scheme 5
J. Chem. Soc., Perkin Trans. 1, 1999, 2877–2881
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dienone 12 (270 mg, 65%) as an oil. IR (neat): νmax 1690, 1620,
900 cmϪ1 1H NMR (300 MHz, CDCl3): δ 6.35 (1 H, dd,
(3 H, s), 1.02 (3 H, s). Peaks due to the minor isomer: δ 4.88
.
(1 H, s), 4.72 (1 H, s), 1.16 (3 H, s), 1.12 (3 H, s), 1.08 (3 H, s).
Mass: m/z 222 (Mϩ, 3%), 138 (30), 123 (100). HRMS: Calcd. for
C15H26O m/z 222.1984. Found: 222.1985.
J = 17.7 and 10.8 Hz), 6.14 (1 H, d, J = 17.7 Hz), 5.68 (1 H, d,
J = 10.8 Hz), 5.00 (1 H, s), 4.85 (1 H, s), 2.80 and 2.72 (2 H, AB
q, J = 14.7 Hz), 1.80–1.25 (6 H, m), 1.22 (3 H, s), 1.16 (3 H, s),
1.14 (3 H, s). 13C NMR (22.5 MHz, CDCl3): δ 199.6 (C), 161.0
(C), 137.9 (CH), 126.9 (CH2), 108.2 (CH2), 50.4 (CH2), 40.5 (C),
39.2 (CH2), 38.4 (CH2), 36.1 (C), 32.3 (CH3), 31.0 (CH3), 29.5
(CH3), 18.3 (CH2). Mass: m/z 206 (Mϩ, 8%), 191 (8), 137 (80),
121 (100), 95 (95). HRMS: Calcd. for C14H22O m/z 206.1670.
Found: 206.1640.
To a magnetically stirred solution of the alcohol (43 mg,
0.2 mmol) in 1.5 mL of dry CH2Cl2 was added a homogeneous
mixture of PCC (83 mg, 0.4 mmol), NaOAc (21 mg, 0.4 mmol)
and 4 Å molecular sieves powder (85 mg) and the mixture
was stirred vigorously for 45 min at room temp. The reaction
mixture was then filtered through a small silica gel column and
eluted with an excess of CH2Cl2. Evaporation of the solvent
and purification of the residue on a silica gel column using ethyl
acetate–hexane (1:4) as eluent furnished the dienone 18 (35 mg,
82%) as an oil, which was found to decompose slowly on stand-
ing and hence was used immediately in the next reaction. IR
(neat): νmax 1660, 895 cmϪ1. 1H NMR (200 MHz, CDCl3): δ 5.90
(1 H, s), 5.73 (1 H, s), 5.00 (1 H, s), 4.86 (1 H, s), 2.97 and 2.84
(2 H, AB q, J = 14.8 Hz), 1.90–1.20 (6 H, m), 1.86 (3 H, s), 1.20
(3 H, s), 1.15 (6 H, s). Mass: m/z 220 (Mϩ, 17%), 205 (13), 137
(95), 122 (100), 109 (35).
2,2,6-Trimethyltricyclo[5.2.2.01,6]undecan-8-one (16)
To a cold (0 ЊC) magnetically stirred solution of the dienone 12
(250 mg, 1.21 mmol) in dry CH2Cl2 (5 mL) was added BF3ؒEt2O
(0.015 mL, 0.12 mmol), and the reaction mixture was stirred
for 20 min at the same temperature. It was then quenched with
aq. NaHCO3 solution and extracted with CH2Cl2 (2 × 8 mL).
The organic layer was washed with saturated aq. NaHCO3
solution and water, and dried (Na2SO4). Evaporation of the
solvent and purification of the residue on a silica gel column
using ethyl acetate–hexane (1:20) as eluent furnished nor-
myltaylanone 16 (123 mg, 60%) as an oil. IR (neat): νmax 1745
2,2,6,7-Tetramethyltricyclo[5.2.2.01,6]undecan-8-one (6-epi-
junicedran-8-one 17)
1
cmϪ1. H NMR (270 MHz, CDCl3): δ 2.50 (1 H, dd, J = 18.6
To a cold (0 ЊC) magnetically stirred solution of the dienone
18 (10 mg, 0.05 mmol) in dry CH2Cl2 (0.4 mL) was added
BF3ؒEt2O (15 µL), and the reaction mixture was stirred for
30 min at the same temperature. It was then quenched with 10%
aq. NH3 solution and extracted with CH2Cl2 (2 × 5 mL). The
organic layer was washed with saturated aq. NaHCO3 solution
and water, and dried (Na2SO4). Evaporation of the solvent and
purification of the residue on a silica gel column using ethyl
acetate–hexane (1:20) as eluent furnished junicedranone 17
(6 mg, 60%) as an oil. IR (neat): νmax 1740 cmϪ1. 1H NMR (400
MHz, CDCl3): δ 2.43 (1 H, dd, J = 18.6 and 3.5 Hz), 2.00–0.90
(10 H, m), 1.80 (1 H, d, J = 18.6 Hz), 1.05 (3 H, s), 0.99 (3 H, s),
0.88 (3 H, s), 0.83 (3 H, s). 13C NMR (100 MHz, Spin Echo FT,
CDCl3): δ 218.4 (C), 60.9 (C), 52.5 (C), 48.1 (C), 45.4 (CH2),
36.1 (CH2), 33.7 (C), 30.1 (CH2), 28.9 (CH2), 28.8 (CH3), 27.4
(CH2), 23.5 (CH3), 18.8 (CH2), 16.5 (CH3), 9.3 (CH3). Mass:
m/z 220 (Mϩ, 90%), 205 (12), 177 (25), 163 (25), 150 (45), 135
(100), 124 (50), 121 (46), 109 (70). HRMS: Calcd. for C15H24O
m/z 220.1827. Found: 220.1816.
and 3.3 Hz), 2.40–1.00 (12 H, m), 1.09 (3 H, s), 1.03 (3 H, s),
0.84 (3 H, s). 13C NMR (22.5 MHz, CDCl3): δ 216.3 (s), 61.8
(d), 52.6 (s), 46.1 (t), 35.8 (2 C, t and s), 33.5 (s), 30.2 (t), 28.6
(q), 26.7 (t), 23.0 (q), 22.3 (t), 18.7 (2 C, t and q). Mass: m/z 206
(Mϩ, 100%), 191 (20), 163 (35), 150 (45), 121 (65), 95 (70).
HRMS: Calcd. for C14H22O m/z 206.1670. Found: 206.1665.
2,4-DNP derivative: mp 161 ЊC. Anal. Calcd. for C20H26N4O4
C 62.16; H 6.78; N 14.5. Found C 61.96; H 6.72; N 14.19%.
2,2,6-Trimethyl-8-methylenetricyclo[5.2.2.01,6]undecane
(myltayl-8(12)-ene 11)
To a cold (0 ЊC), magnetically stirred suspension of methyl-
triphenylphosphonium bromide (690 mg, 1.92 mmol) in
benzene (5 mL) was added potassium tert-amyl oxide [prepared
from potassium (80 mg, 2 mmol) in 2.0 mL tert-amyl alcohol]
in benzene (1 mL) and the resultant yellow reaction mixture
was stirred for 20 min at room temp. To the methylenetri-
phenylphosphorane thus formed, was added a solution of the
ketone 16 (80 mg, 0.39 mmol) in benzene (2 mL) and stirred at
room temp. for 1.5 h. The reaction mixture was then quenched
with water (1 mL) and extracted with ether (2 × 5 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 hexane as eluent furnished myltaylene12
exo-2,2,6,7-Tetramethyltricyclo[5.2.2.01,6]undecan-8-ol (6-epi-
junicedran-8-ol 23)
To a solution of lithium (3 mg) in 25 mL of freshly distilled
(over Na) ammonia was added, dropwise, a solution of the
ketone 24 (6 mg, 0.03 mmol) in 1 mL of dry THF. The reaction
mixture was stirred for 10 min and then quenched with ammo-
nium chloride. Ammonia was evaporated, and the reaction
mixture was diluted with water and extracted with ether (2 × 4
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 (1:20
to 1:10) as eluent furnished 6-epijunicedranol 23 (3 mg, 50%)
1
11 (57 mg, 71%). IR (neat): νmax 1660 cmϪ1. H NMR (270
MHz, CDCl3): δ 4.71 (1 H, br s), 4.52 (1 H, br s), 2.54 (1 H, br d,
J = 16.5 Hz), 2.10–1.15 (10 H, m), 1.00 (3 H, s), 0.96 (3 H, s),
0.81 (3 H, s). 13C NMR (100 MHz, CDCl3): δ 154.7, 101.3, 57.7,
52.8, 46.9, 40.4, 36.5, 33.6, 30.2, 28.7, 27.9, 27.6, 23.2, 19.2,
19.1. Mass: m/z 204 (Mϩ, 15%), 189 (25), 175 (6), 161 (25), 133
(35), 119 (50), 108 (100).
as an oil. IR (neat): νmax 3360 cmϪ1 1H NMR (400 MHz,
.
CDCl3): δ 3.88 (1 H, ddd, J = 10.3, 4.0 and 2.0 Hz), 2.32 (1 H,
ddd, J = 14.0, 10.3 and 4.0 Hz), 1.81 (1 H, ddd, J = 13.4, 9.0
and 4.2 Hz), 1.70–0.70 (11 H, m), 0.89 (3 H, s), 0.85 (3 H, s),
0.76 (3 H, s), 0.70 (3 H, s). 13C NMR (100 MHz, CDCl3): δ 75.5,
53.3, 52.2, 49.0, 41.8, 36.3, 33.9, 28.6, 28.5, 27.6, 25.5, 23.7,
19.2, 17.5 and 13.7. Mass: m/z 222 (Mϩ, 23%), 204 (20), 163
(53), 150 (65), 135 (40), 123 (100), 109 (75), 95 (80). HRMS:
Calcd. for C15H26O m/z 222.1984. Found: 222.1999.
1-(1,3,3-Trimethyl-2-methylenecyclohexyl)-3-methylbut-3-en-2-
one (18)
Reaction of isopropenylmagnesium bromide [prepared from
magnesium (60 mg, 2.5 mmol) and isopropenyl bromide (304
mg, 0.22 mL, 2.5 mmol) and a catalytic amount of iodine] with
the aldehyde 13 (300 mg, 1.68 mmol) in 6 mL of dry THF for 8
h, as described for the preparation of compound 12, furnished
a 3:1 epimeric mixture of the intermediate secondary alcohol
(300 mg, 81%) as an oil. IR (neat): νmax 3380, 1620, 890 cmϪ1. 1H
NMR (300 MHz, CDCl3) peaks due to the major isomer: δ 5.06
(1 H, s), 4.97 (1 H, s), 4.81 (1H, s), 4.67 (1 H, s), 4.07 (1 H, d,
J = 9.0 Hz), 1.69 (3 H, s), 2.10–1.15 (9 H, m), 1.17 (3 H, s), 1.07
Acknowledgements
We thank Dr M. Nethaji for determining the X-ray crystal
structure of the p-nitrobenzoate 20; Dr K. Krishnan for
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8 (a) A. Srikrishna and K. Krishnan, Tetrahedron Lett., 1989, 30,
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generous gift of β-ionone; Professor A. F. Barrero, Universidad
1
de Granada for providing the copies of the H and 13C NMR
spectra of natural junicedranol and its acetate; and the Council
of Scientific and Industrial Research, New Delhi for the award
of a senior research fellowship to P. P. K.
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Paper 9/06706J
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