Cyclic amidinium salts and ruthenium compounds

Abstract

To provide a ruthenium compound useful as a catalyst for olefin metathesis.SOLUTION: A ruthenium compound is represented by the general formula (2) in the figure. (In the formula: Y4, Y5 and Y6 each independently represent a hydrogen atom or a C1-C4 alkyl group, n represents 1 or 2; X1 and X2 each independently represent an anionic ligand; R represents a C1-C4 alkyl group; and Z represents a hydrogen atom, a nitro group, or a trifluoroacetylamino group.)SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to cyclic amidinium salts and ruthenium compounds. [Background technology]

[0002] N-Heterocyclic carbenes are useful ligands for transition metal catalysts and are widely used as ligands for ruthenium catalysts used in olefin metathesis reactions. In particular, it is known that modifying the carbene structure can improve the activity of ruthenium catalysts. Such N-heterocyclic carbenes can be obtained by treating the corresponding cyclic amidinium salts with a base, and the development of cyclic amidinium salts has been actively pursued.

[0003] Fluoroolefins, in which olefins are substituted with fluorine atoms, are widely used as refrigerants, pharmaceuticals, agricultural chemicals, electronic materials, and monomers for fluororesins. Production methods using olefin metathesis reactions have been reported as methods for producing these. For example, Non-Patent Document 1 discloses a method for producing monofluoroolefins by a ring-closing metathesis reaction using a second-generation Grubbs catalyst (imidazolidinylidene ligand). However, the catalyst's high substrate specificity was a problem. Non-Patent Document 2 discloses a method for producing monofluoroolefins by a ring-closing metathesis reaction using a second-generation Hoveyda-Grubbs catalyst (imidazolidinylidene ligand), but it has been reported that olefin metathesis reactions using this catalyst also exhibit high substrate dependency. Furthermore, Patent Document 1 discloses a method for producing fluoroolefins using a ruthenium compound having a six- or seven-membered heterocyclic carbene ligand. Although the metathesis reaction is believed to proceed with a wide range of ruthenium compounds, the carbene ligand of the ruthenium catalyst used in the examples was only a mesityl-substituted carbene ligand.

[0004] As described above, ruthenium compounds containing carbene ligands are used in the metathesis reaction to produce fluoroolefins, but they lack substrate generality. Furthermore, the carbene ligands of ruthenium compounds play a very important role in reactivity and catalytic activity, and it is known that slight differences in the structure of the carbene ligand can significantly affect activity.

[0005] The cyclic amidinium salt and ruthenium compound of the present invention are novel compounds that have never been produced before, and the catalytic activity of the ruthenium compound in the metathesis reaction has also been unknown. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Organic Letters 2003, Vol. 5, 3403-3406. [Non-patent document 2] Organic Letters 2020, Vol. 22, 7064-7067. [Patent documents]

[0007] [Patent Document 1] WO2021 / 177000 Summary of the Invention [Problem to be solved by the invention]

[0008] In view of the above circumstances, the present invention aims to develop a method for efficiently producing a variety of monofluoroolefins by an olefin metathesis reaction, and aims to provide a synthetic precursor of a highly active ruthenium catalyst and a carbene ligand that serves as the ligand therefor. [Means for solving the problem]

[0009] As a result of intensive research conducted by the present inventors to solve the above-mentioned problems, they found that by using a ruthenium compound having a 6- or 7-membered heterocyclic carbene ligand, it is possible to achieve highly efficient synthesis of fluoroolefins by metathesis reaction, which has conventionally not proceeded or been carried out in low yield, and have thus completed the present invention.

[0010] That is, one aspect of the present invention is as follows. [1] The following general formula (1):

[0011] [ka]

[0012] (In the formula, Y 1 , Y 2 and Y 3 each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; Y 1 , Y 2 and Y 3 At least one of Q represents an alkyl group having 1 to 4 carbon atoms. - represents a counter anion, and n represents 1 or 2. [2] Y 1 , Y 2 and Y 3 are each independently a hydrogen atom or a methyl group, and Y 1 , Y 2 and Y 3 The cyclic amidinium salt according to [1] above, wherein at least one of the groups is a methyl group. [3] The following general formula (2):

[0013] [ka]

[0014] (In the formula, Y 4 , Y 5 and Y 6 each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents 1 or 2. X 1 and X 2each independently represents an anionic ligand, R represents an alkyl group having 1 to 4 carbon atoms, and Z represents a hydrogen atom, a nitro group, or a trifluoroacetylamino group. [4] R is an isopropyl group, Z is a hydrogen atom, and X 1 and X 2 is a chlorine atom. [5]Y 4 , Y 5 and Y 6 are each independently a hydrogen atom or a methyl group. [6]Y 4 , Y 5 and Y 6 are each independently a hydrogen atom or a methyl group, and Y 4 , Y 5 and Y 6 The ruthenium compound according to [3] or [4] above, wherein at least one of the groups is a methyl group. [7] The following general formula (1a):

[0015] [ka]

[0016] (In the formula, Y 4 , Y 5 , Y 6 , n and Q - has the same meaning as above.) is reacted with a base, and then a cyclic amidinium salt represented by the following general formula (4)

[0017] [ka]

[0018] (In the formula, X 1 and X 2each independently represents an anionic ligand; R represents an alkyl group having 1 to 4 carbon atoms; and Z represents a hydrogen atom, a nitro group, or a trifluoroacetylamino group.

[0019] [ka]

[0020] (In the formula, Y 4 , Y 5 , Y 6 , n, X 1 , X 2 and R and Z have the same meanings as defined above. [8] A catalyst for olefin metathesis, represented by the following general formula (2):

[0021] [ka]

[0022] (In the formula, Y 4 , Y 5 , Y 6 , n, X 1 , X 2 , R and Z are as defined above. [9] A method for producing a cyclic monofluoroolefin by ring-closing metathesis reaction, characterized by using the olefin metathesis catalyst according to [8] above. [Effects of the Invention]

[0023] According to the present invention, the ruthenium compound of the present invention can be produced from the cyclic amidinium salt of the present invention, and fluorinated olefins can be produced by olefin metathesis using the ruthenium compound of the present invention as a metathesis catalyst. The ruthenium compound of the present invention is characterized in that it is a compound coordinated with a 6- or 7-membered carbene ligand substituted with a methyl group at the 2-position and a phenyl group bearing a hydrogen atom at the 6-position. The activity of the metathesis reaction is increased by reducing the bulkiness of the aryl group on the nitrogen atom of the carbene ligand and by expanding the ring from a 5-membered ring to a 6- or 7-membered ring. DETAILED DESCRIPTION OF THE INVENTION

[0024] The present invention will be described in detail below. <Cyclic amidinium salt> The cyclic amidinium salt (1) of the present invention will now be described.

[0025] Y 1 ,Y 2 and Y 3 The alkyl group having 1 to 4 carbon atoms represented by the formula (I) may be linear, branched, or cyclic, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, etc. A methyl group is preferred in that it provides good activity as a carbene ligand in the metathesis catalyst of a ruthenium compound.

[0026] Q - Examples of the counter anion represented by the formula (I) include chloride ion, bromide ion, iodide ion, tetrafluoroborate ion, hexafluorophosphate ion, trifluoromethanesulfonate ion, p-toluenesulfonate ion, hexafluoroantimonate ion, etc. In terms of ease of production of the ruthenium compound of the present invention, tetrafluoroborate ion or hexafluorophosphate ion is preferred.

[0027] In the cyclic amidinium salt (1) of the present invention, Y 1 ,Y 2 and Y3 Examples of phenyl groups substituted with include a 2,3-dimethylphenyl group, a 2,4-dimethylphenyl group, a 2,5-dimethylphenyl group, a 3-ethyl-2-methylphenyl group, a 4-ethyl-2-methylphenyl group, a 5-ethyl-2-methylphenyl group, a 2-methyl-3-propylphenyl group, a 2-methyl-4-propylphenyl group, a 2-methyl-5-propylphenyl group, a 3-butyl-2-methylphenyl group, a 4-butyl-2-methylphenyl group, a 5-butyl-2-methylphenyl group, a 2,3,4-trimethylphenyl group, a 2,4,5-trimethylphenyl group, and a 2,3,4,5-tetramethylphenyl group.

[0028] As the cyclic amidinium salt (1) of the present invention, for example, compounds represented by the following formulas (1-1) to (1-6) are preferred: Note that the cyclic amidinium salt of the present invention is not limited to the compounds exemplified below.

[0029] [ka]

[0030] <Method of producing cyclic amidinium salt> The method for producing the cyclic amidinium salt (1) of the present invention will be described below.

[0031] The method for producing the cyclic amidinium salt (1) of the present invention is not particularly limited. For example, the salt can be synthesized from the corresponding formamidine derivative (3) according to the following reaction scheme, with reference to a method described in the literature (Chemical Communications, pp. 6044-6047, 2018).

[0032] [ka]

[0033] (In the formula, Y 1 , Y 2 , Y 3 , n and Q - has the same meaning as above, and M+ represents a counter cation.) That is, the formamidine derivative (3) is reacted with 1,3-dibromopropane (n=1) or 1,4-dibromobutane (n=2) to obtain a cyclic compound, and the counter anion, Br - If necessary, M + Q - Using the counter anion Q - can be exchanged for and synthesized.

[0034] Counter cation M + Examples of the cations include sodium ions, potassium ions, and lithium ions. + Q - Examples of suitable salts include metal salts such as lithium chloride, sodium chloride, potassium chloride, sodium iodide, potassium iodide, sodium tetrafluoroborate, sodium hexafluorophosphate, sodium trifluoromethanesulfonate, sodium p-toluenesulfonate, and sodium hexafluoroantimonate. <Ruthenium compounds> The ruthenium compound (2) of the present invention will now be described.

[0035] Y 4 ,Y 5 and Y 6 The alkyl group having 1 to 4 carbon atoms represented by the formula (I) may be linear, branched, or cyclic, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, etc. A methyl group is preferred in view of its good activity as a metathesis catalyst.

[0036] In the ruthenium compound (2) of the present invention, Y 4 ,Y 5 and Y 6Examples of the aryl group substituted with include a 2-methylphenyl group, a 2,3-dimethylphenyl group, a 2,4-dimethylphenyl group, a 2,5-dimethylphenyl group, a 3-ethyl-2-methylphenyl group, a 4-ethyl-2-methylphenyl group, a 5-ethyl-2-methylphenyl group, a 2-methyl-3-propylphenyl group, a 2-methyl-4-propylphenyl group, a 2-methyl-5-propylphenyl group, a 3-butyl-2-methylphenyl group, a 4-butyl-2-methylphenyl group, a 5-butyl-2-methylphenyl group, a 2,3,4-trimethylphenyl group, a 2,4,5-trimethylphenyl group, and a 2,3,4,5-tetramethylphenyl group.

[0037] The alkyl group having 1 to 4 carbon atoms represented by R may be linear, branched, or cyclic, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, etc. An isopropyl group is preferred because of its good catalytic activity in the metathesis reaction.

[0038] In the ruthenium compound (2) of the present invention, Z represents a hydrogen atom, a nitro group, or a trifluoroacetylamino group, with a hydrogen atom being preferred in terms of ease of preparation.

[0039] In the ruthenium compound (2) of the present invention, X 1 and X 2 Each independently represents an anionic ligand, and examples thereof include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. From the viewpoint of reactivity, a chlorine atom is preferred.

[0040] As the ruthenium compound (2) of the present invention, for example, compounds represented by the following formulae (2-1) to (2-8) are preferred: However, the ruthenium compound of the present invention is not limited to the compounds exemplified below.

[0041] [ka]

[0042] <Method of manufacturing ruthenium compounds> The method for producing the ruthenium compound (2) of the present invention will be described below.

[0043] The method for producing the ruthenium compound (2) of the present invention is not particularly limited. For example, the compound can be synthesized from a cyclic amidinium salt (1a), which can be prepared in the same manner as the cyclic amidinium salt (1) of the present invention, according to the following formula, with reference to a method described in a literature (Organometallics, pp. 2278-2284, 2011).

[0044] [ka]

[0045] (In the formula, Y 4 , Y 5 , Y 6 , n, Q - , X 1 , X 2 and Z have the same meaning as above. Cy represents a cyclohexyl group. That is, the ruthenium compound (2) of the present invention can be synthesized by reacting the cyclic amidinium salt (1a) with a base and then reacting it with the ruthenium compound (4).

[0046] The base that can be used in the production method of ruthenium compound (2) is not particularly limited, but examples thereof include alkali metal hydroxides, alkali metal alkoxides, alkali metal amides, alkali metal hydrides, and alkyl (or aryl)lithium compounds. More specific examples include alkali metal amides such as lithium hexamethyldisilazide, lithium diisopropylamide (LDA), lithium 2,2,6,6-tetramethylpiperidide, sodium hexamethyldisilazide, and potassium hexamethyldisilazide; alkyl (or aryl)lithium compounds such as methyllithium, n-butyllithium, and phenyllithium; alkali metal hydrides such as lithium hydride and sodium hydride; and alkali metal alkoxides such as potassium tert-butoxide and sodium tert-butoxide. Among these, sodium bis(trimethylsilyl)amide is preferred because of its good yield.

[0047] The production method of the present invention can be carried out in a solvent. Specific examples of solvents that can be used include ether solvents such as tetrahydrofuran, diethyl ether, 1,4-dioxane, and 1,2-dimethoxyethane; hydrocarbon solvents such as hexane, pentane, and cyclohexane; aromatic hydrocarbon solvents such as benzene, toluene, and o-xylene; aprotic polar solvents such as acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, dimethylacetamide, and N-methylpyrrolidone; and alcohol solvents such as methanol and ethanol. Two or more of these solvents may be mixed and used. The amount of reaction solvent used is not particularly limited. From the viewpoint of high yield, it is preferable to use tetrahydrofuran, 1,4-dioxane, hexane, toluene, or o-xylene.

[0048] The production method of the present invention can be carried out at a temperature appropriately selected from the range of −20° C. to 200° C. In terms of good yield, it is preferably carried out at a temperature appropriately selected from the range of 10° C. to 120° C.

[0049] The molar ratio of the cyclic amidinium salt (1a) to the base used in the production method of the present invention is not particularly limited, but is preferably in the range of 1:0.5 to 1:2 depending on the cyclic amidinium salt (1a), and more preferably 1:0.8 to 1:1.2 in terms of good yield.

[0050] The ruthenium compound (4) used in the production method of the present invention can be synthesized, for example, by referring to a method described in the literature (Journal of American Chemical Society, pp. 791-799, 1999).

[0051] The molar ratio of the cyclic amidinium salt (1a) to the ruthenium compound (4) used in the production method of the present invention is preferably in the range of 1:1 to 1:10, and more preferably 1:1 to 1:5 in terms of good yield.

[0052] After the reaction, the ruthenium compound (2) can be purified as needed. The purification method is not particularly limited, but the ruthenium compound (2) can be purified by a method commonly used by those skilled in the art, such as solvent extraction, silica gel column chromatography, thin-layer preparative chromatography, preparative liquid chromatography, recrystallization, or sublimation. <Olefin metathesis reaction> The ruthenium compound (2) of the present invention can be used, for example, as a catalyst for olefin metathesis. The olefin metathesis reaction can be carried out, for example, by the method described in Non-Patent Document 1 or Non-Patent Document 2. There are no particular limitations on the substrates that can be used in olefin metathesis; for example, cyclic monofluoroolefins can be synthesized by a ring-closing metathesis reaction. For example, 2-fluoro-1,6-heptadiene derivatives, 2-fluoro-1,7-octadiene derivatives, 2-fluoro-1,8-nonadiene derivatives, etc. can be used as reaction substrates, and cyclic monofluoroolefins such as 1-fluorocyclopentene derivatives, 1-fluorocyclohexene derivatives, and 1-fluorocyclopentene derivatives can be synthesized by the ring-closing metathesis reaction. [Example]

[0053] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0054] In addition, 1 H-NMR spectra were measured using a Bruker ASCEND HD (400 MHz; manufactured by BRUKER). 1 The 1 H-NMR spectrum was measured using deuterated chloroform (CDCl 3 ) as a measurement solvent and tetramethylsilane (TMS) as an internal standard. [Example]

[0055] [ka]

[0056] A 100 ml two-neck flask equipped with a stirrer was charged with 20.0 ml (165 mmol) of 2,3-dimethylaniline, 13.7 ml (82.5 mmol) of triethyl orthoformate, and 0.24 ml (4.13 mmol) of acetic acid, and the atmosphere inside the vessel was replaced with argon. The solution was heated to 160 °C and stirred for 3 hours while removing the by-product ethanol as needed. The resulting solution was cooled to room temperature to solidify the target product, which was then transferred to a mortar and 50.0 ml of hexane was added to pulverize the solid. The solid was filtered using a Kiriyama funnel, washed three times with 20 ml of hexane, and dried to obtain the target N,N'-bis(2,3-dimethylphenyl)formamidine in 74% yield (61.2 mmol). 1 H-NMR (400MHz, CDCl3): δ=7.98(s,1H),7.06(dd,J=7.4Hz,7.6Hz,2H),6.92(d,J=7.4Hz,2H),6.88(d,J=7.6Hz,2H),2.31(s,6H),2.23(s,6H)ppm. [Example]

[0057] [ka]

[0058] A 250 ml two-neck flask equipped with a stirrer was charged with 3.07 g (12.0 mmol) of N,N'-bis(2,3-dimethylphenyl)formamidine, 1.35 ml (13.2 mmol) of 1,3-dibromopropane, 0.845 g (6.0 mmol) of potassium carbonate, 9.96 g (60.0 mmol) of potassium iodide, and 48.0 ml of acetonitrile, and the atmosphere inside the vessel was replaced with argon. The solution was heated to 85°C and stirred for 24 hours, after which the solution was cooled to room temperature. The solvent was evaporated, dichloromethane (30 ml) was added, and the solid was filtered off. The solid was further washed three times with dichloromethane (10 ml). The resulting solution was concentrated, ethyl acetate (30 ml) was added, and the precipitated solid was filtered off and washed three times with ethyl acetate (10 ml).

[0059] The resulting solid was then transferred to a 100 ml recovery flask equipped with a stir bar, and 20 ml of dichloromethane, 20 ml of water, and 2.63 g (24.0 mmol) of sodium tetrafluoroborate were added and stirred at room temperature for 12 hours. After the reaction, the organic layer was separated using a separatory funnel, and the aqueous layer was extracted twice with dichloromethane (10 ml). The organic layer was dehydrated over magnesium sulfate, filtered, and the volatile components were removed by distillation. Recrystallization using ethyl acetate and hexane afforded 3.26 g of 3,4,5,6-tetrahydro-1,3-bis(2,3-dimethylphenyl)pyrimidinium tetrafluoroborate in a 71% yield (8.53 mmol). 1 H-NMR (400MHz, CDCl3): δ=7.60(s,1H),7.54(br,2H),7.26-7.16(m,4H),4.56-3.37(br,4H),2.54(br,2H),2.31(s,6H),2.25(s,6H)ppm. [Example]

[0060] [ka]

[0061] In a glovebox, 26.4 mg (0.08 mmol) of 3,4,5,6-tetrahydro-1,3-bis(2-methylphenyl)pyrimidinium tetrafluoroborate, 14.0 mg (0.07 mmol) of potassium hexamethyldisilazide, and 1.0 mL of hexane were added to a 4 mL vial equipped with a stir bar and stirred at room temperature for 15 minutes. Next, 30.0 mg (0.05 mmol) of the first-generation Hoveyda-Grubbs catalyst (Ru-0) was added, the vial was sealed, and the vial was removed from the glovebox and heated and stirred at 50°C for 12 hours. After the reaction, the solution was cooled to room temperature and filtered through Celite. The green solid was washed three times with 3 mL of hexane, extracted with 10 mL of dichloromethane, and then concentrated. By flash column chromatography (eluent: ethyl acetate / hexane = 1 / 5 (volume ratio)), 24.3 mg of the ruthenium compound Ru-1 (compound 2-7) was obtained in a yield of 83% (0.04 mmol) as a mixture of two isomers (molar ratio of isomers = 81:19). 1 H-NMR (400MHz, CDCl3): δ=16.43(s,0.81H),16.35(s,0.19H),8.65(dd,J=7.7Hz,1.2Hz,0.81H),8.55 (dd,J=7.2Hz,2.3Hz,0.19H),7.53-7.21(m,9H),6.94-6.72(m,2H),4.78(sept,J=6.2Hz,1H),3.82-3. 58(m,4H),2.62(s,0.57H),2.58(s,2.43H),2.52(s,2.43H),2.42(s,0.57H),2.44-2.25(m,2H),1.25( d,J=6.2Hz,2.43H),1.13(d,J=6.2Hz,0.57H),1.04(d,J=6.2Hz,0.57H),1.03(d,J=6.2Hz,2.43H)ppm. [Example]

[0062] [ka]

[0063] In a glovebox, a 50 mL Schlenk tube equipped with a stir bar was charged with 0.95 g (2.49 mmol) of 3,4,5,6-tetrahydro-1,3-bis(2,3-dimethylphenyl)pyrimidinium tetrafluoroborate, 0.95 g (2.33 mmol) of potassium hexamethyldisilazide, and 33.3 mL of hexane, and stirred at room temperature for 15 minutes. Next, 1.00 g (1.67 mmol) of the first-generation Hoveyda-Grubbs catalyst (Ru-0) was added, sealed, removed from the glovebox, and heated and stirred at 50 °C for 12 hours. After the reaction, the solution was cooled to room temperature and filtered. The green solid was washed three times with 10 mL of hexane, extracted with 30 mL of dichloromethane, and then concentrated. By flash column chromatography (developing solvent: ethyl acetate / hexane = 1 / 5 (volume ratio)), 0.78 g of ruthenium compound Ru-2 (compound 2-2) was obtained in a yield of 76% (1.27 mmol) as a mixture of two isomers (molar ratio of isomers = 78:22). 1 H-NMR (400MHz, CDCl3): δ=16.51(s,0.78H),16.41(s,0.22H),8.49(d,J=7.8Hz,0.78H),8.38(d,J=7.6Hz,0.22H),7.50-7.44(m,1H), 7.40-7.30(m,2H),7.29-7.22(m,2H),7.20(t,J=7.4Hz,0.22H),7.12(t,J=7.7Hz,0.78H),6.91-6.77(m,2H),6.77-6.70(m,1H),4.76 (sept,J=6.2Hz,1H),3.80-3.55(m,4H),2.45(s,2.34H),2.44(s,0.66H),2.41(s,4.68H),2.38(s,1.32H),2.37(s,2.34H),2.33-2.2 2(m,2H),2.30(s,0.66H),1.23(d,J=6.2Hz,2.34H),1.13(d,J=6.2Hz,0.66H),1.03(d,J=6.2Hz,2.34H),1.02(d,J=6.2Hz,0.66H)ppm. [Reaction Example 1]

[0064] [ka]

[0065] In a glove box, 23.6 mg (0.09 mmol) of diethyl [2-allyl-2-(2-fluoroallyl)]malonate, 1.0 mL of toluene, and 2.7 mg (0.005 mmol) of ruthenium compound (Ru-1) were placed in a 4 mL vial and sealed. The solution was heated to 100°C and stirred for 24 hours. The reaction solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 It was confirmed by 1 H-NMR that diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate was produced in an NMR yield of 73% (0.07 mmol). 1 H-NMR (400MHz, CDCl3): δ=4.90(m,1H),4.22(q,J=7.1Hz,4H),3.09(m,2H),2.91(m,2H),1.26(t,J=7.1Hz,6H)ppm. [Reaction Example 2]

[0066] [ka]

[0067] In a glove box, 25.5 mg (0.10 mmol) of diethyl [2-allyl-2-(2-fluoroallyl)]malonate, 1.0 mL of toluene, and 3.1 mg (0.005 mmol) of ruthenium compound (Ru-2) were placed in a 4 mL vial and sealed. The solution was heated to 100°C and stirred for 24 hours. The reaction solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 It was confirmed by 1 H-NMR that diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate was produced in an NMR yield of 80% (0.08 mmol). [Reaction Example 3]

[0068] [ka]

[0069] In a glove box, 26.5 mg (0.10 mmol) of diethyl [2-allyl-2-(2-fluoroallyl)]malonate, 1.0 ml of toluene, and 1.6 mg (0.0025 mmol) of ruthenium compound (Ru-2) were placed in a 4 ml vial and sealed. The solution was heated to 100°C and stirred for 24 hours. After the reaction, the solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 It was confirmed by 1 H-NMR that diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate was produced in an NMR yield of 62% (0.06 mmol). [Reaction Example 4]

[0070] [ka]

[0071] In a glove box, 26.0 mg (0.10 mmol) of diethyl [2-allyl-2-(2-fluoroallyl)]malonate, 1.0 ml of tetrahydrofuran, and 1.5 mg (0.0025 mmol) of ruthenium compound (Ru-2) were placed in a 4 ml pressure-resistant glass container and sealed. The solution was heated to 100°C and stirred for 24 hours. After the reaction, the solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 It was confirmed by 1 H-NMR that diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate was produced in an NMR yield of 77% (0.08 mmol). [Reaction Example 5]

[0072] [ka]

[0073] In a glove box, 25.6 mg (0.10 mmol) of diethyl [2-allyl-2-(2-fluoroallyl)]malonate, 1.0 mL of cyclopentyl methyl ether, and 1.5 mg (0.0025 mmol) of ruthenium compound (Ru-2) were placed in a 4 mL vial and sealed. The solution was heated to 100°C and stirred for 24 hours. After the reaction, the solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 It was confirmed by 1 H-NMR that diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate was produced in an NMR yield of 73% (0.07 mmol). Comparative Example 1

[0074] [ka]

[0075] In a glove box, 25.3 mg (0.10 mmol) of diethyl [2-allyl-2-(2-fluoroallyl)]malonate, 1.0 ml of toluene, and 3.1 mg (0.005 mmol) of ruthenium compound (Ru-3) were placed in a 4 ml vial and sealed. The solution was heated to 100°C and stirred for 24 hours. After the reaction, the solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 It was confirmed by 1 H-NMR that diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate was produced in an NMR yield of 10% (0.01 mmol). Comparative Example 2

[0076] [ka]

[0077] In a glove box, 26.3 mg (0.10 mmol) of diethyl [2-allyl-2-(2-fluoroallyl)]malonate, 1.0 ml of toluene, and 1.6 mg (0.0025 mmol) of ruthenium compound (Ru-4) were placed in a 4 ml vial and sealed. The solution was heated to 100°C and stirred for 24 hours. After the reaction, the solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 It was confirmed by 1 H-NMR that diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate was produced in an NMR yield of 49% (0.07 mmol).

[0078] The conditions for the metathesis reaction of diethyl [2-allyl-2-(2-fluoroallyl)]malonate using various ruthenium compounds as catalysts in the above synthesis examples and comparative examples (ruthenium compounds used, catalyst amounts, and solvents), as well as the yields of diethyl 3-fluoro-3-cyclopentene-1,1-dicarboxylate obtained, are summarized in Table 1 below.

[0079] [Table 1]

[0080] In Table 1, in metathesis reactions using Ru-1 and Ru-2 in a catalyst amount of 5.0 mol%, the target product was obtained in good yield (Reaction Examples 1 and 2). Furthermore, when the catalyst amount was reduced to 2.5 mol%, the target product was also obtained in good yield (Reaction Examples 3 to 5). Ru-1 and Ru-2 have six-membered cyclic carbene ligands substituted with 2-methylphenyl and 2,3-dimethylphenyl groups. On the other hand, when a five-membered cyclic carbene ligand substituted with 2,4,6-trimethylphenyl groups was used, the yield of the target product decreased (Comparative Example 1). Furthermore, when a six-membered carbene ligand substituted with a 2,4,6-trimethylphenyl group was used, the yield of the target product also decreased (Comparative Example 2).Non-Patent Document 1 also reports that the same metathesis reaction does not proceed when a second-generation Grubbs catalyst is used. [Reaction Example 6]

[0081] [ka]

[0082] In a glove box, 29.7 mg (0.12 mmol) of diethyl [2-(2-fluoroallyl)-2-methallyl]malonate, 1.0 mL of tetrahydrofuran, and 3.1 mg (0.005 mmol) of ruthenium compound (Ru-2) were added to a 4 mL vial and sealed. The solution was heated to 100 °C and stirred for 24 hours. After the reaction, the solution was cooled to room temperature and concentrated. The product was confirmed by flash column chromatography (eluent: ethyl acetate / hexane = 1 / 30 (volume ratio)) to be 26.0 mg of diethyl 3-fluoro-4-methyl-3-cyclopentene-1,1-dicarboxylate in an isolated yield of 87% (0.11 mmol). 1 H-NMR (400MHz, CDCl3): δ=4.21(q,J=7.1Hz,4H),3.10-3.05(m,4H),2.86-2.80(m,4H),1.61-1.57(m,3H),1.26(t,J=7.1Hz,6H)ppm. [Reaction Example 7]

[0083] [ka]

[0084] In a glove box, 28.3 mg (0.10 mmol) of diethyl [2-(2-fluoroallyl)-2-(3-methyl-3-butenyl)]malonate, 1.0 mL of tetrahydrofuran, and 3.1 mg (0.005 mmol) of ruthenium compound (Ru-2) were added to a 4 mL vial and sealed. The solution was heated to 100 °C and stirred for 24 hours. After the reaction, the solution was cooled to room temperature and concentrated. The product was confirmed by flash column chromatography (eluent: ethyl acetate / hexane = 1 / 30 (volume ratio)) to be 25.2 mg of diethyl 3-fluoro-4-methyl-3-cyclohexene-1,1-dicarboxylate in an isolated yield of 99% (0.10 mmol). 1H-NMR (400MHz, CDCl3): δ=4.20(q,J=7.1Hz,4H),2.74-2.69(m,4H),2.12-2.00(m,4H),1.61-1.56(m,3H),1.25(t,J=7.1Hz,6H)ppm. [Reaction Example 8]

[0085] [ka]

[0086] In a glove box, 20.0 mg (0.10 mmol) of 1-ethylhexyl 2-fluoro-2-propenoate, 1.0 mL of tetrahydrofuran, and 3.1 mg (0.005 mmol) of ruthenium compound (Ru-2) were placed in a 4 mL vial and sealed. The solution was heated to 100°C and stirred for 24 hours. The reaction solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 1 H-NMR confirmed that 3-fluoro-5-pentyl-2(5H)-furanone was produced in an NMR yield of 71% (0.07 mmol). 1 H-NMR (400MHz, CDCl3): δ=6.71(dd,J=2.0,1.8Hz,1H),4.98(ddd,J=5.8,1.8,1.7Hz,1H),1.84 - 1.66(m,2H),1.55 - 1.38(m,2H),1.38 - 1.23(m,4H),0.96 - 0.86(m,3H). 13 C-NMR (100MHz, CDCl3): δ=164.76(d,J=32.8Hz),148.49(d,J=279.1Hz),126.03( d,J=5.2Hz),77.78(d,J=6.7Hz),33.75(d,J=2.2Hz),31.48,24.43,22.52,14.03. 19 F-NMR (377 MHz, CDCl): δ = - 142.09(s,1F). [Reaction Example 9]

[0087] [ka]

[0088] In a glove box, 29.8 mg (0.11 mmol) of 2-fluoro-N-[(4-methylphenyl)sulfonyl]-N-2-propen-1-yl-2-propenamide, 1.0 mL of tetrahydrofuran, and 1.2 mg (0.002 mmol) of ruthenium compound (Ru-2) were added to a 4 mL vial and sealed. The solution was heated to 100 °C and stirred for 24 hours. The reaction mixture was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1H-NMR analysis confirmed the formation of 3-fluoro-1,5-dihydro-1-(p-toluenesulfonyl)-2H-pyrrol-2-one in a 79% NMR yield (0.08 mmol). 1 H-NMR (400 MHz, CDCl): δ = 7.99 - 7.93(m,2H),7.39 - 7.33(m,2H),6.50(dt,J=2.5,0.8Hz,1H),4.35(dd,J=6.2,2.5Hz,2H),2.45(s,3H). 19 F-NMR (377 MHz, CDCl): δ = - 140.06(s,1F). [Reaction Example 10]

[0089] [ka]

[0090] In a glove box, 22.2 mg (0.10 mmol) of 2-(1-fluorovinyl)-2'-vinylbiphenyl, 1.0 mL of tetrahydrofuran, and 3.1 mg (0.005 mmol) of ruthenium compound (Ru-2) were placed in a 4 mL vial and sealed. The solution was heated to 100°C and stirred for 24 hours. The reaction solution was cooled to room temperature, and 1,2,4,5-tetramethylbenzene was added as an internal standard. 1 1 H-NMR confirmed that 9-fluorophenanthrene was produced in an NMR yield of >99% (0.10 mmol).1 H-NMR(400MHz,CDCl3):δ=8.69 - 8.64(m,1H),8.63 - 8.58(m,1H),8.18(dd,J=8.0,1.6Hz,1H),7.83 - 7.77(m,1H),7.76 - 7.65(m,2H),7.65 - 7.57(m,2H),7.38(d,J=11.6Hz,1H). 13 C-NMR(100MHz,CDCl3):δ=157.20(d,J=251.7Hz),131.98(d,J=9.8Hz),131.92(d,J=5.4Hz),128.17(d,J=5.3Hz),127.93,127.78,127.37,127.00(d,J=1.1Hz),125.90(d,J=2.2Hz),124.37(d,J=19.0Hz),122.90,122.87,121.42(d,J=6.3Hz),108.06(d,J=19.8Hz). 19 F-NMR(377MHz,CDCl3):δ= - 125.74(s,1F).

Claims

1. The following general formula (1) 【Chemical 1】 (In the formula, Y １ , Y ２ and Y ３ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; Y １ , Y ２ and Y ３ At least one of Q represents an alkyl group having 1 to 4 carbon atoms. － represents a counter anion, and n represents 1 or 2.

2. Y １ , Y ２ and Y ３ are each independently a hydrogen atom or a methyl group, and Y １ , Y ２ and Y ３ The cyclic amidinium salt of claim 1 , wherein at least one of

3. The following general formula (2) 【Chemistry 2】 (In the formula, Y ４ , Y ５ and Y ６ Each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents 1 or 2. １ and X ２ each independently represents an anionic ligand; R represents an alkyl group having 1 to 4 carbon atoms; and Z represents a hydrogen atom, a nitro group, or a trifluoroacetylamino group.

4. R is an isopropyl group, Z is a hydrogen atom, and X １ and X ２ The ruthenium compound according to claim 3, wherein is a chlorine atom.

5. Y ４ , Y ５ and Y ６ 5. The ruthenium compound according to claim 3, wherein each of is independently a hydrogen atom or a methyl group.

6. Y ４ , Y ５ and Y ６ are each independently a hydrogen atom or a methyl group, and Y ４ , Y ５ and Y ６ The ruthenium compound according to claim 3 or 4, wherein at least one of the groups is a methyl group.

7. The following general formula (1a) 【Chemistry 3】 (In the formula, Y ４ , Y ５ and Y ６ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents 1 or 2. － represents a counter anion.) is reacted with a base, and then reacted with a cyclic amidinium salt represented by the following general formula (4): 【Chemistry 4】 (In the formula, X １ and X ２ each independently represents an anionic ligand; R represents an alkyl group having 1 to 4 carbon atoms; and Z represents a hydrogen atom, a nitro group, or a trifluoroacetylamino group. 【Chemistry 5】 (In the formula, Y ４ , Y ５ , Y ６ , n, X １ , X ２ , R and Z have the same meanings as defined above.

8. A catalyst for olefin metathesis, comprising: 【Chemistry 6】 (In the formula, Y ４ , Y ５ and Y ６ Each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents 1 or 2. １ and X ２ each independently represents an anionic ligand; R represents an alkyl group having 1 to 4 carbon atoms; and Z represents a hydrogen atom, a nitro group, or a trifluoroacetylamino group.

9. A method for producing a cyclic monofluoroolefin by ring-closing metathesis reaction, characterized by using the olefin metathesis catalyst according to claim 8.

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