WO2017154948A1 - Method for producing fluorinated compound - Google Patents

Method for producing fluorinated compound Download PDF

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Publication number
WO2017154948A1
WO2017154948A1 PCT/JP2017/009144 JP2017009144W WO2017154948A1 WO 2017154948 A1 WO2017154948 A1 WO 2017154948A1 JP 2017009144 W JP2017009144 W JP 2017009144W WO 2017154948 A1 WO2017154948 A1 WO 2017154948A1
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group
compound
reaction
formula
atom
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PCT/JP2017/009144
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French (fr)
Japanese (ja)
Inventor
誠 松浦
山本　明典
洋介 岸川
日馨 柳
高英 福山
修平 隅野
Original Assignee
ダイキン工業株式会社
公立大学法人大阪府立大学
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Priority claimed from JP2016251305A external-priority patent/JP6585024B2/en
Application filed by ダイキン工業株式会社, 公立大学法人大阪府立大学 filed Critical ダイキン工業株式会社
Priority to CN201780016314.2A priority Critical patent/CN108834409B/en
Priority to US16/082,389 priority patent/US20190071376A1/en
Priority to EP17763288.2A priority patent/EP3428145B1/en
Priority to EP21188721.1A priority patent/EP3925945A1/en
Priority to CN202210679598.6A priority patent/CN115181005A/en
Priority to RU2018135068A priority patent/RU2743037C2/en
Priority to KR1020187028447A priority patent/KR102167454B1/en
Publication of WO2017154948A1 publication Critical patent/WO2017154948A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/272—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions
    • C07C17/275—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions of hydrocarbons and halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C19/00—Acyclic saturated compounds containing halogen atoms
    • C07C19/08—Acyclic saturated compounds containing halogen atoms containing fluorine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C22/00—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom
    • C07C22/02—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings
    • C07C22/04—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings containing six-membered aromatic rings
    • C07C22/08—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings containing six-membered aromatic rings containing fluorine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
    • C07C43/14—Unsaturated ethers
    • C07C43/17—Unsaturated ethers containing halogen
    • C07C43/174—Unsaturated ethers containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C67/347—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
    • C07C69/24—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with monohydroxylic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/608—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
    • C07C69/675—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/02—Addition
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods

Definitions

  • the present invention relates to a method for producing a fluorine-containing compound, particularly a compound having a fluoromethylene group.
  • fluorine-containing methylene compounds such as ⁇ -fluoromethylene compounds and ⁇ -difluoroaldol compounds, which are carbonyl compounds having one or more substituents selected from the group consisting of a fluorine atom and a perfluoroorganic group at the ⁇ -position
  • Non-patent Documents 1 and 2 Non-patent Documents 1 and 2.
  • Non-Patent Document 3 an ⁇ -difluoroaldol compound is obtained from trifluoromethylacetone, but requires five steps. Further, since thiophenol is used as a reagent, a highly toxic reagent such as mercury chloride is required to remove sulfur from the reaction system, and the reaction operation becomes complicated.
  • Non-Patent Document 4 2,2-difluoroenol silyl ether obtained by selective cleavage of a carbon-fluorine bond in trifluoromethyl ketone with magnesium is reacted with benzaldehyde in the presence of trifluoromethyl ketone trimethyl silicon chloride.
  • benzaldehyde in the presence of trifluoromethyl ketone trimethyl silicon chloride.
  • ⁇ -difluoroaldol compound is obtained, but it requires a three-step reaction process and requires a large amount of reagent for the reaction substrate, so there is room for improvement in terms of yield and the like. .
  • an inorganic salt is formed as a by-product, and therefore a step for removing it is required. Further improvement or a completely new production method is required from the viewpoint of production cost, reaction efficiency, and convenience.
  • Non-Patent Document 5 uses a fluorine-free compound mediated by visible light as a substrate, and is substituted with an electron-withdrawing group using an amine and a hunting ester (Hantzsch Ester) as an auxiliary agent.
  • An intermolecular addition reaction of glycosyl halides to olefins is disclosed.
  • Non-Patent Document 6 discloses a method for producing a compound having a fluoromethylene group using a fluorine-free compound as a substrate.
  • An object of the present invention is to provide an efficient and new method for producing a compound having a fluoromethylene group.
  • R 1 represents an organic group
  • R X represents a hydrogen atom or a fluorine atom
  • R 2a , R 2b , R 2c , and R 2d are the same or different and represent —Y—R 21 or —N (—R 22 ) 2
  • R 2b and R 2c may be linked to form a bond
  • Y represents a bond, an oxygen atom, or a sulfur atom
  • R 21 represents a hydrogen atom or an organic group
  • R 22 is the same or different at each occurrence and represents a hydrogen atom or an organic group.
  • the present invention includes the following aspects.
  • R 1 represents an organic group
  • R X represents a hydrogen atom or a fluorine atom
  • R 2a , R 2b , R 2c , and R 2d are the same or different and represent —Y—R 21 or —N (—R 22 ) 2 .
  • R 2b and R 2c may be linked to form a bond
  • Y represents a bond, an oxygen atom, or a sulfur atom
  • R 21 represents a hydrogen atom or an organic group
  • R 22 is the same or different at each occurrence and represents a hydrogen atom or an organic group.
  • Item 7. The production method according to any one of Items 1 to 6, wherein the reaction in Step A is carried out in the presence of a catalyst.
  • Item 8. Item 8. The production method according to Item 7, wherein the catalyst is at least one selected from the group consisting of a transition metal complex and an organic dye compound.
  • phrase “containing” is intended to include the phrase “consisting essentially of” and the phrase “consisting of”.
  • room temperature means a temperature within the range of 10 to 40 ° C.
  • Cn-m (where n and m are natural numbers, respectively) has a carbon number of n or more and m or less, as is commonly used in the field of organic chemistry. Represents.
  • fluoromethylene group includes a monofluoromethylene group and a difluoromethylene group unless otherwise specified.
  • halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • the “organic group” means a group containing one or more carbon atoms as its constituent atoms.
  • examples of the “organic group” include a hydrocarbon group, a cyano group, a carboxy group, an alkoxy group, an ester group, an ether group, and an acyl group.
  • the “hydrocarbon group” means a group containing one or more carbon atoms and one or more hydrogen atoms as its constituent atoms.
  • examples of the “hydrocarbon group” include an aliphatic hydrocarbon group, an aromatic hydrocarbon group (aryl group), and combinations thereof.
  • aliphatic hydrocarbon group may be linear, branched, cyclic, or a combination thereof.
  • the “aliphatic hydrocarbon group” may be saturated or unsaturated.
  • examples of the “aliphatic hydrocarbon group” include an alkyl group, an alkenyl group, an alkynyl group, and a cycloalkyl group.
  • examples of the “alkyl group” include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, and hexyl. And a linear or branched alkyl group having 1 to 10 carbon atoms.
  • the “fluoroalkyl group” is an alkyl group in which at least one hydrogen atom is substituted with a fluorine atom.
  • the number of fluorine atoms of the “fluoroalkyl group” is 1 or more (eg, 1 to 3, 1 to 6, 1 to 12, or the maximum number that can be substituted from one). be able to.
  • a “fluoroalkyl group” includes a perfluoroalkyl group.
  • a “perfluoroalkyl group” is an alkyl group in which all hydrogen atoms are substituted with fluorine atoms.
  • alkenyl group examples include vinyl, 1-propenyl, isopropenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, -Ethyl-1-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, and 5- Examples thereof include linear or branched alkenyl groups having 1 to 10 carbon atoms such as hexenyl.
  • alkynyl group examples include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, Linear or branched alkynyl groups having 2 to 6 carbon atoms, such as 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, and 5-hexynyl Is exemplified.
  • examples of the “cycloalkyl group” include cycloalkyl having 3 to 10 carbon atoms (preferably 4 to 10 carbon atoms) such as cyclopentyl group, cyclohexyl group, and cycloheptyl. Examples are groups.
  • alkoxy group is, for example, a group represented by RO— (wherein R is an alkyl group).
  • ester group is, for example, a group represented by RCO 2 — (wherein R is an alkyl group).
  • the “ether group” means a group having an ether bond (—O—) and includes a polyether group.
  • the polyether group is represented by the formula: Ra— (O—Rb) n—, wherein Ra is an alkyl group, Rb is the same or different at each occurrence, is an alkylene group, and n is an integer of 1 or more.
  • a group represented by the formula: An alkylene group is a divalent group formed by removing one hydrogen atom from the alkyl group.
  • the “acyl group” includes an alkanoyl group.
  • the “alkanoyl group” is, for example, a group represented by RCO— (wherein R is an alkyl group).
  • the “aromatic group” includes an aryl group and a heteroaryl group.
  • examples of the “aryl group” include C6-10 aryl groups such as a phenyl group and a naphthyl group.
  • examples of the “heteroaryl group” include, as a ring constituent atom, 5 to 14 containing 1 to 4 heteroatoms selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom in addition to a carbon atom. Includes membered (monocyclic, bicyclic, or tricyclic) heterocyclic groups.
  • heteroaryl group examples include (1) Furyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl Monocyclic aromatic heterocyclic groups such as tetrazolyl and triazinyl; and (2) quinolyl, isoquinolyl, quinazolyl, quinoxalyl, benzofuryl, benzothienyl, benzoxazolyl, benzisoxazolyl Group, benzothiazolyl group, benzimidazolyl group, benzotriazolyl group, indolyl group, indazolyl group, pyrrolopyrazinyl group, imidazopyrazolyl, thiazolyl, is
  • R 1 represents an organic group
  • R X represents a hydrogen atom or a fluorine atom
  • R 2a , R 2b , R 2c , and R 2d are the same or different and represent —Y—R 21 or —N (—R 22 ) 2
  • R 2b and R 2c may be linked to form a bond
  • Y represents a bond, an oxygen atom, or a sulfur atom
  • R 21 represents a hydrogen atom or an organic group
  • R 22 is the same or different at each occurrence and represents a hydrogen atom or an organic group.
  • Suitable examples of the “organic group” represented by R 1 include an alkyl group, a fluoroalkyl group, an alkoxycarbonyl group, and an aromatic group. More preferred examples of the “organic group” represented by R 1 include a fluoroalkyl group.
  • alkoxycarbonyl group examples include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentaboxycarbonyl, isopentoxycarbonyl, hexyl.
  • a C1-6 alkoxycarbonyl group such as an oxycarbonyl group is included.
  • aromatic group examples include an aryl group, and more preferable examples include a C6-10 aryl group such as a phenyl group and a naphthyl group.
  • R X is preferably a fluorine atom.
  • R 2a , R 2b , R 2c and R 2d can suitably be an electron donating group.
  • one or more of R 2a , R 2b , R 2c , and R 2d can be a hydrocarbon group that may have one or more substituents.
  • substituents are: A heteroaryl group optionally having one or more substituents (more preferably a 5- to 18-membered heteroaryl group optionally having one or more substituents), It includes a thioether group which may have one or more substituents, and a silazane group which may have one or more substituents.
  • Suitable examples of the “substituent” in the “optional silazane group” include a halogen atom (preferably fluorine), a cyano group, an amino group, an alkoxy group, a perfluoro organic group (preferably a perfluoro having 1 to 8 carbon atoms). An organic group, more preferably a trifluoromethyl group) and a pentafluorosulfanyl group (F 5 S—).
  • one or more of R 2a , R 2b , R 2c , and R 2d are an unsubstituted hydrocarbon group (preferably a hydrocarbon group having 1 to 10 carbon atoms). Can be.
  • hydrocarbon group examples include an alkyl group (preferably a C1-10 alkyl group), a cycloalkyl group (preferably a C3-10, preferably a C4-8 cycloalkyl group), and an aryl group ( Preferably, a C6-10 aryl group) is included.
  • R 2a is an alkyl group, or an aryl group
  • R 2b, R 2c, and R 2d is a hydrogen atom
  • Examples of leaving groups represented by X are: Halogen atoms (eg, fluorine, chlorine, bromine, and iodine atoms), Alkylsulfonyloxy groups (eg, C1-6 alkylsulfonyloxy groups such as methanesulfonyloxy group and trifluoromethanesulfonyloxy group) and arylsulfonyloxy groups (eg, C6 such as benzenesulfonyloxy group and p-toluenesulfonyloxy group) -10 arylsulfonyloxy group). More preferred examples of X include a halogen atom. More preferred examples of X include chlorine atom, bromine atom, and iodine atom. Even more preferred examples of X include bromine atoms.
  • Halogen atoms eg, fluorine, chlorine, bromine, and iodine atoms
  • R 1 is a fluoroalkyl group, an alkoxycarbonyl group, or an aryl group
  • R X is a fluorine atom
  • R 2a , R 2b , R 2c and R 2d are the same or different and are an alkyl group (preferably a C1-10 alkyl group), a cycloalkyl group (preferably a C3-10 cycloalkyl group, more preferably C4 -8 cycloalkyl group) or an aryl group (preferably a C6-10 aryl group)
  • X is a bromine atom.
  • the amount of compound (3) used in step A is preferably in the range of 0.5 to 10 mol, more preferably in the range of 1 to 8 mol, and 1 mol of compound (2), and More preferably, it is in the range of 1.2 to 6 mol.
  • compound (1) is Can be a ring-closed derivative of the compound represented by the formula (1).
  • the ring formed by the ring closure reaction can preferably be a 5- to 7-membered ring.
  • the ring formed by the ring-closing reaction is one or more (preferably 1, or 2) selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom in addition to a carbon atom as a carbocyclic ring or a ring-constituting atom. ) Of a heteroatom containing a heteroatom.
  • R 2a is an epoxy group (that is, when the compound (3) is an epoxy compound)
  • the compound (1) is converted into a ring-opened derivative of the compound represented by the formula (1) (ie, by a ring-opening reaction) , Epoxy ring-opening derivatives).
  • step A The reaction in step A is performed in the presence of a reducing agent.
  • the reducing agent used in the present invention may be an inorganic or organic reducing agent, examples of which are hydrogen, formic acid, ammonium formate, sodium formate, formic acid-triethylamine, triethylsilane, tetramethyldisiloxane, poly Including nitrogen-containing unsaturated heterocyclic compounds having methylhydrosiloxane, NaBH 3 CN, NHCBH 3 (N-heterocyclic carbene boranes), and N—H part (imino group).
  • Suitable examples of the reducing agent that can be used in the present invention include nitrogen-containing unsaturated heterocyclic compounds having an N—H moiety.
  • a preferred example of the “nitrogen-containing unsaturated heterocyclic compound having an N—H moiety” as the reducing agent that can be used in the present invention is represented by the formula (4): [Where: R 3a , R 3b , R 3c , and R 3d are the same or different and represent an alkyl group. ] [In this specification, it may be referred to as a compound (4). ] Is included.
  • R 3a is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
  • R 3b is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
  • R 3c is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
  • R 3d is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
  • a more preferable example of the reducing agent that can be used in the present invention includes a compound represented by the following chemical formula. These compounds are so-called Hantzsch esters.
  • halogenated alkane derivatives including compound (2) are susceptible to oxidation, so reducing agents such as hunchesters (Hantzsch Ester) cause direct oxidation-reduction reactions. Therefore, it is considered that the reaction of the step A does not proceed and the compound (1) cannot be obtained. Surprisingly, however, the reaction of Step A proceeded suitably in the presence of compound (4) including a hunchester (Hantzsch Ester). The results are shown in the examples.
  • reducing agents may be used alone or in combination of two or more.
  • an acid removing agent such as amine can be used as desired.
  • amine an acid removing agent
  • other amines can be used suitably.
  • the amount thereof is preferably in the range of 0.5 to 10 mol, more preferably, relative to 1 mol of the compound represented by the formula (2) as the substrate. It is in the range of 1.0 to 5.0 moles, and more preferably in the range of 1.2 to 3.0 moles.
  • step A can be carried out in the presence of a catalyst or in the substantial or complete absence.
  • the reaction of step A is preferably carried out in the presence of a catalyst.
  • Examples of the catalyst that can be used in the present invention include a transition metal complex and an organic dye compound.
  • Examples of the central metal species of the transition metal complex that can be used in the present invention include cobalt, ruthenium, rhodium, rhenium, iridium, nickel, palladium, osmium, and platinum. Suitable examples of the central metal species include ruthenium, iridium, and palladium.
  • Examples of the ligand possessed by the transition metal complex that can be used in the present invention include nitrogen-containing compounds, oxygen-containing compounds, and sulfur-containing compounds.
  • nitrogen-containing compound examples include diamine compounds (eg, ethylenediamine), and nitrogen-containing heterocyclic compounds (eg, pyridine, bipyridine, phenanthroline, pyrrole, indole, carbazole, imidazole, pyrazole, quinoline, Isoquinoline, acridine, pyridazine, pyrimidine, pyrazine, phthalazine, quinazoline, and quinoxaline).
  • diamine compounds eg, ethylenediamine
  • nitrogen-containing heterocyclic compounds eg, pyridine, bipyridine, phenanthroline, pyrrole, indole, carbazole, imidazole, pyrazole, quinoline, Isoquinoline, acridine, pyridazine, pyrimidine, pyrazine, phthalazine, quinazoline, and quinoxaline).
  • oxygen compounds examples include diketones (eg, dipivaloylmethane), and oxygenated heterocyclic compounds (eg, furan, benzofuran, oxazole, pyran, pyrone, coumarin, and benzopyrone). Is included.
  • sulfur-containing compound examples include sulfur-containing heterocyclic compounds (eg, thiophene, thionaphthene, and thiazole).
  • the number of these ligands can be one or more. However, it goes without saying that the number is not necessarily clear.
  • the amount of the catalyst used in Step A is preferably in the range of 0.0001 to 0.1 mol, more preferably 0.001 to 0.05 mol, relative to 1 mol of compound (2). And more preferably in the range of 0.005 to 0.02 mol.
  • the organic dye compound that can be used in the present invention can be a compound that does not contain a metal atom in the molecule.
  • organic dye compounds include rose bengal, erythrosine, eosin (eg, eosin B, eosin Y), acriflavine, lipoflavin, and thionine.
  • Suitable examples of the catalyst include [Ir ⁇ dF (CF 3 ) ppy ⁇ 2 (dtbpy)] PF 6 , [Ir (dtbbpy) (ppy) 2 ] [PF 6 ], Ir (ppy) 3 , Ru (bpy) ) 3 Cl 2 .6H 2 O, [Ru (bpz) 3 ] [PF 6 ] 2 , [Ru (bpm) 3 ] [Cl] 2 , [Ru (bpy) 2 (phen-5-NH 2 )] [ PF 6 ] 2 , [Ru (bpy) 3 ] [PF 6 ] 2 , Ru (phen) 3 Cl 2 , Cu (dap) 2 chloride , 9-mesityl-10-methylacridinium perchlorate, Ir (ppy) 3 and Pd (PPh 3 ) 4 .
  • These catalysts may be used alone or in combination of two or more.
  • the catalyst used in step A can preferably be a photoredox catalyst.
  • the catalyst used in step A may be supported on a carrier (eg, zeolite).
  • a carrier eg, zeolite
  • step A can be carried out in the presence of a solvent, or in the substantial or complete absence.
  • the reaction of step A is preferably carried out in the presence of a solvent.
  • Examples of the solvent that can be used in the present invention include dimethylformamide (DMF), toluene, CH 3 CN, ether, tetrahydrofuran (THF), benzene, dimethyl sulfoxide (DMSO), hexane, and benzotrifluoride (BTF). Include.
  • solvents may be used alone or in combination of two or more.
  • the concentration of compound (2) in the mixture of the reaction system is preferably in the range of 1 to 10000 mM, more preferably in the range of 10 to 1000 mM, and even more preferably 50 to 200 mM. Is within the range.
  • the concentration of compound (3) in the mixture of the reaction system is preferably within the range of 5 to 50000 mM, more preferably within the range of 50 to 5000 mM, and even more preferably 250 to 1000 mM. Is within the range.
  • the concentration of the catalyst in the reaction system mixture is preferably within the range of 0.01 to 100 mM, more preferably within the range of 0.1 to 10 mM, and even more preferably 0. Within the range of 5 to 2 mM.
  • Step A can be performed, for example, by mixing compound (2), compound (3), an optional reducing agent, an optional catalyst, and an optional solvent.
  • a conventional method can be adopted as the mixing method. In the mixing, all substances may be mixed at the same time, or may be mixed sequentially or stepwise.
  • the reaction of step A is performed under light irradiation.
  • irradiation light used for the said light irradiation if it is the light which can start and / or accelerate
  • light sources include low pressure, medium pressure, or high pressure mercury lamps, tungsten lamps, and light emitting diodes (LEDs).
  • the irradiation light can be preferably visible light.
  • the irradiation light can be light containing light having a wavelength of preferably 300 to 600 nm, more preferably light containing 400 to 500 nm.
  • the irradiation time can be preferably in the range of 1 to 24 hours, more preferably 10 to 18 hours.
  • the start of light irradiation can be before, during, simultaneously with, or after the mixing.
  • the intensity of the light irradiation is not limited as long as energy capable of initiating and / or accelerating the reaction in the process A is supplied. This is based on, for example, common general knowledge so that the reaction in the process A proceeds appropriately.
  • the reaction in step A may be performed in the presence of an inert gas.
  • inert gases include nitrogen and argon.
  • the reaction temperature in step A is preferably in the range of 0 to 120 ° C, more preferably in the range of 10 to 80 ° C, and still more preferably in the range of 20 to 60 ° C. If the reaction temperature is too low, the reaction in Step A may be insufficient. If the reaction temperature is too high, it is disadvantageous in cost and an undesirable reaction may occur.
  • the reaction time of step A is preferably in the range of 1 to 24 hours, more preferably in the range of 5 to 18 hours, and still more preferably in the range of 10 to 15 hours. If the reaction time is too short, the reaction in step A may be insufficient. If the reaction time is too long, it is disadvantageous in cost and an undesirable reaction may occur.
  • the reaction in step A can be preferably carried out by a batch system or a flow system.
  • the compound (1) obtained by the production method of the present invention can be purified by a known purification method such as solvent extraction, drying, filtration, distillation, concentration, and a combination thereof, if desired.
  • the conversion rate of the raw material compound (2) is preferably 40% or more, more preferably 60% or more, and further preferably 80% or more.
  • the selectivity of compound (1) is preferably 70% or more, more preferably 80% or more.
  • the yield of compound (1) is preferably 40% or more, more preferably 60% or more.
  • the compound (1) obtained by the production method of the present invention can be used for applications such as pharmaceutical intermediates.
  • the yield is an isolated yield. .
  • Example 1 (1) Add Ru (bpy) 3 Cl 2 ⁇ 6H 2 O (7.5 mg, 1 mol%) and Hantzsch ester a (380.7 mg, 1.5 mmol) as photoredox catalysts to the vessel and dissolve in DMF (5 mL). After that, (bromodifluoromethyl) benzene (206.6 mg, 1.0 mmol), 1-octene (0.78 mL, 5.0 mmol), Et 3 N (201.0 mg, 1.99 mmol), and DMF (5 mL) were added to perform Ar substitution. After that, the mixture was stirred for 12 hours under irradiation with a white lamp.
  • Example 2 The reaction of Example 1 (1) was carried out in the same manner as in Example 1 (1), but under the conditions described in the following table. The results are shown in the following table.
  • Example 3 In the same manner as in Example 1 (1), in a container, (bromodifluoromethyl) benzene (1.0 mmol), 1-octene (5.0 mmol), the photoredox catalyst described in the following table [1 to (bromodifluoromethyl) benzene mol% or 0 mol%], Hantzsch ester a (1.5 mmol), Et 3 N (2.0 mmol), and DMF (10 mL) were added, Ar substitution was performed, and then light was irradiated with the light source described in the following table The mixture was stirred for 12 hours. A white LED (5W) was used as the white light.
  • 5W white LED
  • SOLARBOX 1500e CO.FO.ME.GRA, xenon lamp, soda lime glass UV filter
  • 40 mL of a solution of EtOAc / Hexane 9/1 was added to the solution, and the organic layer was washed 3 times with 20 mL of pure water and once with 30 mL of saturated brine. Thereafter, the organic layer was dehydrated, filtered, and dried, and then 1,1-difluoro-1-phenylnonane was obtained by silica gel column chromatography (developing solvent: Hexane). The conversion rate and GC yield are shown in the following table.
  • Example 4 In a manner similar to that of Example 1 (1), in a container, ethyl 2-bromo-2,2-difluoroacetate (1.0 mmol), 1-butene (amount in the following table), Ru (bpy) 3 Cl 2. Add 6H 2 O [1.0 mol% to ethyl 2-bromo-2,2-difluoroacetate], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL), and replace with Ar. Then, the mixture was stirred for 12 hours under white light irradiation. After the reaction, the solution was purified by the same method as in Example 1 (1) to give compound 4A. The yield and GC yield are shown in the following table.
  • Example 5 In a method similar to that of Example 1 (1), in a container, perfluorohexyl bromide 5 (1.0 mmol), 1-octene (amount in the following table), Ru (bpy) 3 Cl 2 .6H 2 O [perfluorohexyl] 1 mol% with respect to bromide 5 ], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL) were added, and after Ar substitution, stirring for 12 hours under white light irradiation did.
  • the reaction solution was purified by the same method as in Example 1 (1) to give compound 5A.
  • the yield and GC yield are shown in the following table.
  • Example 6 In a manner similar to that of Example 1 (1), in a container, ethyl bromofluoroacetate (1.0 mmol), 1-octene (5 molar equivalents, 10 molar equivalents, or 20 molar equivalents relative to ethyl bromofluoroacetate) ), Ru (bpy) 3 Cl 2 ⁇ 6H 2 O [1 mol% to ethyl bromofluoroacetate], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL) After replacing with Ar, the mixture was stirred for 12 hours under irradiation with a white lamp.
  • the reaction solution was purified by the same method as in Example 1 (1) to give compound 6A.
  • the yield and GC yield are shown in the following table. As shown in this table, increasing the amount of 1-octene from 5 molar equivalents to 20 molar equivalents improved the yield of compound 6A.
  • Example 7 In a manner similar to that of Example 1 (1), in a container, perfluorohexyl iodide 7 (1.0 mmol), 1-octene (5.0 mmol), Ru (bpy) 3 Cl 2 .6H 2 O [perfluorohexyl iodide 1.0 mol% relative de 7], Hantzsch ester a (1.5 mmol), Et 3 N (0, or 2.0 mmol), and placed in DMF (5 from 10 mL), after Ar-substituted, white light illumination The mixture was stirred for 12 hours. The solution after reaction was refine
  • Example 8 In a method similar to that of Example 1 (1), in a container, perfluorooctyl bromide 8 (1.0 mmol), Ru (bpy) 3 Cl 2 .6H 2 O [1.0 mol% with respect to perfluorooctyl bromide 8 ], 1-octene (20 mmol), Hantzsch ester a (1.5 mmol), Et 3 N (0 or 2.0 mmol), and DMF (5 to 10 mL) were added, and after Ar substitution, under white light irradiation, Stir for 12 hours. The solution after reaction was refine
  • Example 9 In the same manner as in Example 1 (1), in a container, (bromodifluoromethyl) benzene (1.0 mmol), acrylonitrile (5.0 mmol), Ru (bpy) 3 Cl 2 .6H 2 O [(bromodifluoromethyl) benzene 1.0 mol%], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL) were added, and after Ar substitution, the mixture was stirred for 12 hours under white light irradiation. The solution after reaction was refine
  • Example 10 (Reaction 1 in a flow system) The reaction of ethyl 2-bromo-2,2-difluoroacetate (1.0 mmol) and 1-octene (5.0 mmol) is converted to Ru (bpy) 3 Cl 2 6H 2 O [ethyl 2-bromo-2,2-difluoroacetate. 1.0 mol%], Hantzsch ester a (1.5 mmol), Et 3 N (2.0 mmol), and DMF (10 ml) in the presence of 1 mm wide, 300 ⁇ m deep, and 2.35 m long channels The flow system was performed using an optical microreactor (white light (white LED) irradiation). As a result, Compound 10A was obtained in a yield of 56% with a residence time of 30 minutes.
  • Example 11 (Reaction 2 in flow system) (bromodifluoromethyl) reaction with benzene (1.5 mmol) and 1-octene (7.5 mmol), Ru (bpy) 3 Cl 2 ⁇ 6H 2 O [(bromodifluoromethyl) 1.0 mol% with respect to benzene], Hantzsch ester a [( In the presence of 1.5 molar equivalent (2.25 mmol)] and DMF (15 mL) with respect to bromodifluoromethyl) benzene, an optical microreactor (white light irradiation) with a channel of 2 mm in width, 1 mm in depth, and 3 m in length is used. The flow system was used. As a result, Compound 10A was obtained in a yield of 56% with a residence time of 30 minutes. The conversion rate at each residence time and the GC yield are shown in the following table.
  • the yield was improved by extending the residence time.
  • a similar reaction was carried out in the reaction (12h).
  • the GC yield of Compound 11A was 86% (yield 64%).
  • the reaction time it was confirmed that the target product can be obtained more efficiently in the flow type reaction than in the batch type reaction.
  • Example 12 (Reaction 3 in flow system) The reaction in the flow system was carried out in the same manner as in Example 11 except that methyl acrylate was used instead of 1-octene as the substrate. The results are shown in the following table. As a result of carrying out the same reaction in the reaction (12h), the GC yield of Compound 12A was 90% (yield 72%). Considering the reaction time, it was confirmed that the target product can be obtained more efficiently in the flow type reaction than in the batch type reaction.

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Abstract

The present invention addresses the problem of providing a novel method for producing a compound having a fluoromethylene group with high efficiency. The problem can be solved by a method for producing a compound represented by formula (1) [wherein R1 represents an organic group; RX represents a hydrogen atom or a fluorine atom; R2a, R2b, R2c and R2d may be the same as or different from one another and independently represent -Y-R21 or -N(-R22)2, or R2b and R2c may be lined to each other to form a bond; Y represents a bond, an oxygen atom or a sulfur atom; R21 represents a hydrogen atom or an organic group; and R22's may be the same as or different from each other in every event, and independently represent a hydrogen atom or an organic group], a ring-closed or ring-opened derivative of the compound, said method comprising step A of reacting a compound represented by formula (2) [wherein X represents a leaving group; and other symbols are as defined above] with a compound represented by formula (3) [wherein the symbols are as defined above] in the presence of a reducing agent under the irradiation with light.

Description

含フッ素化合物の製造方法Method for producing fluorine-containing compound
　本発明は含フッ素化合物、特にフルオロメチレン基を有する化合物の製造方法に関する。 The present invention relates to a method for producing a fluorine-containing compound, particularly a compound having a fluoromethylene group.
　生体内の生理活性物質には、含フッ素メチレン基含有化合物であるものが存在することから、フルオロメチレン基を有する化合物の医薬品等への応用が盛んに研究されている。
　例えば、α位にフッ素原子及びパーフルオロ有機基からなる群より選択される１個以上の置換基を有するカルボニル化合物である、α－フルオロメチレン化合物、およびα－ジフルオロアルドール化合物等の含フッ素メチレン化合物の製造方法の有用性は高い（非特許文献１及び２）。 Since some physiologically active substances in vivo are compounds containing a fluorine-containing methylene group, the application of compounds having a fluoromethylene group to pharmaceuticals and the like has been actively studied.
For example, fluorine-containing methylene compounds such as α-fluoromethylene compounds and α-difluoroaldol compounds, which are carbonyl compounds having one or more substituents selected from the group consisting of a fluorine atom and a perfluoroorganic group at the α-position The production method is highly useful (Non-patent Documents 1 and 2).
　α位にフッ素原子及びパーフルオロ有機基からなる群より選択される１個以上の置換基を有するカルボニル化合物の製造方法として、含フッ素カルボニル化合物であって入手が容易なトリフルオロメチルケトン及びカルボニル化合物を原料とした製造方法については、これまでほとんど報告されておらず、上記の原料を用いた効率的で簡便な製造方法が求められている。 As a method for producing a carbonyl compound having one or more substituents selected from the group consisting of a fluorine atom and a perfluoro organic group at the α-position, a trifluoromethyl ketone and a carbonyl compound which are fluorine-containing carbonyl compounds and are easily available There have been few reports on a production method using a raw material, and an efficient and simple production method using the above-described raw materials has been demanded.
　非特許文献３には、トリフルオロメチルアセトンから、α－ジフルオロアルドール化合物を得ているが、５段階の工程を必要とするものである。また、チオフェノールを試薬として使用することから、反応系から硫黄を取り除くために塩化水銀などの毒性の高い試薬が必要になり、反応操作が煩雑になる。 In Non-Patent Document 3, an α-difluoroaldol compound is obtained from trifluoromethylacetone, but requires five steps. Further, since thiophenol is used as a reagent, a highly toxic reagent such as mercury chloride is required to remove sulfur from the reaction system, and the reaction operation becomes complicated.
　非特許文献４では、トリフルオロメチルケトントリメチル塩化ケイ素の存在下、マグネシウムによるトリフルオロメチルケトン中の炭素－フッ素結合の選択的開裂によって得られた２，２－ジフルオロエノールシリルエーテルを、ベンズアルデヒドと反応させることにより、α－ジフルオロアルドール化合物を得ているが、３段階の反応工程を必要とし、さらに反応基質に対して大量の試薬を必要とするため、収率等の点で改善の余地がある。 In Non-Patent Document 4, 2,2-difluoroenol silyl ether obtained by selective cleavage of a carbon-fluorine bond in trifluoromethyl ketone with magnesium is reacted with benzaldehyde in the presence of trifluoromethyl ketone trimethyl silicon chloride. As a result, α-difluoroaldol compound is obtained, but it requires a three-step reaction process and requires a large amount of reagent for the reaction substrate, so there is room for improvement in terms of yield and the like. .
　また、上記のいずれの方法においても無機塩が副生成することからこれを除去する工程も必要となり、製造コスト、反応効率、簡便性の観点等からさらなる改良あるいは全く新しい製造方法が求められる。 In any of the above methods, an inorganic salt is formed as a by-product, and therefore a step for removing it is required. Further improvement or a completely new production method is required from the viewpoint of production cost, reaction efficiency, and convenience.
　ところで、非特許文献５には、可視光が媒介する、フッ素不含有化合物を基質として用い、ならびにアミン、およびその補助剤としてのハンチエステル（Hantzsch Ester）を用いた、電子吸引性基で置換されたオレフィンへのグリコシルハライドの分子間付加反応が開示されている。 By the way, Non-Patent Document 5 uses a fluorine-free compound mediated by visible light as a substrate, and is substituted with an electron-withdrawing group using an amine and a hunting ester (Hantzsch Ester) as an auxiliary agent. An intermolecular addition reaction of glycosyl halides to olefins is disclosed.
　一方、非特許文献６には、フッ素不含有化合物を基質として用いた、フルオロメチレン基を有する化合物の製造方法が開示されている。 On the other hand, Non-Patent Document 6 discloses a method for producing a compound having a fluoromethylene group using a fluorine-free compound as a substrate.
　本発明は、フルオロメチレン基を有する化合物の、効率的な、新たな製造方法を提供することを目的とする。 An object of the present invention is to provide an efficient and new method for producing a compound having a fluoromethylene group.
　本発明者らは、鋭意検討の結果、
式（１）；
Figure JPOXMLDOC01-appb-C000005
 ［式中、
Ｒ１は、有機基を表し、
ＲＸは、水素原子、又はフッ素原子を表し、及び
Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄは、同一又は異なって、－Ｙ－Ｒ２１、又は－Ｎ（－Ｒ２２）２を表し、或いはＲ２ｂとＲ２ｃとは連結して結合を形成してもよく、
Ｙは、結合手、酸素原子、又は硫黄原子を表し、
Ｒ２１は、水素原子、又は有機基を表し、
Ｒ２２は、各出現において同一又は異なって、水素原子、又は有機基を表す。］
で表される化合物、又はその閉環誘導体、若しくは開環誘導体［本明細書中、化合物（１）と称する場合がある。］の製造方法であって、
式（２）：
Figure JPOXMLDOC01-appb-C000006
 ［式中、Ｘは脱離基を表し、及びその他の記号は前記と同意義を表す。］
で表される化合物［本明細書中、化合物（２）と称する場合がある。］を、
還元剤の存在下、且つ光照射下で、
式（３）：
Figure JPOXMLDOC01-appb-C000007
 ［式中の記号は前記と同意義を表す。］
で表される化合物［本明細書中、化合物（３）と称する場合がある。］と反応させる工程Ａを含む製造方法。
によって、前記課題が解決できることを見出し、本発明を完成するに至った。 As a result of intensive studies, the present inventors have
Formula (1);
Figure JPOXMLDOC01-appb-C000005
 [Where:
R 1 represents an organic group,
R X represents a hydrogen atom or a fluorine atom, and R 2a , R 2b , R 2c , and R 2d are the same or different and represent —Y—R 21 or —N (—R 22 ) 2 . Or R 2b and R 2c may be linked to form a bond,
Y represents a bond, an oxygen atom, or a sulfur atom,
R 21 represents a hydrogen atom or an organic group,
R 22 is the same or different at each occurrence and represents a hydrogen atom or an organic group. ]
Or a ring-closed derivative or ring-opened derivative thereof [in this specification, sometimes referred to as a compound (1). The manufacturing method of
Formula (2):
Figure JPOXMLDOC01-appb-C000006
 [Wherein, X represents a leaving group, and other symbols are as defined above. ]
[In this specification, it may be referred to as a compound (2). ]
In the presence of a reducing agent and under light irradiation,
Formula (3):
Figure JPOXMLDOC01-appb-C000007
 [The symbols in the formula are as defined above. ]
[In this specification, it may be referred to as a compound (3). ] The manufacturing method including the process A made to react.
As a result, the inventors have found that the above problems can be solved, and have completed the present invention.
　本発明は、次の態様を含む。 The present invention includes the following aspects.
項１．
式（１）；
Figure JPOXMLDOC01-appb-C000008
 ［式中、
Ｒ１は、有機基を表し、
ＲＸは、水素原子、又はフッ素原子を表し、及び
Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄは、同一又は異なって、－Ｙ－Ｒ２１、又は－Ｎ（－Ｒ２２）２を表し、或いはＲ２ｂとＲ２ｃとは連結して結合を形成してもよく、
Ｙは、結合手、酸素原子、又は硫黄原子を表し、
Ｒ２１は、水素原子、又は有機基を表し、
Ｒ２２は、各出現において同一又は異なって、水素原子、又は有機基を表す。］
で表される化合物、又はその閉環誘導体、若しくは開環誘導体の製造方法であって、
式（２）：
Figure JPOXMLDOC01-appb-C000009
 ［式中、Ｘは脱離基を表し、及びその他の記号は前記と同意義を表す。］
で表される化合物を、
還元剤の存在下、且つ光照射下で、
式（３）：
Figure JPOXMLDOC01-appb-C000010
 ［式中の記号は前記と同意義を表す。］
で表される化合物と反応させる工程Ａを含む製造方法。
項２．
Ｒ１が、アルキル基、フルオロアルキル基、アルコキシカルボニル基、又は芳香族基基である項１に記載の製造方法。
項３．
Ｒ２ａが、アルキル基、又はアリール基であり、且つＲ２ｂ、Ｒ２ｃ、及びＲ２ｄが、水素原子である項１又は２に記載の製造方法
項４．
Ｘが、臭素原子である項１～３のいずれか１項に記載の製造方法。
項５．
工程Ａの反応が、N－H部を有する含窒素不飽和複素環化合物の存在下で実施される項１～４のいずれか１項に記載の製造方法。
項６．
前記還元剤が、式（４）：
Figure JPOXMLDOC01-appb-C000011
 ［式中、
Ｒ３ａ、Ｒ３ｂ、Ｒ３ｃ、及びＲ３ｄは、同一又は異なって、アルキル基を表す。］
で表される化合物である項１～５のいずれか１項に記載の製造方法。
項７．
工程Ａの反応が、触媒の存在下で実施される項１～６のいずれか１項に記載の製造方法。
項８．
前記触媒が、遷移金属錯体、及び有機色素化合物からなる群より選択される１種以上である項７に記載の製造方法。 Item 1.
Formula (1);
Figure JPOXMLDOC01-appb-C000008
 [Where:
R 1 represents an organic group,
R X represents a hydrogen atom or a fluorine atom, and R 2a , R 2b , R 2c , and R 2d are the same or different and represent —Y—R 21 or —N (—R 22 ) 2 . Or R 2b and R 2c may be linked to form a bond,
Y represents a bond, an oxygen atom, or a sulfur atom,
R 21 represents a hydrogen atom or an organic group,
R 22 is the same or different at each occurrence and represents a hydrogen atom or an organic group. ]
Or a ring-closed derivative or a ring-opened derivative thereof,
Formula (2):
Figure JPOXMLDOC01-appb-C000009
 [Wherein, X represents a leaving group, and other symbols are as defined above. ]
A compound represented by
In the presence of a reducing agent and under light irradiation,
Formula (3):
Figure JPOXMLDOC01-appb-C000010
 [The symbols in the formula are as defined above. ]
The manufacturing method including the process A made to react with the compound represented by these.
Item 2.
Item 2. The production method according to Item 1, wherein R 1 is an alkyl group, a fluoroalkyl group, an alkoxycarbonyl group, or an aromatic group.
Item 3.
Item 3. The production method according to Item 1 or 2, wherein R 2a is an alkyl group or an aryl group, and R 2b , R 2c , and R 2d are hydrogen atoms.
Item 4. The production method according to any one of Items 1 to 3, wherein X is a bromine atom.
Item 5.
Item 5. The production method according to any one of Items 1 to 4, wherein the reaction in Step A is carried out in the presence of a nitrogen-containing unsaturated heterocyclic compound having an NH portion.
Item 6.
The reducing agent is represented by the formula (4):
Figure JPOXMLDOC01-appb-C000011
 [Where:
R 3a , R 3b , R 3c , and R 3d are the same or different and represent an alkyl group. ]
Item 6. The production method according to any one of Items 1 to 5, which is a compound represented by:
Item 7.
Item 7. The production method according to any one of Items 1 to 6, wherein the reaction in Step A is carried out in the presence of a catalyst.
Item 8.
Item 8. The production method according to Item 7, wherein the catalyst is at least one selected from the group consisting of a transition metal complex and an organic dye compound.
　本発明によれば、フルオロメチレン基を有する化合物の、効率的な、新たな製造方法が提供される。 According to the present invention, a new and efficient method for producing a compound having a fluoromethylene group is provided.
　用語
　本明細書中の記号及び略号は、特に限定のない限り、本明細書の文脈に沿い、本発明が属する技術分野において通常用いられる意味に理解できる。 Terms Symbols and abbreviations in this specification can be understood within the context of this specification unless otherwise specified, and can be understood as meanings commonly used in the technical field to which the present invention belongs.
　本明細書中、語句「含有する」は、語句「から本質的になる」、及び語句「からなる」を包含することを意図して用いられる。 In this specification, the phrase “containing” is intended to include the phrase “consisting essentially of” and the phrase “consisting of”.
　特に限定されない限り、本明細書中に記載されている工程、処理、又は操作は、室温で実施され得る。
　本明細書中、室温は、１０～４０℃の範囲内の温度を意味する。 Unless specifically limited, the steps, processes, or operations described herein can be performed at room temperature.
In the present specification, room temperature means a temperature within the range of 10 to 40 ° C.
　本明細書中、「Ｃｎ－ｍ」（ここで、ｎ、およびｍは、それぞれ自然数である。）は、有機化学分野で慣用されている通り、炭素数がｎ以上、且つｍ以下であることを表す。 In this specification, “Cn-m” (where n and m are natural numbers, respectively) has a carbon number of n or more and m or less, as is commonly used in the field of organic chemistry. Represents.
　本明細書中、「フルオロメチレン基」は、特に限定の無い限り、モノフルオロメチレン基、及びジフルオロメチレン基を包含する。 In the present specification, the “fluoromethylene group” includes a monofluoromethylene group and a difluoromethylene group unless otherwise specified.
　本明細書中、特に限定のない限り、「ハロゲン原子」としては、例えば、フッ素原子、塩素原子、臭素原子、及びヨウ素原子が例示される。 In the present specification, unless otherwise specified, examples of the “halogen atom” include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
　本明細書中、特に限定のない限り、「有機基」は、その構成原子として１個以上の炭素原子を含有する基を意味する。
　本明細書中、特に限定のない限り、「有機基」としては、炭化水素基、シアノ基、カルボキシ基、アルコキシ基、エステル基、エーテル基、及びアシル基が例示される。 In the present specification, unless otherwise specified, the “organic group” means a group containing one or more carbon atoms as its constituent atoms.
In the present specification, unless otherwise specified, examples of the “organic group” include a hydrocarbon group, a cyano group, a carboxy group, an alkoxy group, an ester group, an ether group, and an acyl group.
　本明細書中、特に限定のない限り、「炭化水素基」は、その構成原子として、１個以上の炭素原子、及び１個以上の水素原子を含有する基を意味する。
　本明細書中、特に限定のない限り、「炭化水素基」としては、脂肪族炭化水素基、及び芳香族炭化水素基（アリール基）、及びそれらの組み合わせ等が例示される。 In the present specification, unless otherwise specified, the “hydrocarbon group” means a group containing one or more carbon atoms and one or more hydrogen atoms as its constituent atoms.
In the present specification, unless otherwise specified, examples of the “hydrocarbon group” include an aliphatic hydrocarbon group, an aromatic hydrocarbon group (aryl group), and combinations thereof.
　本明細書中、特に限定のない限り、「脂肪族炭化水素基」は、直鎖状、分枝鎖状、環状、又はそれらの組み合わせであることができる。 In the present specification, unless otherwise specified, the “aliphatic hydrocarbon group” may be linear, branched, cyclic, or a combination thereof.
　本明細書中、特に限定のない限り、「脂肪族炭化水素基」は、飽和、又は不飽和であることができる。 In the present specification, unless otherwise specified, the “aliphatic hydrocarbon group” may be saturated or unsaturated.
　本明細書中、特に限定のない限り、「脂肪族炭化水素基」としては、例えば、アルキル基、アルケニル基、アルキニル基、及びシクロアルキル基が例示される。 In the present specification, unless otherwise specified, examples of the “aliphatic hydrocarbon group” include an alkyl group, an alkenyl group, an alkynyl group, and a cycloalkyl group.
　本明細書中、特に限定のない限り、「アルキル基」としては、例えば、メチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、ｓｅｃ-ブチル、ｔｅｒｔ-ブチル、ペンチル、イソペンチル、ネオペンチル、及びヘキシル等の、直鎖状、又は分枝鎖状の、炭素数１～１０のアルキル基が例示される。 In the present specification, unless otherwise specified, examples of the “alkyl group” include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, and hexyl. And a linear or branched alkyl group having 1 to 10 carbon atoms.
　本明細書中、「フルオロアルキル基」は、少なくとも１個の水素原子がフッ素原子で置換されたアルキル基である。
　本明細書中、「フルオロアルキル基」が有するフッ素原子の数は、１個以上（例、１～３個、１～６個、１～１２個、１個から置換可能な最大数）であることができる。
　「フルオロアルキル基」は、パーフルオロアルキル基を包含する。「パーフルオロアルキル基」は、全ての水素原子がフッ素原子で置換されたアルキル基である。 In the present specification, the “fluoroalkyl group” is an alkyl group in which at least one hydrogen atom is substituted with a fluorine atom.
In the present specification, the number of fluorine atoms of the “fluoroalkyl group” is 1 or more (eg, 1 to 3, 1 to 6, 1 to 12, or the maximum number that can be substituted from one). be able to.
A “fluoroalkyl group” includes a perfluoroalkyl group. A “perfluoroalkyl group” is an alkyl group in which all hydrogen atoms are substituted with fluorine atoms.
　本明細書中、特に限定のない限り、「アルケニル基」としては、例えば、ビニル、１－プロペニル、イソプロペニル、２－メチル－１－プロペニル、１－ブテニル、２－ブテニル、３－ブテニル、２－エチル－１－ブテニル、１－ペンテニル、２－ペンテニル、３－ペンテニル、４－ペンテニル、４－メチル－３－ペンテニル、１－ヘキセニル、２－ヘキセニル、３－ヘキセニル、４－ヘキセニル、及び５－ヘキセニル等の、直鎖状、又は分枝鎖状の、炭素数１～１０のアルケニル基が例示される。 In the present specification, unless otherwise specified, examples of the “alkenyl group” include vinyl, 1-propenyl, isopropenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, -Ethyl-1-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, and 5- Examples thereof include linear or branched alkenyl groups having 1 to 10 carbon atoms such as hexenyl.
　本明細書中、特に限定のない限り、「アルキニル基」としては、例えば、エチニル、１－プロピニル、２－プロピニル、１－ブチニル、２－ブチニル、３－ブチニル、１－ペンチニル、２－ペンチニル、３－ペンチニル、４－ペンチニル、１－ヘキシニル、２－ヘキシニル、３－ヘキシニル、４－ヘキシニル、及び５－ヘキシニル等の、直鎖状、又は分枝鎖状の、炭素数２～６のアルキニル基が例示される。 In the present specification, unless otherwise specified, examples of the “alkynyl group” include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, Linear or branched alkynyl groups having 2 to 6 carbon atoms, such as 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, and 5-hexynyl Is exemplified.
　本明細書中、特に限定のない限り、「シクロアルキル基」としては、例えば、シクロペンチル基、シクロヘキシル基、及びシクロヘプチル等の炭素数３～１０（好ましくは、炭素数４～１０）のシクロアルキル基が例示される。 In this specification, unless otherwise specified, examples of the “cycloalkyl group” include cycloalkyl having 3 to 10 carbon atoms (preferably 4 to 10 carbon atoms) such as cyclopentyl group, cyclohexyl group, and cycloheptyl. Examples are groups.
　本明細書中、特に限定のない限り、「アルコキシ基」は、例えば、ＲＯ－（当該式中、Ｒはアルキル基である。）で表される基である。 In the present specification, unless otherwise specified, the “alkoxy group” is, for example, a group represented by RO— (wherein R is an alkyl group).
　本明細書中、特に限定のない限り、「エステル基」は、例えば、ＲＣＯ２－（当該式中、Ｒはアルキル基である。）で表される基である。 In the present specification, unless otherwise specified, the “ester group” is, for example, a group represented by RCO 2 — (wherein R is an alkyl group).
　本明細書中、特に限定のない限り、「エーテル基」は、エーテル結合（－Ｏ－）を有する基を意味し、ポリエーテル基を包含する。ポリエーテル基は、式：Ｒａ－（Ｏ－Ｒｂ）ｎ－（式中、Ｒａはアルキル基であり、Ｒｂは各出現において同一又は異なって、アルキレン基であり、及びｎは１以上の整数である。）で表される基を包含する。アルキレン基は前記アルキル基から水素原子を１個除去して形成される２価の基である。 In this specification, unless otherwise specified, the “ether group” means a group having an ether bond (—O—) and includes a polyether group. The polyether group is represented by the formula: Ra— (O—Rb) n—, wherein Ra is an alkyl group, Rb is the same or different at each occurrence, is an alkylene group, and n is an integer of 1 or more. A group represented by the formula: An alkylene group is a divalent group formed by removing one hydrogen atom from the alkyl group.
　本明細書中、特に限定のない限り、「アシル基」は、アルカノイル基を包含する。本明細書中、特に限定のない限り、「アルカノイル基」は、例えば、ＲＣＯ－（当該式中、Ｒはアルキル基である。）で表される基である。 In the present specification, unless otherwise specified, the “acyl group” includes an alkanoyl group. In the present specification, unless otherwise specified, the “alkanoyl group” is, for example, a group represented by RCO— (wherein R is an alkyl group).
　本明細書中、特に限定のない限り、「芳香族基」は、アリール基、及びヘテロアリール基を包含する。
　本明細書中、「アリール基」の例は、フェニル基、及びナフチル基等のＣ６－１０アリール基を包含する。
　本明細書中、「ヘテロアリール基」の例は、環構成原子として、炭素原子以外に窒素原子、硫黄原子、及び酸素原子からなる群より選ばれる１～４個のヘテロ原子を含む５～１４員（単環、２環、又は３環式）複素環基を包含する。
　本明細書中、「ヘテロアリール基」の具体例は、
（１）フリル基、チエニル基、ピリジル基、ピリミジニル基、ピリダジニル基、ピラジニル基、ピロリル基、イミダゾリル基、ピラゾリル基、チアゾリル基、イソチアゾリル基、オキサゾリル基、イソオキサゾリル基、オキサジアゾリル基、チアジアゾリル基、トリアゾリル基、テトラゾリル基、トリアジニル基等の単環式芳香族複素環基；並びに
（２）キノリル基、イソキノリル基、キナゾリル基、キノキサリル基、ベンゾフリル基、ベンゾチエニル基、ベンズオキサゾリル基、ベンズイソオキサゾリル基、ベンゾチアゾリル基、ベンズイミダゾリル基、ベンゾトリアゾリル基、インドリル基、インダゾリル基、ピロロピラジニル基、イミダゾピリジニル基、イミダゾピラジニル基、イミダゾチアゾリルピラゾロピリジニル基、ピラゾロチエニル基、ピラゾロトリアジニル基等の多環式（例、二環式）芳香族複素環基を包含する。 In the present specification, unless otherwise specified, the “aromatic group” includes an aryl group and a heteroaryl group.
In the present specification, examples of the “aryl group” include C6-10 aryl groups such as a phenyl group and a naphthyl group.
In the present specification, examples of the “heteroaryl group” include, as a ring constituent atom, 5 to 14 containing 1 to 4 heteroatoms selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom in addition to a carbon atom. Includes membered (monocyclic, bicyclic, or tricyclic) heterocyclic groups.
In the present specification, specific examples of the “heteroaryl group” include
(1) Furyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl Monocyclic aromatic heterocyclic groups such as tetrazolyl and triazinyl; and (2) quinolyl, isoquinolyl, quinazolyl, quinoxalyl, benzofuryl, benzothienyl, benzoxazolyl, benzisoxazolyl Group, benzothiazolyl group, benzimidazolyl group, benzotriazolyl group, indolyl group, indazolyl group, pyrrolopyrazinyl group, imidazopyridinyl group, imidazopyrazinyl group, imidazothiazolylpyrazolopyridinyl group, pyrazolothi Including group, a polycyclic (e.g., bicyclic) such as pyrazolotriazole triazinyl group an aromatic heterocyclic group.
　製造方法
　本発明の、式（１）；
Figure JPOXMLDOC01-appb-C000012
 ［式中、
Ｒ１は、有機基を表し、
ＲＸは、水素原子、又はフッ素原子を表し、及び
Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄは、同一又は異なって、－Ｙ－Ｒ２１、又は－Ｎ（－Ｒ２２）２を表し、或いはＲ２ｂとＲ２ｃとは連結して結合を形成してもよく、
Ｙは、結合手、酸素原子、又は硫黄原子を表し、
Ｒ２１は、水素原子、又は有機基を表し、
Ｒ２２は、各出現において同一又は異なって、水素原子、又は有機基を表す。］
で表される化合物、又はその閉環誘導体、若しくは開環誘導体の製造方法は、
式（２）：
Figure JPOXMLDOC01-appb-C000013
 ［式中、Ｘは脱離基を表し、及びその他の記号は前記と同意義を表す。］
で表される化合物を、
還元剤の存在下、且つ光照射下で、
式（３）：
Figure JPOXMLDOC01-appb-C000014
 ［式中の記号は前記と同意義を表す。］
で表される化合物と反応させる工程Ａを含む。 Production method of the present invention, formula (1);
Figure JPOXMLDOC01-appb-C000012
 [Where:
R 1 represents an organic group,
R X represents a hydrogen atom or a fluorine atom, and R 2a , R 2b , R 2c , and R 2d are the same or different and represent —Y—R 21 or —N (—R 22 ) 2 . Or R 2b and R 2c may be linked to form a bond,
Y represents a bond, an oxygen atom, or a sulfur atom,
R 21 represents a hydrogen atom or an organic group,
R 22 is the same or different at each occurrence and represents a hydrogen atom or an organic group. ]
Or a ring-closing derivative or a ring-opening derivative thereof,
Formula (2):
Figure JPOXMLDOC01-appb-C000013
 [Wherein, X represents a leaving group, and other symbols are as defined above. ]
A compound represented by
In the presence of a reducing agent and under light irradiation,
Formula (3):
Figure JPOXMLDOC01-appb-C000014
 [The symbols in the formula are as defined above. ]
The process A is made to react with the compound represented by these.
　以下に、前記各化学式中の記号を説明する。 Hereinafter, symbols in each chemical formula will be described.
　Ｒ１で表される「有機基」の好適な例は、アルキル基、フルオロアルキル基、アルコキシカルボニル基、及び芳香族基を包含する。
　Ｒ１で表される「有機基」のより好適な例は、フルオロアルキル基を包含する。 Suitable examples of the “organic group” represented by R 1 include an alkyl group, a fluoroalkyl group, an alkoxycarbonyl group, and an aromatic group.
More preferred examples of the “organic group” represented by R 1 include a fluoroalkyl group.
　前記「アルコキシカルボニル基」の例は、メトキシカルボニル、エトキシカルボニル、プロポキシカルボニル、イソプロポキシカルボニル、ブトキシカルボニル、イソブトキシカルボニル、ｓｅｃ－ブトキシカルボニル、ｔｅｒｔ－ブトキシカルボニル、ペンタブトキシカルボニル、イソペントキシカルボニル、ヘキシルオキシカルボニル基等のＣ１－６アルコキシカルボニル基等を包含する。 Examples of the “alkoxycarbonyl group” include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentaboxycarbonyl, isopentoxycarbonyl, hexyl. A C1-6 alkoxycarbonyl group such as an oxycarbonyl group is included.
　前記「芳香族基」の好適な例は、アリール基を包含し、及びより好適な例は、フェニル基、及びナフチル基等のＣ６－１０アリール基を包含する。 Preferred examples of the “aromatic group” include an aryl group, and more preferable examples include a C6-10 aryl group such as a phenyl group and a naphthyl group.
　ＲＸは、好ましくはフッ素原子である。 R X is preferably a fluorine atom.
　Ｒ２ｂとＲ２ｃとが連結して結合を形成する場合、当業者が容易に理解する通り、式（１）の構造は、以下の化学式：
Figure JPOXMLDOC01-appb-C000015
 の構造になり、及び式（３）の構造は、以下の化学式：
Figure JPOXMLDOC01-appb-C000016
 の構造になる。 When R 2b and R 2c are linked to form a bond, as the skilled artisan will readily appreciate, the structure of formula (1) has the following chemical formula:
Figure JPOXMLDOC01-appb-C000015
 And the structure of formula (3) has the following chemical formula:
Figure JPOXMLDOC01-appb-C000016
 It becomes the structure of.
　Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄのうちの１個以上は、好適に、電子供与性基であることができる。 One or more of R 2a , R 2b , R 2c and R 2d can suitably be an electron donating group.
　本発明の好適な一態様において、Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄのうちの１個以上は、１個以上の置換基を有していてもよい炭化水素基であることができる。
　当該置換基の例は、
１個以上の置換基を有していてもよいヘテロアリール基（より好ましくは、１個以上の置換基を有していてもよい５～１８員のヘテロアリール基）、
１個以上の置換基を有していてもよいチオエーテル基、及び
１個以上の置換基を有していてもよいシラザン基
を包含する。 In a preferred embodiment of the present invention, one or more of R 2a , R 2b , R 2c , and R 2d can be a hydrocarbon group that may have one or more substituents. .
Examples of such substituents are:
A heteroaryl group optionally having one or more substituents (more preferably a 5- to 18-membered heteroaryl group optionally having one or more substituents),
It includes a thioether group which may have one or more substituents, and a silazane group which may have one or more substituents.
　これらの「１個以上の置換基を有していてもよいヘテロアリール基」、「１個以上の置換基を有していてもよいチオエーテル基」、及び「１個以上の置換基を有していてもよいシラザン基」における「置換基」の好適な例は、ハロゲン原子（好ましくはフッ素）、シアノ基、アミノ基、アルコキシ基、パーフルオロ有機基（好ましくは炭素数１～８のパーフルオロ有機基、より好ましくはトリフルオロメチル基）、ペンタフルオロスルファニル基（Ｆ５Ｓ－）を包含する。
　本発明の好適な一態様において、Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄのうちの１個以上は、無置換の炭化水素基（好ましくは、炭素数１～１０の炭化水素基）であることができる。 These “heteroaryl groups optionally having one or more substituents”, “thioether groups optionally having one or more substituents”, and “having one or more substituents” Suitable examples of the “substituent” in the “optional silazane group” include a halogen atom (preferably fluorine), a cyano group, an amino group, an alkoxy group, a perfluoro organic group (preferably a perfluoro having 1 to 8 carbon atoms). An organic group, more preferably a trifluoromethyl group) and a pentafluorosulfanyl group (F 5 S—).
In a preferred embodiment of the present invention, one or more of R 2a , R 2b , R 2c , and R 2d are an unsubstituted hydrocarbon group (preferably a hydrocarbon group having 1 to 10 carbon atoms). Can be.
　当該「炭化水素基」の好適な例は、アルキル基（好ましくは、Ｃ１－１０アルキル基）、シクロアルキル基（好ましくは、Ｃ３－１０、好ましくはＣ４－８シクロアルキル基）、及びアリール基（好ましくは、Ｃ６－１０アリール基）を包含する。 Suitable examples of the “hydrocarbon group” include an alkyl group (preferably a C1-10 alkyl group), a cycloalkyl group (preferably a C3-10, preferably a C4-8 cycloalkyl group), and an aryl group ( Preferably, a C6-10 aryl group) is included.
　本発明のより好適な一態様においては、Ｒ２ａが、アルキル基、又はアリール基であり、且つＲ２ｂ、Ｒ２ｃ、及びＲ２ｄが、水素原子である。 In a more preferred aspect of the present invention, R 2a is an alkyl group, or an aryl group, and R 2b, R 2c, and R 2d is a hydrogen atom.
　Ｘで表される脱離基の例は、
ハロゲン原子（例、フッ素原子、塩素原子、臭素原子、及びヨウ素原子）、
アルキルスルホニルオキシ基（例、メタンスルホニルオキシ基、トリフルオロメタンスルホニルオキシ基等のＣ１－６アルキルスルホニルオキシ基）、及び
アリールスルホニルオキシ基（例、ベンゼンスルホニルオキシ基、ｐ－トルエンスルホニルオキシ基等のＣ６－１０アリールスルホニルオキシ基）を包含する。
　Ｘのより好適な例は、ハロゲン原子を包含する。
　Ｘの更に好適な例は、塩素原子、臭素原子、及びヨウ素原子を包含する。
　Ｘのより更に好適な例は、臭素原子を包含する。 Examples of leaving groups represented by X are:
Halogen atoms (eg, fluorine, chlorine, bromine, and iodine atoms),
Alkylsulfonyloxy groups (eg, C1-6 alkylsulfonyloxy groups such as methanesulfonyloxy group and trifluoromethanesulfonyloxy group) and arylsulfonyloxy groups (eg, C6 such as benzenesulfonyloxy group and p-toluenesulfonyloxy group) -10 arylsulfonyloxy group).
More preferred examples of X include a halogen atom.
More preferred examples of X include chlorine atom, bromine atom, and iodine atom.
Even more preferred examples of X include bromine atoms.
　本発明の好適な一態様においては、
Ｒ１が、フルオロアルキル基、アルコキシカルボニル基、又はアリール基であり、
ＲＸが、フッ素原子であり、
Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄは、同一又は異なって、アルキル基（好ましくは、Ｃ１－１０アルキル基）、シクロアルキル基（好ましくは、Ｃ３－１０シクロアルキル基、より好ましくはＣ４－８シクロアルキル基）、又はアリール基（好ましくは、Ｃ６－１０アリール基）であり、且つ
Ｘが、臭素原子である。 In a preferred embodiment of the present invention,
R 1 is a fluoroalkyl group, an alkoxycarbonyl group, or an aryl group;
R X is a fluorine atom,
R 2a , R 2b , R 2c and R 2d are the same or different and are an alkyl group (preferably a C1-10 alkyl group), a cycloalkyl group (preferably a C3-10 cycloalkyl group, more preferably C4 -8 cycloalkyl group) or an aryl group (preferably a C6-10 aryl group), and X is a bromine atom.
　工程Ａにおける、化合物（３）の使用量は、化合物（２）の１モルに対して、好ましくは、０．５～１０モルの範囲内、より好ましくは、１～８モルの範囲内、及び更に好ましくは、１．２～６モルの範囲内である。 The amount of compound (3) used in step A is preferably in the range of 0.5 to 10 mol, more preferably in the range of 1 to 8 mol, and 1 mol of compound (2), and More preferably, it is in the range of 1.2 to 6 mol.
　化合物（３）が、式（３）の構造式において示されている炭素－炭素二重結合に加えて１個以上の炭素－炭素二重結合を有する場合、閉環反応により、化合物（１）は、前記式（１）で表される化合物の閉環誘導体になり得る。当該閉環反応により形成される環は、好ましくは５～７員環であることができる。当該閉環反応により形成される環は、炭素環、又は環構成原子として、炭素原子以外に窒素原子、硫黄原子、及び酸素原子からなる群より選ばれる１個以上（好ましくは、１、又は２個）のヘテロ原子を含む複素環であることができる。 When compound (3) has one or more carbon-carbon double bonds in addition to the carbon-carbon double bond shown in the structural formula of formula (3), compound (1) is Can be a ring-closed derivative of the compound represented by the formula (1). The ring formed by the ring closure reaction can preferably be a 5- to 7-membered ring. The ring formed by the ring-closing reaction is one or more (preferably 1, or 2) selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom in addition to a carbon atom as a carbocyclic ring or a ring-constituting atom. ) Of a heteroatom containing a heteroatom.
　Ｒ２ａがエポキシ基である場合（すなわち、化合物（３）がエポキシ化合物である場合）、開環反応により、化合物（１）は、前記式（１）で表される化合物の開環誘導体（すなわち、エポキシ開環誘導体）になり得る。 When R 2a is an epoxy group (that is, when the compound (3) is an epoxy compound), the compound (1) is converted into a ring-opened derivative of the compound represented by the formula (1) (ie, by a ring-opening reaction) , Epoxy ring-opening derivatives).
　工程Ａの反応は、還元剤の存在下で実施される。 The reaction in step A is performed in the presence of a reducing agent.
　本発明で用いられる前記還元剤は、無機、又は有機の還元剤であることができ、その例は、水素、ギ酸、ギ酸アンモニウム、ギ酸ナトリウム、ギ酸－トリエチルアミン、トリエチルシラン、テトラメチルジシロキサン、ポリメチルヒドロシロキサン、ＮａＢＨ３ＣＮ、ＮＨＣＢＨ３（N-heterocyclic carbene boranes）、およびN－H部（イミノ基）を有する含窒素不飽和複素環化合物を包含する。 The reducing agent used in the present invention may be an inorganic or organic reducing agent, examples of which are hydrogen, formic acid, ammonium formate, sodium formate, formic acid-triethylamine, triethylsilane, tetramethyldisiloxane, poly Including nitrogen-containing unsaturated heterocyclic compounds having methylhydrosiloxane, NaBH 3 CN, NHCBH 3 (N-heterocyclic carbene boranes), and N—H part (imino group).
　本発明で用いることができる前記還元剤の好適な例は、N－H部を有する含窒素不飽和複素環化合物を包含する。 Suitable examples of the reducing agent that can be used in the present invention include nitrogen-containing unsaturated heterocyclic compounds having an N—H moiety.
　本発明で用いることができる前記還元剤としての前記「N－H部を有する含窒素不飽和複素環化合物」の好適な例は、式（４）：
Figure JPOXMLDOC01-appb-C000017
 ［式中、
Ｒ３ａ、Ｒ３ｂ、Ｒ３ｃ、及びＲ３ｄは、同一又は異なって、アルキル基を表す。］
で表される化合物［本明細書中、化合物（４）と称する場合がある。］を包含する。 A preferred example of the “nitrogen-containing unsaturated heterocyclic compound having an N—H moiety” as the reducing agent that can be used in the present invention is represented by the formula (4):
Figure JPOXMLDOC01-appb-C000017
 [Where:
R 3a , R 3b , R 3c , and R 3d are the same or different and represent an alkyl group. ]
[In this specification, it may be referred to as a compound (4). ] Is included.
　Ｒ３ａは、好ましくはＣ１－６アルキル基、より好ましくはメチル基、又はエチル基である。 R 3a is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
　Ｒ３ｂは、好ましくはＣ１－６アルキル基、より好ましくはメチル基、又はエチル基である。 R 3b is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
　Ｒ３ｃは、好ましくはＣ１－６アルキル基、より好ましくはメチル基、又はエチル基である。 R 3c is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
　Ｒ３ｄは、好ましくはＣ１－６アルキル基、より好ましくはメチル基、又はエチル基である。 R 3d is preferably a C 1-6 alkyl group, more preferably a methyl group or an ethyl group.
　本発明で用いることができる前記還元剤のより好適な例は、次の化学式の化合物を包含する。これらの化合物は所謂Hantzschエステルである。
Figure JPOXMLDOC01-appb-C000018
 A more preferable example of the reducing agent that can be used in the present invention includes a compound represented by the following chemical formula. These compounds are so-called Hantzsch esters.
Figure JPOXMLDOC01-appb-C000018
　有機化学分野の技術常識によれば、化合物（２）を包含するハロゲン化アルカン誘導体は酸化を受けやすいので、ハンチエステル（Hantzsch Ester）のような還元剤は、これと直接、酸化還元反応を起こし、従って、工程Ａの反応は進行せず、及び化合物（１）は得られない、と考えられる。しかし、意外にも、工程Ａの反応は、ハンチエステル（Hantzsch Ester）を包含する化合物（４）の存在下で、好適に進行した。この結果を実施例に示した。 According to the common general knowledge in the field of organic chemistry, halogenated alkane derivatives including compound (2) are susceptible to oxidation, so reducing agents such as hunchesters (Hantzsch Ester) cause direct oxidation-reduction reactions. Therefore, it is considered that the reaction of the step A does not proceed and the compound (1) cannot be obtained. Surprisingly, however, the reaction of Step A proceeded suitably in the presence of compound (4) including a hunchester (Hantzsch Ester). The results are shown in the examples.
　これらの還元剤は、１種を単独で用いてもよく、２種以上を組み合わせて用いてもよい。 These reducing agents may be used alone or in combination of two or more.
　工程Ａの反応においては、所望により、アミン等の除酸剤を用いることができる。
　ここで、化合物（４）を用いる場合、好適に、その他のアミンを用いないことができる。 In the reaction of Step A, an acid removing agent such as amine can be used as desired.
Here, when using a compound (4), other amines can be used suitably.
　工程Ａにおいて還元剤を用いる場合、その量は、基質である前記式（２）で表される化合物の１モルに対して、好ましくは、０．５～１０モルの範囲内、より好ましくは、１．０～５．０モルの範囲内、及び更に好ましくは、１．２～３．０モルの範囲内である。 When a reducing agent is used in step A, the amount thereof is preferably in the range of 0.5 to 10 mol, more preferably, relative to 1 mol of the compound represented by the formula (2) as the substrate. It is in the range of 1.0 to 5.0 moles, and more preferably in the range of 1.2 to 3.0 moles.
　工程Ａの反応は、触媒の存在下、又は実質的若しくは完全な不存在下で実施することができる。
　工程Ａの反応は、好ましくは触媒の存在下で実施される。 The reaction of step A can be carried out in the presence of a catalyst or in the substantial or complete absence.
The reaction of step A is preferably carried out in the presence of a catalyst.
　本発明で用いることができる前記触媒の例は、遷移金属錯体、及び有機色素化合物を包含する。 Examples of the catalyst that can be used in the present invention include a transition metal complex and an organic dye compound.
　本発明で用いることができる前記遷移金属錯体が有する中心金属種の例は、コバルト、ルテニウム、ロジウム、レニウム、イリジウム、ニッケル、パラジウム、オスミウム、及び白金を包含する。
　当該中心金属種の好適な例は、ルテニウム、イリジウム、及びパラジウムを包含する。 Examples of the central metal species of the transition metal complex that can be used in the present invention include cobalt, ruthenium, rhodium, rhenium, iridium, nickel, palladium, osmium, and platinum.
Suitable examples of the central metal species include ruthenium, iridium, and palladium.
　本発明で用いることができる前記遷移金属錯体が有する配位子の例は、及び含窒素化合物、含酸素化合物、及び含硫黄化合物を包含する。 Examples of the ligand possessed by the transition metal complex that can be used in the present invention include nitrogen-containing compounds, oxygen-containing compounds, and sulfur-containing compounds.
　配位子としての当該「含窒素化合物」の例は、ジアミン化合物（例、エチレンジアミン）、及び含窒素複素環化合物（例、ピリジン、ビピリジン、フェナントロリン、ピロール、インドール、カルバゾール、イミダゾール、ピラゾール、キノリン、イソキノリン、アクリジン、ピリダジン、ピリミジン、ピラジン、フタラジン、キナゾリン、及びキノキサリン）を包含する。 Examples of the “nitrogen-containing compound” as the ligand include diamine compounds (eg, ethylenediamine), and nitrogen-containing heterocyclic compounds (eg, pyridine, bipyridine, phenanthroline, pyrrole, indole, carbazole, imidazole, pyrazole, quinoline, Isoquinoline, acridine, pyridazine, pyrimidine, pyrazine, phthalazine, quinazoline, and quinoxaline).
　配位子としての当該「含酸素化合物」の例は、ジケトン（例、ジピバロイルメタン）、及び含酸素複素環化合物（例、フラン、ベンゾフラン、オキサゾール、ピラン、ピロン、クマリン、及びベンゾピロン）を包含する。 Examples of such “oxygen compounds” as ligands are diketones (eg, dipivaloylmethane), and oxygenated heterocyclic compounds (eg, furan, benzofuran, oxazole, pyran, pyrone, coumarin, and benzopyrone). Is included.
　配位子としての当該「含硫黄化合物」の例は、含硫黄複素環化合物（例、チオフェン、チオナフテン、及びチアゾール）を包含する。 Examples of the “sulfur-containing compound” as the ligand include sulfur-containing heterocyclic compounds (eg, thiophene, thionaphthene, and thiazole).
　前記遷移金属錯体において、これらの配位子の数は１個以上であることができる。但し、いうまでもなく、その数は必ずしも明らかでなくてもよい。 In the transition metal complex, the number of these ligands can be one or more. However, it goes without saying that the number is not necessarily clear.
　工程Ａの反応に触媒を用いる場合、工程Ａにおける、触媒の使用量は、化合物（２）の１モルに対して、好ましくは、0.0001～0.1モルの範囲内、より好ましくは、0.001～0.05モルの範囲内、及び更に好ましくは、0.005～0.02モルの範囲内である。 When a catalyst is used in the reaction of Step A, the amount of the catalyst used in Step A is preferably in the range of 0.0001 to 0.1 mol, more preferably 0.001 to 0.05 mol, relative to 1 mol of compound (2). And more preferably in the range of 0.005 to 0.02 mol.
　本発明で用いることができる前記有機色素化合物は、分子内に金属原子を含有しない化合物であることができる。
　当該有機色素化合物の例は、ローズベンガル、エリスロシン、エオシン（例、エオシンＢ、エオシンＹ）、アクリフラビン、リポフラビン、及びチオニンを包含する。 The organic dye compound that can be used in the present invention can be a compound that does not contain a metal atom in the molecule.
Examples of such organic dye compounds include rose bengal, erythrosine, eosin (eg, eosin B, eosin Y), acriflavine, lipoflavin, and thionine.
　当該触媒の好適な例は、［Ｉｒ｛ｄＦ（ＣＦ３）ｐｐｙ｝２（ｄｔｂｐｙ）］ＰＦ６、［Ｉｒ（ｄｔｂｂｐｙ）（ｐｐｙ）２］［ＰＦ６］、Ｉｒ（ｐｐｙ）３、Ｒｕ（ｂｐｙ）３Ｃｌ２・６Ｈ２Ｏ、［Ｒｕ（ｂｐｚ）３］［ＰＦ６］２、［Ｒｕ（ｂｐｍ）３］［Ｃｌ］２、［Ｒｕ（ｂｐｙ）２（ｐｈｅｎ－５－ＮＨ２）］［ＰＦ６］２、［Ｒｕ（ｂｐｙ）３］［ＰＦ６］２、Ｒｕ（ｐｈｅｎ）３Ｃｌ２、Ｃｕ（ｄａｐ）２クロリド、９－メシチル－１０－メチルアクリジニウム・ペルクロラート、Ｉｒ（ｐｐｙ）３、及びＰｄ（ＰＰｈ３）４を包含する。 Suitable examples of the catalyst include [Ir {dF (CF 3 ) ppy} 2 (dtbpy)] PF 6 , [Ir (dtbbpy) (ppy) 2 ] [PF 6 ], Ir (ppy) 3 , Ru (bpy) ) 3 Cl 2 .6H 2 O, [Ru (bpz) 3 ] [PF 6 ] 2 , [Ru (bpm) 3 ] [Cl] 2 , [Ru (bpy) 2 (phen-5-NH 2 )] [ PF 6 ] 2 , [Ru (bpy) 3 ] [PF 6 ] 2 , Ru (phen) 3 Cl 2 , Cu (dap) 2 chloride , 9-mesityl-10-methylacridinium perchlorate, Ir (ppy) 3 and Pd (PPh 3 ) 4 .
　これらの触媒は、１種を単独で用いてもよく、２種以上を組み合わせて用いてもよい。 These catalysts may be used alone or in combination of two or more.
　工程Ａで用いられる触媒は、好ましくはphotoredox触媒であることができる。 The catalyst used in step A can preferably be a photoredox catalyst.
　工程Ａで用いられる触媒は、担体（例、ゼオライト）に担持されていてもよい。 The catalyst used in step A may be supported on a carrier (eg, zeolite).
　工程Ａの反応は、溶媒の存在下、又は実質的若しくは完全な不存在下で実施することができる。
　工程Ａの反応は、好ましくは、溶媒の存在下で実施される。 The reaction of step A can be carried out in the presence of a solvent, or in the substantial or complete absence.
The reaction of step A is preferably carried out in the presence of a solvent.
　本発明で用いることができる前記溶媒の例は、ジメチルホルムアミド（ＤＭＦ）、トルエン、ＣＨ３ＣＮ、エーテル、テトラヒドロフラン（ＴＨＦ）、ベンゼン、ジメチルスルホキシド（ＤＭＳＯ）、ヘキサン、及びベンゾトリフルオライド（ＢＴＦ）を包含する。 Examples of the solvent that can be used in the present invention include dimethylformamide (DMF), toluene, CH 3 CN, ether, tetrahydrofuran (THF), benzene, dimethyl sulfoxide (DMSO), hexane, and benzotrifluoride (BTF). Include.
　これらの溶媒は、１種を単独で用いてもよく、２種以上を組み合わせて用いてもよい。 These solvents may be used alone or in combination of two or more.
　工程Ａの反応の開始時において、その反応系の混合物における、化合物（２）の濃度は、好ましくは１～１００００ｍＭの範囲内、より好ましくは１０～１０００ｍＭの範囲内、及び更に好ましくは５０～２００ｍＭの範囲内である。 At the start of the reaction in step A, the concentration of compound (2) in the mixture of the reaction system is preferably in the range of 1 to 10000 mM, more preferably in the range of 10 to 1000 mM, and even more preferably 50 to 200 mM. Is within the range.
　工程Ａの反応の開始時において、その反応系の混合物における、化合物（３）の濃度は、好ましくは５～５００００ｍＭの範囲内、より好ましくは５０～５０００ｍＭの範囲内、及び更に好ましくは２５０～１０００ｍＭの範囲内である。 At the start of the reaction in step A, the concentration of compound (3) in the mixture of the reaction system is preferably within the range of 5 to 50000 mM, more preferably within the range of 50 to 5000 mM, and even more preferably 250 to 1000 mM. Is within the range.
　工程Ａの反応に触媒を用いる場合、その反応系の混合物における、触媒の濃度は、好ましくは０．０１～１００ｍＭの範囲内、より好ましくは０．１～１０ｍＭの範囲内、及び更に好ましくは０．５～２ｍＭの範囲内である。 When a catalyst is used in the reaction of Step A, the concentration of the catalyst in the reaction system mixture is preferably within the range of 0.01 to 100 mM, more preferably within the range of 0.1 to 10 mM, and even more preferably 0. Within the range of 5 to 2 mM.
　工程Ａは、例えば、化合物（２）、化合物（３）、所望による還元剤、所望による触媒、及び所望による溶媒を混合することによって、実施できる。
　当該混合の方法としては、慣用の方法を採用できる。
　当該混合は、全ての物質を同時に混合してもよく、又は逐次的若しくは段階的に混合してもよい。 Step A can be performed, for example, by mixing compound (2), compound (3), an optional reducing agent, an optional catalyst, and an optional solvent.
A conventional method can be adopted as the mixing method.
In the mixing, all substances may be mixed at the same time, or may be mixed sequentially or stepwise.
　工程Ａの反応は、光照射下で実施される。
　当該光照射に用いられる照射光としては、例えば、工程Ａの反応を開始、及び／又は促進できる光であれば特に限定なく使用することができる。その光源の例は、低圧、中圧、若しくは高圧の水銀灯、タングステンランプ、及び発光ダイオード（ＬＥＤ）が挙げられる。
　照射光は、好適に可視光であることができる。
　照射光は、好ましくは３００～６００ｎｍの波長の光を含む光、より好ましくは４００～５００ｎｍの光を含む光であることができる。
　照射時間は、好ましくは１～２４時間の範囲内、より好ましくは１０～１８時間であることができる。
　光照射の開始は、前記混合の、前、途中、同時、又は後であることができる。
　光照射の強度は、工程Ａの反応を開始、及び／又は促進できるエネルギーが供給される程度であればよく、これは、例えば、工程Ａの反応が適当に進行するように、技術常識に基づき、光源の出力、及び光源と工程Ａの反応系の距離等を調整することにより適宜調整することができる。 The reaction of step A is performed under light irradiation.
As irradiation light used for the said light irradiation, if it is the light which can start and / or accelerate | stimulate reaction of the process A, for example, it can use without limitation. Examples of such light sources include low pressure, medium pressure, or high pressure mercury lamps, tungsten lamps, and light emitting diodes (LEDs).
The irradiation light can be preferably visible light.
The irradiation light can be light containing light having a wavelength of preferably 300 to 600 nm, more preferably light containing 400 to 500 nm.
The irradiation time can be preferably in the range of 1 to 24 hours, more preferably 10 to 18 hours.
The start of light irradiation can be before, during, simultaneously with, or after the mixing.
The intensity of the light irradiation is not limited as long as energy capable of initiating and / or accelerating the reaction in the process A is supplied. This is based on, for example, common general knowledge so that the reaction in the process A proceeds appropriately. By adjusting the output of the light source, the distance between the light source and the reaction system of step A, etc., it can be adjusted as appropriate.
　工程Ａの反応は、不活性ガスの存在下で実施してもよい。このような不活性ガスの例は、窒素、及びアルゴンを包含する。 The reaction in step A may be performed in the presence of an inert gas. Examples of such inert gases include nitrogen and argon.
　工程Ａの反応温度は、好ましくは、０～１２０℃の範囲内、より好ましくは、１０～８０℃の範囲内、更に好ましくは、２０～６０℃の範囲内である。
　当該反応温度が低すぎると、工程Ａの反応が不十分になる虞がある。
　当該反応温度が高すぎると、コスト的に不利であり、及び望ましくない反応が起こる虞がある。 The reaction temperature in step A is preferably in the range of 0 to 120 ° C, more preferably in the range of 10 to 80 ° C, and still more preferably in the range of 20 to 60 ° C.
If the reaction temperature is too low, the reaction in Step A may be insufficient.
If the reaction temperature is too high, it is disadvantageous in cost and an undesirable reaction may occur.
　工程Ａの反応時間は、好ましくは、１～２４時間の範囲内、より好ましくは、５～１８時間の範囲内、更に好ましくは、１０～１５時間の範囲内である。
　当該反応時間が短すぎると、工程Ａの反応が不十分になる虞がある。
　当該反応時間が長すぎると、コスト的に不利であり、及び望ましくない反応が起こる虞がある。 The reaction time of step A is preferably in the range of 1 to 24 hours, more preferably in the range of 5 to 18 hours, and still more preferably in the range of 10 to 15 hours.
If the reaction time is too short, the reaction in step A may be insufficient.
If the reaction time is too long, it is disadvantageous in cost and an undesirable reaction may occur.
　工程Ａの反応は、好適に、バッチ式、又はフロー系により実施できる。 The reaction in step A can be preferably carried out by a batch system or a flow system.
　本発明の製造方法により得られる化合物（１）は、所望により、所望により、溶媒抽出、乾燥、濾過、蒸留、濃縮、及びこれらの組み合わせ等の公知の精製方法によって精製することができる。 The compound (1) obtained by the production method of the present invention can be purified by a known purification method such as solvent extraction, drying, filtration, distillation, concentration, and a combination thereof, if desired.
　本発明の製造方法によれば、原料である化合物（２）の転化率は、好ましくは４０％以上、より好ましくは６０％以上であり、更に好ましくは８０％以上であることができる。
　本発明の製造方法によれば、化合物（１）の選択率は好ましくは７０％以上であり、より好ましくは８０％以上であることができる。
　本発明の製造方法によれば、化合物（１）の収率は好ましくは４０％以上であり、より好ましくは６０％以上であることができる。 According to the production method of the present invention, the conversion rate of the raw material compound (2) is preferably 40% or more, more preferably 60% or more, and further preferably 80% or more.
According to the production method of the present invention, the selectivity of compound (1) is preferably 70% or more, more preferably 80% or more.
According to the production method of the present invention, the yield of compound (1) is preferably 40% or more, more preferably 60% or more.
　本発明の製造方法で得られる化合物（１）は、例えば、医薬品中間体等の用途に用いることができる。 The compound (1) obtained by the production method of the present invention can be used for applications such as pharmaceutical intermediates.
　以下、実施例によって本発明を更に詳細に説明するが、本発明はこれに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
　以下の実施例において、特に記載の無い場合、収率は単離収率である。
。 In the following examples, unless otherwise stated, the yield is an isolated yield.
.
　実施例１
Figure JPOXMLDOC01-appb-C000019
 　（１）容器に、photoredox触媒としてのRu(bpy)3Cl2・6H2O (7.5 mg, 1mol％)、及びHantzsch ester a （380.7 mg, 1.5 mmol）を加えてDMF（5 mL）で溶かした後、(bromodifluoromethyl)benzene（206.6 mg, 1.0 mmol）、1-octene（0.78 mL, 5.0 mmol）、Et3N（201.0 mg, 1.99 mmol）、及びDMF（5 mL）を加え、Ar置換を行った後、白色灯照射下、12時間攪拌した。
　反応後溶液にEtOAc /Hexane = 9/1の溶液を40 mL加え、有機層を純水20 mLで3回、及び飽和食塩水30 mLで1回、洗浄した。その後有機層を脱水、ろ過、及び乾燥した後、シリカゲルカラムクロマトグラフィー（展開溶媒：Hexane）により1,1-difluoro-1-phenylnonane（151.6 mg, 収率 63%）を得た。
　（２）photoredox触媒を使用しなかったこと以外は、前記（１）の反応と同様の反応を実施した。
　（３）更に、Et3Nを使用しなかったこと以外は、前記（１）の反応と同様の反応を実施した。
　結果を次表に示した。これから理解される通り、photoredox触媒を用いた場合、転換率が向上した。Et3N存在下、及び不存在下のいずれでも、反応が好適に進行した。 Example 1
Figure JPOXMLDOC01-appb-C000019
 (1) Add Ru (bpy) 3 Cl 2 · 6H 2 O (7.5 mg, 1 mol%) and Hantzsch ester a (380.7 mg, 1.5 mmol) as photoredox catalysts to the vessel and dissolve in DMF (5 mL). After that, (bromodifluoromethyl) benzene (206.6 mg, 1.0 mmol), 1-octene (0.78 mL, 5.0 mmol), Et 3 N (201.0 mg, 1.99 mmol), and DMF (5 mL) were added to perform Ar substitution. After that, the mixture was stirred for 12 hours under irradiation with a white lamp.
After the reaction, 40 mL of a solution of EtOAc / Hexane = 9/1 was added to the solution, and the organic layer was washed 3 times with 20 mL of pure water and once with 30 mL of saturated brine. Thereafter, the organic layer was dehydrated, filtered, and dried, and then 1,1-difluoro-1-phenylnonane (151.6 mg, yield 63%) was obtained by silica gel column chromatography (developing solvent: Hexane).
(2) The same reaction as in the above (1) was carried out except that no photoredox catalyst was used.
(3) Further, the same reaction as in the above (1) was carried out except that Et 3 N was not used.
The results are shown in the following table. As will be understood, the conversion rate was improved when the photoredox catalyst was used. The reaction proceeded favorably both in the presence and absence of Et 3 N.
Figure JPOXMLDOC01-appb-T000020
 a undecaneを内部標準として用いてＧＣで決定した。
b NMR 収率
Figure JPOXMLDOC01-appb-T000020
 Determined by GC using a undecane as internal standard.
b NMR yield
　（４）
　前記（１）と同様の方法で、但し、次表の化合物（２）、及び化合物（３）を用いて、次表の化合物（１）を得た。前記（１）の結果とともに、これらの結果を次表に示した。 (4)
In the same manner as in the above (1), except that the compound (2) and the compound (3) in the following table were used, the compound (1) in the following table was obtained. These results are shown in the following table together with the results of (1).
Figure JPOXMLDOC01-appb-T000021
Figure JPOXMLDOC01-appb-T000021
　（５）前記（１）～（４）の反応では、一部の原料化合物（次表）について、目的化合物 a［化合物（１）］以外に臭素原子移動体 b、オレフィンが2分子関与した還元的付加体 c、及びオレフィンが2分子関与した臭素原子移動体 dが同時に得られたことを確認した。次表に、そのそれぞれについて、収率、並びに化合物a、b、c、及びdのGCエリア比を示した。
Figure JPOXMLDOC01-appb-C000022
 （各式中のＲは、Ｒ２ａに対応する。）
Figure JPOXMLDOC01-appb-T000023
 (5) In the reactions (1) to (4) above, reduction of some raw material compounds (following table) involving two molecules of bromine atom transfer body b and olefin in addition to target compound a [compound (1)] It was confirmed that the target adduct c and the bromine atom transfer body d in which two molecules of olefin were involved were obtained at the same time. The following table shows the yield and the GC area ratio of compounds a, b, c and d for each of them.
Figure JPOXMLDOC01-appb-C000022
 (R in each formula corresponds to R 2a .)
Figure JPOXMLDOC01-appb-T000023
　実施例２
　実施例１（１）と同様の方法で、但し、次表に記載の条件で、実施例１（１）の反応を実施した。結果を次表に示した。
Figure JPOXMLDOC01-appb-T000024
Example 2
The reaction of Example 1 (1) was carried out in the same manner as in Example 1 (1), but under the conditions described in the following table. The results are shown in the following table.
Figure JPOXMLDOC01-appb-T000024
　実施例３
　実施例１（１）の方法と同様の方法で、容器に、(bromodifluoromethyl)benzene（1.0 mmol）、1-octene（5.0 mmol）、次表に記載のphotoredox触媒［(bromodifluoromethyl)benzeneに対して1 mol %、又は0 mol %］、Hantzsch ester a （1.5 mmol）、Et3N（2.0 mmol）、及びDMF（10 mL）を入れ、Ar置換を行った後、次表に記載の光源で光照射をしながら12時間攪拌した。白色灯としては、白色LED(5W)を用いた。昼光色灯としては、SOLARBOX 1500e（CO.FO.ME.GRA社、キセノンランプ、ソーダライムガラスUVフィルター)を用いた。
　反応後溶液にEtOAc /Hexane = 9/1の溶液を40 mL加え、有機層を純水20 mLで3回、及び飽和食塩水30 mLで1回、洗浄した。その後有機層を脱水、ろ過、及び乾燥した後、シリカゲルカラムクロマトグラフィー（展開溶媒：Hexane）により1,1-difluoro-1-phenylnonaneを得た。
　転換率、及びGC収率を次表に示した。
Figure JPOXMLDOC01-appb-T000025
 Example 3
In the same manner as in Example 1 (1), in a container, (bromodifluoromethyl) benzene (1.0 mmol), 1-octene (5.0 mmol), the photoredox catalyst described in the following table [1 to (bromodifluoromethyl) benzene mol% or 0 mol%], Hantzsch ester a (1.5 mmol), Et 3 N (2.0 mmol), and DMF (10 mL) were added, Ar substitution was performed, and then light was irradiated with the light source described in the following table The mixture was stirred for 12 hours. A white LED (5W) was used as the white light. As the daylight color lamp, SOLARBOX 1500e (CO.FO.ME.GRA, xenon lamp, soda lime glass UV filter) was used.
After the reaction, 40 mL of a solution of EtOAc / Hexane = 9/1 was added to the solution, and the organic layer was washed 3 times with 20 mL of pure water and once with 30 mL of saturated brine. Thereafter, the organic layer was dehydrated, filtered, and dried, and then 1,1-difluoro-1-phenylnonane was obtained by silica gel column chromatography (developing solvent: Hexane).
The conversion rate and GC yield are shown in the following table.
Figure JPOXMLDOC01-appb-T000025
　実施例４
Figure JPOXMLDOC01-appb-C000026
 　実施例１（１）の方法と同様の方法で、容器に、ethyl 2-bromo-2,2-difluoroacetate（1.0 mmol）、1-butene（次表の量）、Ru(bpy)3Cl2・6H2O［ethyl 2-bromo-2,2-difluoroacetateに対して1.0 mol %］、Hantzsch ester a （1.5 mmol）、Et3N（1.0 mmol）、及びDMF（5 mL）を入れ、Ar置換を行った後、白色灯照射下、12時間攪拌した。
　反応後溶液を実施例１（１）の方法と同様の方法で精製して、化合物4Aを得た。
　収率、及びGC収率を次表に示した。 Example 4
Figure JPOXMLDOC01-appb-C000026
 In a manner similar to that of Example 1 (1), in a container, ethyl 2-bromo-2,2-difluoroacetate (1.0 mmol), 1-butene (amount in the following table), Ru (bpy) 3 Cl 2. Add 6H 2 O [1.0 mol% to ethyl 2-bromo-2,2-difluoroacetate], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL), and replace with Ar. Then, the mixture was stirred for 12 hours under white light irradiation.
After the reaction, the solution was purified by the same method as in Example 1 (1) to give compound 4A.
The yield and GC yield are shown in the following table.
Figure JPOXMLDOC01-appb-T000027
Figure JPOXMLDOC01-appb-T000027
　実施例５
Figure JPOXMLDOC01-appb-C000028
　実施例１（１）の方法と同様の方法で、容器に、ペルフルオロヘキシルブロミド 5（1.0 mmol）、1-octene（次表の量）、Ru(bpy)3Cl2・6H2O［ペルフルオロヘキシルブロミド 5に対して1 mol %］、Hantzsch ester a （1.5 mmol）、Et3N（1.0 mmol）、及びDMF（5 mL）を入れ、Ar置換を行った後、白色灯照射下、12時間攪拌した。
　反応溶液を実施例１（１）の方法と同様の方法で精製して、化合物 5Aを得た。
　収率、及びGC収率を次表に示した。
　これに示される通り、1-オクテンの量を5モル当量から20モル当量に増やした場合、化合物5Aの収率は向上したが、同時に1-octeneが2分子付加した副生成物（化合物5B, 化合物5C）が生じ、化合物5Aの選択性は低下した。
Figure JPOXMLDOC01-appb-T000029
 Example 5
Figure JPOXMLDOC01-appb-C000028
In a method similar to that of Example 1 (1), in a container, perfluorohexyl bromide 5 (1.0 mmol), 1-octene (amount in the following table), Ru (bpy) 3 Cl 2 .6H 2 O [perfluorohexyl] 1 mol% with respect to bromide 5 ], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL) were added, and after Ar substitution, stirring for 12 hours under white light irradiation did.
The reaction solution was purified by the same method as in Example 1 (1) to give compound 5A.
The yield and GC yield are shown in the following table.
As shown, when the amount of 1-octene was increased from 5 molar equivalents to 20 molar equivalents, the yield of compound 5A was improved, but at the same time, a by-product (compound 5B, Compound 5C) was produced and the selectivity of compound 5A was reduced.
Figure JPOXMLDOC01-appb-T000029
　実施例６
Figure JPOXMLDOC01-appb-C000030
 　実施例１（１）の方法と同様の方法で、容器に、ブロモフルオロ酢酸エチル（1.0 mmol）、1-octene(ブロモフルオロ酢酸エチルに対して、５モル当量、１０モル当量、又は２０モル当量)、Ru(bpy)3Cl2・6H2O［ブロモフルオロ酢酸エチルに対して、1 mol %］、Hantzsch ester a （1.5 mmol）、Et3N（1.0 mmol）、及びDMF（5 mL）を入れ、Ar置換を行った後、白色灯照射下、12時間攪拌した。
　反応溶液を実施例１（１）の方法と同様の方法で精製して、化合物 6Aを得た。
　収率、及びGC収率を次表に示した
　これに示される通り、1-octeneの量を5モル当量から20モル当量に増やすと化合物6Aの収率が向上した。 Example 6
Figure JPOXMLDOC01-appb-C000030
 In a manner similar to that of Example 1 (1), in a container, ethyl bromofluoroacetate (1.0 mmol), 1-octene (5 molar equivalents, 10 molar equivalents, or 20 molar equivalents relative to ethyl bromofluoroacetate) ), Ru (bpy) 3 Cl 2 · 6H 2 O [1 mol% to ethyl bromofluoroacetate], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL) After replacing with Ar, the mixture was stirred for 12 hours under irradiation with a white lamp.
The reaction solution was purified by the same method as in Example 1 (1) to give compound 6A.
The yield and GC yield are shown in the following table. As shown in this table, increasing the amount of 1-octene from 5 molar equivalents to 20 molar equivalents improved the yield of compound 6A.
Figure JPOXMLDOC01-appb-T000031
Figure JPOXMLDOC01-appb-T000031
　実施例７
Figure JPOXMLDOC01-appb-C000032
 　実施例１（１）の方法と同様の方法で、容器に、ペルフルオロヘキシルヨージド 7（1.0 mmol）、1-octene（5.0 mmol）、Ru(bpy)3Cl2・6H2O［ペルフルオロヘキシルヨージド 7 に対して1.0 mol %］、Hantzsch ester a （1.5 mmol）、Et3N（0、又は2.0 mmol）、及びDMF（5から10 mL）を入れ、Ar置換を行った後、白色灯照射下、12時間攪拌した。
　反応後溶液を実施例１（１）の方法と同様の方法で精製して、化合物 7Aを得た。
　転換率はいずれも１００％であった。
　収率及びGC収率を次表に示した。
　これに示される通り、トリエチルアミンの有無にかかわらず化合物 7Aが良好な収率で得られた。 Example 7
Figure JPOXMLDOC01-appb-C000032
 In a manner similar to that of Example 1 (1), in a container, perfluorohexyl iodide 7 (1.0 mmol), 1-octene (5.0 mmol), Ru (bpy) 3 Cl 2 .6H 2 O [perfluorohexyl iodide 1.0 mol% relative de 7], Hantzsch ester a (1.5 mmol), Et 3 N (0, or 2.0 mmol), and placed in DMF (5 from 10 mL), after Ar-substituted, white light illumination The mixture was stirred for 12 hours.
The solution after reaction was refine | purified by the method similar to the method of Example 1 (1), and compound 7A was obtained.
The conversion rates were all 100%.
The yield and GC yield are shown in the following table.
As shown, compound 7A was obtained in good yield with or without triethylamine.
Figure JPOXMLDOC01-appb-T000033
Figure JPOXMLDOC01-appb-T000033
　実施例８
Figure JPOXMLDOC01-appb-C000034
 　実施例１（１）の方法と同様の方法で、容器に、ペルフルオロオクチルブロミド 8（1.0 mmol）、Ru(bpy)3Cl2・6H2O［ペルフルオロオクチルブロミド 8 に対して1.0 mol %］、1-octene（20 mmol）、Hantzsch ester a （1.5 mmol）、Et3N（0、又は2.0 mmol）、及びDMF（5から10 mL）を入れ、Ar置換を行った後、白色灯照射下、12時間攪拌した。
　反応後溶液を実施例１（１）の方法と同様の方法で精製して、フッ素化合物 8Aを得た。
　収率を次表に示した。 Example 8
Figure JPOXMLDOC01-appb-C000034
 In a method similar to that of Example 1 (1), in a container, perfluorooctyl bromide 8 (1.0 mmol), Ru (bpy) 3 Cl 2 .6H 2 O [1.0 mol% with respect to perfluorooctyl bromide 8 ], 1-octene (20 mmol), Hantzsch ester a (1.5 mmol), Et 3 N (0 or 2.0 mmol), and DMF (5 to 10 mL) were added, and after Ar substitution, under white light irradiation, Stir for 12 hours.
The solution after reaction was refine | purified by the method similar to the method of Example 1 (1), and the fluorine compound 8A was obtained.
The yield is shown in the following table.
Figure JPOXMLDOC01-appb-T000035
Figure JPOXMLDOC01-appb-T000035
　実施例９
Figure JPOXMLDOC01-appb-C000036
 　実施例１（１）の方法と同様の方法で、容器に、(bromodifluoromethyl)benzene（1.0 mmol）、アクリロニトリル（5.0 mmol）、Ru(bpy)3Cl2・6H2O［(bromodifluoromethyl)benzene に対して1.0 mol %］、Hantzsch ester a （1.5 mmol）、Et3N（1.0 mmol）、及びDMF（5 mL）を入れ、Ar置換を行った後、白色灯照射下、12時間攪拌した。
　反応後溶液を実施例１（１）の方法と同様の方法で精製して、化合物 8Aを得た。
　収率は７７％であった。 Example 9
Figure JPOXMLDOC01-appb-C000036
 In the same manner as in Example 1 (1), in a container, (bromodifluoromethyl) benzene (1.0 mmol), acrylonitrile (5.0 mmol), Ru (bpy) 3 Cl 2 .6H 2 O [(bromodifluoromethyl) benzene 1.0 mol%], Hantzsch ester a (1.5 mmol), Et 3 N (1.0 mmol), and DMF (5 mL) were added, and after Ar substitution, the mixture was stirred for 12 hours under white light irradiation.
The solution after reaction was refine | purified by the method similar to the method of Example 1 (1), and compound 8A was obtained.
The yield was 77%.
　実施例１０（フロー系での反応１）
Figure JPOXMLDOC01-appb-C000037
 　ethyl 2-bromo-2,2-difluoroacetate（1.0 mmol）と１-octene（5.0 mmol）との反応を、Ru(bpy)3Cl2・6H2O［ethyl 2-bromo-2,2-difluoroacetateに対して1.0 mol %］、Hantzsch ester a (1.5 mmol)、Et3N（2.0 mmol）、及びDMF (10 ml)の存在下、幅１mm、深さ300μm、及び長さ2.35mの流路を有する光マイクロリアクター（白色灯（白色LED）照射）を用いて、フロー系で行った。
　その結果、滞留時間30分で、化合物10Aが56％の収率で得られた。 Example 10 (Reaction 1 in a flow system)
Figure JPOXMLDOC01-appb-C000037
 The reaction of ethyl 2-bromo-2,2-difluoroacetate (1.0 mmol) and 1-octene (5.0 mmol) is converted to Ru (bpy) 3 Cl 2 6H 2 O [ethyl 2-bromo-2,2-difluoroacetate. 1.0 mol%], Hantzsch ester a (1.5 mmol), Et 3 N (2.0 mmol), and DMF (10 ml) in the presence of 1 mm wide, 300 μm deep, and 2.35 m long channels The flow system was performed using an optical microreactor (white light (white LED) irradiation).
As a result, Compound 10A was obtained in a yield of 56% with a residence time of 30 minutes.
　実施例１１（フロー系での反応２）
Figure JPOXMLDOC01-appb-C000038
　(bromodifluoromethyl)benzene（1.5 mmol）と１-octene（7.5 mmol）との反応を、Ru(bpy)3Cl2・6H2O［(bromodifluoromethyl)benzeneに対して1.0 mol %］、Hantzsch ester a ［(bromodifluoromethyl)benzeneに対して1.5モル当量(2.25 mmol)］、及びDMF（15 mL）の存在下、幅２mm、深さ１mm、長さ３mの流路を有する光マイクロリアクター（白色灯照射）を用いて、フロー系で行った。
　その結果、滞留時間30分で、化合物10Aが56％の収率で得られた。
　各滞留時間での転換率、及びGC収率を次表に示した。 Example 11 (Reaction 2 in flow system)
Figure JPOXMLDOC01-appb-C000038
(bromodifluoromethyl) reaction with benzene (1.5 mmol) and 1-octene (7.5 mmol), Ru (bpy) 3 Cl 2 · 6H 2 O [(bromodifluoromethyl) 1.0 mol% with respect to benzene], Hantzsch ester a [( In the presence of 1.5 molar equivalent (2.25 mmol)] and DMF (15 mL) with respect to bromodifluoromethyl) benzene, an optical microreactor (white light irradiation) with a channel of 2 mm in width, 1 mm in depth, and 3 m in length is used. The flow system was used.
As a result, Compound 10A was obtained in a yield of 56% with a residence time of 30 minutes.
The conversion rate at each residence time and the GC yield are shown in the following table.
Figure JPOXMLDOC01-appb-T000039
　これに示される通り、滞留時間の延長により、収率の向上が見られた。
　同様の反応を反応（１２ｈ）で実施した結果、化合物 11AのGC収率は８６％（収率６４％）であった。反応時間を考慮すると、フロー系の反応では、バッチ式反応よりも効率よく目的物が得られることが確認された。
Figure JPOXMLDOC01-appb-T000039
As shown, the yield was improved by extending the residence time.
A similar reaction was carried out in the reaction (12h). As a result, the GC yield of Compound 11A was 86% (yield 64%). Considering the reaction time, it was confirmed that the target product can be obtained more efficiently in the flow type reaction than in the batch type reaction.
　実施例１２（フロー系での反応３）
Figure JPOXMLDOC01-appb-I000040
　基質として１-octeneに換えてアクリル酸メチルを用いたこと以外は実施例１１の方法と同様にして、フロー系での反応を実施した。
　結果を次表に示した。
　同様の反応を反応（１２ｈ）で実施した結果、化合物 12AのGC収率は９０％（収率７２％）であった。反応時間を考慮すると、フロー系の反応では、バッチ式反応よりも効率よく目的物が得られることが確認された。 Example 12 (Reaction 3 in flow system)
Figure JPOXMLDOC01-appb-I000040
The reaction in the flow system was carried out in the same manner as in Example 11 except that methyl acrylate was used instead of 1-octene as the substrate.
The results are shown in the following table.
As a result of carrying out the same reaction in the reaction (12h), the GC yield of Compound 12A was 90% (yield 72%). Considering the reaction time, it was confirmed that the target product can be obtained more efficiently in the flow type reaction than in the batch type reaction.
Figure JPOXMLDOC01-appb-T000041
Figure JPOXMLDOC01-appb-T000041

Claims (8)

  1. 式（１）；
    Figure JPOXMLDOC01-appb-C000001
     ［式中、
    Ｒ１は、有機基を表し、
    ＲＸは、水素原子、又はフッ素原子を表し、及び
    Ｒ２ａ、Ｒ２ｂ、Ｒ２ｃ、及びＲ２ｄは、同一又は異なって、－Ｙ－Ｒ２１、又は－Ｎ（－Ｒ２２）２を表し、或いはＲ２ｂとＲ２ｃとは連結して結合を形成してもよく、
    Ｙは、結合手、酸素原子、又は硫黄原子を表し、
    Ｒ２１は、水素原子、又は有機基を表し、
    Ｒ２２は、各出現において同一又は異なって、水素原子、又は有機基を表す。］
    で表される化合物、又はその閉環誘導体、若しくは開環誘導体の製造方法であって、
    式（２）：
    Figure JPOXMLDOC01-appb-C000002
     ［式中、Ｘは脱離基を表し、及びその他の記号は前記と同意義を表す。］
    で表される化合物を、
    還元剤の存在下、且つ光照射下で、
    式（３）：
    Figure JPOXMLDOC01-appb-C000003
     ［式中の記号は前記と同意義を表す。］
    で表される化合物と反応させる工程Ａを含む製造方法。     Formula (1);
    Figure JPOXMLDOC01-appb-C000001
     [Where:
    R 1 represents an organic group,
    R X represents a hydrogen atom or a fluorine atom, and R 2a , R 2b , R 2c , and R 2d are the same or different and represent —Y—R 21 or —N (—R 22 ) 2 . Or R 2b and R 2c may be linked to form a bond,
    Y represents a bond, an oxygen atom, or a sulfur atom,
    R 21 represents a hydrogen atom or an organic group,
    R 22 is the same or different at each occurrence and represents a hydrogen atom or an organic group. ]
    Or a ring-closed derivative or a ring-opened derivative thereof,
    Formula (2):
    Figure JPOXMLDOC01-appb-C000002
     [Wherein, X represents a leaving group, and other symbols are as defined above. ]
    A compound represented by
    In the presence of a reducing agent and under light irradiation,
    Formula (3):
    Figure JPOXMLDOC01-appb-C000003
     [The symbols in the formula are as defined above. ]
    The manufacturing method including the process A made to react with the compound represented by these.
  2. Ｒ１が、アルキル基、フルオロアルキル基、アルコキシカルボニル基、又は芳香族基基である請求項１に記載の製造方法。 The production method according to claim 1, wherein R 1 is an alkyl group, a fluoroalkyl group, an alkoxycarbonyl group, or an aromatic group.
  3. Ｒ２ａが、アルキル基、又はアリール基であり、且つＲ２ｂ、Ｒ２ｃ、及びＲ２ｄが、水素原子である請求項１又は２に記載の製造方法 The production method according to claim 1 or 2, wherein R 2a is an alkyl group or an aryl group, and R 2b , R 2c , and R 2d are hydrogen atoms.
  4. Ｘが、臭素原子である請求項１～３のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 3, wherein X is a bromine atom.
  5. 工程Ａの反応が、N－H部を有する含窒素不飽和複素環化合物の存在下で実施される請求項１～４のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 4, wherein the reaction in Step A is carried out in the presence of a nitrogen-containing unsaturated heterocyclic compound having an NH portion.
  6. 前記還元剤が、式（４）：
    Figure JPOXMLDOC01-appb-C000004
     ［式中、
    Ｒ３ａ、Ｒ３ｂ、Ｒ３ｃ、及びＲ３ｄは、同一又は異なって、アルキル基を表す。］
    で表される化合物である請求項１～５のいずれか１項に記載の製造方法。     The reducing agent is represented by the formula (4):
    Figure JPOXMLDOC01-appb-C000004
     [Where:
    R 3a , R 3b , R 3c , and R 3d are the same or different and represent an alkyl group. ]
    The production method according to any one of claims 1 to 5, wherein the compound is represented by the formula:
  7. 工程Ａの反応が、触媒の存在下で実施される請求項１～６のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 6, wherein the reaction in step A is carried out in the presence of a catalyst.
  8. 前記触媒が、遷移金属錯体、及び有機色素化合物からなる群より選択される１種以上である請求項７に記載の製造方法。 The production method according to claim 7, wherein the catalyst is at least one selected from the group consisting of a transition metal complex and an organic dye compound.
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