Method for selective cleavage of C-SCF3 bonds and analogues

Abstract

The present invention relates to a method for preparing compound A-R by reacting compound A-X in the presence of a metal complex containing nickel, palladium or rhodium(I), a ligand, a nucleophile carrying one R group, and a solvent, where R is a hydrocarbon group optionally containing at least one heteroatom and / or at least one atom other than C or H, A is selected from the group consisting of: (C6-C 10 ) aryl group, heteroaryl group, and vinyl compound, and X is selected from the group consisting of: YCF3, Y(O) n CF3, YCF2SO2Ph, Y(O) n CF2SO2Ph, Y(O) n CF2COOR, Y(O) n CF2CONR2, Y(O) n CF2CH2OH, Y(O) n CN, Y(O) n CHF2, Y(O) n CF2H, Y(O) n CF2C n F 2n+1 , Y(O) n CF2COR, where Y is S or Se, n is 1 or 2, and R is (C1-C6) alkyl.

Description

[Technical Field]

[0001] The present invention relates to a method for selective cleavage of C-SCF3 bonds and analogs of such bonds. [Background technology]

[0002] In a society concerned with the environment, land and water pollution, and a circular economy, the development of new technologies to achieve these objectives is a real challenge and a focus of attention across the entire chemical industry today.

[0003] The field of organofluorine chemistry is unavoidable, with fluorine compounds accounting for a very high proportion in many fields, including materials science, pharmaceuticals, and the agricultural chemistry industry. Indeed, the incorporation of fluorine atoms or fluorinated units has the potential to significantly alter the physicochemical properties of organic molecules, demonstrating the scientific community's interest in this research area. However, the widespread use of these compounds raises questions about their fate and degradation. In recent years, there has been strong scientific and societal interest in chlorofluorocarbons (CFCs), hydrofluorocarbons (HFCs), and perfluoroalkyl and polyfluoroalkyl compounds (PFAs). Furthermore, it is important to consider the fate of emerging fluorinated groups, such as derivatives containing the SCF3 unit (e.g., toltrazuryl and fipronil), which have become indispensable.

[0004] In this situation, developing tools that can enhance the value of these fluorinated derivatives, which are considered waste after a single use, by converting them into high-value compounds, would have a clear environmental impact and enable cost reduction. Therefore, it is essential to address this challenge and develop innovative tools to remove constraints in synthesis.

[0005] Currently, (hetero)aromatic derivatives or C(sp) on the vinyl position 2 )-SRf bond or C(sp 3There is currently no technology that can selectively cleave )-SRf bonds, and any advancements in this area would have significant impacts from both scientific and environmental perspectives.

[0006] N. Barbero et al., Organic Letters, 2012, 14, pp. 796-799 (Supplementary Information, S1-S78), discuss the catalytic reductive cleavage of inactivated C-SMe bonds. As shown in the last paragraph of the left column on page 797, the SMe group, i.e., the electron-donating group on the sulfur atom, is reported to be the most efficient in the reductive cleavage of the CS bond. The optimization processes described in Tables 1-6 of the Supplementary Information (pp. S3-S5) were performed only for this particular thioether. Table 7 of this document (pp. S5) confirms that the SMe group yields the highest yield for CS bond cleavage, while electron-withdrawing groups such as Ac and CONMe2 are less efficient.

[0007] Surprisingly, it has now been discovered that CS bonds and analogues of such bonds on organic molecules can be selectively cleaved in the presence of electron-withdrawing fluorinated groups such as CF3 or similar fluorine-containing groups. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] N. Barbero et al., Organic Letters, 2012, 14, pp. 796-799 (Supplementary Information, S1-S78) [Overview of the project] [Problems that the invention aims to solve]

[0009] Therefore, one object of the present invention is to provide a tool for defluorinating fluorinated compounds.

[0010] One object of the present invention is to provide a method for defluorinating fluorinated compounds, for example, by cleaving a C-SCF3 bond or an analogue of such a bond. [Means for Solving the Problem]

[0011] The present invention relates to a method for preparing a compound having the formula (I): A-R by reacting a compound having the formula (II): A-X in the presence of a metal complex containing nickel, palladium or rhodium (I), a ligand, a nucleophile carrying one R group, and a solvent, where: R is a hydrocarbon group optionally containing at least one heteroatom such as S, N, or O, and / or at least one atom other than C or H such as Se, Si, B, or P; - A is: - an (C6-C ) aryl group 10 (the aryl group is preferably optionally substituted with at least one substituent selected from the group consisting of halogen, (C1-C6) alkyl, (C1-C6) alkoxy, -CN, -CF3, -OCF3, -NR R a R b , -SiR a R b R c , -BR a R b , (C2-C6) alkenyl, (C2-C6) alkynyl, -C(=O)-NR a R b , and -C(=O)-O(CI-C6) alkyl); R a and R b are each independently H or a (C1-C6) alkyl group; R c is a (C1-C6) alkyl group); - a heteroaryl group containing 5 to 10 atoms and containing at least one heteroatom selected from O, N, and S (the heteroaryl group is preferably optionally substituted with at least one substituent selected from the group consisting of halogen, (C1-C6) alkyl, (C1-C6) alkoxy, -CN, -CF3, -OCF3, -NRa R b , -Si(R c )3, -BR a R b (C2~C6) alkenyl, (C2~C6) alkynyl, -C(=O)-NR a R b , and are optionally substituted with at least one substituent selected from -C(=O)-O(C1~C6)alkyl, R a , R b , and R c (As stipulated above) and; The following equation (III):

[0012] [ka]

[0013] Vinyl compounds having (R 1 These include halogens, (C1-C6) alkyls, (C1-C6) alkoxys, -CN, -CF3, -OCF3, and -NR. a R b , -Si(R c )3, -BR a R b (C2~C6) alkenyl, (C2~C6) alkynyl, -C(=O)-NR a R b Selected from the group consisting of -C(=O)-O(C1~C6)alkyl, R a , R b , and R c (as defined above) is selected from the group consisting of; - X is YCF3, YOCF3, YO2CF3, YCF2SO2Ph, YOCF2SO2Ph, YO2CF2SO2Ph, Y(O) n CF2COOR', Y(O) n CF2CONR'2, Y(O) n CF2CH2OH,Y(O) n CN, Y(O) n CHF2, Y(O) n CF2H, Y(O) n CF2C n F2n+1 , Y(O) n Selected from the group consisting of CF2COR', Y is either S or Se. This relates to a method in which n is 1 or 2 and R' is an (C1-C6) alkyl group.

[0014] Therefore, the present invention is based on formula (I): AR Compounds having the following characteristics: In the presence of a nickel-containing metal complex, a ligand, a nucleophile supporting one R group, and a solvent, Formula (II): AX A method for preparing by reacting compounds having the following: R is a hydrocarbon group comprising, optionally, at least one heteroatom such as S, N, or O, and / or at least one atom other than C or H such as Se, Si, B, or P. During the ceremony, - A is as follows: (C6~C 10 ) Aryl group (The aryl group is preferably a halogen, (C1-C6)alkyl, (C1-C6)alkoxy, -CN, -CF3, -OCF3, -NR) a R b , -SiR a R b R c ,-BR a R b (C2~C6) alkenyl, (C2~C6) alkynyl, -C(=O)-NR a R b , and are optionally substituted with at least one substituent selected from the group consisting of -C(=O)-O(C1~C6)alkyl groups; R a and R b These are, independently of each other, H or (C1-C6) alkyl groups; R c (is an alkyl group (C1-C6)); A heteroaryl group containing 5 to 10 atoms, including at least one heteroatom selected from O, N, and S. (The heteroaryl group is preferably a halogen, (C1-C6)alkyl, (C1-C6)alkoxy, -CN, -CF3, -OCF3, -NR) a R b , -Si(R c )3, -BR a R b (C2~C6) alkenyl, (C2~C6) alkynyl, -C(=O)-NR a R b , and are optionally substituted with at least one substituent selected from -C(=O)-O(C1~C6)alkyl, R a , R b , and R c (As stipulated above) and; The following equation (III):

[0015] [ka]

[0016] Vinyl compounds having (R 1 These include halogens, (C1-C6) alkyls, (C1-C6) alkoxys, -CN, -CF3, -OCF3, and -NR. a R b , -Si(R c )3, -BR a R b (C2~C6) alkenyl, (C2~C6) alkynyl, -C(=O)-NR a R b Selected from the group consisting of -C(=O)-O(C1~C6)alkyl, R a , R b , and R c (as defined above) is selected from the group consisting of; - X is YCF3, YOCF3, YO2CF3, YCF2SO2Ph, YOCF2SO2Ph, YO2CF2SO2Ph, Y(O) n CF2COOR', Y(O) n CF2CONR'2, Y(O) n CF2CH2OH,Y(O) n CN, Y(O) nCHF2, Y(O) n CF2H, Y(O) n CF2C n F 2n+1 , Y(O) n selected from the group consisting of CF2COR', Y is S or Se, n is 1 or 2, and R' is (C1-C6) alkyl, relates to a method.

[0017] According to one embodiment, in the above formula (II), X is SCF3, SOCF3, SO2CF3, SCF2SO2Ph, SOCF2SO2Ph, SO2CF2SO2Ph, S(O) n CF2COOR, S(O) n CF2CONR2, S(O) n CF2CH2OH, S(O) n CN, S(O) n CHF2, S(O) n CF2H, S(O) n CF2C n F 2n+1 , S(O) n CF2COR, and all analogs of this list in the selenium series, selected from the group consisting of, R and n are as defined above.

[0018] According to one embodiment, in the above formula (II), X is SCF3, SOCF3, SO2CF3, SCF2SO2Ph, SOCF2SO2Ph, SO2CF2SO2Ph, S(O) n CF2COOR, S(O) n CF2CONR2, S(O) n CF2CH2OH, S(O) n CN, S(O) n CHF2, S(O) n CF2H, S(O) n CF2C n F 2n+1 , S(O) n selected from the group consisting of CF2COR and SeCF3.

[0019] <According to one embodiment, in formula (II) above, X is selected from the group consisting of SCF3, SOCF3, SO2CF3, SCF2SO2Ph, SO2CF2SO2Ph, and SeCF3. [Modes for carrying out the invention]

[0020] The following provisions are provided to illustrate and define the meanings and scopes of various terms used in this specification to describe the present invention.

[0021] "C t ~C z The expression "C1-C3" refers to a carbon chain that can have t to z carbon atoms. For example, C1-C3 refers to a carbon chain that can have 1 to 3 carbon atoms.

[0022] The term "alkyl group" means a linear or branched saturated hydrocarbon aliphatic group containing 1 to 12 carbon atoms, unless otherwise specified. Examples include the methyl group, ethyl group, n-propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, or pentyl group.

[0023] The term "aryl group" refers to a cyclic aromatic group containing between 6 and 10 carbon atoms. Examples of aryl groups include the phenyl group and the naphthyl group.

[0024] The term "heteroaryl group" refers to a 5-10 membered aromatic monocyclic or bicyclic group containing 1-4 heteroatoms selected from O, S, or N. Examples include imidazolyl, thiazolyl, oxazolyl, furanyl, thiophenyl, pyrazolyl, oxadiazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridadinyl, indolyl, benzofuranyl, benzothiophenyl, benzoxazolyl, benzimidazolyl, indazolyl, benzothiazolyl, isobenzothiazolyl, benzotriazolyl, quinolinyl, and isoquinolinyl groups.

[0025] As heteroaryl groups containing 5 to 6 atoms, including 1 to 4 nitrogen atoms, the following representative groups may be specifically mentioned: pyrrolyl group, pyrazolyl group, 1,2,3-triazolyl group, 1,2,4-triazolyl group, tetrazolyl group, and 1,2,3-triazinyl group.

[0026] Examples of heteroaryl groups include thiophenyl, oxazolyl, flazanil, 1,2,4-thiadiazolyl, naphthilidinil, quinoxalinil, phthalazinil, imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazolyl, sinnolinil, benzoflazanil, azaindol, benzimidazolyl, benzothiophenyl, thienopyridyl, thienopyrimidinil, pyrrolopyridyl, imidazopyridyl, benzoazaindole, 1,2,4-triazinil, indolidinil, isoxazolyl, isoquinolinil, isothiazolyl, purinyl, quinazolinil, quinolinil, isoquinolyl, 1,3,4-thiadiazolyl, thiazolyl, isothiazolyl, carbazolyl, and the corresponding groups resulting from their condensation or condensation with a phenyl nucleus.

[0027] When an alkyl group is substituted with an aryl group, the terms "arylalkyl group" or "aralkyl group" are used. An "arylalkyl" group or "aralkyl" group is an arylalkyl group, and the aryl group and alkyl group are as defined above. Among arylalkyl groups, benzyl or phenethyl groups may be specifically mentioned.

[0028] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0029] The term "alkoxy group" means an -O-alkyl group, and alkyl groups are as previously defined. Examples include -O-(C1~C4) alkyl groups, particularly -O-methyl group, -O-ethyl group, -O-propyl group, -O-isopropyl group as -O-C3 alkyl groups, and -O-butyl group, -O-isobutyl group, or -O-tert-butyl group as -O-C4 alkyl groups.

[0030] As used herein, the term "alkynyl" includes an unsaturated non-aromatic hydrocarbon group having 2 to 6 carbon atoms and containing at least one triple bond. Preferably, the alkynyl group is linear. Preferably, the alkynyl group is -(CH2) m -C ≡ CH group, and m is an integer from 1 to 4.

[0031] As used herein, the term "alkenyl" includes an unsaturated non-aromatic hydrocarbon group having 2 to 6 carbon atoms and containing at least one double bond. Preferably, the alkenyl group is linear. Preferably, the alkenyl group is -(CH2) m -CH = 2 CH groups, and m is an integer from 1 to 4.

[0032] The above-mentioned "alkyl," "aryl," and "heteroaryl" groups can be substituted with one or more substituents. Among these substituents, the following groups may be listed: amino, amide, hydroxyl, thiol, oxo, halogen, alkyl, alkoxy, alkylthio, alkylamino, aryloxy, arylalkoxy, cyano, trifluoromethyl, carboxy, or carboxyalkyl.

[0033] The term "alkylthio" means -S-alkyl group, and alkyl groups are defined as described above.

[0034] The term "alkylamino" means -NH-alkyl group, and alkyl groups are defined as described above.

[0035] The term "aryloxy" refers to an -O-aryl group, which is defined above.

[0036] The term "arylalkoxy" refers to an aryl-alkoxy group, where the aryl and alkoxy groups are defined above.

[0037] The term "carboxyalkyl" means HOOC-alkyl group, where the alkyl group is as defined above. Examples of carboxyalkyl groups include carboxymethyl and carboxyethyl.

[0038] The term "haloalkyl group" refers to an alkyl group as defined above, in which one or more hydrogen atoms are replaced by halogen atoms. Examples include fluoroalkyl groups, particularly CF3 or CHF2.

[0039] The term "carboxyl" refers to the COOH group.

[0040] The term "oxo" means "=O".

[0041] The term "hydrocarbon group" refers to a group containing a hydrogen atom and a carbon atom. As mentioned above, R is a group containing at least one carbon atom and at least one hydrogen atom. This group may also contain at least one heteroatom such as O, N, or S, and / or at least one atom other than C or H such as Se, Si, B, or P.

[0042] In one embodiment of the method according to the present invention, the nucleophile is selected from the group consisting of alkylamines, cycloalkylamines, arylamines, alkylthiols, thiophenol compounds, arylselenols, phosphine oxides, Grignard reagents, alcohols, esters, and phosphorus derivatives. Alkylamines, cycloalkylamines, and arylamines may be either primary or secondary amines. The terms "alkyl," "cycloalkyl," and "aryl" are as defined above.

[0043] Preferably, the nucleophile is an RH group, where R is one of the following: (C1~C6) alkyl, heterocycloalkyl, -S-cyclo(C3~C 10 )alkyl, -O-(C1~C 12 ) alkyl, optionally substituted heteroaryl, -NR1 R 2 , -P(=O)-R 1 R 2 -X 1 -Ar 1 -X 1 -(C1~C 12 ) Alkyl-Ar 1 -X 1 -Het 1 -X 1 -(C1~C 12 ) Alkyl-Het 1 Selected from the group consisting of X 1 is S, Se, NH or N-alkyl, and Ar 1 (C6~C 10 ) is an aryl group, Het 1 R is a heteroaryl group that has been optionally substituted, 1 and R 2 These are (C1~C6) alkyl groups or (C6~C) 10 It is an aryl group.

[0044] In particular, when the nucleophile is a cycloalkylamine, R is the cyclo(C3~C) as defined above. 10 ) It may be an alkylamino group.

[0045] In particular, when the nucleophile is a thiol, R can be a -S-(C1~C6) alkyl (as defined above as "alkylthio"), and the alkyl can be optionally substituted as defined above.

[0046] In particular, R is (C1~C6) alkyl, S-cyclo(C3~C 10 )alkyl, O-(C1~C 12 ) Alkyl (as defined above as "alkoxy"), -X 1 -(C1~C 12 ) Alkyl-Ar 1 , X 1 -(C1~C 12 ) Alkyl-Het 1 It could be -X 1 Ar 1 and Het 1The above is as defined, and the alkyl is optionally substituted with at least one substituent as defined above.

[0047] The terms "alkyl," "aryl," "heterocycloalkyl," and "heteroaryl," and their optional substituents, are defined as described above.

[0048] Preferably, R is (C1-C6) alkyl, heterocycloalkyl, -S-cyclo(C3-C) 10 )alkyl, -P(=O)-R 1 R 2 , and -X 1 -Ar 1 Selected from the group consisting of X 1 is S, Se or NH, and Ar 1 (C6~C 10 ) is an aryl group, R 1 and R 2 These are (C1~C6) alkyl groups or (C6~C) 10 It is an aryl group.

[0049] More preferably, the nucleophile is selected from the group consisting of: heterocycloalkyl groups containing at least one nitrogen atom and / or sulfur atom, such as morpholine; aniline groups and their derivatives, such as 4-methylaniline and HS-(cyclo)alkyl groups such as CySH; HS-aryl groups such as 4-methylthiophenol; H-Se-aryl groups such as benzene selenol; phosphine oxides such as HP(=O)Ph2; Grignard reagents such as Alk-MgBr, particularly iPrMgBr; and phosphorus derivatives such as HPPh2, where the pH is a phenyl group.

[0050] In one embodiment, in formulas (I) and (II) defined above, A is selected from a heteroaryl group comprising 5 to 10 atoms and at least one heteroatom selected from O, N, and S, wherein the heteroaryl group is a halogen, (C1-C6) alkyl, (C1-C6) alkoxy, -CN, -CF3, -OCF3, -NR a Rb , -Si(R c )3, -BR a R b (C2~C6) alkenyl, (C2~C6) alkynyl, -C(=O)-NR a R b , and are optionally substituted with at least one substituent selected from -C(=O)-O(C1~C6)alkyl, R a , R b , and R c This is as defined above.

[0051] According to one embodiment, the method of the present invention as defined above further comprises the use of a hydride compound such as LiHMDS. In this embodiment, a compound having formula (II) is reacted with a nucleophile in the presence of a metal complex, ligand, and solvent containing nickel, palladium, or rhodium(I), and is also reacted with a hydride compound.

[0052] In this embodiment, the nucleophile is, in particular, a Grignard reaction substance.

[0053] According to one embodiment, in the method of the present invention, the ligand is selected from the group consisting of 1,5-cyclooctadiene (COD), 1,2-bis(dicyclohexylphosphino)ethane (dcype), 1,1'-bis(diphenylphosphino)ferrocene (dppf), 1,1'-bis(di-tert-butylphosphino)ferrocene (DTBPF), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos), triphenylarsine (AsPh3), and triphenylphosphan (PPh3).

[0054] The term "ligand" refers to a chemical component that can bond with the metal in a metal complex. The initial state of a metal complex is the state in which the metal complex is used in the reaction medium. In the initial state of a metal complex, the ligand can bond with the metal.

[0055] Alternatively, a ligand can be added to the reaction medium in addition to the metal complex. In such a case, the ligand binds to the metal in the reaction medium.

[0056] According to one embodiment of the method, the ligand is bonded to the metal in the initial state of the metal complex.

[0057] According to another embodiment of the method, a ligand is added to the reaction medium in addition to the metal complex.

[0058] In a further embodiment of the method, at least one first ligand is bonded to the metal in the initial state of the metal complex, and at least one second ligand is added to the reaction medium in addition to the metal complex, wherein the first and second ligands are either identical or different.

[0059] Preferably, the metal complex is a Ni(0) complex such as bis(1,5-cyclooctadiene)nickel (Ni[cod]2) or bis(triphenylphosphine)nickel (Ni[PPh3]2).

[0060] In another embodiment, the metal complex comprises nickel, palladium, or rhodium(I). For example, the metal complex may be a Pd(0) complex such as tris(dibenzylideneacetone)dipalladium(O) of formula Pd2dba3, or tetrakis(triphenylphosphine)palladium(O) of formula Pd(PPh3)4. In particular, the metal complex may be a Pd(II) complex such as [1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene](3-chloropyridyl)palladium(II) dichloride (PEPPSI™-SIPr catalyst, 905459-27-0), palladium(II) acetate of formula Pd(OAc)2, or allylpalladium(II) chloride dimer of formula [Pd(π-allyl)Cl]2. Alternatively, the metal complex may be an Rh(I) complex such as rhodium carbonyl chloride of formula [Rh(CO)2Cl]2, or hydroxy(cyclooctadiene)rhodium(I) dimer of formula [Rh(OH)COD]2.

[0061] According to one embodiment, the solvent used in the method according to the present invention is selected from ordinary solvents used in the art. Preferably, the solvent in the method according to the present invention is toluene.

[0062] In one embodiment of the method according to the present invention, the reaction is carried out at a temperature of 90°C to 140°C, and preferably, the reaction may be carried out at 90°C, 110°C, 120°C, and 140°C.

[0063] The present invention also includes formula (I-1):

[0064] [ka]

[0065] (R is as defined above), Compounds having the following characteristics: Formula (II-2):

[0066] [ka]

[0067] (X1 is selected from the group consisting of: SCF3, SOCF3, SO2CF3, SCF2SO2Ph, SOCF2SO2Ph, SO2CF2SO2Ph, and SeCF3) From compounds having, The method for preparation as specified above. [Examples]

[0068] (Example 1: Selective cleavage of C-SCF3 bonds in the presence of alkylamines as nucleophiles)

[0069] [ka]

[0070] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), alkylamine (1.25 mmol, 2 equivalents), and toluene (1.25 mL) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 13a.

[0071] The results indicate that using alkylamines as nucleophiles enables cleavage of the CS bond in the presence of CF3 groups in good yield.

[0072] (Example 2: Selective cleavage of C-SCF3 bonds in the presence of arylamines as nucleophiles)

[0073] [ka]

[0074] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), arylamine (1.25 mmol, 2 equivalents), and toluene (1.25 mL) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to obtain the desired product 14a.

[0075] The results indicate that primary and aromatic amines are suitable nucleophiles in this Ni catalytic conversion, and that cleavage of the CS bond is possible in the presence of a CF3 group.

[0076] (Example 3: Selective cleavage of C-SCF3 bond in the presence of alkylthiol as nucleophile)

[0077] [ka]

[0078] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), alkylthiol (1.25 mmol, 2 equivalents), and toluene (1.25 mL) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to obtain the desired product 15a.

[0079] The results indicate that the SCF3 group was selectively replaced in high yield with a group consisting of a sulfur atom linked to an alkyl group (S-alkyl group).

[0080] (Example 4: Selective cleavage of C-SCF3 bonds in the presence of thiophenol derivatives as nucleophiles)

[0081] [ka]

[0082] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), arylthiol (1.25 mmol, 2 equivalents), and toluene (1.25 mL) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 16a.

[0083] We also successfully replaced the SCF3 portion with a group consisting of a sulfur atom linked to an aryl group (SAr group). These results indicate that chalcogen is well-suited as a class of nucleophiles.

[0084] (Example 5: Selective cleavage of C-SCF3 bonds in the presence of aryl selenol as a nucleophile)

[0085] [ka]

[0086] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), aryl selenol (1.25 mmol, 2 equivalents), and toluene (1.25 mL) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 17.

[0087] The results indicate that aryl selenol is also a suitable nucleophile.

[0088] (Example 6: Selective cleavage of the C-SCF3 bond in the presence of phosphine oxide as a nucleophile)

[0089] [ka]

[0090] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), phosphine oxide (1.25 mmol, 2 equivalents), and toluene (1.25 mL) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (20 mL x 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to obtain the desired product 18.

[0091] The results indicate that phosphine oxide is a suitable nucleophile in this Ni catalytic conversion.

[0092] (Example 7: Selective cleavage of C-SCF3 bonds in the presence of Grignard reagent as a nucleophile)

[0093] [ka]

[0094] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), Grignard reagent (1.25 mmol, 2 equivalents), and toluene (1.25 mL) were charged under argon. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. The residue was concentrated under vacuum and purified by silica gel flash column chromatography to isolate the desired product 19.

[0095] The results indicate that Grignard reagents are suitable nucleophiles for replacing SCF3 groups with alkyl groups.

[0096] (Example 8: Selective cleavage of the C-SOCF3 bond)

[0097] [ka]

[0098] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.5 mmol, 5 equivalents), 20 (0.5 mmol, 1 equivalent), and morpholine (2 mmol, 4 equivalents) were charged under argon. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to obtain the desired product 13a.

[0099] The results indicate that using an aliphatic amine (morpholine) as a nucleophile allows for the cleavage of the CS(O)SCF3 bond, in which the carbon atom is linked to the sulfoxide, in good yield.

[0100] (Example 9: Selective cleavage of the C-SCF2SO2Ph bond)

[0101] [ka]

[0102] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (4 mg, 0.015 mmol, 5 mol%), dcype (6 mg, 0.015 mmol, 5 mol%), LiHMDS in toluene (1.5 mL, 1 M, 251 mg, 1.5 mmol, 5 equivalents), 22 (107 mg, 0.3 mmol, 1 equivalent), and morpholine (1.2 mmol, 4 equivalents) were charged under argon. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 13a. The product and corresponding yield are reported in Scheme 9.

[0103] The results demonstrate that, by the method according to the present invention, it is possible to cleave a CS bond supporting another fluorinated functional group, namely a CF2SO2Ph group, using an amine (morpholine) as a nucleophile.

[0104] (Example 10: Selective cleavage of C-SCF3 bonds in the presence of various metal complexes and various ligands)

[0105] [ka]

[0106] For 10-A and 10-C, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%) or Ni(PPh3)2 (14.6 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.50 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), and morpholine (2.5 mmol, 4 equivalents) were charged under argon. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with toluene (3 × 20 mL), and the combined organic layer was dehydrated with MgSO4 and concentrated under vacuum.

[0107] For 10-A, the residue was purified by silica gel flash column chromatography to isolate the desired product 13a. For 10-B, 10-C, and 10-D, 1,3,5-trimethoxybenzene was used as an internal standard. 1 The yield was determined by 1H NMR. The obtained product and the corresponding yield are reported in Scheme 10 and Table 1, respectively.

[0108] The same procedure was followed for 10-B and 10-D, except that dcype was not added to the solution.

[0109] The metal complex, ligand, and reaction yield are reported in Table 1.

[0110] [Table 1]

[0111] The results indicate that the reaction proceeded smoothly using the metal complex, with and without the addition of dcype as a ligand.

[0112] (Example 11: Selective cleavage of C-SCF3 bond in the presence of a Pd complex)

[0113] [ka]

[0114] Equipped with a stirring rod, in an oven-dried 10 mL tube, prepare the formula:

[0115] [ka]

[0116] [1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene](3-chloropyridyl)palladium(II) dichloride (PEPPSI™-SIPr catalyst, 905459-27-0, 17 mg, 0.025 mmol, 5 mol%) was charged under argon with 1 M LiHMDS (2.5 mL, 418 mg, 2.50 mmol, 5 equivalents, 1 M), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), and morpholine or 4-methylaniline (2 mmol, 4 equivalents) in toluene. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. 10 mL of butyl was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO2 (3 × 20 mL), and the combined organic layer was dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 13a or 14a.

[0117] The results indicate that cleavage of the C-SCF3 bond can be achieved using a Pd catalyst in the presence of a secondary aliphatic amine or aniline derivative.

[0118] (Example 12: Selective cleavage of C-SCF3 bond in the presence of ligand and Pd complex)

[0119] [ka]

[0120] In an oven-dried 10 mL tube equipped with a stirring rod, [1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene](3-chloropyridyl)palladium(II) dichloride (PEPPSI®-SIPr catalyst, 905459-27-0, 17 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS 1 M in toluene (2.5 mL, 418 mg, 2.50 mmol, 5 equivalents, 1 M), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), and 4-methylaniline (2 mmol, 4 equivalents) were charged under argon. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO(10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO(3 × 20 mL), and the combined organic phase was dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 14a.

[0121] The results show that cleavage of the CS bond 12 is achieved in both cases: when the ligand is bonded to the metal in the initial state of the metal complex (Example 11), and when the ligand is added to the reaction medium in addition to the metal complex (Example 12).

[0122] (Example 13: Selective cleavage of C-SCF3 bonds in the presence of a primary amine as a nucleophile)

[0123] [ka]

[0124] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents; or 418 mg, 2.5 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), primary amine of formula H2NR (2 mmol, 4 equivalents), and toluene were charged under argon. The reaction conditions are reported in Table 2 below. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with siRNA (3 × 20 mL), and the combined organic layer was dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to obtain the desired product. The product and corresponding isolation yields are reported in Scheme 14 and Table 2 below.

[0125] [ka]

[0126] [Table 2]

[0127] (Example 14: Selective cleavage of C-SCF3 bonds in the presence of a secondary amine as a nucleophile)

[0128] [ka]

[0129] In an oven-dried 10 mL tube equipped with a stirring rod, combine Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents; or 418 mg, 2.5 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), formula HNR 1 R 2 The secondary amine (2 mmol, 4 equivalents) and toluene were charged under argon. The reaction conditions are reported in Table 3 below. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. 10 mL of ELISA was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with ELISA (3 × 20 mL), and the combined organic phase was dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product. The product and corresponding yield are reported in Scheme 16 and Table 3 below.

[0130] [ka]

[0131] [Table 3]

[0132] (Example 15: Selective cleavage of C-SCF3 bond in the presence of thiol as a nucleophile)

[0133] [ka]

[0134] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (209 mg, 1.25 mmol, 2.5 equivalents; or 418 mg, 2.5 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), thiol 15 or 16 of formula HSR (2 mmol, 4 equivalents), and toluene were charged under argon. The reaction conditions are reported in Table 4 below. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with siRNA (3 × 20 mL), and the combined organic phase was dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to obtain the desired product. The product and corresponding yield are reported in Scheme 18 and Table 4 below.

[0135] [ka]

[0136] [Table 4]

[0137] (Example 16: Selective cleavage of C-SCF3 bonds in the presence of phosphorus derivatives as nucleophiles)

[0138] [ka]

[0139] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS (418 mg, 2.5 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), HPPh2 (2 mmol, 4 equivalents), and toluene were charged under argon. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic phase was dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 23.

[0140] The results show that cleavage of 12 was achieved in high yield in the presence of a phosphorus nucleophile, indicating an interesting exchange between the S-containing group and the P-containing group.

[0141] (Example 17: Selective cleavage of C-SCF3 bonds in the presence of an alcohol as a nucleophile)

[0142] [ka]

[0143] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.5 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), and pentanol (1.25 mL, 33%) as a cosolvent were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 24.

[0144] The results show that cleavage of 12 molecules can be achieved in high yield in the presence of an alcohol nucleophile.

[0145] (Example 18: Selective cleavage of C-SCF3 bonds in the presence of esters as nucleophiles)

[0146] [ka]

[0147] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.5 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), and methyl acetate (1.25 mL, 33%) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 25.

[0148] (Example 19: Selective cleavage of C-SCF3 bonds in the presence of esters as nucleophiles)

[0149] [ka]

[0150] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.5 mmol, 5 equivalents), 2-((trifluoromethyl)thio)benzo[d]thiazole 12 (118 mg, 0.5 mmol, 1 equivalent), and ethyl acetate (1.25 mL, 33%) were charged under argon. The resulting solution was stirred at 100 °C for 16 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 26.

[0151] Examples 17, 18, and 19 demonstrated the possibility of forming CO bonds from 12 cleavages using different nucleophiles.

[0152] (Example 20: Selective cleavage of C-SeCF3 bonds)

[0153] [ka]

[0154] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol%), LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.5 mmol, 5 equivalents), 27 (142 mg, 0.5 mmol, 1 equivalent), and morpholine (2 mmol, 4 equivalents) were charged under argon. The resulting solution was stirred at 100°C for 16 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 13a.

[0155] The results indicate that selective cleavage of the C-SeCF3 bond is achieved in the presence of an amine as a nucleophile.

[0156] (Example 21: Selective cleavage of C-SCF3 bonds on aryl groups)

[0157] [ka]

[0158] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol), LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.5 mmol, 5 equivalents), 28 (0.5 mmol, 1 equivalent), and morpholine (2 mmol, 4 equivalents) were charged under argon. The resulting solution was stirred at 140 °C for 48 hours. The mixture was cooled to 21 °C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 29.

[0159] (Example 22: Selective cleavage of C-SCF3 bonds on vinyl groups)

[0160] [ka]

[0161] In an oven-dried 10 mL tube equipped with a stirring rod, Ni(cod)2 (4 mg, 0.015 mmol, 5 mol%), dcype (6 mg, 0.015 mmol, 5 mol%), LiHMDS in toluene (1.5 mL, 1 M, 251 mg, 1.5 mmol, 5 equivalents), 30 (0.3 mmol, 1 equivalent), and morpholine (1.2 mmol, 4 equivalents) were charged under argon. The resulting solution was stirred at 140°C for 48 hours. The mixture was cooled to 21°C. SiO (10 mL) was added to the mixture, and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with SiO (3 × 20 mL), and the combined organic layers were dehydrated with MgSO4 and concentrated under vacuum. Nitromethane was used as an internal standard. 1 The yield of 31 was determined by 1H NMR.

Claims

1. Equation (I): AR Compounds having the following characteristics: In the presence of a metal complex containing nickel, palladium, or rhodium(I), a ligand, a nucleophile supporting one R group, and a solvent, Formula (II): AX A method for preparing by reacting compounds having the following: R is a hydrocarbon group comprising, optionally, at least one heteroatom and / or at least one atom other than C or H. A is as follows: (C 6 ~C 10 ) Aryl group (The aryl group is preferably halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, -CN, -CF 3 , -OCF 3 , -NR a R b , -SiR a R b R c , -BR a R b , (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, -C(=O)-NR a R b , and -C(=O)-O(C 1 -C 6 )alkyl, and is optionally substituted with at least one substituent selected from the group consisting of; R a and R b These are H or (C) independent of each other. 1 ~C 6 ) is an alkyl group; R c is, (C 1 ~C 6 (It is an alkyl group) and; A heteroaryl group containing 5 to 10 atoms, including at least one heteroatom selected from O, N, and S. (The heteroaryl group is preferably a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Alkoxy, -CN, -CF 3 , -OCF 3 , -NR a R b , -Si(R c ) 3 ,-BR a R b , (C 2 ~C 6 ) Alkenil, (C 2 ~C 6 ) Alkinyl, -C(=O)-NR a R b , and -C(=O)-O(C 1 ~C 6 )Optionally substituted with at least one substituent selected from alkyl groups, R a , R b , and R c (As stipulated above) and; The following equation (III): 【Chemistry 1】 Vinyl compounds having (R 1 is halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Alkoxy, -CN, -CF 3 , -OCF 3 , -NR a R b , -Si(R c ) 3 ,-BR a R b , (C 2 ~C 6 ) Alkenil, (C 2 ~C 6 ) Alkinyl, -C(=O)-NR a R b , and -C(=O)-O(C 1 ~C 6 ) Selected from the group consisting of alkyl groups, R a , R b , and R c (as defined above) is selected from the group consisting of; X is selected from the group consisting of YCF 3 , YOCF 3 , YO 2 CF 3 , YCF 2 SO 2 Ph, YOCF 2 SO 2 Ph, YO 2 CF 2 SO 2 Ph, Y(O) n CF 2 COOR', Y(O) n CF 2 CONR' 2 , Y(O) n CF 2 CH 2 OH, Y(O) n CN, Y(O) n CHF 2 , Y(O) n CF 2 H, Y(O) n CF 2 C n F 2n+1 , Y(O) n CF 2 COR', and Y is S or Se, n is either 1 or 2, and R' is (C 1 ~C 6 ) A method that is alkyl.

2. The method according to claim 1, wherein the metal complex contains nickel.

3. The method according to claim 1 or 2, wherein the ligand is bonded to the metal in the initial state of the metal complex, and / or the ligand is added to the reaction medium in addition to the metal complex.

4. The method according to any one of claims 1 to 3, wherein the nucleophile is selected from the group consisting of alkylamines, cycloalkylamines, arylamines, alkylthiols, thiophenol compounds, arylselenols, phosphine oxides, Grignard reagents, alcohols, esters, and phosphorus derivatives.

5. The nucleophile is an RH group, where R is (C 1 ~C 6 )alkyl, heterocycloalkyl, -S-cyclo(C 3 ~C 10 )alkyl, -O-(C 1 ~C 12 )alkyl, optionally substituted heteroaryl, cyclo(C 3 ~C 10 ) Alkylamino group, alkyl is optionally substituted -S-(C 1 ~C 6 ) Alkyl, -NR 1 R 2 , -P(=O)-R 1 R 2 -X 1 -Ar 1 -X 1 -(C 1 ~C 12 ) Alkyl-Ar 1 -X 1 -Het 1 -X 1 -(C 1 ~C 12 ) Alkyl-Het 1 Selected from the group consisting of, X 1 is S, Se, or NH, and Ar 1 (C) was replaced by choice. 6 ~C 10 ) is an aryl group, Het 1 R is a heteroaryl group that has been optionally substituted, 1 and R 2 They are independent of each other, (C 1 ~C 6 ) Alkyl alkyl group or (C 6 ~C 10 The method according to any one of claims 1 to 4, wherein the group is an aryl group.

6. The nucleophile is an RH group, where R is (C 1 ~C 6 )alkyl, heterocycloalkyl, -S-cyclo(C 3 ~C 10 )alkyl, -P(=O)-R 1 R 2 , and -X 1 -Ar 1 Selected from the group consisting of X 1 is S, Se or NH, and Ar 1 (C) was replaced by choice. 6 ~C 10 ) is an aryl group, R 1 and R 2 They are independent of each other, (C 1 ~C 6 ) Alkyl alkyl group or (C 6 ~C 10 The method according to any one of claims 1 to 4, wherein the group is an aryl group.

7. A is selected from a heteroaryl group comprising 5 to 10 atoms and at least one heteroatom selected from O, N, and S, wherein the heteroaryl group is a halogen, (C 1 ~C 6 ) alkyl, (C 1 ~C 6 ) Alkoxy, -CN, -CF 3 , -OCF 3 , -NR a R b , -Si(R c ) 3 ,-BR a R b , (C 2 ~C 6 ) Alkenil, (C 2 ~C 6 ) Alkinyl, -C(=O)-NR a R b , and -C(=O)-O(C 1 ~C 6 )Optionally substituted with at least one substituent selected from alkyl groups, R a , R b , and R c The method according to any one of claims 1 to 6, wherein the property is as defined in claim 1.

8. The method according to any one of claims 1 to 7, further comprising the use of a hydride compound such as LiHMDS.

9. The ligands are: 1,5-cyclooctadiene (COD), 1,2-bis(dicyclohexylphosphino)ethane (dcype), 1,1'-bis(diphenylphosphino)ferrocene (dppf), 1,1'-bis(di-tert-butylphosphino)ferrocene (DTBPF), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos), triphenylarsine (AsPh 3 ), and triphenylphosphan (PPh 3 The method according to any one of claims 1 to 8, selected from the group consisting of ).

10. The method according to any one of claims 1 to 9, wherein the solvent is toluene.

11. The method according to any one of claims 1 to 10, wherein the reaction is carried out at a temperature of 90°C to 140°C.

12. The method according to any one of claims 1 to 11, wherein the metal complex is a Ni(0) complex such as bis(1,5-cyclooctadiene)nickel.

13. Equation (I-1): 【Chemistry 2】 (R is as defined in any one of claims 1 to 6) Compounds having Formula (II-2): 【Transformation 3】 (X 1 ha:SCF 3 SOCF 3 , SO 2 CF 3 SCF 2 SO 2 Ph, SOCF 2 SO 2 Ph, SO 2 CF 2 SO 2 Ph and SeCF 3 (Selected from the group consisting of) From compounds having, A method according to any one of claims 1 to 12 for preparing

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