Catalyst, modified comopound, and method of preparing modified compound

Abstract

Provided is a catalyst that can be used in a variety of reactions involving a formation of a carbon-carbon bond. The catalyst is represented by a formula (I). In formula (I), R1 is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group; R2 is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group; each R3 is independently selected from the group consisting of CH2, CHF and CF2; R4 and R5 are the same or different and each is a polar organic solvent comprising at least one selected from a nitrogen atom, an oxygen atom, a sulfur atom and a halogen atom; n is an integer larger than 0; and dashed lines connecting Ni (II) and R4 and R5 are coordinate bonds.

Description

CATALYST, MODIFIED COMOPOUND, AND METHOD OF PREPARING MODIFIED COMPOUNDThe present disclosure relates to a catalyst used for a reaction involving a formation of a carbon-carbon bond, a modified compound prepared by a reaction involving a formation of a carbon-carbon bond, and a method of preparing a modified compound.BackgroundThe modification of existing drugs and bioactive molecules has been established as a strategy to alter their activity, improve stability to metabolic degradation, and assist in their passage through the blood / brain barrier. These effects can vary greatly depending on the type of the modification.Therefore, developing a simple and general catalytic protocol that can be used for a wide variety of modifications is an important goal.Over the past decade, nickel has emerged as a cheaper and more sustainable alternative to second and third-row metals for a wide variety of chemical transformations.For example, NPLs 1 and 2 disclose ligand-free, Ni-catalyzed perfluoroalkylation protocols.NPL 1: Deolka, S.; Govindarajan, R.; Vasylevskyi, S.; Roy, M. C.; Khusnutdinova, J. R.; Khaskin, E., Ligand-free nickel catalyzed perfluoroalkylation of arenes and heteroarenes. Chem. Sci. 2022, 13 (44), 12971-12979.NPL 2: Shreiber, S. T.; Vicic, D. A., Solvated Nickel Complexes as Stoichiometric and Catalytic Perfluoroalkylation Agents. Angew. Chem. Int. Ed. 2021, 60 (33), 18162-18167.SummaryHowever, the conventional ligand-free, Ni-catalyzed perfluoroalkylation protocols described above have a significant downside in that a different pre-catalyst (CH3CN)2Ni-(CnF2n+1)2has to be prepared for each perfluoroalkyl -CnF2n+1group.Accordingly, one object of the present disclosure is to provide a catalyst that can be used in a variety of reactions involving a formation of a carbon-carbon bond.Another object of the present disclosure is to provide a modified compound that can be prepared by a reaction involving a formation of a carbon-carbon bond.Another object of the present disclosure is to provide a method of preparing a modified compound that can be prepared by a reaction involving a formation of a carbon-carbon bond.(Solution to Problem)The inventors conducted diligent investigation with the aim of solving the problem set forth above. The inventor discovered that the specific cyclometalated nickel complex can catalyze a reaction involving a carbon-carbon bond formation, and, in this manner, completed the present disclosure.The gist of the present disclosure is as follows:[1] A catalyst used in a reaction involving a formation of a carbon-carbon bond, wherein the catalyst is represented by a formula (I):whereinR1is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group;R2is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group;each R3is independently selected from the group consisting of CH2, CHF and CF2;R4and R5are the same or different and each is a polar organic solvent comprising at least one selected from a nitrogen atom, an oxygen atom, a sulfur atom and a halogen atom;n is an integer larger than 0; anddashed lines connecting Ni (II) and R4andR5are coordinate bonds.[2] The catalyst according to [1], wherein R1is a fluorine atom.[3] The catalyst according to [1] or [2], wherein R2is a fluorine atom.[4] The catalyst according to any one of [1] to [3], wherein each R3is CF2.[5] The catalyst according to any one of [1] to [4], wherein R4and R5are independently selected from the group consisting of an alcohol, an amide, a ketone, an ether, a nitrile, an alkyl halide and a sulfoxide.[6] The catalyst according to any one of [1] to [5], wherein both R4and R5are CH3CN.[7] The catalyst according to any one of [1] to [6], wherein n is an integer from 1 to 3.[8] The catalyst according to any one of [1] to [7], wherein the carbon-carbon bond is formed between a carbon atom of a substrate and a fluorocarbon group of a fluorocarbon compound.[9] The catalyst according to [8], wherein the substrate comprises at least one of an aromatic carbon ring and an aromatic heterocyclic ring.

[0010] The catalyst according to [8] or [9], wherein the fluorocarbon compound comprises at least one -(CF2)m-, wherein m is an integer larger than 0.

[0011] The catalyst according to any one of [8] to

[0010] , wherein the fluorocarbon compound is represented by formula (II-1), (II-2), (II-3) or (II-4):whereinRais selected from the group consisting of a fluorine atom, an aryl group and a heteroaryl group, wherein the aryl group and the heteroaryl group are each optionally substituted by one or more substituents selected from the group consisting of a heteroatom and an alkyl group;Rbis a single bond or an oxygen atom; andm is an integer larger than 0.

[0012] A modified compound prepared by a reaction involving a formation of a carbon-carbon bond, wherein the reaction uses a catalyst represented by a formula (I):whereinR1is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group;R2is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group;each R3is independently selected from the group consisting of CH2, CHF and CF2;R4and R5are the same or different and each is a polar organic solvent comprising at least one selected from a nitrogen atom, an oxygen atom, a sulfur atom and a halogen atom;n is an integer larger than 0; anddashed lines connecting Ni (II) and R4andR5are coordinate bonds.

[0013] A method of preparing a modified compound represented by formula (IV), comprising:reacting a substrate represented by formula (III) with a fluorocarbon compound represented by formula (II-1), (II-2), (II-3) or (II-4) as defined above, in the presence of the catalyst as defined above to obtain the modified compound represented by formula (IV):whereinA is selected from the group consisting of an aromatic carbon ring and an aromatic heterocyclic ring, wherein the aromatic carbon ring and the aromatic heterocyclic ring may be substituted by one or more substituents;A may be a part of a peptide or protein; andRa, Rband m are as defined above.

[0014] The method according to

[0013] , wherein A is selected from the group consisting of a benzene ring and an aromatic heterocyclic ring having 5 to 12 ring atoms.

[0015] The method according to

[0013] or

[0014] , wherein A is an indole ring of a tryptophan residue in a peptide or a protein.(Advantageous Effects)According to the present disclosure, it is possible to provide a catalyst that can be used in a variety of reactions involving a formation of a carbon-carbon bond.Moreover, according to the present disclosure, it is possible to provide a modified compound that can be prepared by a reaction involving a formation of a carbon-carbon bond.Furthermore, according to the present disclosure, it is possible to provide a method of preparing a modified compound that can be prepared by a reaction involving a formation of a carbon-carbon bond.In the accompanying drawings:FIG. 1 shows an example of a modified compound prepared by a reaction using the presently disclosed catalyst;FIG. 2 shows another example of modified compounds prepared by a reaction using the presently disclosed catalyst;FIG. 3 shows another example of a modified compounds prepared by a reaction using the presently disclosed catalyst.DETAILED DESCRIPTIONThe presently disclosed techniques will be described in detail below.(Terms)"Alkyl group" may be linear or branched, and the number of carbon atoms may generally be 1 to 20. "Alkyl group" includes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, tert-pentyl, neopentyl, amyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, etc."Alkenyl group" may be linear or branched, and the number of carbon atoms may generally be 2 to 20. "Alkenyl group" includes vinyl, allyl, butenyl, butadienyl, pentel, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, etc."Alkynyl group" may be linear or branched, and the number of carbon atoms may generally be 2 to 20. "Alkynyl group" includes ethynyl, propagyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, dodecynyl, etc."Cycloalkyl group" may be a monocyclic group or a polycyclic group, and the number of carbon atoms may generally be 3 to 30. "Cycloalkyl group" includes cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, methylcyclohexyl, ethylcyclohexyl, etc."Alkylene group" may be linear or branched, and the number of carbon atoms may generally be 1 to 20. "Alkylene group" includes methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, octylene, nonylene, decylene, undecylene, dodecylene, etc."Alkenylene group" may be linear or branched, and the number of carbon atoms may generally be 2 to 20 carbon atoms. "Alkenylene group" includes vinylene, propenylene, butenylene, butadienylene, octenylene, decenylene, dodecenylene, etc."Alkynylene group" may be linear or branched, and the number of carbon atoms may generally be 2 to 20 carbon atoms. "Alkynylene group" includes ethynylene, propynylene, butynylene, pentynylene, hexynylene, heptynylene, octynylene, noninylene, decynylene, undecinylene, dodecinylene group, etc."Alkoxy group" is an alkyl-O-, and the description of the alkyl group above applies to the alkyl moiety. "Alkoxy group" includes methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, allyloxy, etc."Aryl group" is a monovalent aromatic hydrocarbon group, and the number of carbon atoms may generally be 6 to 20 carbon atoms. "Aryl group" includes phenyl, naphthyl, biphenyl, phenanthryl, etc."Heteroaryl group" is a monovalent aromatic heterocyclic group, and the number of ring atoms may generally be 4 to 10. Hetero atoms may be nitrogen, oxygen and sulfur. "Heteroaryl group" includes pyridinyl, furanyl, thiophenyl, etc."Arylene group" is a divalent group corresponding to an aryl group."Heteroarylene group" is a divalent group corresponding to a heteroaryl group."Heteroatom" is any atom other than hydrogen and carbon atoms."Heteroatom group" is a monovalent group containing at least one heteroatom. "Heteroatom group" includes carboxy group, hydroxy group, sulfo group, phosphate group, amino group, etc."Halogen atom" involves fluorine, chlorine, bromine and iodine atoms."Carbon-carbon bond" is a covalent bond between two carbon atoms. The "carbon-carbon bond" can be a single bond, a double bond, or a triple bond, but preferably a single bond."Fluorocarbon group" is a monovalent or divalent group containing at least one bond connecting a carbon atom and a fluorine atom. "Fluorocarbon group" includes -CF2-, -CFH-, -CF3, -CF2H, -CFH2, -etc."Aromatic carbon ring" may be monocyclic or polycyclic, and the number of ring atoms may generally be 6 to 14. "Aromatic carbon ring" includes benzene, naphthalene, anthracene, etc. "Aromatic carbon ring" may be substituted by one or more substituents. The substituent includes, for example, an alkyl group, an alkoxy group, an aryl group, an aralkyl group and a heteroatom group, which are each optionally substituted by one or more substituents such as an amino group, a halogen atom, a carboxyl group, a hydroxy group, etc. "Aromatic carbon ring" may be a part of a peptide or protein."Aromatic heterocyclic ring" contains at least one atom selected from nitrogen, oxygen and sulfur as a ring atom. "Aromatic heterocyclic ring" may be monocyclic or polycyclic, and the number of ring atoms may generally be 5 to 14. Monocyclic ring includes pyrrole, furan, thiophene, pyrazole, imidazole, oxazole, thiazole, isoxazole, pyridine, pyrimidine, pyrazine, pyridazine, triazine, etc. Polycyclic ring includes indole ring, isoindole, benzofuran, benzoxazole, indazole, benzimidazole, purine, etc. "Aromatic heterocyclic ring" may be substituted by one or more substituents. The substituent includes, for example, an alkyl group, an alkoxy group, an aryl group, an aralkyl group and a heteroatom group, which are each optionally substituted by one or more substituents such as an amino group, a halogen atom, a carboxyl group, a hydroxy group, etc. "Aromatic heterocyclic ring" may be a part of a peptide or protein.(Catalyst)The presently disclosed catalyst is represented by formula (I):wherein, R1is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group;R2is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group;each R3is independently selected from the group consisting of CH2, CHF and CF2;R4and R5are the same or differentand each is a polar organic solvent comprising at least one selected from a nitrogen atom, an oxygen atom, a sulfur atom and a halogen atom;n is an integer larger than 0; anddashed lines connecting Ni (II) and R4andR5are coordinate bonds.Note that in a case in which n in formula (I) is larger than 1, each R3may be the same or different.In formula (I), R1is selected from the group consisting of a hydrogen atom (H), a fluorine atom (F), a hydrocarbon group and a heterocyclic group.Examples of hydrocarbon groups constituting R1include, but are not specifically limited to, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, and an aryl group.Examples of heterocyclic groups constituting R1include, but are not specifically limited to, a thienyl group, a pyrrolyl group, a furyl group, a pyridyl group, a piperidyl group, a quinolyl group, an isoquinolyl group, a triazyl group, a quinazolinyl group, an imidazolyl group, etc.Preferably, R1in formula (I) is a fluorine atom.In formula (I), R2is selected from the group consisting of a hydrogen atom (H), a fluorine atom (F), a hydrocarbon group and a heterocyclic group.The hydrocarbon groups that can constitute R2include the same hydrocarbon groups that can constitute R1.The heterocyclic groups that can constitute R2include the same heterocyclic groups that can constitute R1.Preferably, R2in formula (I) is a fluorine atom.In formula (I), each R3is independently selected from the group consisting of CH2, CHF and CF2. Preferably, each R3in formula (I) is CF2.In formula (I), R4and R5are the same or different and each is a polar organic solvent comprising at least one selected from a nitrogen atom (N), an oxygen atom (O), a sulfur atom (S) and a halogen atom. Examples of such polar organic solvents include, but are not specifically limited to, alcohols such as methanol (CH3OH), ethanol (CH3CH2OH), 1-propanol (CH3CH2CH2OH), 2-propanol (CH3CH(OH)CH3) and 1-butanol (CH3CH2CH2CH2OH); ketones such as acetone (CH3C(=O)CH3); sulfoxides such as dimethyl sulfoxide (CH3S(=O)CH3); nitriles such as acetonitrile (CH3CN); ethers such as tetrahydrofuran (C4H8O) and diethyl ether (CH3CH2OCH2CH3); alkyl halides such as dichloromethane (CH2Cl2); and amides such as N,N-dimethylformamide (HC(=O)N(CH3)2). Of these, acetonitrile (CH3CN) is preferable.Note that R4and R5in formula (I) may be the same or different, but are preferably the same.In formula (I), n is an integer larger than 0, preferably an integer from 1 to 3, more preferably from 1 to 2, and most preferably 1.Dashed lines connecting Ni (II) and R4and R5in formula (I) represent coordinate bonds in which an electron pair is supplied from an electron pair donor (i.e. a nitrogen atom (N), an oxygen atom (O), a sulfur atom (S) or a halogen atom in R4and R5)to an electron pair acceptor (i.e. Ni (II)).<Reaction involving a formation of a carbon-carbon bond>The presently disclosed catalyst set forth above can be used in a reaction involving a formation of a carbon-carbon bond. The reaction, in which the presently disclosed catalyst can be used, is not specifically limited, so long as it involves a formation of a carbon-carbon bond.In some embodiments of the present disclosure, the carbon-carbon bond is formed between a carbon atom of a substrate and a fluorocarbon group of a fluorocarbon compound.<<Substrate>>The substrate is not specifically limited, so long as it has at least one carbon atom that can form a carbon-carbon bond with a fluorocarbon group of a fluorocarbon compound through a reaction using the presently disclosed catalyst.The substrate preferably comprises at least one of an aromatic carbon ring and an aromatic heterocyclic ring. Among aromatic carbon rings, benzene ring is preferable. Among aromatic heterocyclic rings, an aromatic heterocyclic ring having 5 to 12 ring atoms is preferable, an aromatic heterocyclic ring having 5 to 9 ring atoms is more preferable, and a furan ring, a pyrrole ring, a pyrazine ring, a pyrimidine ring and an indole ring are even more preferable.In some embodiments of the present disclosure, the substrate is represented by formula (V):In formula (V), B is an unsubstituted aromatic carbon ring or aromatic heterocyclic ring.R6in formula (V) is selected from the group consisting of an alkyl group, an alkoxy group, an aryl group, an aralkyl group and a heteroatom group, wherein the alkyl group, the alkoxy group, the aryl group, the aralkyl group and the heteroatom group are each optionally substituted by one or more substituents selected from the group consisting of an amino group, a halogen atom, a carboxyl group, and a hydroxy group. In a case in which there are more than 2 substituents, they may be the same or different.The "p" in formula (V) is an integer of not less than 0, and preferably not less than 1, and preferably less than 6, more preferably less than 5, even more preferably less than 4, and most preferably less than 3. In a case in which p in formula (V) is not less than 2, each R6may be the same or different.In some embodiments of the present disclosure, the substrate is a peptide or protein comprising at least one selected from a tryptophan residue, a histidine residue, a tyrosine residue and a phenylalanine residue. Preferably, the substrate is a peptide or protein comprising at least one tryptophan residue. The number of amino acid residues in the peptide or protein is not specifically limited. The number of amino acid residues in the peptide or protein is preferably 200 or less, more preferably 100 or less, and even more preferably 50 or less. Preferably, the protein or peptide has a tryptophan residue, a histidine residue, a tyrosine residue or a phenylalanine residue at the N-terminus or C-terminus of a peptide or protein.<<Fluorocarbon compound>>The fluorocarbon compound is a compound comprising at least one fluorocarbon group. The fluorocarbon group in the fluorocarbon compound can form a carbon-carbon bond with a carbon atom of a substrate through a reaction using the presently disclosed catalyst.The fluorocarbon compound preferably comprises at least one -(CF2)m-, wherein m is an integer larger than 0. Although no specific limitations are placed on the upper limit for m, the upper limit can be set, for example, as 50 or less, 40 or less, or 30 or less.The fluorocarbon compound preferably comprises at least one perfluoroalkyl group. Examples of perfluoroalkyl groups include, but are not specifically limited to, CF3, C2F5, C3F7, C4F9, C5F11, C6F13, C7F15, C8F17,etc.The fluorocarbon compound may be a fluoroalkylating agent (e.g., a trifluoroalkylating agent). Examples of fluorocarbon compounds include, but are not specifically limited to, an acid Togni reagent represent by formula (II-1), an alcohol Togni reagent represent by formula (II-2), an Umemoto reagent represent by formula (II-3), and an Umemoto II reagent represented by formula (II-4):In formula (II-1), (II-2), (II-3) and (II-4), Rais selected from the group consisting of a fluorine atom, an aryl group and a heteroaryl group, wherein the aryl group and the heteroaryl group are each optionally substituted by one or more substituents. The substituent is selected from the group consisting of a heteroatom and an alkyl group, and preferably a halogen atom. In a case in which there are more than 2 substituents, they may be the same or different. Note that the fluorocarbon compound may form a salt.Preferred examples of Rainclude, for example, a fluorine atom and those represented by formula (a-1) to (a-3) shown below:Rbin formula (II-1), (II-2), (II-3) and (II-4) is a single bond or an oxygen atom.The "m" in formula (II-1), (II-2), (II-3) and (II-4) is as defined in -(CF2)m-.The fluorocarbon compound is preferably an acid Togni reagent or an alcohol Togni reagent, and more preferably an acid Togni reagent.<Preparation method of catalyst>The presently disclosed catalyst can be synthesized by a commonly known method such as those described in the literature below.Kaplan, P. T.; Xu, L.; Chen, B.; McGarry, K. R.; Yu, S.; Wang, H.; Vicic, D. A., "Mild, Safe, and Versatile Reagents for (CF2)nTransfer and the Construction of Fluoroalkyl-Containing Rings." Organometallics 2013, 32 (24), 7552-7558.(Modified compound)The presently disclosed modified compound is prepared by a reaction that involves a formation of a carbon-carbon bond using the presently disclosed catalyst set forth above. The reaction used for the preparation of the modified compound is not specifically limited, so long as it involves a formation of a carbon-carbon bond using the presently disclosed catalyst.In some embodiments of the present disclosure, the presently disclosed modified compound is prepared by a reaction in which a carbon-carbon bond is formed between a carbon atom of a substrate and a fluorocarbon group of a fluorocarbon compound in the presence of the presently disclosed catalyst.In the aforementioned embodiment, the substrate and the fluorocarbon compound can be those described above in the "Catalyst" section.In a case in which the substrate is not a peptide or a protein, the amount of a fluorocarbon compound relative to the amount of a substrate used in the reaction is preferably 0.8 molar equivalent or more, and more preferably 1 molar equivalent or more, and preferably 2 molar equivalent or less, and more preferably 1.5 molar equivalent or less.In a case in which the substrate is a peptide or a protein, the amount of a fluorocarbon compound relative to the amount of a substrate used in the reaction is preferably 0.8 molar equivalent or more, and more preferably 1 molar equivalent or more, and preferably 5 molar equivalent or less, and more preferably 4 molar equivalent or less.When the amount of a fluorocarbon compound relative to the amount of a substrate is not less than the lower limit set forth above, the reaction yield can increase. When the amount of a fluorocarbon compound relative to the amount of a substrate is not more than the upper limit set forth above, reagent cost can be reduced.The amount of a catalyst used in the reaction when the amount of a substrate used in the reaction is taken to be 100 mol% is preferably 5 mol% or more, and more preferably 7.5 mol% or more, and preferably 20 mol% or less, and more preferably 15 mol% or less. When the amount of a catalyst is 5 mol% or more, the reaction yield can increase. On the other hand, when the amount of a catalyst is 20 mol% or less, reagent cost can be reduced.The reaction is usually performed in the presence of a solvent. The solvent used includes, but is not limited to, the polar organic solvents described above in the "Catalyst" section.In addition to the catalyst, the substrate, the fluorocarbon compound and the solvent set for above, additives may be added to the reaction mixture. Additives are not specifically limited so long as they do not affect the reaction catalyzed by the presently disclosed catalyst.The reaction temperature is not specifically limited, but the reaction temperature is preferably from 10°C to 120°C, and more preferably 20°C to 100°C. The reaction time can be set as appropriate depending on the desired reaction yield, but the reaction time is preferably 12 hours or more, more preferably 24 hours or more, and even more preferably 36 hours or more. From a viewpoint of increasing reaction yield, it is preferable that the reaction is performed under nitrogen atmosphere.(Method of preparing modified compound)The presently disclosed method of preparing a modified compound represented by formula (IV) comprises reacting a substrate represented by formula (III) with a fluorocarbon compound represented by formula (II-1), (II-2). (II-3) or (II-4) set forth above, in the presence of the presently disclosed catalyst set forth above to obtain the modified compound represented by formula (IV)."A" in formula (III) and (IV) is selected from the group consisting of an aromatic carbon ring and an aromatic heterocyclic ring, wherein the aromatic carbon ring and the aromatic heterocyclic ring may be substituted by one or more substituents. Examples of substituents include, but are not specifically limited to, an alkyl group, an alkoxy group, an aryl group, an aralkyl group and a heteroatom group, which are each optionally substituted by one or more substituents such as an amino group, a halogen atom, a carboxyl group, a hydroxy group, etc.Among aromatic carbon rings that can constitute "A", a benzene ring is preferable. Among aromatic heterocyclic rings that can constitute "A", an aromatic heterocyclic ring having 5 to 12 ring atoms is preferable, an aromatic heterocyclic ring having 5 to 9 ring atoms is more preferable, and a furan ring, pyrrole ring, a pyrazine ring, a pyrimidine ring and an indole ring are even more preferable."A" in formula (III) and (IV) may be a part of a peptide or protein. Specifically, "A" can be a part of a peptide or protein comprising at least one selected from a tryptophan residue, a histidine residue, a tyrosine residue and a phenylalanine residue. Preferably, "A" is an indole ring of a tryptophan residue in a peptide or protein, and the reaction attaches Ra-Rb-(CF2)m- to 2-position of an indole ring in a tryptophan residue shown below.In some embodiments of the present disclosure, the method of preparing a modified compound comprises reacting a substrate represented by formula (V) with a fluorocarbon compound represented by formula (II-1), (II-2), (II-3) or (II-4) set forth above, in the presence of the presently disclosed catalyst set forth above to obtain the modified compound represented by formula (VI)."B", R6, Ra, Rb, "p" and "m" in formula (V) and (VI) are as defined above.The presently disclosed method of preparing a modified compound represented by formula (IV) can further comprise purifying the resultant modified compound. The purification method used to purify the modified compound may be, but is not specifically limited to, a known purification method such as solvent extraction or column chromatography.Also note that purification of the modified compound may be repeated multiple times.The present disclosure also relates to a use of the catalyst represented by formula (I) set forth above in a reaction involving a formation of a carbon-carbon bond.ExamplesThe following provides a more specific description of the present disclosure based on examples.The materials and analytical methods used in the experiments are as follows.Example 1<Materials>All chemicals unless noted otherwise were purchased from commercial suppliers (TCI, Sigma-Aldrich, CF-Plus chemicals and Nacalai Tesque) and used without purification. Anhydrous solvents were dispensed from an MBRAUN solvent purification system and degassed prior to use. Anhydrous deuterated solvents were purchased from Eurisotop / Aldrich / Merck and stored over 4 angstroms molecular sieves. 1-trifluoromethyll-1,2-benziodoxol-3(1H)-one (contains 60 % Diatomaceous earth). Metal precursor (C4F8)Ni(MeCN)2was prepared according to Kaplan, P. T. et al., "Mild, Safe, and Versatile Reagents for (CF2)nTransfer and the Construction of Fluoroalkyl-Containing Rings. " Organometallics 2013, Vol. 32 (24), p. 7552-7558.Synthesis of peptides were performed under the analogue condition reported by Saze and coworkers in Chapter 6, Plant Epigenetics and Epigenomics.<Sample Characterization>NMR spectra were measured on JEOL ECZ600R 600MHz, JEOL ECZ400S 400 MHz and Bruker Avance III Neo 500 MHz (CryoProbe) spectrometers. The following abbreviations are used for describing NMR spectra: s (singlet), d (doublet), t (triplet), br. s (broad singlet), vd (virtual doublet), vt (virtual triplet), tq (triplet of quartets), qt (quartet of triplets), and br (broad).To reference the19F NMR spectra, α,α,α-trifluorotoluene was used and the corresponding chemical shift was appeared at -61.04 ppm in DMSO solvent at ambient conditions.Electrospray Ionization High-Resolution Mass Spectrometry (ESI-HRMS) measurements were performed on a Thermo Scientific ETD apparatus.Absorbance UV / vis spectra were collected using an Agilent Cary 60 instrument.All reactions were performed under a nitrogen atmosphere unless indicated otherwise. NMR yield was based on integration against α,α,α-trifluorotoluene as an internal standard.Example 2 (Development of catalytic protocol)Inside the glovebox, a 20 mL vial equipped with a magnetic stirring bar was charged with 1-phenylpyrrole (10.0 mg, 0.069 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (66.2 mg, 0.082 mmol, acid Togni reagent) and (C4F8)Ni(MeCN)2(2.2 mg, 6.9 μmol). Then anhydrous DMSO (dimethyl sulfoxide) or other solvent (1 mL) was added. The reaction mixture was stirred vigorously at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (8.5 μL, 0.069 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy (Table 1).Table 1. Optimization of reaction conditions for C-H trifluoromethylation using Acid-Togni-CF3as a source.The first catalytic experiment was attempted with acid CF3-Togni reagent), 10 mol% of 1, and 1-phenylpyrrole, under air in DMSO. Already with these conditions we were able to observe 15% of functionalized product (Table 1, entry 1). Performing the same reaction under nitrogen atmosphere gave a more practical 78% yield (entry 2) after 24 h at RT. The reaction can also be performed in other solvents, such as DCM (dichloromethane) and MeCN (acetonitrile), affording the product in 62 and 60% yields (entries 3 and 4) respectively. The yield decreases when using protic MeOH (methanol) solvent, but interestingly there is still 40% of product (entry 5).Control reactions with NiCl2(glyme) and NiBr2(glyme) salts (entries 6 and 7; glyme = dimethoxyethane) as catalysts resulted in 1% and 4% desired product formation (entries 6 and 7). Using Ni(II) trifluoromethanesulfonate as catalyst resulted in 5% product formation after 24 h, (see entry 8). The control reaction in the absence of any nickel additive afforded 7% of trifluoromethylated product (see entry 9).Example 3 (General procedure)Inside the glovebox, a 20 mL vial equipped with a stirring bar was charged with substrate (1equiv), 1-perfluoroalkyl-1,2-benziodoxol-3(1H)one (1-1.2 equiv, see below scheme) and (C4F8)Ni(MeCN)2(10 mol%) dissolved in anhydrous DMSO. The reaction mixture was vigorously stirred for 24-48 hours. After reaction completion, the reaction mixture was transferred to a separatory funnel outside the glovebox and mixed with ethyl acetate and saturated aqueous NaCl. After the first extraction, the organic layer was separated, and the remaining water layer was again extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulfate. Further the reaction mixture was concentrated under vacuum. The reaction mixture was then purified by flash column chromatography on silica gel or HPLC method afforded the desired product.Example 4Inside the glovebox, a 20 mL vial equipped with a magnetic stirring bar was charged with 1-phenylpyrrole (10.0 mg, 0.069 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (66.2 mg, 0.082 mmol) and (C4F8)Ni(MeCN)2(2.2 mg, 6.9 μmol) . Then anhydrous DMSO (1 mL) was added. The reaction mixture was stirred vigorously at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (8.5 μL, 0.069 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 78% (FIG. 1).Example 5The general procedure was followed using 1-(4-Chlorophenyl)-1H-pyrrole (100 mg, 0.56 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)one (534 mg, 0.67 mmol), (C4F8)Ni(MeCN)2(19 mg, 0.056 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 48 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (95:5) gave b as colorless solid (103 mg, 74% yield, FIG. 1).1H NMR (500 MHz, CDCl3, 23 °C): δ 7.44-7.42 (m, 2H), 7.33-7.31 (br.m, 2H), 6.86-6.85 (m, 1H), 6.75-6.73 (m, 1H), 6.29-6.28 (m, 1H).13C NMR (101 MHz, CDCl3, 23 °C): δ 137.7, 134.6, 129.4, 127.9, 127.3 (q, J = 1.7 Hz), 122.4 (q, J = 38.1 Hz), 120.6 (q, J = 268.1 Hz), 113.2 (q, J = 3.4 Hz), 108.7.19F NMR (565 MHz, CDCl3, 23 °C): δ -55.8 (3F)HRMS (ESI) calculated for [M*H]+,C11H7F3N1Cl1: m / z 246.0292; found, 246.0294.Example 6A 20 mL vial equipped with a magnetic stirring bar was charged with N-benzylpyrrole (7.7 μL, 0.05 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (47.4 mg, 0.06 mmol) and (C4F8)Ni(MeCN)2(1.7 mg, 0.005 mmol), and then dissolved in anhydrous DMSO (1 mL). The reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (6.1 μL, 0.05 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 89% (FIG. 1).Example 7A 20 mL vial equipped with a magnetic stirring bar was charged with N-Methyl pyrrole (8.8 μL, 0.10 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (94.8 mg, 0.12 mmol) and (C4F8)Ni(MeCN)2(3.4 mg, 0.01 mmol), were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (12.2 μL, 0.1 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 81% (FIG. 1).Example 8The general procedure was followed using Trimethoxy benzene (100 mg, 0.59 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)one (564 mg, 0.70 mmol), (C4F8)Ni(MeCN)2(20.2 mg, 0.059 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by flash column chromatography was completed (mobile phase: hexane / ethyl acetate (95:5) as colorless solid (88 mg, 62% yield, FIG. 1).1H NMR (400 MHz, CDCl3, 23 °C): δ 6.13 (s, 2H), 3.84 (s, 9H).13C NMR (101 MHz, CDCl3, 23 °C): δ 163.6, 160.6, 124.5 (q, J = 273.1 Hz), 100.7-100.4 (m), 91.4, 56.4, 55.5.19F NMR (376 MHz, CDCl3, 23 °C): δ -54.0 (3F).HRMS (ESI) calculated for [M*H]+,C10H11F3O3: m / z 237.0733; found, 237.0753.Example 9The general procedure was followed using 3-methylindole (50 mg, 0.38 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)one (362 mg, 0.45 mmol), (C4F8)Ni(MeCN)2(13 mg, 0.038 mmol) in anhydrous DMSO (1.5 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (95:5) as colorless solid (37 mg, 48% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 8.18 (br s, 1H), 7.64 (d, J = 8.1 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.19 (t, J = 7. Hz, 1H), 2.44 (m, 3H).13C NMR (151 MHz, CDCl3, 23 °C): δ 135.3, 128.2, 124.9, 123.1 (q, J= 268.4 Hz, CF3), 121.6 (q, J = 36.4 Hz), 120.5, 120.2, 114.2 (q, J = 113.0 Hz), 111.7, 8.5.19F NMR (565 MHz, CDCl3, 23 °C): δ -58.5 (3F).HRMS (ESI) calculated for [M*H]+,C10H9F3N: m / z 200.0682; found, 200.0680.Example 10The general procedure was followed using 3-indolepropionic acid (100 mg, 0.52 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)one (501 mg, 0.62 mmol), (C4F8)Ni(MeCN)2(18 mg, 0.052 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by HPLC afforded g as a pale yellow solid (65 mg, 48% yield, FIG. 1).HPLC conditions: (A) MilliQ water and (B) Acetonitrile-Milli-Q water (90:10), both contained 0.1% formic acid. Gradient: 35% B for 0.0-1.0 min, 35-80% B for 1.0-6.0 min, hold 80% B for 6.0-9.0 min, equilibrate 80% B for 9.1-12.0 min.1H NMR (400 MHz, CD3OD, 23 °C): δ 7.65 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.25 (d, J = 7.5 Hz, 1H), 7.10 (d, J = 7.5 Hz, 1H), 3.19 (t, J = 7.6 Hz, 2H), 2.59 (t, J = 7.6 Hz, 2H). (O-H and N-H protons could not observed)13C NMR (101 MHz, CDCl3, 23 °C): δ 176.6, 137.4, 128.0, 125.3, 125.1 (q, J = 271.1 Hz), 122.7 (q, J = 36.8 Hz), 121.1, 120.7, 116.9 (m), 113.1, 36.6, 20.5.19F NMR (376 MHz, CDCl3, 23 °C): δ -58.3 (3F).HRMS (ESI) calculated for [M*Na]+,C12H10F3NO2: m / z 280.0556; found, 280.0564.Example 11The general procedure was followed using Indole-3-acetamide (50 mg, 0.28 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)one (272 mg, 0.33 mmol), (C4F8)Ni(MeCN)2(9.7 mg, 0.028 mmol) in anhydrous DMSO (2 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by HPLC afforded h as a faint yellow white solid (44 mg, 52% yield, FIG. 1).HPLC conditions: (A) MilliQ water and (B) Acetonitrile-Milli-Q water (90:10), both contained 0.1% formic acid. Gradient: 35% B for 0.0-1.0 min, 35-80% B for 1.0-6.0 min, hold 80% B for 6.0-9.0 min, equilibrate 80% B for 9.1-12.0 min.1H NMR (500 MHz, CDCl3, 23 °C): δ 9.21 (br.s, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 6.59 (br.s, 1H), 5.73 (br.s, 1H), 3.90 (s, 2H).13C NMR (126 MHz, CDCl3, 23 °C): δ 175.1, 135.5, 126.9, 125.6, 123.4 (q, J = 37.1 Hz), 122.1 (q, J = 267.2 Hz), 121.7, 120.0, 112.3, 109.9, 29.8.19F NMR (376 MHz, CDCl3, 23 °C): δ -58.2 (3F).HRMS (ESI) calculated for [M*H]+,C11H9F3N2O: m / z 243.0740; found, 243.0766.Example 12The general procedure was followed using Melatonin (50 mg, 0.21 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)one (204.1 mg, 0.25 mmol), (C4F8)Ni(MeCN)2(7.3 mg, 0.021 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by HPLC afforded i as a faint colorless oil (25 mg, 38% yield, FIG. 1).HPLC conditions: (A) MilliQ water and (B) Acetonitrile-Milli-Q water (90:10), both contained 0.1% formic acid. Gradient: 35% B for 0.0-1.0 min, 35-80% B for 1.0-6.0 min, hold 80% B for 6.0-9.0 min, equilibrate 80% B for 9.1-12.0 min.1H NMR (500 MHz, CDCl3, 23 °C): δ 10.06 (br.s, 1H), 8.47 (br s, 1H), 7.22 (d, J= 8.8 Hz, 1H), 6.97 (d, J= 2.3 Hz, 1H), 6.91 (dd, J= 8.9, 2.3 Hz, 1H), 3.78 (s, 3H), 3.49 (m, 2H), 3.01 (t, J= 6.7 Hz, 2H), 1.95 (s, 3H).13C NMR (151 MHz, CDCl3, 23 °C): δ 173.5, 155, 130.5, 127.7, 122.9 (q, J= 36.6 Hz), 116.4, 113.9 (q, J= 2.6 Hz), 113.1, 100.3, 55.9, 40.6, 23.6, 22.4.19F NMR (565 MHz, CDCl3, 23 °C): δ -58.3 (3F).HRMS (ESI) calculated for [M*H]+, C14H16F3N2O2: m / z 301.1158; found, 301.1180.Example 13The general procedure was followed using N-Cbz-L-Tryptophan (100 mg, 0.29 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)one (281 mg, 0.35 mmol), (C4F8)Ni(MeCN)2(10 mg, 0.029 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by HPLC afforded j as a colorless solid (63 mg, 52% yield, FIG. 1).HPLC conditions: (A) MilliQ water and (B) Acetonitrile-Milli-Q water (90:10), both contained 0.1% formic acid. Gradient: 35% B for 0.0-1.0 min, 35-80% B for 1.0-6.0 min, hold 80% B for 6.0-9.0 min, equilibrate 80% B for 9.1-12.0 min.1H NMR (400 MHz, CD3OD, 23 °C): δ 11.47 (br.s, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.25 (m, 8H), 7.09 (t, J = 7.5 Hz, 1H), 4.49 (dd, J = 8.4, 5.8 Hz, 1H), 3.49 (dd, J = 14.6, 5.1 Hz, 1H), 3.27 (m, 1H). (Two protons overlap with water peak)13C NMR (101 MHz, CD3OD, 23 °C): δ 174.9, 158.2, 138.0, 137.3, 129.4, 128.9, 128.6, 125.3, 123.7 (q, J = 36.2 Hz), 123.4 (q, J = 261.2 Hz), 121.2, 121.1, 113.6, 113.0, 67.5, 56.5, 27.8.19F NMR (376 MHz, CD3OD, 23 °C): δ -59 (3F).HRMS (ESI) calculated for [M*Na]+,C20H17F3N2O4: m / z 429.1033; found, 429.1005.Example 14A 20 mL vial equipped with a magnetic stirring bar was charged with 1-phenylpyrrole (10.0 mg, 0.069 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (25.5 mg, 0.069 mmol) and (C4F8)Ni(MeCN)2(2.3 mg, 0.006 mmol), and then dissolved in anhydrous DMSO (1 mL). The reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (8.5 μL, 0.069 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 78% (FIG. 1).Example 15The general procedure was followed using 1-(4-Chlorophenyl)-1H-pyrrole (100 mg, 0.56 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)one (206 mg, 0.56 mmol), (C4F8)Ni(MeCN)2(19 mg, 0.05 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (85:15) gave l as colorless solid (116 mg, 70% yield, FIG. 1).1H NMR (500 MHz, CDCl3, 23 °C): δ 7.42-7.40 (m, 2H), 7.32-7.30 (br.m, 2H), 6.86 (br. s, 1H), 6.74 (br.s, 1H), 6.32 (m, 1H).13C NMR (126, MHz, CDCl3, 23 °C): δ 138.2, 134.8, 129.1, 128.7, 128.6, 122.6-117.5 (m), 120.1, 115.8- 110.8 (m), 114.8 (m), 109.1.19F NMR (376 MHz, CDCl3, 23 °C): δ -83.0 (3F), -102.6 (2F).HRMS (ESI) calculated for [M*H]+,C12H7F5N1Cl1: m / z 296.0260; found, 296.0261.Example 16A 20 mL vial equipped with a magnetic stirring bar was charged with N-benzylpyrrole (15.4 μL, 0.1 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (36.6 mg, 0.1 mmol) and (C4F8)Ni(MeCN)2(3.4 mg, 0.01 mmol), and then dissolved in anhydrous DMSO (1 mL). The reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (12.2 μL, 0.1 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 70% (FIG. 1).Example 17A 20 mL vial equipped with a magnetic stirring bar was charged with 1-(2- Aminophenyl)pyrrole (10 mg, 0.063 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (23.1 mg, 0.063 mmol) and (C4F8)Ni(MeCN)2(2.1 mg, 0.006 mmol), and then dissolved in anhydrous DMSO (1 mL). The reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (7.7 μL, 0.063 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 42% (FIG. 1).Example 18A 20 mL vial equipped with a magnetic stirring bar was charged with N-Methyl pyrrole (8.8 μL, 0.10 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (36.6 mg, 0.10 mmol) and (C4F8)Ni(MeCN)2(3.4 mg, 0.01 mmol), were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (12.2 μL, 0.1 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 90% (FIG. 1).Example 19A 20 mL vial equipped with a magnetic stirring bar was charged with 2-Methylfuran (4.4 μL, 0.050 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (18.3 mg, 0.050 mmol) and (C4F8)Ni(MeCN)2(1.7 mg, 0.005 mmol), which were dissolved in anhydrous DMSO (1 mL). The reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (6.1 μL, 0.05 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 37% (FIG. 1).Example 20The general procedure was followed using Trimethoxy benzene (100 mg, 0.59 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)one (217.6 mg, 0.59 mmol), (C4F8)Ni(MeCN)2(20.2 mg, 0.059 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (95:5) gave q as a colorless solid (140 mg, 82% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 6.15 (s, 2H), 3.83 (s, 3H), 3.81 (s, 6H).13C NMR (151 MHz, CDCl3, 23 °C): δ 163.9, 161.7, 123.1-116.9 (qt, J = 285.1 Hz, 38.9 Hz), 116.5-112.3 (tq, J = 246.8 Hz, 40.2 Hz), 98.3 (t, J = 21.8 Hz), 91.8, 56.4, 55.4.19F NMR (565 MHz, CDCl3, 23 °C): δ -85.0 (3F), -106.6 (2F).HRMS (ESI) calculated for [M*Na]+,C11H11F5O3: m / z 309.0503; found, 309.0521.Example 21The general procedure was followed using 2,4,6-Trimethoxypyrimidine (100 mg, 0.58 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)one (215 mg, 0.58 mmol), (C4F8)Ni(MeCN)2(20 mg, 0.059 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 48 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (90:10) gave r as a colorless solid (70 mg, 43% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 4.01 (s, 3H), 3.99 (s, 6H).13C NMR (151 MHz, CDCl3, 23 °C): δ 170.8, 165.4, 122.8-116.6 (tq, J = 246.29 Hz, 40.2 Hz), 115.3-111.4 (qt, J = 286.19 Hz, 39.7 Hz), 86.9 (t, J = 25.5 Hz), 55.3, 55.0.19F NMR (565 MHz, CDCl3, 23 °C): δ -85.2 (3F), -109.6 (2F).HRMS (ESI) calculated for [M*H]+,C9H9F5N2O3: m / z 289.0606; found, 289.0605.Example 22The general procedure was followed using 3,4,5-Trimethoxytoluene (50.5 μL, 0.30 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)one (109.8 mg, 0.30 mmol), (C4F8)Ni(MeCN)2(10.2 mg, 0.03 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (90:10) gave s as colorless solid (28% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 6.52 (s, 1H), 3.89-3.88 (overlap of two singlets, 6H), 2.41 (t, J = 4.8 Hz, 3H).13C NMR (151 MHz, CDCl3, 23 °C): δ 155.4, 154.6, 141.1, 135.1, 123.0-113.3 (m), 113.2 (t, J = 21.1 Hz), 111.3, 62, 60.8, 56.0, 22.1 (t, J = 6.6 Hz).19F NMR (565 MHz, CDCl3, 23 °C): δ -84.3 (3F), -105.4 (2F).HRMS (ESI) calculated for [M*Na]+,C12H13F5O3: m / z 323.0677; found, 323.0688.Example 23A 20 mL vial equipped with a magnetic stirring bar was charged with 2,6-Dimethylpyrazine (10.0 mg, 0.092 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (33.8 mg, 0.092 mmol) and (C4F8)Ni(MeCN)2(3.1 mg, 0.009 mmol), and then dissolved in anhydrous DMSO (1 mL). The reaction mixture was stirred at room temperature for 48 hours. After reaction completion, α,α,α-trifluorotoluene (11.3 μL, 0.092 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 22% (FIG. 1).Example 24The general procedure was followed using 3-Methyl indole (50 mg, 0.38 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (139.5 mg, 0.38 mmol), (C4F8)Ni(MeCN)2(12.9 mg, 0.038 mmol) in anhydrous DMSO (1.5 mL). The reaction mixture was vigorously stirred for 48 hours. Purification by preparatory TLC method (mobile phase: hexane / ethyl acetate (95:5) as colorless solid (50 mg, 52% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 8.16 (br s, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.34 (t, J = 7.7 Hz, 1H), 7.21 (t, J = 7.7 Hz, 1H), 2.44 (s, 3H).13C NMR (151 MHz, CDCl3, 23 °C): δ 135.9, 128.5, 125.0, 122.5-118.2 (m), 120.5, 120.1, 116.3 (t, J = 3 Hz), 112.2 (tq, J = 245.2 Hz), 111.6, 8.6.19F NMR (565 MHz, CDCl3, 23 °C): δ -84.7 (3F), -112.7 (2F).HRMS (ESI) calculated for [M*H]+,C11H9F5N1: m / z 250.0650; found, 250.0669.Example 25The general procedure was followed using N-Cbz-L-Tryptophan (100.2 mg, 0.29 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (108.3 mg, 0.29 mmol), (C4F8)Ni(MeCN)2(10 mg, 0.029 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 48 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (85:15) as colorless solid (70.1 mg, 52% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 8.46 (br.s, 1H), 7.74 (d, J = 8 Hz, 1H), 7.38 (d, J = 8 Hz, 1H), 7.34- 7.28 (m, 6H), 7.26-7.24 (m, 2H), 7.17 (t, J = 8 Hz, 1H), 5.35 (d, J = 8 Hz, 1H) 5.02 - 4.98 (m, 1H), , 4.74-4.70 (m, 1H), 3.45-3.42 (m, 1H), 3.31-3.27 (m, 1H).13C NMR (151 MHz, CDCl3, 23 °C): δ 175.8, 156.0, 136.1, 128.6, 128.3, 128.2, 127.5, 125.4, 121.3, 121.2-120.0 (m, coupling constant could not be measured due to signal overlap), 120.2, 114.7, 112.0, 67.2, 54.6, 27.6.19F NMR (376 MHz, CDCl323 °C): δ -82.5 (3F), -111.4 (2F).HRMS (ESI) calculated for [M*H]+,C21H18F5O4N2: m / z 457.1200; found, 457.1184.Example 26The general procedure was followed using Indole-3-propionic acid (100 mg, 0.52 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)one (193.4 mg, 0.52 mmol), (C4F8)Ni(MeCN)2(18 mg, 0.052 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by HPLC afforded w as a faint yellow-colored solid (47 mg, 28% yield, FIG. 1).HPLC conditions: (A) MilliQ water and (B) Acetonitrile-Milli-Q water (90:10), both contained 0.1% formic acid. Gradient: 35% B for 0.0-1.0 min, 35-80% B for 1.0-6.0 min, hold 80% B for 6.0-9.0 min, equilibrate 80% B for 9.1-12.0 min.1H NMR (600 MHz, CDCl3, 23 °C): δ 8.27 (br.s, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.43 (d, J = 8.3 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 3.24 (m, 2H), 2.73 (m, 2H).13C NMR (151 MHz, CDCl3, 23 °C): δ 177.9, 136.1, 127.3, 125.3, 125.0 - 112.2 (spikes of fluorine signals), 121.0, 120.1, 119.5 (t, J = 27.6 Hz), 118.7,111.9, 35.1, 19.4.19F NMR (565 MHz, CDCl3, 23 °C): δ -84.6 (3F), -112.2 (2F).HRMS (ESI) calculated for [M*Na]+,C13H10F5O2N1Na1: m / z 330.0524; found, 330.0538.Example 27A 20 mL vial equipped with a magnetic stirring bar was charged with Indole-3-carbinol (10 mg, 0.0679 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (24.8 mg, 0.0679mmol) and (C4F8)Ni(MeCN)2(2.3 mg, 0.0067 mmol), and then dissolved in anhydrous DMSO (1 mL). The reaction mixture was stirred at room temperature for 24 hours. After reaction completion, α,α,α-trifluorotoluene (8.3 μL, 0.0679 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 45% (FIG. 1).Example 28The general procedure was followed using Melatonin (100 mg, 0.43 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (157.6 mg, 0.43 mmol), (C4F8)Ni(MeCN)2(14.6 mg, 0.043 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 48 hours. Purification by HPLC afforded y as a faint yellow-colored oil (54 mg, 36% yield, FIG. 1).HPLC conditions: (A) MilliQ water and (B) Acetonitrile-Milli-Q water (90:10), both contained 0.1% formic acid. Gradient: 35% B for 0.0-1.0 min, 35-80% B for 1.0-6.0 min, hold 80% B for 6.0-9.0 min, equilibrate 80% B for 9.1-12.0 min.1H NMR (600 MHz, CDCl3, 23 °C): δ 8.42 (br s, 1H), 7.31 (d, J= 8.8 Hz, 1H), 7.14 (br.s, 1H), 7 (dd, J= 9.1, 1.8 Hz, 1H), 5.86 (br. s, 1H), 3.86 (s, 3H), 3.56 (m, 2H), 3.07 (t, J= 6.8 Hz, 2H), 1.98 (s, 3H).13C NMR (151 MHz, CDCl3, 23 °C): δ 171.5, 155.1, 133.4-127.0 (m), 131.3, 128.2, 120.5-120.0 (m), 118.1 (m), 116.6-116.4 (m), 112.9, 110.8, 100.6, 55.9, 40.5, 24.2, 23.1.19F NMR (376 MHz, CDCl3, 23 °C): δ -82.5 (3F), -111.4 (2F).HRMS (ESI) calculated for [M*H]+,C15H16F5O2N2: m / z 351.1126; found, 351.1135.Example 29The general procedure was followed using 1,3,5-trimethoxybenzene (50 mg, 0.29 mmol), 1-heptafluoropropyl-1,2-benziodoxol-3(1H)one (123.6 mg, 0.29 mmol), (C4F8)Ni(MeCN)2(10 mg, 0.02 mmol) in anhydrous DMSO (1.5 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (95:5) gave z as colorless solid (66 mg, 66% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 6.14 (s, 2H), 3.84 (s, 3H), 3.80 (s, 6H).13C NMR (151 MHz, CDCl3, 23 °C): δ 164.0, 161.8, 121.6 - 107.6 (m, fluorine splitting overlap), 98.4 (t, J = 21.7 Hz), 91.8, 56.4, 55.5.19F NMR (565 MHz, CDCl3, 23 °C): δ -80.5 (3F), -103.4 (2F), -126.8 (2F).HRMS (ESI) calculated for [M*H]+,C12H11F7O3: m / z 337.0669; found, 337.0667.Example 30The general procedure was followed using 2,4,6-Trimethoxypyrimidine (50 mg, 0.29 mmol), 1-heptafluoropropyl-1,2-benziodoxol-3(1H)one (122.2 mg, 0.29 mmol), (C4F8)Ni(MeCN)2(10 mg, 0.02 mmol) in anhydrous DMSO (1.5 mL). The reaction mixture was vigorously stirred for 24 hours. Purification by flash column chromatography (mobile phase: hexane / ethyl acetate (90:10) gave a1 as colorless solid (38 mg, 38% yield, FIG. 1).1H NMR (600 MHz, CDCl3, 23 °C): δ 4.01 (s, 3H), 3.98 (s, 6H).13C NMR (151 MHz, CDCl3, 23 °C): δ 170.9, 165.4, 121.3-113.4 (m, fluorine splitting overlap), 109.5 (qt, J = 287.2, 41.5 Hz), 87.1 (t, J = 25.5 Hz), 55.3, 55.19F NMR (565 MHz, CDCl3, 23 °C): δ -80.5 (3F), -106.5 (2F), -127.1 (2F).HRMS (ESI) calculated for [M*H]+,C10H9F7O3N2: m / z 339.0574; found, 339.0570.Example 31The general procedure was followed using 1,3,5-Trimethoxybenzene (100 mg, 0.59 mmol), 3,3-Dimethyl-1-(perfluorooctyl)-1,3-dihydro-1λ3-benzo[d][1,2]iodaoxole (404.3 mg, 0.59 mmol), (C4F8)Ni(MeCN)2(20.2 mg, 0.05 mmol) in anhydrous DMSO (3 mL). The reaction mixture was vigorously stirred for 48 hours. Purification by HPLC method afforded a2 as a colorless solid (190 mg, 54% yield, FIG. 1).HPLC conditions: (A) MilliQ water and (B) Acetonitrile-Milli-Q water (90:10), both contained 0.1% formic acid. Gradient: 35% B for 0.0-1.0 min, 35-80% B for 1.0-6.0 min, hold 80% B for 6.0-9.0 min, equilibrate 80% B for 9.1-12.0 min.1H NMR (600 MHz, CDCl3, 23 °C): δ 6.13 (s, 2H), 3.84 (s, 3H), 3.80 (s, 6H).13C NMR (151 MHz, CDCl3, 23 °C): δ 164.0, 161.9, 120.4-106.4 (m, fluorine splitting), 98.8 (t, J = 21.8 Hz), 56.4, 55.5.19F NMR (565 MHz, CDCl3, 23 °C): δ -80.7 (3F), -102.6 (2F), -121.6 - -122.7 (10F), -126.1 (2F).HRMS (ESI) calculated for [M*H]+,C17H11F17O3: m / z 587.0510; found, 587.0347.Example 32Inside the glovebox, a 20 mL vial equipped with a stirring bar was charged with 1-(4-Chlorophenyl)-1H-pyrrole (50 mg, 0.28 mmol), 1-(1,1,2,2-Tetrafluoro-2-(1H-imidazol-1-yl)ethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (116.5 mg, 0.28 mmol), and (C4F8)Ni(MeCN)2(9.5 mg, 0.02 mmol) dissolved in anhydrous DMSO (2 mL). The reaction mixture was vigorously stirred for 48 hours. After reaction completion, the reaction mixture was transferred to a separatory funnel outside the glovebox and mixed with ethyl acetate and saturated aqueous NaCl. After the first extraction, the organic layer was separated, and the remaining water layer was again extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulfate. Further the reaction mixture was concentrated under vacuum. The reaction mixture was then purified by flash column chromatography to obtain A1 as a colorless solid (48 mg, 50% yield, FIG. 2).1H NMR (400 MHz, CDCl3, 23 °C): δ 7.97 (dd, J = 26.9, 7.4 Hz, 1H), 7.70 (br.s, 1H), 7.39-7.37 (m, 2H), 7.20-7.15 (m, 2H), 6.99 (s, 1H), 6.83 (br.s, 1H), 6.64 (br.s, 1H), 6.32 (br.s, 1H).13C NMR (151 MHz, CDCl3, 23 °C): δ 169.2, 141.5, 138, 135.7, 135.4-135.2 (m), 134.8, 132.6, 131.4, 129.7-128 (m), 119.5 (t, J = 27.8 Hz), 117.0, 115.4, 109.4, 94.4.19F NMR (565 MHz, CDCl3, 23 °C): δ -94.6 (2F), -102.2 (2F).HRMS (ESI) calculated for [M*H]+,C15H10F4N3Cl: m / z 344.0572; found, 344.0558.Example 33Inside the glovebox, a 20 mL vial equipped with a magnetic stirring bar was charged with 1-Phenylpyrrole (10 mg, 0.0698 mmol), 1-(1,1,2,2-Tetrafluoro-2-(1H-imidazol-1-yl)ethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (28.9 mg, 0.0698 mmol) and (C4F8)Ni(MeCN)2(2.3 mg, 0.0067 mmol), and then dissolved in anhydrous deuterated DMSO (1 mL). The reaction mixture was stirred at room temperature for 48 hours. After reaction completion, α,α,α-trifluorotoluene (8.5 μL, 0.0698 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 51% (FIG. 2).Example 34Inside the glovebox, a 20 mL vial equipped with a stirring bar was charged with 1,3,5-Trimethoxybenzene (50 mg, 0.29 mmol), 1-(1,1,2,2-Tetrafluoro-2-(1H-imidazol-1-yl)ethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (123.1 mg, 0.29 mmol) and (C4F8)Ni(MeCN)2(10.1 mg, 0.029 mmol) dissolved in anhydrous DMSO (2 mL). The reaction mixture was vigorously stirred for 48 hours. After reaction completion, the reaction mixture was transferred to a separatory funnel outside the glovebox and mixed with ethyl acetate and saturated aqueous NaCl. After the first extraction, the organic layer was separated, and remaining water layer was again extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulfate. Further, the reaction mixture was concentrated under vacuum. The reaction mixture was then purified by flash column chromatography to obtain A3 as a colorless solid (42.8 mg, 43 % yield, FIG. 2).1H NMR (400 MHz, CDCl3, 23 °C): δ 7.62 (br.s, 1H), 7.07-7.02 (br.d, 2H), 6.05 (s, 2H), 3.81 (s, 3H), 3.64 (s, 6H).13C NMR (151 MHz, CDCl3, 23 °C): δ 164.0, 161.6, 141.3, 132.3-128.0 (m), 117.9-115.9 (m), 97.3 (t, J = 21.6 Hz), 91.2, 56.1, 55.5.19F NMR (565 MHz, CDCl3, 23 °C): δ -98.2 (2F), -105.6 (2F).HRMS (ESI) calculated for [M*H]+,C14H14F4O3N2: m / z 335.1000; found, 335.1013.Example 35A septum vial equipped with a magnetic stirring bar was charged with 1,3,5-Trimethoxybenzene (10 mg, 0.059 mmol), 1-(2-(4-Bromophenoxy)-1,1,2,2-tetrafluoroethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (30.8 mg, 0.059 mmol) and (C4F8)Ni(MeCN)2(2 mg, 0.0059 mmol), and then dissolved in anhydrous deuterated DMSO (1 mL). The reaction mixture was transferred to an oil bath at 100 ℃ for 24 hours. After reaction completion, α,α,α-trifluorotoluene (7.3 μL, 0.059 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 50% (FIG. 2).Example 36Inside the glovebox, a 20 mL vial equipped with a stirring bar was charged with 1-(4-Chlorophenyl)-1H-pyrrole (50 mg, 0.28 mmol), 1-(2-(4-Bromophenoxy)-1,1,2,2-tetrafluoroethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (146 mg, 0.28 mmol) and (C4F8)Ni(MeCN)2(9.5 mg, 0.02 mmol) dissolved in anhydrous DMSO (2 mL). The reaction mixture was then transferred to an oil bath at 100 ℃ for 24 hours. After reaction completion, the reaction mixture was transferred to a separatory funnel outside the glovebox and mixed with ethyl acetate and saturated aqueous NaCl. After the first extraction, the organic layer was separated, and the remaining water layer was again extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulfate. Further the reaction mixture was concentrated under vacuum. The reaction mixture was then purified by flash column chromatography to obtain A5 as a yellow oil (66 mg, 52% yield, FIG. 2).1H NMR (400 MHz, CDCl3, 23 °C): δ 7.48-7.45 (m, 2H), 7.41-7.33 (m, 4H), 7.02-7 (m, 2H), 6.85-6.84 (m, 1H), 6.82-6.80 (m, 1H), 6.34-6.32 (m, 1H).13C NMR (101 MHz, CDCl3, 23 °C): δ 148.2, 148.0, 138.6, 134.5, 132.9, 132.8, 128.9, 128.7, 128.3, 128.2, 123.4, 121.5 (t, J = 27.4 Hz), 119.7, 117.5 (t, J = 35.4 Hz), 114.7 (m), 113.4 (m), 112.4 (t, J = 37.8 Hz), 108.9.19F NMR (376 MHz, CDCl3, 23 °C): δ -99.3 (2F), -107.0 (2F).HRMS (ESI) calculated for [M*H]+,C18H11F4OBrClN: m / z 449.9701; found, 449.9357.Example 37A septum vial equipped with a magnetic stirring bar was charged with 1-(4-Chlorophenyl)-1H-pyrrole (10 mg, 0.056 mmol), 1-(2-(4-Fluorophenoxy)-1,1,2,2-tetrafluoroethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (25.7 mg, 0.056 mmol) and (C4F8)Ni(MeCN)2(1.9 mg, 0.0056 mmol), and then dissolved in anhydrous deuterated DMSO (1 mL). The reaction mixture was transferred to an oil bath at 100 ℃ for 24 hours. After reaction completion, α,α,α-trifluorotoluene (6.9 μL, 0.069 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 60% (FIG. 2).Example 38A septum vial equipped with a magnetic stirring bar was charged with 1-Benzyl-pyrrole (7.7 μL, 0.05 mmol), 1-(2-(4-Fluorophenoxy)-1,1,2,2-tetrafluoroethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (22.9 mg, 0.05 mmol) and (C4F8)Ni(MeCN)2(1.7 mg, 0.005 mmol), and then dissolved in anhydrous deuterated DMSO (1 mL). The reaction mixture was transferred to an oil bath at 100 ℃ for 24 hours. After reaction completion, α,α,α-trifluorotoluene (6.1 μL, 0.05 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 38% (FIG. 2).Example 39A septum vial equipped with a magnetic stirring bar was charged with 1,3,5-Trimethoxybenzene (10 mg, 0.059 mmol), 1-(2-(4-Fluorophenoxy)-1,1,2,2-tetrafluoroethyl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (27.2 mg, 0.059 mmol) and (C4F8)Ni(MeCN)2(2 mg, 0.0059 mmol), and then dissolved in anhydrous deuterated DMSO (1 mL). The reaction mixture was transferred to an oil bath at 100 ℃ for 24 hours. After reaction completion, α,α,α-trifluorotoluene (7.3 μL, 0.059 mmol) was added as a standard and the yield was determined by19F NMR spectroscopy. The yield was 35% (FIG. 2).Example 40A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-A-NH2) (5 mg, 0.018 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (17.2 mg, 0.021 mmol) and (C4F8)Ni(MeCN)2(0.6 mg, 0.001 mmol), which were dissolved in anhydrous DMSO (0.5 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 79% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 41A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (V-W-V-NH2) (4.2 mg, 0.010 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (9.9 mg, 0.012 mmol) and (C4F8)Ni(MeCN)2(0.3 mg, 0.001 mmol), which were dissolved in anhydrous DMSO (0.5 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 94% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 42A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (G-G-W-R-NH2) (6.7 mg, 0.014 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (13.4 mg, 0.016 mmol) and (C4F8)Ni(MeCN)2(0.4 mg, 0.001 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 89% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 43A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-V-G-A-NH2) (5 mg, 0.011 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (11 mg, 0.013 mmol) and (C4F8)Ni(MeCN)2(0.3 mg, 0.001 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 99% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 44A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-G-V-A-S-G-R-NH2) (7 mg, 0.009 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (9 mg, 0.011 mmol) and (C4F8)Ni(MeCN)2(0.3 mg, 0.0009 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 96% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 45A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-G-V-A-S-G-R-S-T-Q-NH2) (5 mg, 0.004 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (13.5 mg, 0.014 mmol) and (C4F8)Ni(MeCN)2(0.1 mg, 0.0004 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 99% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 46A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-G-V-A-S-G-R-S-T-Q-A-V-NH2) (5 mg, 0.004 mmol), 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (11.6 mg, 0.014 mmol) and (C4F8)Ni(MeCN)2(0.1 mg, 0.0004 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 98% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 47A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-G-V-A-S-G-R-S-T-Q-NH2) (5 mg, 0.004 mmol), 1-pentafluoroethyl-1,2-benziodoxol-3(1H)-one (5.1 mg, 0.014 mmol) and (C4F8)Ni(MeCN)2(0.1 mg, 0.0004 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 88% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 48A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-G-V-A-S-G-R-S-T-Q-A-V-NH2) (5 mg, 0.004 mmol), 1-pentafluoro-1,2-benziodoxol-3(1H)-one (4.5 mg, 0.012 mmol) and (C4F8)Ni(MeCN)2(0.1 mg, 0.0004 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 92% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 49A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-G-V-A-S-G-R-S-T-Q-A-V-NH2) (5 mg, 0.004 mmol), 1-heptafluoropropyl-1,2-benziodoxol-3(1H)-one (5.1 mg, 0.012 mmol) and (C4F8)Ni(MeCN)2(0.1 mg, 0.0004 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 98% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.Example 50A 5 mL vial equipped with a magnetic stirring bar was charged with peptide (W-G-V-A-S-G-R-S-T-Q-A-V-NH2) (5 mg, 0.004 mmol), 3,3-Dimethyl-1-(perfluorooctyl)-1,3-dihydro-1λ3-benzo[d][1,2]iodaoxole (8.3 mg, 0.012 mmol) and (C4F8)Ni(MeCN)2(0.1 mg, 0.0004 mmol), which were dissolved in anhydrous DMSO (1 mL). Further the reaction mixture was stirred at room temperature for 36 hours. After reaction completion, the reaction mixture was analyzed by LC-MS. The yield was 84% (FIG. 3).Note: the nickel precursor was added to the reaction mixture by preparing a stock solution in DMSO.According to the present disclosure, it is possible to provide a catalyst that can be used in a variety of reactions involving a formation of a carbon-carbon bond.Moreover, according to the present disclosure, it is possible to provide a modified compound that can be prepared by a reaction involving a formation of a carbon-carbon bond.Furthermore, according to the present disclosure, it is possible to provide a method of preparing a modified compound that can be prepared by a reaction involving a formation of a carbon-carbon bond.

Claims

1. A catalyst used in a reaction involving a formation of a carbon-carbon bond, wherein the catalyst is represented by a formula (I): wherein R1is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group; R2is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group; each R3is independently selected from the group consisting of CH2, CHF and CF2; R4and R5are the same or different and each is a polar organic solvent comprising at least one selected from a nitrogen atom, an oxygen atom, a sulfur atom and a halogen atom; n is an integer larger than 0; and dashed lines connecting Ni (II) and R4andR5are coordinate bonds.

2. The catalyst according to claim 1, wherein R1is a fluorine atom.

3. The catalyst according to claim 1, wherein R2is a fluorine atom.

4. The catalyst according to claim 1, wherein each R3is CF2.

5. The catalyst according to claim 1, wherein R4and R5are independently selected from the group consisting of an alcohol, an amide, a ketone, an ether, a nitrile, an alkyl halide and a sulfoxide.

6. The catalyst according to claim 1, wherein both R4and R5are CH3CN.

7. The catalyst according to claim 1, wherein n is an integer from 1 to 3.

8. The catalyst according to claim 1, wherein the carbon-carbon bond is formed between a carbon atom of a substrate and a fluorocarbon group of a fluorocarbon compound.

9. The catalyst according to claim 8, wherein the substrate comprises at least one of an aromatic carbon ring and an aromatic heterocyclic ring.

10. The catalyst according to claim 8, wherein the fluorocarbon compound comprises at least one -(CF2)m-, wherein m is an integer larger than 0.

11. The catalyst according to claim 8, wherein the fluorocarbon compound is represented by formula (II-1), (II-2), (II-3) or (II-4): wherein Rais selected from the group consisting of a fluorine atom, an aryl group and a heteroaryl group, wherein the aryl group and the heteroaryl group are each optionally substituted by one or more substituents selected from the group consisting of a heteroatom and an alkyl group; Rbis a single bond or an oxygen atom; andm is an integer larger than 0.

12. A modified compound prepared by a reaction involving a formation of a carbon-carbon bond, wherein the reaction uses a catalyst represented by a formula (I): wherein R1is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group; R2is selected from the group consisting of a hydrogen atom, a fluorine atom, a hydrocarbon group and a heterocyclic group; each R3is independently selected from the group consisting of CH2, CHF and CF2; R4is a polar organic solvent comprising at least one selected from a nitrogen atom, an oxygen atom, a sulfur atom and a halogen atom; R5is a polar organic solvent comprising at least one selected from a nitrogen atom, an oxygen atom, a sulfur atom and a halogen atom; n is an integer larger than 0; and dashed lines connecting Ni (II) and R4andR5are coordinate bonds.

13. A method of preparing a modified compound represented by formula (IV), comprising: reacting a substrate represented by formula (III) with a fluorocarbon compound represented by formula (II-1), (II-2), (II-3) or (II-4) as defined in claim 11, in the presence of the catalyst according to claim 1 to obtain the modified compound represented by formula (IV): wherein A is selected from the group consisting of an aromatic carbon ring and an aromatic heterocyclic ring, wherein the aromatic carbon ring and the aromatic heterocyclic ring may be substituted by one or more substituents; A may be a part of a peptide or protein; and Ra, Rband m are as defined in claim 11.

14. The method according to claim 13, wherein A is selected from the group consisting of a benzene ring and an aromatic heterocyclic ring having 5 to 12 ring atoms.

15. The method according to claim 13, wherein A is an indole ring of a tryptophan residue in a peptide or a protein.

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