First total synthesis of (±)-prelunularin

Article abstract of DOI:10.1055/s-2004-831240

The first total synthesis of (±)-prelunularin is described employing an intramolecular aldol addition/sulfinate elimination tandem reaction. Investigations on the mechanism of the one-pot cyclization reaction using time-dependent NMR spectroscopy suggested that the sulfinate elimination took place before the intramolecular ring-closing aldol addition.

Full text of DOI:10.1055/s-2004-831240

PAPER
2493
First Total Synthesis of ( )-Prelunularin
Total
S
ynthesis of
o
(
)-Prelunul
rarin acio Comas, Enrique Pandolfi*
Departamento de Química Orgánica, Facultad de Química, Universidad de la República., Av. Gral. Flores 2124, CC 1157, Montevideo,
Uruguay
Fax +598(2)9241906; E-mail: epandolf@fq.edu.uy
Received 20 May 2004; revised 14 June 2004
structure, prompted us to attempt the total synthesis of 1.
Abstract: The first total synthesis of ( )-prelunularin is described
Prelunularin and prelunularic acid were easily converted
employing an intramolecular aldol addition/sulfinate elimination
into the corresponding aromatic compounds lunularin and
tandem reaction. Investigations on the mechanism of the one-pot
lunularic acid1,6 under mild basic as well as acidic condi-
cyclization reaction using time-dependent NMR spectroscopy sug-
gested that the sulfinate elimination took place before the intramo- tions. These results suggested the difficulties to synthesize
lecular ring-closing aldol addition.
and handle these natural products.
Key words: tandem reactions, natural products, intramolecular cy-
clization
In our preliminary studies, aimed at the preparation of the
model structures 3-alkyl-5-hydroxycyclohex-2-enones,
we attempted an intramolecular cyclization of a 1,5-dicar-
bonyl compound to obtain the central core of the molecule
in the last step of our synthesis. We chose this strategy due
to the easy elimination of the hydroxyl group.10 Herein we
report the first total synthesis of racemic prelunularin (1)
via aldol addition/sulfinate elimination tandem reactions.
Bryophytes contain a large number of structurally novel
natural compounds.1,2 In particular, we focused on the
synthesis of cyclic and acyclic bisbibenzylic structures
with biological activities.3–5
In 1994 Kunz and Becker6 reported for the first time the
isolation of prelunularin (1) from the acetone extract of
Ricciocarpos natans, a liverwort found in Central Europe.
Later, prelunularin was also isolated from Conocephalum
Starting with the aldehyde 2, available from 3-(4-hydro-
xyphenyl)propionic acid by a known procedure,11 Wittig
reaction with acetonyltriphenylphosphonium chloride
was performed under Boden’s conditions12 to yield 3 as a
single E-isomer. Michael type addition of p-toluenesulfin-
ic acid sodium salt to the a,b-unsaturated ketone 3 was
performed in acetic acid/ethanol medium affording 4 in
90% yield. The carbonyl group of the d-oxosulfone was
protected as a ketal using ethylene glycol in the presence
of catalytic amount of p-toluenesulfonic acid to give 5 in
80% yield. At this point, our synthetic strategy was based
on the formation of a-sulfonylcarbanion from 5 using tert-
butyllithium in anhydrous tetrahydrofuran. Further addi-
tion of allyl bromide provided the alkylated compound 6,
which was treated under reductive ozonolysis to afford al-
dehyde 7 in 60% overall yield. Our strategy called for the
protection of the carbonyl group with 1,2-ethanedithiol in
presence of BF3·OEt2 to prevent aldehyde decomposition
in acidic conditions, according to our previously report.10
This treatment afforded thioacetal 8, where the removal of
the ketal group took place simultaneously to the formation
of the dithiolane (Scheme 2).
7
conicum, one of the most widespread liverwort species
in Japan. The authors suggested that this secondary me-
tabolite plays an important biochemical role as a genuine
precursor of lunularin (Scheme 1), a bibenzylic com-
pound found in many liverwort species.8,9
Prelunularin (1) is, to the best of our knowledge, the only
reported natural product containing a 3-substituted 5-hy-
droxycyclohex-2-enone skeleton. Not only this unique
structural feature, but also the difficulty to obtain such a
Deprotection of 8 with HgCl2/CaCO3 in aqueous acetoni-
trile afforded keto aldehyde 9 in 50% yield after six hours.
According to studies on kinetics and mechanism, dithio-
lane hydrolysis proceeds much faster at lower chloride ion
concentration.13,14 We found an efficient method by add-
ing silver nitrate to the reaction mixture in order to de-
crease the chloride ion concentration. Under this new
procedure the reaction occurred quantitatively to render
keto aldehyde 9 in one hour.
Scheme 1 Suggested biogenesis of lunularin and lunularic acid.
SYNTHESIS 2004, No. 15, pp 2493–2498
Advanced online publication: 22.09.2004
DOI: 10.1055/s-2004-831240; Art ID: M03704SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4
Compound 9 was conceived as a structural entity, called
holosynthon, specifically designed to make the subse-

2494
H. Comas, E. Pandolfi
PAPER
Scheme 2 Preparation of compound 9 from 3.
quent tandem reactions.15 In particular intramolecular cy- niques allowed the unambiguous assignment of all 1H and
clization was accomplished as shown in Scheme 3 by 13C signals, along with two reassignments (data available
means of aldol addition/sulfinate elimination tandem re- on request from authors).
actions.
Having established the synthetic route to prelunularin (1),
Using the optimized conditions, 9 was stirred with potas- we turned our attention to study the mechanism of the in-
sium carbonate in methanol at 0 °C for three hours and tramolecular aldol addition/sulfinate elimination tandem
then the reaction mixture was left in a freezer overnight, reactions. In order to determine which of the two possible
affording 10 in 45% yield as a racemic mixture. Deprotec- mechanisms (sulfinate elimination followed by intramo-
tion of tert-butyldimethylsilyloxy ether using tetrabutyl- lecular aldol addition, or the inverse pathway) is correct,
ammonium fluoride proceeded straightforward giving these tandem reactions were monitored by 1H NMR spec-
prelunularin (1) in 75% yield.
troscopy with a previously reported analogue molecule.10
The 1H and 13C NMR spectra of the natural and synthetic When after 60 minutes the reaction was quenched and the
1
samples were compared. According to Kunz and Becker’s mixture worked up, its H NMR spectrum (Figure 1) re-
assignment,6 two proton and two carbon signals could be vealed the presence of compounds, 12, traces of 13 and 14
exchanged. Application of two-dimensional NMR tech- (mixture of Z/E-isomers). After 240 minutes (Figure 2)
compound 12 was totally consumed and the signals of the
final product 13 were easily identified (see experimental).
The first step in this mechanism involves exclusively the
formation of the thermodynamic (E)-enolate of 11 and the
subsequent sulfinate elimination. Surprisingly, under
these thermodynamic conditions, which normally permit
equilibration between all the enolates, compound 15 was
not detected. The second step can be regarded as the ring-
closing aldol addition of the intermediate 12 according to
Scheme 4.
In summary, we have achieved the first total synthesis of
( )-prelunularin (1) in 8 steps with 9% overall yield from
3. We have shown the relevance of the ‘holosynthon’ con-
cept to access prelunularin using tandem aldol addition/
sulfinate elimination reactions. Based on spectroscopic
and experimental data, we proposed a mechanism for
these reactions with a sulfinate elimination as the first step
Scheme 3 Preparation of prelunularin (1) from keto aldehyde 9 via
aldol addition/sulfinate elimination tandem reactions.
Synthesis 2004, No. 15, 2493–2498 © Thieme Stuttgart · New York

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Total Synthesis of (±)-Prelunularin
2495
Scheme 4 Proposed mechanistic pathway for the tandem reaction.
followed by intramolecular ring-closing by means of aldol
addition.
NMR and 13C NMR were recorded on Bruker AM 400 spectrome-
ter. The chemical shifts are expressed in ppm (d) downfield from
TMS as internal standard. Mass spectra were obtained with a Shi-
madzu QP 1100 EX mass spectrometer. Elemental analyses were
carried out on a Fision EA 1108 CHNS-O analyzer.
Solvents were purified and dried by standard procedures before use.
Petroleum ether used had bp 40–60 °C. Ozone was generated with
Fisher Ozone 500. Melting points are uncorrected. IR spectra were
1
recorded on Bomen, Hartman & Braun FT-IR spectrometer. H
Figure 1 1H NMR spectrum after 60 minutes in CDCl3
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H. Comas, E. Pandolfi
PAPER
Figure 2 1H NMR spectrum after 240 minutes in CDCl3
(3E)-6-[4-(tert-Butyldimethylsilyloxy)phenyl]hex-3-en-2-one (3)
To a stirred solution of 2 (1.50 g, 9.4 mmol) in toluene (50 mL),
were added acetonyltriphenylphosphonium chloride (5.0 g, 14.1
mmol), K2CO3 (1.9g, 14.1 mmol) and 18-crown-6 ether (20 mg).
The reaction mixture was refluxed for 2 h and poured into H2O. The
mixture was extracted with EtOAc (3 × 50 mL), the combined ex-
tracts were washed with brine and dried (Na2SO4). The solvent was
removed under reduced pressure and the crude material was puri-
fied by flash chromatography (silica gel, petroleum ether–EtOAc,
95:05) to afford 2.3 g (80%) of 3 as a colorless oil.
IR (KBr): 1725, 1600, 1512, 1289, 1142, 1256, 912 cm–1.
1H NMR (CDCl3): d = 7.75 (d, 2 H, J = 8.2 Hz), 7.35 (d, 2 H, J = 8.2
Hz), 6.91 (d, 2 H, J = 8.4 Hz), 6.72 (d, 2 H, J = 8.4 Hz), 3.78–3.70
(m, 1 H), 3.14 (dd, 1 H, J = 18.1, 5.3 Hz), 2.62 (dd, 1 H, J = 18.1,
5.3 Hz), 2.64–2.46 (m, 2 H), 2.46 (s, 3 H), 2.15 (s, 3 H), 2.15–2.05
(m, 1 H), 1.80–1.70 (m, 1 H), 1.00 (s, 9 H), 0.20 (s, 6 H).
13C NMR (CDCl3): d = 204.3, 254.4, 145.2, 135.1, 133.4, 130.3 (2),
129.5 (2), 129.2 (2), 120.4 (2), 59.6, 41.9, 32.4, 31.1, 30.5, 26.1 (3),
22.0, 18.6, –4.0.
MS (EI 70 eV): m/z (%) = 461 (M+, 5), 286 (24), 247 (77), 221 (83),
141 (100).
IR (KBr): 1676, 1611, 1509, 1253, 914 cm–1.
1H NMR (CDCl3): d = 7.04 (d, 2 H, J = 8.4 Hz), 6.85–6.80 (m, 1 H),
6.78 (d, 2 H, J = 8.4 Hz), 6.09 (d, 1 H, J = 16.0 Hz), 2.72–2.76 (m,
2 H), 2.55–2.50 (m, 2 H), 2.23 (s, 3 H), 1.00 (s, 9 H), 0.20 (s, 6 H).
Anal. Calcd for C25H36O4SSi: C, 65.18; H, 7.88; S, 6.96. Found: C,
64.77; H, 7.89; S, 7. 10.
13C NMR (CDCl3): d = 198.8, 154.4, 147.6, 133.7, 132.0, 129.6 (2),
2-({4-[4-(tert-Butyldimethylsilyloxy)phenyl]}-2-[(4-methylphe-
nyl)sulfonyl]butyl)-2-methyl-1,3-dioxolane (5)
120.4 (2), 34.7, 34.0, 27.2, 26.1 (3), 18.6, –4.0.
MS (EI 20 eV): m/z (%) = 304 (M+, 5), 247 (49), 221 (100), 141
(97).
To a solution of 4 (0.95 g, 2.1 mmol) in anhyd toluene (30 mL) was
added ethylene glycol (0.4 mL, 7.2 mmol) and p-toluenesulfonic
acid (20 mg). The solution was refluxed for 2.5 h using a Dean–
Stark apparatus and allowed to cool. The reaction mixture was
washed with an 10% aq solution of NaHCO3 (20 mL), followed by
brine and dried (Na2SO4). The solvent was removed under reduced
pressure and the crude material was purified by flash chromatogra-
phy (silica gel, petroleum ether–EtOAc, 7:3) to afford 0.85 g (80%)
of 5 as a colorless oil.
Anal. Calcd for C18H28O2Si: C, 71.00; H, 9.27. Found: C, 70.58, H,
9.52.
6-[4-(tert-Butyldimethylsilyloxy)phenyl]-4-[(4-methylphe-
nyl)sulfonyl)]hexan-2-one (4)
To a stirred solution of 3 (3.0 g, 9.7 mmol) in EtOH (25 mL) was
added AcOH (1.2 mL) and p-toluenesulfinic acid sodium salt dihy-
drate (4.2 g, 19.4 mmol). The mixture was stirred at r.t. for 48 h, di-
luted with Et2O (100 mL) and washed with an aq sat. solution of
NaHCO3 (30 mL), followed by brine and dried (Na2SO4). The sol-
vent was removed under reduced pressure and the crude material
was purified by flash chromatography (silica gel, petroleum ether–
EtOAc, 7:3) to afford 4.0 g (90%) of 4 as a colorless oil.
IR (KBr): 1609, 1510, 1256, 1144, 916 cm–1.
1H NMR (CDCl3): d = 7.78 (d, 2 H, J = 8.0 Hz), 7.36 (d, 2 H, J = 8.0
Hz), 7.01 (d, 2 H, J = 8.2 Hz), 6.75 (d, 2 H, J = 8.0 Hz), 3.95–3.80
(m, 2 H), 3.75–3.60 (m, 2 H), 3.25–3.15 (m, 1 H), 2.90–2.75 (m, 1
H), 2.75–2.60 (m, 1 H), 2.46 (s, 3 H), 2.32 (d, 1 H, J = 14.7 Hz),
Synthesis 2004, No. 15, 2493–2498 © Thieme Stuttgart · New York

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Total Synthesis of (±)-Prelunularin
2497
2.20–2.00 (m, 2 H), 1.90–1.80 (dd, 1 H, J = 14.7, 8.8 Hz) 1.19 (s, 3
H), 1.00 (s, 9 H), 0.20 (s, 6 H).
13C NMR (CDCl3): d = 154.2, 144.8, 135.6, 134.3, 130.1 (2), 129.9
(2), 129.3 (2), 120.3 (2), 109.2, 65.0, 64.6, 60.2, 37.5, 32.5, 32.0,
26.1 (3), 24.5, 22.0, 18.6, –4.0.
MS (IE 20 eV): m/z (%) = 504 (M+, 15), 286 (39), 221 (89), 87
(100).
6-[4-(tert-Butyldimethylsilyloxy)phenyl]-4-(1,3-dithiolan-2-yl-
methyl)-4-[(4-methylphenyl)sulfonyl]hexan-2-one (8)
To a cooled (–20 °C) solution of 7 (1.7g, 3.2 mmol) in anhyd
CH2Cl2 (60 mL) were added 1,2-ethanedithiol (0.3 mL, 3.2 mmol)
and BF3·OEt2 (0.15 mL). The reaction mixture was kept at this tem-
perature for 15 h and then washed with brine and dried (Na2SO4).
The solvent was removed under reduced pressure and the crude ma-
terial was purified by flash chromatography (silica gel, petroleum
ether–EtOAc, 7:3) to afford 1.02 g (55%) of 8 as a white solid;
mp 139.5–140.0 °C.
Anal. Calcd for C27H40O5SSi: C, 64.25; H, 7.99; S, 6.35. Found: C,
64.65; H, 8.28; S, 6.05.
1H NMR (CDCl3): d = 7.79 (d, 2 H, J = 8.2 Hz), 7.40 (d, 2 H, J = 8.2
Hz), 7.00 (d, 2 H, J = 8.4 Hz), 6.74 (d, 2 H, J = 8.4 Hz), 5.15 (dd, 1
H, J = 8.6, 3.9 Hz), 3.44 (d, 1 H, J = 18.3 Hz), 3.30–3.05 (m, 5 H),
2.90–2.70 (m, 1 H), 2.60–2.40 (m, 5 H), 2.40–2.30 (m, 1 H), 2.28
(s, 3 H), 2.25–2.10 (m, 1 H), 2.00–1.90 (m, 1 H), 1.00 (s, 9 H), 0.20
(s, 6 H).
13C NMR (CDCl3): d = 204.8, 154.3, 145.8, 134.3, 132.4, 130.8 (2),
130.3 (2), 129.6 (2), 120.4 (2), 69.0, 48.7, 43.1, 40.7, 39.1, 38.6,
36.3, 31.9, 29.8, 26.1 (3), 22.0, 18.6, –4.0.
2-(2-{2-[4-(tert-Butyldimethylsilyloxy)phenyl]ethyl}-2-[(4-
methylphenyl)sulfonyl]pent-4-enyl)-2-methyl-1,3-dioxolane (6)
A solution of t-BuLi (1.4 mL, 1.3 M, 1.8 mmol) in hexane was add-
ed dropwise to a cooled (0 °C) solution of 5 (0.90 g, 1.8 mmol) in
anhyd THF (40 mL). After 20 min, allyl bromide (0.15 mL, 1.8
mmol) was added and the resulting solution was allowed to reach
r.t. After 12 h, the reaction mixture was poured into H2O and ex-
tracted with EtOAc (3 × 50 mL). The combined extracts were
washed with brine and dried (Na2SO4). The solvent was removed
under reduced pressure and the crude material was purified by flash
chromatography (silica gel, petroleum ether–EtOAc, 8:2) to afford
0.73 g (75%) of 6 as a colorless oil.
MS (EI 20 eV): m/z (%) = 424 (5), 149 (12), 105 (100).
Anal. Calcd for C29H42O4S3Si: C, 60.17; H, 7.31; S, 16.61. Found:
C, 59.76; H, 7.41; S, 16.46.
IR (KBr): 1600, 1509, 1288, 1136, 1256, 916, 1638 cm–1.
3-{2-[4-(tert-Butyldimethylsilyloxy)phenyl]ethyl}-5-oxo-3-[(4-
methylphenyl)sulfonyl]hexanal (9)
1H NMR (CDCl3): d = 7.81 (d, 2 H, J = 8.2 Hz), 7.36 (d, 2 H, J = 8.2
Hz), 7.04 (d, 2 H, J = 8.4 Hz), 6.75 (d, 2 H, J = 8.4 Hz), 6.20–6.05
(m, 1 H), 5.10–5.00 (m, 2 H), 4.00–3.85 (m, 4 H), 3.05–2.80 (m, 2
H), 2.70–2.60 (dd, 1 H, J = 15.5, 6.8 Hz), 2.62–2.55 (d, 1 H,
J = 15.3 Hz), 2.55–2.50 (dd, 1 H, J = 15.5, 6.2 Hz), 2.46 (s, 3 H),
2.39 (d, 1 H, J = 15.3 Hz), 2.20–2.00 (m, 1 H), 2.00–1.90 (m, 1 H),
1.39 (s, 3 H), 1.00 (s, 9 H), 0.20 (s, 6 H).
13C NMR (CDCl3): d = 154.2, 144.9, 135.5, 133.2. 130.8 (2), 130.0
(2), 129.8 (2), 120.3 (2), 110.2, 69.9, 64.1, 63.9, 41.6, 39.2, 38.5,
37.2, 36.4, 36.0, 32.2, 30.3, 30.0, 26.6, 26.0 (3), 22.0, 21.9, 18.5,
–4.0.
To a stirred solution of 8 (50 mg, 0.09 mmol) in MeCN–H2O (8:2,
40 mL) were added CaCO3 (17 mg, 0.18 mmol), HgCl2 (103 mg,
0.38 mmol) and AgNO3 (130 mg, 0.76 mmol). The reaction mixture
was heated at 60 °C for 1 h. Then Et2O (100 mL) was added, the so-
lution was filtered and washed with brine and dried (MgSO4). The
solvent was removed under reduced pressure to afford 45 mg of 9
quantitatively as a colorless oil.
1H NMR (CDCl3): d = 9.78 (m, 1 H), 7.77 (d, 2 H J = 8.2 Hz), 7.41
(d, 2 H, J = 8.2 Hz), 6.99 (d, 2 H, J = 8.4 Hz), 6.75 (d, 2 H, J = 8.4
Hz), 3.32 (d, 1 H, J = 18.0 Hz), 3.22 (d, 1 H, J = 18.0 Hz), 3.04 (dd,
1 H, J = 16.7, 2.5 Hz), 2.92 (dd, 1 H, J = 16.7, 1.5 Hz), 2.86–2.78
(td, 1 H, J = 12.5, 5.2 Hz), 2.63–2.55 (td, 1 H, J = 12.5, 5.6 Hz),
2.49 (s, 3 H), 2.24 (s, 3 H), 2.24–2.10 (m, 2 H), 1.00 (s, 9 H), 0.20
(s, 6 H).
MS (EI 20 eV): m/z (%) = 326 (21), 221 (19), 87 (100).
Anal. Calcd for C30H44O5SSi: C, 64.14; H, 8.14; S, 5.88. Found: C,
64.40; H, 8.22; S, 5.95.
13C NMR (CDCl3): d = 205.0, 198.3, 146.2, 133.7, 132.1, 130.9 (2),
130.4 (2), 129.6 (2), 120.5 (2), 67.8, 45.4, 41.7, 36.4, 32.0, 29.9,
26.1 (3), 22.1, 18.6, –4.0.
5-[4-(tert-Butyldimethylsilyloxy)phenyl]-3-(2-methyl-1,3-diox-
olan-2-ylmethyl)-3-[(4-methylphenyl)sulfonyl]pentanal (7)
Oxygen containing 0.8 mmol of ozone per litre was passed through
a cooled (–78 °C) solution of 6 (0.4 g, 0.68 mmol) in CH2Cl2 (30
mL) at a rate of 50 L/h during 10 min. After excess of ozone was
purged under reduce pressure, the solution was cooled (–78 °C) and
AcOH (0.25 mL) and zinc dust (0.1 g, 1.60 mmol) were added. The
resulting solution was allowed to reach r.t. and after 2 h was filtered
and washed with H2O (20 mL), NaHCO3 (10%) (20 mL), brine and
dried (Na2SO4). The solvent was removed under reduced pressure
to afford 0.30 g (80%) of 7 as a yellow oil.
1H NMR (CDCl3): d = 9.88 (m, 1 H), 7.78 (d, 2 H, J = 8.2 Hz), 7.40
(d, 2 H, J = 8.2 Hz), 7.00 (d, 2 H, J = 8.4 Hz), 6.75 (d, 2 H, J = 8.4
Hz), 4.10–3.80 (m, 4 H), 3.00–2.80 (m, 3 H), 2.72 (d, 1 H, J = 15.6
Hz), 2.65 (d, 1 H, J = 17.8 Hz), 2.55–2.45 (m, 4 H), 2.10–2.00 (m,
1 H), 2.00–1.85 (m, 1 H), 1.43 (s, 3 H), 1.00 (s, 9 H), 0.20 (s, 6 H).
MS (EI 20 eV): m/z (%) = 328 (43), 221 (100), 121 (30).
Anal. Calcd for C27H38O5SSi: C, 64.51; H, 7.62; S, 6.38. Found: C,
64.63; H, 7.48; S, 6.11.
3-[2-(4-tert-Butyldimethylsilyloxy)phenyl]ethyl-5-hydroxy-
cyclohex-2-enone (10)
K2CO3 (26 mg, 0.18 mmol) was added to a cooled (0 °C) solution
of 9 (48 mg, 0.09 mmol) in anhyd MeOH (15 mL). The reaction
mixture was stirred at 0 °C for 3 h and then kept overnight in a
freezer. The mixture was poured into H2O and extracted with
EtOAc (3 × 20 mL). The combined organic extracts were washed
with brine and dried (MgSO4). The solvent was removed under re-
duced pressure and the crude material was purified by flash chroma-
tography (silica gel, petroleum ether–EtOAc, 4:6) to afford 15 mg
(45%) of 10 as a colorless oil.
1H NMR (CDCl3): d = 7.03 (d, 2 H, J = 8.2 Hz), 6.77 (d, 2 H, J = 8.2
Hz), 5.96 (s, 1 H), 4.30 (m, 1 H), 2.80–2.77 (m, 2 H J = 7.7 Hz),
2.68 (dd, 1 H, J = 16.1, 4.0 Hz), 2.60 (dd, 1 H, J = 17.5, 4.1 Hz) 2.54
(t, 2 H, J = 7.7 Hz), 2.46 (dd, 1 H, J = 16.1, 8.7 Hz), 2.40 (dd, 1 H,
J = 17.5, 6.8 Hz), 1.00 (s, 9 H), 0.20 (s, 6 H).
13C NMR (CDCl3): d = 199.5, 154.3, 145.8, 134.7, 132.0, 131.0 (2),
130.2 (2), 129.5 (2), 120.4 (2), 110.5, 68.3, 64.2, 63.1, 46.8, 37.8,
34.1, 29.7, 26.1, 26.0 (3), 22.0, 18.6, –4.0.
Anal. Calcd for C29H42O6SSi: C, 63.70; H, 7.74; S, 5.86. Found: C,
63.87; H, 7.64; S, 6.00.
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2498
H. Comas, E. Pandolfi
PAPER
13C NMR (CDCl3): d = 197.9, 161.8, 156.2, 133.4, 129.5 (2), 120.52
(2), 126.6, 67.2, 46.8, 40.1, 39.1, 32.9, 26.1 (3), 18.6, –4.0.
PhCH2CH2 and CH2C=C), 2.50–2.38 (m, 2 H, CH2C=O and
CH2C=C).
MS (EI 20 eV): m/z (%) = 290 (11), 289 (72), 221 (100).
13C NMR (CDCl3): d = 198.2, 161.9, 140.8, 129.0 (2), 128.6 (2),
126.8, 126.6, 67.1, 46.7, 39.9, 39.1, 33.6.
Anal. Calcd for C20H30O3Si: C, 69.32; H, 8.73. Found: C, 69.65; H,
8.53.
MS (EI 70 eV): m/z (%) = 216 (M+, 3), 198 (M+ – H2O, 7%), 91
(100).
Prelunularin (1)
A solution of TBAF (15mg, 0.06 mmol) in anhyd THF (1 mL) was
added dropwise to a cooled (0 °C) solution of 10 (20 mg, 0.06
mmol) in anhyd THF (14 mL). After that, the reaction mixture was
poured into H2O and extracted with EtOAc (3 × 20 mL). The com-
bined extracts were washed with brine and dried (Na2SO4). The sol-
vent was removed under reduced pressure and the crude material
was purified by flash chromatography (silica gel, EtOAc) to afford
10.4 mg (75%) of 1 as a white solid; mp 66.2–66.7 °C.
5-Oxo-3-phenethylhex-3-enal (14) (1:2 Mixture of Z/E Isomers)
1H NMR (CDCl3): d = 9.82 (d, 2 H, J = 6.1 Hz, CHO, alkene E),
9.77 (d, 1 H, J = 7.7 Hz, CHO, alkene Z), 7.40–7.10 (m, 15 H, ArH,
alkene E and Z), 6.14 (d, 2 H, J = 6.1 Hz, CHCHO, alkene E), 5.90
(d, 1 H, J = 7.7 Hz, CHCHO, alkene Z), 3.73 (s, 4 H, CH2COCH3,
alkene E), 3.32 (s, 2 H, CH2COCH3, alkene Z), 3.00–2.40 [m, 12 H,
Ph(CH2)2, alkene Z and E], 2.25 (s, 3 H, CH2COCH3, alkene E),
2.20 (s, 3 H, CH2COCH3, alkene Z).
IR (disposable IR card): 3319, 2910, 2849, 1650, 1617, 1595, 1515,
1448, 1413, 1372, 1247 cm–1.
1H NMR (MeOD): d = 7.04 (d, 2 H, J = 8.8 Hz), 6.72 (d, 2 H, J = 8.8
Hz), 5.85 (s, 1 H), 4.19 (m, 1 H), 2.77 (m, 2 H), 2.66 (dd, 1 H,
J = 17.9, 4.2 Hz), 2.61 (dd, 1 H, J = 16.1, 4.2 Hz), 2.55 (m, 2 H),
2.40 (dd, 1 H, J = 17.9, 6.6 Hz), 2.39 (dd, 1 H, J = 16.1, 8.1 Hz).
Acknowledgment
Thanks are due to PEDECIBA (Project URU/97/016) for a magister
fellowship to H.C., Dr. David González for constant support and en-
couragement, Dr. Gabriel Cavalli for his assistance with the correc-
tion of this article and Dr. Gustavo Seoane for helpful discussion.
13C NMR (MeOD): d = 200.1, 164.7, 155.8, 131.9, 129.3 (2), 126.6,
115.2 (2), 66.4, 45.8, 40.2, 38.4, 32.5.
MS (IE 20 eV): m/z (%) = 232 (M+, 5), 107 (100).
References
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Anal. Calcd for C14H16O3: C, 72.39; H, 6.94. Found: C, 72.22, H,
7.02.
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5-Oxo-3-phenethyl-3-[(4-methylphenyl)sulfonyl]hexanal (11)
IR (KBr): 1717, 1597, 1497, 1287, 1138 cm–1.
1H NMR (CDCl3): d = 9.78 (dd, 1 H, J = 2.5, 1.7 Hz, CHO), 7.78
(d, 2 H, J = 8.2 Hz, ArSO2), 7.40 (d, 2 H, J = 8.2 Hz, ArSO2), 7.27
(m, 2 H, ArH), 7.18 (m, 3 H, ArH), 3.33 (d, 1 H, J = 18.0 Hz,
CH2COCH3), 3.22 (d, 1 H, J = 18.0 Hz, CH2COCH3), 3.05 (dd, 1
H, J = 16.7, 2.6 Hz, CH2CHO), 2.93 (dd, 1 H, J = 16.7, 1.7 Hz,
CH2CHO), 2.93–2.88 (m, 1 H, PhCH2CH2), 2.72–2.62 (m, 1 H,
PhCH2CH2), 2.48 (s, 3 H, CH3Ph), 2.25 (s, 3 H, CH3C=O), 2.30–
2.10 (m, 2 H, PhCH2CH2).
13C NMR (CDCl3): d = 205.1, 198.3, 146.2, 141.1, 132.0, 130.9 (2),
130.8 (2), 129.0 (2), 128.9 (2), 126.7, 67.8, 45.4, 41.7, 36.4, 32.0,
30.1, 22.1.
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MS (EI 20 eV): m/z (%) = 205 (9), 143 (12), 86 (100).
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(13) Penn, D.; Satchell, D. P. N. J. Chem. Soc., Perkin Trans. 2
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5-Hydroxy-3-phenethylcyclohex-2-enone (13)
1H NMR (CDCl3): d = 7.31–7.38 (m, 5 H, ArH), 5.97 (s, 1 H,
C=CH), 4.31 (m, 1 H, CHOH), 2.85 (t, 2 H, J = 7.8 Hz, PhCH2),
2.70 (dd, 1 H, J = 16.3, 3.7 Hz, CH2C=O), 2.64–2.52 (m, 3 H,
Synthesis 2004, No. 15, 2493–2498 © Thieme Stuttgart · New York