Facile access to optically active ring C aromatic diterpene derivatives from manool. Highly efficient syntheses of (+)-12-methyl-7-oxo-podocarpa-8,11,13-triene-13-carboxylic acid, (+)-13-methyl-7-oxopodocarpa-8,11,13-triene-12-carboxylic acid and (+)-nimbiol

Article abstract of DOI:10.1039/a708795k

The extension of our recently developed strategy using the key intermediate 2, obtainable in two steps (52% overall yield) from manool 1, to the synthesis of naturally occurring ring C aromatic diterpene derivatives provides in three steps (+)-12-methyl-7-oxopodocarpa-8,11,13-triene-13-carboxylic acid 4b and its isomer 6b, and in seven steps (+)-nimbiol 11b, in good overall yields. This synthesis discloses that the structure 4b assigned to margolone isolated from Azadirachta indica A. Juss is incorrect and needs to be reinvestigated.

Full text of DOI:10.1039/a708795k

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Facile access to optically active ring C aromatic diterpene derivatives
from manool. Highly efficient syntheses of (؉)-12-methyl-7-oxo-
podocarpa-8,11,13-triene-13-carboxylic acid, (؉)-13-methyl-7-
oxopodocarpa-8,11,13-triene-12-carboxylic acid and (؉)-nimbiol
Tatsuhiko Nakano,*,a Randolph Alonso,a María Aracelis Maillo,a
Alfonso Martína and Ramona Avila Núñezb
a Centro de Química, Instituto Venezolano de Investigaciones Científicas (I.V.I.C.),
Apartado 21827, Caracas 1020-A, Venezuela
b Universidad Nacional Experimental Francisco de Miranda, Coro, Edo. Falcón, Venezuela
The extension of our recently developed strategy using the key intermediate 2, obtainable in two steps
(52% overall yield) from manool 1, to the synthesis of naturally occurring ring C aromatic diterpene
derivatives provides in three steps (؉)-12-methyl-7-oxopodocarpa-8,11,13-triene-13-carboxylic acid 4b
and its isomer 6b, and in seven steps (؉)-nimbiol 11b, in good overall yields. This synthesis discloses that
the structure 4b assigned to margolone isolated from Azadirachta indica A. Juss is incorrect and needs to
be reinvestigated.
a biogenetic point of view since it possesses carbon substituents
at both C-12 and C-13 in the podocarpane skeleton.
Introduction
We have recently developed a highly efficient, short route to the
synthesis of naturally occurring, biologically active drimane-
type sesquiterpenes,1 (ϩ)-confertifolin, (ϩ)-isodrimenin, (ϩ)-
euryfuran and (Ϫ)-warburganal,2 and also bicyclofarnesane-
type sesquiterpenes, (ϩ)-albicanol and (ϩ)-bicyclofarnesol.3 In
all these syntheses, the diene 2,4 obtained in two steps (52%
overall yield) (Scheme 1) from commercially available manool
Results and discussion
Diels–Alder reaction of the diene 2 with methyl but-2-ynoate
was carried out by heating the neat mixture in a sealed tube.
No reaction took place below 160 ЊC. Above 180 ЊC, however,
reaction was accompanied by a considerable degree of pyrolytic
aromatization8 and the major products were not the diene
adducts but ring C aromatic compounds. At 214 ЊC almost
quantitative aromatization occurred and a mixture of two iso-
meric products 3 and 5 (ratio of 3:2) was obtained in 80% yield.
These two compounds were separated by medium pressure
liquid chromatography over silica gel and their structures were
OH
O
H
H
1
differentiated by means of 2D NMR H and 13C single and
H
H
H
multiple bond correlation studies.5 The less polar product was
assigned the structure 5 and the other more polar isomer, the
structure 3, which appeared to be that required for the synthesis
of margolone. On benzylic oxidation with tert-butyl hydro-
peroxide and chromium hexacarbonyl9 compound 3 afforded
the 7-oxo-derivative 4a (80% yield). Subsequent alkaline
hydrolysis led to the desired compound 4b (100% yield). When,
however, the physical and spectroscopic properties of this
synthetic compound 4b were compared with those6 reported
for natural margolone, some significant discrepancies5
were observed between them. We report here that the structure
published for margolone is not correct and needs to be
reinvestigated. The diterpene having the structure 4b cannot be
coloured yellow as reported with UV λmax 360 and 383 nm.
Probably the isolated compound was impure and needs to be
properly characterised.
Benzylic oxidation of the isomeric compound 5 with tert-
butyl hydroperoxide and pyridinium dichromate10 afforded the
other ring C aromatic diterpene 6a (78% yield). Subsequent
alkaline hydrolysis led to compound 6b (100% yield).
Nimbiol was isolated from the trunk bark of Melia
azadirachta Linn. (syn. Azadirachta indica Juss) and was
shown to possess the structure 11b.11 Two independent groups
of chemists12 previously synthesised this diterpene from
podocarpic acid. In our synthesis compound 6b, one of the
1
2
Scheme 1
1, has been used as a common key intermediate. This paper
aims to demonstrate another utility of this diene for the syn-
thesis of optically active ring C aromatic diterpene derivatives,5
such as compounds 4b, 6b and 11b.
Because of its wide range of therapeutic and pesticidal prop-
erties, the study of the constituents of Azadirachta indica A.
Juss (Meliaceae), commonly known as neem, has attracted
much interest among natural product chemists during the
past two decades.6,7 A series of new terpenoidal constituents
have been isolated from the various parts of neem. The tricyclic
diterpenoid margolone was one of them and its chemical struc-
ture has been assigned the structure 4b on the basis of spectro-
scopic evidence. This compound appears to be interesting from
R2
3
R1 = H2, R2 = CH3, R3 = CO2CH3
R3
12
4a R1 = O, R2 = CH3, R3 = CO2CH3
4b R1 = O, R2 = CH3, R3 = CO2H
11
20
13
14
5
R1 = H2, R2 = CO2CH3, R3 = CH3
1
9
6
6a R1 = O, R2 = CO2CH3, R3 = CH3
6b R1 = O, R2 = CO2H, R3 = CH3
2
10
8
7
5
3
4
R1
H
19
18
J. Chem. Soc., Perkin Trans. 1, 1998
1423

View Article Online
R1 = H2, R2 = CH2OH
R1 = H2, R2 = CHO
R1 = H2, R2 = OCHO
(C-3), 33.37 (C-4), 50.26 (C-5), 18.72 (C-6), 30.17 (C-7), 140.02
(C-8), 147.72 (C-9), 37.41 (C-10), 127.02 (C-11), 126.64 (C-12),
7
8
9
R2
CH3
136.66 (C-13), 132.18 (C-14), 21.22 (ArCH ), 168.21 (C᎐O),
᎐
3
10a R1 = H2, R2 = OH
10b R1 = H2, R2 = OAc
11a R1 = O, R2 = OAc
11b R1 = O, R2 = OH
51.50 (OCH3), 33.21 (C-18), 21.53 (C-19) and 24.74 (C-20)
(Found: Mϩ, 300.2102. C20H28O2 requires 300.2089).
The more polar fraction afforded compound 3 (0.17 g, 30%)
as an oil; δH(300 MHz) 1.37 (1H, m, 1α-H), 2.29 (1H, br d, J
10.5, 1β-H), 1.64 (2H, m, 2-H), 1.23 (1H, m, 3-H), 1.47 (1H, br
d, J 13.5, 3-H), 1.28 (1H, dd, J 12.8, 3.8, 5-H), 1.74 (1H, m,
6-H), 1.87 (1H, m, 6-H), 2.85 (2H, m, 7-H), 7.09 (1H, s, 11-H),
7.62 (1H, s, 14-H), 2.54 (3H, s, ArCH3), 3.84 (3H, s, OCH3),
0.94 (3H, s, 18-CH3), 0.92 (3H, s, 19-CH3) and 1.16 (3H, s,
20-CH3); δC(75.45 MHz) 38.52 (C-1), 19.12 (C-2), 41.52 (C-3),
33.42 (C-4), 50.05 (C-5), 18.88 (C-6), 36.65 (C-7), 132.58 (C-8),
154.31 (C-9), 37.87 (C-10), 127.58 (C-11), 137.04 (C-12), 126.25
R1
H
intermediates obtained earlier, was employed as a convenient
precursor.
Reduction of compound 5 with lithium aluminium hydride
afforded the alcohol 7 (94% yield). Oxidation of alcohol 7 with
tetra-n-propylammonium perruthenate and N-methylmorph-
oline N-oxide13 gave the aldehyde 8 (94%). Baeyer–Villiger
oxidation14 of the aldehyde 8 was effected by heating with m-
chloroperoxybenzoic acid in methylene chloride at refluxing
temperature for 24 h. The resulting formate 9 (64% yield) was
hydrolysed with methanolic potassium hydroxide to the phenol
10a (96% yield). Acetylation of the phenol 10a with acetic
anhydride in pyridine afforded the acetate 10b (90% yield)
which was then oxidised with tert-butyl hydroperoxide and
pyridinium dichromate10 to give the 7-oxo derivative 11a (74%
yield). Subsequent alkaline hydrolysis afforded compound 11b,
identical with natural (ϩ)-nimbiol11,12 (100% yield).
(C-13), 131.39 (C-14), 21.55 (ArCH ), 167.99 (C᎐O), 51.40
᎐
3
(OCH3), 33.18 (C-18), 21.13 (C-19) and 24.47 (C-20) (Found:
Mϩ, 300.2095. C20H28O2 requires 300.2089).
Benzylic oxidation of compound 3
To a stirred solution of compound 3 (70 mg, 0.23 mmol) in
benzene (4 ml) and Celite (0.2 g) was added pyridinium
dichromate (0.351 g, 0.93 mmol) followed by the addition of
tert-butyl hydroperoxide (0.5 ml, 5.21 mmol) at 10 ЊC. After 15
min at 10 ЊC, the reaction mixture was stirred for 24 h at room
temperature. The excess reagents were decomposed by addition
of methanol and the reaction mixture was filtered through a
pad of Celite by eluting with hexane. The eluate was evaporated
in vacuo to dryness. The crude product thus obtained was puri-
fied by chromatography over silica gel in hexane–ether to afford
compound 4a (57 mg, 78%) as colourless crystals, mp 99–100 ЊC;
The importance of the diene 2 as a key precursor in this
synthesis has now been well demonstrated. Our strategy
using the diene 2 as a building block will continue to find wide
application in the synthesis of many other similar naturally
occurring ring C aromatic diterpenes.
λmax(EtOH)/nm 229 (log ε 4.5),† 256 (4.11) and 310 (3.27); νmax
/
Experimental
cmϪ1 3400 (OH), 1719 (ester C᎐O) and 1678 (C᎐O); δ (300
᎐
᎐
H
Melting points were measured on a Kofler hot-stage apparatus
and are uncorrected. IR spectra were recorded with a Nicolet
5DXC FT-IR spectrometer. UV spectra were determined with a
UV–VIS Milton Roy 3000 array instrument. NMR spectra were
obtained for solutions in CDCl3 on a Bruker AM 300 spec-
trometer. J Values are given in Hz. The assignments of carbon
MHz) 0.90 (3H, s, 18-CH3), 0.96 (3H, s, 19-CH3), 1.20 (3H, s,
20-CH3), 2.60 (3H, s, ArCH3), 3.84 (3H, s, OCH3), 7.19 (1H, s,
11-H) and 8.50 (1H, s, 14-H) (Found: C, 76.37; H, 8.31.
C20H26O3 requires C, 76.40; H, 8.34%).
Hydrolysis of compound 4a
1
signals were made by means of 2D NMR H and 13C single
Compound 4a (50 mg, 0.15 mmol) was treated with 10% meth-
anolic potassium hydroxide (10 ml) at room temperature for
24 h. The solution was then acidified with hydrochloric acid,
diluted with water, and then extracted with ether. The ether
extract was dried and evaporated to afford compound 4b (46 mg,
98%) as colourless crystals, mp 254–255 ЊC; [α]D 10 (c 6.4);
λmax(MeOH)/nm 224, 263 and 320; νmax(KBr)/cmϪ1 3475 (OH)
and 1686 (COOH and CO); m/z 300 (Mϩ, 40%), 285 (Mϩ Ϫ
CH3, 100), 217 (75), 128 (40) and 69 (65); δH(300 MHz) 0.91
(3H, s, 19-CH3), 0.97 (3H, s, 18-CH3), 1.22 (3H, s, 20-CH3), 1.28
(1H, m, 3-H), 1.50 (1H, m, 3-H), 1.53 (1H, m, 1α-H), 1.69 (2H,
br m, 2-H), 1.82 (1H, dd, J 12.9, 4.2, 5-H), 2.32 (1H, br d,
J 12.7, 1β-H), 2.61 (1H, dd, J 18.5, 12.9, 6β-H), 2.65 (3H, s,
ArCH3), 2.73 (1H, dd, J 18.5, 4.2, 6α-H), 7.23 (1H, s, 11-H) and
8.65 (1H, s, 14-H) (Found: C, 75.67; H, 8.26. C19H24O3 requires
C, 75.97; H, 8.05%).
bond and multiple bond correlation studies. Mass spectra were
determined on a Kratos MS 25 RFA spectrometer at 70 eV
using a direct inlet system. Rotations were measured in chloro-
form solutions at 25 ЊC with a Zeiss ‘0.01’ polarimeter. For
column chromatography, silica gel 60 (Merck, 70–230 mesh)
was used. Thin layer chromatograms were prepared on silica gel
G or silica gel GF254 60 (Merck) and the spots were observed by
exposure to iodine vapour or UV light. All organic extracts
were dried over anhydrous sodium sulfate and evaporated
under reduced pressure below 60 ЊC. Ether refers to diethyl
ether.
Diels–Alder reaction of the diene 2 with methyl but-2-ynoate
A mixture of the diene 2 (0.512 g, 0.25 mmol) and methyl but-2-
ynoate (0.247 g, 0.25 mmol) was heated in a sealed tube at
250 ЊC for 24 h. The reaction mixture was chromatographed
over silica gel and elution with 2% ether in hexane afforded in
80% yield a mixture of compounds 3 and 5 as a yellow oil, as
evidenced by the 1H NMR spectrum. The mixture of these two
compounds was chromatographed over a 1:1 mixture of silica
gel Merck 60 (230–400 mesh) and TLC silica gel without binder
under medium pressure. Elution was effected with 2% ethyl-
acetate in hexane, the less polar fractions consisted of com-
pound 5 (0.11 g, 20%) as an oil; δH(300 MHz) 1.39 (1H, m,
1α-H), 2.32 (1H, br d, J 12.5, 1β-H), 1.62 (2H, m, 2-H), 1.24
(1H, m, 3-H), 1.48 (1H, br d, J 13.5, 3-H), 1.27 (1H, dd, J 12.3,
2.6), 1.72 (1H, m, 6-H), 1.87 (1H, m, 6-H), 2.49 (3H, ArCH3),
2.84 (2H, m, 7-H), 7.81 (1H, s, 11-H), 6.88 (1H, s, 14-H), 3.80
(3H, s, OCH3), 0.93 (3H, s, 18-CH3), 0.91 (3H, s, 19-CH3), 1.15
(3H, s, 20-CH3); δC(75.45 MHz) 38.77 (C-1), 19.13 (C-2), 41.56
Benzylic oxidation of compound 5
Treatment of compound 5 (0.122 g) in the same way as
described for compound 3 afforded compound 6a (0.100 g,
78%), mp 134–135 ЊC; δH(300 MHz) 0.90 (3H, s, 18-Me), 0.97
(3H, s, 19-Me), 1.20 (3H, s, 20-Me), 2.52 (3H, ArMe), 3.88 (3H,
s, OMe), 7.81 (1H, s, 11-H) and 7.83 (1H, s, 14-H) (Found: Mϩ,
314.1845. C20H26O3 requires 314.1881).
Hydrolysis of compound 6a
Compound 6a (100 mg) was hydrolysed in the same way
described for compound 4a. Compound 6b (93 mg, 98%) was
† ε Values are given in units of dm3 molϪ1 cmϪ1
.
1424
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
obtained as colourless crystals, mp 198–200 ЊC; [α]D 18 (c 3.1);
λmax(MeOH)/nm 210, 266 and 320 (shoulder); νmax(KBr)/cmϪ1
3387 (OH) and 1686 (COOH and CO); m/z 300 (Mϩ, 40%), 285
(Mϩ Ϫ CH3, 80), 217 (70), 203 (60) and 69 (100); δH(300 MHz)
0.92 (1H, s, 18-CH3), 0.98 (1H, s, 19-CH3), 1.23 (1H, s, 20-CH3),
1.28 (1H, dd, J 13.2, 4.5, 3-H), 1.51 (1H, br m, 3-H), 1.56 (1H,
m, 1α-H), 1.71 (2H, br m, 2-H), 1.84 (1H, dd, J 13.2, 4.5, 5-H),
2.38 (1H, br d, J 12.5, 1β-H), 2.60 (3H, s, ArCH3), 2.64 (1H, dd,
J 18.4, 13.2, 6β-H), 2.75 (1H, dd, J 18.4, 4.5, 6α-H), 7.85 (1H, s,
14-H) and 8.02 (1H, s, 11-H); δC(75.45 MHz) 37.87 (C-1), 18.75
(C-2), 41.28 (C-3), 33.28 (C-4), 49.28 (C-5), 36.24 (C-6), 199.35
(C-7), 133.30 (C-8), 153.30 (C-9), 37.90 (C-10), 127.21 (C-11),
133.11 (C-12), 138.29 (C-13), 130.28 (C-14), 21.30 (ArCH3),
171.98 (CO), 32.50 (C-18), 21.24 (C-19) and 23.37 (C-20)
(Found: C, 75.86; H, 8.25. C19H24O3 requires C, 75.97; H,
8.05%).
Hydrolysis of compound 9
Compound 9 (0.138 g) was hydrolysed with 10% methanolic
potassium hydroxide (30 ml). Usual work-up afforded com-
pound 10a as an oil (0.119 g, 96%); δH(300 MHz) 0.89 (3H,
s, 18-CH3), 0.91 (3H, s, 19-CH3), 1.14 (3H, s, 20-CH3), 1.30–
1.79 (6H, m, 1-, 2-, 3-H), 1.72 (1H, m, 5-H), 1.80–1.84 (2H, m,
6-H), 2.15 (3H, s, ArCH3), 2.71–2.81 (2H, m, 7-H), 4.55 (1H,
br s, OH), 6.65 (1H, s, 14-H) and 6.77 (1H, s, 11-H); δC(75.45
MHz) 38.89 (C-1), 19.27 (C-2), 41.64 (C-3), 33.39 (C-4), 50.39
(C-5), 19.11 (C-6), 29.45 (C-7), 120.75 (C-8), 149.22 (C-9),
37.53 (C-10), 110.57 (C-11), 151.68 (C-12), 127.17 (C-13),
131.19 (C-14), 33.25 (C-18), 21.56 (C-19), 24.73 (C-20) and
15.19 (ArCH3); m/z 258 (Mϩ, 60%), 243 (Mϩ Ϫ CH3, 60), 121
(40), 69 (100) and 41 (90).
Acetylation of compound 10a
Compound 10a (130 mg) was treated with pyridine (15 ml)
and acetic anhydride (15 ml) and the solution was refluxed for
3 h. After addition of water the product was extracted with
ether and chromatographed in hexane–ether over silica gel.
Compound 10b (135 mg, 90%) was obtained; δH(300 MHz) 0.91
(3H, s, 18-CH3), 0.97 (3H, s, 19-CH3), 1.23 (3H, s, 20-CH3), 2.15
(3H, s, ArCH3), 2.31 (3H, s, OAc), 6.97 and 6.98 (1H each,
s, 11-H, 14-H).
Lithium aluminium hydride reduction of compound 5
A solution of 5 (200 mg, 0.66 mmol) in ether (20 ml) was stirred
with lithium aluminium hydride (200 mg, 5.26 mmol) under
nitrogen at room temperature for 24 h. The excess reagent was
decomposed with water and after addition of 30% aqueous
potassium hydroxide the product was extracted with ether.
Evaporation of the ether extract and subsequent purification
with hexane–ether over silica gel yielded compound 7 (142 mg,
94%) as an oil; νmax(liquid film)/cmϪ1 3374 (OH) and 1719
(C᎐O); m/z 272 (Mϩ, 40%), 257 (Mϩ Ϫ CH , 80), 69 (80) and 41
Benzylic oxidation of compound 10b
Benzylic oxidation of compound 10b (100 mg) in the same
manner as described for compound 5b, afforded compound 11a
(80 mg, 74%); δH(300 MHz) 0.91 (3H, s, 18-CH3), 0.97 (3H, s,
19-CH3), 1.23 (3H, s, 20-CH3), 2.15 (3H, s, ArCH3), 2.31 (3H, s,
OAc), 6.98 (1H, s, 11-H) and 7.87 (1H, s, 14H).
᎐
3
(100); δH(300 MHz) 0.90 (3H, s, 18-CH3), 0.92 (3H, s, 19-CH3),
1.23 (3H, s, 20-CH3), 1.30–1.70 (2H, m, 1-H; 2H, br m, 2-H;
2H, m, 3-H), 1.73 (1H, dd, J 12.7, 6.3, 5-H), 1.82 (1H, dd, J 7.1,
3.3, 6-H), 1.88 (1H, dd, J 7.1, 3.3, 6-H), 2.27 (3H, s, ArCH3),
2.78 (1H, m, J 18.0, 10.9, 7.1, 7-H), 2.88 (1H, dd, J 18.0, 7.1,
7-H), 4.62 (2H, s, CH2OH), 6.85 (1H, s, 14-H) and 7.19 (1H, s,
11-H); δC(75.45 MHz) 38.89 (C-1), 19.24 (C-2), 41.68 (C-3),
33.40 (C-4), 50.51 (C-5), 18.02 (C-6), 29.66 (C-7), 135.93 (C-8),
147.97 (C-9), 37.91 (C-10), 124.11 (C-11), 132.94 (C-12), 134.89
(C-13), 130.95 (C-14), 33.28 (C-18), 21.57 (C-19), 24.82 (C-20),
18.97 (ArCH3) and 63.87 (CH2OH).
Hydrolysis of compound 11a
Compound 11a (70 mg) was hydrolysed with 10% methanolic
potassium hydroxide (5 ml). After usual work-up compound
11b, mp 235 ЊC, was obtained (70 mg, 100%); [α]D 32 (c 1.7);
δH(300 MHz) 0.89 (3H, s, 18-CH3), 0.95 (3H, s, 19-CH3), 1.17
(3H, s, 20-CH3), 1.49 (1H, m, 1α-H), 1.82 (1H, dd, J 12.9, 4.7,
5-H), 2.14 (1H, m, 1β-H), 2.16 (3H, s, ArCH3), 2.54 (1H, dd,
J 18.2, 12.9, 6β-H), 2.66 (1H, dd, J 18.2, 4.7, 6α-H), 5.86 (1H,
br s, OH), 6.75 (1H, s, 11-H) and 7.81 (1H, s, 14-H); δC(75.45
MHz) 37.91 (C-1), 18.93 (C-2), 41.38 (C-3), 33.33 (C-4), 49.61
(C-5), 36.03 (C-6), 199.34 (C-7), 127.53 (C-8), 157.22 (C-9),
37.10 (C-10), 109.62 (C-11), 160.01 (C-12), 124.02 (C-13),
130.80 (C-14), 32.62 (C-18), 21.42 (C-19), 23.20 (C-20) and
15.35 (ArCH3); m/z 272 (Mϩ, 100%), 257 (Mϩ Ϫ CH3, 90), 183
(70), 175 (60), 69 (50) and 41 (60) (Found: C, 79.21; H, 8.67.
C18H24O2 requires C, 79.37; H, 8.88%).
Oxidation of compound 7 with tetra-n-propylammonium
perruthenate
Compound 7 (152 mg, 0.55 mmol) was dissolved in dichloro-
methane (5 ml) containing both 4 Å molecular sieves (0.279 g,
0.55 mmol) and N-methylmorpholine N-oxide (98 mg, 0.83
mmol). After stirring the mixture for 5 min, tetra-n-propyl-
ammonium perrutherate (10 mg, 0.02 mmol) was added and the
reaction followed by TLC until complete. The reaction mixture
was filtered through silica gel and elution with hexane afforded
compound 8 (140 mg, 94%) as an oil; δH(300 MHz) 0.91 (3H, s,
18-CH3), 0.93 (3H, s, 19-CH3), 1.16 (3H, s, 20-CH3), 1.20–1.26
(2H, m, 3-H), 1.30 (1H, m, 5-H), 1.74 (1H, m, 6-H), 1.40 (1H,
m, 1β-H), 1.65 (2H, br m, 2-H), 1.87 (1H, m, 6-H), 2.35 (1H,
m, 1α-H), 2.55 (3H, s, ArCH3), 7.66 (1H, s, 11-H), 2.83–2.92
(2H, m, 7-H), 6.89 (1H, s, 14-H) and 10.14 (1H, s, CHO);
δC(75.45 MHz) 38.71 (C-1), 19.10 (C-2), 41.56 (C-3), 33.41
(C-4), 50.19 (C-5), 18.67 (C-6), 30.47 (C-7), 142.35 (C-8),
148.54 (C-9), 37.51 (C-10), 128.86 (C-11), 132.17 (C-12), 136.95
(C-13), 132.31 (C-14), 33.20 (C-18), 21.55 (C-19), 24.76 (C-20),
18.89 (ArCH3) and 192.73 (CHO).
Acknowledgements
We thank M. Sc. M. Gómez, Ing. P. Hernández, and Dr F.
Vargas for the measurements of the NMR, IR and UV spectra.
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references cited therein.
2 T. Nakano and A. Martín, J. Chem. Res. (S), 1989, 52.
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8 J. C. Loperfido, J. Org. Chem., 1973, 38, 339; K. Mori and
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Liebigs Ann. Chem., 1989, 107.
Baeyer–Villiger oxidation of compound 8
Compound 8 (66 mg, 0.24 mmol) in dichloromethane (10 ml)
was heated under reflux with m-chloroperoxybenzoic acid
(0.127 g, 0.73 mmol) for 24 h. The reaction mixture was filtered
through silica gel and evaporation of the solvent afforded com-
pound 9 as an oil (45 mg, 64%); δH 0.96 (3H, s, 19-CH3), 0.89
(3H, s, 18-CH3), 1.16 (3H, s, 20-CH3), 2.10 (3H, s, ArCH3), 6.85
(1H, s, 11-H), 6.89 (1H, s, 14-H) and 8.26 (1H, s, OCHO); m/z
286 (Mϩ, 10%), 271 (Mϩ Ϫ CH3, 20), 258 (40), 243 (40), 69 (80)
and 43 (100).
J. Chem. Soc., Perkin Trans. 1, 1998
1425

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Paper 7/08795K
Received 8th December 1997
Accepted 29th January 1998
1426
J. Chem. Soc., Perkin Trans. 1, 1998