The synthesis of 2-alkylated cyclopentene-1,3-diones: Novel compounds with olfactory properties

Article abstract of DOI:10.1081/SCC-120015556

The syntheses of 2-butyl-4,5-dimethylcyclopent-4-ene-1,3-dione, possessing a buttery jasmine odor, and a series of analogues have been carried out via the synthesis of butenolactones, with subsequent conversion to 4,5-dimethylcyclopent-4-ene-1,3-dione and an alkylation strategy. The compound with the strongest odor characteristics, has also been synthesised using a Pauson-Khand reaction and selective oxidative route.

Full text of DOI:10.1081/SCC-120015556

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The Synthesis of 2-Alkylated Cyclopentene-1,3-diones:
Novel Compounds with Olfactory Properties
a c
b
a
Helen C. Hailes
, Ben Isaac & M. Hashim Javaid
a
Department of Chemistry, University College London, London, UK
Bush Boake Allen Ltd., London, UK
b
c
Department of Chemistry, University College London, 20 Gordon Street, London, WC1H
AJ, UK
0
Version of record first published: 20 Aug 2006
To cite this article: Helen C. Hailes, Ben Isaac & M. Hashim Javaid (2003): The Synthesis of 2-Alkylated Cyclopentene-1,3-
diones: Novel Compounds with Olfactory Properties, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:1, 29-41
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 1, pp. 29–41, 2003
The Synthesis of 2-Alkylated
Cyclopentene-1,3-diones: Novel Compounds
with Olfactory Properties
1
,
2
1
Helen C. Hailes, * Ben Isaac, and M. Hashim Javaid
1
Department of Chemistry, University College London, London,
UK
2
Bush Boake Allen Ltd., London, UK
ABSTRACT
The syntheses of 2-butyl-4,5-dimethylcyclopent-4-ene-1,3-dione,
possessing a buttery jasmine odor, and a series of analogues have
been carried out via the synthesis of butenolactones, with subsequent
conversion to 4,5-dimethylcyclopent-4-ene-1,3-dione and an alkyla-
tion strategy. The compound with the strongest odor characteristics,
has also been synthesised using a Pauson–Khand reaction and
selective oxidative route.
Key Words: Butenolactones; Cyclopentene-1,3-diones; Pauson-
Khand.
*
Correspondence: Helen C. Hailes, Department of Chemistry, University College
London, 20 Gordon Street, London, WC1H 0AJ, UK. Fax: +44 (0)20 7679 7463;
E-mail: h.c.hailes@ucl.ac.uk.
2
9
DOI: 10.1081/SCC-120015556
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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3
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Hailes, Isaac, and Javaid
[
1]
2-Butyl-4,5-dimethylcyclopent-4-ene-1,3-dione 1 was first identified
during the synthesis of bovilide 2, an ylidenebutenolactone found in, for
[2]
[3]
example, peppermint oil and green tea leaves. It possesses a buttery
jasmine odor, and since the jasmonate fragrances are both highly prized
and sought after, as well as being extensively used, its synthesis, together
with analogues, was of great interest for potential use in
perfumery applications. Compound 1 is structurally related to calythrone
3
, a member of a unique group of naturally occurring cyclopentene-
Calythrone itself possesses a floral odor,
[4–7]
1,3-dione b-triketones.
reminiscent of cis-jasmone 4. Herein we report the synthesis of 1 and
related analogues via a 2-ylidenebutenolactone and also the synthesis
of 1 using a Pauson–Khand and selective oxidative strategy.
Due to previous work on the rearrangement of ylidenebutenolac-
[6,7]
tones, and our aimof generating analogues of 1, the synthetic
route shown in Sch. 1 was explored. The treatment of 2,3-dimethylmaleic
Scheme 1.

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2
-Alkylated Cyclopentene-1,3-diones
31
anhydride with ethoxycarbonylmethylenetriphenylphosphorane in
toluene gave the butenolactones 5a and 5b in 76% yield, in an isomeric
[8,9]
ratio of E:Z of 2:3.
Whilst a geometric mixture of isomers was not
problematical due to the rearrangement in the next step, we noted that
the use of THF or aqueous CTAB (cetyltrimethylammonium bromide)
media led to product formation in higher E:Z ratios (yields 69% and
52% and ratios of 1:1 and 3:2 respectively) due to solvent effects on
the stability and rate of decomposition of the threo and erythro betaines.
The mixture of 5a and 5b was treated with sodiumin methanol followed
by hydrolysis and decarboxylation to generate 4,5-dimethylcyclopent-
[
10]
4-ene-1,3-dione 6, in an overall yield of 83%.
We noted that the use
of methoxide, rather than ethoxide, led to superior yields in this system.
The selective C-alkylation of 1,3-dicarbonyl compounds is often pro-
blematical due to competing self condensation and O-alkylation. We
initially wished to access quantities of the mono and dialkylated materials
(
alumina impregnated with sodium ethoxide
Compounds 1, 7–11) for analysis purposes. An alkylation method using
[
11]
unfortunately led to the
formation of self condensation products only. However, the use of a
biphasic procedure using tetrabutylammonium bromide as a phase trans-
[
12]
fer catalyst
dialkylated products 1 and 7, which were readily separable, in 57% and
1% yields respectively. The use of pentyl- and hexylbromide generated
with bromobutane led to the formation of the mono and
1
the corresponding analogues (8–11), and further attempts to improve the
yields of the monoalkylated materials were not fruitful. 2-Butyl-4,5-
dimethylcyclopent-4-ene-1,3-dione 1 possessed the strongest odor char-
acteristics, and therefore a novel alternative route to 1 was sought which
would avoid the alkylation procedure which had led to a mixture of
products.
The Pauson–Khand reaction has emerged as a useful method
for the construction of five membered rings, particularly with the
use of allenic compounds as unsaturated partners to the alkyne cobalt
[13,14]
complexes.
We envisaged using this technique to assemble the five
membered ring, together with a selective oxidative cleavage, and the route
explored is given in Sch. 2.
Dicobalthexacarbonylbut-2-yne complex was prepared from but-
[
14,15]
2-yne in almost quantitative yield as previously reported.
yn-5-ol
Undec-6-
was heated with tributyltin hydride and AIBN to give
[16]
the completely regioselective hydrostannylation product which was
converted into the mesylate, and which underwent spontaneous elimina-
[
17]
tion to form5,6-undecadiene 12 in 77% yield. The Pauson–Khand
reaction was then carried out in the presence of N-methylmorpholine

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Hailes, Isaac, and Javaid
Scheme 2.
N-oxide monohydrate to generate 4-pentylidene-5-butyl-2,3-dimethyl-
[
cyclopent-2-enone 13 in 80% yield.
14]
Since exocyclic alkenes are normally more reactive than endocyclic
alkenes, we anticipated high selectivity in the oxidation of the trisubsti-
tuted olefin to afford 1. When using a catalytic osmium tetraoxide/
[
18,19]
sodiumperiodate oxidation procedure
was isolated at best in 65% yield. The use of an ozonolysis procedure
under various conditions,
1
was then investigated to improve the yield, together with an azo-dye to
serve as a marker to indicate completion of the required oxidation. Ozone
was expected to react with the more electron-rich trisubstituted olefin first
prior to oxidation of the azo-dye, the consumption of which will result in
[
20]
a color loss. Sudan Red 7B (also known as Solvent Red 19) served as
an excellent indicator, and the use of this procedure gave rise to 1 in an
isolated yield of 87%.
In summary, we have synthesised the novel compounds 1 and 7–11
via a rearrangement and alkylation strategy, and also 1 via a
Pauson–Khand reaction and oxidative route. Compound 1 possessed
the strongest odor characteristics, and is an important addition to the
family of compounds with jasmine-like fragrance properties.
EXPERIMENTAL
Unless otherwise indicated, reagents were obtained from commercial
suppliers and were used without further purification. THF was freshly
distilled fromsodiu m/ benzophenone. Toluene was freshly distilled
fromsodiu m. Triethyla mi ne was distilled fromand stored over potas-
siumhydroxide. Methanol was distilled from ma gnesiumturnings and

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2
-Alkylated Cyclopentene-1,3-diones
33
˚
stored over 3 A molecular sieves. ‘Ethanol’ refers to absolute ethanol
[
21]
(
>99.7%) and was used as received. Flash column chromatography
was carried out using silica gel (particle size 40–63 mm) purchased
fromBDH.
Proton NMR spectra were recorded at 400 MHz on a Varian VXR-
4
1
00 instrument or at 200 MHz, on a Varian XL-200 instrument. Carbon-
3 NMR spectra were recorded at 100.6 MHz on a Varian VXR-400
instrument. Residual protic solvent was taken as internal standard,
˚
with CDCl as solvent unless otherwise stated, stored over 4 A molecular
3
sieves and filtered through basic alumina prior to use. Coupling constant
(
J) values are given in Hz.
Mass spectra were taken on an Autospec Q, VG 7070, or VG 7070B
instrument with sources for EI. Infra red spectra were recorded on a
Perkin–Elmer FT-IR 1605 spectrometer. CHN analyses were carried
out on a Perkin–Elmer 2400 CHN Elemental Analyzer. Melting points
were taken on a Reichert hot stage instrument and are uncorrected.
Ethoxycarbonylmethylenetriphenylphosphorane was prepared as
[
22]
previously reported.
as previously reported.
Dicobalt hexacarbonylbut-2-yne was prepared
[
14,15]
Ethyl (E)-3,4-dimethyl-5-oxo-2,5-dihydrofuran-2-ylidene ethanoate (5a)
Ethyl (Z)-3,4-dimethyl-5-oxo-2,5-dihydrofuran-2-ylidene ethanoate (5b):
To a solution of 2,3-dimethylmaleic anhydride (3.50 g, 27.8 mmol), in
dry toluene (140 mL), ethoxycarbonylmethylenetriphenylphosphorane
(
8.88 g, 27.8 mmol) was added in one portion, and the mixture was stirred
for 18h at room temperature. The solvent was removed in vacuo to
afford a white solid. The crude material was dissolved in petroleum
ꢀ
spirit (40–60 C) (50 mL) and the triphenylphosphinoxide removed
by filtration. The filtrate was reduced in vacuo to give an oil (containing
1
the E:Z compounds in a ratio of 2:3 by H NMR) which was purified by
ꢀ
flash column chromatography (petroleum ether 40–60 C/ethyl acetate,
20:1 to 5:1). The two products (5a and 5b) were isolated in a combined
yield of 76%, R 0.75 (E), 0.45 (Z) (7:1 petroleumether 40–60 C/ethyl
o
f
[
9]
acetate). Due to confusion arising froma previous publication
which
reported the Z-isomer as having the higher R , more comprehensive
f
NMR spectral data was obtained for 5a and 5b to confirmtheir
assignment below.
Ethyl (E )-3,4-dimethyl-5-oxo-2,5-dihydrofuran-2-ylidene ethanoate
[
9]
ꢁ1
(
1
(
5a) : ꢀmax(film)/cm 2985s, 2938s, 1787s (C¼O), 1723s (C¼O), and
649s (C¼C); ꢁ (400 MHz; CDCl ) 1.29 (3H, t, J 7.1, OCH CH ), 1.93
H
3
2
3
3H, s, C4-Me), 2.29 (3H, s, C3-Me), 4.18 (2H, q, J 7.1, OCH CH ), and
2 3
5
.90 (1H, s, CHCO Et); ꢁ (100 MHz; CDCl ) 9.0, 13.4, 14.1 (CH CH ),
2 C 3 2 3

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Hailes, Isaac, and Javaid
6
0.9 (OCH ), 102.9 (CHCO Et), 131.7 and 146.5 (C-3 and C-4), 158.8
2
2
þ
(
(
C-2), 164.4 (C¼O), and 168.8 (C¼O); m/z (EI) 196 (M , 16%), 151
M ꢁ OEt, 60), and 127 (100).
Ethyl (Z)-3,4-dimethyl-5-oxo-2,5-dihydrofuran-2-ylidene ethanoate
ꢀ
[9]
ꢀ
[9]
(
5b) : M.p. 45–46 C (fromethyl acetate/hexane) (lit.,
ꢁ
39–40 C);
1
ꢀmax(KBr)/cm 3085s, 2981s, 1786s (C¼O), 1720s (C¼O), and 1654m
C¼C); ꢁ (400 MHz; CDCl ) 1.30 (3H, t, J 7.1, OCH CH ), 1.96 (3H, s,
(
C4-Me), 2.05 (3H, s, C3-Me), 4.24 (2H, q, J 7.1, OCH CH ), and 5.40
H
3
2
3
2
3
(
(
1H, s, CHCO Et); ꢁ (100 MHz; CDCl ) 9.1 (C-4), 9.9 (C-3), 14.2
2 C 3
CH CH ), 60.8 (OCH ), 96.7 (CHCO Et), 129.0 and 147.4 (C-3 and
2
3
2
2
C-4), 157.6 (C-2), 163.5 (C¼O), and 169.1 (C¼O); NOE (2%) observed
þ
betweenC3-MeandCHCO Et;m/z(EI)196(M ,15%),151(M ꢁ OEt,59),
2
and 127 (100).
Use of THF as a solvent: The same procedure was used as outlined
above but using 2,3-dimethylmaleic anhydride (0.350 g, 2.78 mmol), dry
THF (14 mL), and ethoxycarbonylmethylenetriphenylphosphorane
(
0.888 g, 2.78 mmol), and the mixture was stirred for 18 h at room tem-
perature. The work-up and purification were as described above to yield
the two products (5a and 5b) in a combined yield of 69% and an E:Z
ratio of 1:1.
Use of CTAB in wateras a solvent: The same procedure was used as
outlined above but using 2,3-dimethylmaleic anhydride (0.350 g,
2
.78 mmol), cetyltrimethylammonium bromide (CTAB) (14 mL; 1 mmol
ꢁ
3
dm solution in distilled water), and ethoxycarbonylmethylenetriphenyl-
phosphorane (0.888 g, 2.78 mmol), and the mixture was stirred for 18 h at
roomtemperature. The work-up and purification were as described above
to yield the two products (5a and 5b) in a combined yield of 52% and an
E:Z ratio of 3:2.
4
,5-Dimethylcyclopent-4-ene-1,3-dione (6): To a stirred solution of
the butenolactone mixture (5a and 5b) (500 mg, 2.55 mmol), in methanol
100%, 15 mL), was added sodium (90 mg, 3.91 mmol). The reaction
(
was heated to reflux and stirred for 15 h. The orange precipitate
formed was filtered and washed with methanol (15 mL), dried,
ꢀ
added to hydrochloric acid (2 M, 10 mL) and stirred for 2 h at 50 C.
The product was extracted into ethyl acetate (3 ꢂ 40 mL) and the com-
bined organics washed with saturated sodiumhydrogencarbonate
(30 mL), dried (magnesium sulfate), and reduced in vacuo to afford
a yellow solid. This was purified by flash column chromatography
ꢀ
(
(
(
petroleumether 40–60 C/ethyl acetate, 15:1) to give the title compound
261 mg, 83%) as a pale yellow waxy solid which readily decomposed
Found: C, 67.7; H, 6.5. C H O requires C, 67.7; H, 6.5%);
7
8
2

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2
-Alkylated Cyclopentene-1,3-diones
35
ꢁ
1
ꢀmax(KBr)/cm
2912s, 2887s, 1698s (C¼O), and 1640 m(C ¼C);
ꢁH(400 MHz; CDCl ) 1.99 (6H, s, 2 ꢂ CH ), and 2.83 (2H, s, 2-H);
3
3
ꢁC(100 MHz; CDCl ) 9.3 (2 ꢂ CH ), 40.8 (C-2), 156.4 (C-4, C-5),
3
3
þ
and 200.5 (C-1, C-3); m/z (EI) 124 (M , 100%), 108 (25), 96
M ꢁ CO, 90), 54 (85).
-Butyl-4,5-dimethylcyclopent-4-ene-1,3-dione (1) and 2,2-dibutyl-4,5-
(
2
dimethylcyclopent-4-ene-1,3-dione (7): To a stirred solution of the dike-
tone (6) (1.24 g, 10.0 mmol) in toluene (30 mL), was added anhydrous
potassium carbonate (6.17 g, 44.6 mmol) and tetra n-butylammonium
bromide (35 mg, 0.11 mmol). The reaction mixture was heated at reflux
for 2 h then cooled to roomte mp erature. Butylbro mi de (1.37 g,
10.0 mmol) was added in one portion and the reaction stirred for 24 h.
The reaction mixture was filtered through Celite and washed with hexane.
The filtrate was concentrated in vacuo to afford a brown oil (containing
1
the mono and dialkylated material in a ratio of 5:1 by H NMR) which
was purified by flash column chromatography (petroleum ether
ꢀ
40–60 C/ethyl acetate, 25:1), to yield 2-butyl-4,5-dimethylcyclopent-4-
ene-1,3-dione (1) as an oil (1.03 g, 57%) and 2,2-dibutyl-4,5-dimethylcy-
clopent-4-ene-1,3-dione (7) as an oil (264 mg, 11%), (unreacted starting
diketone (6) was also recovered (180 mg)).
ꢁ
1
2
-Butyl-4,5-dimethylcyclopent-4-ene-1,3-dione (1): ꢀmax(film)/cm
2
929s, 2859s, 1701s (C¼O), and 1647m(C ¼C); ꢁ (400 MHz; CDCl ) 0.86
H
3
(
(
3H, t, J 7.9, (CH ) CH ), 1.34 (4H, m, (CH ) CH ), 1.75 (2H, m, CH
2 3 3 2 2 3 2
CH ) CH ), 2.02 (6H, s, C4-Me, C5-Me), and 2.60 (1H, t, J 6.1, 2-H);
2
2
3
ꢁC(100 MHz; CDCl ) 9.3, 13.8, 22.7, 26.7, 28.3, 48.8 (C-2), 155.3 (C-4, C-
3
þ
5
), and 204.2 (C-1, C-3); m/z (EI) 180.1145 (M , 45%. C H O requires
1
1
16
2
1
80.1150), 166 (10), and 124 (100).
,2-Dibutyl-4,5-dimethylcyclopent-4-ene-1,3-dione (7): ꢀmax(film)/cm
931s, 2862s, 1706s (C¼O), and 1649m(C ¼C); ꢁ (400 MHz; CDCl )
ꢁ
1
2
2
0
1
H
3
.75 (6H, t, J 7.4, 2 ꢂ (CH ) CH ), 0.86 (4H, m, 2 ꢂ CH CH CH ),
2
3
3
2
2
3
.13(4H,quin,J7.4,2 ꢂ CH CH CH ),1.58(4H,m,2 ꢂ CH CH CH CH ),
2
2
3
2
2
2
3
and 1.91 (6H, s, C4-Me, C5-Me); ꢁ (100 MHz; CDCl ) 9.1, 13.7, 23.0,
C
3
2
2
6.8, 34.4, 53.8 (C-2), 155.4 (C-4, C-5), and 207.9 (C-1, C-3); m/z (EI)
þ
36.1770 (M , 35%. C H O requires 236.1776), 208 (9), 194 (6), 152
2
1
5
24
(
5), and 124 (100).
-Pentyl-4,5-dimethylcyclopent-4-ene-1,3-dione (8) and 2,2-dipentyl-
,5-dimethylcyclopent-4-ene-1,3-dione (9): The same procedure as that
2
4
described above was used, but with the diketone (6) (124 mg,
1
4
.00 mmol) in toluene (3 mL), anhydrous potassium carbonate (617 mg,
.46 mmol) and tetra n-butylammonium bromide (4 mg, 0.01 mmol).
The reaction mixture was heated at reflux for 2 h before being cooled

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Hailes, Isaac, and Javaid
to roomte mp erature and n-pentylbromide (175 mg, 1.2 mmol) added.
The work-up and purification procedure was carried out as previously
described to yield 2-pentyl-4,5-dimethylcyclopent-4-ene-1,3-dione (8) as an
oil (37 mg, 19%) and 2,2-dipentyl-4,5-dimethylcyclopent-4-ene-1,3-dione
(
(
9) as an oil (7 mg, 4%), (unreacted starting diketone was also recovered
48 mg, 38%)).
ꢁ
1
2
-Pentyl-4,5-dimethylcyclopent-4-ene-1,3-dione (8): ꢀmax(film)/cm
930s, 2856s, 1701s (C¼O), and 1643m(C ¼C); ꢁ (400 MHz; CDCl )
.85 (3H, t, J 7.1, (CH ) CH ), 1.27 (6H, m, (CH ) CH ), 1.73 (2H, m, CH
2
2
0
H
3
2
4
3
2 3
3
(
CH ) CH ), 2.00 (6H, s, C4-Me, C5-Me), and 2.60 (1H, t, J 6.1, 2-H);
2 2 3
ꢁC(100 MHz; CDCl ) 9.3, 14.0, 22.3, 25.8, 26.9, 31.8, 48.9 (C-2), 155.3
3
þ
(C-4, C-5), and 204.1 (C-1, C-3); m/z (EI) 194.1302 (M , 30%. C H O
1
requires 194.1307), 152 (7), and 124 (100).
2
18
2
ꢁ1
2
,2-Dipentyl-4,5-dimethylcyclopent-4-ene-1,3-dione (9): ꢀmax(film)/cm
2
0
1
931s, 2851s, 1697s (C¼O), and 1639 m(C ¼C); ꢁ (400 MHz; CDCl )
H
3
.79 (6H, t, J 7.5, 2 x (CH ) CH ), 0.92 (4H, m, 2 ꢂ CH CH CH ),
2
4
3
2
2
3
.19 (8H, m, 2 ꢂ (CH ) CH CH ), 1.60 (4H, m, 2 ꢂ CH (CH ) CH ),
2
2
2
3
2
2 3
3
and 2.03 (6H, s, C4-Me, C5-Me); ꢁ (100 MHz; CDCl ) 9.3, 14.0, 19.1,
C
3
22.8, 26.8, 34.5, 53.8 (C-2), 155.4 (C-4, C-5), and 204.6 (C-1, C-3);
m/z (EI) 264.0156 (M , 25%. C H O requires 264.0161), 249 (10),
þ
1
7
28
2
2
35 (15), 194 (40), and 124 (100).
-Hexyl-4,5-dimethylcyclopent-4-ene-1,3-dione (10) and 2,2-dihexyl-
,5-dimethylcyclopent-4-ene-1,3-dione (11): The same procedure as that
2
4
described above was used, but with the diketone (6) (124 mg,
1
4
.00 mmol) in toluene (3 mL), anhydrous potassium carbonate (617 mg,
.46 mmol) and tetra n-butylammonium bromide (4 mg, 0.01 mmol).
The reaction mixture was heated at reflux for 2 h before being cooled
to roomtemperature and n-hexylbromide (175 mg, 1.2 mmol) added. The
work-up and purification procedure was carried out as previously
described to yield 2-hexyl-4,5-dimethylcyclopent-4-ene-1,3-dione (10) as
an oil (32 mg, 11%) and 2,2-dihexyl-4,5-dimethylcyclopent-4-ene-1,3-
dione (11) as an oil (9 mg, 3%), (unreacted starting diketone also
recovered (51 mg, 42%)).
ꢁ
1
2-Hexyl-4,5-dimethylcyclopent-4-ene-1,3-dione (10): ꢀmax(film)/cm
2
0
929s, 2860s, 1699s (C¼O), and 1641w (C¼C); ꢁ (400 MHz; CDCl )
H
3
.85 (3H, t, J 6.6, (CH ) CH ), 1.27 (8H, m, (CH ) CH ), 1.74 (2H,
2
5
3
2 4
3
m , CH (CH ) CH ), 2.01 (6H, s, C4-Me, C5-Me), and 2.59 (1H, t,
3
2
2 4
J 6.0, 2-H); ꢁ (100 MHz; CDCl ) 9.3, 14.1, 22.6, 27.0, 29.3, 29.7,
C
3
3
2
1
1.5, 48.9 (C-2), 155.3 (C-4, C-5), and 204.2 (C-1, C-3); m/z (EI)
þ
08.1458 (M , 32%. C H O requires 208.1453), 178 (10), and
20
1
3
2
24 (100).

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2
-Alkylated Cyclopentene-1,3-diones
37
2
,2-Dihexyl-4,5-dimethylcyclopent-4-ene-1,3-dione (11): ꢀmax(film)/
ꢁ
1
cm
CDCl ) 0.83 (6H, t, J 7.2, 2 ꢂ (CH ) CH ), 0.90 (4H, m, 2 ꢂ CH CH ),
2927s, 2856s, 1696s (C¼O), and 1648w (C¼C); ꢁ (400 MHz;
2 5 3 2 3
H
3
1
.19 (12H, m, 2 ꢂ (CH ) CH CH ), 1.65 (4H, m, 2 ꢂ CH (CH ) CH ),
2
3
2
3
2
2 4
3
and 2.02 (6H, s, C4-Me, C5-Me); ꢁ (100 MHz; CDCl ) 9.0, 13.5, 19.3,
C 3
20.4, 23.0, 26.6, 34.4, 53.8 (C-2), 155.4 (C-4, C-5), and 204.1 (C-1, C-3);
m/z (EI) 292.1658 (M . C H O requires 292.1653).
þ
1
9
32
2
[16]
Undec-6-yn-5-ol : To a solution of 1-hexyne (5.60 mL, 48.8 mmol)
ꢀ
at ꢁ78 C in dry tetrahydrofuran was added n-butyllithium (48.8 mmol)
ꢀ
dropwise. The reaction was warmed to ꢁ55 C over 20 min and then
ꢀ
cooled to ꢁ78 C. n-Valeraldehyde (5.20 mL, 48.8 mmol) was added and
the reaction mixture stirred for a further 2 h (a low reaction temperature
was required to avoid the formation of 8-propyl-tridec-6-yne-5,9-diol).
The reaction was quenched by the addition of saturated ammonium
chloride solution (30 mL) and extracted with ethyl acetate (3 ꢂ 30 mL).
The combined organic extracts were dried (magnesium sulfate) and con-
centrated in vacuo to give a yellow oil. This was purified by flash column
ꢀ
chromatography (petroleum ether 40–60 C/ethyl acetate, 10:1) to afford
1
ꢁ
the title compound as a colorless oil (7.12 g, 87%). ꢀmax(film)/cm
346br s (OH), 2220s (alkyne), and 2953s; ꢁ (400 MHz; CDCl ) 0.89
3
H
3
(
4
6H, m, 1-H, 11-H), 1.40 (8H, m, 2-H, 3-H, 10-H, 9-H), 1.66 (2H, m,
-H), 1.97 (1H, s, OH), 2.19 (2H, td, J 5.1 and 2.0, 8-H), and 4.33 (1H, tt,
J 2.8 and 2.0, 5-H); ꢁ (100 MHz; CDCl ) 13.6 and 14.0 (C-1 and C-11),
C
3
18.4, 21.9, 22.4, 27.4, 30.8, 37.9, 62.7 (C-5), 81.4 (C-6), and 85.4 (C-7);
m/z (EI) 168.1510 (M . C H O requires 168.1514).
þ
1
1
20
Undec-6-yn-5-ol was stored under nitrogen to avoid aerial oxida-
ꢁ
1
tion to the corresponding ketone undec-6-yn-5-one. ꢀmax(film)/cm
[
23]
2
960s, 2872s, 2214s (alkyne), and 1672s; ꢁ (400 MHz; CDCl )
0.91
6H, m, 1-H and 11-H), 1.38 (4H, m, 2-H, 10-H), 1.58 (4H, m, 9-H,
-H), 2.35 (2H, t, J 7.3, 8-H), and 2.50 (2H, t, J 7.3, 4-H); ꢁ (100 MHz;
H
3
(
3
C
CDCl ) 13.4 and 13.8 (C-1 and C-11), 18.6, 21.9, 22.1, 26.2, 29.7, 45.2
3
þ
(
C-4), 80.8 (C-6), 94.2 (C-7), and 188.5 (C-5); m/z (EI) 166 (M , 30%),
137 (35), and 123 (100).
Undeca-5,6-diene (12): To a mixture of undec-6-yn-5-ol (1.71 g,
0.2 mmol) and n-tributyltin hydride (2.9 mL, 11 mmol), was added
AIBN (5 mg). The mixture was heated (in the absence of solvent) at
1
ꢀ
90 C for 4 h then cooled to roomte mp erature and diluted with
dichloromethane (20 mL). Triethylamine (2.8 mL, 20.0 mmol) was
ꢀ
added dropwise. The reaction was further cooled to 0 C, methanesulfo-
nyl chloride (1.71 g, 15.1 mmol) was added and the mixture was then
warmed to room temperature over 30 min. The reaction was quenched

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3
8
Hailes, Isaac, and Javaid
by adding to hydrochloric acid (2 M, 20 mL). The product was extracted
with ethyl acetate (3 ꢂ 30 mL) and the combined organic extracts
washed with dilute sodiumhydrogencarbonate solution (5%, 20 mL ),
dried (magnesium sulfate) and concentrated in vacuo to yield an oil.
The oil was purified by flash column chromatography (hexane) and then
distilled under reduced pressure using a Vigreux column to afford the
ꢁ
1
title compound as a colorless liquid (1.19 g, 77%). ꢀmax(film)/cm
874s, 2953s, 1963w (allene), and 1926w (allene); ꢁ (400 MHz;
CDCl ) 0.89 (6H, t, J 7.0, 1-H, 11-H), 3.71 (8H, m, 2-H, 3-H, 9-H,
2
H
3
10-H), 1.91 (4H, m, 4-H, 8-H), and 5.06 (2H, m, 5-H, 7-H);
ꢁC(100 MHz; CDCl ), 13.9 (C-1, C-11), 22.2 (C-2, C-10), 28.7 (C-3, C-
3
9
), 31.4 (C-4, C-9), 90.9 (C-5, C-7), and 203.8 (C-6); m/z (EI) 152.1560
þ
(
M , 17%. C H requires 152.1565) and 95 (100).
1
1
20
(E )- and (Z )-4-Pentylidene-5-butyl-2,3-dimethylcyclopent-2-enone
13): To a stirred solution of dicobalthexacarbonylbut-2-yne (2.72 g,
(
8
.0 mmol) and the allene (12) (1.88 g, 12.2 mmol) in dry dichloromethane
ꢀ
(80 mL) at 0 C was added N-methylmorpholine N-oxide monohydrate
(6.48 g, 48.0 mmol) gradually over 2 min. The reaction was then stirred
for 16 h at room temperature. The reaction mixture was filtered through
silica gel and the filtrate was concentrated in vacuo to afford a dark
brown oil which was purified by flash column chromatography, (petro-
ꢀ
leumether 40–60 C/ethyl acetate, 20:1). The product was isolated as a
colorless oil containing an inseparable mixture of the E and Z isomers
(
1.49 g, 80%). Although extensive spectral analysis was not carried out
because the alkene generated was cleaved in the subsequent step the
NMR spectra were consistent with the formation of the isomers in a
ratio of 12:1 (E:Z) based upon extensive literature precedent for the
[
14]
ꢁ1
selectivity with this reaction.
(
ꢀmax(film)/cm
2928s, 2856s, 1667s
C¼O), 1643m(C ¼C), and 1616s (C¼C); E isomer ꢁ (400 MHz;
H
CDCl ) 0.87 (6H, m, 2 ꢂ (CH ) CH ), 1.20 (6H, m, 3 ꢂ CH ), 1.65 (2H,
3
2 3
3
2
m , CH ), 1.78 (3H, s, C3-Me), 1.93 (2H, m, CH ), 2.04 (3H, s, C2-Me),
2
2
2
.56 (2H, m, C¼CHCH ), 2.90 (1H, t, J 4.5, 5-H), and 5.67 (1H, t, J 7.7,
2
C¼CH); E isomer ꢁ (100 MHz; CDCl ) 13.9, 14.0, 22.5, 23.0, 26.6, 29.1,
C 3
2
1
9.4, 29.7, 30.1, 31.7, 46.3, 124.7, 137.4 (C-2), 141.2, 163.3, and 208.5 (C-
); Z isomer ꢁ (400 MHz; CDCl ) 0.87 (6H, m, 2 x (CH ) CH ), 1.20
H
3
2 3
3
(
6H, m, 3 ꢂ CH ), 1.65 (2H, m, CH ), 1.78 (3H, s, C3-Me), 1.93 (2H, m,
2 2
2
2
CH ), 2.04 (3H, s, C2-Me), 2.56 (2H, m, C¼CHCH ), 2.90 (1H, t, J 4.5,
5
1
1
-H), and 5.67 (1H, t, J 7.7, C¼CH); Z isomer ꢁ (100 MHz; CDCl ) 13.9,
C
3
4.0, 22.5, 23.0, 26.6, 29.1, 29.4, 29.7, 30.1, 31.7, 46.3, 124.7, 137.4 (C-2),
þ
41.2, 163.3, and 208.5 (C-1); m/z (EI) 234.1978 (M , 14%. C H O
26
1
6
requires 234.1984), 178 (MꢁBu, 40), 136 (MꢁBu-Pr, 100).

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2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2
-Alkylated Cyclopentene-1,3-diones
39
2-Butyl-4,5-dimethylcyclopent-4-ene-1,3-dione (1): Osmium tetra-
oxide/periodate procedure : To a solution of tetrahydrofuran (3 mL)
ꢀ
and osmium tetraoxide (0.2 mL of 0.04 M solution), at 0 C was added
the enone (13) (102 mg, 0.44 mmol) which was stirred for 10 min. Sodium
periodate (307 mg, 1.44 mmol) was added gradually over 20 min and the
reaction was sealed and stirred for 72 h at roomtemperature. The reac-
tion was filtered though a pad of Celite and the filtrate concentrated in
vacuo. The crude oil was purified by flash column chromatography (pet-
ꢀ
roleumether 40–60 C/ethyl acetate, 30:1) to give the target compound as
a yellow oil (51 mg, 65%) with identical spectral properties to those
above.
Ozone procedure: To a solution of enone (13) (0.50 g, 2.14 mmol) in
ethanol (30 mL), was added Sudan Red 7B (1 mL of a saturated solution
ꢀ
of Sudan Red 7B in ethanol), the reaction mixture was cooled to ꢁ78 C
and ozone was bubbled through. After 40 min the red color had
almost disappeared, and the reaction was purged with nitrogen. The
mixture was warmed to room temperature and concentrated in vacuo.
The yellow oil was purified by flash column chromatography (petroleum
ꢀ
ether 40–60 C/ethyl acetate, 30:1) to afford the target compound
(335 mg, 87%) as an oil with identical spectroscopic properties to those
above.
ACKNOWLEDGMENTS
We thank Bush Boake Allen for a studentship (MHJ), John Janes
for helpful discussions, and Dirk Uwe Hahn. The ULIRS Mass
Spectrometry Facility at the University of London School of Pharmacy
are acknowledged for high resolution mass spectra.
REFERENCES
1
2
. Janes, J. Personal Communication; Bush Boake Allen Ltd., 1995.
. Takahashi, K.; Somega, T.; Muraki, S.; Yoshida, T. Chemical
composition of fragrant materials part IV. A new keto-alcohol, (ꢀ)-
mintlactone, (þ)-isomintlactone and minor components in
peppermint oil. Agric. Biol. Chem. 1980, 44, 1535–1543.
3. Horita, H.; Hara, T.; Sannai, A.; Fujimori, T. The light produced
volatile components of green tea. Agric. Biol. Chem. 1985, 49,
3601–3603.

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2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4
0
Hailes, Isaac, and Javaid
4. Birch, A.J.; Elliott, P. Studies in relation to biosynthesis VIII.
Tasmanone, dehydroangustione and calythrone. Aust. J. Chem.
1956, 9, 95–103.
5
6
7
. Elliott, M.; Janes, N.F.; Jeffs, K.A. Condensation of ketones with
dimethyl dimaleate. A synthesis of calythrone. J. Chem. Soc. (C)
1969, 1845–1847.
. Gedge, D.R.; Pattenden, G. Rearrangement of 4-ylidenebutenolides
to cyclopentene-1,3-diones: synthesis of calythrone and related
compounds. J. Chem. Soc., Chem. Commun. 1978, 880–882.
. Clemo, N.G.; Gedge, D.R.; Pattenden, G. Synthesis of calythrone
and related cyclopentene-1,3-diones via rearrangement of 4-ylidene-
butenolides. J. Chem. Soc., Perkin Trans. 1 1981, 1448–1453.
. Massy-Westropp, R.A.; Price, M.F. The synthesis of 5-oxo-2,5-dihy-
drofuran-2-ylideneacetic acids. Aust. J. Chem. 1980, 33, 333–341.
. Ingham, C.F.; Massy-Westropp, R.A.; Reynolds, G.D.; Thorpe,
W.D. A synthesis of enol-lactones. Aust. J. Chem. 1975, 28,
8
9
2499–2510.
1
1
0. Massy-Westropp, R.A.; Price, M.F. Some reactions of enol-lactones
with metal alkoxides. Aust. J. Chem. 1981, 34, 2369–2383.
1. Ranu, B.C.; Bhar, S. Surface-mediated solid-phase reaction. 2.
Highly selective mono-C-alkylation and di-C-alkylation of 1,3-
dicarbonyl compounds on the surface of alumina. J. Chem. Soc.,
Perkin Trans. 1 1992, 365–368.
1
2. Taber, D.F.; Gleave, D.M.; Herr, R.J.; Moody, K.; Hennessy, M.J.
A new method for the construction of a-diazoketones. J. Org.
Chem. 1995, 60, 2283–2285.
1
3. Geis, O.; Schmalz, H.-G. New developments in the Pauson–Khand
reaction. Angew. Chem., Int. Eng. Ed. 1998, 37, 911–914.
4. Ahmar, M.; Antras, F.; Cazes, B. Pauson–Khand reaction with
allenic compounds I: synthesis of 4-alkylidene-2-cyclopentenones.
Tetrahedron Lett. 1995, 36, 4417–4420.
1
1
5. Khand, I.U.; Knox, G.R.; Pauson, P.L.; Watts, W.E.; Foreman,
M.I. Organocobalt complexes. Part II. Reaction of acetylenehexa-
1
carbonyldicobalt complexes, (R C R )Co (CO) , with norbornene
2
2
2
6
and its derivatives. J. Chem. Soc., Perkin Trans. 1 1973, 977–981.
6. Colas, Y.; Cazes, B.; Gore, J. Reduction de derives d’alcools pro-
pargyliques catalysee par un complexe de palladium zerovalent.
Bull. Soc. Chim. Fr. 1987, 165–173.
7. Konoike, T.; Araki, Y. Concise allene synthesis frompropargylic
alcohols by hydrostannation and deoxystannylation: a new route to
chiral allenes. Tetrahedron Lett. 1992, 33, 5093–5096.
1
1
´
´
´
´
´

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2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2
-Alkylated Cyclopentene-1,3-diones
41
1
8. Majetich, G.; Defauw, J.; Ringold, C. Intramolecular additions
of allylsilanes to conjugated dienones. The synthesis of 3 perforanes.
J. Org. Chem. 1988, 53, 50–68.
1
2
9. Shing, T.K.M. Oblongolide-synthesis and absolute configuration.
J. Chem. Soc., Chem. Commun. 1986, 49–50.
0. Veysoglu, T.; Mitscher, L.A.; Swayze, J.K. A convenient method for
the control of selective ozonizations of olefins. Synthesis 1980,
807–810.
21. Still, W.C.; Kahn, M.; Mitra, A. Rapid chromatographic technique
for preparative separations with moderate resolution. J. Org. Chem.
1978, 43, 2923–2925.
2
2
2. Maercker, A. The Wittig reaction. Org. React. 1965, 14, 270–490.
3. Gleiter, R.; Merger, M. Cyclic 2-ynones fromcyclic alkynes via ring
enlargement. Synthesis 1995, 8, 969–972.
Received in the UK December 18, 2001

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