Method for producing fragrance intermediate

Abstract

The present invention relates to the field of organic synthesis, and more particularly to a method for preparing compounds of formula (I) by cross-metathesis reaction, which compounds of formula (I) are valuable novel chemical intermediates for the preparation of perfuming ingredients and are also part of the present invention.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and more specifically, to a method for producing a compound of formula (I) by cross-metathesis reaction. The compound of formula (I) above is a valuable novel chemical intermediate for producing fragrance components and is also part of the present invention.

[0002] Background Some of the most sought-after components in the fragrance field are those that impart a floral impression. In this odor family, methyldihydrojasmonate and cis-jasmone are major natural-derived fragrance components that impart an odor similar to the floral feel of jasmine. One of the valuable intermediates for producing them is (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one. However, the presence of the double bond in the Z configuration generally makes it difficult to obtain those compounds obtained by the Wittig reaction or the selective hydrogenation of the corresponding triple bond. Most of the reported methods for obtaining (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one use expensive starting materials, expensive conditions such as Wittig conditions, and may additionally require protection / deprotection steps.

[0003] Helvetica Chimica Acta, 1978, 2524 reports that (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one is obtained by adding 1,4-dibromo-2-pentene to cyclopentanone to form a spiro compound, followed by a [1,5] hydrogen shift. However, the production of 1,4-dibromo-2-pentene requires the use of highly toxic bromine.

[0004] Therefore, there is still a need to develop a more inexpensive and direct approach to (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one.

[0005] The present invention enables the obtaining of compounds of formula (I) which can be readily converted to (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one via basic treatment and pyrolysis by cross-metathesis between commercially available or readily accessible compounds of formula (II) and (III).

[0006] Summary of the Invention The present invention relates to a novel method that enables the production of compounds of formula (I) starting from compounds of formula (II) and (III) while avoiding the use of toxic reagents.

[0007] Accordingly, a first object of the present invention is a compound of formula (I) [Chemical formula] [wherein n is an integer from 1 to 4; R 1 and R 2 are, independently of one another, a hydrogen atom or a C 1~3 alkyl group; and X represents a halogen atom or an OR' group, where R' is a hydrogen atom, a C 1~6 alkyl group, a C 2~6 alkenyl group, a benzyl group, a trimethylsilyl group, a tetrahydrofuran-2-yl group, a tetrahydro-2H-pyran-2-yl group, a CO(O) m R'' group, a CH 2 (OR''') group, a CH(OR''')CH 3 group or a SO 2 R'''' group, where m is 0 or 1, R'' is a hydrogen atom, a C 1~6 alkyl group or a phenyl group, R''' is a C 1~6 alkyl group, and R'''' represents a methyl group, a trifluoromethyl group, a phenyl group or a tolyl group], in the form of any one of its stereoisomers or a mixture thereof, in the presence of a metathesis catalyst, with a compound of formula (II) [Chemical formula] [wherein n and R 1has the same meaning as defined in formula (I), and R 3 and R 4 each independently represent a hydrogen atom or a C 1~6 alkyl group optionally substituted by an oxo group], a compound in the form of any one of its stereoisomers or a mixture thereof, and formula (III) [Chemical formula] [wherein X and R 2 have the same meaning as defined in formula (I), and R 5 each independently represent a hydrogen atom or a C 1~5 alkyl group optionally substituted by the X group defined above, especially optionally substituted by a halogen atom], a compound in the form of any one of its stereoisomers or a mixture thereof, and is produced by cross-metathesis between them.

[0008] A second object of the present invention is a compound of the formula [Chemical formula] [wherein n is an integer from 1 to 4; R 1 and R 2 each independently represent a hydrogen atom or a C 1~3 alkyl group; and X represents a halogen atom or an OR' group, where R' is a hydrogen atom, a C 1~6 alkyl group, a C 2~6 alkenyl group, a benzyl group, a trimethylsilyl group, a tetrahydrofuran-2-yl group, a tetrahydro-2H-pyran-2-yl group, a CO(O) m R'' group, a CH 2 (OR''') group, a CH(OR''')CH 3 group or a SO 2 R'''' group, where m is 0 or 1, R'' represents a hydrogen atom, a C 1~6 alkyl group or a phenyl group, and R''' represents a C 1~6A compound that represents an alkyl group and R'''' represents a methyl group, a trifluoromethyl group, a phenyl group, or a tolyl group, and is a compound in the form of any one of its stereoisomers or a mixture thereof.

[0009] Description of the Invention Surprisingly, here, by performing a cross-metathesis reaction between a compound of formula (II) and a compound of formula (III), followed by basic treatment, and then [1,5] hydrogen shift, it has been found that (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one, which is a major structural unit for fragrance components, can be produced in an advantageous manner. Under the conditions of the present invention, direct acquisition of (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one with high selectivity for Z stereochemistry becomes possible.

[0010] Therefore, a first object of the present invention is a compound of formula (I)

Chemical formula

[0011] For the sake of clarity, the wave bond or its analogue in the compound of formula (I) has the ordinary meaning understood by those skilled in the art, i.e., the double bond can have a cis configuration, a trans configuration or a mixture thereof.

[0012] The term "optionally" is understood to mean that a particular group to be optionally substituted can or cannot be substituted by a particular functional group.

[0013] The terms "alkyl" and "alkenyl" are understood to include cyclic, branched, and straight-chain alkyl and alkenyl groups, preferably straight-chain alkyl and alkenyl groups. The term "alkenyl" is understood to include one, two, or three olefinic double bonds, preferably one olefinic double bond.

[0014] The term "oxo group" is understood to mean any group of the formula =O; that is, including, for example, ketones or aldehydes. In other words, a C optionally substituted by an oxo group 1~6 The alkyl group is an alkyl group having 1 to 6 carbon atoms, and one of these carbon atoms (including the terminal carbon) may be substituted with an =O group in place of two hydrogen atoms.

[0015] According to any embodiment of the present invention, regardless of the specific aspect, compound (I) and the corresponding compounds (II) and (III) can be in the form of any one of their stereoisomers or a mixture thereof.

[0016] For clarity, the term stereoisomer means any diastereoisomer, enantiomer, racemate.

[0017] In fact, the compounds (I), (II) or (III) may have at least one stereocenter that can have different stereochemistries (i.e., if two stereocenters are present, the compounds (I), (II) or (III) may have an (R,R), (S,S), (S,R) or (R,S) configuration). Each of the above stereocenters can be in the relative configuration R or S or a mixture thereof. In other words, the compounds of the above formula (I), (II) or (III) can be in the form of pure enantiomers or pure diastereoisomers or in the form of a mixture of stereoisomers. In addition, the compounds of the above formula (I), (II) or (III) may be in the form of their E isomers or Z isomers or a mixture thereof. For example, the present invention includes a composition comprising one or more compounds of formula (I), (II) or (III) having the same chemical structure but different stereoconfigurations of the double bond.

[0018] According to any one of the above embodiments of the present invention, the compound of the above formula (I) is a C 9 ~C 15 compound.

[0019] According to any embodiment of the present invention, n can be 1 or 2. In particular, n can be 1.

[0020] According to any embodiment of the present invention, R 1 can be a hydrogen atom or a methyl group, particularly a hydrogen atom.

[0021] According to any embodiment of the present invention, R 2 can represent a C 1~3 alkyl group. In particular, R 2 can represent a methyl group or an ethyl group. Even more specifically, R 2 can represent a methyl group.

[0022] According to any embodiment of the present invention, X can be a halogen atom or an OR' group, where R' is a C 1~6 alkyl group, a C 2~6 alkenyl group, a trimethylsilyl group, CO(O) mThe group R'', CH(OR''')CH 3 group or SO 2 represents the group R'''', where m is 0 or 1, and R'' represents a C 1~6 alkyl group, R''' represents a C 1~6 alkyl group, and R''' represents a methyl, trifluoromethyl, phenyl or tolyl group. In particular, X may be a halogen atom, an OR' group, where R' is a hydrogen atom, C 1~6 alkyl group, C 2~6 alkenyl group, acetyl group, methoxymethyl group, ethoxymethyl group, 1-butoxyethyl group, 1-ethoxyethyl group, trimethylsilyl group, methanesulfonyl group, benzenesulfonyl group or toluenesulfonyl group. In particular, X may be a halogen atom, an OR' group, where R' is a C 1~6 alkyl group, C 2~6 alkenyl group, acetyl group, methanesulfonyl group, benzenesulfonyl group, or toluenesulfonyl group. In particular, X may be a halogen atom, an OR' group, where R' is a hydrogen atom, acetyl group, methoxymethyl group, ethoxymethyl group, 1-butoxyethyl group, 1-ethoxyethyl group or trimethylsilyl group. In particular, X may be a halogen atom, an OR' group, where R' is a C 1~6 alkyl group, methanesulfonyl group, benzenesulfonyl group, or toluenesulfonyl group. In particular, X may be a halogen atom. Even more specifically, X may be a chloride atom.

[0023] According to any embodiment of the present invention, R 3 may represent a hydrogen atom or a C 1~3 alkyl group. In particular, R 3 may represent a hydrogen atom or a methyl group. Even more specifically, R 3 may represent a hydrogen atom.

[0024] According to any embodiment of the present invention, R 4 may represent a hydrogen atom, a C 1~3 alkyl group or a (2-oxocyclopentyl)methyl group. In particular, R4 may represent a hydrogen atom, a methyl group or an ethyl group. More specifically, R 4 may represent a hydrogen atom.

[0025] According to any embodiment of the present invention, R 5 may, independently of one another, represent a hydrogen atom, a C 1~3 alkyl group optionally substituted by a halogen atom or an OR' group, where R' represents a trimethylsilyl group, a COR'' group, a CH 2 (OR''') group or a CH(OR''')CH 3 group, where R'' represents a hydrogen atom, a C 1~6 alkyl group or a phenyl group, and R''' represents a C 1~6 alkyl group. In particular, one R 5 may be a hydrogen atom, and the other R 5 may be a hydrogen atom, a C 1~3 alkyl group optionally substituted by a halogen atom or an OR' group, where R' represents a trimethylsilyl group, a COR'' group, a CH 2 (OR''') group or a CH(OR''')CH 3 group, R'' represents a hydrogen atom, a C 1~6 alkyl group or a phenyl group, and R''' represents a C 1~6 alkyl group. In particular, one R 5 may be a hydrogen atom, and the other R 5 may be a hydrogen atom, a C 1~3 alkyl group optionally substituted by a halogen atom. In particular, one R 5 may be a hydrogen atom, and the other R 5 may be a hydrogen atom, a C 1~2 alkyl group optionally substituted by a chloride atom. More specifically, one R 5 may be a hydrogen atom, and the other R 5 may represent a hydrogen atom, an ethyl group or a 1-chloroethyl group. More specifically, R 5 may represent a hydrogen atom.

[0026] According to any embodiment of the present invention, R' is a C1~3 It may represent an alkyl group, particularly a methyl group or an ethyl group.

[0027] According to any embodiment of the present invention, R’’ represents a phenyl group or a C 1~3 It may represent an alkyl group, particularly a methyl group or an ethyl group.

[0028] According to any embodiment of the present invention, R’’’ is a C 1~4 alkyl group, particularly a C 1~3 alkyl group, and more specifically may represent a methyl group or an ethyl group.

[0029] Non-limiting examples of suitable compounds of formula (I) include 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 5-(2-oxocyclopentyl)penta-3-en-2-yl acetate, 5-(2-oxocyclopentyl)penta-3-en-2-yl methanesulfonate, 2-(4-bromopent-2-en-1-yl)cyclopentan-1-one, 2-(4-(1-butoxyethoxy)pent-2-en-1-yl)cyclopentan-1-one, 2-(4-(1-ethoxyethoxy)pent-2-en-1-yl)cyclopentan-1-one, 2-(4-((tetrahydro-2H-pyran-2-yl)oxy)pent-2-en-1-yl)cyclopentan-1-one, 2-(4-((tetrahydrofuran-2-yl)oxy)pent-2-en-1-yl)cyclopentan-1-one or 2-(4-((trimethylsilyl)oxy)pent-2-en-1-yl)cyclopentan-1-one.

[0030] Non-limiting examples of suitable compounds of formula (II) include 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one, 2-(pent-2-en-1-yl)cyclopentan-1-one, 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 2-allylcyclopentan-1-one, 2-(hex-2-en-1-yl)cyclopentan-1-one or 2-(oct-2-enyl)cyclopentan-1-one.

[0031] Non-limiting examples of suitable compounds of formula (III) include 2-chlorohex-3-ene, 2-chloropent-3-ene, 2,5-dichlorohex-3-ene, but-3-en-2-yl acetate, hex-3-ene-2,5-diyl diacetate, 2-bromohex-3-ene, 4-chloropent-2-ene, 4-bromopent-2-ene, 3-chlorobut-1-ene, 3-bromobut-1-ene, 3-(1-butoxyethoxy)but-1-ene, 3-(1-ethoxyethoxy)but-1-ene, 2-(but-3-en-2-yloxy)tetrahydrofuran, 2-(but-3-en-2-yloxy)tetrahydro-2H-pyran, (but-3-en-2-yloxy)trimethylsilane, but-3-en-2-ol or hex-3-ene-2,5-diol may be included.

[0032] The compounds of formulas (II) and (III) are commercially available compounds or can be prepared by a plurality of methods, for example, for the compound of formula (II), the method reported in J.K. Crandall, H.S. Magaha, G.K. Widener, G.A. Tharp Tetrahedron Lett., 21 (1980), pages 4807 - 4810, or for the compound of formula (III), the method reported in Journal of Organic Chemistry, 3, 409 - 413; 1938 by Kharasch, M.S. et al.

[0033] According to any embodiment of the present invention, the metathesis catalyst can be a cross-metathesis catalyst. In particular, the metathesis catalyst can be a ruthenium-based catalyst, a molybdenum-based catalyst, a rhenium-based catalyst or a tungsten-based catalyst. In particular, the metathesis catalyst can be a ruthenium-based catalyst. The ruthenium-based metathesis catalyst can be a ruthenium(II) carbene complex. The nature and type of the ruthenium-based metathesis catalyst used in the method of the present invention are not guaranteed to be described in more detail herein, nor are they exhaustive in any case, and those skilled in the art can select them based on their general knowledge. The above catalysts are listed in any case in references such as Grubbs, R.H. Handbook of Metathesis; Wiley-VCH: New York, 2003; page 1204, Volume 3, The Strem Chemiker - Vol. XXVIII No. 1, June, 2015, pages 1-24. Booklet Strem Metathesis Catalysts 2 / 2020, R. H. Grubbs, A. G. Wenzel, D. J. OLeary, E. Khosravi, Handbook of Metathesis, Wiley-VCH, Weinheim, 2015, K. Grela, Olefin Metathesis: Theory and Practice, Wiley, Hoboken, 2014 or other papers of similar nature as well as numerous patent documents in the field of metathesis processes. Non-limiting examples of suitable metathesis catalysts include (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II), (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)diiodo(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II), (1,3-dimesitylimidazolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), dichloro[1,3-bis(2,4,6 - (Trimethylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), benzylidene-bis(tricyclohexylphosphine)dichlororuthenium, dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(2-i-propoxy-5-nitrobenzylidene)ruthenium(II) diiodide, 1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(2-i-propoxy-5-nitrobenzylidene)ruthenium(II) dichloride, (1,3-dimesitylimidazolidin-2-ylidene)iodo(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), bis(1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)(3-phenyl-1H-inden-1-ylidene)ruthenium(II) dichloride, (1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), (1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)iodo(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), (2-(2,6-diethylphenyl)-3,3-dimethyl-2-azaspiro[4.5]dec-1-yl)(2-isopropoxy-5-nitrobenzylidene)ruthenium(II) dichloride, [2-(1-methylethoxy-O)phenylmethyl-C](nitrato-O,O’){rel-(2R,5R,7R)-adamantan-2,1-diyl[3-(2,4,6-(Trimethylphenyl)-1-imidazolidinylidene-2-ylidene]ruthenium, dichloro(2-isopropoxyphenylmethylene)(tricyclohexylphosphine)ruthenium(II), dichloro(3-phenyl-1H-inden-1-ylidene)bis(tricyclohexylphosphine)ruthenium(II), 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride (resin-supported), tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene][3-phenyl-1H-inden-1-ylidene]ruthenium(II) dichloride, dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(tricyclohexylphosphine)ruthenium(II), [1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]-[2-[[(4-methylphenyl)imino]methyl]-4-nitrophenolyl]-[3-phenyl-1H-inden-1-ylidene]ruthenium(II) chloride, dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][[5-[(dimethylamino)sulfonyl]-2-(1-methylethoxy-O)phenyl]methylene-C]ruthenium(II), dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-methyl-2-butenylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-methyl-2-butenylidene)(dipyridine)ruthenium(II), [1,3-bis(2,4,6-trimethylphenyl)-4-[(trimethylammonio)methyl]imidazolidin-2-ylidene]-(2-i-propoxy-5-nitrobenzylidene)dichlororuthenium(II) chloride, dichloro[1-(2,6-diisopropylphenyl)-2,2,4-Trimethyl-4-phenyl-5-pyrrolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene]dichloro[(2-isopropoxy)(5-trifluoroacetamido)benzylidene]ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](2-methoxyphenylmethylene)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-methyl-2-butenylidene)(dipyridine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(diphenylmethoxyphosphine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(triphenylphosphine)ruthenium(II), dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)diphenylphenoxiphosphine]ruthenium(II), dichloro[1,3-bis(2-isopropylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), dichloro[1-(2,4,6-trimethylphenyl)-2,2,4-trimethyl-4-phenyl-5-pyrrolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), dichloro[1-(2,6-diisopropylphenyl)-2,2,4-trimethyl-4-phenyl-5-pyrrolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), dichloro(3-methyl-2-butenylidene)bis(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][2-(N,Dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene][2-(N,N-dimethylamino)phenylmethylene]ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)(tri-n-butylphosphine)ruthenium(II), dichlorobis[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)ruthenium(II), dichlorobis[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), (1,3-di-o-tolylimidazolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), dichloro(2-isopropoxy-5-nitrophenylmethylene)(tricyclohexylphosphine)ruthenium(II), 1,3-bis(2,4,6-trimethylphenylimidazolidin-2-ylidene)chloro(tricyclohexylphosphine)-(2-oxobenzylidene)ruthenium(II), 1,3-bis(2,4,6-trimethylphenylimidazolidin-2-ylidene)chloro(tricyclohexylphosphine)-(2-oxo-5-nitrobenzylidene)ruthenium(II), 1,3-bis(2,4,6-trimethylphenylimidazolidin-2-ylidene)iodo(tricyclohexylphosphine)-(2-oxobenzylidene)ruthenium(II), (1,3-dimesitylimidazolidin-2-ylidene)dichloro(2-((2-ethoxy-2-oxoethylidene)amino)benzylidene)ruthenium(II), (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((2-ethoxy-2-oxoethylidene)amino)benzylidene)ruthenium(II), (4-((4-ethyl-4-methylpiperazin-1-ium-1-yl)methyl)-1,3-dimesitylimidazolidin-2-ylidene)dichloro(2-isopropoxybenzylidene)ruthenium(II) chloride, (4-((4-ethyl-4-methylpiperazin-1-ium-1-yl)methyl)-1,3-Dimesitylimidazolidin-2-ylidene)dichloro(2-isopropoxybenzylidene)ruthenium(II) hexafluorophosphate, (1,3-dimesityl-4-((trimethylammonio)methyl)imidazolidin-2-ylidene)dichloro(2-isopropoxybenzylidene)ruthenium(II) hexafluorophosphate, (1,3-dimesityl-4-((trimethylammonio)methyl)imidazolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II),, (1,3-Dimesityl-4-((trimethylammonio)methyl)imidazolidin-2-ylidene)dichloro(2-isopropoxybenzylidene)ruthenium(II) tetrafluoroborate, (1,3-bis(2,6-diisopropylphenyl)-4-((4-ethyl-4-methylpiperazin-1-ium-1-yl)methyl)imidazolidin-2-ylidene)dichloro(2-isopropoxybenzylidene)ruthenium(II) chloride, (1,3-bis(2,6-diisopropylphenyl)-4-((4-ethyl-4-methylpiperazin-1-ium-1-yl)methyl)imidazolidin-2-ylidene)dichloro(2-isopropoxybenzylidene)ruthenium(II) hexafluorophosphate, bis(2-(2,6-diethylphenyl)-3,3-dimethyl-2-azaspiro[4.5]decane-1-ylidene)dichloro(3-phenyl-1H-inden-1-ylidene)ruthenium(II) dichloromethane complex, [1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(tricyclohexylphosphine)-(2-oxobenzylidene)ruthenium(II) chloride, bis(tricyclohexylphosphine)[(phenylthio)methylene]ruthenium(II) dichloride, [1,3-bis(2,4,6-trimethylphenyl)-2-imidazolinylidene]-[2-[[(2-methylphenyl)imino]methyl]phenolyl]-[3-phenyl-1H-inden-1-ylidene]ruthenium(II) chloride, 1,3-bis(2,4,6-trimethylphenyl)-2-imidazolinylidene)(3-phenyl-1H-inden-1-ylidene)(4,5-dichloro-1,3-diethyl-1,3-dihydro-2H-imidazol-2-ylidene)ruthenium(II) dichloride, 3-phenyl-1H-inden-1-ylidene[bis(i-butylhovane)]ruthenium(II) dichloride, {[2-(i-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene}(tricyclohexylphosphine)ruthenium(II) dichloride, tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-Dihydroimidazol-2-ylidene[(phenylthio)methylene]ruthenium(II) dichloride, tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene][2-thienylmethylene]ruthenium(II) dichloride, tricyclohexylphosphine[2,4-dihydro-2,4,5-triphenyl-3H-1,2,4-triazol-3-ylidene][2-thienylmethylene]ruthenium(II) dichloride, tricyclohexylphosphine[4,5-dimethyl-1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene][2-thienylmethylene]ruthenium(II) dichloride, tri(i-propoxy)phosphine(3-phenyl-1H-inden-1-ylidene)[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene]ruthenium(II) dichloride, dichloro[1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene][(5-(2-ethoxy-2-oxoethanamide))-(2-isopropoxy)benzylidene]ruthenium(II), dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene][(2-isopropoxy)(5-pentafluorobenzoylamino)benzylidene]ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]{[5-(2-ethoxy-2-oxoethanamide)]-2-isopropoxybenzylidene}ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][(2-isopropoxy)(5-pentafluorobenzoylamino)benzylidene]ruthenium(II), (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-3-methyl-1-oxobutan-2-yl)oxy)benzylidene)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(pyridyl)ruthenium(II), dichloro[1,3-bis(2,4,{[2-(1-Methylacetoxy)phenyl]methylene}-(6-trimethylphenyl)-2-imidazolidinylidene ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][(2-isopropoxy)(5-trifluoroacetamido)benzylidene]ruthenium(II), dichloro[1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene][(5-isobutoxycarbonylamino)-(2-isopropoxy)benzylidene]ruthenium(II) or dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(triphenylphosphine)ruthenium(II) may be included. More specifically, the metathesis catalyst is (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II), (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)diiodo(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II), (1,3-dimesitylimidazolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), benzylidene-bis(tricyclohexylphosphine)dichlororuthenium, dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(2-i-propoxy-5-nitrobenzylidene)ruthenium(II) diiodide, 1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(2-i-propoxy-5-nitrobenzylidene)ruthenium(II) dichloride, (1,Diiodo(2-isopropoxy-5-nitrobenzylidene)(3-dimesitylimidazolidin-2-ylidene)ruthenium(II), bis(1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)(3-phenyl-1H-inden-1-ylidene)ruthenium(II) dichloride, (1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), (1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)diiodo(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride (resin supported), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(tricyclohexylphosphine)ruthenium(II), [1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]-[2-[[(4-methylphenyl)imino]methyl]-4-nitrophenyl]-[3-phenyl-1H-inden-1-ylidene]ruthenium(II) chloride, dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][[5-[(dimethylamino)sulfonyl]-2-(1-methylethoxy-O)phenyl]methylene-C]ruthenium(II), dichloro[1-(2,6-diisopropylphenyl)-2,2,4-trimethyl-4-phenyl-5-pyrrolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene]dichloro[(2-isopropoxy)(5-trifluoroacetamido)benzylidene]ruthenium(II), dichloro[1,3-bis(2,It may be selected from the group consisting of (6 - diisopropylphenyl)-2 - imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1-(2,4,6 - trimethylphenyl)-2,2,4 - trimethyl - 4 - phenyl - 5 - pyrrolidinylidene](2 - isopropoxyphenylmethylene)ruthenium(II), dichloro[1-(2,6 - diisopropylphenyl)-2,2,4 - trimethyl - 4 - phenyl - 5 - pyrrolidinylidene](2 - isopropoxyphenylmethylene)ruthenium(II), dichloro[1,3 - bis(2,6 - diisopropylphenyl)-2 - imidazolidinylidene][(2 - isopropoxy)(5 - pentafluorobenzoylamino)benzylidene]ruthenium(II), dichloro[1,3 - bis(2,4,6 - trimethylphenyl)-2 - imidazolidinylidene]{[5-(2 - ethoxy - 2 - oxoethanamide)] - 2 - isopropoxybenzylidene}ruthenium(II), dichloro[1,3 - bis(2,4,6 - trimethylphenyl)-2 - imidazolidinylidene][(2 - isopropoxy)(5 - pentafluorobenzoylamino)benzylidene]ruthenium(II), (1,3 - bis(2,6 - diisopropylphenyl)imidazolidine - 2 - yliden)dichloro(2 - ((1-(methoxy(methyl)amino)-3 - methyl - 1 - oxobutan - 2 - yl)oxy)benzylidene)ruthenium(II), dichloro[1,3 - bis(2,4,6 - trimethylphenyl)-2 - imidazolidinylidene](3 - phenyl - 1H - inden - 1 - yliden)(pyridyl)ruthenium(II), dichloro[1,3 - bis(2,4,6 - trimethylphenyl)-2 - imidazolidinylidene][(2 - isopropoxy)(5 - trifluoroacetamide)benzylidene]ruthenium(II), dichloro[1,3 - bis(2,6 - diisopropylphenyl)imidazolidine - 2 - yliden][(5 - isobutoxycarbonylamino)-(2 - isopropoxy)benzylidene]ruthenium(II) and dichloro[1,3 - bis(2,6 - diisopropylphenyl)-2 - imidazolidinylidene](3 - phenyl - 1H - inden - 1 - yliden)(triphenylphosphine)ruthenium(II).

[0034] The metathesis catalyst can be added to the reaction medium of the method of the present invention in a wide range of concentrations. As a non-limiting example, metal concentration values in the range of 2 ppm to 200,000 ppm can be mentioned with respect to the total amount of the compound of formula (II). Preferably, the metal concentration is 10 ppm to 1000 ppm, or even 30 ppm to 100 ppm. Of course, this method will also function with more catalyst. However, the optimal concentration of the metal depends on the nature of the metal, the nature of the substrate, the temperature and the desired reaction time, as is known to those skilled in the art.

[0035] According to any embodiment of the present invention, a scavenger may be added to the method of the present invention. In particular, the scavenger may be added after 30 minutes, 1 hour, 2 hours, 3 hours, 10 hours, 20 hours, 24 hours, 36 hours. Non-limiting examples of suitable scavengers include amines, 1,4-bis(2-isocyanopropyl)piperazine, pyridine, imidazole nitrile (polynitrile), sulfoxides such as DMSO, amides, thiols, Pb(OAc) 4 , 2-mercaptonicotinic acid (MNA), cysteine, chelating phosphine, triphenylphosphine oxide (TPPO), di(ethylene glycol) vinyl ether, phosphanetriyltrimethanol (THMP), Na 2 S 2 O 5 , H 2 O 2 or silica-based heterogeneous particles are included.

[0036] The scavenger can be added to the reaction medium of the method of the present invention in a wide range of concentrations. Non-limiting examples include values in the range of 5 equivalents to 10 equivalents with respect to the amount of the metathesis catalyst as scavenger concentration values. Of course, the optimal concentration of the scavenger depends on the nature of the scavenger, the nature of the substrate, the temperature used in the process and the catalyst, as well as the desired reaction time, as is known to those skilled in the art.

[0037] The compound of formula (III) can be added in a wide range of concentrations in the reaction medium of the process of the present invention. As non-limiting examples, the concentration values of the compound of formula (III) can range from 0.5 equivalents to 50 equivalents, or even from 1 equivalent to 5 equivalents, relative to the amount of the compound of formula (II). Naturally, the optimal concentration of the compound of formula (III) will depend on the nature of the compound of formula (III), the nature of the compound of formula (II), the temperature and catalyst used during the process, as well as the desired reaction time, as known to those skilled in the art.

[0038] The process of the present invention is carried out under batch conditions, semi-batch conditions or continuous conditions.

[0039] This reaction can be carried out in the absence of a solvent. If a solvent is required or used for practical reasons, any solvent currently used in metathesis reactions can be used for the purposes of the present invention. Non-limiting examples include C 6~10 aromatic solvents such as toluene or xylene; C 5~12 hydrocarbon solvents such as hexane, heptane or cyclohexane; C 4~8 ethers such as tetrahydrofuran, 2-MeTHF or MTBE; C 4~10 esters such as ethyl acetate and i-PrOAc; C 1~2 chlorinated hydrocarbons such as dichloromethane, dichloroethane, or chlorobenzene; C 2~6 primary or secondary alcohols such as isopropanol, methanol or ethanol; C 2~6 polar solvents such as acetone or HOAc; and water (neutral / acidic); or mixtures thereof are included. In particular, the above solvents can be solvents such as dichloromethane or toluene, or can be solvent-free. The choice of solvent varies depending on the metathesis catalyst and the nature of the compounds of formulas (II) and (III). Those skilled in the art can successfully select the most convenient solvent in each case to optimize the process of the present invention.

[0040] The temperature of the method of the present invention can be in the range of -10°C to 150°C, more preferably 20°C to 70°C. Of course, those skilled in the art can also select a preferred temperature according to the melting point and boiling point of the starting materials and the final product as well as the desired reaction time or conversion time.

[0041] The method of the present invention can be carried out under atmospheric pressure or reduced pressure. The method of the present invention can be carried out under an inert atmosphere, for example, under nitrogen and / or argon.

[0042] The method of the present invention can result in the formation of by-products such as dimers of compounds of formula (II) such as 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), or dimers of compounds of formula (III) such as 2,5-dichlorohex-3-ene and hex-3-ene-2,5-diyl diacetate. Most of the by-products formed can be recycled in the method of the present invention. In addition, unreacted starting materials can also be recycled in the method of the present invention.

[0043] According to any embodiment of the present invention, the compound of formula (I) is of formula (IV)

Chemical formula

Chemical formula

[0044] In other words, the method for producing the compound of formula (IV) defined above comprises the following steps: i) A step of producing a compound of formula (I) [wherein n is an integer from 1 to 4; R 1 and R 2 are, independently of each other, a hydrogen atom or a C 1~3 alkyl group; X is a halogen atom or SO 2 represents an R'''' group, where R'''' represents a methyl group, a trifluoromethyl group, a phenyl group or a tolyl group], which is a cross-metathesis step between the compound of formula (II) defined above and the compound of formula (III) defined above in the presence of a metathesis catalyst; ii) A step of producing spirocyclopropyl and subsequently performing pyrolysis; iii) Optionally performing 1,4-addition and optionally decarboxylation is included.

[0045] According to any embodiment of the present invention, in step i) of producing the compound of formula (IV), when cross-metathesis is carried out using a compound of formula (III) [wherein X is an OR' group, where R' is a C 1~6 alkyl group, a C 2~6 alkenyl group, a benzyl group, a tetrahydrofuran-2-yl group, a tetrahydro-2H-pyran-2-yl group, a trimethylsilyl group, a CO(O) m R'' group, a CH 2 (OR''') group or a CH(OR''')CH 3 group, where m is 0 or 1, R'' represents a hydrogen atom, a C 1~6 alkyl group or a phenyl group, and R''' represents a C 1~6 alkyl group], the X group is a chlorine atom or OSO2 It may further include a step of converting to an R'''' group.

[0046] According to any embodiment of the present invention, the production of spirocyclopropyl in step ii) is carried out in the presence of a base.

[0047] According to any embodiment of the present invention, R a may represent a methyl group or an ethyl group.

[0048] For the sake of clarity, the expression "one dotted line represents a carbon-carbon single bond or a carbon-carbon double bond" or a similar expression means the ordinary meaning understood by those skilled in the art, that is, all bonds (solid lines and dotted lines) between the carbon atoms connected by the above dotted line are carbon-carbon single bonds or carbon-carbon double bonds.

[0049] The compound of formula (I) is generally a novel compound and presents a number of advantages as described above and shown in the examples.

[0050] Therefore, another object of the present invention is a compound of the formula [Chemical formula] [wherein n is an integer from 1 to 4; R 1 and R 2 are, independently of each other, a hydrogen atom or a C 1~3 alkyl group; and X represents a halogen atom or an OR' group, where R' is a hydrogen atom, a C 1~6 alkyl group, a C 2~6 alkenyl group, a benzyl group, a trimethylsilyl group, a tetrahydrofuran-2-yl group, a tetrahydro-2H-pyran-2-yl group, a CO(O) m R'' group, a CH 2 (OR''') group, a CH(OR''')CH 3 group or a SO 2 R'''' group, where m is 0 or 1, R'' represents a hydrogen atom, a C 1~6 alkyl group or a phenyl group, and R''' represents a C 1~6A compound that represents an alkyl group and R'''' represents a methyl group, a trifluoromethyl group, a phenyl group or a tolyl group, and is a compound in the form of any one of its stereoisomers or a mixture thereof.

[0051] According to any embodiment of the present invention, the compound of formula (I) is as defined above for formula (I), provided that 2-(4-chlorobuta-2-enyl)cyclohexanone, cis-2-(4-hydroxy-2-penten-1-yl)cyclohexanone and cis-2-(4-hydroxy-2-penten-1-yl)cyclopentanone are excluded.

[0052] According to any embodiment of the present invention, the compound of formula (I) is of the formula

Chemical formula

[0053] Typical methods for carrying out the method of the present invention are reported in the following examples herein.

Examples

[0054] The present invention will now be described in more detail by the following examples, where the abbreviations have their usual meanings in the art and the temperature is indicated in degrees Celsius (°C). The NMR spectra were recorded on a Bruker Avance II Ultrashield 400 plus operating at 400 MHz ( 1 H) and 100 MHz ( 13 C), or a Bruker Avance III 500 operating at 500 MHz ( 1 H) and 125 MHz ( 13 C), or a Bruker Avance III 500 operating at 600 MHz ( 1 H) and 150 MHz ( 13It was obtained using a Bruker Avance III 600 cryoprobe operating at (C). The spectra were internally referenced to 0.0 ppm of tetramethylsilane. 1 1H NMR signal shifts are expressed in δ ppm, and coupling constants (J) are expressed in Hz with the following multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; b, broad (indicating unresolved coupling), and were interpreted using Bruker Topspin software. 13 13C NMR data are chemical shifts δ ppm as well as hybridization from DEPT 90 and DEPT 135 experiments, C, quaternary (s); CH, methine (d); CH 2 , methylene (t); CH 3 , methyl (q).

[0055] [Example 1] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) In a 10 mL flask, 1 g (8.05 mmol) of 2-allylcyclopentan-1-one was mixed with 2.19 g (24.16 mmol, 3 equiv) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 9.2 mg (0.0121 mmol, 0.15 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added over 3 hours (3 times, 3.05 mg). Gas evolution was observed each time the catalyst was added. Next, the mixture was stirred at room temperature overnight. After the addition of 26 mg (1.5 mol%) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) and stirring for 1 hour at room temperature, the mixture was filtered through a silica gel column and the solvent was evaporated under reduced pressure. The crude product (2.40 g) was purified by Kugelrohr distillation (45 - 140 °C, 1.6 Torr). 1.43 g (purity 80.0%) of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one (6.13 mmol, 76.1% yield) was obtained as a colorless liquid (containing 17.4% GC of 2,5-dichlorohex-3-ene). [Chemical formula]

[0056] [Example 2] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) In a 10 mL flask, 1 g (8.05 mmol) of 2-allylcyclopentan-1-one was mixed with 1.46 g (16.11 mmol, 2 equiv) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 9.2 mg (0.0121 mmol, 0.15 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added over 3 hours (3 times, 3.05 mg). Gas evolution was observed each time the catalyst was added. Next, the mixture was stirred at room temperature overnight. After the addition of 26 mg (1.5 mol%) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) and stirring for 1 hour at room temperature, the mixture was filtered through a silica gel column and the solvent was evaporated under reduced pressure. The crude product (2.03 g) was purified by Kugelrohr distillation (45 - 140 °C, 1.6 Torr). 1.2 g (purity 78.9%) of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one (5.07 mmol, 62.9% yield) was obtained as a colorless liquid (containing 15.8% GC of 2,5-dichlorohex-3-ene).

[0057] [Example 3] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene in the presence of a solvent) In a 100 mL flask, 1 g (8.05 mmol) of 2-allylcyclopentan-1-one was mixed with 1.46 g (16.11 mmol, 2 eq) of 3-chlorobut-1-ene and 40 mL of dichloromethane at room temperature under an argon atmosphere. 63 mg (0.0805 mmol, 1 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added. Next, the mixture was stirred at 40 °C for 4 h. After the addition of 88.7 mg (5 mol%) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4), the mixture was stirred at room temperature for 1 h, and then the mixed solvent was evaporated under reduced pressure (crude product 2.05 g). The crude product (2.05 g) was purified by Kugelrohr distillation (45 - 140 °C, 1.6 Torr). 1.48 g (purity 68.9%) of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one (5.46 mmol, yield 67.9%) was obtained as a colorless liquid (containing 11.1% of 2,5-dichlorohex-3-ene, 9.6% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 1.0% of 2-allylcyclopentan-1-one by GC).

[0058] [Example 4] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) In a 10 mL Schlenk tube, 2 g (16.10 mmol) of 2-allylcyclopentan-1-one was mixed with 2.92 g (32.21 mmol, 2 eq) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 13 mg (0.0167 mmol, 0.1 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added, and gas evolution was observed after the addition of the catalyst. The mixture was stirred at room temperature for 1 hour, and then 12 mg (0.0154 mmol, 0.1 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was further added. Again, gas evolution was observed, and the mixture was stirred at room temperature for 3 hours. 35 mg (1 mol%) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added, and after stirring at room temperature for 1 hour, the crude product (4.10 g) was purified by Kugelrohr distillation. The first fraction (80 °C, 1 atm) gave 1.0 g (11.04 mmol) of 3-chlorobut-1-ene. The second fraction (45 °C to 140 °C, 1.5 Torr) gave 1.70 g (54.0% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 1.4% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 17.1% of 2,5-dichlorohex-3-ene, 5.5% of 3-chlorobut-1-ene, 14.0% of 2-allylcyclopentan-1-one). The third fraction (45 °C to 140 °C, 1.5 Torr) gave 0.70 g (GC 86.8% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 3.0% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one)).The final fraction yields 0.43 g of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one).

[0059] Total amount of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one: 1.53 g (8.20 mmol, yield 51%). Total amount of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one): 475 mg (2.16 mmol, yield 26.8% - reusable in cross-metathesis reaction) Total amount of 2-allylcyclopentan-1-one: 238 mg (1.91 mmol, yield 11.9% - reusable in cross-metathesis reaction) Total amount of 3-chlorobut-1-ene: 1.09 g (12.04 mmol, yield 37.4% - reusable in cross-metathesis reaction) Total amount of 2,5-dichlorohex-3-ene: 291 mg (1.90 mmol, yield 11.8% - reusable in cross-metathesis reaction)

[0060] 2-allylcyclopentan-1-one ( 1 1H-NMR) spectral data was the same as the published data (Journal of the American Chemical Society 2011, 133, 2418 - 2420).

Chemical Structure

[0061] [Example 5] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one (0.05 mol% - 0.1 mol% of metathesis catalyst) by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) In a 5 mL Schlenk tube, 1 g (purity 98.5%, 7.93 mmol) of freshly distilled 2-allylcyclopentan-1-one was mixed with 1.46 g (15.95 mmol, 2 eq) of freshly distilled 3-chlorobut-1-ene at room temperature under an argon atmosphere, and 3.15 mg (0.0040 mmol, 0.05 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added (gas evolution was observed). Next, the mixture was stirred at room temperature for 1 hour (GC analysis: 51.7% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 16.9% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 4.9% 2,5-dichlorohex-3-ene, 23.8% 2-allylcyclopentan-1-one). The mixture was stirred at room temperature for 23 hours (GC analysis: 52.5% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 16.3% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 4.7% 2,5-dichlorohex-3-ene, 23.9% 2-allylcyclopentan-1-one), and then 3.15 mg (0.0040 mmol, 0.05 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was further added. Again, gas evolution was observed, and the mixture was stirred at room temperature for 94 hours (GC analysis: 66.9% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 11.0% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 11.2% 2,5-dichlorohex-3-ene, 8.2% 2-allylcyclopentan-1-one).8.7 mg of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added and the mixture was stirred at room temperature for 1 hour. The mixture was then filtered through a pad of SiO₂ (without addition of solvent). 2 The mixture was then filtered through a pad of SiO₂ (without addition of solvent).

[0062] [Example 6] Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one (0.016 mol% - 0.1 mol% of a metathesis catalyst) by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene In a 10 mL Schlenk tube, 3 g (purity 98.5%, 23.796 mmol) of freshly distilled 2-allylcyclopentan-1-one was mixed with 4.41 g (48.167 mmol, 2 equiv) of freshly distilled 3-chlorobut-1-ene at room temperature under an argon atmosphere, and 3.15 mg (0.0040 mmol, 0.016 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added (gas evolution was observed). Next, the mixture was stirred at room temperature for 1 hour (GC analysis: 14.4% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 7.5% 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 0.7% 2,5-dichlorohex-3-ene, 75.7% 2-allylcyclopentan-1-one). The mixture was stirred at room temperature for 23 hours (GC analysis: 14.6% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 7.9% 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 0.7% 2,5-dichlorohex-3-ene, 74.9% 2-allylcyclopentan-1-one), and then 15.75 mg (0.020 mmol, 0.084 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was further added. Again, gas evolution was observed, and the mixture was stirred at room temperature for 94 hours (GC analysis: 63.7% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 12.3% 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 8.7% 2,5-dichlorohex-3-ene, 12.3% 2-allylcyclopentan-1-one).26.5 mg of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added and the mixture was stirred at room temperature for 1 hour. The mixture was then filtered through a pad of SiO₂ (without addition of solvent). 2 through a pad of SiO₂ (without addition of solvent).

[0063] [Example 7] [Preparation of 2-(4-chloropenta-2-en-1-yl)cyclopentan-1-one (0.033 mol% to 0.1 mol% of metathesis catalyst) by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene] In a 10 mL Schlenk tube, 2 g (purity 98.7%, 15.896 mmol) of freshly distilled 2-allylcyclopentan-1-one was mixed with 2.92 g (31.893 mmol, 2 equivalents) of freshly distilled 3-chlorobut-1-ene at room temperature under an argon atmosphere, and 4.2 mg (0.00535 mmol, 0.033 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added (gas evolution was observed). Next, the mixture was stirred at room temperature for 1 hour (GC analysis: 27.6% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 12.6% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 1.3% 2,5-dichlorohex-3-ene, 56.3% 2-allylcyclopentan-1-one). The mixture was stirred at room temperature for 69 hours (GC analysis: 27.6% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 12.8% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 1.3% 2,5-dichlorohex-3-ene, 56.3% 2-allylcyclopentan-1-one), and then 8.4 mg (0.0107 mmol, 0.067 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was further added. Again, gas evolution was observed, and the mixture was stirred at room temperature for 24 hours (GC analysis: 67.0% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 9.5% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 11.8% 2,5-dichlorohex-3-ene, 8.8% 2-allylcyclopentan-1-one).17.7 mg of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added and stirred at room temperature for 1 h, after which the mixture was cooled to 10° C. 2 The mixture was filtered through a pad of (no solvent added).

[0064] A total of 6 g of 2-allylcyclopentan-1-one (48.32 mmol) and 8.79 g of 3-chlorobut-1-ene (97.07 mmol) were used (37.8 mg of GreenCat®, (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6), 49.2 mg of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS The crude product (11.416 g, 64.9% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one) of three reactions (Examples 5-7) using 51641-96-4) was purified by Kugelrohr distillation (85 °C, atm, 30 min to 130 °C, 1.1 Torr, 17 min). 5.304 g of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one (27.39 mmol, 58.8% yield) was obtained as a colorless liquid.

[0065] Total amount of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one: 5.304 g (27.39 mmol, 58.8% yield) as a colorless liquid. Total amount of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one): 780 mg (3.53 mmol, 14.6% yield - was reusable in cross-metathesis reactions) Total amount of 2-allylcyclopentan-1-one: 810 mg (6.52 mmol, 13.5% yield - was reusable in cross-metathesis reactions) Total amount of 3-chlorobut-1-ene: 2.711 g (29.94 mmol, yield 30.8% - reusable in cross-metathesis reaction). 2.32 g of 3-chlorobut-1-ene was lost due to its volatility. Total amount of 2,5-dichlorohex-3-ene: 814 mg (6.53 mmol, yield 13.5% - reusable in cross-metathesis reaction)

[0066] [Example 8] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) In a 5 mL Schlenk tube, 1 g (purity 92.3%, 7.473 mmol) of 2-allylcyclopentan-1-one was mixed with 1.46 g (16.124 mmol, 2 equivalents) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 11.66 mg (0.0121 mmol, 0.15 mol%) of (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)diiodo(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II) (CAS 2380295-90-7) was added over 3 hours (3 times, 3.87 mg). Gas evolution was observed each time the catalyst was added. Next, the mixture was stirred at room temperature overnight and analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 ).

[0067] GC analysis after 24 hours at room temperature: 6.3% of 2-allylcyclopentan-1-one, 63.4% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 12.8% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 8.7% of 2,5-dichlorohex-3-ene.

[0068] [Example 9] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) In a 5 mL Schlenk tube, 1 g (purity 92.3%, 7.473 mmol) of 2-allylcyclopentan-1-one was mixed with 1.46 g (16.124 mmol, 2 eq) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 8.59 mg (0.0121 mmol, 0.15 mol%) of dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II) (CAS 635679-24-2) was added over 3 hours (3 times, 2.86 mg). Gas evolution was observed each time the catalyst was added. Next, the mixture was stirred overnight at room temperature and analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 .

[0069] GC analysis after 24 hours at room temperature: 11.5% 2-allylcyclopentan-1-one, 55.9% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 16.9% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 6.2% 2,5-dichlorohex-3-ene.

[0070] [Example 10] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) In a 5 mL Schlenk tube, 1 g (purity 92.6%, 7.457 mmol) of 2-allylcyclopentan-1-one was mixed with 1.46 g (16.011 mmol, 2.1 eq) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 11.33 mg (0.0121 mmol, 0.15 mol%) of [1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(2-i-propoxy-5-nitrobenzylidene)ruthenium(II) diiodide (CAS 1874265-00-5) was added over 3 hours (3 times, 3.78 mg). Gas evolution was observed each time the catalyst was added. Next, the mixture was stirred at room temperature overnight and analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 .

[0071] GC analysis after 24 hours at room temperature: 5.6% 2-allylcyclopentan-1-one, 64.7% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 11.6% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 10.7% 2,5-dichlorohex-3-ene.

[0072] [Example 11] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-chlorobut-1-ene) General procedure: In a 10 mL Schlenk tube equipped with a reflux condenser, 250 mg (purity 98.2%, 1.977 mmol) of 2-allylcyclopentan-1-one was mixed with 358 mg (3.954 mmol, 2 equivalents) of 3-chlorobut-1-ene in 2.5 mL of dichloromethane at room temperature under an argon atmosphere, and 1 mol% of a catalyst was added. Next, the mixture was stirred at room temperature for 1 hour and analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a SiO 2 pad). The mixture was warmed to 40 °C (reflux), and after 1 hour, it was analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a SiO 2 pad). After adding 4 mol% of the catalyst, the mixture was stirred (refluxed) at 40 °C for an additional 2 hours and analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a SiO 2 pad).

[0073] (2-(2,6-Diethylphenyl)-3,3-dimethyl-2-azaspiro[4.5]decan-1-yl)(2-isopropoxy-5-nitrobenzylidene)ruthenium(II) dichloride cross-metathesis: GC analysis (5 mol%) after 1 hour at room temperature and 3 hours at 40 °C: 8.3% 2-allylcyclopentan-1-one, 45.5% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 25.2% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 5.6% 2,5-dichlorohex-3-ene.

[0074] Cross-metathesis with (1,3-dimesitylimidazolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II) (CAS 502964-52-5): GC analysis (5 mol%) after 1 hour at room temperature and 3 hours at 40 °C: 0.9% of 2-allylcyclopentan-1-one, 53.4% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 5.6% of 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 21.1% of 2,5-dichlorohex-3-ene.

[0075] Cross-metathesis with (1,3-dimesitylimidazolidin-2-ylidene)iodo(2-isopropoxy-5-nitrobenzylidene)ruthenium(II) (CAS 1874264-99-9): GC analysis (1 mol%) after 1 hour at room temperature and 1 hour at 40 °C: 10.3% of 2-allylcyclopentan-1-one, 55.3% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 15.6% of 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 8.4% of 2,5-dichlorohex-3-ene.

[0076] Cross-metathesis with dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolinylidene](2-isopropoxyphenylmethylene)ruthenium(II) (CAS 301224-40-8): GC analysis after 1 hour at room temperature and 1 hour at 40 °C: 3.0% of 2-allylcyclopentan-1-one, 63.3% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 10.1% of 2,2'-g(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 17.0% of 2,5-dichlorohex-3-ene.

[0077] Cross-metathesis with benzylidene-bis(tricyclohexylphosphine)dichlororuthenium (CAS 172222-30-9): GC analysis after 1 hour at room temperature and 1 hour at 40 °C (1 mol%): 2.6% 2-allylcyclopentan-1-one, 64.0% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 9.8% 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 17.2% 2,5-dichlorohex-3-ene. GC analysis after 1 hour at room temperature and 3 hours at 40 °C (5 mol%): 1.5% 2-allylcyclopentan-1-one, 65.0% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 9.8% 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 16.3% 2,5-dichlorohex-3-ene.

[0078] Cross-metathesis with bis(1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)(3-phenyl-1H-inden-1-ylidene)ruthenium(II) dichloride (CAS 2055540-61-7): GC analysis after 1 hour at room temperature and 3 hours at 40 °C (5 mol%): 4.6% 2-allylcyclopentan-1-one, 60.6% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 6.7% 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 6.1% 2,5-dichlorohex-3-ene.

[0079] Cross-metathesis with (1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)(2-isopropoxy-5-nitrobenzylidene)ruthenium(II) dichloride (CAS 2106819-64-9): GC analysis after 1 hour at room temperature and 3 hours at 40 °C (5 mol%): 0.4% 2-allylcyclopentan-1-one, 64.3% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 6.8% 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 10.4% 2,5-dichlorohex-3-ene.

[0080] (1-(2,6-Diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)(2-isopropoxy-5-nitrobenzylidene)ruthenium(II) diiodide cross-metathesis: GC analysis (5 mol%) after 1 hour at room temperature and 3 hours at 40 °C: 1.2% 2-allylcyclopentan-1-one, 44.3% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 29.4% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 9.8% 2,5-dichlorohex-3-ene.

[0081] Cross-metathesis with dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II) (CAS 246047-72-3): GC analysis (5 mol%) after 1 hour at room temperature and 3 hours at 40 °C: 0.9% 2-allylcyclopentan-1-one, 61.6% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 7.1% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 17.1% 2,5-dichlorohex-3-ene.

[0082] Cross-metathesis with dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II) (CAS 927429-61-6): GC analysis (5 mol%) after 1 hour at room temperature and 3 hours at 40 °C: 2.5% 2-allylcyclopentan-1-one, 66.0% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 5.6% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 13.8% 2,5-dichlorohex-3-ene.

[0083] Cross-metathesis with dichloro[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][2-(isopropoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) (supported on resin): GC analysis (5 mol%) after 1 h at room temperature and 3 h at 35 °C: 3.9% of 2-allylcyclopentan-1-one, 60.1% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 13.7% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 14.5% of 2,5-dichlorohex-3-ene.

[0084] Cross-metathesis with dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][[5-[(dimethylamino)sulfonyl]-2-(1-methylethoxy-O)phenyl]methylene-C]ruthenium(II) (CAS 918870-76-5): GC analysis (5 mol%) after 1 h at room temperature and 3 h at 35 °C: 2.5% of 2-allylcyclopentan-1-one, 56.1% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 8.5% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 19.9% of 2,5-dichlorohex-3-ene.

[0085] Cross-metathesis with dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II) (CAS 927429-60-5): GC analysis (5 mol%) after 1 h at room temperature and 3 h at 35 °C: 15.2% of 2-allylcyclopentan-1-one, 49.9% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 16.7% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 6.2% of 2,5-dichlorohex-3-ene.

[0086] Cross-metathesis with dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(tricyclohexylphosphine)ruthenium(II) (CAS 536724-67-1): GC analysis (5 mol%) after 1 h at room temperature and 3 h at 40 °C: 1.6% 2-allylcyclopentan-1-one, 59.8% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 8.9% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 14.8% 2,5-dichlorohex-3-ene.

[0087] Cross-metathesis with dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-methyl-2-butenylidene)(dipyridine)ruthenium(II) (CAS 357186-58-4): GC analysis (5 mol%) after 1 h at room temperature and 3 h at 35 °C: 15.1% 2-allylcyclopentan-1-one, 47.9% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 17.8% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 7.4% 2,5-dichlorohex-3-ene.

[0088] Cross-metathesis with [1,3-bis(2,4,6-trimethylphenyl)-4-[(trimethylammonio)methyl]imidazolidin-2-ylidene]-(2-i-propoxy-5-nitrobenzylidene)dichlororuthenium(II) chloride (CAS 1452227-72-3): GC analysis (5 mol%) after 1 h at room temperature and 3 h at 35 °C: 4.6% 2-allylcyclopentan-1-one, 58.2% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 15.8% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 10.1% 2,5-dichlorohex-3-ene.

[0089] Cross-metathesis with [[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene]dichloro[(2-isopropoxy)(5-trifluoroacetamido)benzylidene]ruthenium(II)] (CAS 1212008-99-5): GC analysis (1 mol%) after 1 hour at room temperature: 12.1% 2-allylcyclopentan-1-one, 59.6% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 10.5% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 7.6% 2,5-dichlorohex-3-ene. GC analysis (1 mol%) after 1 hour at room temperature and 1 hour at 35 °C: 2.7% 2-allylcyclopentan-1-one, 71.1% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 6.7% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 15.0% 2,5-dichlorohex-3-ene.

[0090] [Example 12] (Preparation of 5-(2-oxocyclopentyl)penta-3-en-2-yl acetate by cross-metathesis of 2-allylcyclopentan-1-one and but-3-en-2-yl acetate) In a 20 mL Schlenk tube, 5 g (purity 98.2%, 39.54 mmol) of 2-allylcyclopentan-1-one was mixed with 9.938 g (purity 98.1%, 85.414 mmol, 2 eq) of but-3-en-2-yl acetate at room temperature under an argon atmosphere. 46.6 mg (0.0593 mmol, 0.15 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added over 3 hours (15.5 mg per hour), and the mixture was stirred at room temperature for 24 hours. 65.4 mg (0.296 mmol) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the mixture, and stirring was continued at room temperature for 1 hour (GC analysis: 4.3% allylcyclopentan-1-one, 22.5% but-3-en-2-yl acetate, 42.6% 5-(2-oxocyclopentyl)penta-3-en-2-yl acetate, 4.8% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 15.9% hexa-3-ene-2,5-diyl diacetate). The mixture was filtered through a pad of SiO 2 (crude product 12.254 g) and purified by Kugelrohr distillation (40 °C to 170 °C, 0.39 Torr, 15 min).

[0091] Total amount of 5-(2-oxocyclopentyl)penta-3-en-2-yl acetate: 5.71 g (27.15 mmol, yield 68.7%) Total amount of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one): 0.690 g (3.13 mmol, yield 15.8% - reusable in cross-metathesis reaction) Total amount of 2-allylcyclopentan-1-one: 511 mg (4.10 mmol, yield 10.4% - reusable in cross-metathesis reaction) Total amount of hexa-3-ene-2,5-diyl diacetate: 2.00 g (9.989 mmol, yield 23.4% - reusable in cross-metathesis reaction) Total amount of but-3-en-2-yl acetate: 2.303 g (20.17 mmol, yield 23.6% - reusable in cross-metathesis reaction) [Chemical formula]

[0092] [Example 13] (Preparation of 2-(4-hydroxypent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and but-3-en-2-ol) In a 30 mL Schlenk tube, 10 g (purity 98.2%, 79.087 mmol) of 2-allylcyclopentan-1-one was mixed with 11.405 g (purity 98.1%, 158.17 mmol, 2 equivalents) of but-3-en-2-ol at room temperature under an argon atmosphere. 91.1 mg (0.1186 mmol, 0.15 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added over 3 hours (31.04 mg per hour), and the mixture was stirred at room temperature for 24 hours. 130.7 mg (0.593 mmol) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the mixture, and stirring was continued at room temperature for 1 hour (GC analysis, ratio of allylcyclopentan-1-one and hexa-3-ene-2,5-diol 68 / 32, 22.9% of 3-buten-2-ol, 27.9% of 2-(4-hydroxypent-2-en-1-yl)cyclopentan-1-one, 4.4% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one)). The mixture was passed through SiO 2Filtered through the pad (crude product 16.28 g, (GC analysis: ratio of allylcyclopentan-1-one and hex-3-ene-2,5-diol 68 / 32, 6.5% 3-buten-2-ol, 36.3% 2-(4-hydroxypent-2-en-1-yl)cyclopentan-1-one, 2.8% 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one)), and purified by Kugelrohr distillation (40 °C to 170 °C, 0.39 Torr, 15 minutes).

[0093] Total amount of 2-(4-hydroxypent-2-en-1-yl)cyclopentan-1-one: 5.656 g (33.62 mmol, yield 42.5%) Total amount of 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one): 0.494 g (2.24 mmol, yield 5.6% - reusable in cross-metathesis reaction) Ratio of total amount of 2-allylcyclopentan-1-one and hex-3-ene-2,5-diol 68 / 32: 7.45 g (5.06 g of 2-allylcyclopentan-1-one, 40.7 mmol, yield 51.4% - reusable in cross-metathesis reaction, 2.38 g of hex-3-ene-2,5-diol, 20.48 mmol, yield 25.9% - reusable in cross-metathesis reaction) Total amount of but-3-ene-2-ol: 0.277 g (3.13 mmol, yield 3.9% - reusable in cross-metathesis reaction) [Chemical formula]

[0094] [Example 14] (Preparation of 2-(4-(1-butoxyethoxy)pent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and 3-(1-butoxyethoxy)but-1-ene) In a 5 mL Schlenk tube, 0.250 g (purity 98.2%, 1.977 mmol) of 2-allylcyclopentan-1-one was mixed with 0.680 g (3.954 mmol, 2 equiv) of 3-(1-butoxyethoxy)but-1-ene at room temperature in 2.5 mL of dichloromethane under an argon atmosphere. 15.5 mg (0.0198 mmol, 1 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added and the mixture was stirred at room temperature for 24 h. The mixture was analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 ).

[0095] GC analysis: 1.2% 2-allylcyclopentan-1-one, 73.8% 2-(4-(1-butoxyethoxy)penta-2-en-1-yl)cyclopentan-1-one, 8.3% 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 1.7% 6,8,11,13-tetramethyl-5,7,12,14-tetraoxaoctadec-9-ene.

[0096] Characteristic signals of the purified sample (purity 85%) 2-(4-(1-butoxyethoxy)penta-2-en-1-yl)cyclopentan-1-one (4 major diastereomers) Characteristic signals:

Chem.

[0097] 3-(1-butoxyethoxy)but-1-ene could be prepared from but-3-en-2-ol and 1-(vinyloxy)butane (cat CF3 COOH or PPTS, THF, room temperature, 5 h, R. Menicagli, C. Malanga, M. Dell’Innocenti, L. Lardicci J. Org. Chem. 1987, 52, 5700-5704).

[0098] Characteristic signals of a purified sample (purity 85%) of 3-(1-butoxyethoxy)but-1-ene (diastereomer). [Chemical formula]

[0099] [Example 15] [Preparation of 2-(4-((trimethylsilyl)oxy)penta-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-allylcyclopentan-1-one and (but-3-en-2-yloxy)trimethylsilane] In a 5 mL Schlenk tube, 0.159 g (purity 98.2%, 1.257 mmol) of 2-allylcyclopentan-1-one was mixed with 0.389 g (2.515 mmol, 2 equiv) of (but-3-en-2-yloxy)trimethylsilane (CAS 18269-41-5) at room temperature in 1.6 mL of dichloromethane under an argon atmosphere. 9.9 mg (0.0126 mmol, 1 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added and the mixture was stirred at room temperature for 24 h. The mixture was analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 ).

[0100] GC analysis: 0.7% of 2-allylcyclopentan-1-one, 43.0% of 2-(4-((trimethylsilyl)oxy)penta-2-en-1-yl)cyclopentan-1-one, 33.2% of 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 5.1% of 2,2,4,7,9,9-hexamethyl-3,8-dioxa-2,9-disiladec-5-ene.

[0101] Characteristic signals of the purified sample (purity 96%) 2-(4-((trimethylsilyl)oxy)penta-2-en-1-yl)cyclopentan-1-one (two main diastereomers)

Chemical formula

[0102] [Example 16] (Preparation of 2-(4-chloropenta-2-en-1-yl)cyclopentan-1-one by cross-metathesis of ((E)-2-(penta-2-en-1-yl)cyclopentanone and 3-chlorobut-1-ene) In a 10 mL Schlenk tube, 2 g (13.14 mmol) of (E)-2-(penta-2-en-1-yl)cyclopentanone was mixed with 2.38 g (26.28 mmol, 2 equiv) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 51 mg (0.0657 mmol, 0.5 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added, and the mixture was stirred at room temperature for 2 hours. After adding 87 mg (5 mol%) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4), the mixture was stirred at room temperature for 1 hour. The crude product (3.98 g, GC analysis of the crude product: 29% of 2-(4-chloropenta-2-en-1-yl)cyclopentan-1-one, 12.6% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 8.6% of 2,5-dichlorohex-3-ene, 23.9% of 2-chlorohex-3-ene, 8.4% of (E)-2-(penta-2-en-1-yl)cyclopentanone) was purified by Kugelrohr distillation. The first fraction (75 °C, 1 atm) gave 0.400 g (4.43 mmol) of 3-chlorobut-1-ene. The second fraction (45 °C to 140 °C, 1.6 Torr) gave 2.72 g (GC 34.2% of 2-(4-chloropenta-2-en-1-yl)cyclopentan-1-one, 24.3% of 2-chlorohex-3-ene, 10.8% of 2,5-dichlorohex-3-ene, 11.8% of (E)-2-(penta-2-en-1-yl)cyclopentanone, 11.2% of 2-allylcyclopentan-1-one). The third fraction gave 0.63 g (10.3% of 2-(4-chloropenta-2-en-1-yl)cyclopentan-1-one, 79.0% of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one)).

[0103] Total amount of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one: 994 mg (5.32 mmol, yield 40.5%) Total amount of 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one): 498 mg (2.26 mmol, yield 34.4% - recyclable in cross-metathesis reaction) Total amount of 3-chlorobut-1-ene: 0.400 g (4.43 mmol, yield 16.8% - recyclable in cross-metathesis reaction) Total amount of 2-allylcyclopentan-1-one: 0.305 g (2.45 mmol, yield 18.7% - recyclable in cross-metathesis reaction) Total amount of 2,5-dichlorohex-3-ene: 0.294 g (1.92 mmol, yield 14.6% - recyclable in cross-metathesis reaction) Total amount of 2-chlorohex-3-ene: 0.662 g (5.57 mmol, yield 21.2% - recyclable in cross-metathesis reaction).

[0104] 2-Chlorohex-3-ene (for property evaluation) could be prepared by cross-metathesis from (E)-hex-3-ene and 2 equivalents of 3-chlorobut-1-ene using 1 mol% of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) (without solvent at room temperature). [Chemical formula]

[0105] [Example 17] [Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one) and 3-chlorobut-1-ene] In a 10 mL Schlenk tube, 1 g (4.54 mmol) of 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one) was mixed with 1.64 g (18.15 mmol, 4 eq) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 18 mg (0.0227 mmol, 0.5 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added and the mixture was stirred at room temperature for 1 hour. After the addition of 25 mg (2.5 mol%) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4), the mixture was stirred at room temperature for 30 minutes. The crude product (2.23 g, GC analysis of the crude product: 30.7% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 46.8% 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 8.6% 2,5-dichlorohex-3-ene, 10.7% 2-allylcyclopentan-1-one) was purified by Kugelrohr distillation. 0.500 g (5.52 mmol) of 3-chlorobut-1-ene was obtained with the first fraction (80 °C, 1 atm). 0.800 g (GC 51.2% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 3.4% 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 16.7% 2,5-dichlorohex-3-ene, 19.5% 2-allylcyclopentan-1-one) was obtained with the second fraction (45 °C to 130 °C, 1 atm). 0.510 g (7.0% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 81.3% 2,2’-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one), 1.9% 2-allylcyclopentan-1-one) was obtained with the third fraction.

[0106] Total amount of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one: 446 mg (2.39 mmol, yield 52.6%) Total amount of 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one): 442 mg (2.01 mmol, yield 44.3% - recyclable in cross-metathesis reaction) Total amount of 3-chlorobut-1-ene: 0.500 g (5.52 mmol, yield 30.3% - recyclable in cross-metathesis reaction) Total amount of 2-allylcyclopentan-1-one: 0.157 g (1.26 mmol, yield 13.9% - recyclable in cross-metathesis reaction) Total amount of 2,5-dichlorohex-3-ene: 0.294 g (1.92 mmol, yield 14.6% - recyclable in cross-metathesis reaction)

[0107] [Example 18] [Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one) and 2,5-dichlorohex-3-ene] In a 5 mL Schlenk tube, 200 mg (0.908 mmol) of 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one) was mixed with 166 mg (1.089 mmol, 1.2 equiv) of 2,5-dichlorohex-3-ene at room temperature under an argon atmosphere. 18 mg (0.027 mmol, 3 mol%) of NitroGrela ((1,3-dimesitylimidazolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), Apeiron CAS 502964-52-5) was added. Next, the mixture was stirred at room temperature for 6 hours and analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 ).

[0108] GC analysis after 6 hours at room temperature: 8.4% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 65.2% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 26.4% 2,5-dichlorohex-3-ene.

[0109] 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one) (purity 97%) could be prepared from 2-allylcyclopentan-1-one by cross-metathesis using 0.3 mol% of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) (without solvent, 2 hours at room temperature).

[0110] 2,5-dichlorohex-3-ene (purity 98%) could be prepared from 3-chlorobut-1-ene by cross-metathesis using 0.2 mol% of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) (without solvent, 2 hours at room temperature).

[0111] [Example 19] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis of 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one and 3-chlorobut-1-ene) In a 10 mL Schlenk tube, 2 g (13.14 mmol) of 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one was mixed with 2.38 g (26.28 mmol, 2 equiv) of 3-chlorobut-1-ene at room temperature under an argon atmosphere. 52 mg (0.0657 mmol, 0.5 mol%) of GreenCat® (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II); manufacturer: Apeiron; CAS 1448663-06-6) was added, and the mixture was stirred at room temperature for 2 h. After 2 h at room temperature, 72 mg (2.5 mol%) of SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the mixture, and stirring was continued at room temperature for 30 min. The crude product (4.02 g, GC analysis: 12.5% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 3.1% 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one), 20.3% 2,5-dichlorohex-3-ene, 53.3% 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one, 4.3% 2-allylcyclopentan-1-one, 4.0% 4-chloro-2-methylpent-2-ene) was purified by Kugelrohr distillation. The first fraction (90 °C, 1 atm) gave 0.500 g (5.52 mmol) of 3-chlorobut-1-ene. The second fraction (45 °C - 130 °C, 1 atm) gave 0.750 g (GC 2.0% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 6.0% 2,5-dichlorohex-3-ene, 88.0% 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one, 1.4% 2-allylcyclopentan-1-one). The third fraction gave 1.050 g (56.2% 2,5-dichlorohex-3-ene, 33.0% 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one, 10.7% 2-allylcyclopentan-1-one).The fourth fraction yields 0.700 g (42.6% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 43.0% 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one). The last fraction yields 0.250 g (14.4% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 8% 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one, 48.2% 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one)).

[0112] Total amount of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one: 0.349 mg (1.87 mmol, 14.2% yield) Total amount of 2,2'-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one): 0.121 g (0.55 mmol, 8.3% yield) - recyclable in cross-metathesis reaction Total amount of 2-(3-methylbut-2-en-1-yl)cyclopentan-1-one: 1.328 g (8.72 mmol, 66.4% yield - recyclable in cross-metathesis reaction) Total amount of 3-chlorobut-1-ene: 0.500 g (5.52 mmol, 21.0% yield - recyclable in cross-metathesis reaction) Total amount of 2,5-dichlorohex-3-ene: 0.635 g (4.15 mmol, 31.6% yield - recyclable in cross-metathesis reaction) Total amount of 2-allylcyclopentan-1-one: 0.111 mg (0.893 mmol, 6.8% yield - recyclable in cross-metathesis reaction) Total amount of 4-chloro-2-methylpent-2-ene: 0.161 mg (1.35 mmol, 5.2% yield - recyclable in cross-metathesis reaction)

[0113] [Example 20] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one by cross-metathesis between (2-allylcyclopentan-1-one (2,2’-but-2-ene-1,4-diyl)bis(cyclopentan-1-one) formed in situ) and 5-dichlorohex-3-ene) In a 5 mL Schlenk tube, 200 mg (1.582 mmol, purity 98.2%) of 2-allylcyclopentan-1-one was mixed with 537 mg (purity 90%, 3.16 mmol, 2 equiv) of 2,5-dichlorohex-3-ene in 2 mL of dichloromethane at room temperature under an argon atmosphere. 65 mg (0.0791 mmol, 5 mol%) of Hoveyda-Grubbs Catalyst® M71 SIPr ([1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene]dichloro[(2-isopropoxy)(5-trifluoroacetamido)benzylidene]ruthenium(II), CAS number 1212008-99-5) was added in two portions (1 mol% at room temperature, stirred at room temperature for 1 hour and at 40 °C for 1 hour, 4 mol% at 40 °C, stirred at 40 °C for 2 hours). Next, the mixture was analyzed by GC (GC analysis: SnatchCat® (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 ).

[0114] GC analysis after 1 hour at room temperature and 3 hours at 40 °C (without 2,5-dichlorohex-3-ene) (5 mol%): 0.9% of 2-allylcyclopentan-1-one, 52.0% of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 30.3% of 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one). GC analysis showed that 2,2’-(but-2-ene-1,4-diyl)bis(cyclopentan-1-one) was formed before the formation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one.

[0115] In a 5 mL Schlenk tube, 200 mg (1.582 mmol, purity 98.2%) of 2-allylcyclopentan-1-one was mixed with 537 mg (purity 90%, 3.16 mmol, 2 equivalents) of 2,5-dichlorohex-3-ene in 2 mL of dichloromethane at room temperature under an argon atmosphere. 45 mg (0.0791 mmol, 5 mol%) of dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II) (Hoveyda-Grubbs catalyst (registered trademark) M72 SI(o-Tol)(C571), Stewart-Grubbs catalyst, CAS number 927429-61-6) was added in two portions (1 mol% at room temperature, stirred at room temperature for 1 hour and at 40 °C for 1 hour, 4 mol% at 40 °C, stirred at 40 °C for 2 hours). Next, the mixture was analyzed by GC (GC analysis: SnatchCat (registered trademark) (1,4-bis(2-isocyanopropyl)piperazine, CAS 51641-96-4) was added to the sample, stirred at room temperature, and filtered through a pad of SiO 2 ).

[0116] GC analysis (without 2,5-dichlorohex-3-ene) after 1 hour at room temperature and 3 hours at 40 °C (5 mol%): 3% 2-allylcyclopentan-1-one, 30.2% 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one, 44.7% 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one). GC analysis showed that 2,2'-(buta-2-ene-1,4-diyl)bis(cyclopentan-1-one) was formed before the formation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one.

[0117] [Example 21] (Conversion of 5-(2-oxocyclopentyl)penta-3-en-2-yl acetate, 2-(4-(1-butoxyethoxy)penta-2-en-1-yl)cyclopentan-1-one or 2-(4-((trimethylsilyl)oxy)penta-2-en-1-yl)cyclopentan-1-one to 2-(4-hydroxypenta-2-en-1-yl)cyclopentan-1-one) 5-(2-oxocyclopentyl)penta-3-en-2-yl acetate, 2-(4-(1-butoxyethoxy)penta-2-en-1-yl)cyclopentan-1-one or 2-(4-((trimethylsilyl)oxy)penta-2-en-1-yl)cyclopentan-1-one can be fully deprotected to 2-(4-hydroxypenta-2-en-1-yl)cyclopentan-1-one by using standard deprotection protocols (NaOH, MeOH for 5-(2-oxocyclopentyl)penta-3-en-2-yl acetate, AcOH, H 2 O for 2-(4-(1-butoxyethoxy)penta-2-en-1-yl)cyclopentan-1-one, CF 3 COOH, MeOH for 2-(4-((trimethylsilyl)oxy)penta-2-en-1-yl)cyclopentan-1-one).

[0118] J. E. Baeckvall, S. E. Bystroem, R. E. Nordberg. J. Org. Chem. 1984, 49, 4619 - 4631 (NaOH, MeOH). N. Pendem, C. Douat, P. Claudon, M. Laguerre, S. Castano, B. Desbat, D. Cavagnat, E. Ennifar, B. Kauffmann, G. Guichard, J. Am. Chem. Soc. 2013, 135, 4884 - 4892 (CF 3 COOH, MeOH). B. B. Snider, X. Gao, Org. Lett. 2005, 7, 4419 - 4422 (AcOH, H 2 O).

[0119] [Example 22] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one and (E)-2-(2-chloropent-3-en-1-yl)cyclopentan-1-one from 2-(4-hydroxypent-2-en-1-yl)cyclopentan-1-one) 200 mg (purity 96.5%, 1.148 mmol) of 2-(4-hydroxypent-2-en-1-yl)cyclopentan-1-one was stirred in 0.50 mL of EtOH under water cooling. 0.721 g (9.18 mmol, 8 eq) of acetyl chloride was added slowly and the mixture was stirred at room temperature for 1 h (complete conversion of the starting material). 5 mL of Et 2 O was added and the mixture was washed twice with 2 mL of saturated NaHCO 3 aqueous solution. After filtration through a plug of SiO 2 (for drying), the solvent was evaporated under reduced pressure (40 °C, 15 mbar). 204 mg (purity 93%, 1.016 mmol) of a 64 / 36 mixture of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one and (E)-2-(2-chloropent-3-en-1-yl)cyclopentan-1-one was isolated (88% yield).

[0120] [Example 23] (Preparation of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one and (E)-2-(2-chloropent-3-en-1-yl)cyclopentan-1-one from 5-(2-oxocyclopentyl)pent-3-en-2-yl acetate) 5-(2-Oxocyclopentyl)penta-3-en-2-yl acetate (200 mg, purity 97.5%, 0.9269 mmol) was stirred in 0.41 mL of EtOH under water cooling. 0.582 g (7.42 mmol, 8 eq) of acetyl chloride was added slowly, and the mixture was stirred at room temperature for 1 h (complete conversion of the starting material). 5 mL of dichloromethane was added, and the solvent was evaporated under reduced pressure (40 °C, 150 mbar). This procedure was repeated twice. 178 mg (purity 91%, 0.870 mmol) of a 63 / 37 mixture of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one and (E)-2-(2-chloropent-3-en-1-yl)cyclopentan-1-one was isolated (94% yield). [Chemical formula]

[0121] [Example 24] (Preparation of (1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one)) 400 mg of KOH was mixed with 4 g of ethanol and 600 mg of water. 0.485 g (0.691 mmol KOH) of this solution was added slowly with stirring at 0 °C. 4.51 g of this solution was added slowly to 864 mg (4.628 mmol) of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one with stirring at room temperature. The mixture was warmed to room temperature and stirred for an additional 1.5 h. After neutralization with 5% aqueous HCl, EtOAc was added. The aqueous phase was separated, and the organic phase was washed with saturated NaHCO 3 aqueous solution and saturated NaCl aqueous solution. The solvent was evaporated under reduced pressure to give 1.08 g of a crude product. Kugelrohr distillation of the crude product gave 528 mg (3.515 mmol, 76% yield) of (1SR,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (1RS,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (Z)-1-(prop-1-en-1-yl)spiro[2.4]heptan-4-one (ratio 82 / 9 / 9). [Chemical formula]

[0122] Spectral data ( 1 H-NMR) was identical to the published spectral data (Helvetica Chimica Acta, 1978, 2524).

[0123] [Example 25] (Preparation of 1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one from a mixture of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one and (E)-2-(2-chloropent-3-en-1-yl)cyclopentan-1-one) 1.6 g of KOH was mixed with 16 g of ethanol and 2.4 g of water. 0.485 g of this solution (0.691 mmol KOH) was slowly added to a 141 mg (purity 91.4%, 0.691 mmol) 63 / 37 mixture of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one and (E)-2-(2-chloropent-3-en-1-yl)cyclopentan-1-one while stirring at 0 °C. After 1.5 hours, GC analysis ((E)-2-(2-chloropent-3-en-1-yl)cyclopentan-1-one reacted quickly) gave a mixture of (1SR,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (1RS,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (Z)-1-(prop-1-en-1-yl)spiro[2.4]heptan-4-one in a ratio of 83 / 8 / 10 at a conversion rate of 96%.

[0124] [Example 26] (Preparation of 1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one) 19.2 mg (0.804 mmol, 1.5 eq) of NaH was washed with heptane and 3 mL of THF was added. After heating to 65 °C, 100 mg (0.536 mmol) of 2-(4-chloropent-2-en-1-yl)cyclopentan-1-one was slowly added with stirring. After 2 h at 65 °C, complete conversion was observed (GC analysis: 89% of (1SR,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (1RS,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (Z)-1-(prop-1-en-1-yl)spiro[2.4]heptan-4-one (ratio 15 / 63 / 19)).

[0125] [Example 27] (Preparation of 1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one from (E)-5-(2-oxocyclopentyl)penta-3-en-2-yl methanesulfonate) ((E)-5-(2-oxocyclopentyl)penta-3-en-2-yl methanesulfonate (prepared from 2-(4-hydroxypent-2-en-1-yl)cyclopentan-1-one (MsCl, NEt 3 , dichloromethane) and used as a crude product) could be completely converted to a mixture of (1SR,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one and (1RS,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one (minor isomer) (KOH, EtOH, H 2 O). [Chemical formula]

[0126] [Example 28] (Preparation of (Z)-2-(pent-2-en-1-yl)cyclopent-2-en-1-one) A glass (quartz) column (15 cm) filled with a 5g quartz ring was connected to a heating system (pyrolysis furnace) via a condenser at the bottom of the column. The glass column was heated to 400 °C (in the pyrolysis furnace). A mixture of 1.13 g (7.51 mmol) of (1SR,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (1RS,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (Z)-1-(prop-1-en-1-yl)spiro[2.4]heptan-4-one (82 / 9 / 9) and 6 mL of toluene obtained in Example 24 was slowly introduced from the top using a syringe pump under a stream of argon from the top. This crude product was collected at the bottom using a cooled 25 mL flask. The solvent of the crude product was evaporated under reduced pressure to obtain 836 mg (5.56 mmol) of (Z)-2-(penta-2-en-1-yl)cyclopenta-2-en-1-one in a yield of 74% and 242 mg (1.61 mmol, recycled starting material in a yield of 21%) of a mixture of (1SR,3RS)-1-((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (1RS,3RS)-1((E)-prop-1-en-1-yl)spiro[2.4]heptan-4-one / (Z)-1-(prop-1-en-1-yl)spiro[2.4]heptan-4-one (52 / 8 / 40) by GC analysis of the crude product.

[0127] (Z)-2-(penta-2-en-1-yl)cyclopenta-2-en-1-one could be separated by column chromatography (80 g of SiO 2 , eluent cyclohexane / EtOAc 9 / 1).

[0128] Preparation of methyl jasmonate and (Z)-jasmon: Both of these compounds were obtained from (Z)-2-(penta-2-en-1-yl)cyclopent-2-en-1-one by known methods; for details of the experiments, see the following references: G. Buechi, B. Egger, J. Org. Chemistry 1971, 36, 2021. P. Jaunky, J. Buirey, C. Mahaim, Flavour Fragr. J. 2017, 32, 388-391.

Chemical formula

[0129] The spectral data were the same as the published ones ( 1 1H-NMR): G. Buechi, B. Egger, J. Org. Chemistry 1971, 36, 2021. H. Kataoka, T. Yamada, K. Goto, J. Tsuji, An efficient synthetic method of methyl (±)‐jasmonate. Tetrahedron. 1987, 43, 4107‐4112.

Claims

1. in the presence of a metathesis catalyst, Formula (I) 【Chemical 1】 [wherein, n is an integer of 1 to 4; R １ and R ２ are each independently a hydrogen atom or a C １～３ alkyl group; and X represents a halogen atom or an OR' group, where R' is a hydrogen atom, C １～６ alkyl group, C ２～６ alkenyl group, benzyl group, trimethylsilyl group, tetrahydrofuran-2-yl group, tetrahydro-2H-pyran-2-yl group, CO(O) ｍ R'' group, CH ２ (OR''') group, CH(OR''')CH ３ group or SO ２ R'''' group, where m is 0 or 1, R'' represents a hydrogen atom, C １～６ alkyl group or phenyl group, R''' represents a C １～６ -alkyl group, and R'''' represents a methyl group, trifluoromethyl group, phenyl group or tolyl group], a compound in the form of any one of its stereoisomers or a mixture thereof, Formula (II) [Chemical Formula 2] [wherein, n and R １ have the same meaning as defined in formula (I), and R ３ and R ４ each independently represents a hydrogen atom or a C １～６ alkyl group optionally substituted by an oxo group], a compound in the form of any one of its stereoisomers or a mixture thereof, and Formula (III) 【Chemical Formula 3】 [wherein, X and R ２ have the same meaning as defined in formula (I), and R ５ independently of one another represents a hydrogen atom or a C １～５ alkyl group optionally substituted by the X group defined above] and a compound in the form of any one of its stereoisomers or a mixture thereof, a method of manufacturing by cross-metathesis between.

2. The method according to claim 1, wherein n is 1.

3. R １ The method according to claim 1 or 2, wherein R is a hydrogen atom.

4. R ２ The method according to any one of claims 1 to 3, wherein R represents a methyl group or an ethyl group.

5. X may be a halogen atom or an OR' group, where R' represents a hydrogen atom, an acetyl group, a methoxymethyl group, an ethoxymethyl group, a 1-butoxyethyl group, a 1-ethoxyethyl group or a trimethylsilyl group. The method according to any one of claims 1 to 4.

6. The method according to any one of claims 1 to 5, wherein X is a halogen atom.

7. R ３ 、 R ４ and R ５ wherein R, R, and R each represents a hydrogen atom, the method according to any one of claims 1 to 6.

8. The method according to any one of claims 1 to 7, wherein the metathesis catalyst is a ruthenium-based catalyst.

9. The metathesis catalyst is 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II), (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)diiodo(2-((1-(methoxy(methyl)amino)-1-oxopropan-2-yl)oxy)benzylidene)ruthenium(II), (1,3-dimesitylimidazolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolinylidene](2-isopropoxyphenylmethylene)ruthenium(II), benzylidene-bis(tricyclohexylphosphine)dichlororuthenium, dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(2-i-propoxy-5-nitrobenzylidene)ruthenium(II) diiodide, 1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene)(2-i-propoxy-5-nitrobenzylidene)ruthenium(II) dichloride, (1,3-dimesitylimidazolidin-2-ylidene)diiodo(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), bis(1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)(3-phenyl-1H-inden-1-ylidene)ruthenium(II) dichloride, (1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)dichloro(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), (1-(2,6-diethylphenyl)-3,5,5-trimethyl-3-phenylpyrrolidin-2-ylidene)diiodo(2-isopropoxy-5-nitrobenzylidene)ruthenium(II), dichloro[1,3-bis(2-methylphenyl)-2-imidazolinylidene](2-isopropoxyphenylmethylene)ruthenium(II), 1,3-Bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride (resin-supported), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(tricyclohexylphosphine)ruthenium(II), [1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]-[2-[[(4-methylphenyl)imino]methyl]-4-nitrophenolyl]-[3-phenyl-1H-inden-1-ylidene]ruthenium(II) chloride, dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][[5-[(dimethylamino)sulfonyl]-2-(1-methylethoxy-O)phenyl]methylene-C]ruthenium(II), dichloro[1-(2,6-diisopropylphenyl)-2,2,4-trimethyl-4-phenyl-5-pyrrolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene]dichloro[(2-isopropoxy)(5-trifluoroacetamido)benzylidene]ruthenium(II), dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1-(2,4,6-trimethylphenyl)-2,2,4-trimethyl-4-phenyl-5-pyrrolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), dichloro[1-(2,6-diisopropylphenyl)-2,2,4-trimethyl-4-phenyl-5-pyrrolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene][(2-isopropoxy)(5-pentafluorobenzoylamino)benzylidene]ruthenium(II), dichloro[1,3-bis(2,4,6-(Trimethylphenyl)-2-imidazolidinylidene]{[5-(2-Ethoxy-2-oxoethanamide)]-2-isopropoxybenzylidene}ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][(2-isopropoxy)(5-pentafluorobenzoylamino)benzylidene]ruthenium(II), (1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)dichloro(2-(((1-(methoxy(methyl)amino)-3-methyl-1-oxobutan-2-yl)oxy)benzylidene)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(pyridyl)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][(2-isopropoxy)(5-trifluoroacetamide)benzylidene]ruthenium(II), dichloro[1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene][(5-isobutoxycarbonylamino)-(2-isopropoxy)benzylidene]ruthenium(II) and dichloro[1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene](3-phenyl-1H-inden-1-ylidene)(triphenylphosphine)ruthenium(II), a method according to any one of claims 1 to 8, selected from the group consisting of.,

10. The compound of formula (I) is converted into formula (IV) 【Chemical Formula 4】 [wherein, R １ , R ２ and n have the same meanings as defined in claim 1, the dotted line represents a carbon-carbon single bond or a carbon-carbon double bond, and R ６ represents a hydrogen atom or a C ａ alkyl group optionally substituted by a COOR １～３ group, where R ａ is a C １～３ alkyl group], the method according to any one of claims 1 to 9, further comprising the step of converting to a compound of].

11. Formula [Chemical Formula 5] [wherein, n is an integer of 1 to 4; R １ and R ２ each independently represents a hydrogen atom or a C １～３ alkyl group; and X represents a halogen atom or an OR' group, where R' represents a hydrogen atom, a C １～６ alkyl group, a C ２～６ alkenyl group, a benzyl group, a trimethylsilyl group, a tetrahydrofuran-2-yl group, a tetrahydro-2H-pyran-2-yl group, a CO(O) ｍ R'' group, a CH ２ (OR''') group, a CH(OR''')CH ３ group or a SO ２ R'''' group, where m is 0 or 1, R'' represents a hydrogen atom, a C １～６ alkyl group or a phenyl group, R''' represents a C １～６ alkyl group, and R'''' represents a methyl group, a trifluoromethyl group, a phenyl group or a tolyl group], a compound in the form of any one of its stereoisomers or a mixture thereof (provided that 2-(4-chlorobut-2-enyl)cyclohexanone, cis-2-(4-hydroxy-2-penten-1-yl)cyclohexanone, cis-2-(4-hydroxy-2-penten-1-yl)cyclopentanone, 2-(4-hydroxy-2-buten-1-yl)cyclohexanone, 2-(5-hydroxy-3-hexen-2-yl)cyclohexanone, and 2-(4-bromo-2-penten-1-yl)cyclopentanone are excluded).

12. The compound of formula (I) is of the formula 【Chemical Formula 6】 [In the formula, R １ , R ２ and X have the same meanings as defined in claim 11], a compound according to claim 11, which is a compound in the form of any one of its stereoisomers or a mixture thereof.

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