Synthesis of the enantiomeric forms of α- and γ-damascone starting from commercial racemic α-ionone

Article abstract of DOI:10.1016/j.tetasy.2006.05.024

A straightforward synthesis of both enantiomers of α- and γ-damascone is described. The title compounds were prepared by a divergent pathway starting from the enantiomeric forms of (6RS,7SR,9RS)-7-hydroxy-7,8-dihydro-α-ionol and of (6RS,7SR,9RS)-7-hydroxy

Full text of DOI:10.1016/j.tetasy.2006.05.024

Tetrahedron: Asymmetry 17 (2006) 1573–1580
Synthesis of the enantiomeric forms of a- and c-damascone
starting from commercial racemic a-ionone
Stefano Serra* and Claudio Fuganti
C.N.R. Istituto di Chimica del Riconoscimento Molecolare, Presso Dipartimento di Chimica,
Materiali ed Ingegneria Chimica del Politecnico, Via Mancinelli 7, 20131 Milano, Italy
Received 12 May 2006; accepted 31 May 2006
Abstract—A straightforward synthesis of both enantiomers of a- and c-damascone is described. The title compounds were prepared by a
divergent pathway starting from the enantiomeric forms of (6RS,7SR,9RS)-7-hydroxy-7,8-dihydro-a-ionol and of (6RS,7SR,9RS)-7-
hydroxy-7,8-dihydro-c-ionol. These building blocks were obtained from racemic a-ionone in four and five steps, respectively. The 7-
hydroxy group was introduced by regio- and diastereoselective epoxidation of the conjugated double bond followed by reductive opening
of the oxirane ring. The hydroxy-ketone obtained was reduced diastereoselectively to trans-a-diol that could be converted to the trans-c-
diol by photochemical isomerization. Both diols were then resolved by lipase-mediated acetylation.
ꢀ 2006 Elsevier Ltd. All rights reserved.
O
1. Introduction
O
The norterpenoid ketones a- and c-damascone are relevant
chiral flavors which possess a typical fruity–flowery rose
scent.1 a-Damascone was first synthesized in 19702 and
can be found in black tea,3 where it occurs as its (S)-(ꢀ)-
enantiomer, and as trace component in tobacco4 and differ-
ent essential oils.5 More recently, c-damascone has been
recognized as an original fragrance material,6 which can
favorably complement the above-mentioned a-isomer
(Fig. 1).
1
2
(S)-(−)-α-damascone
(R)-(+)-α-damascone
O
O
3
4
(R)-(−)-γ-damascone
(S)-(+)-γ-damascone
O
O
Olfactory evaluation of these isomers shows that the regio-
isomeric and enantiomeric composition greatly affected
their fragrance properties,7 either in terms of features or
as odor thresholds. For example, (S)-(ꢀ)-a-damascone is
the more powerful enantiomer.8 (odor threshold =
1.5 ppb) and was described as floral, reminiscent of
rose petals also having a winy character. Otherwise, the
(R)-(+)-a-isomer is weaker (odor threshold = 100 ppb)
with a cork and green apple off-note. In the same way,
the (S)-(+)-c-damascone showed superior organoleptic
properties rather than those of the (R)-(ꢀ)-isomer.6 These
noteworthy results exhibit a behavior similar to that of
5
6
γ-ionone
α-ionone
Figure 1.
the a- and c-ionone isomers, where (S)-enantiomers are
again the most pleasant and powerful compounds.9
In spite of these astounding differences among the iso-
meric series, damascones and ionone share the same diffi-
cult accessibility by chemical synthesis, particularly in
their enantiomerically pure forms. In this context, many
enantioselective pathways to damascones have been devel-
oped (Scheme 1). Early studies on the conversion of
a-ionone 5 and c-ionone 6 into a- and c-damascones,2,10
respectively needed the scarcely available enantioenriched
*
Corresponding author. Tel.: +39 02 2399 3076; fax: +39 02 2399 3080;
e-mail: stefano.serra@polimi.it
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.05.024

1574
S. Serra, C. Fuganti / Tetrahedron: Asymmetry 17 (2006) 1573–1580
OM
racemic α-ionone
O
O
X
(S)-7
X
(R)-7
9
OH OH
11
(S)-(−)-α-damascone
(S)-(+)-γ-damascone
α-ionone
γ-ionone
(R)-(+)-α-damascone
(R)-(−)-γ-damascone
OH OH
O
O
12
OM
X
X
(S)-8
(R)-8
10
Scheme 1. Retrosynthetic approaches to damascone isomers.
ionone isomers11 and led only to the preparation of (R)-
(+)-2 in modest ee.2,10b A more general approach is based
on the employment of enantioenriched (S)- and (R)-
cyclocitral derivatives 7 and 8. In 1973, Yamada et al.12
achieved an asymmetric synthesis of 2 via (R)-a-cyclo-
citral, obtained in poor ee by cyclization of a chiral
enamine of citral.
Since the acetylation of the hydroxy functionality at the
9-position of the ionone framework is catalyzed by differ-
ent types of lipases, we envisaged that diols of type 11
and 12 could be ideal substrates for enzymic resolution.
Afterwards, the latter compounds are easily convertible
in their corresponding damascone isomers. Herein, we
reported the accomplishment of this original approach to
enantioenriched compounds 1–4.
Later, Mori et al.13 prepared almost enantiopure 1 from (S)-
7 (X = H). The latter aldehyde was synthesized starting
from a chiral precursor, obtained in turn by enantioselective
enzyme-mediated resolution. Moreover, the enantiomers of
a- and c-cyclocitral, and therefore the damascones 1–4 were
prepared by Vidari et al.14 by a multistep enantioselective
synthesis that involved the cyclization of enantioenriched
epoxyderivatives. Two different approaches based on the
enantioselective protonation of enolates were developed
by Fehr et al.15 Thioesters (S)- and (R)-7 and (S)- and
(R)-8 (X = SPh) were obtained6 in high ee (99% and 96%,
respectively) and employed in the synthesis of compounds
1–4. In addition, a more direct path to the latter ketones
has been accomplished by the enantioselective protonation
of enolates of type 9 and 1015 to afford damascone isomers
in high and moderate ee (98% and 75%, respectively). Even
with the above-mentioned number of studies, all the latter
approaches are difficult to apply industrially and damas-
cone is still commercialized as a racemic flavor.
According to Scheme 2 diols, 11 and 12 can be prepared
straightforwardly from inexpensive racemic a-ionone.
The 7-hydroxy group was introduced diastereoselectively
in two steps. Epoxidation of the conjugated double bond
of 5 by means of H2O2/NaOH occurs with complete regio-
and diastereoselectivity 2 to afford ketone 13 in good yield.
The following reductive opening of the oxirane ring is a
demanding synthetic transformation. Indeed the presence
of a reducible ketonic functionality and the intrinsic insta-
O
OH
O
O
b
a
5
14
13
OH OH
OH OH
15
c
+
11
OAc OAc
OAc OAc
2. Results and discussion
e
d
11
2.1. Preparation of racemic diols 11 and 12
16
17
OH OH
As part of a program of the synthesis of enantioenriched
norterpenoid odorants, we achieved the preparation of
the enantiomers of ionone11 and irone16 isomers through
enantioselective lipase-mediated resolution of the related
ionols and irols. In order to extend the latter procedure
to damascone synthesis, we performed some preliminary
experiments on the damascol isomers. The most common
lipases were tested and none of them are able to
mediate he esterification. This behavior is probably
due to the steric crowding around position 7 (carotenoid
numbering).
f
12
Scheme 2. Preparation of racemic diols 11 and 12. Reagents and
conditions: (a) H2O2/H2O, MeOH, NaOH, 4 ꢁC, 81% (after recrystalli-
zation from hexane); (b) Al/Hg, THF/EtOH/H2O, 0 ꢁC!rt, 87% (after
recrystallization from hexane); (c) Me4NHB(OAc)3, MeCN/MeCO2H,
97% (87% of isolated 11); (d) Ac2O, Py; (e) high-pressure Hg lamps light,
iPrOH/xylene; (f) KOH, MeOH, recrystallization from hexane; 64%
from 11.

S. Serra, C. Fuganti / Tetrahedron: Asymmetry 17 (2006) 1573–1580
1575
bility of the b-hydroxy-ketone system could give rise to
different regioisomers and/or side products. Only one
example of this type of reaction was previously performed
on compound 13 using lithium naphthalenide as a reduc-
ing agent.17 Our attempts to reproduce the latter proce-
dure furnished hydroxy-ketone 14 in modest yields
(39%), even when carefully controlling the experimental
conditions.
lowing a photochemical double bond isomerization proto-
col previously employed in ionone and dehydroionone a–c
conversion.20
As a result of the latter studies diacetate 16 was irradiated,
with high-pressure Hg lamps using xylene as activator. The
reaction was interrupted until the a isomer became less
than 5% of the mixture; then saponification, chromato-
graphic purification and crystallization afforded diol 12 in
satisfactory yield (64%) and in the isomerically pure form
(98% chemical purity, 99% de).
We found that aluminum amalgam18 was the optimal
reagent for this transformation. Indeed, the reduction of
13 dissolved in THF–H2O–ethanol at 0 ꢁC smoothly affor-
ded crystalline hydroxy derivative 14 in good yield (87%).
2.2. Lipase-mediated resolution of diols 11 and 12.
Preparation of damascone isomers 1–4
Moreover, the product was diastereoisomerically pure and
the selective reduction of the ketone functionality could
then afford diol 11 or 15 stereoselectively. A preliminary
lipase-mediated acetylation experiment was performed on
a mixture of 11 and 15 (6:4) obtained by NaBH4 reduction
of 14. We observed that only diol 11 was transformed,
therefore demonstrating that the latter compound should
be used in the resolution procedure. In the synthesis of this
target, 14 was submitted to the diastereoselective reducing
procedure developed by Evans et al.19
Scheme 3 summarizes the enzyme-mediated resolution of
the latter diols and their conversion into damascones 1–4.
As verified before with racemic diol 11, lipases also cata-
lyzed the acetylation of diol 12. Lipase PS (Pseudomonas
cepacia) was the enzyme of choice for the resolution proce-
dure since diastereoisomerically pure diols were used and,
on the basis of our previous experience, the latter lipase
gives the best results in terms of enantioselectivity.
Accordingly, both diols 11 and 12 were submitted to
kinetic acetylation procedure using vinyl acetate as acyl
donor and t-BuOMe as the solvent. The reactions
were performed at rt and then interrupted at about 50%
conversion. For both substrates we observed complete
regioselectivity as indicated by the exclusive formation
of 9-acetoxy-derivatives 18 and 20.
Accordingly,
tetramethylammonium
triacetoxyboro-
hydride quantitatively converted the latter hydroxy-ketone
into diols 11 and 15 with good selectivity (anti:syn = 93:7).
Moreover, the purity of the devised compound 11 could be
increased to 99% de by chromatography or crystallization
from hexane. Our second target, diol 12, was prepared fol-
OH OAc
O
OAc
O
b
95%
c
95%
(−)-18
(−)-19
(−)-α-damascone 1
OAc
44%
48%
OH OAc
O
a
O
11
OH OH
b
93%
c
(+)-19
(+)-18 (51%)
OAc OAc
92%
d
(+)-11
(+)-α-damascone 2
+
e
(+)-16 (24%)
OH OAc
O
OAc
O
c
b
95%
(+)-21
OH OAc
(+)-γ-damascone 3
OAc
(+)-20
93%
49%
43%
O
O
a
12
c
b
94%
OH OH
(−)-20 (78%)
(−)-21
94%
d
(−)-γ-damascone 4
+
(−)-12
OAc OAc
e
(+)-17 (5%)
Scheme 3. Resolution of diols 11 and 12 and synthesis of enantioenriched a- and c-damascone. Reagents and conditions: (a) lipase PS, t-BuOMe, vinyl
acetate, column chromatography; (b) Dess–Martin periodinane, CH2Cl2, rt; (c) DBU, CH2Cl2, rt; (d) Ac2O, Py, CH2Cl2, rt, column chromatography;
(e) KOH, MeOH.

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S. Serra, C. Fuganti / Tetrahedron: Asymmetry 17 (2006) 1573–1580
Concerning the enantioselectivity of the processes, the re-
sults were again very good. Diol 11 gave monoacetate
(ꢀ)-18 in 99% ee and diol (+)-11 in 94% ee whereas diol
12 afforded monoacetate (+)-20 in 99% ee and diol (ꢀ)-
12 in 98% ee. Hence, all the stereoisomers of damascone
were accessible by simple chemical transformations. Oxida-
tion of monoacetate (ꢀ)-18 with the Dess–Martin period-
inane reagent21 gave almost quantitatively (95% yield),
acetoxy-ketone (ꢀ)-19 that underwent the elimination reac-
tion smoothly by DBU treatment in CH2Cl2 solution at rt.
tiomeric purity and compares favorably to the previously
reported syntheses.
4. Experimental
4.1. General experimental
All moisture-sensitive reactions were carried out under a
static atmosphere of nitrogen. All reagents were of com-
mercial quality and used without further purification.
Yields are reported for spectroscopically pure isolated
compounds. All the photoisomerization experiments were
carried out using a Rayonet photochemical reactor
equipped with twelve 8-W high-pressure Hg lamps. Lipase
PS from P. cepacia (Amano Pharmaceuticals Co., Japan,
30 U mgꢀ1 was employed in this work. TLC: Merk silica
gel 60 F254 plates. Column chromatography (CC): silica
gel. Gas chromatographic (GC) analyses: HP-6890 gas
chromatograph; determined on a HP-5 column (30 m ·
0.32 mm; Hewlett Packard) with the following temp. pro-
gram 60 ꢁC (1 min)–6 ꢁC/min–150 ꢁC (1 min)–12 ꢁC/min–
280 ꢁC (5 min); tR (min): 13 (17.07), 14 (16.86), 11
(18.27), 15 (18.02), 12 (19.44), 16 (20.19), 17 (20.55), 18
(19.26), 19 (19.54), 20 (19.03), 21 (18.87), 1 (14.42), 3
(13.70). Chiral GC analyses: DANI-HT-86.10 gas chro-
matograph; enantiomer excesses determined on a CHIRA-
SIL DEX CB-Column (25 m · 0.25 mm; Chrompack) with
the following temp. program 80 ꢁC–1 ꢁC/min–95 ꢁC
(1 min)–0.3 ꢁC/min–105 ꢁC–25 ꢁC/min–180 ꢁC; tR (min)
of the corresponding acetates: (ꢀ)-18 (40.52), (+)-11
(46.17), (+)-20 (45.19), (ꢀ)-12 (45.77). Optical rotations:
Jasco-DIP-181 digital polarimeter. 1H and 13C NMR spec-
tra: CDCl3 solutions. at rt; Bruker-AC-400 spectrometer;
chemical shifts in parts per million rel to internal SiMe4
(= 0 ppm), J values in Hertz. Mass spectra were measured
on a Finnigan-Mat TSQ 70 spectrometer; m/z (rel.%). IR
spectra were recorded on a Perkin–Elmer 2000 FT-IR spec-
trometer; films; m in cmꢀ1. Melting points were measured
on a Reichert apparatus, equipped with a Reichert micro-
scope, and are uncorrected. Microanalyses were deter-
mined on an analyzer 1106 from Carlo Erba.
(ꢀ)-(S)ꢀa-Damascone 1 was obtained in good yield (95%)
and without
a decrease of enantiomeric excess as
judged from the comparison of the measured specific
20
rotation value, ½aꢁD ¼ ꢀ520:5 ðc 2; CHCl3Þ, with that
23
reported in the lit.13 ½aꢁD ¼ ꢀ514 ðc 4; CHCl3Þ for
(ꢀ)-1 with 100% ee. Afterwards, (+)-a-damascone 2 was
prepared from diol (+)-11 by chemical acetylation. Treat-
ment of the latter compound with a slight excess of acetic
anhydride in pyridine gave separable monoacetate (+)-18
(51%), diacetate (+)-16 (24%) and the unreacted starting
material. The overall efficiency of the process could be in-
creased for recovering further diol (+)-11 by treatment of
diacetate (+)-16 with KOH in methanol. Application of
the oxidation–elimination protocol described above for
the compound (+)-18 afforded (+)-(R)-a-damascone 2,
whose ee was quantifiable from the measured specific
20
rotation value f½aꢁD ¼ þ489:7 ðc 2; CHCl3Þg as higher
then 94%, in perfect accordance with the ee of the starting
diol.
The preparation of c-damascone enantiomers 3 and 4 was
performed starting from monoacetate (+)-20 and diol (ꢀ)-
12, respectively. The synthetic path, the behavior of the
reactions and the yields were the same of those described
above for a-isomers 1 and 2. For the sake of brevity we
underlined only one difference found during the chemical
acetylation of (ꢀ)-12. In this case, (ꢀ)-20 was obtained
with better regioselectivity (78% yield). According to
Scheme 2, (S)-(+)-c-damascone 3 and (R)-(ꢀ)-c-damas-
cone 4 were obtained from acetoxy-ketone (+)- and (ꢀ)-
21 in 93% and 94% yields, respectively.
The enantiomeric purities were reasonably similar to the
4.2. Synthesis of racemic (6RS,7SR,9RS)-7-hydroxy-7,8-
dihydro-a-ionol and of (6RS,7SR,9RS)-7-hydroxy-7,8-
dihydro-c-ionol
starting compounds (+)-20 and (ꢀ)-12 as of 99% and
98% ee as judged from the comparison of the measured
20
specific rotation value, ½aꢁD ¼ þ272:3 ðc 2; CHCl3Þ and
20
½aꢁD ¼ ꢀ270:5 ðc 2; CHCl3Þ, respectively with those
4.2.1. (6RS,7RS,8SR)-7,8-Epoxy-a-dihydroionone 13. H2O2
(30% in water, 110 ml, 1.08 mol) and 6 M NaOH aq (25 ml,
150 mmol) were successively added dropwise to a cooled
(0 ꢁC) and stirred solution of a-ionone 5 (50 g, 260 mmol)
in methanol (300 ml). The resulting mixture was stirred for
6 days at 4 ꢁC and then further H2O2 (50 ml) and methanol
(30 ml) were added each day. The reaction was then
quenched with water (300 ml) and extracted with ether.
The organic phase was washed with brine, dried over
Na2SO4 and concentrated under reduced pressure. The resi-
due (55 g) was submitted to chromatography (eluting from
hexane to hexane/Et2O 8:2) and the obtained 13 (52 g) was
further purified by crystallization from hexane to afford pure
(6RS,7RS,8SR)-7,8-epoxy-a-dihydroionone 13 (44 g, 81%
yield, 99% chemical purity, up to 99% de (GC)) as colorless
20
reported in the lit6 ½aꢁD ¼ þ259 for (+)-3 of 96% ee
20
and ½aꢁD ¼ ꢀ267 ðc 0:02; CHCl3Þ for (ꢀ)-4 of 98% ee.
3. Conclusions
Several results have been achieved. We have reported a new
chemio-enzymatic approach to all the isomeric forms of the
norterpenoid flavor damascone. Our synthetic pathway is
divergent, compact, and operationally simple and does
not require demanding reaction conditions or reagents.
The starting material is a racemic a-ionone that is inexpen-
sive and commercially available. The procedure described
gives access to the title compounds in high regio- and enan-

S. Serra, C. Fuganti / Tetrahedron: Asymmetry 17 (2006) 1573–1580
1577
crystals: mp 38–39 ꢁC (lit.2 mp 38 ꢁC); 1H NMR (400 MHz,
CDCl3) d 5.52 (br s, 1H), 3.29 (d, J = 2 Hz, 1H), 2.91 (dd,
J = 2, 8.6 Hz, 1H), 2.07–1.99 (m, 2H), 2.06 (s, 3H), 1.72–
1.69 (m, 3H), 1.53 (dt, J = 8.2, 13.4 Hz, 1H), 1.40 (d,
J = 8.6 Hz, 1H), 1.29 (dt, J = 4.8, 13.4 Hz, 1H), 1.10 (s,
3H), 0.93 (s, 3H); 13C NMR (100 MHz) d 205.7, 130.3,
124.5, 59.1, 58.5, 52.4, 32.6, 31.7, 27.2, 26.9, 24.3, 23.5,
22.9. IR (CHCl3, cmꢀ1) 1711, 1365, 1246, 881, 846. MS
(EI) m/z (rel intensity) 208 (M+, 1), 193 (2), 175 (8), 165
(40), 147 (42), 135 (48), 123 (35), 109 (99), 95 (88), 81
(100), 67 (22), 55 (23). Anal. Calcd for C13H20O2: C, 74.96;
H, 9.68. Found: C, 74.90; H, 9.70.
87% yield, 97% chemical purity, 99% de (GC)) as a colorless
oil that crystallized on standing: mp 63–65 ꢁC; H NMR
1
(400 MHz, CDCl3) d 5.42 (br s, 1H), 4.27 (dt, J = 2.4,
10.8 Hz, 1H), 4.13–4.04 (m, 1H), 2.80 (br s, 1H), 2.70 (br s,
1H), 2.01–1.90 (m, 2H), 1.78–1.75 (m, 3H), 1.73–1.62 (m,
2H), 1.47–1.35 (m, 2H), 1.22 (d, J = 6.4 Hz, 3H), 1.16–1.07
(m, 1H), 1.01 (s, 3H), 0.87 (s, 3H); 13C NMR (100 MHz) d
133.3, 122.5, 69.1, 65.9, 56.0, 42.3, 32.2, 31.5, 28.6, 28.6,
25.6, 23.1, 22.8. IR (Nujul, cmꢀ1) 3372, 1378, 1363, 1131,
1063, 818. MS (EI) m/z (rel intensity) 194 (M+ꢀH2O, 3),
179 (1), 161 (2), 153 (1), 135 (2), 124 (38), 109 (100), 93
(8), 89 (11), 81 (15), 71 (11), 68 (16), 55 (4). Anal. Calcd
for C13H24O2: C, 73.54; H, 11.39. Found: C, 73.40; H,
11.45.
4.2.2. (6RS,7SR)-7-Hydroxy-a-dihydroionone 14. An alu-
minum amalgam (freshly prepared from 25 g of aluminum
foil) was added portionwise to a stirred solution of epoxide
13 (12 g, 57.7 mmol), THF (90 ml), water (30 ml), and eth-
anol (30 ml) at 0 ꢁC. The reaction was allowed to proceed
for 2 h at 0 ꢁC. Cooling was then removed and the stirring
prolonged until no more starting material was detected by
TLC analysis (1 h). The mixture was diluted with ether
(250 ml), filtered, and the filtrate then washed with ether
(100 ml). The organic phase was washed with brine, dried
over Na2SO4, and concentrated under reduced pressure.
The residue was submitted to chromatography (eluting
from hexane to hexane/Et2O 7:3) and the obtained 14
(11.5 g) was further purified by crystallization from hexane
to afford pure (6RS,7SR)-7-hydroxy-a-dihydroionone 14
(10.6 g, 87% yield, 98% chemical purity, up to 99% de
(GC)) as colorless crystals: mp 67–68 ꢁC; 1H NMR
(400 MHz, CDCl3) d 5.46 (br s, 1H), 4.34 (dq, J = 3,
9.6 Hz, 1H), 2.94 (d, J = 3 Hz, 1H), 2.56 (ddd, J = 3, 9.6,
17.8 Hz, 2H), 2.17 (s, 3H), 2.05–1.95 (m, 2H), 1.80–1.75
(m, 4H), 1.41–1.30 (m, 1H), 1.22–1.13 (m, 1H), 1.02 (s,
3H), 0.90 (s, 3H); 13C NMR (100 MHz) d 210.3, 133.3,
122.7, 68.1, 54.5, 48.5, 32.1, 31.4, 30.8, 28.5, 28.2, 25.6,
22.9. IR (Nujul, cmꢀ1) 3435, 1709, 1167, 1063, 815. MS
(EI) m/z (rel intensity) 192 (M+ꢀH2O, 2), 177 (1), 152
(3), 136 (2), 134 (2), 123 (15), 121 (14), 109 (38), 93 (21),
91 (22), 87 (34), 81 (43), 67 (18), 55 (12), 43 (100). Anal.
Calcd for C13H22O2: C, 74.24; H, 10.54. Found: C, 74.30;
H, 10.55.
4.2.4. (6RS,7SR,9RS)-7-Hydroxy-c-dihydroionol 12.
A
sample of diol 11 (1.4 g, 6.6 mmol) was dissolved in pyri-
dine (15 ml) and acetic anhydride (15 ml) and set aside at
rt until the complete formation of diacetate 16 (24 h).
The reaction was concentrated under reduced pressure
and the residue dissolved in a mixture of isopropanol
(80 ml) and xylene (20 ml). The resulting solution was
poured in a quartz vessel under a static atmosphere of
nitrogen and irradiated with twelve 8-W high-pressure
Hg lamps. The reaction was monitored by NMR analysis
and the irradiation interrupted until compound 16 became
less than 5% of the mixture (6 days). The solution was then
concentrated under reduced pressure to afford an oil that
was treated with a solution of KOH (2 g, 35.6 mmol) in
methanol (30 cm3), stirring at rt until no more starting ace-
tate was detected by TLC analysis. The mixture was diluted
with water (80 cm3) and extracted with diethyl ether
(3 · 100 cm3). The combined organic phases were washed
with brine, dried over Na2SO4, and concentrated under re-
duced pressure. The residue was purified by chromatogra-
phy (eluting from hexane/AcOEt 9:1 to hexane/AcOEt
1:1) to afford 12 (1.04 g, 90% de) that was further purified
by crystallization from hexane to give diol 12 as a single
isomer (0.9 g, 64% yield, 98% chemical purity, 99% de);
mp 98–99 ꢁC; 1H NMR (400 MHz, CDCl3) d 4.79 (t,
J = 2.1 Hz, 1H), 4.64 (s, 1H), 4.27–4.10 (m, 2H), 2.29 (br
s, 2H), 2.12 (dm, J = 13.3 Hz, 1H), 1.95 (d, J = 8.0 Hz,
1H), 1.83–1.70 (m, 1H), 1.65–1.43 (m, 5H), 1.31–1.19 (m,
1H), 1.21 (d, J = 6.4 Hz, 3H), 1.11 (s, 3H), 0.94 (s, 3H);
13C NMR (100 MHz) d 148.2, 111.9, 67.6, 65.3, 60.5,
43.1, 35.2, 34.5, 32.8, 29.7, 28.5, 23.5, 23.1. IR (nujol,
cmꢀ1) 3291, 1646, 1377, 1135, 1058, 1031, 889, 867, 829.
MS (EI) m/z (rel intensity) 194 (M+ꢀH2O, 1), 179 (2),
161 (3), 153 (2), 150 (2), 135 (4), 124 (21), 109 (100),
95 (6), 93 (5), 89 (7), 81 (14), 69 (13), 55 (5). Anal. Calcd
for C13H24O2: C, 73.54; H, 11.39. Found: C, 73.40; H,
11.40.
4.2.3. (6RS,7SR,9RS)-7-Hydroxy-a-dihydroionol 11. Tetra-
methylammonium triacetoxyborohydride (15 g, 57 mmol)
was stirred at rt for 30 min in anhydrous acetonitrile
(20 ml) and acetic acid (20 ml). The solution obtained was
cooled to ꢀ20 ꢁC and hydroxyketone 14 (3 g, 14.3 mmol)
in anhydrous acetonitrile (10 ml) added dropwise. The reac-
tion was stirred at ꢀ10 ꢁC until no more starting material
was detected by TLC analysis (15 h), then quenched with
1 M aqueous sodium potassium tartrate (80 ml). The mixture
was diluted with CH2Cl2 (150 ml) and the aqueous layer
extracted again with CH2Cl2 (2 · 100 ml). The combined
organic phases were washed with satd NaHCO3 (50 ml),
dried over Na2SO4, and concentrated under reduced pres-
sure. The GC analysis of the residue (2.95 g) indicated a
93:7 ratio of isomeric diols. The mixture was separated by
chromatography (eluting from hexane/AcOEt 9:1 to hex-
ane/AcOEt 1:1). The first-eluted fractions afforded diol 15
contaminated with diol 11 as a colorless oil (0.25 g, 20% de
(GC)). The last-eluted fractions gave pure diol 11 (2.65 g,
4.3. Lipase-mediated resolution of racemic substrates
4.3.1. Resolution of (6RS,7SR,9RS)-7-hydroxy-a-dihydro-
ionol 11. A mixture of ( )-11 (2.2 g, 10.4 mmol), lipase
PS (2 g), vinyl acetate (15 ml), and t-BuOMe (50 ml) was
stirred at rt for 6 days. After filtration and evaporation
of the filtrate, the residue was chromatographed (hexane/
AcOEt 8:2). The first-eluted fractions afforded (ꢀ)-(6S,
7R,9S)-7-hydroxy-a-dihydroionol acetate 18 as a colorless

1578
S. Serra, C. Fuganti / Tetrahedron: Asymmetry 17 (2006) 1573–1580
oil (1.17 g, mmol; 44%; 98% chemical purity, 99% de (GC),
4.4.1. Regioselective acetylation of diols 11. Acetylation of
(+)-11 (0.9 g, 4.2 mmol) according to general procedure
gave three fractions. The first-eluted fraction afford di-
20
ee 99% (chiral GC)); ½aꢁD ¼ ꢀ122:8 ðc 2; CHCl3Þ. 1H
NMR (400 MHz, CDCl3) d 5.45 (br s, 1H), 5.22–5.10 (m,
1H), 3.91–3.79 (m, 1H), 2.56 (br s, 1H), 2.05 (s, 3H),
2.03–1.95 (m, 2H), 1.80–1.75 (m, 3H), 1.63–1.53 (m, 2H),
1.49–1.39 (m, 1H), 1.26 (d, J = 6.4 Hz, 3H), 1.19–1.10
(m, 1H), 0.99 (s, 3H), 0.90 (s, 3H); 13C NMR (100 MHz)
d 171.5, 133.2, 122.5, 69.0, 68.1, 55.2, 42.0, 32.0, 31.5,
28.5, 28.5, 25.5, 22.8, 21.1, 20.8. IR (film, cmꢀ1) 3505,
1736, 1374, 1247, 1138, 1055, 1037, 1019, 957. MS (EI)
m/z (rel intensity) 236 (M+ꢀH2O, 2), 194 (3), 176 (4),
150 (6), 131 (57), 123 (26), 109 (68), 93 (12), 81 (20), 71
(100), 61 (44), 55 (6). Anal. Calcd for C15H26O3: C,
70.83; H, 10.30. Found: C, 70.95; H, 10.25. The last-eluted
fractions gave (+)-(6R,7S,9R)-7-hydroxy-a-dihydroionol
11 as a colorless oil that crystallized on standing
20
acetate (+)-16 (0.3 g, 24%) as a colorless oil: ½aꢁD
¼
þ148:8 ðc 2; CHCl3Þ. 1H NMR (400 MHz, CDCl3) d
5.51 (br s, 1H), 5.32 (dm, J = 9.4 Hz, 1H), 4.95–4.86 (m,
1H), 2.08–1.96 (m, 1H), 2.01 (s, 3H), 2.01 (s, 3H), 1.81
(br s, 1H), 1.75–1.70 (m, 3H), 1.67–1.59 (m, 2H), 1.47–
1.35 (m, 1H), 1.30–1.15 (m, 2H), 1.21 (d, J = 6.4 Hz,
3H), 1.11 (s, 3H), 0.90 (s, 3H); 13C NMR (100 MHz) d
170.6, 170.3, 131.8, 123.6, 71.0, 67.6, 52.4, 38.2, 31.9,
31.8, 28.7, 28.0, 25.1, 22.7, 21.3, 21.1, 20.6. IR (film,
cmꢀ1) 1738, 1456, 1437, 1372, 1245, 1096, 1020, 957, 827.
MS (EI) m/z (rel intensity) 237 (1), 236 (M+ꢀAcOH, 5),
193 (1), 176 (85), 172 (30), 161 (49), 147 (6), 131 (100),
123 (59), 113 (75), 105 (16), 93 (18), 81 (22), 71 (73), 61
(19), 55 (7). Anal. Calcd for C17H28O4: C, 68.89; H, 9.52.
Found: C, 69.00; H, 9.55. The second eluted fractions affor-
ded (+)-7-hydroxy-a-dihydroionol acetate 18 (0.55 g, 51%)
(1.05 g, mmol; 48%; 98% chemical purity, 99% de (GC),
20
ee 94% (chiral GC)); mp 62–63 ꢁC; ½aꢁD ¼ þ160:5
1
ðc 2; CHCl3Þ. IR, H NMR, MS: in accordance with that
20
1
of ( )-(6RS,7SR,9RS)-7-hydroxy-a-dihydroionol 11.
as a colorless oil: ½aꢁD ¼ þ111:5 ðc 2; CHCl3Þ. H NMR,
MS: in accordance with that of (ꢀ)-7-hydroxy-a-dihyd-
roionol acetate 18. The last-eluted fraction afforded start-
ing diol (+)-11 (0.15 g, 17%).
4.3.2. Resolution of (6RS,7SR,9RS)-7-hydroxy-c-dihydro-
ionol 12. A mixture of ( )-12 (1.2 g, 5.7 mmol), lipase PS
(1 g), vinyl acetate (10 ml), and t-BuOMe (40 ml) was stir-
red at rt for 4 days. After filtration and evaporation of the
filtrate, the residue was chromatographed (hexane/AcOEt
8:2). The first-eluted fractions afforded (+)-(6S,7R,9S)-7-
hydroxy-c-dihydroionol acetate 20 as a colorless oil that
crystallized upon standing (0.71 g, mmol; 49%; 98% chemi-
4.4.2. Regioselective acetylation of 12. Acetylation of (ꢀ)-
12 (0.6 g, 2.8 mmol) according to the general procedure
gave three fractions. The first-eluted fractions afforded
20
(+)-diacetate 17 (45 mg, 5%) as a colorless oil: ½aꢁD
¼
1
þ5:8 ðc 2; CHCl3Þ. H NMR (400 MHz, CDCl3) d 5.33
(ddd, J = 2.6, 8.4, 10.2 Hz, 1H), 4.84 (t, J = 2.0 Hz, 1H),
4.83–4.73 (m, 1H), 4.68 (s, 1H), 2.17 (dm, J = 13 Hz,
1H), 2.10 (d, J = 8.4 Hz, 1H), 2.03 (s, 3H), 1.99 (s, 3H),
1.91–1.80 (m, 1H), 1.82 (ddd, J = 2.6, 10.2, 15.1 Hz, 1H),
1.66–1.46 (m, 4H), 1.31–1.17 (m, 1H), 1.18 (d,
J = 6.2 Hz, 3H), 0.91 (s, 3H), 0.90 (s, 3H); 13C NMR
(100 MHz) d 170.6, 170.4, 147.3, 112.7, 68.9, 66.8, 57.3,
40.0, 35.2, 32.6, 28.4, 28.1, 23.0, 21.4, 21.2, 20.6, 20.6. IR
(film, cmꢀ1) 1741, 1647, 1451, 1372, 1244, 1144, 1091,
1021, 959, 894. MS (EI) m/z (rel intensity) 236
(M+ꢀAcOH, 4), 221 (2), 194 (12), 176 (56), 173 (53), 161
(67), 151 (22), 133 (78), 131 (100), 123 (21), 113 (89), 105
(25), 93 (33), 81 (25), 71 (69), 69 (33), 61 (21), 55 (14). Anal.
Calcd for C17H28O4: C, 68.89; H, 9.52. Found: C, 70.00; H,
9.55. The second eluted fractions afforded (ꢀ)-7-hydroxy-
c-dihydroionol acetate 20 (0.56 g, 78%); mp 69–71 ꢁC;
cal purity, 99% de (GC), ee 99% (chiral GC)); mp 70–
20
71 ꢁC; ½aꢁ ¼ þ25:8 ðc 2; CHCl3Þ; 1H NMR (400 MHz,
CDCl3) dD 5.22–5.13 (m, 1H), 4.78 (t, J = 2.2 Hz, 1H),
4.63 (s, 1H), 3.79–3.72 (m, 1H), 2.58 (d, J = 5.2 Hz, 1H),
2.13 (dm, J = 13.4 Hz, 1H), 2.08 (s, 3H), 1.87 (d,
J = 7.9 Hz, 1H), 1.79–1.67 (m, 1H), 1.63–1.46 (m, 4H),
1.41 (ddd, J = 2.4, 10.8, 14.6 Hz, 1H), 1.29–1.21 (m, 1H),
1.25 (d, J = 6.4 Hz, 3H), 1.07 (s, 3H), 0.92 (s, 3H); 13C
NMR (100 MHz) d 171.7, 148.0, 112.0, 68.6, 65.8, 60.1,
43.1, 35.4, 34.4, 32.9, 29.6, 28.4, 23.0, 21.2, 20.9. IR (film,
cmꢀ1) 3492, 3063, 1720, 1645, 1440, 1373, 1276, 1218,
1132, 1055, 1020, 889, 808. MS (EI) m/z (rel intensity)
236 (M+ꢀH2O, 1), 194 (M+ꢀAcOH, 2), 179 (5), 161 (7),
151 (6), 131 (59), 124 (13), 109 (100), 93 (13), 81 (20), 71
(84), 61 (33), 55 (9). Anal. Calcd for C15H26O3: C, 70.83;
H, 10.30. Found: C, 70.70; H, 10.30. The last-eluted frac-
tions gave (ꢀ)-(6R,7S,9R)-7-hydroxy-c-dihydroionol 12
as a white crystals (0.52 g, 43%; 98% chemical purity,
99% de (GC), ee 98% (chiral GC)); mp 123–124 ꢁC;
20
1
½aꢁD ¼ ꢀ24:1 ðc 2; CHCl3Þ. H NMR, MS: in accordance
with that of (+)-7-hydroxy-c-dihydroionol acetate 20.
The last-eluted fraction afforded starting diol (ꢀ)-12 (75
mg, 12%).
20
1
½aꢁD ¼ ꢀ8:6 ðc 2; CHCl3Þ. IR, H NMR, MS: in accor-
dance with that of ( )-(6RS,7SR,9RS)-7-hydroxy-c-di-
hydroionol 12.
4.5. General procedure for oxidation of stereoisomers of
7-hydroxy-a-dihydroionol acetate and 7-hydroxy-c-dihydro-
ionol acetate
4.4. General procedure for regioselective acetylation
of diols 11 and 12
Dess–Martin periodinane (1.45 g, 3.4 mmol) was added to
a stirred solution of 18 or 20 (0.75 g, 2.9 mmol) in CH2Cl2
(40 ml) at rt. After 1 h the reaction was quenched by the
addition of ether (100 ml), satd aq NaHCO3 (50 ml), and
satd aq Na2S2O3 (50 ml). Stirring was continued until the
clear phases were obtained (15 min). The aq layer was ex-
tracted with ether and the combined organic phases washed
with brine, dried over Na2SO4, and concentrated under
Acetic anhydride (0.48 ml, 5.1 mmol) was added to a stir-
red solution of diol 11 or 12 (0.9 g, 4.2 mmol) in pyridine
(5 ml) and CH2Cl2 (10 ml) at rt. After 24 h, water
(0.1 ml) was added and the mixture concentrated under
reduced pressure. The residue was purified by chroma-
tography (eluting from hexane/AcOEt 9:1 to hexane/
AcOEt 1:1).

S. Serra, C. Fuganti / Tetrahedron: Asymmetry 17 (2006) 1573–1580
1579
reduced pressure. The residue was purified by chromato-
graphy (eluting with hexane/AcOEt 9:1).
detected by TLC analysis (3 h) then water (50 ml), ether
(100 ml), and 5% aq HCl (30 ml) were added. The aq layer
was extracted with ether (50 ml) and the combined organic
phases were washed with aq NaHCO3 (50 ml), water, and
brine. The solution obtained was dried over Na2SO4 and
concentrated by distillation of the solvent at atmospherical
pressure. The residue was purified by chromatography
(eluting with hexane/ether 95:5) and bulb-to-bulb distilla-
tion (bp 95–100 ꢁC/0.1 mmHg).
4.5.1. (ꢀ)-(6S,9S)-7-Oxy-a-dihydroionol acetate 19. Oxi-
dation of (ꢀ)-18 (0.75 g, 2.9 mmol) according to the gen-
eral procedure afforded (ꢀ)-(6S,9S)-7-oxy-a-dihydroionol
20
acetate 19 (0.71 g, 95%) as a colorless oil. ½aꢁD
¼
ꢀ378:4 ðc 2; CHCl3Þ. 1H NMR (400 MHz, CDCl3) d
5.59 (br s, 1H), 5.34–5.25 (m, 1H), 2.89 (dd, J = 6.9,
17.7 Hz, 1H), 2.72 (s, 1H), 2.62 (dd, J = 5.9, 17.7 Hz,
1H), 2.18–1.96 (m, 2H), 1.98 (s, 3H), 1.78–1.67 (m, 1H),
1.61–1.58 (m, 3H), 1.26 (d, J = 6.4 Hz, 3H), 1.21–1.13
(m, 1H), 0.93 (s, 3H), 0.90 (s, 3H); 13C NMR (100 MHz)
d 210.0, 170.0, 129.8, 123.7, 66.9, 63.8, 50.8, 32.3, 30.7,
27.7, 27.7, 23.2, 22.5, 21.1, 19.8. IR (film, cmꢀ1) 1741,
1713, 1451, 1367, 1243, 1140, 1048, 1021, 958. MS (EI)
m/z (rel intensity) 252 (M+, 1), 193 (6), 192 (M+ꢀAcOH,
45), 177 (4), 149 (2), 135 (4), 123 (35), 107 (12), 91 (7), 81
(18), 69 (100), 55 (3). Anal. Calcd for C15H24O3: C,
71.39; H, 9.59. Found: C, 71.45; H, 9.60.
4.6.1. (ꢀ)-a-Damascone 1. Base-mediated elimination of
acetate (ꢀ)-19 (0.62 g, 2.5 mmol) according to the general
procedure afforded (ꢀ)-a-damascone 1 (0.45 g, 95% yield,
99% chemical purity (GC)) as a colorless oil that crystal-
20
lized on cooling; mp 20–25 ꢁC; ½aꢁD ¼ ꢀ520:5 ðc 2;
1
CHCl3Þ. H NMR (400 MHz, CDCl3) d 6.88 (dq, J = 6.9,
15.3 Hz, 1H), 6.31 (dq, J = 1.7, 15.3 Hz, 1H), 5.64–5.58
(m, 1H), 2.89 (s, 1H), 2.20–1.99 (m, 2H), 1.89 (dd,
J = 1.7, 6.9 Hz, 3H), 1.71 (ddd, J = 6.9, 10.3, 13.3 Hz,
1H), 1.58–1.54 (m, 3H), 1.17 (ddd, J = 2.6, 5.8, 13.3 Hz,
1H), 0.95 (s, 3H), 0.86 (s, 3H); 13C NMR (100 MHz) d
202.0, 142.0, 132.2, 130.5, 123.4, 61.3, 32.3, 31.3, 27.9,
27.7, 23.2, 22.6, 18.1. IR (film, cmꢀ1) 1687, 1668, 1625,
1443, 1365, 1318, 1292, 1178, 1082, 972, 824. MS (EI)
m/z (rel intensity) 193 (M++1, 6), 192 (M+, 47), 177 (7),
163 (1), 149 (3), 135 (8), 123 (36), 107 (9), 91 (10), 81
(30), 69 (100), 55 (4), 41 (15). Anal. Calcd for C13H20O:
C, 81.20; H, 10.48. Found: C, 81.30; H, 10.50.
4.5.2. (+)-(6R,9R)-7-Oxy-a-dihydroionol acetate (+)-
19. Oxidation of (+)-18 (0.4 g, 1.6 mmol) according to
the general procedure afforded (+)-(6R,9R)-7-oxy-a-di-
hydroionol acetate (+)-19 (0.37 g, 93%) as a colorless oil.
20
½aꢁD ¼ þ346:8 ðc ¼ 2; CHCl3Þ. IR, 1H NMR, MS: in
accordance with that of (ꢀ)-(6S,9S)-7-oxy-a-dihydroionol
19.
4.5.3. (+)-(6S,9S)-7-Oxy-c-dihydroionol acetate 21. Oxi-
dation of (+)-20 (0.7 g, 2.8 mmol) according to general
procedure afforded (+)-(6S,9S)-7-oxy-c-dihydroionol ace-
4.6.2. (+)-a-Damascone 2. Base-mediated elimination of
acetate (+)-19 (0.3 g, 1.2 mmol) according to the general
procedure afforded (+)-a-damascone 2 (0.21 g, 92% yield,
20
tate 21 (0.66 g, 95%) as
a
colorless oil. ½aꢁD
¼
98% chemical purity (GC)) as
a
colorless oil.
20
þ287:4 ðc ¼ 2; CHCl3Þ. 1H NMR (400 MHz, CDCl3) d
5.27 (sext, J = 6.3 Hz, 1H), 4.89 (s, 1H), 4.74 (s, 1H),
3.03 (s, 1H), 2.92 (dd, J = 6.8, 16.8 Hz, 1H), 2.49 (dd,
J = 6.2, 16.8 Hz, 1H), 2.23–2.12 (m, 1H), 2.08 (dt,
J = 4.5, 13.5 Hz, 1H), 2.02–1.92 (m, 1H), 1.97 (s, 3H),
1.68–1.58 (m, 1H), 1.55–1.41 (m, 1H), 1.25 (d,
J = 6.2 Hz, 3H), 1.18 (dt, J = 4.5, 13.5 Hz, 1H), 0.95 (s,
3H), 0.89 (s, 3H); 13C NMR (100 MHz) d 207.1, 170.0,
144.5, 112.1, 66.8, 66.4, 49.6, 35.3, 35.0, 31.6, 27.6, 26.6,
22.9, 21.0, 19.8. IR (film, cmꢀ1) 1741, 1712, 1643, 1449,
1366, 1242, 1138, 1053, 1038, 959, 895. MS (EI) m/z (rel
intensity) 252 (M+, 1), 193 (6), 192 (M+ꢀAcOH, 40), 177
(12), 164 (2), 149 (6), 135 (14), 129 (13), 123 (22), 107
(13), 93 (8), 81 (16), 69 (100), 55 (6). Anal. Calcd for
C15H24O3: C, 71.39; H, 9.59. Found: C, 71.45; H, 9.60.
½aꢁD ¼ þ489:7 ðc 2; CHCl3Þ. IR, H NMR, MS: in accor-
1
dance with that of (ꢀ)-a-damascone 1.
4.6.3. (+)-c-Damascone 3. Base-mediated elimination of
acetate (+)-21 (0.55 g, 2.2 mmol) according to general
procedure afforded (+)-c-damascone 3 (0.39 g, 93% yield,
20
98% chemical purity (GC)) as a colorless oil. ½aꢁD
¼
þ272:3 ðc 2; CHCl3Þ. 1H NMR (400 MHz, CDCl3) d
6.81 (dq, J = 6.9, 15.6 Hz, 1H), 6.16 (dq, J = 1.8,
15.6 Hz, 1H), 4.85 (t, J = 1.8 Hz, 1H), 4.69 (s, 1H), 3.21
(s, 1H), 2.32–2.23 (m, 1H), 2.09 (dt, J = 4.7, 13.4 Hz,
1H), 1.98 (ddd, J = 4.4, 11.3, 13.4 Hz, 1H), 1.86 (dd,
J = 1.8, 6.9 Hz, 3H), 1.68–1.60 (m, 1H), 1.56–1.45 (m,
1H), 1.20 (dt, J = 4.7, 13.4 Hz, 1H), 0.95 (s, 3H), 0.91 (s,
3H); 13C NMR (100 MHz) d 199.2, 145.2, 141.3, 132.8,
111.7, 63.8, 35.8, 34.9, 31.9, 27.8, 26.6, 22.9, 17.9. IR (film,
cmꢀ1) 3072, 1693, 1668, 1628, 1443, 1364, 1279, 1185, 1124,
1075, 967, 895. MS (EI) m/z (rel intensity) 193 (M++1, 4),
192 (M+, 26), 177 (10), 159 (3), 149 (9), 136 (9), 122 (16),
109 (12), 91 (7), 81 (16), 69 (100), 55 (5), 41 (20). Anal.
Calcd for C13H20O: C, 81.20; H, 10.48. Found: C, 81.35;
H, 10.50.
4.5.4. (ꢀ)-(6R,9R)-7-Oxy-c-dihydroionol acetate 21. Oxi-
dation of (ꢀ)-20 (0.45 g, 1.8 mmol) according to the general
procedure afforded (ꢀ)-(6R,9R)-7-oxy-c-dihydroionol
20
acetate 21 (0.42 g, 94%) as a colorless oil. ½aꢁD
¼
1
ꢀ287:2 ðc 2; CHCl3Þ. IR, H NMR, MS: in accordance
with that of (+)-(6RS,9RS)-7-oxy-c-dihydroionol 21.
4.6. General procedure for base-mediated elimination of 7-
oxy-a-dihydroionol acetate and 7-oxy-c-dihydroionol acetate
4.6.4. (ꢀ)-c-Damascone 4. Base-mediated elimination of
acetate (ꢀ)-21 (0.35 g, 1.4 mmol) according to general
procedure afforded (ꢀ)-c-damascone 4 (0.25 g, 94% yield,
20
DBU (0.7 ml, 4.7 mmol) was added to a solution of acetate
19 or 21 (0.62 g, 2.5 mmol) in CH2Cl2 (40 ml) at rt. The
mixture was stirred until no more starting acetate was
99 % chemical purity) as a colorless oil. ½aꢁD ¼ ꢀ270:5
1
ðc 2; CHCl3Þ. IR, H NMR, MS: in accordance with that
of (+)-c-damascone 3.

1580
S. Serra, C. Fuganti / Tetrahedron: Asymmetry 17 (2006) 1573–1580
Gelsomini, N.; Taddei, M. J. Org. Chem. 1990, 55, 1106–
Acknowledgements
1108; (c) Sarandeses, L. A.; Luche, J.-L. J. Org. Chem. 1992,
57, 2757–2760.
11. Brenna, E.; Fuganti, C.; Serra, S.; Kraft, P. Eur. J. Org.
Chem. 2002, 967–978.
Financial support from COFIN-MURST is acknowledged.
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