Enantioselective synthesis of (+)-decipienin A

Article abstract of DOI:10.1016/S0040-4020(01)00048-5

The enantioselective synthesis of (+)-decipienin A has been carried out. The oxidation of 7-epi-cyperone 2 with molecular oxygen in the presence of methanolic KOH provides de C-6-hydroxylated derivative in quantitative yield. The oxidation of glycols 5a t

Full text of DOI:10.1016/S0040-4020(01)00048-5

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 2171±2178
Enantioselective synthesis of (1)-decipienin A
Â
F. Javier Aladro, Francisco M. Guerra, F. Javier Moreno-Dorado, Jesus M. Bustamante,
p
Â
Zacarõas D. Jorge and Guillermo M. Massanet
   Â
Departamento de Quõmica Organica, Facultad de Ciencias, Universidad de Cadiz, Apartado 40, 11510 Puerto Real, Cadiz, Spain
Received 8 November 2000; revised 2 January 2001; accepted 11 January 2001
AbstractÐThe enantioselective synthesis of (1)-decipienin A has been carried out. The oxidation of 7-epi-cyperone 2 with molecular
oxygen in the presence of methanolic KOH provides de C-6-hydroxylated derivative in quantitative yield. The oxidation of glycols 5a
through a Swern oxidation and 14a with TEMPO radical opens up a route to the synthesis of 11-hydroxy sesquiterpenolides. All attempts of
oxidation of 5a or 14a with other different oxidation reagents led invariably to fragmentation products. q 2001 Elsevier Science Ltd. All
rights reserved.
1. Introduction
Herein, we want to present how this problem was solved
through oxidation with TEMPO (2,2,6,6-tetramethylpiperi-
dinyl-1-oxy radical) in the presence of a catalytic amount of
NaClO and a stoichiometric amount of NaClO2. We have
successfully applied this methodology to the enantioselec-
tive synthesis of a-hydroxy acids starting from terminal
ole®ns.7
Eudesmanolides belong to a class of substances widely
spread in nature.1 Antitumor, antiulcer, cardiotonic, and
neurotoxic activities have been reported in some members
of this diverse group.2
In the course of our programme, aimed at the synthesis and
study of biological activities of sesquiterpene lactones, we
have carried out the synthesis of decipienin A, 1, an
eudesmanolide isolated from Melanoselinum decipiens
(Umbelliferae), a shrub endemic to the archipelago of
Madeira (Portugal; Fig. 1).3
2. Results and discussion
We envisioned an approach in which the skeleton of the
Although most eudesmanolides isolated to date from plants
of Compositae family (their main source) display an
a-methylene system conjugated to the carbonyl group of
the lactone, this eudesmanolide bears an angeloyloxy
function instead.4
Our group has already reported two syntheses of 1, in its
racemic5 and enantiomerically pure forms.6 In the latter
synthesis, the oxidation of the glycol A formed at the iso-
propenyl group of the eudesmane skeleton was proposed as
the simplest method to get the a-hydroxy-g-lactone moiety
B. However, this route had to be initially abandoned as an
attempt of oxidation of the vicinal diol led to the methyl
ketone C through an oxidative cleavage process (Fig. 2).
Figure 1.
Providing a solution to this problem was considered
interesting as not many ef®cient methods of oxidation of
1,2-diols, avoiding the cleavage of glycol, were available.
Keywords: decipienin A; eudesmanolides; sesquiterpenolides; oxidation;
Umbelliferae.
p
Corresponding author. Fax: 134-956-016288;
e-mail: francisco.guerra@uca.es
Figure 2.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00048-5

2172
F. J. Aladro et al. / Tetrahedron 57 (2001) 2171±2178
chemistry of the resulting tertiary alcohol was con®rmed
in the subsequent steps.
The next step was the oxidation of the primary alcohol to
give the corresponding carboxylic acid. As previously
pointed out, this reaction required extremely mild con-
ditions since this glycol was easily cleaved to furnish a
methyl ketone under most oxidation conditions. This oxi-
dation was also impossible when the hydroxyl group at C-6
was unprotected. After trying several conditions, ®nally the
Swern oxidation led to the desired aldehyde, as could be
deduced from the spectrum of the crude mixture. However,
this aldehyde resulted to be a very unstable compound,11 and
its isolation was impossible due to its rapid decomposition.
The best results were obtained when the resulting mixture
from the Swern oxidation was immediately submitted to
treatment with NaClO2/NaH2PO4/SO3HNH2.12 Methylation
with diazomethane then furnished 6 with an overall yield of
60% over three steps.
Scheme 1.
molecule is built starting from 7-epi-cyperone (2). Its trans-
formation into decipienin A would mainly involve oxidative
reactions in order to functionalise the appropriate centres.
The ®rst reaction involved the basic treatment of 7-epi-
cyperone 28 with 10% methanolic KOH in the presence of
molecular oxygen, affording the 6-hydroxylated derivative
3 in quantitative yield (Scheme 1). When the reaction was
carried out under N2 atmosphere, the reaction did not
proceed at all. No differences were observed when O2 was
bubbled or introducing vigorous stirring open to air.
Although oxidation of enolates with molecular oxygen is
a well documented reaction,9 the main advantages of this
procedure are its technical simplicity and its high yield.
Under the conditions of the reaction (see Section 3), we did
not observe any self-condensation product. We examined
several other substrates and con®rmed its generality as
long as the substrate presents certain key features, a methyl
group located a to the carbonyl group seems to be needed to
prevent decomposition of the molecule.10
At this point, the stereochemistry of the acetate at C-6 had to
be inverted. Acetate 6 was saponi®ed with methanolic
KOH, producing the dihydroxyacid 7 in quantitative yield.
Several conditions of the Mitsunobu reaction on the free
hydroxyl did not produce the desired b-hydroxyl group.
Finally, treatment of 7 with MsCl/Et3N following the
Landsbury procedure yielded the cis-lactone 8 in a 16%
yield (Scheme 2).13
The low yields of the Landsbury inversion of the stereo-
chemistry at C-6 prompted us to seek an alternative route
to the target molecule.
2.1. First method of oxidation of the glycol: use of the
Swern reaction
At this point, it was necessary to protect the hydroxyl group
at C-6 in order to prevent secondary reactions in the subse-
quent oxidation steps (vide infra). Several protective groups
were checked, acetate being the most effective one. Thus,
we proceeded to acetylate 3 with Ac2O/Py, yielding the
acetate 4 quantitatively. Osmylation-mediated dihydroxyl-
ation of the exocyclic double bond was achieved employing
AD-mix a, affording a 97:3 mixture of the desired/
undesired products, 5a/5b. No change was observed in the
product ratio when AD-mix b was used. The stereo-
2.2. Second method of oxidation of the glycol: use of
TEMPO
Therefore we decided to use an oxidation±reduction
sequence to invert the stereochemistry at C-6 in the early
stages of the synthesis. Thus, oxidation of 6a-hydroxy-
cyperone 3 with freshly prepared PCC on alumina afforded
the enedione 9 in a 96% yield. Subsequent reduction of 9
with NaBH4 under Luche conditions14 led to 10 in a 80%
yield. Careful oxidation of 10 with PCC on alumina
Scheme 2.

F. J. Aladro et al. / Tetrahedron 57 (2001) 2171±2178
2173
Scheme 3.
furnished 11, which displayed the hydroxyl at C-6 with the
desired stereochemistry. Although in this step, the yield was
moderate (54%), the rest of the recovered material was
starting material 10 (38%) and the overoxidation product
9 (8%), which could be recycled.
ing triols 14a and 14b. This reaction was accompanied by
removal of the acetate group (Scheme 3).
All our attempts to oxidize triol 14a through a Swern reac-
tion as in 5a were unfruitful. At the same time that this
research was taking place, we were studying the use of
TEMPO in the preparation of optically active hydroxyacids.
We discovered that TEMPO smoothly oxidized glycols to
their corresponding hydroxyacids avoiding the cleavage of
such a labile system.7
With the hydroxyenone 11 in hand, we proceeded to intro-
duce an acetate group by treatment with Ac2O in pyridine,
affording 12 in 94% yield. Sharpless asymmetric
dihydroxylation of 11 and 12 was attempted with negative
results. Treatment of 11 with either AD-mix a or b led back
to the enedione 9. In the case of 12, no reaction was
observed. When MCPBA was employed, a 3:1 mixture of
the epoxides 13a/13b was produced, favouring the desired
diastereomer. Opening of the epoxide ring was accom-
plished with a 7% HClO4 solution in aqueous THF, afford-
Triol 14a was then oxidised with TEMPO in the presence of
catalytic NaClO and stoichiometric NaClO2, directly
furnishing lactone 8 in a 57% yield (72% yield from
recovered material). It is noteworthy that the allylic alcohol
at C-6 in 14a remains unaltered toward the oxidation under
Scheme 4.

2174
F. J. Aladro et al. / Tetrahedron 57 (2001) 2171±2178
these conditions.15 Lactone 8 was dehydrogenated with
DDQ in re¯uxing dioxane, affording 15 in a 89% yield
(Scheme 4).
3. Yellow oil. [a]D ˆ44 (c 0.1, CHCl3). IR (thin ®lm) n
20
3454, 2923, 2862, 1662, 1464, 1343, 1199, 1021, 991, 895,
748 cm21. MS, m/z (relative intensity) 234 [M]1 (63.8), 219
[M2CH3]1 (20.2), 205 [M2CO]1 (42.9), 191 [M2CO±
CH3]1 (35.0), 135 [C8H7O2]1 (78.5), 123 [C7H7O2]1
(92.4), 107 [C7H7O]1 (76.5), 91 (82.9), 55 (100.0). HRMS
Finally, the angeloylation was achieved following the
Yamaguchi procedure with angelic acid and 2,4,6-trichloro-
benzoyl chloride in the presence of Et3N.5,6,16
1
calcd for C15H22O2 234.1620, found 234.1610. H NMR d
(400 MHz, CDCl3): 4.90 (1H, d, Jˆ1.3 Hz, H-6), 4.82 (1H,
d, Jˆ1.7 Hz, H-12), 4.37 (1H, d, Jˆ1.7 Hz, H-120), 2.60
(1H, ddd, Jˆ17.9, 14.8, 5.4 Hz, H-2a), 2.54 (1H, bs,
H-7), 2.40 (1H, ddd, Jˆ17.9, 5.1, 2.2 Hz, H-2b), 2.21
(1H, dddd, Jˆ13.6, 13.6, 5.3, 2.9 Hz, H-8a), 1.88 (3H, s,
3H-15), 1.83 (1H, ddd, Jˆ14.8, 13.4, 5.1 Hz, H-1b), 1.74
(3H, s, 3H-13), 1.65 (1H, ddd, Jˆ13.4, 5.4, 2.2 Hz, H-1a),
1.38 (3H, s, 3H-14), 1.52±1.36 (3H, m, H-8b, H-9a, H9b).
13C NMR d (100 MHz, CDCl3): 200.5 (C-3), 160.6 (C-5),
145.8 (C-11), 132.5 (C-4), 111.9 (C-12), 70.0 (C-6), 48.2
(C-7), 39.3 (C-1), 35.6 (C-9), 35.6 (C-10), 34.6 (C-2), 26.2
(C-14), 23.5 (C-13), 19.1 (C-8), 10.9 (C-15).
Summing up, we have synthesized enantiomerically pure
(1)-decipienin A. The control of the involved oxidative
processes is of primary importance. The oxidation of the
7-epi-cyperone 2 with oxygen in the presence of methanolic
KOH provides the C6-hydroxylated derivative in quanti-
tative yield. The oxidation of the glycols 5a through a
Swern reaction and 14a with the TEMPO radical opens up
a route to the synthesis of 11-hydroxy sesquiterpenolides.
Other attempts of oxidation of 5a or 14a with different
oxidation reagents led almost invariably to fragmentation
products.
3.1.2. Acetylation of 3. Acetic anhydride (2 mL) was added
to a solution of 3 (76 mg, 0.324 mmol) in pyridine (1 mL).
The reaction was stirred at room temperature for 18 h. Then
it was poured onto water (10 mL) and the mixture was
vigorously stirred for 15 min and then extracted with Et2O
(3£25 mL). The combined organic layers were washed with
1N HCl (2£20 mL), saturated aqueous NaHCO3 (2£
20 mL), brine, and dried over anhydrous Na2SO4. The
solvent was removed under reduced pressure to yield 4
(89 mg, 100%).
3. Experimental
3.1. General
All non-aqueous reactions were carried out under nitrogen
atmosphere unless otherwise noted. Air- and moisture-
sensitive liquids and solutions were transferred via syringe.
Reactions were monitored through TLC on commercial
silica gel plates. Visualization of the developed plate was
performed by ¯uorescence quenching and/or aqueous ceric
ammonium molybdate/anisaldehyde stains. HPLC puri®-
cation was carried out in a Merck-Hitachi L6270 equipped
with a silica gel column (LiChrosorb Si 60, 7 mm particle
size, 1£25 cm). THF, dioxane, diethyl ether, and toluene
were distilled from sodium metal. Dichloromethane and
triethylamine were distilled from calcium hydride prior to
use. Melting points are uncorrected and were measured in a
Reichert±Jung apparatus. NMR spectra were recorded on a
Varian Gemini 200 or on a Varian Unity 400. Spectra were
referenced internally to residual solvent signals. Data for 1H
are reported as follows: chemical shift (d, ppm), integration,
multiplicity and coupling constant (J, Hz). Data for 13C are
reported in terms of chemical shift (d, ppm). IR spectra were
recorded in a Mattson Genesis Series FTIR, using NaCl
plates, data are reported in cm21. Mass spectra were
obtained using a Voyager GCMS or a VG Autospec-Q.
TEMPO and AD-mixes a and b were purchased from
Aldrich and used without further puri®cation.
20
4. Yellow oil. [a]D ˆ126.4 (c 0.1, CHCl3). IR (thin ®lm) n
2938, 2867, 1738, 1681, 1451, 1388, 1227, 1023, 964,
890 cm21. MS, m/z (relative intensity) 276 [M]1 (3.1),
234 [M2CH3CO]1 (18.6), 216 [M2CH3CO±H2O]1
(100.0), 105 (35.7), 91 (66.5), 77 (54.5). HRMS calcd for
C17H24O3 276.1725, found 276.1709. 1H NMR d (400 MHz,
CDCl3): 5.97 (1H, bs, H-6), 4.77 (1H, bs, H-12), 4.41 (1H,
bs, H-120), 2.55 (1H, ddd, Jˆ17.7, 14.7, 5.3 Hz, H-2a), 2.41
(1H, bs, H-7), 2.34 (1H, ddd, Jˆ17.7, 4.9, 2.2 Hz, H-2b),
2.01 (1H, dddd, Jˆ13.8, 13.6, 5.0, 3.7 Hz, H-8a), 1.97 (3H,
bs, ±OAc), 1.80 (1H, ddd, Jˆ14.7, 13.0, 4.9 Hz, H-1b),
1.79 (3H, s, 3H-15), 1.65 (3H, bs, 3H-13), 1.57 (1H, ddd,
Jˆ13.0, 5.3, 2.2 Hz, H-1a), 1.50 (1H, ddd, Jˆ13.8, 13.6,
4.0 Hz, H-8b), 1.42 (1H, m, H-9b), 1.33 (1H, ddd, Jˆ13.7,
4.0, 3.7 Hz, H-9a), 1.26 (3H, s, 3H-14). 13C NMR d
(100 MHz, CDCl3): 199.2 (C-3), 169.1 (±OCO±CH3),
155.0 (C-5), 133.7 (C-4), 143.9 (C-11), 111.7 (C-12), 71.1
(C-6), 45.6 (C-7), 38.5 (C-1), 35.0 (C-10), 34.8 (C-9), 33.8
(C-2), 24.3 (C-14), 22.6 (C-13), 21.0 (±OCO±CH3), 19.0
(C-8), 10.8 (C-15).
3.1.1. 6a-Hydroxy-7-epi-a-cyperone (3). 7-epi-Cyperone
(2) (4.54 g, 0.021 mmol) was dissolved in a 10% methanolic
solution of KOH (70 mL) and vigorously stirred open to the
air at room temperature for 48 h. Then it was neutralised
with 1N HCl. MeOH was removed under reduced pressure.
Saturated aqueous NH4Cl (200 mL) was added to the
remaining aqueous layer which was subsequently extracted
with EtOAc (3£100 mL). The combined organic layers
were washed with water, brine, and dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure
and the residue was chromatographed (SiO2, EtOAc/
hexanes, 1:4) to yield 3 (5.02 g, 0.021 mol, 100%).
3.1.3. Dihydroxylation of 4. A solution of 4 (601 mg,
2.18 mmol) in tBuOH/H2O (10 mL, 1:1) was added over
an AD-mix a (3.25 g) solution in the same solvent mixture
(10 mL) at 08C. The mixture was stirred at 08C for 2 h and at
room temperature for 22 h. The reaction was quenched with
Na2SO3 (3.45 g) and the suspension was stirred for 1
additional hour. Then it was poured onto water (20 mL)
and extracted with EtOAc (3£50 mL). The combined
organic layers were dried over anhydrous Na2SO4 and the
solvent was removed under reduced pressure. The mixture
was cromatographed (SiO2, EtOAc/hexanes 1:1) yielding

F. J. Aladro et al. / Tetrahedron 57 (2001) 2171±2178
2175
632 mg of a mixture of 5a/5b (92%, 97:3). Analytical
samples were obtained by HPLC (EtOAc/hexanes 1:2).
Na2SO3 (800 mg) and extracted with EtOAc (2£100 mL).
The combined organic layers were washed with brine
(100 mL), dried over anhydrous Na2SO4 and the solvent
was removed under reduced pressure affording 1.12 g of
crude material which was treated with ethereal diazo-
methane. The solvent was removed under vacuum and the
residue was chromatographed (SiO2, EtOAc/hexanes 1:4) to
yield 6 (1.00 g, 2.97 mmol, 60%).
5a. Colourless crystals. Mp (EtOAc/hexanes) 104±1068C.
20
[a]D ˆ30.5 (c 0.1, CHCl3). IR (thin ®lm) n 3455, 2934,
2866, 1752, 1661, 1456, 1394, 1238, 1183, 1061, 1017, 940,
754 cm21. MS, m/z (relative intensity) 310 [M]1 (,1.0),
250 [M2CH3CO±H2O]1 (3.0), 232 [M2CH3CO±2H2O]1
(9.9), 217 [M2CH3CO±2H2O±CH3]1 (6.0), 177 [C12H17O]1
(100.0), 161 (14.2), 91 (11.6), 75 (16.9). HMRS calcd for
C17H26O5 310.1780, found 310.1763. 1H NMR d (400 MHz,
CDCl3): 6.08 (1H, s, H-6), 3.45 (1H, d, Jˆ11.3 Hz, H-12),
3.40 (1H, d, Jˆ11.3 Hz, H-120), 2.67 (1H, ddd, Jˆ18.7,
14.2, 5.8 Hz, H-2a), 2.46 (1H, ddd, Jˆ18.7, 5.6, 1.6 Hz,
H-2b), 2.23 (1H, dd, Jˆ10.9, 6.7 Hz, H-7), 2.15 (1H, m,
H-1b), 2.07 (3H, s, OCO±Me), 1.89 (3H, s, 3H-15), 1.80±
1.52 (4H, m, H-8a, H-8b, H-9b, H-9a), 1.32 (3H, s, 3H-13),
0.95 (3H, s, 3H-14). 13C NMR d (100 MHz, CDCl3): 199.6
(C-3), 171.1 (OCO±Me), 156.7 (C-5), 133.7 (C-4), 74.3
(C-11), 72.2 (C-6), 68.6 (C-12), 48.9 (C-7), 36.1 (C-1),
35.8 (C-9), 35.2 (C-10), 34.0 (C-2), 27.3 (C-13), 21.5
(OCO±CH3), 20.2 (C-14), 20.0 (C-8), 11.7 (C-15).
20
6. Yellow oil. [a]D ˆ34.8 (c 0.1, CHCl3). IR (thin ®lm) n
3494, 2935, 2869, 1738, 1667, 1471, 1374, 1234, 1186,
1019, 963 cm21. MS, m/z (relative intensity) 339 [M11]1
(7.1), 278 [M2COOCH3]1 (3.3), 235 [M11-COOCH3±
COCH3]1 (45.2), 219 [M11-COOCH3±COCH3±CH3]1
(10.3), 193 [C13H21O]1 (100.0), 177 [C12H17O]1 (53.9),
91 (29.1). HMRS calcd for C18H27O6 339.1808, found
1
339.1781. H NMR d (400 MHz, CDCl3): 6.02 (1H, bs,
H-6), 3.59 (3H, s, COO±Me), 2.46 (1H, ddd, Jˆ18.5,
14.6, 5.4 Hz, H-2a), 2.25 (1H, dd, Jˆ18.5, 4.4 Hz, H-2b),
2.08 (1H, dd, Jˆ10.1, 6.5 Hz, H-7), 1.89 (3H, s, OCO±Me),
1.74 (3H, s, 3H-15), 1.42±1.32 (2H, m, H-1a, H-9b), 1.35
(3H, s, 3H-13), 1.16 (2H, m, H-9a, H-8b), 1.12 (3H, s,
3H-14). 13C NMR d (100 MHz, CDCl3): 199.5 (C-3),
183.3 (C-12), 169.1 (OCO±Me), 155.9 (C-5), 133.4 (C-4),
76.2 (C-11), 75.6 (C-6), 52.4 (COO±Me), 49.4 (C-7), 35.9
(C-1), 35.7 (C-9), 34.7 (C-10), 33.6 (C-2), 26.4 (C-14), 24.3
(C-13), 20.8 (OCO-Me), 19.2 (C-8), 10.5 (C-15).
20
5b. Yellow oil. [a]D ˆ23.9 (c 0.1, CHCl3). IR (thin ®lm) n
3447, 2933, 2869, 1739, 1662, 1649,1472, 1374, 1173,
1045, 1020, 756 cm21. MS, m/z (relative intensity)
310 [M]1 (, 1.0), 250 [M2CH3CO±H2O]1 (3.0), 177
[C12H17O]1 (100.0), 161 (17.4), 91 (14.8), 75 (27.4).
1
HMRS calcd for C17H26O5 310.1780, found 310.1747. H
3.1.5. Saponi®cation of 6. Compound 6 (675 mg, 2 mmol)
was treated with 10% methanolic KOH (50 mL) at room
temperature for 24 h. An aqueous saturated solution of
NH4Cl (25 mL) was then added and the reaction was
extracted with EtOAc (3£25 mL), washed with saturated
aqueous NH4Cl (3£25 mL) and brine (3£25 mL), and
dried over anhydrous Na2SO4, furnishing 7 (560 mg,
1.98 mmol, 99%).
NMR d (400 MHz, CDCl3): 5.99 (1H, s, H-6), 3.55 (1H, d,
Jˆ11.2 Hz, H-12), 3.36 (1H, d, Jˆ11.2 Hz, H-120), 3.14
(1H, OH), 2.89 (1H, OH), 2.60 (1H, ddd, Jˆ18.5, 14.3,
5.6 Hz, H-2a), 2.40 (1H, ddd, Jˆ18.5, 4.0, 1.7 Hz, H-2b),
2.12±1.93 (3H, m, H-1b, H-7a, H-8a), 2.02 (3H, s, OCO±
Me), 1.84 (3H, s, 3H-15), 1.57±1.49 (3H, m, H-1a, H-8b,
H-9b), 1.26 (3H, s, 3H-13), 1.09 (3H, s, 3H-14). 13C NMR d
(100 MHz, CDCl3): 199.8 (C-3), 170.3 (OCO±Me), 156.7
(C-5), 133.6 (C-4), 73.9 (C-11), 71.5 (C-6), 67.7 (C-12),
49.1 (C-7), 36.3 (C-1), 36.2 (C-9), 35.1 (C-10), 33.9
(C-2), 26.9 (C-13), 22.1 (C-14), 21.3 (OCO±Me), 18.7
(C-8), 11.4 (C-15).
7. Colourless crystals. Mp (EtOAc/hexanes) 162±1648C.
20
[a]D ˆ28 (c 0.1, MeOH). IR (thin ®lm) n 3415, 2932,
2866, 1643, 1413, 1009, 711 cm21. MS, m/z (relative
intensity) 282 [M]1 (4.0), 250 [M2H2O±CH3]1 (8.5), 236
[M2CO2H2]1 (12.5), 220 [M2CO2H2±CH3]1 (17.3), 193
[C13H21O]1 (100.0), 177 [C12H17O2]1 (49.5), 133 (35.7),
105 (36.6), 91 (41.3). HMRS calcd for C15H22O5
3.1.4. Swern oxidation of 5a. DMSO (1.56 g, 1.42 mL,
20 mmol) dissolved in dry CH2Cl2 (2 mL) was added
drowpwise to a solution of oxalyl chloride (0.9 mL,
10 mmol) in dry CH2Cl2 (5 mL) under N2 atmosphere at
608C. The mixture was stirred for 5 min and then a solution
of 5a (1.536 g, 4.95 mmol) in dry CH2Cl2 (5 mL) was added
dropwise. After 15 min DIPEA (5.5 mL) was added drop-
wise and then it was allowed to reach room temperature.
After 30 min, the reaction was poured onto water (50 mL)
and stirred for 15 min. The mixture was extracted with
CH2Cl2 (3£100 mL) and the combined organic layers
were washed with 1N HCl (100 mL), H2O (100 mL),
aqueous 2% Na2CO3 (100 mL) and brine (100 mL), and
dried with anhydrous Na2SO4. The solvent was removed
under reduced pressure.
282.1467, found 282.1473. 1H NMR
d (400 MHz,
CDCl3): 4.84 (1H, d, Jˆ1.7 Hz, H-6), 2.45 (1H, ddd, Jˆ
18.5, 13.8, 5.6 Hz, H-2a), 2.19 (1H, ddd, Jˆ18.5, 5.2,
1.7 Hz, H-2b), 1.95 (1H, ddd, Jˆ10.2, 5.6, 1.7 Hz, H-7),
1.84 (1H, ddd, Jˆ13.8, 13.3, 5.2 Hz, H-1b), 1.64 (3H, s,
3H-15), 1.56 (1H, ddd, Jˆ12.8, 12.2, 2.5 Hz, H-8a), 1.47±
1.28 (3H, m, H-1a, H-8b, H-9a), 1.30 (3H, s, 3H-13), 1.17
(3H, s, 3H-14), 1.11 (1H, ddd, Jˆ12.2, 10.8, 10.8 Hz,
H-9b). 13C NMR d (100 MHz, CDCl3): 201.5 (C-3), 177.9
(C-12), 162.9 (C-5), 131.4 (C-4), 75.5 (C-11), 67.4 (C-6),
51.3 (C-7), 36.3 (C-9), 36.3 (C-1), 34.8 (C-10), 33.7 (C-2),
27.0 (C-14), 23.9 (C-13), 19.5 (C-8), 9.9 (C-15).
3.1.6. Preparation of lactone 8. Et3N (1.7 mL, 12 mmol)
was added to a solution of 7 (166 mg, 0.59 mmol) in dry
THF (10 mL) under N2 atmosphere at 08C. Then, MsCl
(0.78 mL, 10 mmol) was added dropwise. After 1.5 h, a
1N solution of NaOH (15 mL) was added. The mixture
was re¯uxed for 40 min, allowed to reach room temperature
The crude material was dissolved in tBuOH (5 mL). Sul-
famic acid (SO3HNH2) (780 mg, 8 mmol) and NaH2PO4
(500 mg) dissolved in H2O (10 mL) was added. Then, a
NaClO2 solution (2.5 mL, 25% w/w, 8.5 mmol) was added
dropwise. After 30 min, the reaction was quenched with

2176
F. J. Aladro et al. / Tetrahedron 57 (2001) 2171±2178
and then poured onto 1N HCl (50 mL), being stirred for
30 min at room temperature. The mixture was extracted
with EtOAc (2£100 mL) and the combined organic layers
were washed with 1N HCl (100 mL), water (100 mL) and
brine (100 mL) and dried over anhydrous Na2SO4. The
solvent was removed under reduced pressure. The crude
was chromatographed (SiO2, EtOAc/hexanes 3:7) to yield
8 (24 mg, 16%).
NaHCO3. It was extracted with EtOAc (2£50 mL), washed
with brine, and dried over anhydrous Na2SO4. The solvent
was removed under vacuum. The residue was chromato-
graphed (SiO2, EtOAc/hexanes, 2:8) to yield diol 10
(133 mg, 80%).
10. Colourless crystals. Mp (EtOAc/hexanes) 108±1108C.
20
[a]D ˆ69.2 (c 0.1, CHCl3). IR (thin ®lm) n 3418, 2934,
2869, 1661, 1451, 1386, 1260, 1212, 1114, 1017, 932, 887,
819, 754 cm21. MS, m/z (relative intensity) 236 [M]1 (5.1),
218 [M2H2O]1 (41.7), 203 [M2H2O±CH3]1 (36.4), 177
[C12H17O2]1 (20.6), 154 (49.8), 123 (60.3), 109 (100.0), 93
(74.6). HRMS calcd for C15H24O2 236.1776, found
8. Yellow crystals. Mp (EtOAc/hexanes) 134±1368C.
20
[a]D ˆ60.8 (c 0.1, CHCl3). IR (thin ®lm) n 3421, 2930,
2868, 1784, 1669, 1521, 1198, 1097, 1043, 1018, 942,
770 cm21. MS, m/z (relative intensity) 264 [M]1 (12.2),
236 [M2CO]1 (10.4), 220 [M2CO2]1 (100.0), 205
[M2CO2±CH3]1 (47.2), 177 [C12H17O2]1 (85.4), 161
(27.7), 137 (43.9), 124 (64.4), 91 (55.9). HMRS calcd for
C15H20O4 264.1362, found 264.1330. 1H NMR d (400 MHz,
CDCl3): 5.51 (1H, dq, Jˆ6.7, 1.2 Hz, H-6), 2.73 (1H, ddd,
Jˆ9.1, 8.3, 6.7 Hz, H-7), 2.62 (1H, ddd, Jˆ17.9, 13.6,
5.4 Hz, H-2a), 2.47 (1H, ddd, Jˆ17.9, 5.3, 2.8 Hz, H-2b),
1.96 (1H, ddd, Jˆ13.6, 13.3, 5.3 Hz, H-1b), 1.87 (3H, d,
Jˆ1.2 Hz, 3H-15), 1.71 (1H, ddd, Jˆ13.3, 5.4, 2.8 Hz,
H-1a), 1.64±1.52 (2H, m, H-9a, H-9b), 1.40 (3H, s,
3H-13), 1.21 (3H, s, 3H-14). 13C NMR d (100 MHz,
CDCl3): 198.8 (C-3), 177.9 (C-12), 154.2 (C-5), 134.7
(C-4), 76.7 (C-6), 75.6 (C-11), 44.9 (C-7), 36.7 (C-1),
35.4 (C-9), 35.0 (C-10), 33.8 (C-2), 25.4 (C-14), 20.2
(C-13), 17.7 (C-8), 11.6 (C-15).
1
236.1755. H NMR d (400 MHz, CDCl3): 4.96 (1H, s, H-
12), 4.94 (1H, s, H-120), 4.54 (1H, d, Jˆ1.7 Hz, H-6), 4.07
(1H, dd, Jˆ8.4, 8.2 Hz, H-3), 2.51 (1H, dd, Jˆ9.3, 9.3 Hz,
H-7), 2.04 (2H, m, H-2a, H-2b), 1.83 (3H, s, 3H-15), 1.81
(3H, s, 3H-13), 1.15 (3H, s, 3H-14). 13C NMR d (100 MHz,
CDCl3): 146.2 (C-11), 140.7 (C-5), 133.7 (C-4), 111.6
(C-12), 71.4 (C-3), 66.5 (C-6), 41.9 (C-7), 39.3 (C-1),
34.1 (C-9), 33.1 (C-10), 29.0 (C-2), 26.3 (C-14), 23.2
(C-13), 18.9 (C-8), 14.5 (C-15).
3.1.9. Oxidation of 10 with PCC on neutral alumina. A
solution of 10 (200 mg, 0.85 mmol) in CH2Cl2 (10 mL) was
added to a suspension of PCC on neutral alumina (1.05 g,
0.85 mmol, 1mmol/806 mg) in CH2Cl2 (20 mL) at 08C. The
mixture was stirred until the formation of overoxidation
products began (followed by TLC). Then, Et2O (40 mL)
was added and the mixture was ®ltered through a plug of
celite. The solvent was removed under vacuum and the
residue was chromatographed (SiO2, EtOAc/hexanes,
3:17) to yield 11 (107 mg, 54%), 10 (76 mg, 38%) and 9
(15.7 mg, 8%).
3.1.7. Oxidation of 3 with PCC on neutral alumina. A
solution of 3 (2.36 g, 10 mmol) in CH2Cl2 (10 mL) was
added to a suspension of PCC on neutral alumina (13.97 g,
11.25 mmol, 1 mmol/806 mg) in CH2Cl2 (30 mL) and was
stirred at room temperature for 20 h. Then, Et2O (100 mL)
was added and the mixture was ®ltered through a plug of
celite. The solvent was removed under vacuum to yield 9
(2.23 g, 96%).
11. Colourless crystals. Mp (EtOAc/hexanes) 81±838C.
20
[a]D ˆ136.7 (c 1.0, CHCl3). IR (thin ®lm) n 3458, 2930,
2878, 1661, 1456, 1117, 1020, 888 cm21. MS, m/z (relative
intensity) 234 [M]1 (11.1), 219 [M2CH3]1 (7.1), 205
[M22CH3]1 (21.3), 191 [C13H19O]1 (17.5), 177 [C12H17O]1
(13.9), 118 (100.0), 107 (79.0), 95 (69.9). HMRS calcd for
C15H22O2 234.1620, found 234.1600. 1H NMR d (400 MHz,
CDCl3): 5.06 (1H, bs, H-12), 4.99 (1H, bs, H-120), 4.65 (1H,
bs, H-6), 2.66 (1H, ddd, Jˆ18.7, 14.5, 5.7 Hz, H-2a), 2.54
(1H, dd, Jˆ8.9, 7.7 Hz, H-7), 2.44 (1H, ddd, Jˆ18.7, 5.3,
1.7 Hz, H-2b), 1.88±1.79 (4H, m, H-1b, H-8a, H-8b,
H-9a), 1.87 (3H, bs, 3H-15), 1.85 (3H, bs, 3H-13), 1.68
(1H, ddd, Jˆ12.9, 5.7, 1.7 Hz, H-1a), 1.54 (1H, ddd, Jˆ
11.1, 7.7, 3.7 Hz, H-9b), 1.25 (3H, s, 3H-14). 13C NMR d
(100 MHz, CDCl3): 200.0 (C-3), 160.6 (C-5), 145.4 (C-11),
132.4 (C-4), 112.3 (C-12), 67.2 (C-6), 41.6 (C-7), 38.8
(C-1), 34.2 (C-10), 33.9 (C-2), 33.4 (C-9), 24.3 (C-14),
23.2 (C-13), 18.9 (C-8), 10.8 (C-15).
20
9. Yellow oil. [a]D ˆ333.8 (c 0.1, CHCl3). IR (thin ®lm) n
2734, 2877, 1684, 1471, 1378, 1260, 1211, 1034, 939,
894 cm21. MS, m/z (relative intensity) 232 [M]1 (100.0),
217 [M2CH3]1 (52.8), 204 [M2CO]1 (34.0), 189
[M2CO±CH3]1 (96.3), 161 [M22CO±CH3]1 (61.1), 147
(47.0), 81 (97.6). HMRS calcd for C15H20O2 232.1463,
1
found 232.1453. H NMR d (400 MHz, CDCl3): 4.81 (1H,
bs, H-12), 4.59 (1H, bs, H-120), 2.97 (1H, dd, Jˆ5.0, 5.0 Hz,
H-7), 2.47 (1H, dddd, Jˆ17.4, 14.5, 4.8, 0.6 Hz, H-2a), 2.31
(1H, ddd, Jˆ17.4, 3.1, 3.1 Hz, H-2b), 1.93 (3H, m, H-1a,
H-8a, H-8b), 1.78 (1H, ddd, Jˆ13.8, 11.1, 3.8 Hz, H-9b),
1.71 (1H, dddd, Jˆ13.3, 4.8, 3.1, 0.7 Hz, H-1b), 1.63 (3H, s,
3H-13), 1.62 (3H, s, 3H-15), 1.41 (1H, ddd, Jˆ13.8, 4.4,
3.6 Hz, H-9a), 1.07 (3H, s, 3H-14). 13C NMR d (100 MHz,
CDCl3): 206.1 (C-6), 199.0 (C-3), 155.9 (C-5), 141.3
(C-11), 132.6 (C-4), 112.9 (C-12), 57.4 (C-7), 38.5
(C-10), 36.6 (C-1), 35.9 (C-9), 33.5 (C-2), 23.7 (C-8),
23.3 (C-14), 22.2 (C-13), 12.2 (C-15).
3.1.10. Acetylation of 11. Ac2O (2 mL) was added to a
solution of 11 (76 mg, 0.32 mmol) in pyridine (1 mL).
The reaction was stirred for 18 h after which time was
poured onto water and vigorously stirred for 15 additional
min. Then, it was extracted with Et2O (3£25 mL). The
combined organic layers were washed with 1N HCl (2 £
20 mL), aqueous saturated NaHCO3 (2 £ 20 mL), brine, and
dried with anhydrous Na2SO4. The solvent was removed
under reduced pressure to yield 12 (84 mg, 94%).
3.1.8. Reduction of 9 with NaBH4 and CeCl3´7H2O. To a
solution of 9 (163 mg, 0.70 mmol) in MeOH (15 mL) was
added CeCl3´7H2O (312.5 mg, 0.84 mmol). The mixture
was cooled to 2188C and NaBH4 was added until no
more starting material was observed (TLC). The reaction
was quenched by the addition of saturated aqueous

F. J. Aladro et al. / Tetrahedron 57 (2001) 2171±2178
2177
20
12. Yellow oil. [a]D ˆ40.5 (c 0.1, CHCl3). IR (thin ®lm) n
14b. Colourless crystals. Mp (EtOAc/hexanes) 265±2678C.
2934, 2870, 1739, 1669, 1463, 1373, 1226, 1018 cm21. MS,
m/z (relative intensity) 276 [M]1 (2.3), 234 [M2COCH3]1
(12.0), 216 [M2COCH3±H20]1 (46.4), 105 (59.8), 91
(100.0), 77 (79.5). HMRS calcd for C17H24O3 276.1725,
[a]D ˆ40.0 (c 0.1, CHCl3). IR (thin ®lm) n 3378, 2927,
20
1652, 1436, 1379, 1353, 1260, 1116, 799 cm21. MS, m/z
(relative intensity) 268 [M]1 (7.1), 250 [M2H2O]1 (8.0),
177 [C12H17O]1 (100.0), 164 (20.9), 123 (26.5). HMRS
1
1
found 276.1660. H NMR d (400 MHz, CDCl3): 6.00 (1H,
calcd for C15H24O4 268.1675, found 268.1668. H NMR d
d, Jˆ2.9 Hz, H-6), 4.88 (1H, bs, H-12), 4.81 (1H, bs,
H-120), 2.64 (1H, ddd, Jˆ18.5, 14.2, 5.7 Hz, H-2a), 2.53
(1H, ddd, Jˆ9.3, 9.3, 2.9 Hz, H-7), 2.42 (1H, ddd, Jˆ18.5,
5.4, 1.9 Hz, H-2b), 1.95 (3H, s, OCO±Me), 1.87±1.63 (5H,
m, H-1a, H-1b, H-8a, H-8b, H-9a), 1.79 (3H, bs, 3H-15),
1.76 (3H, bs, 3H-13), 1.56 (1H, m, H-9b), 1.25 (3H, s,
3H-14). 13C NMR d (100 MHz, CDCl3): 199.6 (C-3),
169.5 (OCO±Me), 157.8 (C-5), 144.2 (C-11), 132.9 (C-4),
112.0 (C-12), 69.4 (C-6), 41.5 (C-7), 38.3 (C-1), 34.7
(C-10), 33.8 (C-2), 33.7 (C-9), 24.6 (C-14), 23.1 (C-13),
20.9 (OCO±Me), 19.5 (C-8), 11.2 (C-15).
(400 MHz, CDCl3): 5.10 (1H, s, H-6), 3.78 (1H, d, Jˆ
11.9 Hz, H-12), 3.62 (1H, d, Jˆ11.9 Hz, H-120), 3.14 (1H,
bs, OH), 2.68 (1H, ddd, Jˆ18.7, 5.0, 1.7 Hz, H-2a), 2.45
(1H, ddd, Jˆ18.7, 14.1, 5.7 Hz, H-2b), 2.07 (2H, m, H-7,
H-8b), 1.87±1.78 (3H, m, H-1b, H-8a, H-9b), 1.85 (3H, s,
3H-15), 1.71 (1H, m, H-1a), 1.57 (1H, m, H-9a), 1.23 (3H,
s, 3H-13), 1.19 (3H, s, 3H-14). 13C NMR d (100 MHz,
CDCl3): 200.5 (C-3), 160.9 (C-5), 131.6 (C-4), 75.7
(C-11), 69.2 (C-12), 67.5 (C-6), 38.6 (C-1), 38.0 (C-7),
34.0 (C-2), 34.0 (C-10), 33.1 (C-9), 23.5 (C-14), 22.8
(C-13), 15.8 (C-8), 10.7 (C-15).
3.1.11. Epoxidation of 12. MCPBA (92 mg, 0.30 mmol)
was added to a solution of 12 (56 mg, 0.20 mmol) in
iPrOH/H2O (15 mL, 4:1). After stirring for 14 h, iPrOH
was removed under reduced pressure and the remaining
aqueous layer was extracted with EtOAc (2£50 mL). The
combined organic layers were washed with aqueous satu-
rated Na2S2O3 (2£50 mL), NaOH (1N, 2£50 mL), brine,
and dried over anhydrous Na2SO4. The residue was puri®ed
by ¯ash chromatography (SiO2, EtOAc/hexanes, 1:4) to
provide a 3:1 mixture of the epoxides 13a/13b (47 mg,
81%). We were unable to obtain analytical samples of
epoxides 13a and 13b due to their rapid decomposition on
different chromatographic systems.
3.1.13. Lactonization of 14a. The triol 14a (148 mg,
0.55 mmol) was dissolved in CH3CN (6 mL) and sodium
phosphate buffer (4,5 mL, pH 6.5). Then, TEMPO (22 mg,
0.25 mmol), NaClO2 solution (0.329 mL, 25% w/w,
2 mmol) and diluted bleach (37 mL, 0.02 mmol, 4% active
chlorine) was added and the mixture was heated to 558C.
After four days, the reaction was allowed to cool to room
temperature and 1N NaOH was added until pH 8. Then, a
saturated solution of Na2SO3 (5 mL) was added and the pH
was set to 2 by adding 1N HCl. The mixture was extracted
with EtOAc (2£50 mL) and the combined organic layers
was dried over Na2SO4 and the solvent was removed
under reduced pressure. The crude was puri®ed by ¯ash
chromatography (SiO2, EtOAc/hexanes 3:7) to provide
lactone 8 (84 mg, 57%) and 14a (22 mg, 15%).
3.1.12. Triols 14a and 14b. A 7% solution of HClO4 in H2O
(10 mL) was added to a 3:1 mixture of epoxides 13a/13b
(169 mg, 0.72 mmol) in THF/H2O (60 mL, 4:1). The
reaction was stirred for 18 h, after which time, was carefully
neutralised with 1N NaOH and THF was removed under
reduced pressure. The aqueous layer was extracted with
EtOAc (2£50 mL) and the combined organic layers were
washed with brine, dried over anhydrous Na2SO4 and the
solvent was removed under reduced pressure to provide a
mixture of triols 14a and 14b. The mixture was chromato-
graphed (SiO2, MeOH/CHCl3 2:98) affording 14a (131 mg,
0.48 mmol, 90% from 13a) and 14b (43 mg, 0.17 mmol,
90% from 13b).
3.1.14. Dehydrogenation of 8. DDQ (30 mg, 0.128 mmol)
dissolved in dry dioxane (5 mL) was added to a solution of
lactone 8 (17 mg, 0.064 mmol) in dry dioxane (5 mL) under
N2 atmosphere. The reaction was re¯uxed for 24 h, after
which time, a saturated solution of Na2S2O3 (5 mL) was
added. The mixture was then extracted with EtOAc
(3£25 mL) and the combined organic layers were washed
with 1N HCl (25 mL), saturated solution of NaHCO3
(25 mL), brine, and dried over Na2SO4. The crude mixture
was chromatographed (SiO2, EtOAc/hexanes 1:3) to yield
lactone 15 (15 mg, 89%).
14a. Colourless crystals. Mp (EtOAc/hexanes) 167±1698C.
15. Colourless crystals. Mp (EtOAc/hexanes) 155±1578C.
20
20
[a]D ˆ58.7 (c 0.1, CHCl3). IR (thin ®lm) n 3373, 2929,
[a]D ˆ20.4 (c 0.1, CHCl3). IR (thin ®lm) n 3445, 2963,
1651, 1463, 1260, 1045, 1025, 799 cm21. MS, m/z (relative
intensity) 268 [M]1 (7.2), 250 [M2H2O]1 (8.0), 177
[C12H17O]1 (100.0), 164 (22.1), 123 (27.3). HMRS calcd
for C15H24O4 268.1675 found 268.1671. 1H NMR d
(400 MHz, CDCl3): 5.09 (1H, s, H-6), 3.73 (1H, d, Jˆ
11.2 Hz, H-12), 3.34 (1H, d, Jˆ11.2 Hz, H-120), 2.69 (1H,
ddd, Jˆ18.6, 5.3, 1.7 Hz, H-2a), 2.46 (1H, ddd, Jˆ18.6,
14.1, 5.7 Hz, H-2b), 1.88 (3H, s, 3H-15), 1.80±1.70 (5H,
m, H-1b, H-7, H-8a, H-8b, H-9a), 1.71 (1H, ddd, Jˆ12.9,
5.7, 1.7 Hz, H-1a), 1.55 (1H, m, H-9b), 1.34 (3H, s, 3H-13),
1.21 (3H, s, 3H-14). 13C NMR d (100 MHz, CDCl3): 200.9
(C-3), 161.5 (C-5), 131.4 (C-4), 74.8 (C-11), 66.2 (C-12),
66.2 (C-6), 40.4 (C-7), 38.5 (C-1), 34.0 (C-10), 33.9 (C-2),
32.6 (C-9), 24.4 (C-13), 23.9 (C-14), 16.3 (C-8), 10.5
(C-15).
2954, 2935, 2863, 1773, 1655, 1542, 1473, 1419, 1313,
1208, 1042, 986 cm21. MS, m/z (relative intensity) 262
[M]1 (6.6), 244 [M2H2O]1 (3.2), 218 [M2CO2]1 (7.4),
203 [M2CO2±CH3]1 (14.6), 175 [M2C3H3O3]1 (47.7),
135 (100.0), 91 [C7H7]1 (32.0), 77 [C6H5]1 (19.6). HRMS
1
calcd for C15H18O4 262.1205, found 262.1188. H NMR d
(400 MHz, CDCl3): 6.75 (1H, d, Jˆ10.0 Hz, H-1), 6.23 (1H,
d, Jˆ10.0 Hz, H-2), 5.62 (1H, dq, Jˆ7.2 1.6 Hz, H-6), 2.93
(1H, ddd, Jˆ7.2, 7.2, 7.2 H-7), 2.41 (1H, s, OH), 2.09 (3H,
d, Jˆ1.6 Hz, 3H-15), 1.98 (1H, m, H-8a), 1.79 (1H, td,
Jˆ13.8, 6.9, H-9b), 1.75 (1H, m, H-9a), 1.62 (1H, dddd,
Jˆ13.7, 7.2, 6.9, 6.9, H-8b), 1.34 (3H, s, 3H-13), 1.31
(3H, s, 3H-14). 13C NMR d (100 MHz, CDCl3): 185.9
(C-3), 177.3 (C-12), 155.6 (C-1), 151.0 (C-5), 134.8
(C-4), 125.4 (C-2), 76.5 (C-6), 74.8 (C-11), 45.3 (C-7),

2178
F. J. Aladro et al. / Tetrahedron 57 (2001) 2171±2178
Table 1.
Â
J. L.; Galindo, A.; Cabrera, I. Rev. Latinoamer. Quõm. 1976, 7,
37.
39.5 (C-10), 32.8 (C-9), 26.9 (C-14), 20.7 (C-8), 18.3
(C-13), 12.5 (C-15).
4. (a) Holub, M.; Budesinsky, M. Phytochemistry 2015, 25,
1986. (b) Holub, M.; Toman, J.; Herout, V. Biochem. Sys.
Ecol. 1987, 15, 321.
3.1.15. Esteri®cation of 15. 2,4,6-Trichlorobenzoyl
chloride (17 mL, 0.11 mmol) and Et3N (15 mL, 0.11
mmol) was added to a solution of angelic acid (11 mg,
0.11 mmol) in CH2Cl2 (1.5 mL). The mixture was stirred
for 2 h at room temperature. After that time, a solution of
lactone 15 (13 mg, 0.05 mmol) in CH2Cl2 (2 mL) was
added. The mixture was re¯uxed for 48 h, then diluted
with Et2O (15 mL) and ®ltered. Solvent was removed
under reduced pressure and the crude was chromatographed
(SiO2, EtOAc/hexanes 3:7) to provide (1)-decipienin A 15,6
(4.7 mg, 0.013 mmol, 26%). Spectroscopic data and optical
activity were in agreement with those of the natural
compound.
5. Moreno-Dorado, F. J.; Guerra, F. M.; Aladro, F. J.;
Bustamante, J. M.; Jorge, Z. D.; Massanet, G. M. Tetrahedron
1999, 55, 6997.
Â
Â
6. Macõas, F. A.; Aguilar, J. M.; Molinillo, J. M. G.; Rodrõguez-
Luis, F.; Collado, I. G.; Massanet, G. M.; Fronczek, F. R.
Tetrahedron 2000, 56, 3409.
7. Aladro, F. J.; Guerra, F. M.; Moreno-Dorado, F. J.;
Bustamante, J. M.; Jorge, Z. D.; Massanet, G. M. Tetrahedron
Lett. 2000, 41, 3209.
8. For a complete reference about the syntheses of chiral
decalones see: A. A. Verstegen-Haaksma, S-(1)-Carvone as
Starting Material in the Enantioselective Synthesis of Natural
Products; Ph.D. Thesis, Wageningen Agricultural University,
Wageningen, The Netherlands, 1994.
Acknowledgements
9. For a general reference see: Larock, R. C. In Comprehensive
Organic Transformations; VCH: New York, 1989; pp 486±
491.
Financial support for this work from the Ministerio de
Â
Educacion y Ciencia of Spain (PB97-1360) is gratefully
acknowledged. F. J. A. and J. M. B. thank the University
10. The same conditions were employed with different but related
substrates (see Table 1).
Â
Â
of Cadiz and the Ministerio de Educacion for providing
11. This behaviour has already been reported. See: Jung, M. E.;
Angelica, S.; D'Amico, D. C. J. Org. Chem. 1997, 62, 9182.
12. Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51, 567.
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mixture.
fellowships.
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