New straightforward synthesis of β-damascenone and β-damascone derivatives from β-ionone via retro-α-ionol

Article abstract of DOI:10.1080/00397910701196546

β-Damascenone and β-damascone derivatives, important fragrant compounds, were directly obtained from β-ionone by a new way via retro-α-ionol. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701196546

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New Straightforward Synthesis of
β‐Damascenone and β‐Damascone Derivatives
from β‐Ionone via Retro‐α‐ionol
M. Campagnole a & Bernard Delmond a
a Laboratoire de Chimie des Substances Végétales , Université Bordeaux ,
Talence Cedex, France
Published online: 13 Oct 2010.
To cite this article: M. Campagnole & Bernard Delmond (2007) New Straightforward Synthesis of
β‐Damascenone and β‐Damascone Derivatives from β‐Ionone via Retro‐α‐ionol, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:7, 1077-1090, DOI:
10.1080/00397910701196546
To link to this article: http://dx.doi.org/10.1080/00397910701196546
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Synthetic Communicationsw, 37: 1077–1090, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701196546
New Straightforward Synthesis of
b-Damascenone and b-Damascone
Derivatives from b-Ionone via Retro-a-ionol
M. Campagnole and B. Delmond
´ ´ ´
Laboratoire de Chimie des Substances Vegetales, Universite Bordeaux,
Talence Cedex, France
Abstract: b-Damascenone and b-damascone derivatives, important fragrant
compounds, were directly obtained from b-ionone by a new way via retro-a-ionol.
Keywords: aroma, b-damascenone, b-damascone derivatives, b-ionone, perfumes,
retro-a-ionol, rose ketones
INTRODUCTION
b-Damascenone 1 with damascones exemplified by b-damascone 2 (Fig. 1)
belongs to a family of fragrant natural products called rose ketones.[1,2]
These highly odoriferous compounds are very important in the flavor and
fragrance industry because of their olfactory potential.[3–5] Owing to their
fruity-flowery scent with rose undertone, but especially to their exceptional
odor strength,[6] they found applications for the creation of various fragrances;
b-damascenone 1 has a very low odor threshold (0.002 ppb in water).[7]
b-Damascenone 1 was first isolated in 1970 as a minor constituent but an
important flavor component of Bulgarian rose oil (Rosa damascena var.
bulgaria)[8,9] and in 1974 in grapes (Vitis species)[10] and wines,[11] to
which it significantly contributes to their aroma. It has since been detected
as a trace component in several plant species[12,13] (rose, tobacco, grapes,
Received in Poland August 4, 2006
Address correspondence to Bernard Delmond, Laboratoire de Chimie des Sub-
´ ´ ´ ´
stances Vegetales, Universite Bordeaux 1, 351 cours de la Liberation, 33405,
Talence Cedex, France. E-mail: b.delmond@lcsv.u-bordeaux1.fr
1077

1078
M. Campagnole and B. Delmond
Figure 1. Rose ketones: b-damascenone and b-damascone.
fruits) and numerous beverages[14–16] (tea, beer, coffee, rum, wine varieties,
fruit juices).
Soon thereafter, b-damascenone 1 was introduced in the perfume
industry[17] [Cetylia base (M. Erni; 1970), Dorinia (A. F. Morris; 1973),
Damascenia (P. H. Sauvegrain; 1975), Nahema (Guerlain; 1979)] and since
has been widely used, as a key substance, for perfumes, cosmetics, and foods.
Because of its limited availability from natural sources, numerous
chemical syntheses of b-damascenone 1 have been developed (Scheme 1).
Some of these routes used b-damascone 2 as intermediate; the cyclohex-
adiene moiety of b-damascenone 1 was generated from b-damascone deriva-
tives (epoxy-damascone, hydroxy-damascone, bromo-damascone).[9,18–20]
However, the more efficient syntheses of b-damascenone 1 involved
various homologation reactions:
. C10 þ C3 starting from safranal 3 or alkyl safranate 4[21,22] by condensation
of organometallic C3 units.
Scheme 1.

b-Damascenone and b-Damascone Derivatives
1079
. C9 þ C4 from 2,6,6-trimethylcyclohexen-2-one 5 by reaction with an
acetylure.[19]
. C11 þ C2 from 6 via aldolization reaction.[23]
RESULTS
As ionones, rose ketones have a C13 megastigmane skeleton (A) (Fig. 1), and
subsequently damascones can be obtained from ionones.[8,18,20,24–29]
However, to our knowledge, no direct route to b-damascenone 1 from
ionones has been reported. We have investigated a new approach, involving
a direct way to b-damascenone 1 from commercialy available b-ionone 7
(Scheme 2).
The key intermediate of this synthetic sequence is retro-a-ionol 8, which
may be readily obtained from b-ionone 7.[30] However, in a first step, the
retro-a-ionol 8 was converted into its methyl ether derivative 9 on the one
hand to avoid later reactions of the hydroxyl group during the epoxidation
of dienic system and on the other hand to allow the easy formation of an
unsaturation.
A preliminary epoxidation experiment of retro-methoxy-a-ionol 9 in
standard conditions (1 equivalent of m-chloroperbenzoic acid in methylene
chloride solution) has shown a low stability of reaction products: epoxides
could not be isolated. We observed the isomerization of endocyclic epoxide
11 to b,g-unsaturated ketone 13 and the hydrolysis of exocyclic epoxide 10
to diol 12 during the workup; these behaviors have been subsequently
confirmed.
However, the addition of anhydrous sodium carbonate to epoxidation
mixture (mCPBA/CH2Cl2) and a neutral workup allowed the quantitative
conversion of 9 to a mixture of 10 and 11 in the ratio of about 50/50. Each
of these epoxidic isomers could be separated by flash-column chromatography
(deactivated alumina) and then successfully characterized (Scheme 3).
Taking advantage of the particular sensitivity of these epoxides in acid
medium, the original mixture of 10 and 11, without separation, was directly
subjected to an acid treatment with diluted sulfuric acid solution; we
obtained (94% yield) a mixture (ꢀ60:40) of diol 12 (diastereoisomers) and
b,g-unsaturated ketone 13.
Scheme 2.

1080
M. Campagnole and B. Delmond
Scheme 3.
After separation, these two compounds could be used as raw
material to access b-damascenone 1 according to Schemes 4 and 5
respectively.
Under acetylation conditions with acetyl chloride (1 equivalent), 12
underwent selectively hydroxy-acetate 14 (91% yield), resulting in the
exclusive acylation of cyclic hydroxyl group (Scheme 4). Oxidation of
hydroxy-acetate 14 with pyridinium chlorochromate afforded keto-acetate
15 in good yield (84%).
For the first time, to characterize each intermediate derivatives, the gen-
eration of unsaturated systems was successively realized.
Treatment of keto-acetate 15 with activated alumina (overnight stirring
at room temperature) caused the formation of 4-acetoxy-b-damascone 16
(78% yield), resulting in the formation of the butenone unit. The generation
of cyclohexadiene system was obtained by treatment of 16 with para toluene
sulfonic acid (PTSA) at 508C in benzene solution for 12 h; the b-damasce-
none 1 was obtained in 70% yield.
However treatment of keto-acetate 15 by APTS (identical conditions)
led directly to b-damascenone 1 (73% yield), involving a simultaneous
elimination of methoxyl and acetoxyl groups. More, some transformations
can be directly realized from crude material, without previous
purification of reaction mixtures. Thus, according this procedure,
b-damascenone 1 can be obtained from diol 12 in three steps with 60%
overall yield.

b-Damascenone and b-Damascone Derivatives
1081
Scheme 4.
On the other hand, from the b,g-unsaturated ketone 13 previously
obtained, we have also developed a new route to b-damascenone 1 via diol
12 (Scheme 5). Treatment of 13 with m-chloroperbenzoic acid in the
presence of sodium carbonate afforded epoxidic derivative 17, which
without isolation was stirred (12 h; room temperature) with activated
alumina to give hydroxy-ketone 18 (74% overall yield from 13). This
compound could be quantitatively reduced (AlLiH4) to diol 12, precursor of
b-damascenone 1 according to Scheme 4.
Oxidation (PCC) of the hydroxy-ketone 18 and then treatment of diketone
19 with APTS or activated alumina led to 4-oxo-b-damascone 20[31] (64%
overall yield from 13).
Scheme 5.

1082
M. Campagnole and B. Delmond
CONCLUSION
On the basis of these results, retro-a-ionol 8 commercially obtained from
available b-ionone 7 is a new key intermediate for the syntheses of b-damas-
cenone 1 and b-damascone derivatives (4-acetoxy-b-damascone 16 and
4-oxo-b-damascone 20). All these compounds are widely used in the aroma
and perfume industries.
EXPERIMENTAL
All reactions were performed under nitrogen. Solvents were freshly distilled
prior to use. Purification of the products were achieved by flash chromato-
graphy (neutral alumina or silica gel).1H NMR and 13C NMR spectra
1
were recorded in CDCl3 solution on Bruker AC 250 (250 MHz for H and
1
62.89 MHz for 13C) or Bruker DPX 300 (300 MHz for H and 75.46 MHz
for 13C). The attributions for 1H and 13C shifts were realized using 1D
and 2D NMR experiments (distortionless (DEPT), correlation spectroscopy
(COSY) 1H/1H, heteronuclear multiple bond (HMBC), heteronuclear
multiple quanta correlation (HMQC)). High-resolution mass spectra
(HRMS) and liquid secondary ion mass spectrometry (LSIMS) were
performed on a Micromass autospec-Q (10000 resolution).
Preparation of Retro-a-ionol 8[30]
b-Ionone 7 (5 g, 26 mmol), isopropenyl acetate (26 mL, 0.23 mol), and
p-toluene sulfonic acid monohydrate (32 mg, 0.16 mmol) were refluxed
under an inert gas atmosphere for 24 h. After evaporation of excess isoprope-
nyl acetate by distillation under a vacuum, the reaction mixture was treated
three times with petroleum ether, then concentrated. The residue was
extracted with ether; the combined organic layers were washed successively
with H2O and saturated aqueous NaCl, dried over Na2SO4, and evaporated
under reduced pressure.
Without purification, the resulting crude material (6.14 g) was dissolved
in EtOH (96%) (23 mL) solution and added dropwise to a suspension of
NaBH4 (1.15 g, 30 mmol) in 96% EtOH (35 mL) at room temperature.
After being stirred for 15 min, the mixture was refluxed for a further 1.5 h,
poured on to ice-cold saturated NH4Cl solution, and extracted with
petroleum ether. The organic layer was washed, dried, and concentrated
under reduced pressure to give crude stereoisomeric retro-a-ionols 8
[4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-butan-2-ol]
(4.52 g;
90%
overall yield). Purification by silica-gel column chromatography (elution
with petroleum ether/ether 8:2) provided a pure sample (.95% purity) of
(Z)-isomer 8, which is the main component; spectroscopic data were
identical with those reported.[32]

b-Damascenone and b-Damascone Derivatives
1083
1H NMR (dH; CDCl3): 1.17 (3H, s), 1.19 (3H, s), 1.21 (3H, d, J ¼ 6.4 Hz), 1.79
(3H, bs, J ¼ 1.5 Hz), 3.85 (1H, m), 5.35 (1H, t, J ¼ 7 Hz), 5.62 (1H, bt). 13
C
NMR (dC; CDCl3): 21.8 (CH3-13), 22.7 (CH2-3), 23.0 (CH3-10), 28.1
(CH3-11), 28.2 (CH3-12), 34.6 (C-1), 39.7 (CH2-8), 40.2 (CH2-2), 68.6
(CH-9), 121.2 (CH-7), 126.0 (CH-4), 133.3 (C-5), 145.3 (C-6). MS (m/z,
%): 194 (77), 135 (100). HRMS (C13H22O): calcd. 194.1671, found 194.1676.
Preparation of Retro-methoxy-a-ionol 9
To a suspension of 95% sodium hydride (1.04 g, 43.2 mmol) in DMF
(140 mL), retro-a-ionol 8 (2.79 g, 14.4 mmol) was added at 08C under a
nitrogen atmosphere. The reaction mixture was stirred for 15 min, and
methyl iodide (6.2 g, 43.2 mmol) was added at 08C. After being stirred for
36 h at room temperature, the mixture was hydrolyzed with H2O, then
extracted with ether. The combined organic layers were washed with
sodium bisulfite solution, H2O, and aqueous saturated NaCl solution and
dried over Na2SO4. Concentration under reduced pressure provided retro-
methoxy-a-ionol
9
[4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-butan-2-
methoxy] (2.87 g; 96% yield); bp 93–958–12 mm.
1H NMR (dH; CDCl3): 1.16 (3H, d, J ¼ 6.1 Hz), 1.18 (3H, s), 1.19 (3H, s),
1.80 (3H, bs, J ¼ 1.5 Hz), 3.34 (3H, s), 3.35 (1H, m), 5.36 (1H, t,
J ¼ 6.9 Hz), 5.61 (1H, bt). 13C NMR (dC; CDCl3): 19.1 (CH3-10), 21.8
(CH3-13), 22.8 (CH2-3), 27.8 (CH3-11 or CH3-12), 28.2 (CH3-11 or
CH3-12), 34.6 (C-1), 36.4 (CH2-8), 40.2 (CH2-2), 56.1 (CH3O), 77.4 (CH-
9), 121.4 (CH-7), 125.5 (CH-4), 133.5 (C-5), 144.2 (C-6).
Epoxidation of Retro-methoxy-a-ionol 9
Retro-methoxy-a-ionol 9 (312 mg, 1.5 mmol) in CH2Cl2 solution (15 mL) was
treated in the presence of Na2CO3 (3.18 mg, 3 mmol) with a solution of
¨
m-chloroperbenzoıc acid (325 mg, 1.35 mmol) in CH2Cl2 (6 mL). The
mixture was stirred for 8 h at room temperature. The solution was filtered,
washed with H2O, and evaporated at room temperature under reduced
pressure to give an oil (330 mg; 98% yield). This was a mixture (ꢀ1:1) of two
epoxides 10 and 11; pure samples of each epoxide were obtained by flash
deactivated alumina column chromatography (elution with petroleum ether).
Exocyclic Epoxide 10
1H NMR (dH; CDCl3): 0.99 (3H, s), 1.00 (3H, s), 1.24 (3H, d, J ¼ 6.4 Hz),
1.54 (3H, bs, J ¼ 1.5 Hz), 3.16 (1H, m), 3.34 (3H, s), 3.50 (1H, m), 5.75
(1H, bt). 13C NMR (dC; CDCl3): 18.0 (CH3-13), 19.0 (CH3-10), 22.8
(CH2-3), 24.2 (CH3-11 or CH3-12), 26.0 (CH3-11 or CH3-12), 33.5 (C-1),

1084
M. Campagnole and B. Delmond
35.4 (CH2-8), 37.5 (CH2-2), 56.0 (CH3O), 64.8 (C-6), 75.8 (CH-9), 129.1
(CH-4), 133.5 (C-5). MS (m/z, %): 224 (4), 121 (100).
Endocyclic Epoxide 11
1H NMR (dH; CDCl3): 0.98 (3H, s), 1.10 (3H, d, J ¼ 6.4 Hz), 1.19 (3H, s),
1.38 (3H, s), 3.04 (1H, m), 3.28 (3H, s), 3.30 (1H, m), 5.68 (1H, m). 13C
NMR (dC; CDCl3): 19.0 (CH3-10), 21.5 (CH2-3), 23.4 (CH3-13), 26.4
(CH3-11 or CH3-12), 30.3 (CH3-11 or CH3-12), 33.9 (C-1), 34.2 (CH2-2),
36.0 (CH2-8), 56.0 (CH3O), 57.9 (C-5), 61.7 (CH-4), 77.0 (CH-9), 127.5
(CH-7), 142.6 (C-6). MS (m/z, %): 224 (12), 165 (100).
Acid Hydrolysis of Epoxides 10/11
An aqueous solution of 2% H2SO4 (7 mL) was added to a crude epoxide
mixture (530 mg, 2.37 mmol) in ether (7 mL). The resultant solution was
stirred for 6 h at room temperature, saturated with NaCl, and extracted with
ether. The combined extracts were washed with saturated NaCl solution,
dried (Na2SO4), and evaporated to yield an oil (540 mg). NMR and gas chrom-
atography (GC) analysis of this residue showed the presence of a carbonyl
compound and diol in the ratio of 40/60. The purification was performed
by silica column chromatography:
Elution with petroleum ether/ether (8:2) gave b,g-unsaturated ketone 13
(200 mg; 38% yield) as an oil: 1H NMR (dH; CDCl3): 1.10 (3H, d, J ¼ 6 Hz),
1.11 (3H, d, J ¼ 5.9 Hz), 1.24 (3H, s), 1.27 (3H, s), 3.30 (3H, s), 3.32 (1H, m),
5.07 (1H, m). 13C NMR (dC; CDCl3): 12.3 (CH3-13), 18.8 (CH3-10), 27.1
(CH3-11 or CH3-12), 28.6 (CH3-11 or CH3-12), 35.5 (CH2-3), 35.7 (C-1),
35.9 (CH2-8), 37.2 (CH2-2), 49.5 (CH-5), 56.1 (CH3O), 77.0 (CH-9), 121.9
(CH-7), 142.9 (C-6), 212.6 (C-4). MS (m/z, %): 224 (4), 59 (100). HRMS
(C14H24O2): calcd. 224.1776, found 224.1765.
Elution with ether gave a mixture of diols 12 (220 mg, 56% yield) as an
oil from which a further purification allowed us to obtain pure samples of two
diastereoisomers.
12A
1H NMR (dH; CDCl3): 0.95 (3H, s), 1.05 (3H, s), 1.19 (3H, d, J ¼ 6.4 Hz),
1.95 (3H, s), 3.38 (3H, s), 3.64 (1H, m), 3.82 (1H, t, J ¼ 4.1 Hz), 4.60 (1H,
dd, J ¼ 10.9 Hz, J0 ¼ 1.9 Hz). 13C NMR (dC; CDCl3): 18.1 (CH3-10), 18.3
(CH3-13), 26.3 (CH3-11 or CH3-12), 28.0 (CH2-3), 28.3 (CH3-11 or
CH3-12), 34.2 (CH2-2), 35.1 (C-1), 41.7 (CH2-8), 56.1 (CH3O), 66.8
(CH-7), 70.7 (CH-4), 74.9 (CH-9), 131.8 (C-5), 143.7 (C-6). LSIMS (m/z,
%): 265 ([M þ Na]þ, 100), 225 (MHþ, 25). HRSM (C14H26O3Na): calcd.
265.1779, found 265.1773.

b-Damascenone and b-Damascone Derivatives
1085
12B
1H NMR (dH; CDCl3): 0.92 (3H, s), 1.14 (3H, s), 1.19 (d, 3H, J ¼ 6.4 Hz),
1.92 (3H, bs), 3.34 (3H, s), 3.63 (1H, m), 3.85 (1H, t, J ¼ 5.3 Hz), 4.61
(1H, dd, J ¼ 10.5 Hz, J0 ¼ 1.5 Hz). 13C NMR (dC; CDCl3): 17.4 (CH3-13),
18.5 (CH3-10), 27.5 (CH3-11 or CH3-12), 27.9 (CH3-11 or CH3-12), 28.5
(CH2-3), 35.0 (C-1), 35.3 (CH2-2), 41.8 (CH2-8), 56.2 (CH3O), 66.9 (C-7),
70.8 (CH-4), 74.9 (CH-9), 132.4 (C-5), 143.6 (C-6).
Acetylation of Diol 12
To the diol 12 (mixture of isomers) (150 mg, 0.62 mmol) in Et2O solution
(10 mL), pyridine (59 mg, 0.74 mmol) and acetyl choride (53 mg,
0.68 mmol) were added at 08C, and the solution was stirred for 12 h at
room temperature. It was then poured into ice-cold water and extracted with
ether. The combined extracts were washed with diluted HCl solution and
aqueous saturated NaCl, dried (Na2SO4), and evaporated to afford the crude
acetates 14 (160 mg, 91% yield) as an oil. The residue was chromatographed
(desactivated alumina, petroleum ether–ether 7:3) to give the following.
Hydroxy-acetate 14A
1H NMR (dH; CDCl3): 0.98 (3H, s), 1.07 (3H, s), 1.20 (3H, d, J ¼ 6.0 Hz),
1.82 (3H, s), 2.03 (3H, s), 3.34 (3H, s), 3.65 (1H, m), 4.63 (1H, dd,
J ¼ 10.9 Hz, J0 ¼ 1.9 Hz), 5.05 (1H, t, J ¼ 4.8 Hz). 13C NMR (dC; CDCl3):
17.9 (CH3-13), 18.3 (CH3-10), 21.3 (CH3C55O), 25.0 (CH2-3), 26.1 (CH3-
11 or CH3-12), 28.2 (CH3-11 or CH3-12), 34.5 (CH2-2), 35.0 (C-1), 41.7
(CH2-8), 56.2 (CH3O), 66.8 (CH-7), 73.2 (CH-4), 74.9 (CH-9), 128.2 (C-5),
146.2 (C-6), 171.0 (CH3C55O).
Hydroxy-acetate 14B
1H NMR (dH; CDCl3): 0.96 (3H, s), 1.18 (3H, s), 1.21 (3H, d, J ¼ 6.4 Hz),
1.80 (3H, s), 2.05 (3H, s), 3.35 (3H, s), 3.62 (1H, m), 4.67 (1H, dd,
J ¼ 11.3 Hz, J0 ¼ 1.8 Hz), 5.13 (1H, t, J ¼ 4.5 Hz). 13C NMR (dC; CDCl3):
17.1 (CH3-13), 18.4 (CH3-10), 21.3 (CH3C55O), 25.2 (CH2-3), 27.3
(CH3-11 or CH3-12), 27.9 (CH3-11 or CH3-12), 35.1 (C-1), 35.4 (CH2-2),
41.8 (CH2-8), 56.3 (CH3O), 67.1 (CH-7), 73.4 (CH-4), 74.9 (CH-9), 128.7
(C-5), 146.0 (C-6), 171.2 (CH3C55O).
Oxidation of Hydroxy-acetate 14
To a solution of hydroxy acetate 14 (mixture of isomers) (120 mg, 0.42 mmol) in
CH2Cl2 (3 mL), pyridinium chlorochromate (146 mg, 0.68 mmol) was added.

1086
M. Campagnole and B. Delmond
After being stirred for 4 h at room temperature, the mixture was diluted with
ether and filtered through an alumina column. The filtrate was washed with
HCl solution, H2O, and saturated NaCl solution; dried; and concentrated to
give keto-acetate 15 as an oil (100 mg; 84% yield).
1H NMR (dH; CDCl3): 1.04 (3H, s), 1.05 (3H, s), 1.15 (3H, d, J ¼ 6.4 Hz),
1.53 (3H, s), 2.02 (3H, s), 3.28 (3H, s), 3.87 (1H, m), 5.12 (1H, t,
J ¼ 4.5 Hz). 13C NMR (dC; CDCl3): 17.0 (CH3-13), 19.0 (CH3-10), 21.1
(CH3C55O), 25.1 (CH2-3), 27.1 (CH3-11 or CH3-12), 28.3 (CH3-11 or
CH3-12), 33.5 (C-1), 34.7 (CH2-2), 52.2 (CH2-8), 56.3 (CH3O), 70.7
(CH-4), 72.1 (CH-9), 126.2 (C-5), 148.3 (C-6), 170.7 (OC55O), 208.0
(C55O). MS (m/z, %): 282 (13), 59 (100). HRMS (C16H26O4): calcd.
282.1831, found 282.1836.
Preparation of 4-Acetoxy-b-damascone 16
Keto-acetate 15 (70 mg, 0.25 mmol) in Et2O solution (20 mL) was stirred for
12 h at room temperature with active neutral alumina (7 g). The mixture was
filtered, and the filtrate was concentrated to give 4-acetoxy-b-damascone 16 as
an oil (48 mg, 78% yield) (bp 96–988/0.01 mm).
1H NMR (dH; CDCl3): 1.01 (3H, s), 1.02 (3H, s), 1.48 (3H, s), 1.92 (3H, dd,
J ¼ 6.8 Hz, J0 ¼ 1.5 Hz), 2.05 (3H, s), 5.19 (1H, t, J ¼ 4.9 Hz), 6.12 (1H, dq,
J ¼ 15.8 Hz, J0 ¼ 1.5 Hz), 6.76 (1H, dq, J ¼ 6.8 Hz, J0 ¼ 15.8 Hz). 13C NMR
(dC; CDCl3): 17.7 (CH3-13), 18.4 (CH3-10), 21.2 CH3C55O), 25.3 (CH2-3),
27.4 (CH3-11 or CH3-12), 28.5 (CH3-11 or CH3-12), 33.7 (C-1), 34.7
(CH2-2), 70.9 (CH-4), 127.5 (C-5), 133.8 (CH-8), 145.7 (C-6), 146.5
(CH-9), 170.8 (OC55O), 200.2 (C55O). MS (m/z, %): 250 (18), 69 (100).
HRMS (C15H22O3): calcd. 250.1569, found 250.1570.
Preparation of b-Damascenone 1 from 16
4-Acetoxy-b-damascone 16 (170 mg, 0.68 mmol) in benzene solution
(10 mL) was stirred at 508C with p-toluene sulfonic acid (24 mg,
0.13 mmol) for 12 h. The mixture was taken up in ether and successively
washed with sodium bicarbonate solution, H2O, and aqueous saturated NaCl
solution. The drying and the removal of solvents under reduced pressure
left crude b-damascenone (90 mg, 70% yield), which was purified by
column chromatography. Elution with petroleum ether/ether (98:2) give a
very pure sample (ꢀ100% purity) of b-damascenone 1; spectroscopic data
were identical with those reported.[9]
1H NMR (dH; CDCl3): 1.01 (6H, s), 1.61 (3H, s), 1.91 (3H, dd, J ¼ 6.8 Hz,
J0 ¼ 1.5 Hz), 5.79 (2H, m), 6.16 (1H, dq, J ¼ 15.8 Hz, J0 ¼ 1.5 Hz), 6.81
(1H, dq, J ¼ 6.8 Hz, J0 ¼ 15.8 Hz). 13C NMR (dC; CDCl3): 18.3 (CH3-10),
19.4 (CH3-13), 26.2 (CH3-11 and CH3-12), 33.8 (C-1), 39.4 (CH2-2), 127.3

b-Damascenone and b-Damascone Derivatives
1087
(CH-3 or CH-4), 127.9 (CH-3 or CH-4), 128.0 (C-5), 134.5 (CH-8), 139.3 (C-
6), 146.1 (CH-9), 200.9 (C55O). MS (m/z, %): 190 (19), 69 (100). HRMS
(C13H18O): calcd. 190.1358, found 190.1358.
Preparation of b-Damascenone 1 from 15
Keto-acetate 15 (450 mg, 1.6 mmol) in benzene solution (10 mL) was stirred
at 508C with p-toluene sulfonic acid (61 mg, 0.32 mmol) for 12 h. The mixture
was taken up in ether and successively washed with sodium bicarbonate
solution, H2O, and aqueous saturated NaCl solution. The drying and the
removal of solvents under reduced pressure left crude b-damascenone 1
(222 mg, 73% yield).
Preparation of Hydroxy-ketone 18
b,g-Unsaturated ketone 13 (690 mg, 3.1 mmol) in CH2Cl2 solution (30 mL)
was treated in the presence of Na2CO3 (653 mg, 6.16 mmol) with a solution
of m-chloroperbenzoic acid (478 mg, 2.77 mmol) in CH2Cl2 (8 mL). The
mixture was stirred for 7 h at room temperature. The solution was filtered,
washed with H2O, and evaporated at room temperature under reduced
pressure to give an oil (epoxidic derivative 17). This, in Et2O solution
(80 mL), was stirred for 12 h at room temperature with active neutral
alumina (22 g). After filtration, the alumina was washed with MeOH/Et2O,
and the filtrate was concentrated to give hydroxy-ketone 18 (551 mg, 74%
overall yield) as a mixture (ꢀ1:1) of two diastereoisomers; bp 112–1148/
0.01 mm).
Pure samples of each isomer were isolated by alumina column
chromatography.
Elution with Petroleum Ether/Ether (50/50) Gave 18A
1H NMR (dH; CDCl3): 1.11 (3H, s), 1.15 (3H, d, J ¼ 6.1 Hz), 1.25 (3H, s),
1.88 (3H, s), 3.34 (3H, s), 3.65 (1H, m), 4.67 (dd, J ¼ 10.4 Hz,
J0 ¼ 1.5 Hz). 13C NMR (dC; CDCl3): 12.4 (CH3-13), 19.0 (CH3-10), 26.1
(CH3-11 or CH3-12), 27.0 (CH3-11 or CH3-12), 34.0 (CH2-3), 36.0 (C-1),
38.0 (CH2-2), 42.1 (CH2-8), 55.8 (CH3O), 72.2 (CH-7), 78.7 (CH-9), 131.8
(C-5), 162.9 (C-6), 200.0 (C-4). MS (m/z, %): 240 (4), 59 (100).
Elution with Petroleum/Ether (40/60) Gave 18B
1H NMR (dH; CDCl3): 1.12 (3H, s), 1.20 (3H, d, J ¼ 6.4 Hz), 1.26 (3H, s),
1.88 (3H, s), 3.33 (3H, s), 3.65 (1H, m), 4.82 (dd, J ¼ 10.8 Hz,
J0 ¼ 1.8 Hz). 13C NMR (dC; CDCl3): 12.3 (CH3-13), 18.2 (CH3-10), 26.0

1088
M. Campagnole and B. Delmond
(CH3-11 or CH3-12), 27.3 (CH3-11 or CH3-12), 34.1 (CH2-3), 36.1 (C-1), 37.8
(CH2-2), 40.9 (CH2-8), 56.2 (CH3O), 67.7 (CH-7), 74.6 (CH-9), 131.6 (C-5),
163.9 (C-6), 200.0 (C-4). MS (m/z, %): 240 (4), 59 (100).
Reduction of Hydroxy-ketone 18
To a suspension of LiAlH4 (95 mg, 2.5 mmol) in Et2O (15 mL), a solution of
hydroxy-ketone 18 (mixture of isomers) (470 mg, 2 mmol) in ether (10 mL)
was added at 08C. After stirring for 1 h at room temperature, the reaction
mixture was hydrolyzed; usual workup gave diols 12 (480 mg; ꢀ100%
yield) as an oil.
Oxidation of Hydroxy-ketones 18
To a solution of hydroxy-ketones 18 (mixture of isomers) (95 mg, 0.40 mmol)
in CH2Cl2 (3 mL), pyridinium chlorochromate (160 mg, 0.74 mmol) was
added. After being stirred for 4 h at room temperature, the mixture was
diluted with ether (3 mL) and filtered through an alumina column (elution
with ether). The filtrate was washed with HCl solution, H2O, and saturated
NaCl solution; dried; and concentrated to give diketone 19 as an oil (70 mg;
86% yield).
1H NMR (dH; CDCl3): 1.19 (3H, s), 1.20 (3H, d, J ¼ 6.8 Hz), 1.23 (3H, s),
1.65 (3H, s), 3.31 (3H, s), 3.95 (1H, m). 13C NMR (dC; CDCl3): 12.2 (CH3-
13), 19.0 (CH3-10), 26.8 (CH3-11 or CH3-12), 27.0 (CH3-11 or CH3-12),
34.0 (CH2-3), 34.3 (C-1), 38.0 (CH2-2), 51.4 (CH2-8), 56.3 (CH3O), 71.7
(CH-9), 127.9 (C-5), 162.3 (C-6), 198.8 (C-4), 205.6 (C-7). MS (m/z, %):
238 (22), 59 (100). HRMS (C14H22O3): calcd. 238.1569, found 238.1569.
Preparation of 4-Oxo-b-damascone 20
Diketone 19 (140 mg, 0.59 mmol) in benzene solution (35 mL) was refluxed
with p-toluene sulfonic acid (3.3 mg) for 2 h. The mixture was taken up in
ether and successively washed with sodium bicarbonate solution, H2O, and
aqueous saturated NaCl solution. The drying and the removal of solvents
under reduced pressure left 4-oxo-b-damascone 20 (150 mg, ꢀ 100%
yield); mp 48–508 (hexane).
1H NMR (dH; CDCl3): 1.11 (6H, s), 1.53 (3H, s), 1.90 (3H, dd, J ¼ 6.7 Hz,
J0 ¼ 1.5 Hz), 6.11 (1H, dq, J ¼ 16.0 Hz, J0 ¼ 1.5 Hz), 6.68 (1H, dq,
J ¼ 6.7 Hz, J0 ¼ 16.0 Hz).
13C NMR (dC; CDCl3): 12.9 (CH3-13), 18.5 (CH3-10), 27.1 (CH3-11 and
CH3-12), 34.0 (CH2-3), 34.5 (C-1), 37.8 (CH2-2), 129.2 (C-5), 132.6
(CH-8), 148.0 (CH-9), 160.7 (C-6), 197.7 (C-7),198.6 (C-4). MS (m/z, %):
206 (22), 69 (100). HRMS (C13H18O2): calcd. 206.1307, found 206.1304.

b-Damascenone and b-Damascone Derivatives
1089
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