The Nazarov cyclization of β-carbonyl-β′-furyl-divinyl ketones and related compounds as induced by perchloric acid

Article abstract of DOI:10.1016/S0040-4020(00)01092-9

Diluted solutions of perchloric acid and acetic anhydride are introduced as a new catalyst for cationic cyclizations. The influence of the strong acid concentration and the nature of the anhydride have been studied in four types of Nazarov substrates.

Full text of DOI:10.1016/S0040-4020(00)01092-9

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1049±1057
The Nazarov cyclization of b-carbonyl-b0-furyl-divinyl ketones
and related compounds as induced by perchloric acid
p
A. Fernandez Mateos, E. M. Martõn de la Nava and R. Rubio Gonzalez
Â
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Departamento de Quõmica Organica, Facultad de C. Quõmicas, Universidad de Salamanca, Plaza de los Caõdos 1-5,
37008 Salamanca, Spain
In respectful memory of the late Professor J. de Pascual Teresa
Received 17 July 2000; accepted 20 November 2000
AbstractÐDiluted solutions of perchloric acid and acetic anhydride are introduced as a new catalyst for cationic cyclizations. The in¯uence
of the strong acid concentration and the nature of the anhydride have been studied in four types of Nazarov substrates. q 2001 Elsevier
Science Ltd. All rights reserved.
Over the past few years we have developed a procedure
aimed at the synthesis of model limonoid insect anti-
feedants,1 based on D ring construction by cationic electro-
cyclization, called the Nazarov reaction (Fig. 1).2
in the C ring, and also the oxirane ring between C-14 and C-
15 in the D ring (Fig. 2).3
These highly oxygenated limonoids show a wide range
of biological activities, including insect antifeedant and
inhibition of a type of lymphocytic leukemia. Moreover,
limonoids with the structure represented by D are con-
sidered to be biosynthetic precursors of limonoids with the
C-ring opened (C-seco limonoids), such as nimbolidin,
salannin and azadirachtin, which are the most potent insect
antifeedants of the limonoid family.3 The above relevant
characteristics make the group of limonoids represented
by partial structures A±D an interesting target, although
one for which to date no general method of synthesis has
been developed.
The approach reported by our group would gain further
relevance if it could be successfully applied to the synthesis
of bioactive limonoids such as those corresponding to the
CDE structural fragments represented by A (anthotecol), B
(amoorastatin), C (sendanin and trichilin), D (sendanal
epoxide), one of whose most relevant characteristics are
the oxygenated functions on the C-11/C-12 carbon atoms
In this work we describe our approach to the synthesis of the
limonoid group represented in Fig. 1, based on the Nazarov
reaction.
Electrocyclization studies were carried out with the divinyl
ketone models 5a, 6a and 7a. The aim of the cyclizations in
Figure 1.
Figure 2.
Keywords: Nazarov reaction; perchloric acid; antifeedant; limonoids.
Corresponding author. Fax: 1923-294574; e-mail: afmateos@gugu.usal.es
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01092-9

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1050
Scheme 1.
Scheme 1 was to obtain the indenones 8a, 17a and 15a,
which would be excellent intermediates in the synthesis
of limonoid models with the functionalization shown by
A, B, C and D (Fig. 2) through appropriate and selective
reactions.
temperature range between 25 and 1008C, but without
success. Only a complex mixture and starting material
were recovered. At ®rst sight we attributed the failure in
cyclization to the extreme sensitivity of the furan ring of
compound 6a to acids, but with the phenyl analog 6b we
were also unable to obtain a cyclization product and only the
starting material was recovered. Attempts with trimethyl-
silyl tri¯uoracetate also failed.5 The same behaviour was
found for 5a, 5b, 7a and 7b.
The Nazarov substrates were obtained from a-cyclocitral 1
by the procedure represented in Scheme 2.4
We have not found any reported examples of the Nazarov
cyclization for the substrates represented by the structures E
and F (Fig. 3). There are not many examples of the trienone
model G cyclization, and in most of them the conjugated
diene is part of an aromatic ring.2
After all these unsuccessful experiments, we decided to
introduce as a cyclization promoter a very strong acid,
such as perchloric acid, which has been used successfully
in the preparation of enol acetates from ketones.6 We found
that diluted solutions of perchloric acid in a mixture of
Our ®rst target was the cyclization of the diketones 6a and
6b. Cyclization of 6a was tested with several protonic
acids such as sulfuric, phosphoric, formic, methanesulfonic,
p-toluensulfonic and mixtures of acids such as sulfuric/
acetic, phosphoric/formic, methanesulfonic/phosphoric and a
acetic anhydride and ethyl acetate (1023 or 1022
M
HClO4/1 M Ac2O/ethyl acetate) promoted the Nazarov
cyclization of type E diketones at room temperature. Treat-
ment of the diketone 6b with the 1023 M HClO4 solution
afforded the bicyclic ketone 9b in 62% yield after 160 h at
Scheme 2. (a) MeLi, ether, 2108C, 90%; (b) PCC, CH2Cl2, 92%; (c) mCPBA, CH2Cl2, 86%; (d) NaOH, ArCHO, EtOH, 61% Arˆ3-Furyl, 96% ArˆPhenyl;
(e) PCC, CH2Cl2, 86% Arˆ3-Furyl, 93% ArˆPhenyl; (f) HCO2H, 708C, 48% Arˆ3-Furyl, 78% ArˆPhenyl.

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1051
10 and 12 are less prone to cyclization than the non-acylated
6a. Thus, treatment of 10 or 12 with the 1022 M perchloric
acid solution afforded 50% conversion in 11 or 13 after 65 h
at room temperature.
To avoid the undesired acylation of furan in the cyclization
of 6a we tried a more diluted solution in acetic anhydride
(1022 M HClO4/0.5 M Ac2O/ethyl acetate). However, under
these conditions conversion was very low (30% after 26 h)
and the products consisted of a 1:1 mixture of 9a and 10. A
more concentrated solution in perchloric acid and diluted in
acetic anhydride (1021 M HClO4/0.5 M Ac2O/ethyl acetate)
did not induce the cyclization of 6a at all after 17 h.
Figure 3.
room temperature, while most of the starting material was
recovered (Table 1). A 1022 M HClO4 solution afforded 9b
in 75% yield in only 9 h at room temperature with total
consumption of diketone 6b.
The reaction of 6a with the 1023 M HClO4 solution was
very slow (Table 2). These kinetics afforded suf®cient
time for degradation of the furane. Furan acylation also
occurred. A more complicated reaction took place with
the diketone 6a and the 1022 M HClO4 solution. After
24 h at room temperature, a mixture of ®ve products in
53% yield was obtained.
To determine the in¯uence of the anhydride component
in the cyclization we replaced the acetic anhydride by
propionic, isobutyric and pivalic anhydride. The aim of
these changes was also to suppress furan acylation by
increasing steric hindrance around the anhydride carbonyl
group. In all three cases the concentration of perchloric
solution was 1022 M HClO4, 1 M anhydride. No new results
were obtained with propionic anhydride with respect to
acetic anhydride. For the isobutyric anhydride solution the
major product was that corresponding to 9a, although a
minor furan acylated product corresponding to 13 was
detected by NMR analysis. With the pivalic anhydride
solution a short study was carried out by tuning the concen-
tration of the acid and the anhydride (Table 3). Fortunately,
to our interest no furan acylated products were found. An
increase in the concentration of the anhydride caused a
decrease in the reaction time, but did not improve the
yield. For 1 M anhydride solutions, the one most concen-
trated in perchloric acid, gave better yields in cyclization
products and a lower proportion of enolic esters.
The more nucleophilic character of the furan ring in 6a as
compared to the phenyl ring in 6b is responsible for the
difference in the behaviour of both compounds; the acyl-
ation competes with the electrocyclization in 6a and does
not occur in 6b. Another interesting observation was that
enol acetylation only occurred in cyclized products. We did
not ®nd enol acetates from compounds 6a, 6b, 10 or 12. This
could mean that these enol acetates are transient inter-
mediates that cyclize immediately. The acylated diketones
Table 1.
Our next targets were the hydroxy ketones 5a and 5b. Treat-
M
ment of the furyl derivative 5a with 1022 and 1023
perchloric acid and 1 M acetic anhydride solutions afforded
a Nazarov cyclization product 15a, but in dehydrated form
(Table 4). The yield of 15a increased with the reaction time,
while that of the acetylated product 16a decreased.
HClO4 (M)
Time (h)
Conversion (%)
Yield (%)
1023
1022
160
9
22
100
62
75
This relationship could be interpreted in terms of acetate
16a being the precursor of 15a. Treatment of 16a with a
Table 2.
HClO4 (M)
Time (h)
Yield (%)
11
9a
10
12
13
1023
1022
48
24
±
13
6
9
±
6
6
7
6
18

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1052
Table 3.
HClO4 (M)
(CH3)3CCO)2O (M)
Time (h)
Conversion (%)
14 (%)
8a (%)
1022
1022
1022
0.5
1
2
20
15
9
70
94
100
54
57
53
11
5
±
1021
0.5
1
46
16
30
100
27
24
28
35
1021
Table 4.
Substrate
HClO4 (M)
Time
Yield (%)
15a/b
16a/b
17b
5a
5a
5a
5a
5a
5b
5b
1023
1023
1023
1022
1022
1023
1022
1 h
14
26
32
45
42
43
64
36
10
7
11
3
±
±
±
±
±
2 h 30 min
6 h 30 min
30 min
1 h
30 h
45 min
13
±
5
16
1022 M perchloric acid solution gave the ketone 15a quanti-
tatively in 1 h 30 min. The time required for cyclization was
longer for the acetate 16a than for alcohols 5a and 5b,
implying the existence of other intermediates that would
be the dehydration products arising from the alcohols 5a
and 5b, i.e. the trienones 7a and 7b, respectively. Our sus-
picion was con®rmed when we observed that the trienones
7a and 7b instantaneously gave cyclization with 1022 M
HClO4 reagent to afford 15a and 15b in quantitative yield
(Schemes 1 and 3).
substrates for the Nazarov reaction if diluted solutions of
perchloric acid are used as the catalyst. We also observed
that the presence of an anhydride of the type shown before
is absolutely essential for the success of the cyclization.
Phthalic anhydride does not work at all.
After these experiments, we were interested in comparing
the catalytic power of the perchloric acid solutions with the
classic acids employed in the Nazarov reaction. The
selected substrate employed was the divinyl ketone 18a.
As described, cyclization of this ketone with a formic/
phosphoric acid mixture required 1/2 h at 708C (70%
yield).2 With the 1022 M perchloric acid solution, the reac-
tion was instantaneous at room temperature, affording a 7:3
mixture of the enone 20a and the enol acetate 19a in 70%
yield (Table 5). Substitution of 3-furyl group by the phenyl
group afforded similar results.
This result is in agreement with the absence of enol acetates
of compounds 6a, 6b, 10 or 12 among the products from the
treatment of diketones 6a and 6b with perchloric acid. In
other words, compounds of the G type (Fig. 3) are excellent
We carried out three experiments with 18b and a solution
of 1022 M HClO4, 1 M anhydride in ethyl acetate. For
propionic and isobutyric anhydride the result was identical
to that obtained for acetic anhydride. For pivalic anhydride
the product was exclusively the enone 20b. A qualitatively
similar result was obtained with a solution of 1021 M
HClO4, 0.5 M acetic anhydride.
Scheme 3.

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1053
Table 5.
Substrate
HClO4 (M)
Anhydride
Yield (%)
19a/b
20a/b
18a
18b
18b
18b
18b
18b
1022
1022
1022
1022
1022
1021
1 M acetic
1 M acetic
1 M propionic
1 M isobutyric
1 M pivalic
0.5 M acetic
21 (RˆAc)
32 (RˆAc)
17 (RˆProp)
16 (RˆiBut)
±
49
54
66
70
83
85
±
1. Experimental
(49 mmol) of pivalic anhydride. The solution was ®lled up
to 50 mL with ethyl acetate.
1.1. General methods
1.1.4. 1-(2,6,6-Trimethyl-cyclohex-2-enyl)-ethan-1-ol (2).
To a stirred solution of a-cyclocitral (4.30 g, 28.3 mmol) in
diethyl ether (138 mL) at 2108C under argon, was added a
solution of MeLi 1.6 M in diethyl ether (17.7 mL,
28.3 mmol). The reaction mixture was stirred at 2108C
for 10 min, then warmed to 08C and saturated NH4Cl was
added. The organic layer was separated and the aqueous
phase was extracted with diethyl ether. The combined
organic extracts were washed with brine and then dried.
Distillation of the solvent with a Vigreux column afforded
an epimeric mixture of alcohols 2 as an orange oil, which
was puri®ed by ¯ash chromatography. The major alcohol
(95/5 hexane/diethyl ether) was obtained as a colourless oil
(3.04 g, 18.1 mmol, 64%): IR n 3430, 2928 cm21, 1H NMR
d 0.85 (3H, s), 0.97 (3H, s), 1.28 (3H, d, Jˆ6.6 Hz), 1.80
(3H, s), 4.00 (1H, m), 5.65 (1H, m) ppm; 13C NMR d 23.3,
25.7, 27.6, 28.1, 28.5, 30.5, 32.5, 56.6, 65.6, 125.0,
132.1 ppm; MS m/z (relative intensity) 168 (M1, 20), 153
(24), 150 (29), 135 (99), 123 (57), 107 (92), 103 (100), 79
(84), 67 (63), 55 (89). The minor alcohol (90/10 hexane/
diethyl ether) was obtained as a colourless oil (1.24 g,
Commercial reagents were used as received. Dichloro-
methane was distilled under argon over calcium hydride.
Diethyl ether was distilled under argon from sodium. Hex-
ane, ethyl acetate and ethanol were distilled before use.
Melting points were determined with a BuÈchi 500 apparatus
and are not corrected. IR spectra were obtained on a Bomem
1
FT MB-100 as thin ®lms. H and 13C NMR spectra were
recorded in CDCl3 solution on a Bruker WP 200 SY (200
and 50 MHz, respectively) or on a Bruker Advance DRX
400 (400 and 100 MHz, respectively). Mass spectra were
obtained on a Shimadzu 17A GC/QP 5000 MS at 70 eV
(EI). High-resolution mass spectra were measured on a
VG-TS 250 at 70 eV (EI). Elemental analyses were obtained
on a LECO CHNS-932 instrument. All reactions were
carried out under argon atmosphere in glassware dried
overnight and cooled under argon. Reactions were moni-
tored by TLC. Flash column chromatographies were carried
out using silica gel 60 (0.040±0.063 mm Merck). Organic
extracts were dried with anhydrous Na2SO4 and concen-
trated under reduced pressure with the aid of a rotary
evaporator.
1
7.36 mmol, 26%): IR n 3430, 2928 cm21, H NMR d 0.87
(3H, s), 0.99 (3H, s), 1.14 (3H, d, Jˆ6.5 Hz), 1.80 (3H, s),
4.11 (1H, m), 5.48 (1H, m) ppm; 13C NMR d 21.4, 22.9,
25.8, 28.6 (2C), 31.3, 32.0, 56.5, 68.6, 122.5, 133.2 ppm.
1.1.1. Solution of 1023 M HClO4/1 M acetic anhydride
(50 mL). To 50 mL of absolute ethyl acetate was added
0.05 ml of 72% perchloric acid (0.58 mmol). Then 5 mL
of this solution was added to 30 mL of absolute ethyl acetate
and 4.8 mL (51 mmol) of acetic anhydride. The solution
was ®lled up to 50 mL with ethyl acetate.
1.1.5. 1-(2,6,6-Trimethyl-cyclohex-2-enyl)-ethanone (3).7
To a stirred suspension of pyridinium chlorochromate
(8.11 g, 37.6 mmol) and silica (8.11 g) in CH2Cl2
(198 mL), was added dropwise a solution of alcohols 2
(4.20 g, 25.0 mmol) in CH2Cl2 (51 mL). The reaction
mixture was vigorously stirred at room temperature under
argon atmosphere for 2 h. The resulting dark brown slurry
was ®ltered through a short column of silica and eluted with
CH2Cl2. Removal of the solvent with a Vigreux column
afforded 3 (3.82 g, 23.0 mmol, 92%) as a pale yellow oil:
IR n 2922, 1711 cm21; 1H NMR d 0.89 (3H, s), 0.90 (3H, s),
1.15 (1H, m), 1.56 (3H, s), 1.70 (1H, m), 2.07 (2H, m), 2.15
(3H, s), 2.71 (1H, s), 5.56 (1H, s) ppm; 13C NMR d 22.5,
1.1.2. Solution of 1022 M HClO4/1 M acetic anhydride
(50 mL). To 40 mL of absolute ethyl acetate was added
0.05 mL of 72% perchloric acid (0.58 mmol) and 4.8 mL
(51 mmol) of acetic anhydride. The solution was ®lled up to
50 mL with ethyl acetate.
1.1.3. Solution of 1021 M HClO4/1 M pivalic anhydride
(50 mL). To 30 mL of absolute ethyl acetate was added
0.5 mL of 72% perchloric acid (5.8 mmol) and 10 mL

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1054
23.0, 27.5, 27.7, 30.9, 31.7, 31.9, 64.4, 123.3, 130.2,
210.9 ppm; MS m/z (relative intensity) 166 (M1, 31), 123
(94), 109 (19), 91 (39), 81 (100), 67 (32), 53 (28).
128.7 (2C), 130.4, 131.5, 134.5, 143.4, 145.4, 200.7 ppm;
MS m/z (relative intensity) 270 (M1, 7), 252 (8), 237 (4),
139 (42), 131 (91), 103 (82), 77 (100), 55 (25). Anal. Calcd
for C18H22O2: C, 80.0; H, 8.2. Found: C, 79.7; H, 8.2.
1.1.6. 1-(1,3,3-Trimethyl-7-oxa-bicyclo[4.1.0]hept-2-yl)-
ethanone (4). To a stirred solution of ketone 3 (3.70 g,
22.3 mmol) in CH2Cl2 (136 mL) was added m-chloro-
perbenzoic acid (3.85 g, 22.3 mmol). The reaction mixture
was stirred under argon atmosphere at room temperature for
1 h. A solution of Na2SO3 (5%) was added and the resulting
heterogeneous mixture was vigorously stirred for 15 min.
The organic layer was separated and the aqueous phase
was extracted with CH2Cl2. The combined organic extracts
were washed with brine and dried. Removal of the solvent
under reduced pressure afforded 4 (3.49 g, 19.2 mmol, 86%)
as a colourless oil: IR n 2963, 1719 cm21; 1H NMR d 0.89
(3H, s), 0.90 (3H, s), 1.02 (1H, m), 1.35 (3H, s), 1.70 (1H,
m), 1.95 (2H, m), 2.26 (3H, s), 2.47 (1H, s), 2.99 (1H, m)
ppm; 13C NMR d 21.4, 24.5, 25.7, 29.1, 29.9, 30.8, 31.2,
56.2, 58.5, 61.9, 207.6 ppm; MS m/z (relative intensity) 182
(0.41, M1), 167 (0.85), 111 (29), 107 (100), 91 (30), 84 (56),
69 (59), 55 (76).
1.3. Oxidation of 5a and 5b
1.3.1. General procedure. To a stirred suspension of
pyridinium chlorochromate (1.62 g, 7.50 mmol) and silica
(1.62 g) in CH2Cl2 (40 mL) was added dropwise a solution
of the hydroxy ketone (5.00 mmol) in CH2Cl2 (10 mL). The
reaction mixture was vigorously stirred at room temperature
under argon atmosphere for 1 h. The resulting dark brown
slurry was ®ltered through a short column of silica and
eluted with CH2Cl2. Removal of the solvent under reduced
pressure afforded the diketone.
1.3.2. E-3-(3-Furan-3-yl-acryloyl)-2,4,4-trimethylcyclo-
hex-2-enone (6a). According to the general procedure, reac-
tion of 5a (1.30 g, 5.00 mmol) afforded 6a (1.11 g,
4.3 mmol, 86%) as a colourless solid: mp 112±1148C; IR
1
n 2924, 1669, 1620 cm21; H NMR d 1.22 (6H, s), 1.66
(3H, s), 1.96 (2H, t, Jˆ6.6 Hz), 2.60 (2H, t, Jˆ6.6 Hz),
6.48 (1H, d, Jˆ16 Hz), 6.63 (1H, m), 7.29 (1H, d,
Jˆ16 Hz), 7.49 (1H, m), 7.72 (1H, s) ppm; 13C NMR d
12.9, 27.3 (2C), 34.2, 34.8, 38.1, 107.4, 122.8, 127.0,
129.6, 138.5, 144.8, 145.5, 160.7, 197.2, 198.6 ppm; MS
m/z (relative intensity) 258 (M1, 37), 243 (6), 121 (100),
93 (29), 67 (14), 65 (50), 55(19). Anal. Calcd for C16H18O3:
C, 74.4; H, 7.0. Found: C, 74.4; H, 7.0.
1.2. Condensation of 4 with 3-furaldehyde and
benzaldehyde
1.2.1. General procedure. To a stirred solution of epoxide
ketone 4 (1.82 g, 10.0 mmol) in EtOH (45 mL) were added
gradually the aldehyde (10.0 mmol) and NaOH (800 mg,
20.0 mmol). The reaction mixture was stirred at room
temperature under argon atmosphere for 12 h and then
concentrated under vacuo to afford a residue, which was
dissolved in water and extracted with diethyl ether. The
combined organic extracts were washed with brine and
then dried. Removal of the solvent under reduced pressure
afforded the hydroxy ketone, which was puri®ed by ¯ash
chromatography (65/35 hexane/ethyl acetate).
1.3.3. E-2,4,4-Trimethyl-3-(3-phenyl-acryloyl)-cyclohex-
2-enone (6b). According to the general procedure, reaction
of 5b (500 mg, 1.85 mmol) afforded 6b (461 mg, 1.72
mmol, 93%) as a colourless solid: mp 94±968C; IR n
1
2930, 1678, 760, 700 cm21; H NMR d 1.23 (6H, s), 1.68
(3H, s), 1.98 (2H, t, Jˆ6.8 Hz), 2.62 (2H, t, Jˆ6.8 Hz), 6.78
(1H, d, Jˆ16 Hz), 7.38 (1H, d, Jˆ16 Hz), 7.40±7.60 (5H,
m) ppm; 13C NMR d 13.0, 27.3 (2C), 34.2, 34.8, 38.0, 126.9,
128.6 (2C), 129.0 (2C), 129.5, 131.1, 134.2, 146.7, 160.7,
197.4, 198.3 ppm; MS m/z (relative intensity) 268 (M1, 25),
253 (6), 131 (100), 103 (45), 91 (19), 77 (43), 67 (15), 55
(15). Anal. Calcd for C18H20O2: C, 80.6; H, 7.5. Found: C,
80.5; H, 7.5.
1.2.2. (E)-3-(Furan-3-yl)-1-(3-hydroxy-2,6,6-trimethyl-
cyclohex-1-enyl)-prop-2-en-1-one (5a). According to the
general procedure, reaction of 4 (2.40 g, 13.2 mmol) with
3-furaldehyde (1.14 mL, 1.27 g, 13.2 mmol) afforded 5a
(2.09 g, 8.05 mmol, 61%) as a pale yellow solid: mp 70±
728C; IR n 3404, 2926, 1626 cm21; 1H NMR d 1.05 (6H, s),
1.45 (1H, m), 1.60±1.85 (2H, m), 1.66 (3H, s), 1.97 (1H, m),
4.02 (1H, t, Jˆ4.8 Hz), 6.47 (1H, d, Jˆ16 Hz), 6.61 (1H,
m), 7.34 (1H, d, Jˆ16 Hz), 7.43 (1H, m), 7.69 (1H, s) ppm;
13C NMR d 17.8, 27.7, 28.7 (2C), 34.1, 34.7, 68.9, 107.5,
123.0, 128.4, 131.4, 135.5, 143.6, 144.5, 145.1, 200.6 ppm;
MS m/z (relative intensity) 260 (M1, 17), 245 (14), 242 (11),
139 (43), 121 (100), 93 (48), 67 (18), 65 (80), 55 (33). Anal.
Calcd for C16H20O3: C, 73.8; H, 7.7. Found: C, 73.7; H, 7.8.
1.4. Dehydratation of 5a and 5b
1.4.1. General procedure. To a solution of the hydroxy
divinyl ketone (0.50 mmol) in toluene (0.5 mL) was added
90% HCO2H (0.25 mL). The reaction mixture was stirred at
708C under argon atmosphere for 3 h. After cooling to room
temperature the mixture was poured onto water and
extracted with diethyl ether. The combined organic extracts
were washed with NaOH (2%), brine and then dried.
Removal of the solvent under reduced pressure followed
by ¯ash chromatography (90/10 hexane/diethyl ether)
afforded the trienone.
1.2.3. E-1-(3-Hydroxy-2,6,6-trimethylcyclohex-1-enyl)-
3-phenylprop-2-en-1-one (5b). According to the general
procedure, reaction of 4 (1.00 g, 5.49 mmol) with benzalde-
hyde (0.55 mL, 0.58 g, 5.5 mmol) afforded 5b (1.42 g,
5.27 mmol, 96%) as a white solid: mp 94±968C; IR n
1
3412, 2936, 1624, 760 cm21; H NMR d 1.09 (6H, s),
1.4.2. E-3-(3-Furyl)-1-(2,6,6-trimethylcyclohex-1,3-dienyl)-
prop-2-en-1-one (7a). According to the general procedure,
reaction of 5a (110 mg, 0.42 mmol) afforded 7a (49 mg,
1.49 (1H, m), 1.70 (3H, s), 1.70±1.90 (2H, m), 2.00 (1H,
m), 4.05 (1H, t, Jˆ5.4 Hz), 6.76 (1H, d, Jˆ16 Hz), 7.47
(1H, d, Jˆ16 Hz), 7.37±7.60 (5H, m) ppm; 13C NMR d
17.7, 27.6, 28.5, 28.6, 34.0, 34.7, 66.6, 128.1, 128.2 (2C),
0.20 mmol, 48%) as a yellow oil: IR n 2964, 1627 cm21
;
1H NMR d 1.07 (6H, s), 1.67 (3H, s), 2.14 (2H, d,

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1055
Jˆ3.0 Hz), 5.85 (2H, m), 6.51 (1H, d, Jˆ16 Hz), 6.62 (1H,
m), 7.40 (1H, d, Jˆ16 Hz), 7.45 (1H, m), 7.68 (1H, m) ppm.
Jˆ2.0 Hz), 7.51 (1H, d, Jˆ2.0 Hz), 8.09 (1H, d, Jˆ17 Hz)
ppm; 13C NMR d 13.0, 26.9, 27.3 (2C), 34.2, 34.8, 38.0,
110.2, 127.1, 130.1, 131.6, 137.6, 145.1, 149.8, 160.0,
188.9, 198.2 (2C) ppm; MS m/z (relative intensity) 300
(M1, 2), 258 (4), 243 (3), 135 (100), 121 (33), 177 (15), 55
(14). Anal. Calcd for C18H20O4: C, 72.0; H, 6.7. Found: C,
71.7; H, 6.8. 70/30 hexane/ethyl acetate afforded acetic acid
(3aRS,7aSR)-3-(2-acetyl-furan-3-yl)-3a,7,7-trimethyl-1-oxo-
3a,6,7,7a-tetrahydro-1H-inden-4-yl ester 11 (17 mg,
0.049 mmol, 6%) as a white solid: mp 82±848C; IR n 2922,
1759, 1703 cm21; 1H NMR d 1.17 (3H, s), 1.26 (3H, s), 1.43
(3H, s), 1.77 (3H, s), 2.04 (1H, dd, J1ˆ5.1 Hz, J2ˆ17 Hz),
2.12 (1H, dd, J1ˆ4.0 Hz, J2ˆ17 Hz), 2.31 (1H, s), 2.48 (3H,
s), 5.41 (1H, dd, J1ˆ4.0 Hz, J2ˆ5.1 Hz), 6.03 (1H, s), 6.53
(1H, d, Jˆ2.0 Hz), 7.55 (1H, d, Jˆ2.0 Hz) ppm; 13C NMR d
20.6, 24.6, 26.5, 27.0, 29.1, 34.5, 38.1, 51.1, 64.8, 114.2,
115.1, 126.3, 133.7, 143.9, 146.9, 147.9, 168.5, 168.7,
187.1, 207.2 ppm; MS m/z (relative intensity) 342 (M1, 4),
300 (14), 282 (15), 257 (100), 216 (43), 201 (45), 162 (46), 77
(26), 55 (82). Anal. Calcd for C20H22O5: C, 70.2; H, 6.5.
Found: C, 70.2; H, 6.4. 60/40 hexane/ethyl acetate afforded
a mixture of two products. The ®rst one was identi®ed as E-3-
[3-(5-acetyl-furan-3-yl)-acryloyl]-2,4,4-trimethyl-cyclohex-2-
enone 12 (17 mg, 0.057 mmol, 7%): 1H NMR d 1.19 (6H, s),
1.62 (3H, s), 1.95 (2H, t, Jˆ7.0 Hz), 2.47 (3H, s), 2.60 (2H, t,
Jˆ7.0 Hz), 6.55 (1H, d, Jˆ16 Hz), 7.25 (1H, d, Jˆ16 Hz),
7.35 (1H, s), 7.85 (1H, s) ppm. The second product was iden-
ti®ed as acetic acid (3aRS,7aSR)-3-(5-acetyl-furan-3-yl)-
3a,7,7-trimethyl-1-oxo-3a,6,7,7a-tetrahydro-1H-inden-4-yl
ester 13 (51 mg, 0.15 mmol, 18%): IR n 2932, 1761, 1688,
1609, 756 cm21; 1H NMR d 1.17 (3H, s), 1.26 (3H, s), 1.55
(3H, s), 1.98 (2H, m), 2.03 (3H, s), 2.05 (2H, m), 2.28 (1H, s),
2.50 (3H, s), 5.41 (1H, t, Jˆ5.0 Hz), 6.19 (1H, s), 7.35 (1H,
m), 7.91 (1H, m) ppm; 13C NMR d 21.0, 25.6, 26.0 (2C), 29.2,
34.8, 37.3, 50.2, 65.7, 116.6 (2C), 122.9, 130.6, 145.0, 147.2,
153.2, 166.8, 168.8, 186.5, 206.2 ppm; MS m/z (relative inten-
sity) 342 (M1, 2), 300 (7), 282 (15), 257 (49), 201 (30), 162
(38), 77 (32), 55 (100); HRMS 342.1473 (M1), Calcd for
C20H22O5 342.1467.
1.4.3. E-3-Phenyl-1-(2,6,6-trimethylcyclohex-1,3-dienyl)-
prop-2-en-1-one (7b). According to the general procedure,
reaction of 5b (104 mg, 0.38 mmol) afforded 7b (75 mg,
0.30 mmol, 78%) as a yellow oil: IR n 2959, 1630, 782,
691 cm21; 1H NMR d 1.10 (6H, s), 1.71 (3H, s), 2.18 (2H, d,
Jˆ3.0 Hz), 5.88 (2H, m), 6.81 (1H, d, Jˆ16 Hz), 7.45 (1H,
d, Jˆ16 Hz), 7.40±7.60 (5H, m) ppm.
1.5. Nazarov cyclizations with HClO4/anhydride/ethyl
acetate
1.5.1. General procedure. The substrate (1.00 g) was
dissolved in 100 mL of HClO4/anhydride/ethyl acetate
reagent. The solution was allowed to stand at room tempera-
ture under argon atmosphere. Saturated NaHCO3 was added
to quench the reaction. The organic layer was separated and
the aqueous phase was extracted with diethyl ether. The
combined organic extracts were washed with Na2CO3
(5%), with brine and then dried. Removal of the solvent
under reduced pressure afforded a residue, which was puri-
®ed by ¯ash chromatography.
1.5.2. Reaction of 6b with 1022 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction
of 6b (100 mg, 0.37 mmol) after 9 h, followed by ¯ash
chromatography (90/10 hexane/ethyl acetate) afforded
acetic acid (3aRS,7aSR)-3a,7,7-trimethyl-1-oxo-3-phenyl-
3a,6,7,7a-tetrahydro-1H-inden-4-yl ester 9b (87 mg,
0.28 mmol, 75%) as a colourless solid: mp 66±688C; IR n
2959, 1761, 1697, 700 cm21; 1H NMR d 1.01 (3H, s), 1.20
(3H, s), 1.43 (3H, s), 1.56 (3H, s), 1.93 (1H, dd, J1ˆ4.0 Hz,
J2ˆ17 Hz), 2.09 (1H, dd, J1ˆ5.6 Hz, J2ˆ17 Hz), 2.25 (1H,
s), 5.35 (1H, dd, J1ˆ4.0 Hz, J2ˆ5.6 Hz), 5.88 (1H, s), 7.20±
7.33 (5H, m) ppm; 13C NMR d 20.1, 24.3, 27.4, 28.6, 34.1,
38.2, 50.4, 65.3, 114.8, 127.1 (2C), 127.7 (2C), 128.0,
131.9, 136.7, 146.6, 166.3, 178.1, 207.2 ppm; MS m/z (rela-
tive intensity) 310 (M1, 8), 267 (12), 250 (21), 172 (100), 77
(16), 55 (46). Anal. Calcd for C20H22O3: C, 77.4; H, 7.1.
Found: C, 77.2; H, 7.2.
1.5.4. Reaction of 6a with 1021 M HClO4/1 M pivalic
anhydride. According to the general procedure, reaction
of 6a (97 mg, 0.38 mmol) after 16 h afforded a crude
which was puri®ed by ¯ash chromatography. 93/7 hexane/
diethyl ether afforded 2,2-dimethyl-propionic acid
(3aRS,7aSR)-3-furan-3-yl-3a,7,7-trimethyl-1-oxo-3a,6,7,7a-
tetrahydro-1H-inden-4-yl ester 14 (31 mg, 0.091 mmol,
24%) as a colourless solid: mp 83±858C, IR n 2969,
1.5.3. Reaction of 6a with 1022 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction
of 6a (210 mg, 0.81 mmol) after 24 h afforded a crude,
which was puri®ed by ¯ash chromatography. 80/20 Hexane/
ethyl acetate afforded acetic acid (3aRS,7aSR)-3-furan-3-yl-
3a,7,7-trimethyl-1-oxo-3a,6,7,7a-tetrahydro-1H-inden-4-yl
ester 9a (33 mg, 0.11 mmol, 13%) as a yellow oil: IR n
1
1748, 1694, 735 cm21; H NMR d 1.17 (9H, s), 1.25 (3H,
s), 1.27 (3H, s), 1.49 (3H, s), 1.98 (2H, m), 2.25 (1H, s), 5.31
(1H, dd, J1ˆ3.8, J2ˆ6.3 Hz), 6.10 (1H, s), 6.55 (1H, m),
7.44 (1H, m), 7.83 (1H, m) ppm; 13C NMR d 24.4, 26.7,
27.0 (3C), 29.5, 35.5, 36.6, 39.1, 50.8, 66.0, 110.7, 116.4,
120.6, 129.7, 141.9, 143.1, 148.5, 169.1, 177.6, 206.8 ppm;
MS m/z (relative intensity) 342 (M1, 2), 327 (2), 300 (2),
285 (2), 257 (30), 240 (40), 174 (100), 77 (24). Anal. Calcd
for C21H26O4: C, 73.7; H, 7.6. Found: C, 73.7; H, 7.6. 90/10
hexane/diethyl ether afforded (3aRS,7aSR)-3-furan-3-yl-
3a,7,7-trimethyl-3a,6,7,7a-tetrahydro-5H-indene-1,4-dione
8a (33 mg, 0.13 mmol, 35%) as a colourless solid: mp 108±
1108C; IR n 2926, 1682, 1605, 1458 cm21; 1H NMR d 1.09
(3H, s), 1.15 (3H, s), 1.54 (3H, s), 1.65 (1H, m), 1.97 (1H,
m), 2.27 (1H, s), 2.46 (1H, m), 2.53 (1H, m), 6.38 (1H, s),
1
2928, 1763, 1692, 756 cm21; H NMR d 1.18 (3H, s),
1.25 (3H, s), 1.55 (3H, s), 2.01 (3H, s), 2.05 (2H, m), 2.25
(1H, s), 5.39 (1H, t, Jˆ5.0 Hz), 6.11 (1H, s), 6.58 (1H, m),
7.45 (1H, m), 7.82 (1H, s) ppm; 13C NMR d 20.9, 25.4, 25.7,
29.3, 34.8, 37.2, 50.2, 65.7, 110.7, 116.2, 120.7, 129.6,
142.6, 143.1, 147.7, 168.6, 168.9, 206.6 ppm; MS m/z (rela-
tive intensity) 300 (M1, 12), 257 (37), 174 (40), 162 (100),
91 (17), 55 (55). 75/25 hexane/ethyl acetate afforded E-3-[3-
(2-acetyl-furan-3-yl)-acryloyl]-2,4,4-trimethyl-cyclohex-2-
enone 10 (21 mg, 0.073 mmol, 9%) as a pale yellow solid: mp
1
174±1768C; IR n 2924, 1669, 1642 cm21; H NMR d 1.24
(6H, s), 1.64 (3H, s), 2.01 (2H, t, Jˆ7.0 Hz), 2.52 (3H, s), 2.61
(2H, t, Jˆ7.0 Hz), 6.60 (1H, d, Jˆ17 Hz), 6.77 (1H, d,

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1056
6.57 (1H, m), 7.44 (1H, m), 7.80 (1H, m) ppm; 13C NMR d
25.2, 26.2, 28.5, 33.5, 34.5, 35.4, 58.7, 67.6, 109.5, 119.3,
129.1, 143.6, 144.3, 166.7, 206.8, 213.8 ppm; MS m/z (rela-
tive intensity) 258 (M1, 12), 243 (2), 174 (100), 69 (52), 55
(34). Anal. Calcd for C16H18O3: C, 74.4; H, 7.0. Found: C,
74.4; H, 7.0.
(100), 172 (88), 131 (84), 77 (97). Anal. Calcd for C20H24O3:
C, 76.9; H, 7.7. Found: C, 76.7; H, 7.7. 80/20 hexane/ethyl
acetate afforded acetic acid (3aRS,4RS,7aSR)-3a,7,7-
trimethyl-1-oxo-3-phenyl-3a,4,5,6,7,7a-hexahydro-1H-inden-
4-yl ester 17b (8.0 mg, 0.025 mmol, 5%) as a colourless
solid: mp 104±1068C; IR n 2961, 1738, 1696, 698 cm21
;
1H NMR d 1.00 (3H, s), 1.25 (3H, s), 1.40±1.70 (3H, m),
1.54 (3H, s), 1.57 (3H, s), 1.88 (1H, m), 2.21 (1H, s), 5.30
(1H, dd, J1ˆ5.0 Hz, J2ˆ5.5 Hz), 6.04 (1H, s), 7.30±7.42
(5H, m) ppm; 13C NMR d 20.4, 23.9, 24.3, 25.1, 32.4,
34.0, 35.0, 50.2, 64.7, 72.6, 127.2 (2C), 128.3 (2C), 128.8,
131.8, 136.1, 169.8, 180.9, 207.7 ppm; MS m/z (relative
intensity) 312 (M1, 7), 270 (25), 237 (20), 131 (100), 103
(61), 91 (34), 77 (58). Anal. Calcd for C20H24O3: C, 76.9; H,
7.7. Found: C, 76.7; H, 7.8.
1.5.5. Reaction of 5a with 1022 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction
of 5a (95 mg, 0.37 mmol) after 30 min afforded a crude,
which was puri®ed by ¯ash chromatography (90/10 hexane/
ethyl acetate). The ®rst fraction was a pale yellow solid
identi®ed as (3aRS,7aSR)-3-furan-3-yl-3a,7,7-trimethyl-
3a,6,7,7a-tetrahydro-inden-1-one 15a (41 mg, 0.17 mmol,
1
45%): mp 48±508C; IR n 2961, 1688 cm21; H NMR d
0.85 (3H, s), 1.22 (3H, s), 1.42 (3H, s), 1.80 (1H, m), 1.96
(1H, m), 2.14 (1H, s), 5.76 (1H, m), 5.99 (1H, m), 6.09 (1H,
s), 6.59 (1H, m), 7.48 (1H, m), 7.83 (1H, s) ppm; 13C NMR d
24.0, 29.2, 30.6, 34.3, 39.1, 47.8, 64.1, 110.0, 119.7, 126.7
(2C), 129.6, 142.4, 143.7, 170.3, 208.8 ppm; MS m/z (rela-
tive intensity) 242 (M1, 100), 227 (89), 199 (77), 174 (99),
115 (52), 91 (80), 77 (64), 65 (49), 63 (75), 55 (45). Anal.
Calcd for C16H18O2: C, 79.3; H, 7.5. Found: C, 79.4; H, 7.4.
The second fraction was a pale yellow solid identi®ed as
acetic acid 3-(3-furan-3-yl-acryloyl)-2,4,4-trimethyl-cyclo-
hex-2-enyl ester 16a (12 mg, 0.041 mmol, 11%): mp 112±
1148C; IR n 2969, 1730, 1626 cm21; 1H NMR d 1.08 (3H,
s), 1.10 (3H, s), 1.49 (1H, m), 1.55 (3H, s), 1.60±1.90 (2H,
m), 2.01 (1H, m), 2.10 (3H, s), 5.27 (1H, t, Jˆ5.0 Hz), 6.48
(1H, d, Jˆ16 Hz), 6.62 (1H, d, Jˆ2.0 Hz), 7.33 (1H, d,
Jˆ16 Hz), 7.46 (1H, m), 7.71 (1H, s) ppm; 13C NMR d
17.2, 20.7, 25.0, 27.2, 28.1, 33.5, 34.5, 70.6, 107.2, 122.6,
127.6, 127.8, 135.1, 144.2, 144.9, 145.4, 170.2, 199.2 ppm;
MS m/z (relative intensity) 302 (M1, 7), 260 (22), 227 (23),
139 (19), 121 (100), 93 (32), 65 (45). Anal. Calcd for
C18H22O4: C, 71.5; H, 7.3. Found: C, 71.5; H, 7.3.
1.5.7. Reaction of 7a with 1022 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction
of 7a (39 mg, 0.16 mmol) after 1 min, followed by ¯ash
chromatography (90/10 hexane/ethyl acetate) afforded 15a
(36 mg, 0.15 mmol, 95%).
1.5.8. Reaction of 7b with 1022 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction
of 7b (50 mg, 0.20 mmol) after 1 min, followed by ¯ash
chromatography (90/10 hexane/ethyl acetate) afforded 15b
(48 mg, 0.19 mmol, 97%).
1.5.9. Reaction of 18a with 1022 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction
of 18a (125 mg, 0.51 mmol) after 1 min afforded a crude,
which was puri®ed by ¯ash chromatography. 96/4 hexane/
diethyl ether afforded acetic acid 3-furan-3-yl-3a,7,7-
trimethyl-3a,5,6,7-tetrahydro-4H-inden-1-yl ester 19a
(31 mg, 0.11 mmol, 21%) as a yellow oil: IR n 2932,
1
1765 cm21; H NMR d 1.10±2.10 (6H, m), 1.23 (3H, s),
1.29 (3H, s), 1.30 (3H, s), 2.20 (3H, s), 6.29 (1H, s), 6.51
(1H, s), 7.36 (1H, m), 7.46 (1H, s) ppm; 13C NMR d 19.4,
21.0, 23.1, 26.4, 30.9, 35.2, 36.2, 43.4, 52.3, 109.3, 120.2,
122.2, 137.9, 141.6, 142.0, 142.6, 146.4, 169.0 ppm. 90/10
hexane/diethyl ether afforded (3aRS,7aSR)-3-furan-3-yl-
3a,7,7-trimethyl-3a,4,5,6,7,7a-hexahydro-inden-1-one 20a
(61 mg, 0.25 mmol, 49%) as a pale yellow solid: mp 58±
1.5.6. Reaction of 5b with 1023 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction
of 5b (135 mg, 0.50 mmol) after 30 h afforded a crude
which was puri®ed by ¯ash chromatography. 90/10 hexane/
ethyl acetate afforded (3aRS,7aSR)-3a,7,7-trimethyl-3-
phenyl-3a,6,7,7a-tetrahydro-inden-1-one 15b (53 mg,
0.21 mmol, 43%) as a white solid: mp 100±1028C; IR n
1
598C; IR n 2980, 1690 cm21; H NMR d?0.92 (3H, s),
1
2924, 1690, 700 cm21; H NMR d 0.87 (3H, s), 1.23 (3H,
1.15±1.95 (6H, m), 1.23 (3H, s), 1.39 (3H, s), 1.94 (1H,
s), 6.13 (1H, s), 6.58 (1H, m), 7.47 (1H, m), 7.78 (1H, m)
ppm; 13C NMR d 17.0, 24.4, 28.8, 30.7, 32.6, 34.0, 35.6,
46.0, 63.6, 109.8, 119.5, 126.9, 142.5, 143.5, 173.9,
209.7 ppm; MS m/z (relative intensity) 244 (M1, 16), 229
(16), 175 (25), 162 (42), 145 (20), 131 (3), 115 (51), 91
(100), 77 (75), 63 (78). Anal. Calcd for C16H20O2: C,
78.6; H, 8.2. Found: C, 78.7; H, 8.3.
s), 1.40 (3H, s), 1.81 (1H, m), 1.99 (1H, m), 2.19 (1H, s),
5.75 (1H, m), 5.85 (1H, m), 6.03 (1H, s), 7.41 (5H, s) ppm;
13C NMR d 23.8, 28.9, 31.1, 34.1, 39.3, 48.2, 64.4, 126.0,
127.7 (2C), 128.4 (2C), 129.0, 129.2 (2C), 134.8, 180.1,
209.7 ppm; MS m/z (relative intensity) 252 (M1, 32), 237
(43), 184 (52), 115 (49), 102 (55), 91 (100), 77 (82), 65 (51),
55 (51), 51 (68). Anal. Calcd for C18H20O: C, 85.7; H, 8.0.
Found: C, 85.7; H, 8.0. 85/15 hexane/ethyl acetate afforded
acetic acid E-2,4,4-trimethyl-3-(3-phenyl-acryloyl)-cyclo-
hex-2-enyl ester 16b (20 mg, 0.064 mmol, 13%) as a
1.5.10. Reaction of 18b with 1022 M HClO4/1 M acetic
anhydride. According to the general procedure, reaction of
18b (120 mg, 0.47 mmol) after 1 min afforded a crude
which was puri®ed by ¯ash chromatography (96/4 hexane/
ethyl acetate). The ®rst fraction was a yellow solid identi®ed
as acetic acid 3a,7,7-trimethyl-3-phenyl-3a,5,6,7,-tetrahy-
dro-4H-inden-1-yl ester 19b (44 mg, 0.15 mmol, 32%):
white solid: mp 116±1188C; IR n 2924, 1738, 1630 cm21
;
1H NMR d 1.09 (3H, s), 1.11 (3H, s), 1.48 (1H, m), 1.57
(3H, s), 1.60±1.90 (2H, m), 1.99 (1H, m), 2.10 (3H, s), 5.27
(1H, t, Jˆ5.0 Hz), 6.76 (1H, d, Jˆ16 Hz), 7.45 (1H, d,
Jˆ16 Hz), 7.40±7.60 (5H, m) ppm; 13C NMR d 17.6,
21.1, 25.4, 27.6, 28.5, 34.0, 35.0, 71.1, 128.1, 128.2, 128.3
(2C), 128.9 (2C), 130.6, 134.7, 145.4, 146.1, 170.6,
199.8 ppm; MS m/z (relative intensity) 312 (M1, 30), 252
1
mp 124±1268C, IR n 2930, 1755, 698 cm21; H NMR d
1.20±1.90 (5H, m), 1.24, (3H, s) 1.29 (3H, s), 1.32 (3H,
s), 2.22 (3H, s), 2.35 (1H, m), 6.43 (1H, s), 7.22±7.49

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A. Fernandez Mateos et al. / Tetrahedron 57 (2001) 1049±1057
1057
(5H, m) ppm; 13C NMR d 19.5, 21.0, 22.3, 26.2, 31.0, 35.3,
35.7, 42.7, 53.2, 124.2, 126.8, 127.2 (2C), 128.2 (2C),
135.7, 141.5, 142.0, 154.2, 169.0 ppm. Anal. Calcd for
C20H24O2: C, 81.0; H, 8.2. Found: C, 80.9; H, 8.2. The
Â
Rubio Gonzalez, R.; Tapia Hernandez, C. Synthesis 1997,
Â
1381.
2. (a) Santelli-Rouvier, C.; Santelli, M. Synthesis 1983, 429. (b)
Habermas, K. L.; Denmark, S. E.; Jones, T. K. Org. React.
1994, 45, 1.
second fraction was
a
yellow oil identi®ed as
(3aRS,7aSR)-3a,7,7-trimethyl-3-phenyl-3a,4,5,6,7,7a-hexa-
3. (a) Champagne, D. E.; Koul, O.; Isman, M. B.; Scudder, G. G.
E.; Towers, G. H. N. Phytochemistry 1992, 31, 377. (b) Kraus,
W. Biologically active compounds from Meliaceae. In Chem-
istry and Biotechnology of Biologically Active Natural
Products, Szantay, Cs., Ed.; In Studies in Organic Chemistry,
Elsevier: Amsterdam, 1984; Vol. 17, pp 331±345 (Proceed-
ings of the Second International Conference; Budapest, 15±19
August, 1983).
hydro-inden-1-one 20b (53 mg, 0.21 mmol, 45%): IR n
1
2947, 1694, 768 cm21; H NMR d 0.95 (3H, s), 1.22 (3H,
s), 1.30±1.70 (5H, m), 1.37 (3H, s), 1.98 (1H, m), 2.02 (1H,
s), 6.07 (1H, s), 7.40 (5H, m) ppm; 13C NMR d 18.0, 25.1,
30.7, 31.4, 32.4, 34.1, 36.9, 47.1, 64.5, 127.6 (2C), 128.4
(2C), 129.2, 130.2, 135.1, 182.6, 210.1 ppm; MS m/z (rela-
tive intensity) 254 (24, M1), 239 (58), 185 (60), 172 (100),
115 (30), 91 (46), 77 (44), 55 (46); HRMS 254.1676 (M1),
Calcd for C18H22O 254.1671.
 Â
4. (a) Fernandez Mateos, A.; Martõn de la Nava, E. M.; Pascual
Â
Coca, G.; Ramos Silvo, A.; Rubio Gonzalez, R. Synlett 1998,
12, 1372. (b) All compounds synthesized are racemic although
only one enantiomer is depicted.
Acknowledgements
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Financial support for this work and the fellowship to
Â
E. M. M. N. from Ministerio de Educacion y Ciencia of
Spain PB 98±0251 and Junta de Castilla y Leon SA 24/
Â
7. (a) BuÈchi, G.; Pickenhagen, W. J. Org. Chem. 1973, 38, 894.
(b) Cookson, R. C.; Tuddenham, R. M. J. Chem. Soc., Perkin
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00B is gratefully acknowledged.
References
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1. Fernandez Mateos, A.; Lopez Barba, A.; Pascual Coca, G.;