New preparation methods for α-damascone, γ-damascone, and β-damascenone using pyronenes

Article abstract of DOI:10.1080/00397910701462898

γ- and δ-Pyronenes are terpenic synthons easily available from myrcene. They are used as intermediates in the synthesis of α-damascone, γ-damascones, and β-damascenone. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701462898

This article was downloaded by: [University of Haifa Library]
On: 13 June 2013, At: 01:49
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
New Preparation Methods for α‐Damascone,
γ‐Damascone, and β‐Damascenone using
Pyronenes
Bertrand Boulin a , Martine Taran a b , Bernadette Arreguy‐San Miguel a b
Bernard Delmond a
&
a Laboratory of Natural Products, University of Bordeaux 1, Talence, France
b Laboratory of Organic Chemistry, School of Pharmacy, University of
Bordeaux 1, Talence, France
Published online: 09 Aug 2007.
To cite this article: Bertrand Boulin , Martine Taran , Bernadette Arreguy‐San Miguel & Bernard Delmond
(2007): New Preparation Methods for α‐Damascone, γ‐Damascone, and β‐Damascenone using Pyronenes,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:15, 2579-2591
To link to this article: http://dx.doi.org/10.1080/00397910701462898
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the
contents will be complete or accurate or up to date. The accuracy of any instructions, formulae,
and drug doses should be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or
howsoever caused arising directly or indirectly in connection with or arising out of the use of this
material.

Synthetic Communicationsw, 37: 2579–2591, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701462898
New Preparation Methods for
a-Damascone, g-Damascone, and
b-Damascenone using Pyronenes
Bertrand Boulin
Laboratory of Natural Products, University of Bordeaux 1,
Talence, France
Martine Taran and Bernadette Arreguy-San Miguel
Laboratory of Natural Products, University of Bordeaux 1, Talence
Cedex, France and Laboratory of Organic Chemistry, School of
Pharmacy, University of Bordeaux 1, Talence, France
Bernard Delmond
Laboratory of Natural Products, University of Bordeaux 1,
Talence, France
Abstract: g- and d-Pyronenes are terpenic synthons easily available from myrcene.
They are used as intermediates in the synthesis of a-damascone, g-damascones, and
b-damascenone.
Keywords: a-damascone, b-damascenone, g-damascone, pyronenes, terpenes,
terpenoids
INTRODUCTION
Damascones 1–3 and b-damascenone 4 (Fig. 1), also commonly named rose
ketones, are among the most sought-after fragrant compounds in the perfume
industry for their pleasant flower fragrance with fruity tones,[1–3] and most of
Received in Poland October 3, 2006
Address correspondence to Bernadette Arreguy-San Miguel, Laboratory of Natural
´
Products, University of Bordeaux 1, 351 cours de la Liberation, 33405, Talence,
France. E-mail: b.arreguy@lcsv.u-bordeaux1.fr
2579

2580
B. Boulin et al.
Figure 1. Damascones and b-damascenone.
all for their exceptional scent. Each one of them has an intrinsic olfactory
characteristic; thus, for example, b-damascenone has a floral (white rose)
fragrance that is exceptionally strong and may be felt in water at concen-
trations of less than 0.01%.[3]
b-Damascenone 4 and b-damascone 2 were the first compounds of this
type to be identified in the essential oil of Bulgarian rose (Rosa
damascena).[3] They are the essential olfactive constituent elements of this
oil, which is rated among the most prestigious ones. Since then, the rose
ketones, or most of the time just traces of them, have been found in many
essential oils extracted from plants (roses, tobacco, fruits, etc.)[4] and in
certain beverages (tea, beer, coffee, cider, wine, etc.).[5]
Although these fragrant compounds are commonly used in perfumes or
cosmetics as well as to give aroma to dishes, their extraction from their
natural sources cannot be envisaged; this is why many syntheses have been
developed to obtain them.
Because of their common biogenetic origin, damascones and damasce-
nones are, from a structural point of view, connected to ionones also known
to have a C13 megastigmane skeleton (Fig. 2).
Therefore, it is logical that several methods of synthesis would start from
ionones,[6] that is, molecules that are easily obtained industrially. Thus,
several synthesis schemes were applied to obtain such interconversion via
ionone derivatives, such as epoxyhydrazones,[6a] (Wharton’s reaction), isoxa-
zoles[6b] (Bu¨chi’s reaction), amine N-oxides[6c] (Meisenheimer’s rearrange-
ment), epoxyketones,[6d] or allylsilanes.[6e]
Figure 2. C13 megastigmane skeleton.

a-Damascone, g-Damascone, and b-Damascenone
2581
We also point out that damascones may be obtained by a methodology
similar to that developed to synthesize ionones, and that involves an acid-
catalyzed cyclization of linear polyenic precursors, the pseudo-damascones.[7]
However, for the most important syntheses of damascones and
b-damascenone pattern, couplings of the C10 þ C3 type are involved. For their
homologation, a condensation is required between a C3 (Grignard reagent or
organolithium compound) and either a C10 aldehyde (cyclocitral, safranal)[8]
or a C10 ester (cyclogeraniate and derivatives, dithiocyclogeraniate, safranate).[9]
Schemes of the C9 þ C4 type have also been developed from 1-bromo-
methyl-3,3-dimethylcyclohex-1-ene[10] and 2,6,6-trimethylcyclohex-2-ene-1-
one.[11]
RESULTS AND DISCUSSION
In this work, we considered the possibility of obtaining damascones and damas-
cenones via a C10 þ C3 scheme by condensing a C3 organomagnesium
compound (allylmagnesium bromide) and C10 aldehydes (cyclocitral and func-
tional cyclocitral) obtained from g- and d-pyronenes 5 and 6. The retrosynthetic
scheme (Scheme 1), for example, shows that it is possible to consider the
synthesis of a-damascone 1 and b-damascenone 4 from g-pyronene 5.
Pyronenes are monoterpenic hydrocarbons with a cyclogeranyl skeleton
(1,1,2,6-tetramethylcyclohexane) that are available on the semi-industrial
scale (Fig. 3).[12]
Earlier works[13] have shown that these compounds are very well adapted
to get access to cyclocitrals via the corresponding epoxides.[14]
Access to Damascones 1 and 3
The exocyclic epoxides 7 and 9, respectively derived from g- and d-pyronenes
5 and 6, will isomerize in the presence of Lewis acids and in particular MgBr2
Scheme 1.

2582
B. Boulin et al.
Figure 3. g- and d-pyronenes.
to form the corresponding cyclocitrals. This is why we considered treating
these epoxides directly with allylmagnesium bromide; the epoxides will first
isomerize to aldehydes (cyclocitrals), which, then, will condense in the
presence of the organomagnesium compound.
This way, epoxide 7 is treated at 08C by an ether solution of allylmagne-
sium bromide. After hydrolysis and purification on a deactivated alumina
column, we isolate a mixture of diastereoisomeric alcohols 8 with 91%
yield. Their oxidation by pyridinium chlorochromate diluted in dichloro-
methane followed by purification on a deactivated alumina column gives
a-damascone 1 with 90% yield (Scheme 2).
In the same way, we prepared g-damascone 3 from epoxide 9 derived
from d-pyronene 6. Epoxide 9 is treated at 08C under the same conditions
as mentioned before, that is, by an ether solution of allyl magnesium
bromide. After hydrolysis and purification on a deactivated alumina
column, we obtain the diastereoisomeric alcohols 10 with a 65% yield.
Their oxidation by pyridinium chlorochromate diluted in dichloromethane
gives g-damascone 3 with an 80% yield (Scheme 3).
Scheme 2.
Scheme 3.

a-Damascone, g-Damascone, and b-Damascenone
2583
Scheme 4.
Access to b-Damascenone 4
Regarding b-damascenone 4, we succeeded in preparing it from 4-bromocy-
clocitral 11. This compound was obtained by the treatment of epoxide 7
(derived from g-pyronene 5) by action of the mixture of copper bromide/
lithium bromide in ethyl acetate solution.[15] The instable 4-bromo-b-cycloci-
tral 11 is, without any prior purification, reacted with sodium thiophenate.
After hydrolysis and purification on an alumina column, 4-phenylsulfanyl-
b-cyclocitral 12 is obtained with a 40% yield.
Then, the 4-phenylsulfanyl-b-cyclocitral 12 is treated with an ether
solution of allylmagnesium bromide. After purification on a silica column,
the corresponding homoallylic alcohol 13 is obtained with an 87% yield. Its
oxidation with pyridine chlorochromate and purification on an alumina
column leads to the production of keto-sulphide 14 with 51% yield. Then,
the latter is oxidized with m-chloroperbenzoic acid at a low temperature
(2788C) to obtain a mixture of keto-sulfoxides 15. After purification on a
silica column, we obtain two keto-sulfoxides with a 62% yield. The
treatment of these compounds with sodium bicarbonate in boiling carbon
tetrachloride produces b-damascenone 4 with a 46% yield (Scheme 4).
CONCLUSION
Thus, with g- and d-pyronenes 5 and 6, molecules that may easily be obtained
by a semi-industrial procedure, we have been able to produce syntheses of
a-damascone 1, g-damascone 3, and b-damascenone 4. These natural
fragrant molecules are interesting from an organoleptic point of view.
Pyronenes thus are valuable substrates on which natural terpenoids of high
added value may be synthesized, which are used in the domain of perfume
and aroma generation.

2584
B. Boulin et al.
EXPERIMENTAL
Neutral active alumina is deactivated by addition of water (6%) before use. All
reactions are run under argon. The solvents are freshly distilled before use.
1
The HNMR and 13CNMR spectra are registered in CDCl3 solution on two
Bruker AC 250 and DPX 300 instruments at 250 and 300 MHz (1H) and
62.9 and 75.46 MHz (13C) respectively. The attributions for 1H and 13C
1
shifts are carried out by 2D NMR: COSY H/1H, HMBC, and HMQC tech-
niques. The mass spectrometry studies were made at 70 eV electronic
impact and under high resolution (HRMS) using a 10000-resolution power
Micromass autospec-Q spectrometer. For some compounds, a more suitable
technique, such as liquid secondary ion mass spectrometry (LSIMS) was
applied with the same apparatus.
Synthesis of a-Damascone 1
An ether solution (10 mL) of allylmagnesium bromide prepared with 1.59 g
(13.2 mmol) of allylbromide and 730 mg (30.4 mmol) of magnesium is
slowly added at 08C to a solution of 1 g (6.6 mmol) of exocyclic epoxide 7
in 3 mL of anhydrous ether. After 4 h of stirring at room temperature, the
solution is quenched with 50 mL of 10% chlorhydric acid and then
extracted with ether. The organic phase is washed with a solution of sodium
bicarbonate and then with brine. After drying on MgSO4, filtration, and
evaporation of the solvents, the crude product is purified on a deactivated
alumina column. One obtains 1.16 g of a mixture of diastereoisomeric
alcohols 8 (yield 91%).
First Diastereoisomer
1HNMR (dppm): 0.82 (3H, s), 0.92 (3H, s), 1.75 (3H, se), 3.81 (1H, m),
5.05 (2H, m), 5.63 (1H, m), 5.80 (1H, m). 13CNMR (dppm): 23.3 (C-3), 26.0
(C-13), 27.5 and 28.2 (C-11 and C-12), 30.6 (C-2), 32.5 (C-1), 44.0 (C-8),
54.0 (C-6), 69.4 (C-7), 116.9 (C-10), 125.8 (C-4), 131.7 (C-5), 136.0 (C-9).
MS [m/z (%)]: 194 (Mþ, 1), 109 (100). IR (CCl4): 3494 cm21 (nOH).
Second Diastereoisomer
1HNMR (dppm): 0.88 (3H, s), 1.02 (3H, s), 1.76 (3H, se), 3.85 (1H, m),
4.71 (2H, m), 5.10 (2H, m), 5.43 (1H, m), 5.85 (1H, m). 13CNMR (dppm):
22.9 (C-3), 25.7 (C-13), 28.4 and 28.8 (C-11 and C-12), 31.5 (C-2), 32.2
(C-1), 40.2 (C-8), 54.8 (C-6), 71.4 (C-7), 117.8 (C-10), 122.6 (C-4), 133.2
(C-5), 136.5 (C-9).
Starting from a solution of 1.26 g (5.84 mmol) of pyridium chlorochro-
mate in 7 mL of anhydrous dichloromethane, one adds, while stirring,
810 mg (4.17 mmol) of a mixture of alcohols 8 in 7 mL of dichloromethane.
Mixture stirring is maintained at ambient temperature for 4 h. Then 20 mL of

a-Damascone, g-Damascone, and b-Damascenone
2585
ether are added, and the solution is rapidly filtered on a deactivated alumina
column. After evaporation of the solvents, the crude product is purified
on a deactivated alumina column. After elution by petroleum ether/
ether (9/1 and then 8/2), 728 mg of a-damascone 1 are obtained
(yield ¼ 90%).
1HNMR (dppm): 0.78 (3H, s), 0.87 (3H, s), 1.48 (3H, d, J ¼ 1.4 Hz),
1.82 (3H, dd, J ¼ 6.9 and 1.4 Hz), 2.82 (1H, s), 5.53 (1H, m), 6.27 (1H,
d, J ¼ 15.4 Hz), 6.80 (1H, dq, J ¼ 15.4 and 6.9 Hz). 13CNMR (dppm):
18.1 (C-10), 22.5 (C-3), 23.2 (C-13), 27.7 and 27.9 (C-11 and C-12),
31.2 (C-2), 32.3 (C-1), 61.1 (C-6), 123.4 (C-4), 130.4 (C-5), 132.1 (C-8),
142.1 (C-9), 202.1 (C-7). MS[m/z, (%)]: 192 (Mþ, 19), 69 (100). HRMS
calcd. for C13H20O: 192.1514; found: 192.1517. IR (CCl4): 1687 cm21
(nC55O).
Synthesis of g-Damascone 3
An ether solution (10 mL) of allylmagnesium bromide (13.2 mmol) is added
to a solution of 1 g (6.6 mmol) of exocyclic epoxide 9 in 3 mL of
anhydrous ether, under conditions that are identical to those described
previously.
After purification of the crude material on a deactivated alumina column
and elution with petroleum ether/ether (9/1 then 8/2), 830 mg (yield ¼ 65%)
of a mixture of diastereoisomeric alcohols 10 are obtained.
First Diastereoisomer
1HNMR (dppm): 0.90 (3H, s), 1.03 (3H, s), 3.91 (1H, m), 4.73 (2H., m),
5.09 (2H, m), 5.82 (1H, m). 13CNMR (dppm): 23.1 (C-3), 28.6 and 28.8 (C-
11 and C-12), 33.7 (C-4), 34.4 (C-1), 35.7 (C-2), 42.4 (C-8), 57.7 (C-6),
69.8 (C-7), 112.3 (C-13), 117.9 (C-10), 135.8 (C-9), 147.9 (C-5). MS [m/
z,(%)]: 194 (Mþ, 1), 109 (100). IR (CCl4): 3480 cm21 (nOH)).
Second Diastereoisomer
1HNMR (dppm): 0.90 (3H, s), 1.07 (3H, s), 3.83 (1H, m), 4.71 (2H, m),
5.12 (2H, m), 5.81 (1H, m). 13CNMR (dppm): 23.1 (C-3), 28.4 and 29.8 (C-
11 and C-12), 32.8 (C-4), 34.5 (C-1), 35.3 (C-2), 41.0 (C-8), 60.4 (C-6),
68.6 (C-7), 111.9 (C-13), 118.4 (C-10), 135.8 (C-9), 148.1 (C-5).
A mixture of alcohols 10 (600 mg, 3.09 mmol), in solution in 5 mL of
CH2Cl2, is added to a solution of 930 mg (4.32 mmol) of pyridinium chloro-
chromate in 5 mL of CH2Cl2. The mixture is stirred at room temperature for
4 h. After addition of 20 mL of ether, the mixture is filtered on a deactivated
alumina column. Elution with ether and evaporation of the solvents give a
crude product that is purified on a deactivated alumina column. Elution
with petroleum ether/ether (9/1 and 8/2) gives 475 mg of g-damascone 3
(yield ¼ 80%).

2586
B. Boulin et al.
1HNMR (dppm): 0.78 (3H, s), 0.87 (3H, s), 1.84 (3H, dd, J ¼ 6.8 and
1.6 Hz), 3.19 (1H, s), 4.75 (2H, m), 6.15 (1H, dq, J ¼ 15.5 and 1.6 Hz),
6.80 (1H, dq, J ¼ 15.5 and 6.8 Hz). 13CNMR (dppm): 18.1 (C-10), 23.0 (C-3),
26.8 and 27.8 (C-11 and C-12), 32.0 (C-4), 35.0 (C-1), 35.8 (C-2), 63.8
(C-6), 111.9 (C-13), 132.8 (C-8), 141.7 (C-9), 145.0 (C-5), 199.2 (C-7). MS
[m/z, (%)]: 192 (Mþ, 14), 69(100). HRMS calcd. for C13H20O: 192.1514;
found: 192.1517. IR (CCl4): 1693 cm21 (nc55o).
Synthesis of b-Damascenone 4
4-Phenylsulfanyl-b-cyclocitral 12
Epoxide 7 (912 mg, 6 mmol) is dissolved in 15 mL of anhydrous ethyl acetate.
Copper bromide (2.67 g, 12 mmoles) and 522 mg (6 mmol) of lithium
bromide are added. After 30 min of heating at 908C, the mixture is cooled
and filtered, and the ethyl acetate is evaporated under reduced pressure. The
4-bromo-b-cyclocitral 11 is, without any purification, directly added to
sodium thiophenate, prepared with 152 mg (6 mmol) of sodium hydride and
660 mg (6 mmol) of thiophenol in 40 mL of anhydrous dimethylformamide.
The mixture is stirred for 3 h at ambient temperature and then hydrolyzed.
The aqueous phase is extracted with ether, and after the usual treatment, the
crude product is purified on a column of deactivated alumina. Elution with
petroleum ether/ether (95/5) gives 600 mg (yield ¼ 40%) of 4-phenylsulfa-
nyl-b-cyclocitral 12.
1HNMR (dppm): 1.1 (6H, s), 2.3 (3H, s), 3.6 (1H, s), 7.2–7.4 (5H, Ph),
10.1 (1H, s). 13CNMR (dppm): 18.8 (C-10), 25.2 (C-3), 27.0 and 28.4 (C-8
and C-9), 33.3 (C-1), 35.7 (C-2), 54.4 (C-4), 127.4 (CH, Ph), 129.1 (2 CH,
Ph), 131.8 (2 CH, Ph), 135.8 (C, Ph), 142.4 (C-6), 151.8 (C-5), 193.0 (C-7).
Alcohol 13
4-Phenylsulfanyl-b-cyclocitral 12 (820 mg, 3.1 mmol) is dissolved in
10 mL of anhydrous ether. A 30-mL ether solution of allylmagnesium
bromide prepared with 1.08 g (9 mmol) of allylbromide and 496 mg (20.6
mmol) of magnesium is slowly added at 08C. The solution is stirred for
4 h at ambient temperature. Then the mixture reaction is hydrolyzed with
a 10% solution of hydrochloric acid and immediately extracted with
ether. The organic phase is washed with a saturated solution of NaHCO3,
then with brine, and finally dried on MgSO4. After evaporation of the
solvents under reduced pressure, the product is purified on a silica
column. A mixture of diastereosomeric alcohols 13 (708 mg, 87% yield)
is obtained. They are separated by eluting them with petroleum ether/
ether (8/2).

a-Damascone, g-Damascone, and b-Damascenone
2587
First Diastereoisomer.
1HNMR (dppm): 0.99 (3H, s), 1.14 (3H, s), 2.12 (3H, s), 3.56 (1H, t), 4.38
(1H, m), 5.15 (2H, m), 5.89 (1H, m), 7.17–7.44 (5H, Ph). 13CNMR (dppm):
20.0 (C-13), 25.8 (C-3), 27.9 and 29.2 (C-11 and C-12), 35.1 (C-1), 35.4
(C-2), 41.3 (C-8), 53.7 (C-4), 70.7 (C-7), 117.6 (C-10), 126.7 (CH, Ph),
129.0 (2CH, Ph), 130.3 (C-5), 131.3 (2CH, Ph), 136.2 (C-9), 137.3 (C, Ph),
144.8 (C-6).
Second Diastereoisomer.
1HNMR (dppm): 0.99 (3H, s), 1.09 (3H, s), 2.16 (3H, s), 3.56 (1H, t), 4,31
(1H, m), 5.20 (2H, m), 5.89 (1H, m), 7.17–7.43 (5H, Ph). 13CNMR (dppm):
20.5 (C-13), 25.5 (C-3), 27.2 and 28.9 (C-11 and C-12), 34.5 (C-1), 36.1
(C-2), 41.0 (C-8), 53.9 (C-4), 70.4 (C-7), 118.0 (C-10), 126.7 (CH, Ph),
130.0 (2CH, Ph), 130.1 (C-5), 131.4 (2CH, Ph), 135.9 (C-9), 137.2 (C, Ph),
144.3 (C-6). IR (CCl4): 3482 cm21 (nOH). LSIMS [m/z, (%)]: 325
([M þ Na]þ, 15). HRMS calcd. for C19H26SONa: 325.1602; found: 325.1603.
Keto-Sulfide 14
Acohol 13 (1.12 g, 3.70 mmol) in 10 mL of CH2Cl2 is added to the solution of
1.11 g (5.18 mmol) of pyridinium chlorochromate in 2 mL of CH2Cl2. The
mixture is stirred for 4 h at room temperature. After solvent evaporation,
the crude product is put onto a deactivated alumina column for 3 h, then
elution with petroleum ether/ether 9/1 gives 568 mg (yield 51%) of keto-
sulfide 14.
1HNMR (dppm): 0.90 (3H, s), 1.06 (3H, s), 1.72 (3H, s), 1.89 (3H, dd,
J ¼ 1.5 Hz and 6.8 Hz), 3.58 (1H, t), 6.08 (1H, dq, J ¼ 15.8 Hz and
J ¼ 1.5 Hz), 6.71 (1H, dq, J ¼ 15.8 Hz and J ¼ 6.8 Hz), 7.2–7.4 (5H, Ph).
13CNMR (dppm): 18.7 (C-10), 20.6 (C-13), 25.8 (C-3), 27.9 and 29.4 (C-11
and C-12), 34.0 (C-2), 34.2 (C-1), 51.2 (C-4), 126.0 (CH, Ph), 128.9 (C-5),
128.1 (2CH, Ph), 131.6 (2CH, Ph), 133.2 (C-8), 136.6 (C, Ph), 144.6 (C-6),
146.7 (C-9). LSIMS [m/z, (%)]: 323 ([M þ Na]þ, 100), 301 (MHþ, 95).
HRSM calcd. for C19H24SONa: 323.1450; found: 323.1445.
Keto-Sulfoxide 15
The solution of 601 mg (1.89 mmol) of keto-sulfide 14 in 40 mL of anhydrous
CH2Cl2 is cooled to –788C, and 455 mg of m-chloroperbenzoic acid (71.6%)
in 5 mL of CH2Cl2 are added. After 3 h of stirring, the reaction mixture is
poured into the mixture 1/1 of CH2Cl2 and a 10% solution of Na2SO3. The
organic phase is washed with a solution of NaHCO3, then with brine, and
dried on MgSO4. After evaporation of the solvent, the mixture of sulfoxides
15 is purified on a silica column. Elution with petroleum ether/ether (5/5
then 4/6) and with ether gives 300 mg (yield 62%) of diastereoisomeric sulf-
oxides 15.

2588
B. Boulin et al.
First Diastereoisomer.
1HNMR (dppm): 0.98 (3H, s), 1.02 (3H, s), 1.8 (3H, s), 1.92 (3H, dd,
J ¼ 6.8 and 1.6 Hz), 3.03 (1H, t), 6.15 (1H, dq, J ¼ 15.8 Hz and 1.6 Hz),
6.93 (1H, dq, J ¼ 15.8 and 6.8 Hz), 7.45–7.59 (5H, Ph). 13CNMR (dppm):
16.4 (C-3), 18.9 (C-10), 20.1 (C-13), 28.3 and 28.9 (C-11 and C-12), 33.8
(C-1), 36.3 (C-2), 67.3 (C-4), 124.1 (C-5), 124.6 (2CH, Ph), 129.3 (2CH,
Ph), 130.8 (CH, Ph), 134.0 (C-8), 142.3 (C, Ph), 148.7 (C-9), 149.5 (C-6),
200.9 (C-7).
Second Diastereoisomer.
1HNMR (dppm): 0.72 (3H, s), 1.03 (3H, s), 1.7 (3H, s), 1.97 (3H, dd,
J ¼ 6.8 and 1.6 Hz), 3.54 (1H, s), 6.13 (1H, dq, J ¼ 15.6 Hz and 1.6 Hz),
6.99 (1H, dq, J ¼ 15.6 Hz and 6.8 Hz), 7.50–7.57 (5H, Ph). 13CNMR
(dppm): 18.8 (C-10), 18.8 (C-3), 21.6 (C-13), 28.0 and 28.8 (C-11 and
C-12), 33.8 (C-1), 34.8 (C-2), 67.3 (C-4), 124.0 (C-5), 124.9 (2CH, Ph),
129.1 (2CH, Ph), 131.3 (CH, Ph), 133.8 (C-8), 142.8 (C, Ph), 147.8 (C-9),
148.4 (C-6), 200.7 (C-7). IR (CCl4): 1644 cm21(nc55o). LSIMS [m/z, (%)]:
339 ([M þ Na]þ, 100), 317 (MHþ, 7). HRMS calcd. for C19H24O2SNa:
339.1389; found: 339.1394.
b-Damascenone 4
A mixture of the sulfoxides 15 (231 mg, 0.73 mmoles) and 61 mg (0.73 mmol)
of sodium bicarbonate in 10 mL of carbon tetrachloride is stirred for 5 h at
808C. After filtration, the solvent is evaporated. The crude product is
purified on a deactivated alumina column. Elution with petroleum ether/
ether (9/1 then 8/2) yields 64 mg (Rdt ¼ 46%) of b-damascenone 4.
1HNMR (dppm): 1.02 (6H, s), 1.61 (3H, s), 1.91 (3H, d, J ¼ 6.9 Hz), 2.09
(2H, d), 5.70 (2H, m), 6.16 (1H, d, J ¼ 15.7 Hz), 6.81 (1H, dq, J ¼ 15.7 and
6.9 Hz). 13CNMR (dppm): 18.3 (C-10), 19.4 (C-13), 26.2 (C-11 and C-12), 33.8
(C-1), 39.3 (C-2), 127.2 (C-3), 127.9 (C-4), 128.3 (C-5), 134.5 (C-8), 139.3
(C-6), 146.1 (C-9), 200.9 (C-7). IR (CCl4): 1670 cm21 (nc55o). LSIMS [m/z,
(%)]: 191 (MHþ, 41). HRMS calcd. for C13H19O (M þ H): 191.1435;
found: 191.1428.
ACKNOWLEDGMENTS
´ ´ ´ ´
The authors are grateful to D. R. T. (Derives Resiniques et Terpeniques; Dax)
for financial support to B. Boulin and for supplying g- and d-pyronenes, and to
´
Christiane Vitry (Centre d’Etudes Structurales et d’Analyse des Molecules
´
Organiques, Universite Bordeaux I) for the mass spectra.

a-Damascone, g-Damascone, and b-Damascenone
2589
REFERENCES
1. (a) Ohloff, G. Scent and Fragances: The Fascination of Fragrances and their
Chemical Perspectives; Springer-Verlag: Berlin, 1994; (b) Pybus, D. H.;
Sell, C. S. The Chemistry of Fragrances; Royal Society of Chemistry, 1999,
Cambridge, UK.
¨
¨
2. Ohloff, G.; Uhde, G. Uber eine ungewohnliche cyclisations reaktion bei dre
umsetzung von (þ)-Epoxy-a-dihydrojonon mit hydrazinhydrat. Helv. Chim.
Acta 1970, 53, 531–541.
`
¨
3. Demole, E.; Enggist, P.; Sauberli, U.; Stoll, M.; Kovats, S. E. Structure et synthese
´
´
`
de la damascenone (trimethyl-2,6,6-trans-crotonyl-1-cyclohexadiene-1,3), consti-
tuant odorant de l’essence de rose bulgare (Rosa damascena Mill.). Helv. Chim.
Acta 1970, 53, 541–551.
´
4. (a) Demole, E.; Berthet, D. Identification de la damascenone et de la b-damascone
dans le tabac de Burley. Helv. Chim. Acta 1971, 54, 681–682; (b) Enzell, C. Bio-
¨
degradation of carotenoıds-man important route to aroma compounds. Pure Appl.
Chem. 1985, 57, 693–700; (c) Tressl, R.; Friese, L.; Fendesack, F.; Koppler, H.
¨
Gas chromatographic–mass spectrometric investigation of hop aroma constituents
in beer. J. Agric. Food Chem. 1978, 26, 1422–1426; (d) Tressl, R.; Friese, L.;
¨
Fendesack, F.; Koppler, H. Studies of the volatile composition of hops during
storage. J. Agric. Food Chem. 1978, 26, 1426–1430; (e) Derail, C.;
Hofmann, T.; Schieberle, P. Differences in key odorants of handmade juice of
yellow-flesh peaches (Prunus persica L.) induced by workup procedure.
J. Agric. Food Chem. 1999, 47, 4742–4745; (f) Ong, P. K. C.; Acree, T. E.;
Lavin, E. H. Characterization of volatiles in Rambutan fruit (Nephelium
lappaceum L.). J. Agric. Food Chem. 1998, 46, 611–615.
¨
5. (a) Konig, W. A.; Evers, P.; Krebber, R.; Schulz, S.; Fehr, C.; Ohloff, G. Determi-
nation of the absolute configuration of a-damascone and a-ionone from black tea
by enantioselective capillary gas chromatography. Tetrahedron 1989, 45,
7003–7006; (b) Lermusieau, G.; Bullens, M.; Collin, S. Use of GC-olfactomery
to identify the hop aromatic compounds in beer. J. Agric. Food Chem. 2001, 49,
3867–3874; (c) Buttery, R. G.; Teranishi, R.; Ling, L. C.; Turnbaugh, J. G. Quan-
titative and sensory studies on tomato paste volatiles. J. Agric. Food Chem. 1990,
38, 336–340; (d) Kotseridis, Y.; Baumes, R. L.; Skouroumounis, G. K. Quantitat-
ive determination of free and hydrolytically liberated b-damascenone in red grapes
and wines using a stable isotope dilution assay. J. Chromatogr. A 1999, 849,
245–254; (e) Kotseridis, Y.; Baumes, R. L. Identification of impact odorants in
Bordeaux red grape juice, in the commercial yeast used for its fermentation and
in the produced wine. J. Agric. Food Chem. 2000, 48, 400–406; (f) Cerny, M.;
Grosch, W. Potent odorants of raw arabica coffee: Their changes during
roasting. J. Agric. Food Chem. 2000, 48, 868–872.
6. Synthesis of damascones and damascenones from ionones derivatives epoxihydra-
zones: (a) Dupuy, C.; Luche, J. L. New developements of the Wharton transposi-
tion. Tetrahedron 1989, 45, 3437–3444; (b) Sarandeses, L. A.; Luche, J. L. A new
synthesis of a- and b-damascones from the ionones. J. Org. Chem. 1992,
2757–2760; (c) Schulte-Elte, K. H.; Rautenstrauch, V.; Ohloff, G. Synthesen
der stereoisomeren (þ)-g-damascone. Helv. Chim. Acta 1971, 54, 1805–1812;
(d) isoxazoles: Bu¨chi, G.; Vederas, J. C. Interchange of functionality in conjugated
carbonyl compounds through isoxazoles. J. Am. Chem. Soc. 1972, 27, 9128–9132;
(e) Schulte-Elte, K. H.; Mu¨ller, B. L.; Ohloff, G. Synthetische u¨bergange von der
jonon—in die damasconreihe. Helv. Chim. Acta 1973, 56, 310–320; (f) amines

2590
B. Boulin et al.
N-oxides: Godfrey, A. G.; Ganem, B. Ready oxidation of halides to aldehydes
using trimethylamine N-oxide in dimethylsulfoxyde. Tetrahedron Lett. 1990,
31(34), 4825–4826; (g) Suzuki, S.; Onishi, T.; Fujita, Y.; Misawa, H.; Otera, J.
A convenient method for conversion of allylic chlorides to a,b-unsatured
aldehydes. J. Bull. Chem. Soc. Jpn. 1986, 59, 3287–3288; (h) Rautenstrauch, V.
Controlled allylic transformations via the Meisenheimer rearrangement. Helv.
Chim. Acta 1973, 56, 2492–2508; (i) Epoxiketones: Sarandeses, L. A.;
Luche, J. L. A new synthesis of a- and b-damascones from the ionones. J. Org.
Chem. 1992, 57, 2757–2760; (j) Allylsilanes: Azzari, E.; Faggi, C.;
Gelsomini, N.; Taddei, M. Transformation of a- and b-ionones into a-and
b-damascone and b-damascenone using allylsilane chemistry. J. Org. Chem.
1990, 55, 1106–1108.
7. (a) Synthesis of damascones and damascenones from pseudo-damascones:
Schulte-Elte, K. H.; Strickler, H.; Gautschi, F.; Pickenhagen, W.; Gadola, M.;
Limacher, J.; Muller, B. L.; Wuffli, F.; Ohloff, G. Synthesen und Cyclisierrungs-
reaktionen der Pseudodamascone Ein neuer Zugang zu a-Damasconverbindungen.
Liebigs Ann. Chem. 1975, 484–508; (b) Nakatani, Y.; Kubota, K.; Tahara, R.;
Shigematsu, Y. New synthesis of a-damascone. Agricultural and Biological
Chemistry 1974, 38, 1351–1354.
8. Synthesis of damascones and damascenones from cyclocitral and safranal:
(a) Mori, K.; Amaike, M.; Itou, M. Synthesis of (S)-a-damascone. Tetrahedron
1993, 49, 1871–1878; (b) Beszant, S.; Giannini, E.; Zanoni, G.; Vidari, G. Enan-
tioselective synthesis of both enantiomers of g-ionone, g-damascone, karahana
lactone and karahana ether. Tetrahedron: Asymmetry 2002, 13, 1245–1255;
(c) Takazama, O.; Saigo, K.; Narasaka, K.; Mukaiyama, T. New synthesis of
g-damascone. Chem. Letters 1977, 757–758; (d) Bovolenta, M.; Castronovo, F.;
`
Vadala, A.; Zanoni, G.; Vidari, G. A simple efficient highly enantioselective
synthesis of a-ionone and a-damascone. J. Org. Chem. 2004, 69, 8959–8962;
(e) Kutney, J. P.; Gunning, P. J.; Clewley, R. G.; Somerville, J.; Rettig, S. J.
The chemistry of thujone: Versatile and efficient routes to safronitrile, b-cyclo-
geranonitrile, b-cyclocitral, damascones, and their analogues. Can. J. Chem.
1992, 70, 2094–2112.
9. Synthesis of damascones and damascenones: (i) from methyl cyclogeraniate
(a) Fehr, C. Enantioselective protonation of enolates and enols. Angew. Chem.
Int. Ed. Engl. 1996, 35, 2566–2587; (b) Fehr, C.; Galindo, J. Synthesis of (R)-
(þ)- and (S)-(-)-a-damascone by tanden Grignard reaction—Enantioselective pro-
tonation: Evidence for the intermediacy of a chiral complex. J. Am. Chem. Soc.
1988, 110, 6909–6911; (c) Fehr, C.; Galindo, J. Reaction of ester enolates with
nucleophiles. Stereocontrolled formation of ketone and aldehyde enolates.
J. Org. Chem. 1988, 53, 1828–1830; (d) Fehr, C.; Galindo, J. Synthesis of (E)-
1-propenyl ketones from carboxylic esters and carboxamides by use of mixed
organolithium-magnesium reagents. Helv. Chim. Acta 1986, 69, 228–235;
(e) Fehr, C.; Galindo, J. Syntheses of the enantiomers of g-cyclogeranic acid,
g-cyclocitral, and g-damascone: Enantioselective protonation of enolates.
J. Helv. Chim. Acta 1995, 78, 539–552; (f) Snowden, R. L.; Linder, S. M.;
Mu¨ller, B. L.; Schulte-Elte, K. H. b-Cleavage of bis(homoallylic) potassium
alkoxides. Two-step preparation of propenyl ketones from carboxylic esters:
Synthesis of ar-turmerone, a-damascone, b-damascone, and b-damascenone.
Helv. Chim. Acta 1987, 70, 1858–1878; (g) Fehr, C.; Galindo, J. Pat. Appl
(Firmenich S. A. Switz). Eu. Pat. Appl. EP 89-100930, 1989; (h) Fehr, C.;
Galindo, J (Firmenich S. A. Switz). Eu. Pat. Appl. EP 87-112138, 1988;

a-Damascone, g-Damascone, and b-Damascenone
2591
(i) Naef, F.; Decorzant, R. Grignard and hydride addition to a ketene intermediate:
A novel access to a-damascone and a-cyclocitral. Tetrahedron 1986, 42,
3245–3250; (j) Fehr, C.; Stempf, I.; Galindo, J. Highly enantioselective protona-
tion of thiol ester enolates. Angew. Chem. Int. Ed. 1993, 32, 1042–1044; (ii) From
´
methyl dithiocyclogeraniate: (k) Gosselin, P. Hydrolyse acido-catalysee d’un
sulfure de dienyle; Application a la synthese de la g-Damascone. Tetrahedron
´
`
`
´
1988, 44, 1979–1990; (l) Gosselin, P. Nouvelle application de la reaction des orga-
nomagnesiens sur les dithioesters: synthese de la g-Damascone. Tetrahedron Lett.
`
1986, 27, 5495–5496; (iii) From methyl and ethyl safranate: (m) Bu¨chi, G.,
Wu¨est, H. Synthesis studies on damascenones. Helv. Chim. Acta 1971, 54,
1767–1776; (n) Torii, S.; Uneyama, K.; Ichimura, H. Synthesis of b-damascenone
from prenyl phenyl sulfone: A (C5 þ C5 þ C3) procedure. J. Org. Chem. 1979, 44,
2292–2294; (o) Lee, W. Y.; Jang, S. E.; Lee, J. G.; Chae, W. K. Novel synthesis of
isomers of damascenone from ethyl 2,6,6-trimethyl-4-oxo-2-cyclohexene-1-car-
boxylate. Bull. Korean Chem. Soc. 1991, 12, 31–35.
´
10. (a) Amorallah-Madjabadi, A.; Stella, L. Utilisation du N,N-dimethylamino-aceto-
nitrile pour la synthese regioselective de diallylcetones masques: Application a la
´
`
´
´
´
`
`
synthese de la g-damascone. Bull. Soc. Chim. Fr. 1987, 350–354; (b) Stella, L.
Application CH 86-4473, (Firmenich S.A. Switz) 1988 Patentschrift (Switz).
11. (a) Ohloff, G.; Rautenstrauch, V.; Schulte-Elte, K. Modellreacktionen zur Bio-
synthese von Verbindungen der Damascon-Reihe und ihre preparative
Anwendung H. Helv. Chim. Acta 1973, 56, 1503–1513; (b) Isoe, S.;
Katsumura, S.; Sakan, T. The synthesis of damascenone and b-damascone and
the possible mechanism of their formation from carotenoids. Helv. Chim. Acta
1973, 56, 1514–1516; (c) Frankhauser, P. DE 80-3040248, Ger. Offen. Appli-
cation (Firmenich S. A. Switz) 1981.
12. (a) Kane, B. J.; Von Geak, R. A. (SCM Corporation). Brevets US-4, 179, 468, 1979
ˆ
and 4244,890; (b) Duchesne, J. P. (Rhone-Poulenc Nutrition Animale). Brevets
FR-902,724, 1990 and EP-446,116, 1991.
13. (a) Serramedan, D.; Marc, F.; Pereyre, M.; Filliatre, C.; Chabardes, P.;
`
Delmond, B. Delta-pyronene: Epoxydation selective et acces aux cyclocitrals.
Tetrahedron Lett. 1992, 33, 4457–4460; (b) Marc, F.; Soulet, B.;
`
´
Serramedan, D.; Delmond, B. L’epoxy-pyronene: Synthon d’acces aux cycloci-
trals et aux ionones et precurseur de nouveaux composes terpenoıdes. Tetrahedron
`
`
´
´
´
¨
1994, 50, 3381–3388.
14. Boulin, B.; Arreguy-San Miguel, B.; Delmond, B. Le g-pyronene: Synthon d’acces
`
au safranal et precurseur d’intermediaires de synthese de la Forskoline et du
`
´
Strigol. Tetrahedron 1998, 54, 2753–2762.
`
15. Eletti-Bianchi, G.; Centini, F.; Re, L. A two-step synthesis of (E)-4-chloro-2-
methylcrotonaldehyde from isoprene: An unprecedend oxidative chlorination of
1,3-diene monoepoxyde by cupric chloride. J. Org. Chem. 1976, 41, 1648–1650.