Background of the Invention Five-membered ring is included as basic structure in many natural compounds such as prostaglandin with physio- logical activity, and also shown as basic structure in perfumery chemicals such as jasmone, etc.

Cyclopentenones play an important role in prepara- tion of physiologically active compounds with five- membered ring, and so have various uses thereof.

There are so many reports on the process for preparation of cyclopentenones, but the followings are ones closely relevant to this invention.

It has been reported in 1973 that cyclopentenones were obtained by reacting acetylene and olefin with carbon monoxide in the presence of one equivalent of dicobalt octacarbonyl [Co2 (CO) 8], in which dicobalt octacarbonyl was used to form intermediate (J. Chem.

Perkin Trans. l 1973,977; Tetrahedron 1985,41, 5855: Chem. Rev. 1988,88,1081; Org. React. 1991,40, 1). in which R, to Rlo are hydrogen or alkyl or aryl group substituted with functional group such as ketone, ester, halide, ether, and so on.

X is substituted alkyl group, oxygen, sulfur, nitrogen, substituted silicon, and so forth. n is an integer of 0 to 2.

This reaction was extensively applied to the synthesis of natural compounds, but it has serious

limitation that the functional groups sensitive to temperature could not be used in this reaction because the reaction required long reaction time and high temperature, thus the yield of resultant product is very low.

There have been another report on the process for preparation of cyclopentenones with operational simplicity and high yield. Cyclopentenones were obtained by reacting acetylene and olefin with carbon monoxide in organic solvents in the presence of homogeneous metal catalysts such as cobalt (Co), tungsten (W) or ruthenium (Ru ! (Angew. Chem. Int. Ed. Engl. 1990, 29, 1413 ; J. Ain.

('hem. Soc. 1993,115,1154; J. Am. Chem. Soc. 1994,716, 3159 ; J. Am. Chem. Soc. 1994, zu 8793; J. Am. Chem.

Soc. 1994,118,2285; J. Org. Chem. 1997,62,3762 ; J Am. Chem. Soc. 1997,119,6187). 0 54 rus Ri 4 _ R4 I I RS R CO R2 R6 Co, W or Ru catalyst RZ R Rs organic solvent 6 RgRe R, o % F2io C X R9 fizz zu organic solvent organ! c sotventp

in which R, to RIO are hydrogen; or alkyl or aryl group substituted with functional group such as ketone, ester, halide, ether, and so on.

X is substituted alkyl group, oxygen, sulfur, nitrogen, substituted silicon, and so forth. n is an integer of 0 to 2.

This reaction has merits of operational simplicity and high yield, but also has demerits of difficult in separation and refining of the final product, cyclopente- nones, and of severe pollution by the used organic solvent. This reaction cannot be used industrially due to these demerits.

It has been also reported that cyclopentenones were successfully obtained at room temperature with the help of promoters such as trialkylamine N-oxide or sulfoxide, etc. (Tetrahedron Lett. 1990,31,5289; Synlett. 1991, 204; Organometallics, 1992,11,2044). This reaction is very efficient to prepare cyclopentenones in the labora- tory scale, thus provides chances to introduce various previously formidable functional groups, such as halides, selenides, etc. However, this condition is not applicable to industry because of the high cost of promoter, tri- alkylamine N-oxide in addition to the previously mentioned problems.

Still also, KR application No. 93-27719 discloses the process for preparation of cyclopentenones using catalysts, dicobalt octacarbonyl and triaryl phosphite; dicobalt octacarbonyl and trialkyl phosphite; or dicobalt hexacarbonyl bis-triaryl phosphite and dicobalt hexa- carbonyl bis-trialkyl phosphite. Although this reaction provided very efficient way for industrial scale, considerable amount of organic solvent is still required.

In order to solve the above mentioned problems such as difficult separation, refining of the final product, and pollution by organic solvent, we, inventors of this invention, completed this invention by using supercriti- cal fluids as reaction solvent.

Summary of the Invention The present invention provides a process for preparation of cyclopentenones, which are one of the frequently included basic structure in materials of pharmaceuticals or perfumes, by reacting acetylenes and olefins with carbon monoxide using supercritical fluids as reaction solvent in the presence of homogeneous metal catalysts.

The present invention also providse a process for preparation of cyclopentenones by reacting enyne compound

with carbon monoxide using supercritical fluids as reaction media in the presence of homogeneous metal catalysts.

Homogeneous metal catalyst of this invention comprises catalysts containing cobalt such as dicobalt octacarbonyl, dicobalt heptacarbonyl triphenylphosphite and so on.

Supercritical fluids as reaction solvent comprises supercritical carbon dioxide and supercritical olefins.

Detailed Description of the Invention In order to attain the object of the invention, the present invention provides process for preparation of cyclopentenones by reacting i) enyne compound; or ii) mixture of compound having triple bond and compound having double bond using homogeneous metal catalyst and supercritical fluids as reaction solvent under carbon monoxide atmosphere.

The present invention will now be described in detail.

The present invention provides process for prepara- tion of cyclopentenones using supercritical fluid as reaction solvent, wherein cyclopentenone is obtained by reacting acetylenes and olefins under carbon monoxide atmosphere in the presence of homogeneous metal catalyst (Scheme I).

Scheme I

1 R3 R, 0 cru a R Rs/catalyst Rz Rs R2 I. Rs R2 R6 supercritical fluid R6 in which Ri to R6 are hydrogen; or alkyl or aryl group substituted with functional group such as ketone, ester, halide, ether, hydroxy and so on.

The present invention provides process for prepara- tion of cyclopentenones using supercritical fluid as reaction solvent, wherein cyclopentenone is obtained by reacting enyne compound under carbon monoxide atmosphere in the presence of homogeneous metal catalyst (Scheme II).

Scheme II R9 Ro CO X Ra R R9 catalyst supercriticalfluid

in which R7 to Rlo are hydrogen; or alkyl or aryl group substituted with functional group such as ketone, ester, halide, ether, hydroxy and so on.

X is substituted alkyl, oxygen, sulfur, nitrogen, substituted silicon, etc. n is an integer of 0 to 2.

Cyclopentenones can be obtained in high yield by heating reactants using supercritical fluid as a reaction solvent in the presence of homogeneous metal catalyst.

In this invention, pressure of carbon monoxide is 1 to 20 atm, and preferable to 5 to 15 atm.

In this invention, carbon dioxide or olefin compound can be used as supercritical fluid. Supercritical carbon dioxide and olefin compound are prepared by pressurizing in the reactor to the range of 100 to 200 atm at about 34°C. Ethylene and propylene can be preferably included in supercritical olefin.

Reaction temperature is higher than 60°C for maintaining supercritical state, and preferably below than 100°C for smooth proceeding of the reaction. Thus, reaction temperature is controlled at 60 to 100°C.

Also, homogeneous metal catalyst used in this invention comprises catalyst containing cobalt such as dicobalt octacarbonyl, dicobalt heptacarbonyl triphenyl-

phosphite, and so on. Dicobalt octacarbonyl is refined by sublimation before using it, and added in the range of 0.1 to 2.5 molt, and dicobalt heptacarbonyl triphenyl- phosphite is added in the range of 0.1 to 5 mol%.

Furthermore, catalysts of this invention can also include other metal, such as Ru and Rh used in carbonyla- tion of acetylenes or olefins.

In this invention, reaction is carried out using supercritical carbon dioxide or supercritical olefin as reaction solvent. Supercritical carbon dioxide is easily removed, not pollutive and has no toxicity, no smell, and no ignition property; and supercritical olefin can be obtained economically in large amount from petrochemical complex. Thus, organic solvent may not be used, the solvent is collected easily, and so the above-mentioned problems in the process for preparation of cyclopente- nones can be solved. On the other hand, scheme I is characterized that olefin is used as reactant and solvent at the same time when supercritical olefin is used as reaction solvent.

The present invention is applicable to the same category of reaction, and supercritical fluid in this invention can be properly used in industrial scale.

The present invention will now be described by

reference to specific examples chosen for the purpose of illustration, but it is apparent that the present inven- tion should not be limited by the specific embodiments hereinafter.

<Example 1> Preparation of 3,3-dicarboethoxybicyclo [3,3, 0]-oc-5-ten-7-one Diethyl propargyl allyl malonate (2.38 g, 10 mmol) and dicobalt octacarbonyl (85. 5 mg, 0.25 mmol, 2.5 molk) were charged in a reactor, and hereto was filled with carbon monoxide to 15 atm. Reaction mixture was warmed up to 34°C, then hereto was injected carbon dioxide to 60 atm, and more injected to 120 atm using liquid compress- or. It was heated at 90°C for 24 hour, then cooled down to room temperature, and excess carbon monoxide was discharged in a well ventilated hood. Reaction mixture was washed with solvent, and then distilled under reduced pressure to remove the solvent. The resultant was distilled with kugelrohr to obtain 2.18 g of the title compound as oil (8.2 mmol, yield 81 %).

<Example 2> Preparation of 3,3-dicarboethoxybicyclo [3,3, 0]-6-methyl-oc-5-ten-7-one Using diethyl methylpropargyl allyl malonate (2.52 g, 10 mmol) and dicobalt octacarbonyl (85.5 mg, 0.25 mmol, 2.5 molt) as a catalyst in supercritical carbon

dioxide by similar procedure for the example 1, 2.25 g of the title compound as oil was prepared (9.1 mmol, yield 91 %).

<Example 3> Preparation of 3, 3-dimethyl [3,3,0]-oc-5-ten-7 -one Using diethyl 4,4-dimethyl 1-heptyn-6-ene (1.22 g, 10 mmol) and dicobalt octacarbonyl (85.5 mg, 0.25 mmol, 2.5 mol%) as a catalyst in supercritical carbon dioxide by similar procedure for the example 1,1.17 g of the title compound as oil was prepared (7.8 mmol, yield 78 <BR> <BR> %).<BR>

<Example 4> Preparation of 1-benzyloxymethyl-3, 3-dicarbo- ethoxy bicyclo [3,3,0]-oc-5-ten-7-one Using diethyl methylpropargyl 2-benzyloxymethylallyl malonate (3.58 g, 10 mmol) and dicobalt octacarbonyl (85.5 mg, 0.25 mmol, 2.5 molt) as a catalyst in super- critical carbon dioxide by similar procedure for the example 1,3.17 g of the title compound as oil was prepared (8.2 mmol, yield 82 %).

Example 5> Preparation of 3,3-dicarboethoxy-8-acetoxy- methyl bicyclo [3,3,0]-oc-5-ten-7-one Using diethyl methylpropargyl 1-acetoxymethylallyl malonate (3.1 g, 10 mmol) and dicobalt octacarbonyl (85.5

mg, 0.25 mmol, 2.5 mol%) as a catalyst in supercritical carbon dioxide by similar procedure for the example 1, 2.88 g of the title compound as oil was prepared (8.5 mmol, yield 85 %).<BR>

Example 6> Preparation of 3-oxa-6-phenyl-bicyclo [3,3, 0]-oc-5-ten-7-one Using phenylpropargyl allyl ether (3.58 g, 10 mmol) and dicobalt octacarbonyl (85.5 mg, 0.25 mmol, 2.5 mol%) as a catalyst in supercritical carbon dioxide by similar procedure for the example 1,3.17 g of the title compound as oil was prepared (8.2 mmol, yield 82 %).

<Example 7> Preparation of 2-phenyl cyclopent-2-en-l-one Phenyl acetylene (1.02 g, 10 mmol) and dicobalt heptacarbonyl triphenylphosphite (0.30 g, 0.5 mmol, 5 mol%) were charged in a reactor at 34°C, and hereto was filled with carbon monoxide to 5 atm. Ethylene was injected to the reaction mixture to 50 atm, and more injected to 110 atm using liquid compressor. The reaction mixture was heated at 85°C for 48 hours, then cooled down to room temperature, and excess carbon monoxide was discharged in a well ventilated hood. The reaction mixture was washed with solvent, and then distilled under reduced pressure to remove the solvent.

The resultant was distilled with kugelrohr to obtain 1.22

g of the title compound as solid (7.7 mmol, yield 77 %).

Example 8> Preparation of 2-pentyl cyclopent-2-en-l-one Using 1-heptyne (0.96 g, 10 mmol) and dicobalt heptacarbonyl triphenylphosphite (0. 30 g, 0.5 mmol, 5 mol%) as a catalyst in supercritical ethylene by similar procedure for the example 7,1.02 g of the title compound as oil was prepared (6.7 mmol, yield 67 %).

Example 9> Preparation of 2- (3'-hydroxy) propyl cyclopent -2-en-l-one 1-Trimethylsilyloxy-4-pentyne (1.56 g, 10 mmol) and dicobalt heptacarbonyl triphenylphosphite (0.30 g, 0.5 mmol, 5 mol%) as a catalyst were reacted in supercritical ethylene by similar procedure for the example 7. Then, the reaction mixture was washed with solvent and distilled under reduced pressure to remove the solvent.

The residue was dissolved in methanol, then hereto was added 1-2 drop of IN HCl, and stirred for 1 hour. The solvent was removed under reduced pressure, and the residue was distilled with kugelrohr to obtain 1.14 g of the title compound as oil (8.1 mmol, yield 81 %).

Example 10> Preparation of 2- (2'-hydroxy) propyl cyclo- pent-2-en-1-one 2-Trimethylsilyloxy-4-pentyne (1.56 g, 10 mmol) and

dicobalt heptacarbonyl triphenylphosphite (0.30 g, 0.5 mmol, 5 mol%) as a catalyst were reacted in supercritical ethylene by similar procedure for the example 7. Then, the reaction mixture was washed with solvent and distilled under reduced pressure to remove the solvent.

The residue was dissolved in methanol, then hereto was added 1-2 drop of 1N HC1, and stirred for 1 hour. The solvent was removed under reduced pressure, and the residue was distilled with kugelrohr to obtain 1.05 g of the title compound as oil (7.5 mmol, yield 75 %).

Example 11> Preparation of 2- (1'-hydroxy) propyl cyclo- pent-2-en-1-one 3-Trimethylsilyloxy-4-pentyne (1.56 g, 10 mmol) and dicobalt heptacarbonyl triphenylphosphite (0.30 g, 0.5 mmol, 5 mol%) as a catalyst were reacted in supercritical ethylene by similar procedure for the example 7. Then, the reaction mixture was washed with solvent and distilled under reduced pressure to remove the solvent.

The residue was dissolved in methanol, then hereto was added 1-2 drop of 1N HC1, and stirred for 1 hour. The solvent was removed under reduced pressure, and the residue was distilled with kugelrohr to obtain 0.98 g of the title compound as oil (7.0 mmol, yield 70 t).

Effect of the Invention The present invention can solve the problems of prior process for preparation of cyclopentenones, like difficulty of refining reaction product and pollution due to organic solvent, by using supercritical fluids such as i) supercritical carbon dioxide, which has no smell, toxicity and ignition property; and ii) supercritical olefin, which can be obtained economically in a large amount from petrochemical complex, as reaction solvent, wherein cyclopentenone is obtained by reacting i) acety- lene compound and olefin compound; or ii) enyne compound in carbon monoxide atmosphere under the presence of homogeneous metal catalyst.