Synthesis and olfactory evaluation of (+)- and (-)-γ-ionone

Article abstract of DOI:10.1002/1522-2675(20001004)83:10<2761::AID-HLCA2761>3.0.CO;2-9

The synthesis of enantiomerically pure (+)- and (-)-γ-ionone 3 is reported. The first step in the synthesis is the diastereoisomeric enrichment of 4-nitrobenzoate derivatives of racemic γ-ionol 12. The enantioselective lipase-mediated kinetic acetylation

Full text of DOI:10.1002/1522-2675(20001004)83:10<2761::AID-HLCA2761>3.0.CO;2-9

Helvetica Chimica Acta ± Vol. 83 '2000)
2761
Synthesis and Olfactory Evaluation of ꢀ‡)- and ꢀÀ)-g-Ionone
by Claudio Fuganti, Stefano Serra*, and Alessandro Zenoni
Dipartimento di Chimica del Politecnico, Centro CNR per la Chimica delle Sostanze Organiche Naturali, Via
Mancinelli 7, I-20133 Milano
The synthesis of enantiomerically pure '‡)-and ' À)-g-ionone 3 is reported. The first step in the synthesis is
the diastereoisomeric enrichment of 4-nitrobenzoate derivatives of racemic g-ionol 12. The enantioselective
lipase-mediated kinetic acetylation of g-ionol 13b afforded the acetate 14 and the alcohol 15, which are suitable
precursors of the desired products 'À)-and ' ‡)-3, respectively. The olfactory evaluation of the g-ionone isomers
shows a great difference between the two enantiomers both in fragrance response and in detection threshold.
The selective reduction of 'À)-3 and '‡)-3 to the g-dihydroionones 'À)-'R)-16 and '‡)-'S)-17, respectively,
allowed us to assign unambiguously the absolute configuration of the g-ionones.
1. Introduction. ± Ionones and irones are considered among the historically most
important flavor and fragrance materials [1]. The distribution of these C13 and C14
norterpenoids, respectively, in Nature varies depending on the plant origin and also on
the thermodynamic stability imparted by the substitution differences between ionones
and irones. In particular, cis-g-irone '6) is the main component of the Iris essential oil
[2], where it is accompanied by the a-isomer 4 'cis > trans) and by minor quantities of
the b-material 5. On the other side, a-and b-ionone '1 and 2, resp.) have been found,
usually as a mixture, in a number of plant materials [3]. Conversely, the natural
occurrence of g-ionone '3) is restricted to a Chinese rose oil [4]. Apart from this
naturalistic curiosity, g-ionone '3) and g-irone '6) share the difficult accessibility by
chemical synthesis, particularly in enantiomerically pure form [5][6]. In this context,
the first preparation of partially enantiomerically enriched g-ionone '3) goes back to
the work of Eugster, Ohloff, and co-workers [7], designed to the stereochemical
correlation of manool and ambrein with a-and e-carotenes. These authors converted,
by H3PO4 treatment, a sample of 3 showing [a]2D0 ˆ À4.0 'CHCl3), obtained by partial
resolution of the racemic material via crystallizations of the derivative with 'À)-
menthyl aminocarbamate, into 'À)-a-ionone '[a]2D0 ˆ À17 'neat); À7.8 'CHCl3)), of
'S)-absolute configuration. By this correlation, the 'S)-configuration is assigned to the
enantiomer of 3 that shows a negative optical rotation. Subsequently, Oritani and
Yamashita [6] revised this result, repeating the synthesis reported by Ohloff and Mignat
[8] for racemic 3, which provides from the acetate of 4',5'-dihydro-5'-hydroxy-a-
ionone, by thermal decomposition, a mixture of a-and g-ionone '1 and 3, resp.).
Indeed, starting from '‡)-'R)-cyclogeranic acid '[a]2D0 ˆ ‡320 'EtOH)), they obtained
a sample of g-ionone '3), separated from the prevailing '‡)-a-isomer 1, possessing
[a]2D1 ˆ ‡241 'c ˆ 2, EtOH), by SiO2 column chromatography in the presence of
AgNO3, showing [a]2D0 ˆ À20 'c ˆ 1.5, CHCl3) and À15.6 'c ˆ 1.6, EtOH), respectively.
Confirmatory evidence in favor of the stereochemical revision arose from the

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Helvetica Chimica Acta ± Vol. 83 '2000)
experiments performed on 'À)-'S)-cyclogeranic acid, which led to 'À)-'S)-a-ionone
'[a]2D0 ˆ À301 'c ˆ 2, EtOH)) and '‡)-'S)-g-ionone '[a]2D0 ˆ ‡19.5 'c ˆ 0.5, EtOH)).
Judging from the reported optical-rotation values, the enantiomeric purities of a-
ionone '1)1) and of the accompanying g-isomer 32) seem to be modest.
In light of these observations, it seemed of interest to have access to the
enantiomerically pure forms of 3 through a procedure not necessarily involving the
troublesome separation from the accompanying isomer 1. Recently, we succeeded in
the separation of the enantiomers of a-ionone '1) [9] and of cis-and trans-a-irone 4 [10]
through the enantioselective lipase-mediated acetylation of the diastereoisomerically
pure allylic alcohols obtained upon NaBH4 reduction of the racemic ketones, followed
by MnO2 oxidation. The latter approach to enantiomerically pure forms of odorants
that possess the ionane skeleton seems rather flexible, since it was applied with success
also to the preparation of the enantiomers of the structurally similar synthetic odorant
Timberol ꢀ [11].
Accordingly, we extended the acquired enzymic methodology to the preparation of
the enantiomers of g-ionone '3) starting from the racemic material, and we report here
the results. The study first involved the synthesis of racemic 3, followed by the enzymic
resolution of the corresponding diastereoisomerically pure alcohols. Of the single
enantiomers of 3 obtained by this method, it is here also reported the olfactory
evaluation, kindly provided by Givaudan-Roure. Moreover, the selective reduction of
'À)-and ' ‡)-g-ionone gave the enantiomerically pure 'À)-16 and '‡)-g-dihydroionone
17, respectively 'cf. Scheme 2). Since our synthesis afforded these two compounds of
known absolute configuration without formation of a-and/or b-isomers, the absolute
configuration of the g-ionones was assigned unambiguously.
2. Results. ± 2.1. Synthesis of Racemic g-Ionone. The preparation of enantiomeri-
cally pure '‡)-3 and 'À)-3 by our synthetic method required the availability of racemic
g-ionone. In addition, for the chemical and olfactory characterization of the title
compounds, we needed a starting material without the presence of the accompanying a-
and/or b-isomers. Many different approaches to g-ionone are described in the
literature. The most straightforward ones afforded the g-ionone starting from a
suitable and easily available C13 precursor, but, unfortunately, the mixture of the
isomers [8][12] was invariably obtained. The same difficulties were encountered in the
preparation of the related g-irones. In consideration of the solution adopted in this
latter case [5b][13], the construction of the g-ionone framework by condensation of g-
For optically pure 1, [a]2D0 ˆ ‡422 'c ˆ 1, CHCl3), see [9a].
1
)
)
In this work, we found [a]2D0 ˆ ‡30.2 'c ˆ 0.5, EtOH) for a sample of '‡)-3 showing 98% ee 'chiral GC).
2

Helvetica Chimica Acta ± Vol. 83 '2000)
2763
cyclocitral with 'acetylmethylidene)triphenylphosphorane seems to be the most
promising approach. The required aldehyde 11 was prepared combining some
procedures reported in the literature. Scheme 1 shows in detail our synthetic path to
the monocyclic building block 11. Alkylation of the dianion of ethyl acetoacetate '7)
with dimethylallyl bromide '8), followed by cyclization with SnCl4 afforded the b-keto
ester '9)3) [14a], which was converted to the g-cyclogeraniol '10)4) on Wittig
methylenation5) of the ketone function, followed by LiAlH4 reduction of the ester
group. The Swern oxidation of the obtained alcohol 10 afforded pure g-cyclocitral6)
without isomerization of the exocyclic CˆC bond. This latter compound was not
purified but used directly for the synthesis of 3. Wittig reaction of crude 11 with
'acetylmethylidene)triphenylphosphorane in refluxing toluene gave racemic 3 and a
small amount of isomerized b-cyclocitral. It is noteworthy that the g-ionone is the
exclusive condensation product, though b-cyclocitral was formed under these reaction
conditions.
Scheme 1
i) THF, 1 equiv. NaH. ii) 1 Equiv. BuLi, then 8. iii) SnCl4, CH2Cl2. iv) Ph3PCH2, THF, reflux. v) LiAlH4, THF.
vi) ClCOCOCl, DMSO, Et3N, CH2Cl2. vii) Ph3PCHCOMe, toluene, reflux.
2.2. Enzymic Resolution of the Racemic g-Ionone. As in the case of a-and b-ionone,
the NaBH4 reduction of racemic 3 afforded 12 'Scheme 2) as a 1:1 mixture of two
racemic diastereoisomers, inseparable by the usual chromatographic procedures.
Moreover a preliminary enzymic esterification experiment on racemic 12, in the
presence of lipase PS 'Pseudomonas cepacia), with vinyl acetate in t-BuOMe solution,
provided a 1:1 mixture of enantiomerically pure acetate 'GC analysis, second and
fourth peaks). These observations show that the isomeric ionols display the same
behavior toward the enzymic esterification. Since our resolution method is based on the
enantioselective enzyme-mediated acetylation of the diastereisomerically pure allylic
alcohols, we converted 12 to its p-nitrobenzoate derivative in order to separate the
diastereoisomeric esters by fractional crystallization. Three crystallizations of the
3
)
)
)
)
For an alternative synthesis of keto ester 9, see [14b].
For optically pure 10, see [15a,b].
For a similar Wittig reaction on the methyl ester of 9, see [15a].
For optically pure 11, see [15b].
4
5
6

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Helvetica Chimica Acta ± Vol. 83 '2000)
mixture from hexane afforded 13a '27% overall yield, 98% de), which was hydrolyzed
with methanolic KOH to diastereomerically pure 13b. This latter was treated with vinyl
acetate in t-BuOMe solution in the presence of lipase PS 'Amano) to afford acetate 14
and unreacted alcohol 15. The acetate 14 was then hydrolyzed with methanolic KOH,
and the derived alcohol was oxidized with MnO2 in refluxing CHCl3 to give
enantiomerically pure 'À)-g-ionone 3. Similarly, the oxidation of the alcohol 13
afforded enantiomerically pure '‡)-g-ionone 3.
Scheme 2
i) NaBH4, MeOH. ii) 4-Nitrobenzoyl chloride 'PNB-Cl), pyridine, CH2Cl2. iii) Three crystallizations from
hexane. iv) KOH, MeOH. v) Vinyl acetate, t-BuOMe, lipase PS. vi) MnO2, CHCl3, reflux. vii) Bu3SnH,
'Ph3P)2PdCl2, THF.

Helvetica Chimica Acta ± Vol. 83 '2000)
2765
2.3. Olfactory Evaluation of '‡)- and 'À)-g-Ionone. The olfactory evaluation of
'‡)-and ' À)-g-ionone 3 was performed together with that of '‡)-and ' À)-a-ionone
17) 'Givaudan-Roure Research Ltd., Dübendorf, Switzerland). The results are
described in the Table and suggest some interesting considerations: a) '‡)-and ' À)-
g-ionone 3 show very different olfactory features, and the '‡)-'S)-g-ionone is the most
pleasant and powerful of the ionone isomers. b) The two isomeric a-ionones show
similar odor description and the olfactory threshold is almost the same. Otherwise, '‡)-
g-ionone is ca. 150 time more powerful than the 'À)-isomer.
Table. Olfactory Evaluation of a- and g-Ionone Isomers
Ionone
isomer
Olfactory evaluation
Odor threshold
[ng/l of air]
'‡)-'R)-a
Linear woody, floral odor, with an additional honey aspect.
Its odor remains linear within 10 h, but is weaker than that of
the 'S)-isomer.
3.2
'‡)-'S)-g
Linear, very pleasant, floral, green, woody odor with a very
natural violet tonality. On the blotter, it is the most powerful
and pleasant of the isomers. After 10 h, slightly earthy
nuances are also detectable in the scent.
0.07
'À)-'S)-a
'À)-'R)-g
Floral, woody, with an additional honey aspect. More
powerful than the 'R)-isomer, though, after 10 h on blotter, the
odors of both isomers are quite similar.
Weak green, fruity, pineapple-like odor with metallic aspects,
quite different from the typical ionone odor. It is, however,
also slightly woody, ionone-type. With the time this woody-
ionone tonality comes more and more to the fore, but fruity
aspects remain present, even after 10 h.
2.7
10.8
2.4. Correlation of '‡)- and 'À)-g-Ionone with '‡)- and 'À)-g-Dihydroionone. As
mentioned in the Introduction, the absolute configuration of '‡)-and ' À)-3 was first
assigned by Eugster, Ohloff, and co-workers [7], and then corrected by Oritani and
Yamashita [6]. Moreover, in the light of our results, the optical-rotation values obtained
by the latter authors are modest. Though the sense and the amplitude of the chiroptical
properties reported by Oritani and Yamashita seem to be sufficient to determine the
absolute configuration of g-ionone, we decided to verify this assignment with our
enantiomerically pure '‡)-and ' À)-g-ionone free of any a-and/or b-isomers.
Consequently, we decided to reduce '‡)-3 and 'À)-3 to the related dihydroionones
16 and 17, respectively, of known absolute configuration [17]. A preliminary hydro-
genation experiment, performed with Raney-Ni as catalyst, was unsatisfactory for our
purpose. In effect, partial isomerization of the double bond occurred, and a small
amount '<10%) of the a-dihydroionone was formed. To develop a regiospecific path to
g-dihydroionone, we used a radical reduction method that was previously employed
[18] in the reduction of dehydroionones. Accordingly, we found that Bu3SnH and
catalytic amounts of 'Ph3P)2PdCl2 converted the 'À)-g-ionone and the '‡)-g-ionone to
the enantiomerically pure 'À)-g-dihydroionone ''À)-16) and '‡)-g-dihydroionone
7
)
For earlier evaluation of '‡)-and ' À)-a-ionone, see [16]. For a pronounced aptitude to perceive either one
or the other enantiomer of a-ionone, see [16d].

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Helvetica Chimica Acta ± Vol. 83 '2000)
''‡)-17), respectively, without isomerization of the CˆC bond. The measured optical
rotation values '[a]2D0 ˆ À19.8 'c ˆ 1.3, CHCl3) and [a]D20 ˆ ‡19.4 'c ˆ 1.2, CHCl3),
resp.) are in good agreement with those reported for the natural [17] '‡)-'S)-g-
dihydroionone '[a]2D0 ˆ ‡20.9 'c ˆ 10.4, CHCl3)). In conclusion, the absolute config-
urations of the '‡)-g-ionone and 'À)-g-ionone were assigned unambiguously as 'S)
and 'R), respectively.
3. Conclusion. ± The preparation of enantiomerically pure '‡)-and ' À)-g-ionone
was achieved by the lipase-mediated kinetic resolution of allylic alcohol 13b. This
synthetic path was an extension of a previously developed method that shows great
versatility. However, the high-quality results obtained in terms of chemical and
enantiomeric purity of the products are superior to those previously reported for the
synthesis of '‡)-and ' À)-g-ionone. These results allowed the olfactory evaluation of
the g-ionone isomers and a strict confirmation of their absolute configuration by
conversion in the related g-dihydroionone isomers.
The authors would like to thank Dr. Philip Kraft, Givaudan-Roure Research Ltd., Dübendorf, Switzerland,
for his kind co-operation. We gratefully acknowledge Caroline Denis, for the olfactory descriptions and Heinz
Koch for the threshold determinations. We thank MURST for partial financial support.
Experimental Part
1. General. Lipase PS Pseudomonas cepacia 'Amano Pharmaceuticals Co., Japan) was employed. TLC:
Merck silica gel 60 F254 plates. Column chromatography 'CC): silica gel. GC: DANI-HT-86.10 gas
chromatography; ee and de values were determined on a Chirasil DEX CB column '25 m  0.25 mm;
Chrompack) with the following temp. program 708 '3 min) À3.58/min À1408 À88/min À1808 '2 min); analysis
of g-ionol acetates: tR 19.05, 19.19, 19.26, 19.72; analysis of g-ionones: tR 17.10, 17.41; analysis of g-
dihydroionones: tR 16.32, 16.59; tR in min. Optical rotations: Jasco-DIP-181 digital polarimeter. IR Spectra:
Perkin-Elmer 2000 FT-IR spectrometer; films; nÄ in cmÀ1. 1H-and 13C-NMR spectra: CDCl3 solns. at r.t.; Bruker-
AC-250 spectrometer at 250 MHz '1H); chemical shifts 'd) in ppm rel. to internal Me4Si 'ˆ0 ppm), J values in
Hz. MS: Finnigan-Mat TSQ 70 spectrometer; m/z 'rel.%). Microanalyses: analyzer 1106 from Carlo Erba.
2. 'Æ)-g-Cyclogeraniol ''Æ)-10). BuLi '30.1 ml of a 10m soln. in hexane) was added dropwise to a cooled
‡
'À 788) suspension of Ph3P MeBrÀ '110 g, 0.307 mol) in dry THF '300 ml). The resulting mixture was warmed
to r.t. and stirred at this temp. until the phosphonium salt disappeared almost completely. The keto ester 9 '50 g,
0.252 mol) was added to the resulting soln. of ylide and the mixture was heated at reflux for 2 h. After cooling,
the mixture was poured into H2O and extracted with Et2O. The org. phase was successively washed with sat.
NH4Cl soln. and brine, dried 'Na2SO4), and concentrated under reduced pressure. The residue was dissolved in
hexane, and the triphenylphosphine oxide was eliminated by crystallization 'ice-bath cooling). The liquid phase
was diluted with dry THF '300 ml), was cooled '08), and LiAlH4 '9 g, 0.237 mol) was added under stirring.
After reduction of the ester, workup afforded the crude product. Purification by distillation under reduced
pressure 'b.p. 958/10 mm) gave 'Æ)-10 '34 g, 0.221 mol; 88%); 97% chemical purity 'GC). IR: 3371, 2932, 1648,
1441, 1029, 889. 1H-NMR: 4.96 'm, HÀCHˆC'5)); 4.76 'm, HÀCHˆC'5)); 3.76 ± 3.67 'dd, J ˆ 10.4, 4.9,
HÀC'7)); 3.62 't, J ˆ 10.4, HÀC'7)); 2.18 ± 2.08 'm, CH2'4)); 2.08 ± 2.00 'dd, J ˆ 10.9, 4.9, HÀC'6)); 1.64 ± 1.20
‡
'm, CH2'2), CH2'3)); 1.49 's, OH); 0.95 's, MeÀC'1)); 0.87 's, MeÀC'1)). MS: 154 '1, M ), 136 '36), 123 '49),
121 '64), 109 '51), 93 '94), 81 '70), 69 '100), 55 '31), 41 '53). Anal. calc. for C10H18O: C 77.87, H 11.76; found:
C 77.95, H 11.70.
3. 'Æ)-g-Ionone ''Æ)-3). DMSO '25 g, 0.320 mol) was added dropwise to a cooled soln. 'À 788) of
ClCOCOCl '21 g, 0.165 mol) in CH2Cl2 '200 ml). Alcohol 10 '20 g, 0.130 mol) was then added, and the mixture
was stirred for 15 min at the same temp. The resulting suspension was treated with Et3N '50 g, 0.494 mol), and
the mixture was allowed to warm to r.t. After 2 h, the mixture was diluted with CH2Cl2 and washed with H2O.
The org. phase was dried 'Na2SO4), and the solvent was evaporated. The obtained crude g-cyclocitral '92%
chemical purity 'GC)) was dissolved in toluene '150 ml) and treated with 'acetylmethylidene)triphenylphos-
phorane '50 g, 0.157 mol) under reflux for 8 h. After cooling, hexane was added to the mixture, and the Ph3PO

Helvetica Chimica Acta ± Vol. 83 '2000)
2767
was eliminated by crystallization 'ice-bath cooling). The liquid phase was concentrated under reduced pressure
and submitted to CC 'hexane/AcOEt 9.1). The eluted fractions provided b-cyclocitral '2.5 g, 16 mmol) and g-
ionone, which was then further purified by distillation under reduced pressure to give pure 'Æ)-3 '18.1 g,
1
94 mmol; 72%; 98% chemical purity 'GC)). IR: 2932, 1675, 1364, 1254, 990, 895. H-NMR: 6.93 'dd, J ˆ 15.7,
10.1, HÀC'7)); 6.08 'd, J ˆ 15.7, HÀC'8)); 4.78 's, HÀCHˆC'5)); 4.53 's, HÀCHˆC'5)); 2.57 'd, J ˆ 10.1,
HÀC'6)); 2.33 ± 2.18 'm, HÀC'4)); 2.26 's, Me'10)); 2.13 ± 1.97 'm, HÀC'4)); 1.67 ± 1.26 'm, CH2'3), CH2'2));
0.89 's, MeÀC'1)); 0.85 's, MeÀC'1)). 13C-NMR: 198.3; 148.4; 147.2; 132.7; 109.6; 57.6; 38.6; 35.6; 34.1; 29.2;
‡
27.3; 23.9; 23.1. MS: 192 '10, M ), 177 '31), 164 '13), 159 '14), 149 '100), 135 '13), 121 '70), 109 '54), 91 '27),
81 '49), 69 '48), 43 '57). Anal. calc. for C13H20O: C 81.20, H 10.48; found: C 81.25, H 10.50.
'Æ)-g-Ionol ''Æ)-12). NaBH4 '2.5 g, 66 mmol) reduction of racemic 3 '20 g, 104.2 mmol) in MeOH
'100 ml) afforded, after purification by CC 'hexane/AcOEt 8 :2), 12 '19.5 g, 100.5 mmol, 96%) as a 1:1 mixture
of two racemic diastereoisomers; 97% chemical purity 'GC). Chiral GC 'corresponding acetates): tR 19.05,
19.19, 19.26, 19.72.
Fractional Crystallization of the 4-Nitrobenzoates of 'Æ)-12 '4 stereoisomers). The ionol 12 '16 g,
82.5 mmol) in CH2Cl2 was treated with 4-nitrobenzoyl chloride '18.2 g, 98 mmol) and pyridine '20 ml). After
workup, the crude product was purified by CC 'hexane/AcOEt 9 :1) to give a racemic mixture of 4-
nitrobenzoates '25.9 g, 75.5 mmol; 91%). Three crystallizations from hexane afforded the crystalline racemic 4-
nitrobenzoate 13a '7.9 g, yield of recrystallizations 30%). M.p. 748. GC 'corresponding acetates): tR 19.05, 19.19;
de 98%. IR: 3418, 2927, 1717, 1524, 1338, 1277, 1104, 1037, 717. 1H-NMR: 8.34 ± 8.15 'm, 4 arom. H); 6.02 ± 5.90
'dd, J ˆ 14.7, 9.4, HÀC'7)); 5.71 ± 5.51 'm, HÀC'8), HÀC'9)); 4.75 's, HÀCHˆC'5)); 4.53 's, HÀCHˆC'5));
2.43 'd, J ˆ 9.4, HÀC'6)); 2.34 ± 2.21 'dt, J ˆ 13.5, 5.2, HÀC'4)); 2.10 ± 1.95 'm, HÀC'4)); 1.63 ± 1.24
‡
'm, CH2'3), CH2'2)); 1.49 'd, J ˆ 6, Me'10)); 0.86 's, MeÀC'1)); 0.79 's, MeÀC'1)). MS: 343 '3, M ), 300
'22), 270 '3), 216 '6), 193 '19), 176 '40), 161 '41), 150 '100), 133 '37), 120 '83), 105 '51), 91 '63), 79 '34), 69
'74). Anal. calc. for C20H25NO4: C 69.95, H 7.34, N 4.08; found: C 70.05, H 7.38, N 4.15.
'Æ)-'6RS,9RS)-g-Ionol ''Æ)-13b). The crystalline 4-nitrobenzoate 13a '7.7 g, 22.5 mmol) was treated with
KOH '3 g, 53.5 mmol) in MeOH '60 ml) under reflux for 2 h. After the usual workup, the alcohol obtained was
purified by CC 'hexane/AcOEt 8 :2) to afford 'Æ)-13b '4.1 g, 21.1 mmol; 94%). GC 'corresponding acetates):
tR 19.05, 19.19; de 98%. IR: 3341, 2930, 1643, 1366, 1060, 980, 890. 1H-NMR: 5.81 ± 5.72 'dd, J ˆ 15.3, 9.4,
HÀC'7)); 5.58 ± 5.50 'dd, J ˆ 15.3, 6.3, HÀC'8)); 4.72 's, HÀCHˆC'5)); 4.53 's, HÀCHˆC'5)); 4.32
'quint., J ˆ 6.3, HÀC'9)); 2.41 'd, J ˆ 9.4, HÀC'6)); 2.30 ± 2.22 'dt, J ˆ 13.4, 5.4, HÀC'4)); 2.07 ± 1.98
'm, HÀC'4)); 1.65 ± 1.43 'm, 3 H); 1.46 's, OH); 1.36 ± 1.26 'm, 1 H); 1.27 'd, J ˆ 6.4, Me'10)); 0.9
's, MeÀC'1)); 0.81 's, MeÀC'1)). 13C-NMR: 203.8; 190.1; 182.9; 161.9; 130.9; 130.6; 130.3; 122.5; 110.8; 92.7;
‡
88.8; 88.2; 83.1. MS: 194 '1, M ), 176 '17), 161 '35), 136 '100), 121 '87), 109 '60), 93 '65), 79 '44), 69 '72), 55
'25), 43 '78). Anal. calc. for C13H22O: C 80.35, H 11.41; found: C 80.43, H 11.48.
Enzymic Acetylation of 'Æ)-13b. A mixture of 'Æ)-13b '4 g, 20.6 mmol; de 99%), lipase PS 'Pseudomonas
cepacia; 4 g), and vinyl acetate '20 ml) in t-BuOMe '100 ml) was stirred at r.t. for 72 h. After filtration and
evaporation of the filtrate, the residue was chromatographed 'hexane/AcOEt 9 :1). The first-eluted fractions
afforded '6R,9R)-g-ionol acetate '14; 1.95 g, 8.3 mmol; 40%; 97% chemical purity 'GC)). Chiral GC: tR 19.19;
ee 99%. [a]2D0 ˆ ‡77.3 'c ˆ 2, CHCl3). IR: 2932, 1739, 1369, 1241, 1044, 890. 1H-NMR: 5.88 ± 5.76 'dd, J ˆ 14.5,
9.7, HÀC'7)); 5.51 ± 5.29 'm, HÀC'8), HÀC'9)); 4.73 's, HÀCHˆC'5)); 4.51 's, HÀCHˆC'5)); 2.39 'd, J ˆ
9.7, HÀC'6)); 2.32 ± 2.20 'dt, J ˆ 13.9, 5.2, HÀC'4)); 2.11 ± 1.94 'm, HÀC'4)); 2.04 's, MeCOO); 1.68 ± 1.24
‡
'm, CH2'3), CH2'2)); 1.31 'd, J ˆ 6.6, Me'10)); 0.87 's, MeÀC'1)); 0.79 's, MeÀC'1)). MS: 236 '2, M ), 203
'3), 193 '21), 176 '56), 161 '63), 133 '50), 119 '35), 105 '85), 91 '100), 79 '65), 69 '64), 55 '23), 43 '86). Anal.
calc. for C15H24O2: C 76.23, H 10.24; found: C 76.35, H 10.16.
The last-eluted fractions gave '6S,9S)-g-ionol '15; 1.8 g, 9.3 mmol; 45%; 96% chemical purity 'GC)).
Chiral GC 'corresponding acetate): tR 19.05; ee 95%. [a]2D0 ˆ ‡2.2 'c ˆ 2, CHCl3). IR, 1H-NMR, MS: in
accordance with those of 'Æ)-13b. Anal. calc. for C13H22O: C 80.35, H 11.41; found: C 80.30, H 11.45.
'À)-g-Ionone ''À)-3). A sample of 14 '1 g, 4.2 mmol) was hydrolyzed with KOH '1 g, 18 mmol) in MeOH
'30 ml). The crude ionol obtained was then oxidized with MnO2 '2 g, 23 mmol) in CHCl3 '50 ml) under reflux
for 4 h. After filtration and evaporation of the filtrate, the residue was chromatographed 'hexane/AcOEt 9 :1).
Bulb-to-bulb distillation of the product afforded pure 'À)-3 '650 mg, 3.4 mmol; 81%; 98% chemical purity
'GC)). Chiral GC: tR 17.10; ee 99%. [a]D20 ˆ À37.4 'c ˆ 1, CHCl3), [a]2D0 ˆ À30.9 'c ˆ 0.5, EtOH). IR, 1H-NMR,
13C-NMR, MS: in accordance with those of 'Æ)-3. Anal. calc. for C13H20O: C 81.20, H 10.48; found: C 81.25,
H 10.50.
'‡)-g-Ionone ''‡)-3). A sample of 15 '1 g, 5.1 mmol) was oxidized with MnO2 '3 g, 34 mmol) in CHCl3
'50 ml) under reflux for 4 h. After filtration and evaporation of the filtrate, the residue was chromatographed

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Helvetica Chimica Acta ± Vol. 83 '2000)
'hexane/AcOEt 9 :1). Bulb-to-bulb distillation of the product afforded pure '‡)-3 '850 mg, 4.4 mmol; 86%;
98% chemical purity 'GC)). Chiral GC: tR 17.41; ee 98%. [a]2D0 ˆ ‡36.2 'c ˆ 1, CHCl3), [a]D20 ˆ ‡30.2 'c ˆ 0.5,
EtOH). IR, 1H-NMR, 13C-NMR, MS: in accordance with those of 'Æ)-3. Anal. calc. for C13H20O: C 81.20,
H 10.48; found: C 81.28, H 10.45.
'À)-g-Dihydroionone ''À)-16). Bu3SnH '1.22 g, 4.2 mmol) was added dropwise to a stirred soln. of 'À)-3
'400 mg, 2.1 mmol), 'Ph3P)2PdCl2 '70 mg, 0.1 mmol), NH4Cl '250 mg, 4.7 mmol), and H2O '0.1ml, 5.6 mmol)
in 20 ml of THF under N2. After 3 h, Et2O '60 ml) was added, and the soln. was washed with brine and then
concentrated in vacuo. The residue was dissolved in AcOEt '40 ml) and stirred with a sat. soln. of NaF '10 ml)
for 5 h. The precipitate formed was filtered, and the org. phase was separated and evaporated. The residue was
chromatographed 'hexane/AcOEt 95 :5) on an alumina column 'activity grade 1). Bulb-to-bulb distillation of
the product afforded pure 'À)-16 '295 mg, 1.5 mmol; 72% yield; 95% chemical purity 'GC)). Chiral GC:
tR 16.31; ee 99%. [a]2D0 ˆ À19.8 'c ˆ 1.3, CHCl3). IR: 2934, 2868, 1717, 1645, 1363, 1162, 890, 757. 1H-NMR: 4.77
't, J ˆ 1.1, HÀCHˆC'5)); 4.52 'd, J ˆ 2.2, HÀCHˆC'5)); 2.48 ± 2.16 'm, CH2'8)); 2.09 's, Me'10)); 2.03 ± 1.90
'm, CH2'4)); 1.84 ± 1.36 'm, 6 H), 1.28 ± 1.06 'm, 1 H) 'CH2'3), CH2'2), CH'6), CH2'7)); 0.89 's, MeÀC'1));
0.84 's, MeÀC'1)). 13C-NMR: 209.4; 149.0; 109.4; 53.3; 42.3; 35.6; 34.7; 31.9; 30.1; 28.2; 26.5; 23.4; 20.2. MS: 194
‡
'3, M ), 176 '38), 161 '51), 136 '100), 121 '97), 109 '46), 93 '61), 81 '36), 69 '63), 55 '18), 43 '88). Anal. calc.
for C13H22O: C 80.35, H 11.41; found: C 80.40, H 10.45.
'‡)-g-Dihydroionone ''‡)-17). The same procedure described above was applied to reduce '‡)-3 and
afforded '‡)-17 in 75% yield and 95% chemical purity 'GC). Chiral GC: tR 16.59; ee 98%. [a]2D0 ˆ ‡19.4 'c ˆ
1.2, CHCl3). IR, 1H-NMR, 13C-NMR, MS: in accordance with those of 'À)-16. Anal. calc. for C13H22O: C 80.35,
H 11.41; found: C 80.45, H 10.40.
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Received May 22, 2000