Process for the preparation of (+)-(1R) -cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid

A method for preparing 3-oxo-2-pentyl-1-cyclopentaneacetic acid or methyl 3-oxo-2-pentyl-1-cyclopentaneacetate, essentially in the form of the (+)-(1R)-cis isomer thereof. The method includes the steps of PA1 (a) catalytically hydrogenating a compound of the formula (I), ##STR1## wherein M is a hydrogen atom, an alkali metal or alkaline earth metal atom, or a group NR.sub.4, where R is a hydrogen or a lower alkyl radical, in a suitable solvent and in the presence of a catalyst consisting of an Ru(II) complex comprising chiral ligands that contain a 2,2'-bis(diphenylphosphino)-1,1'-dinaphthyl (BINAP) radical or a 1,2-bis(2,5-dialkylphospholano)benzyl (DuPHOS) radical, wherein the alkyl is a C.sub.2 or C.sub.3 radical, to give a compound of formula (II), ##STR2## wherein M has the meaning given above, essentially in the form of the (+)-(1R)-cis isomer thereof; PA1 (b) if required, acidifying, in a per se known manner, the compound of formula (II), wherein M is an alkali metal or alkaline earth metal atom, or a group N.sub.4, where R is hydrogen or a lower alkyl radical, to give (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid; and PA1 (c) if required, esterifying the resulting (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid under suitable conditions to form methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate.

This application is a 371 of PCT/IB1995/00505 filed Jun. 21, 1995. 
TECHNICAL FIELD AND PRIOR ART 
The present invention relates to the field of organic synthesis and, more 
particularly, to that of the stereoselective and enantioselective 
synthesis of optically active compounds. It concerns in particular the 
preparation of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid, or 
(+)-(1R,2S)-3-oxo-2-pentyl-1-cyclopentaneacetic acid, in a pure optically 
active form, as well as its methyl ester. 
The structure of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid is 
known. It has in fact been described by O. Miersch et al. in Phytochem. 
26, 1037 (1987). According to these authors, the above-mentioned acid was 
extracted from a culture of Botryodiplodia theobromae isolated from Cuban 
origin oranges. However, to our knowledge, there is no prior art 
description of any synthetic method for preparing this acid which is 
susceptible of convenient industrial application. 
The present invention brings precisely a solution to this problem. It 
provides the above-mentioned acid with excellent optical purity and 
essentially in the form of its (+)-(1R)-cis configuration isomer. This is 
all the more important in that 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid is a useful product 
for the preparation of methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate, the preferred isomer, 
from an olfactive point of view, of methyl dihydrojasmonate, also known 
under the tradename of Hedione.RTM. (origin: Firmenich SA, Geneva, 
Switzerland), a much appreciated ingredient of vast use in perfumery. 
Amongst the four optically active isomers of methyl dihydrojasmonate or 
Hedione.RTM., it is in fact known that methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate possesses at best the 
sought-after Hedione.RTM. odor characters, and namely its jasmine note. 
Thus, obtaining optically pure methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate is of capital importance 
in perfumery. If one considers, in addition, that to this day there is no 
synthesis of this compound that can be exploited on an industrial scale, 
the value of the present invention becomes quite understandable, since the 
latter renders it possible to industrially produce a starting product that 
can be converted on a large scale and in a profitable manner into methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate. 
DESCRIPTION OF THE INVENTION 
An object of the invention is therefore a process for the preparation of 
3-oxo-2-pentyl-1-cyclopentaneacetic acid, or of methyl 
3-oxo-2-pentyl-1-cyclopentaneacetate, essentially in the form of their 
(+)-(1R)-cis configuration isomer, characterized in that it comprises the 
following steps: 
a) the catalytic hydrogenation, in an appropriate solvent and in the 
presence of a catalyst composed of a Ru (II) complex comprising chiral 
ligands which contain a 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl 
(BINAP) type ligand or a 1,2-bis(2,5-dialkylphospholano)benzenyl (DuPHOS) 
type ligand, wherein the alkyl is a C.sub.2 or C.sub.3 radical, of a 
compound of formula 
##STR3## 
wherein M represents a hydrogen atom, an atom of an alkaline or 
alkaline-earth metal, or a NR.sub.4 group, R representing hydrogen or a 
lower alkyl radical, to obtain a compound of formula 
##STR4## 
wherein M has the meaning indicated above, essentially in the form of an 
isomer of (+)-(1R)-cis configuration; 
b) if necessary, the acidification, in a generally known manner, of the 
compound of formula (II) wherein M represents an atom of an alkaline or 
alkaline-earth metal or a NR.sub.4 group, R representing hydrogen or a 
lower alkyl radical, to obtain 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid; and 
c) if necessary, the esterification, under appropriate conditions, of the 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid thus obtained to 
form methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate. 
By alkaline or alkaline-earth metal, it is understood here any one of the 
elements in group I, or respectively II, of Mendelejev's Periodic Table. 
In this context, there can be cited more particularly sodium, potassium, 
lithium, cesium, calcium and magnesium. 
On the other hand, the lower alkyl radicals represented by symbol R, 
typically include linear or branched alkyl radicals, having 1 to 3 carbon 
atoms. 
The catalysts used in the process of the invention are ruthenium (II) 
complexes in which this metal is bonded to chiral ligands of the BINAP 
type, i.e. derived from 2,2'-bis(diphenylphosphino)-1,1-binaphthalene, or 
of the family of 1,2-bis(phospholano)benzenes or DuPHOS. Concerning the 
latter, they contain, more particularly, radicals of the 
1,2-bis(2,5-dialkylphospholano)benzenyl type, it being understood that 
"alkyl" means here a radical having 1 to 3 carbon atoms. Particular 
examples of commercially available products are 
1,2-bis(2,5-dimethylphospholano)benzenyl, currently defined as Me-DuPHOS, 
and 1,2-bis(2,5-diethylphospholano)benzenyl or Et-DuPHOS (see, for 
example, M. J. Burk, J. Amer. Chem. Soc. 1991, 113,8518). 
They are optically active compounds known for their high catalytic activity 
and which are currently used in the reactions of selective hydrogenation 
of olefines. However, in spite of the vast literature there-relative, 
namely in what concerns those containing BINAP type ligands, we were 
unable to find a single example of the use of such a catalyst in the 
hydrogenation of a cyclic and tetrasubstituted double bond, i.e. in which 
all the substituents are distinct from hydrogen, as is the case in the 
present process. It is with surprise that we observed that the 
above-mentioned hydrogenation provided a product having an essentially cis 
configuration, and this in excellent yield, even in the case where the 
starting product is 3-oxo-2-pentyl-1-cyclopentene-1-acetic acid and in 
spite of its instability. 
The hydrogenation reaction which characterizes the process of the invention 
is the result of a large number of experiments carried out by means of a 
variety of catalysts, for instance rhodium based, the structure of which 
was furthermore sometimes very close to that of the Ru(II) catalysts 
presently used. The success of the latter is all the more surprising in 
that, in spite of the prior knowledge that said rhodium based catalysts 
favored the reduction of functions analogous to that of, in particular, 
the starting acid in the process of the invention, they turned out to be 
less efficient in the reduction of 3-oxo-2-pentyl-1-cyclopentene-1-acetic 
acid, unlike the ruthenium (II) catalysts used according to the invention. 
Following a particular embodiment of the invention, the process is 
characterized in that 3-oxo-2-pentyl-1-cyclopentene-1-acetic acid is 
subjected to catalytic hydrogenation in an organic solvent, in the 
presence of bis(trifluoroacetato)(+)-(R)-BINAP!ruthenium (II) or of 
bis(trifluoroacetato) (-)-(R,R)-Et-DuPHOS!ruthenium (II). 
As the organic solvent, there can be used any solvent of current use in 
this type of reactions, for example a chlorinated hydrocarbon, an alcohol 
or other. Improved yields were obtained when using a mixture of 
dichloromethane and methanol or of tetrahydrofuran and methanol. 
Moreover, it was also observed that it was preferable to carry out the 
reaction in the presence of a nitrogen-containing organic base, for 
example a trialkylamine or a pyridine. The concentration in which this 
base can be added to the reaction medium varies within a molar ratio of 
1:1 to 4:1, relative to the Ru (II) catalyst. Very good yields in final 
product were realized when triethylamine was added in a molar ratio 
comprised between 1,5:1 up to 4:1. 
According to a particular embodiment of the process of the invention, the 
above-mentioned Ru (II) catalysts are prepared in situ, starting from 
commercial origin products and according to methods which are themselves 
known see for example, B. Heiser et al., Tetrahedron: Asymmetry 1991, 2, 
pm. 43 and 51!. 
The starting 3-oxo-2-pentyl-1-cyclopentene-1-acetic acid is prepared by 
hydrolysis of methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate described in 
U.S. Pat. No. 5,302,745 or EP 583 564! under the conditions described 
further on. 
The (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid thus obtained can 
then be used according to the invention to prepare methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate, for example through 
treatment with an excess of diazomethane in ether solution. 
Clearly, whenever the hydrogenation takes place in the presence of 
bis(trifluoroacetato)(-)-(S)-2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl 
! ruthenium (II) or of bis(trifluoroacetato)(+)-(S,S)-Et-DuPHOS!ruthenium 
(II), there is obtained (-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic 
acid, which can be used to prepare methyl 
(-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate. 
Another preferred embodiment of the invention is a process characterized in 
that a compound of formula (I) wherein M represents an atom of an alkaline 
or alkaline-earth metal, or a NR.sub.4 group, R representing hydrogen or a 
lower alkyl radical, is subjected to catalytic hydrogenation, in an 
appropriate solvent and in the presence of a catalyst composed of a 
ruthenium (II) complex and(+)-(R)-BINAP-sulfonated. 
The catalyst mentioned here-above is a ruthenium (II) complex with 
sulfonated (+)-(R)-2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl, this 
chiral ligand being obtained by sulfonation of BINAP, in a manner 
analogous to that described by Kam-to Wan et al., J. Chem. Soc. Chem. 
Comm. 1993, 1262. According to these authors, the product of said 
sulfonation seems to be mainly a tetrasulfonated BINAP, i.e. 
BINAP(SO.sub.3 Na.sub.4, the sulfonate groups being apparently attached to 
the phenyl substituents of BINAP. The detailed conditions of the 
preparation of this type of catalyst are described further on. 
Amongst the formula (I) compounds above-mentioned, used as starting 
products in this preferred embodiment of the invention, lithium 
3-oxo-2-pentyl-1-cyclopentene-1-acetate will be preferably used. 
Furthermore, these compounds of formula (I) wherein M represents an atom of 
an alkaline or alkaline-earth metal, or a NR.sub.4 group, R representing 
hydrogen or a lower alkyl radical, are novel compounds which are also an 
object of the invention. They are prepared from 
3-oxo-2-pentyl-1-cyclopentaneacetic acid as is described further on. 
As the solvent, there will be preferably used a solvant which makes it 
possible to obtain a homogeneous reaction medium. To this end, an aqueous 
solvent can be used, namely water or a mixture of water with an alcohol, 
such as for example methanol. The relative proportions of water and the 
alcohol in these mixtures were not critical. 
This embodiment of the process of the invention turned out to be very 
advantageous, allowing an easier and more efficient recovery of the 
catalyst, as well as of the hydrogenation product. 
Furthermore, if desired, the process which is the object of the present 
invention can comprise additional steps which make it possible to further 
purify the products obtained as has been described up to here and namely 
improve the cis/trans isomeric ratio of these products in the cases where 
this could prove useful. Therefore, the invention also provides a process 
such as previously described, characterized in that it further comprises 
the purification of the obtained 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid or methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclo-pentaneacetate, which purification 
comprises: 
a) the reduction of methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentane-acetate by means of lithium 
tri-(sec-butyl)-borohydride; 
b) the treatment of the thus obtained reaction mixture with H.sub.2 O.sub.2 
and an excess of NaOH, followed by the acidification of the resulting 
salt, to obtain a mixture which contains essentially 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid and 
(-)-(1R,2S,3S)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid; 
c) the thermal treatment of said mixture in toluene, with water separation 
via azeotropic distillation, followed by a treatment with potassium 
carbonate to isolate the formed (-)-(1R,8S)-8-pentyl-2-oxabicyclo 
3.2.1!octan-3-one; and 
d) the treatment of this lactone with NaOH, followed by acidification, to 
obtain practically pure 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentane-acetic acid; 
e) the oxidation of this acid by means of pyridinium chlorochromate, in the 
presence of sodium acetate; and, if necessary, 
f) the esterification, under appropriate conditions, of the thus formed 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid, to obtain 
practically pure methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate. 
The above-mentioned purification method is based on the discovery that, 
unlike the classical processes for the reduction of compounds such as 
methyl 3-oxo-2-pentyl-1-cyclopentaneacetate and analogues, which processes 
resort to the use of, for example, sodium borohydride and lead to the 
formation of mixtures of all the isomers of 
3-hydroxy-2-pentyl-1-cyclopentaneacetic acid see for example, E. Demole 
et al., Helv. Chim. Acta 45, 675 (1962)!, the use according to the 
invention of lithium tri-(sec-butyl)-borohydride or L-Selectride.RTM. 
(Aldrich), to reduce methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentane-acetate containing small 
amounts of trans isomers, turns out to be totally selective, providing 
only the compounds whose configuration is represented hereinafter (for 
racemic species) 
##STR5## 
This unexpected result proved to be of capital importance. In fact, it was 
established that, upon the saponification of these esters by means of 
NaOH, and the subsequent acidification of the resulting salts, which 
generates the formation of the corresponding acids, only the strictly 
cis-configuration acid having the formula 
##STR6## 
is able to form a lactone when subjected to thermal treatment in toluene, 
with azeotropic stripping of the water, such that the acid corresponding 
to the ester of formula (VI) remains inert under these conditions and can 
thus be separated from said formed lactone by means of potassium 
carbonate. This lactone, i.e. 8-pentyl-2-oxabicyclo3.2.1!octan-3-one, or, 
as the case may be, one of its optically active isomers, can then be 
converted into acid (Va) by way of conventional methods. This entirely 
cis-configuration acid then makes it possible to obtain 
cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid or, as the case may be, one 
of its enantiomers, in a pure form, by straight oxidation with pyridinium 
chlorochromate (PCC). 
The process of the invention above-described thus makes it possible to 
eliminate the trans configuration isomers that may eventually be present 
in any one of the products obtained as described previously, i.e. by 
hydrogenation of compounds (I), eventually followed by the acidification 
of compounds (II) and the esterification of the formed 
3-oxo-2-pentyl-1-cyclopentaneacetic acid having an essentially (1R)-cis 
configuration. This complementary purification method reveals itself 
particularly useful whenever the desired products previously obtained have 
a content in cis configuration isomers which is inferior to 95%. 
According to a preferred embodiment of the invention, the pratically pure 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid obtained in 
step d) of the process above is treated, before its oxidation, with an 
amine of formula 
##STR7## 
wherein R represents a phenyl or 1-naphthyl radical, the resulting salt 
being then crystallized in an appropriate organic solvent and the thus 
obtained crystalline salt subsequently acidified. 
This preferred embodiment is most advantageous when it is desired to also 
eliminate all traces of (-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic 
acid eventually present in the product of hydrogenation of compounds (I). 
One can thus obtain (+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic 
acid with a purity of at least 95%, the oxidation of which will enable the 
formation, with similar purity, of the desired acid mentioned earlier. 
It is clear from the above that the purification method according to the 
invention described hereabove is of far more general application than just 
the purification of the mentioned hydrogenation product. It is in fact an 
alternative process for preparing 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid, or its methyl 
ester, in a pure form, starting from racemic or optically active 
Hedione.RTM. in the form of any cis/trans isomer mixture whatsoever. 
Thanks to the essential and original steps of this process, to whit, the 
selective reduction of the starting Hedione.RTM. by means of 
L-Selectride.RTM. and the separation of the enantiomers of the 
c-3-hydroxy-c-2-pentyl-r-1-cyclopentaneacetic acid by means of the 
above-mentioned amines and their enantiomers, one can in this way prepare 
the desired (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid with a 
purity of at least 95%. The latter can then be converted, as is described 
above, into pure methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate, 
or (+)-cis-Hedione.RTM., the preferred isomer of this perfuming 
ingredient. 
According to a variant of the invention, there is thus provided a process 
for the preparation of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentane-acetic 
acid or of methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate, 
having a purity of at least 95%, characterized in that 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid is oxidized by 
means of pyridinium chlorochromate, in the presence of sodium acetate, 
and, if applicable, the thus formed 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid is esterified under 
appropriate conditions. 
The (+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid, used as 
starting product according to this variant of the process of the 
invention, is prepared via treatment of 
c-3-hydroxy-c-2-pentyl-r-1-cyclopentaneacetic acid with an amine of 
formula (V) such as defined above, followed by crystallization of the 
resulting salt in an appropriate organic solvent and the acidification of 
the crystallin salt thus obtained. 
c-3-Hydroxy-c-2-pentyl-r-1-cyclopentaneacetic acid is in turn prepared in a 
pure state according to a method consisting in: 
a) reducing methyl 3-oxo-2-pentyl-1-cyclopentaneacetate by means of lithium 
tri-(sec-butyl)-borohydride; 
b) treating the reaction product with H.sub.2 O.sub.2 and an excess of 
NaOH, followed by acidification, to obtain a mixture of 
c-3-hydroxy-c-2-pentyl-r-1-cyclopentaneacetic and 
t-3-hydroxy-t-2-pentyl-r-1-cyclopentaneacetic acids; 
c) thermally treating said mixture in toluene, with water separation by 
azeotropic distillation, followed by a treatment with potassium carbonate, 
to isolate the formed (1RS,8SR)-8-pentyl-2-oxabicyclo 3.2.1!octan-3-one; 
and 
d) treating this lactone with NaOH, followed by acidification. 
As previously cited, esterification of the practically pure 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid obtained according 
to this variant can be carried out by means of diazomethane, to provide 
methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate, or 
(+)-cis-Hedione.RTM., with equivalent purity. 
Other esterification methods can also be used, as long as they retain the 
stereochemistry of the above-mentioned acid. According to a preferred 
embodiment, there is used dimethyl dicarbonate in methanol. According to 
another advantageous embodiment, there is used dimethyl sulfate and 
potassium carbonate in an appropriate solvent, for example acetone. 
It is to be noted that 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid, used as 
starting product in this variant of the process of the invention, can also 
be directly methylated, for example by reacting it with an excess of 
diazomethane in ether solution, to provide pratically pure methyl 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetate, which can then be 
converted into (+)-cis-Hedione.RTM. via oxidation. 
If desired, the trans configuration optically active isomers of 
Hedione.RTM. can of course also be obtained in a pure form through 
epimerization of their (+)-(1R)-cis and (-)-(1S)-cis diastereomers 
prepared as mentioned above. 
The processes above-described thus enable the preparation of 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid and of methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate, the preferred isomer of 
Hedione.RTM., with an optical purity of at least 95% and a strictly cis 
configuration. And this, thanks to conversions which can be practiced on 
an industrial scale. These products, having such stereochemical and 
optical purity, are novel compounds which are also the object of the 
invention. 
The processes above further provide optically pure intermediate products 
which can be obtained on an industrial scale and are novel compounds. The 
invention also relates to these intermediate products, the use of which 
according to the invention enables the preparation of the above-cited 
optically pure final products. 
The invention will now be described in further detail by way of the 
following examples, wherein the temperatures are indicated in degrees 
centigrade and the abreviations have the usual meaning in the art.

EMBODIMENTS OF THE INVENTION 
EXAMPLE 1 
Preparation of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid 
a) (1RS,8SR)-8-pentyl-2-oxabicyclo3.2.1!octan-3-one 
A 2 l three-neck double walled flask, equipped with a thermostat, a 
magnetic stirrer and an introduction funnel, kept under argon, was charged 
with a tetrahydrofuran (THF; 1M; 200 ml) solution of L-Selectride.RTM. 
introduced into the flask via cannula. The mixture was stirred, the 
temperature kept at -20.degree. and a solution of Hedione.RTM. (methyl 
3-oxo-2-pentyl-1-cyclopentaneacetate; 40 g; 177 mmole; cis/trans mixture 
67:33) in 82 ml of THF was introduced dropwise during ca. 35 min. The 
mixture was stirred for 2 h at -20.degree. and the temperature increased 
to 0.degree.. Aqueous NaOH (3N; 250 ml) was added dropwise. After stopping 
the Ar flow, H.sub.2 O.sub.2 (30%; 250 ml; Fluka) was introduced dropwise. 
After overnight heating at 65.degree. and stirring, the product was 
allowed to cool and the THF stripped under reduced pressure. 
The resulting aqueous alcaline solution was extracted 2.times. with ether. 
The aq. alcaline phase was acidified with 3N HCl, extracted 2.times. with 
ether, dried over MgSO.sub.4 and concentrated. The product was retaken in 
100 ml of toluene and heated to reflux with a water separator for 18 h to 
cyclize into lactone. After concentrating, there were obtained 29.1 g of a 
raw mixture containing the desired lactone. 
This mixture was taken in ether and extracted 2.times. avec 100 ml of 1M 
aq. K.sub.2 CO.sub.3. The aqueous phases were extracted 3.times. with 
ether and the ether extracts washed to neutrality with water. After drying 
over MgSO.sub.4 and concentrating, 14.1 g of raw lactone were obtained. 
After bulb-to-bulb distillation under 13 Pa at 170.degree., 11.3 g of 
(1RS,8SR)-8-pentyl-2-oxabicyclo3.2.1!octan-3-one (purity: 97%; 58 mmole; 
yield 48%) were obtained. 
NMR(.sup.1 H,360 MHz): 0.89(t, J=7, 3H); 1.20-1.63(8H); 1.63-1.78(2H); 
1.87-2.03(2H); 2.06-2.18(.sup.1 H); 2.36(d, J=20, 1H, covered by broad s, 
2.32, 1H); 2.74(dxdxd, J=20, 2.0, 1.6, 1H); 4.61(broad s, 1H) .delta. ppm 
NMR(.sup.13 C): 14.0(q); 22.6(t); 25.4(t); 28.0(t); 30.0(t); 31.9(t); 
32.2(t); 34.5(d); 36.2(d); 44.8(d); 82.4(d); 171.1(s) .delta. ppm MS: 
196(2,M+), 98(50), 84(95), 83(100), 82(81), 81(75), 67(50), 55(59) 
Odor: lactonic, mushroom, fruity, floral 
All the aqueous phases resulting from the operation above were combined and 
acidified with HCl 1N, extracted 3 times with ether, dried over MgSO.sub.4 
and concentrated under reduced pressure to provide 12.4 g of raw 
t-3-hydroxy-t-2-pentyl-r-1-cyclopentaneacetic acid. 
b) c-3-hydroxy-c-2-pentyl-r-1-cyclopentaneacetic acid 
A flask was charged with 16.08 g (82.0 mmole) of the lactone obtained under 
a), 33 ml of an aqueous solution of NaOH (99 mmole) and 57 ml of THF. It 
was stirred and heated to 70.degree. during 4.5 h. Most of the THF was 
stripped by distillation. The mixture was cooled and extracted 2 times 
with ether, the extracts having been eliminated. The aqueous phase was 
acidified with aq. 3N HCl. After extracting 2 times with ether, the 
combined extracts were washed with water, dried over MgSO.sub.4, filtered 
and concentrated. The thus obtained raw residue (16.2 g; yield 82%) formed 
crystals (m.p. 74.degree.-76.degree.). The desired acid thus obtained can 
be used as such in the following step or recrystallized in 
cyclohexane/ethyl acetate to provide a product having m.p. 
79.degree.-81.degree. (colorless crystals). NMR(.sup.1 H,360 MHz): 0.89(t, 
J=6, 3H); 1.22-1.53(8H); 1.57-1.95(5H); 2.32-2.53(3H); 4.22(t, J=3.5, 1H); 
ca 5.9-7.0(broad, 2 OH) .delta. ppm NMR(.sup.13 C): 14.1(q); 22.6(t); 
25.1(t); 28.3(t); 29.5(t); 32.3(t); 33.6(t); 36.3(d); 36.5(t); 47.9(d); 
74.8(d); 179.9(s) .delta. ppm MS: 84(82), 83(98), 82(70), 81(71), 79(56), 
77(63), 55(94), 41(100) 
c) (+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid and 
(-)-(1S,2R,3S)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid 
The crystalline acid obtained under b) (8.63 g; 40.3 mmole) was dissolved 
in ethanol (190 ml) and (+)-(R)-1-phenylethylamine 4.88 g; 40.3 mmole; 
Fluka purum, enantiomeric ratio (e.r.) 98:2!. The product was concentrated 
under reduced pressure and the residue was dissolved in 300 ml of a hot 
mixture of cyclohexane/ethyl acetate 5:1 (v/v), which was allowed to 
crystallize overnight. After filtration and air drying, 5.93 g of 
crystalline product having m.p. 127.degree.-130.degree.. This product was 
recrystallized in 250 ml of a mixture of solvents identical to that 
above-mentioned to provide 4.78 g of 
(1S,2R,3S)-3-hydroxy-2-pentyl-1-cyclopentaneacetate of 
(R)-1-phenylethylammonium m.p. 132.degree.-135.degree.; 
.alpha.!.sub.20.sup.D =-4.degree. (c=1.10 g/100 ml, ethanol)!. This salt 
was taken in ether and extracted once with 35 ml of NaOH 1N. The ether 
phase was washed 2.times. with water and the combined aqueous phases 
extracted with ether. Drying of the combined organic phases over 
MgSO.sub.4, filtration and concentration provide 
(+)-(R)-1-phenylethylamine which can be recycled. 
The combined aqueous phases were acidified with 40 ml of aq. HCl (1N) and 
extracted 2.times. with ether. The product was dried over MgSO.sub.4, 
filtered and concentrated to give 2.80 g of 
(-)-(1S,2R,3S)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid, in the form 
of a colorless oil (13.1 mmole; yield 92%). 
This acid presented the analytical characters of the racemic acid described 
under b) and a .alpha.!.sub.20.sup.D =-12.degree. (c=1.15, ethanol) 
(purity: 99%; e.r. 99.2:0.8). Proceeding in a manner analogous to that 
described here-above, but using (-)-(S)-1-penylethylamine (Fluka purum; 
e.r. 98:2), there was obtained 
(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetate of 
(S)-1-phenyl-ethylammonium (m.p. 131.degree.-132.degree.; 
.alpha.!.sub.20.sup.D =+4.degree.; c=1.05, ethanol) and 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid having 
.alpha.!.sub.20.sup.D =+11.degree. (c=1.10, ethanol) (purity: 99%; e.r. 
96.5:3.5). 
These experiments were repeated with (+)-(R)-1-(1-naphthyl)ethylamine 
(Fluka purum; e.r.&gt;99:1), which provided 
(1S,2R,3S)-3-hydroxy-2-pentyl-1-cyclopentaneacetate of 
(R)-1-(1-naphthyl)ethylammonium m.p. 134.degree.-136.degree.; 
.alpha.!.sub.20.sup.D =+4.degree. (c=1.145, ethanol)!, leading to 
(-)-(1S,2R,3S)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid. The absolute 
configuration of this acid was confirmed by X-rays of the intermediate 
salt. 
On the other hand, (-)-(S)-1-(1-naphthyl)ethylamine (Fluka purum; 
e.r.&gt;99:1) gave (1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetate of 
(S)-1-(1-naphthyl)ethylammonium m.p. 134.degree.-135.degree. 
.alpha.!.sub.20.sup.D =-4.degree.(c=1.05, ethanol)! and 
(+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid. 
d) (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid and 
(-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid 
These acids were prepared from the hydroxyacids described under c), as 
follows. 
A flask equipped with a thermometer and a cooling mantle, was charged with 
5.66 g of PCC (26.3 mmole), 322 mg of anhydrous sodium acetate (3.93 
mmole) and 30 ml of CH.sub.2 Cl.sub.2. The suspension was cooled to 
-10.degree., stirred and the hydroxyacid (.about.13 mmole) in 10 ml of 
CH.sub.2 Cl.sub.2 was added all at once. The mixture was stirred at 
-10.degree. during 20 h. The reaction mixture was passed through a column 
of SiO.sub.2 in ether, and likewise the solution of CH.sub.2 Cl.sub.2 and 
the solutions from the washing of the reaction flask (with ether). The 
eluted solutions were concentrated to yield 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid having a purity of 
95% and an enantiomeric ratio of 99:1. 
The analytical characters of this compound were the following: 
.alpha.!.sub.20.sup.D =+71.degree. (c=0.985, ethanol) 
NMR(1H,360 MHz): 0.88(t, J=7, 3H); 1.17-1.47(7H); 1.55-1.69(1H); 
1.80-1.95(1H); 1.98-2.22(1H); 2.13(dxd, J=15, 10, 1H); 2.20-2.37(3H); 2.46 
(dxd, J=15, 5, 1H); 2.84(broad septet, J=5, 1H) .delta. ppm NMR(.sup.13 
C): 14.0(q); 22.5(t); 24.6(t); 25.6(t); 27.1(t); 31.8(t); 33.7(t); 
35.1(t); 35.5(d); 52.6(d); 178.6(s); 219.5(s) .delta. ppm MS: 212(2,M+), 
153(20), 142(31), 84(7), 83(100), 82(21), 67(6), 88(8) 
Its (-)-(1S)configuration enantiomer was also obtained. 
EXAMPLE 2 
Preparation of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid 
Into a Schlenk type vessel, kept anhydrous and under Ar, there was injected 
the precatalytic solution (6.75 ml) containing 47 mg (0.05 mmole) of 
bis(trifluoro-acetato)(+)-(R)-2,2'-bis-(diphenylphosphino)-1,1'-binaphthy 
l!ruthenium (II), 3-oxo-2-pentyl-1-cyclopentene-1-acetic acid (0.5 g, 2.4 
mmole), CH.sub.2 Cl.sub.2 (5 ml), methanol (5 ml) and triethylamine (10.28 
mg, 0.1 mmole, 14 .mu.l, dist. over KOH). After stirring for 5 min, the 
orange soltion was filtered through a single use filter (Acrodisc 0.45 
.mu.m) in a dry autoclave (100 ml/10.sup.7 Pa) under Ar. The autoclave was 
then connected to a source of hydrogen and rinsed 5.times. with hydrogen 
at a pressure of 10.sup.6 Pa. The autoclave was then pressurized at 
9.times.10.sup.6 Pa. Stirring at this pressure and 25.degree. was carried 
out during 120 h. Afterwards, the pressure was gently released, the 
autoclave opened and the orange solution concentrated. 
Analysis of the thus obtained 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid was carried out via 
the methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate obtained upon 
adding diazomethane in ether solution. After the usual treatment, analysis 
by gas-liquid chromatography on chiral column (commercial origin alkylated 
cyclodextrine) of the ester thus obtained showed that it consisted of a 
mixture having 85% by weight of cis configuration isomers, of which 85% of 
(+)-(1R) and 15% of (-)-(1S) (enantiomeric excess e.e. 70%), and 15% of 
impurities, amongst which 5% of trans configuration isomers of said acid. 
Identical experiments, but using triethylamine in molar ratios comprised 
between 1.4:1 and 4:1, relative to the catalyst, provided the final 
product with equivalent optical purity. 
The catalyst used was prior prepared in situ, according to the method 
described by B. Heiser, ref. cited, in this manner. 
Ru(COD)(.eta..sup.3 -methallyl).sub.2 (origin: Intex Chemikalien, Muttenz, 
Switzerland; 16 mg, 0.05 mmole) was mixed under Ar and in anhydrous 
conditions with trifluoroacetic acid (11.4 mg, 0.1 mmole) and methanol 
(0.25 ml). To the resulting suspension, there was added a solution of 
(+)-(R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (R-BINAP; origin: 
Fluka; 31 mg, 0.05 mmole) in a mixture of methanol (3 ml) and 
dichloromethane (3.5 ml) and the mixture was allowed to react under 
stirring at room temperature during 3 days. The pale yellow solution 
containing the catalyst (7.4 mmole/l) was used as such in the 
hydrogenation. 
The 3-oxo-2-pentyl-1-cyclopentene-1-acetic acid used as starting product in 
this hydrogenation was prepared as follows, by saponification of methyl 
3-oxo-2-pentyl-1-cyclopentene-1-acetate obtained as is described in U.S. 
Pat. No. 5,302,745 or EP-A1-583 564!. 
LiOH (9.48 g; 0.4 mole) was dissolved in demineralized water (160 ml). A 
solution of methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate (10 g; 94%; 42 
mmole,) in THF (200 ml) and 10 drops of ethanol were added thereto. The 
resulting mixture was stirred during 24 h at room temperature. Afterwards, 
the mixture was poured over 1000 ml of demineralized water, cooled to 
0.degree.-5.degree. and neutralised with concentrated HCl. Extraction with 
dichloromethane provided 9 g of a raw oil containing about 85% of 
3-oxo-2-pentyl-1-cyclopentene-1-acetic acid. 
NMR(1H,360 MHz): 0.87(t, 3H); 1.2-1.4(m, 6H); 2.2(t, 2H); 2.45(m, 2H); 
2.66(m, 2H); 3.5(s, 2H); 8.4(broad s, 1H) .delta. ppm NMR(.sup.13 C): 
13.95(q); 22.44(t); 23.23(t); 27.97(t); 29.84(t); 31.79(t); 34.37(t); 
36.56(t); 143.54(s); 163.86(s); 173.65(s); 210.01(s) .delta. ppm 
EXAMPLE 3 
Preparation of (-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid 
Prepared in identical manner to that described in Example 2, by 
hydrogenation of 3-oxo-2-pentyl-1-cyclopentene-1-acetic acid, in the 
presence of 
bis(trifluoroacetato)(-)-(S)-2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl 
! ruthenium (II) the latter having been obtained as described in Example 
2, starting from Ru(COD)(.eta..sup.3 -methallyl).sub.2 and S-BINAP 
(origin: Fluka)!. The (-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic 
acid presented a purity analogous to that of its enantiomer described in 
Example 2. 
EXAMPLE 4 
Preparation of methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate 
A. By methylation of (+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetic 
acid described in Example 1 c) and subsequent oxidation of the resulting 
product. 
To the above-mentioned acid (2.67 g; 12.5 mmole) dissolved in 5 ml of 
ether, cooled by means of an ice bath, there was slowly added a solution 
of diazomethane in ether (0.2M), until the yellow color persisted. After 
addition of still a slight excess of this solution, the mixture was left 
at room temperature overnight. After evaporating the solvent, 2.85 g of 
methyl (+)-(1R,2S,3R)-3-hydroxy-2-pentyl-1-cyclopentaneacetate 
(purity.about.99%; e.r. 96.5:3.5) were obtained. 
.alpha.!.sub.20.sup.D =+17.degree. (c=1.795, methanol) NMR(.sup.1 H,360 
MHz): 0.89(t, J=7, 3H); 1.22-1.50(8H); 1.53-1.93(5H); 2.32-2.52(3H); 
3.67(s, 3H); 4.20(dxt, J=4, 1.5, 1H) .delta. ppm NMR(.sup.13 C): 14.1(q); 
22.7(t); 25.1(t); 28.4(t); 29.5(t); 32.3(t); 33.7(t); 36.4(d); 36.6(t); 
47.9(d); 51.4(q); 74.8(d); 174.8(s) .delta. ppm MS: 136(62), 84(63), 
83(79), 81(71), 74(100), 67(58),55(66), 41(62) 
This ester (2.85 g) was then oxidized by means of PCC, in the presence of 
sodium acetate, in a manner analogous to the method described in Example 1 
d), to yield 2.68 g of the desired methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate (colorless oil; purity 
98.5%; yield 92.7%). 
.alpha.!.sub.20.sup.D =+69.degree. (c=1.49, methanol); +83.5.degree. 
(c=1.19, chloroform) cis/trans ratio 95:5 e.r. 97.0:3.0 NMR(.sup.1 H,360 
MHz): 0.89(t,J=6.7, 3H); 1.13-1.45(7H); 1.52-1.69(1H); 1.77-1.88(m, 8 
peaks, 1H); 1.95-2.08(1H); 2.08(dxd, J=15.4, 10.1, 1H); 2.14-2.33(3H); 
2.39(dxd, J=15.4, 5.3, 1H); 2.83(broad septet, J=5.3), 3.70(s, 3H) .delta. 
ppm NMR(.sup.13 C): 14.0(q); 22.5(t); 24.7(t); 25.7(t); 27.2(t); 31.9(t); 
33.7(t); 35.1(t); 35.8(d); 51.7(q); 52.7(d); 173.0(s); 219.2(s) .delta. 
ppm MS: 226(8,M+), 156(29), 153(29), 96(11), 83(100), 82(31), 55(23), 
41(22) 
By methylation of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid 
described in Example 1 
Upon applying to this acid the treatment with diazomethane analogous to 
that described under A., the desired product was obtained with similar 
characteristics to those described above. 
C. By methylation of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid 
described in Example 2 
To the (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid obtained 
according to Example 2 (residue resulting from the concentration of the 
orange solution) there was added an excess of diazomethane in the form of 
a 2% solution in sulfuric ether and the mixture was stirred during 15 min. 
After concentration under reduced pressure, pentane (12 ml) was added to 
precipitate the catalyst. Filtering over 150 mg of silica gel (0.04-0.063 
mm) in a pasteur pipette and rinsing with pentane (12 ml) were carried 
out. The filtrate was concentrated. Thus, 0.5 g of a mixture containing 
85% of methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate with an 
enantiomeric excess of 70% (determined through analysis by gas-liquid 
chromatography on chiral column) were obtained. 
The product thus obtained was purified following the process described in 
Example 1, to obtain a starting 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid of enhanced purity, 
which was then methylated by means of diazomethane, in an analogous manner 
to that described above, to yield methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate with identical purity to 
that of the product described under A. 
EXAMPLE 5 
Preparation of methyl (-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate 
This compound was prepared from 
(-)-(1S,2R,3S)-3-hydroxy-2-pentyl-1-cyclopentaneacetic acid see Example 1 
c)! in an analogous manner to that described in Example 4 A. 
The methyl (-)-(1S)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate (colorless 
oil; purity 98.6%) possessed identical analytical characters to those of 
its (+)-(1R) cis configuration enantiomer, excepting: 
.alpha.!.sub.20.sup.D =-66.degree. (c=1.39, methanol); -88.degree. 
(c=1.24, chloroform) cis/trans ratio 94:6 e.r. 98.0:2.0 
The intermediate methyl (-)-(1S,2R,3S)-3-hydroxy-2-pentyl-1-cyclopentane 
acetate presented a .alpha.!.sub.20.sup.D =-16.degree. (c=1.805, 
methanol) 
EXAMPLE 6 
Preparation of methyl (+)-(1S)-trans-3-oxo-2-pentyl-1-cyclopentaneacetate 
and of methyl (-)-(1R)-trans-3-oxo-2-pentyl-1-cyclopentaneacetate 
These two optically active isomers of Hedione.RTM. were prepared by 
epimerization of their respective diastereomers described in Examples 4 
and 5, by means of KNH.sub.2 in liquid NH.sub.3 at -75.degree.. 
The obtained compounds possessed analytical characters which were identical 
to those described in the literature T. Kitahara et al., Agric. Biol. 
Chem. 50, 1867 (1986)!, excepting: 
(-)-(1R)-trans configuration isomer 
.alpha.!.sub.20.sup.D =41.degree. (c=1.15, methanol); -50.degree. (c=1.20, 
chloroform) purity: 99.9% ds/trans ratio 4:96 r.e. 93.2:6.8 
(+)-(1S)-trans configuration isomer 
.alpha.!.sub.20.sup.D =+46.degree. (c=1.08, methanol); +55.degree. 
(c=1.36, chloroform) cis/trans ratio 4:96 r.e. 97.4:2.6 
EXAMPLE 7 
Preparation of (+)-(1R)-3-oxo-2-pentyl-1-cyclopentaneacetic acid and of 
methyl (+)-(1R)-3-oxo-2-pentyl-1-cyclopentaneacetate 
a) Preparation of lithium 3-oxo-2-pentyl-1-cyclopentene-1-acetate 
3-Oxo-2-pentyl-1-cyclopentene-1-acetic acid (0.5 g; 2.38 mmole) and 
Li.sub.2 CO.sub.3 (Fluka; 0.0876 g; 1.18 mmole) were mixed in water (1 
ml). After 1 h stirring, there was obtained a dear solution which was 
concentrated to dry. The residual crystals were then dissolved in 2 ml of 
methanol and the obtained solution added to 20 ml of isopropyl ether for 
crystallization. The crystals were filtered and dried under vacuum during 
60 min. The above-mentioned lithium acetate was thus obtained, in the form 
of very stable (decomposition at 190.degree.) white crystals, the 
analytical data of which were as follows: 
NMR(.sup.1 H,360 MHz,H.sub.2 O): 0.87(t, 3H); 1.1-1.4(m, 6H); 2.17(t, 2H); 
2.47(m, 2H); 2.68(m, 2H); 3.45(s, 2H) .delta. ppm NMR(.sup.13 C,H.sub.2 
O): 16.14(q); 24.65(t); 25.07(t); 30.11(t); 33.05(t); 33.7(t); 37.19(t); 
43.23(t); 143.89(s); 176.96(s); 179.76(s); 218.28(s) .delta. ppm MS: 
193(2), 167(100), 151(54), 137(13), 123(11), 110(57), 95(10), 91(4) 
The structure of the product was also confirmed by electron spray mass 
spectrometry. 
The other analogue acetates were prepared in identical manner, by means of 
the appropriate carbonates, to whit, sodium, potassium, cesium, ammonium, 
triethylammonium carbonate and others. 
The compound described above will generally be prepared in situ by 
admixture of the starting acid and Li.sub.2 CO.sub.3 in water, as 
described above, the clear solution obtained after 1 h stirring being used 
as such in the hydrogenation. 
b) Preparation of bis(trifluoroacetato)(+)-(R)-BINAP-sulfonated!ruthenium 
(II) 
We prepared the (+)-(R)-BINAP-sulfonated starting from (+)-(R)-BINAP or 
(+)-(R)-2,2'-bis(diphenylphosphino)-1,1-binaphthalene (see Example 2), 
proceeding in identical manner to that described by Kam-to Wan et al. 
(ref. cited) and illustrated in the following scheme: 
##STR8## 
The structure of the (+)-(R)-BINAP-sulfonated is represented according to 
the hypothesis formulated by said authors. Moreover, it is possible to 
increase the BINAP sulfonation, i.e. the number of SO.sub.3 Na groups 
bonded thereto, by modifying the reaction conditions. 
The obtained (+)-(R)-BINAP-sulfonated (112 mg) was added to 4 ml of 
methanol and 2 ml of water and the solution stirred during 24 h at room 
temperature, under argon. This solution was then mixed with the suspension 
obtained by reacting Ru(COD)(.eta..sup.3 -methallyl).sub.2 and 
trifluoroacetic acid as is described in Example 2. The mixture was stirred 
during 3 days at room temperature and under Ar to obtain an almost clear 
brown-orange containing the desired catalyst and which was used as such in 
the hydrogenation. 
The (-)-(S)-BINAP-sulfonated and the corresponding Ru(II) complex were 
prepared in an analogous manner. 
c) The solutions obtained under a) and b) were mixed and the mixture 
stirred during 3-5 days under Ar. The resulting solution was charged in an 
autoclave and hydrogenated at 90.times.10.sup.5 Pa and r.t. during 42 h 
until 97% conversion. The autoclave was decompressed, the reaction mixture 
recovered and brought to pH 3.5 by adding 1N HCl. This mixture was 
extracted with sulfuric ether, once with (5 ml) and once with (3 ml). The 
ether extract was treated with an excess of diazomethane and then 
concentrated. Pentane (1 ml) and a spatula of Na.sub.2 SO.sub.4 were added 
to the residue and it was stirred for 5 min. It was filtered and 
concentrated. There were thus obtained 0.5 g of pure methyl 
(+)-(1R)-3-oxo-2-pentyl-1-cyclopentaneacetate (chromatography of this 
product indicated a cis/trans ratio of 95:5; ratio 
(+)-(1R)-cis/(-)-(1S)-cis 95:5, therefore 90% e.e.). 
The (+) -(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid obtained in the 
form of the above-mentioned ether solution (before treatment with 
diazomethane) had the same purity characteristics as its mentioned methyl 
ester. 
The enantiomers of these products were prepared with comparable purity in 
an analogous manner. 
EXAMPLE 8 
Preparation of (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid and of 
methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate 
a) Preparation of bis(trifluoroacetato)(-)-(R,R)-Et-DuPHOS!ruthenium (II) 
A solution of Ru(COD)(.eta..sup.3 -methallyl).sub.2 (48 mg; 0.15 mmole) in 
3 ml of tetrahydrofuran (THF) was treated with 46 .mu.l (0.60 mmole, 4 
eq.) of CF.sub.3 COOH and the resulting solution stirred during 2 h at 
r.t. The THF and the excess of CF.sub.3 COOH were stripped under strong 
vacuum and the yellow solid thus obtained was taken in 3 ml of THF. There 
were added 54.3 mg (0.15 mmole) of (-)-Et-DuPHOS (origin: Strem) and the 
resulting solution was left under stirring at r.t. during 4 days, 
protected from the light. 9 Ml of methanol were then added and the 
obtained solution containing the desired catalyst was used as such in the 
following hydrogenation. All the operations were carried out under Ar and 
with degassed solvents. 
b) To a solution of 252 mg (1.20 mmole) 3-oxo-2-pentyl-1 
cyclopentene-1-acetic acid, in a mixture of 7 ml of THF and 21 ml of 
methanol, there were added 2 ml of the catalyst solution obtained in a) 
(0.025 mmole, 0.021 eq.) and 10.4 .mu.l of triethylamine (0.075 mmole, 3 
eq.) under stirring at r.t. This solution, prepared in the glass container 
of a standard autoclave, was introduced in this autoclave, which was 
locked, put under a pressure of 45.times.10.sup.5 Pa of hydrogen and 
stirred at r.t. The reaction was followed by gas chromatography and was 
completed in about 4 h. After 1 night, the contents were evaporated under 
vacuum at r.t., the residue taken in ether, washed with HCl 10.1N and then 
water, dried over MgSO.sub.4 and filtered. The thus obtained 
(+)-(1R)-3-oxo-2-pentyl-1-cyclopentaneacetic acid was esterified by means 
of diazomethane to yield methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate, the chromatographic 
analysis (GC) of which indicated 97% purity, 96:4 cis/trans ratio and 95:5 
(+)-(1R)-cis/(-)-(1S)-cis ratio. 
EXAMPLE 9 
Preparation of methyl (+)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate 
a) 104 Mg (0.49 mmole) of (+)-cis-3-oxo-2-pentyl-1-cyclopentaneacetic acid 
(97:3 cis/trans ratio) in 0.5 ml of methanol were treated with 76 .mu.l of 
dimethyl dicarbonate CH.sub.3 O(CO)O(CO)OCH.sub.3, origin: Bayer; 96 mg, 
0.72 mmole, 1.5 eq.!. The resulting solution was heated to 45.degree. 
during 16 h and then evaporated under vacuum. After distillation of the 
residue in a bulb-to-bulb apparatus (oven t. 150.degree./10 Pa), there 
were obtained 100 mg (0.44 mmole, yield 90%) of pure methyl 
(.+-.)cis-3-oxo-2-pentyl-1-cyclopentaneacetate (97:3 cis/trans ratio). 
b) To 104 mg (0.49 mmole) of (.+-.)cis-3-oxo-2-pentyl-1-cyclopentaneacetic 
acid (93:7 cis/trans ratio) in 1 ml of (CH.sub.3).sub.2 CO there were 
added, first 56 .mu.l of (CH.sub.3).sub.2 SO.sub.4 (74 ml, 0.59 mmole, 1.2 
eq.) and then 81 mg (0.59 mmole, 1.2 eq.) of anhydrous solid K.sub.2 
CO.sub.3. The resulting suspension was heated at r.t. during 4 h and taken 
in water and with ether. The ether phase was separated and the aqueous 
phase once more extracted with ether. The combined organic phases were 
washed with water, dried over MgSO.sub.4, filtered and concentrated. The 
residue was distilled in a bulb-to-bulb apparatus (oven t.: 180.degree./7 
Pa) to provide 93 mg (0.44 mmole, yield 84%) of methyl 
(.+-.)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate (92/8 cis/trans ratio). 
When one used as starting product in the processes described above an 
optically active acid such as obtained in Example 8, one obtained methyl 
(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate with the same optical 
and stereochemical characteristics as that described in Example 8.