WO2017006929A1 - Procédé de production d'un composé optiquement actif, et sel de triazolium utilisé en tant que catalyseur dans ledit procédé - Google Patents

Procédé de production d'un composé optiquement actif, et sel de triazolium utilisé en tant que catalyseur dans ledit procédé Download PDF

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WO2017006929A1
WO2017006929A1 PCT/JP2016/069888 JP2016069888W WO2017006929A1 WO 2017006929 A1 WO2017006929 A1 WO 2017006929A1 JP 2016069888 W JP2016069888 W JP 2016069888W WO 2017006929 A1 WO2017006929 A1 WO 2017006929A1
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group
optionally substituted
alkyl group
general formula
optically active
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貴史 大井
亨介 大松
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国立大学法人名古屋大学
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • 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
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • 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 an optically active compound and a triazolium salt used as a catalyst therefor.
  • Optically active ⁇ -tetrasubstituted ⁇ -amino nitrile derivatives and optically active ⁇ -tetrasubstituted ⁇ -amino acids are widely used as intermediates for the synthesis of medicines and agricultural chemicals.
  • a method for synthesizing an ⁇ -tetrasubstituted ⁇ -amino nitrile derivative and an optically active ⁇ -tetrasubstituted ⁇ -amino acid for example, a method using a step of performing a cyanation reaction (Strecker reaction) using ketimine is known.
  • ketoimine has low reactivity, and it is difficult to catalytically control stereochemistry in the cyanation reaction (Strecker reaction), and it is difficult to synthesize with good yield and stereoselectivity.
  • a method for synthesizing such ⁇ -tetrasubstituted ⁇ -amino nitrile derivatives and optically active ⁇ -tetrasubstituted ⁇ -amino acids there is also known a method using a step of proceeding the reaction using hydrogen cyanide or silyl cyanide in the presence of an optically active catalyst. (For example, Non-Patent Documents 1 and 2).
  • hydrogen cyanide is volatile and difficult to handle, and silyl cyanide is expensive.
  • An object of the present invention is to provide a production method capable of easily obtaining an optically active ⁇ -tetrasubstituted ⁇ -amino nitrile derivative or an intermediate for the synthesis thereof with good yield and stereoselectivity.
  • the present inventors have conducted intensive research to solve the above problems.
  • direct cyanation of the ketoimine derivative is achieved by reacting with a specific ketoimine derivative using an inexpensive and easy-to-handle metal cyanide as the cyano source. It has been found that a Strecker reaction can be caused.
  • the optically active compound obtained by this method the desired ⁇ -tetrasubstituted ⁇ -amino nitrile derivative can be easily obtained with good yield and stereoselectivity.
  • the present inventors have further studied and completed the present invention. That is, the present invention includes the following configurations.
  • R 1 and R 2 are different and each represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, or an optionally substituted aryl group.
  • R 5 and R 8 to R 10 are the same or different and each represents an optionally substituted alkyl group or an optionally substituted aryl group.
  • R 6 represents an optionally substituted primary alkyl group.
  • R 7 represents an optionally substituted aliphatic alkyl group or an optionally substituted cycloalkyl group.
  • X 1 represents a halogen atom or a monovalent anion.
  • a compound represented by A production method comprising a reaction step of reacting with a metal cyanide.
  • R 1 and R 2 are both an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aryl group.
  • Item 2 The production method according to Item 1.
  • Item 3. The production method according to Item 1 or 2, wherein R 1 and R 2 in the general formulas (1) and (3) are both an optionally substituted alkyl group or an optionally substituted cycloalkyl group. .
  • Item 4. The production method according to any one of Items 1 to 3, wherein the metal cyanide is potassium cyanide.
  • Item 5 The production method according to any one of Items 1 to 4, wherein R 5 and R 8 to R 10 in the general formula (2) are all optionally substituted aryl groups.
  • Item 6. The production method according to any one of Items 1 to 5, wherein R 6 in the general formula (2) is a primary alkyl group substituted with an alkoxy group.
  • Item 7. The production method according to any one of Items 1 to 6, wherein R 10 in the general formula (2) is an aryl group substituted with a halogenated alkyl group.
  • a production method comprising a step of neutralizing an optically active compound obtained by the production method according to Item 8.
  • R 5 and R 8 to R 10 are the same or different and each represents an optionally substituted alkyl group or an optionally substituted aryl group.
  • R 6 represents an optionally substituted primary alkyl group.
  • R 7 represents an optionally substituted aliphatic alkyl group or an optionally substituted cycloalkyl group.
  • X 1 represents a halogen atom or a monovalent anion.
  • Item 11 The catalyst according to Item 10, wherein R 5 and R 8 to R 10 in the general formula (2) are all optionally substituted aryl groups.
  • R 1 and R 2 are different and each represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, or an optionally substituted aryl group.
  • R 3 represents an organic group.
  • R 1 and R 2 are both an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aryl group.
  • Item 13 The catalyst according to Item 12.
  • R 5 and R 8 to R 10 are the same or different and each represents an optionally substituted alkyl group or an optionally substituted aryl group.
  • R 6A represents a primary alkyl group substituted with an alkoxy group.
  • R 7 represents an optionally substituted aliphatic alkyl group.
  • X 1 represents a halogen atom or a monovalent anion.
  • Item 15 The triazolium salt according to Item 14, wherein R 5 and R 8 to R 10 in the general formula (2) are all optionally substituted aryl groups.
  • Item 16 The triazolium salt according to Item 14 or 15, wherein R 10 is an aryl group substituted with a halogenated alkyl group.
  • R 1 and R 2 are different and each represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, or an optionally substituted aryl group.
  • R 3A represents a dialkylphenyl group.
  • R 1 and R 2 in the general formula (1A) are both an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aryl group.
  • an inexpensive and easy-to-handle metal cyanide is used as a cyano source to react with a specific ketoimine derivative, thereby reducing the ketoimine derivative.
  • a Strecker reaction that causes direct cyanation can occur.
  • an optically active compound can be obtained by effectively reacting a specific ketoimine derivative with a metal cyanide in the presence of a specific triazolium salt.
  • various optically active compounds can be usually obtained by reacting a specific ketoimine derivative with a metal cyanide in a solvent in the presence of a specific triazolium salt.
  • Substrate Compound The compound used as a substrate to be subjected to the reaction is not particularly limited.
  • R 1 and R 2 are different and each represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, or an optionally substituted aryl group.
  • the alkyl group represented by R 1 and R 2 is not particularly limited, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, sec And acyclic aliphatic alkyl groups such as a butyl group and a tert-butyl group (preferably an acyclic aliphatic alkyl group having 1 to 10 carbon atoms, particularly 3 to 6 carbon atoms).
  • a linear acyclic aliphatic alkyl group can also be employ
  • alkyl groups include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), alkoxy groups described below, alkenyl groups described below, aryl groups described below, alkoxycarbonyl groups described below, aryloxy groups described below, etc. It may have about 1 to 6 (particularly 1 to 3) substituents.
  • the alkyl group having such a substituent is an aralkyl group (preferably having 7 to 20 carbon atoms, particularly carbon atoms) such as a benzyl group, a methylbenzyl group, a phenethyl group, a methylphenethyl group, a naphthylmethyl group, and a methylnaphthylmethyl group.
  • an aralkyl group of 7 to 14 is an aralkyl group (preferably having 7 to 20 carbon atoms, particularly carbon atoms) such as a benzyl group, a methylbenzyl group, a phenethyl group, a methylphenethyl group, a naphthylmethyl group, and a methylnaphthylmethyl group.
  • an aralkyl group of 7 to 14 such as a benzyl group, a methylbenzyl group, a phenethyl group, a methylphenethy
  • the cycloalkyl group represented by R 1 and R 2 is not particularly limited, and examples thereof include a cyclopropyl group, a cyclopropylmethyl group, a cyclobutyl group, a cyclobutylmethyl group, a cyclopentyl group, and a cyclopentylmethyl.
  • a cycloalkyl group such as a group, a cyclohexyl group, a cyclohexylmethyl group, a cyclohexylethyl group, an adamantyl group (preferably a cycloalkyl group having 3 to 10 carbon atoms, particularly 5 to 8 carbon atoms, etc.).
  • Substituents such as halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), alkoxy groups described below, alkenyl groups described below, aryl groups described below, alkoxycarbonyl groups described below, aryloxy groups described below, etc. It can also have about 3 (especially 1 to 3).
  • the alkenyl group represented by R 1 and R 2 is not particularly limited, and examples thereof include alkenyl groups such as vinyl groups and allyl groups (preferably having 2 to 11 carbon atoms, particularly 4 to 4 carbon atoms). 7 alkenyl group) and the like.
  • alkenyl groups include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), the above alkyl group, an alkoxy group described below, the above alkenyl group, an aryl group described below, an alkoxycarbonyl group described below, It may have about 1 to 6 (especially 1 to 3) substituents such as an aryloxy group.
  • the aryl group represented by R 1 and R 2 is not particularly limited, and examples thereof include a phenyl group, a tolyl group (o-tolyl group, m-tolyl group, p-tolyl group), xylyl Group (o-xylyl group, m-xylyl group, p-xylyl group), naphthyl group and the like.
  • aryl groups include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), the above alkyl group, an alkoxy group described below, an alkenyl group described below, an aryl group described above, an alkoxycarbonyl group described below, It may have about 1 to 6 (especially 1 to 3) substituents such as an aryloxy group.
  • halogen atom fluorine atom, chlorine atom, bromine atom, iodine atom, etc.
  • an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, etc. are preferable, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and the like are more preferable, and an unsubstituted acyclic aliphatic alkyl group, an unsubstituted cycloalkyl group, and the like are more preferable.
  • R 1 and R 2 are different.
  • the organic group represented by R 3 is not particularly limited, and is a hydrocarbon group (alkyl group, cycloalkyl group, alkenyl group, aryl group), alkoxy group, alkoxycarbonyl group, aryloxy group. Etc.
  • the alkoxy group represented by R 3 is not particularly limited, and examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, and a sec-butoxy group.
  • an acyclic aliphatic alkoxy group such as a tert-butoxy group (preferably an acyclic aliphatic alkoxy group having 1 to 10 carbon atoms, particularly 3 to 6 carbon atoms).
  • an acyclic linear aliphatic alkoxy group can also be employ
  • These alkoxy groups include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc.), the alkyl group, the cycloalkyl group, the alkoxy group, the alkenyl group, the aryl group, which will be described later. It may have about 1 to 6 (especially 1 to 3) substituents such as an alkoxycarbonyl group and an aryloxy group described later.
  • the alkoxycarbonyl group as the organic group represented by R 3 is not particularly limited, and examples thereof include a methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group, n- Aliphatic alkoxycarbonyl groups such as butoxycarbonyl group, isobutoxycarbonyl group, sec-butoxycarbonyl group, tert-butoxycarbonyl group (preferably an aliphatic alkoxycarbonyl group having 2 to 11 carbon atoms, particularly 4 to 7 carbon atoms), etc. Is mentioned.
  • a linear aliphatic alkoxycarbonyl group can also be employ
  • These alkoxycarbonyl groups include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), the alkyl group, the alkoxy group, the alkenyl group, the aryl group, the alkoxycarbonyl group, which will be described later. 1-6 (especially 1 to 3) of substituents such as aryloxy groups may be included.
  • the aryloxy group as the organic group represented by R 3 is not particularly limited, and examples thereof include phenoxy group, tolyloxy group (o-tolyloxy group, m-tolyloxy group, p-tolyloxy group). And xylyloxy group (o-xylyloxy group, m-xylyloxy group, p-xylyloxy group), naphthyloxy group and the like.
  • aryloxy groups include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), the alkyl group, the alkoxy group, the alkenyl group, the aryl group, the alkoxycarbonyl group, 1-6 (especially 1 to 3) of substituents such as aryloxy groups may be included.
  • an aryl group which may be substituted is preferable from the viewpoint of yield, stereoselectivity, and the like, a substituted aryl group is more preferable, and an aryl group substituted with 1 to 3 alkyl groups Is more preferable.
  • Etc. are more preferable.
  • a metal cyanide is used in order to introduce a cyano group into the substrate compound (compound (3)).
  • the metal cyanide include alkali metal cyanides such as potassium cyanide and sodium cyanide; alkaline earth metal cyanides such as calcium cyanide and magnesium cyanide. Of these, alkali metal cyanide is preferable and potassium cyanide is more preferable from the viewpoint of yield, stereoselectivity, and the like.
  • the cyanation reaction can proceed without using a cyanating agent that is difficult to handle, such as hydrogen cyanide.
  • the amount of metal cyanide used is not particularly limited, and from the viewpoint of yield, stereoselectivity, etc., for example, it is usually preferably about 0.5 to 20 moles, preferably about 1 to 10 moles per mole of compound (3). Is more preferable.
  • R 5 and R 8 to R 10 are the same or different and each represents an optionally substituted alkyl group or an optionally substituted aryl group.
  • R 6 represents an optionally substituted primary alkyl group.
  • R 7 represents an optionally substituted aliphatic alkyl group or an optionally substituted cycloalkyl group.
  • X 1 represents a halogen atom or a monovalent anion. ] (Hereinafter also referred to as “triazolium salt (2)”).
  • alkyl group and aryl group represented by R 5 those described above can be employed.
  • the kind and number of substituents are the same.
  • an aryl group which may be substituted is preferable, a substituted aryl group is more preferable, and 1 to 6, particularly 1 to 3 halogen atoms (fluorine atom, chlorine) are preferable.
  • Atom, bromine atom, iodine atom, etc.) an aryl group substituted with the aryl group or the like is more preferred.
  • aryl group substituted with the aryl group or the like is more preferred.
  • the primary alkyl group represented by R 6 is not particularly limited, and examples thereof include acyclic groups such as a methyl group, an ethyl group, an n-propyl group, an n-butyl group, and an isobutyl group. And an aliphatic primary alkyl group (preferably an acyclic aliphatic primary alkyl group having 1 to 6 carbon atoms, particularly 1 to 4 carbon atoms).
  • These primary alkyl groups include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), the alkoxy group, the alkenyl group, the aryl group, the alkoxycarbonyl group, the aryloxy group. It may have about 1 to 6 (especially 1 to 3) substituents such as groups.
  • the primary alkyl group having such a substituent is an aromatic primary alkyl group such as an aralkyl group such as a benzyl group, a methylbenzyl group, a phenethyl group, a methylphenethyl group, a naphthylmethyl group, or a methylnaphthylmethyl group.
  • a group preferably an aromatic primary alkyl group such as an aralkyl group having 7 to 20 carbon atoms, particularly 7 to 14 carbon atoms).
  • an acyclic aliphatic primary alkyl group When an acyclic aliphatic primary alkyl group is used, a linear acyclic aliphatic primary alkyl group can also be used, and a branched acyclic primary aliphatic alkyl group is also used. You can also Among them, from the viewpoint of yield, stereoselectivity, etc., an aromatic primary alkyl group which may be substituted is preferable, an optionally substituted aralkyl group is more preferable, a substituted aralkyl group is more preferable, and 1 Aralkyl groups substituted with up to 3 alkoxy groups and the like are particularly preferred.
  • the aliphatic alkyl group represented by R 7 is not particularly limited, and examples thereof include a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec- And acyclic aliphatic alkyl groups such as a butyl group and a tert-butyl group (preferably an acyclic aliphatic alkyl group having 1 to 6 carbon atoms, particularly 1 to 4 carbon atoms).
  • a linear acyclic aliphatic alkyl group can also be employ
  • These aliphatic alkyl groups include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), the alkoxy group, the alkenyl group, the aryl group, the alkoxycarbonyl group, and the aryloxy group. It can also have about 1 to 6 (especially 1 to 3) substituents such as.
  • R 8 and R 9 as the alkyl group and aryl group represented by R 8 and R 9 , those described above can be adopted.
  • the kind and number of substituents are the same. Among these, from the viewpoints of yield, stereoselectivity, etc., an aryl group which may be substituted is preferable, an unsubstituted aryl group or an aryl group substituted with one halogen atom is more preferable, a phenyl group or chlorophenyl Groups are more preferred.
  • R 8 and R 9 may be the same or different.
  • alkyl group and aryl group represented by R 10 those described above can be employed.
  • the kind and number of substituents are the same.
  • an aryl group which may be substituted is preferable from the viewpoints of yield, stereoselectivity, etc., an unsubstituted aryl group or two alkyl groups (preferably a halogenated alkyl group, particularly a perfluoroalkyl group).
  • An aryl group substituted with the alkoxy group or the like is more preferable, and a phenyl group, a dimethoxyphenyl group, or a bis (trifluoromethyl) phenyl group is more preferable.
  • a chlorine atom, a bromine atom, an iodine atom or the like can be adopted as the halogen atom represented by X 1 .
  • X 1 is preferably a halogen atom, more preferably a chlorine atom, a bromine atom, or the like, and further preferably a bromine atom, from the viewpoints of yield, stereoselectivity, and the like.
  • triazolium salts (2) may be known or commercially available compounds, and may be synthesized according to the methods described in the previous reports (J. Am. Chem. Soc. 2011, 133, 1307-1309., Etc.). You can also
  • the amount of the triazolium salt (2) to be used is not particularly limited, and from the viewpoint of yield, stereoselectivity, etc., for example, usually about 0.002 to 0.1 mol is preferable with respect to 1 mol of compound (3), and 0.005 to 0.05 A molar degree is more preferable.
  • Such a triazolium salt (2) is not limited to the production method of the present invention, and can be used as a catalyst for Strecker reaction.
  • R 5 , R 7 to R 10 and X 1 are the same as defined above.
  • R 6A represents the primary alkyl group substituted with the alkoxy group. ] Is a novel compound not described in any literature.
  • solvent examples include water; aromatic hydrocarbons such as toluene, xylene, benzene and mesitylene; aliphatic halogenated carbonization such as dichloromethane, chloroform, carbon tetrachloride and dichloroethane.
  • chain ethers such as diethyl ether, dimethoxyethane, diisopropyl ether, and tert-butyl methyl ether
  • esters such as ethyl acetate and ethyl propionate
  • ketones such as acetone and methyl ethyl ketone.
  • a mixed solvent of water and aromatic hydrocarbons is preferable from the viewpoint of yield, stereoselectivity, and the like.
  • the content ratio is not particularly limited, and from the viewpoint of yield, stereoselectivity, etc., the volume ratio is water: aromatic. It is preferable to adjust the hydrocarbons to 1: 5 to 100, particularly 1:10 to 50.
  • the reaction can proceed without using a base.
  • the present invention is preferably carried out under an inert gas atmosphere (nitrogen gas, argon gas, etc.), and the reaction temperature is usually about ⁇ 78 ° C. to room temperature (25 ° C.), preferably about ⁇ 70 to 20 ° C.
  • the temperature is preferably about ⁇ 60 to 0 ° C., more preferably about ⁇ 50 to ⁇ 20 ° C.
  • the reaction time may be a time for which the reaction proceeds sufficiently, and is usually about 10 minutes to 72 hours, preferably about 1 to 48 hours.
  • the target compound After completion of the reaction, the target compound can be obtained through normal isolation and purification steps as necessary.
  • R 3A represents a dialkylphenyl group (a dimethylphenyl group such as a 3,5-dimethylphenyl group or a 2,5-dimethylphenyl group; a diethylphenyl group).
  • R 3A represents a dialkylphenyl group (a dimethylphenyl group such as a 3,5-dimethylphenyl group or a 2,5-dimethylphenyl group; a diethylphenyl group).
  • any of the optically active compounds obtained in Examples described later is a novel compound not described in any literature, and is useful as an intermediate for the synthesis of medical and agricultural chemicals.
  • optically active compound (1) is obtained by the production method of the present invention described above, a cyano group is converted to a carboxy group and a —SO 2 R 3 group is converted according to a conventional method.
  • a desired amino acid can also be obtained by conversion to an amino group or —NH 3 X group (X is a halogen atom such as chlorine, bromine, iodine, etc.). For example, removal of a sulfonyl group described in J. Am. Chem. Soc., 2006, 128, 2548., etc., hydrolysis of a nitrile group described in Org. Proc. Res. Dev., 2008, 12, 298.
  • the amino acid can be obtained from the optically active compound (1) according to the above.
  • the amino acid thus obtained has the general formula (4):
  • R 1 and R 2 are the same as defined above.
  • X represents a halogen atom.
  • It is an optically active compound represented by these.
  • the desired amino acid can also be obtained by neutralization according to a conventional method.
  • the amino acid thus obtained has the general formula (5):
  • Me represents a methyl group.
  • t-Bu represents a tert-butyl group.
  • Et represents an ethyl group.
  • Ar represents a 3,5-dimethylphenyl group. The same applies hereinafter.
  • 4-OMeC 6 H 4 represents a 4-methoxyphenyl group.
  • 3,5-CF 3 C 6 H 3 represents a 3,5-di (trifluoromethyl) phenyl group.
  • the same applies hereinafter. was synthesized according to the synthesis method described in the previous report (J. Am. Chem. Soc. 2011, 133, 1307-1309.) (In the same manner except that the substituents of the raw materials were changed).
  • Example 1-2 The same treatment as in Example 1-1 was performed, except that various compounds were used as substrate compounds and any of the triazolium salts obtained in Synthesis Examples 2-1 and 2-2 was used as a catalyst. As a result, it was confirmed that an optically active compound having a substituent shown in Table 1 below was obtained. The results are shown in Table 1.
  • entry 4 1 H NMR (400 MHz, CDCl 3 ) ⁇ 7.55 (2H, s), 7.22 (1H, s), 4.86 (1H, brs), 2.39 (6H, s), 2.09 (3H, br), 1.74 -1.61 (12H, m), 1.56 (3H, s).
  • TFA trifluoroacetic acid.
  • BzCl represents benzoyl chloride.
  • DCM dichloromethane.
  • a test tube was charged with compound 3 (29.4 mg, 0.1 mmol) obtained in Example 1-1, trifluoroacetic acid (0.9 mL), thioanisole (0.1 mL) and methanesulfonic acid (10 ⁇ L), and the mixture was stirred at room temperature for 10 hours. Stir. After the reaction, concentrate in an evaporator, add dichloromethane (0.5 mL), water (0.5 mL) and potassium carbonate (55.3 mg, 0.4 mmol) to the test tube containing the crude product, and benzoyl chloride (20 ⁇ L, 0.15 mmol).

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Abstract

La présente invention permet d'obtenir facilement, en présentant un rendement important et une bonne stéréosélectivité, un dérivé de nitrile α-amino, α-tétrasubstitué optiquement actif, ou un intermédiaire pour la synthèse dudit dérivé, en faisant réagir un cyanométallate avec un composé représenté par la formule (3), selon laquelle R1-R3 sont tels que décrits, en présence d'un sel de triazolium représenté par la formule (2), selon laquelle R5 et R8-R10 sont identiques ou différents et représentent un groupe aryle qui peut être substitué, R6 représente un groupe alkyle primaire qui peut être substitué, R7 représente un groupe alkyle gras qui peut être substitué, ou un groupe cycloalkyle qui peut être substitué, et X1 représente un atome d'halogène ou un anion monovalent.
PCT/JP2016/069888 2015-07-06 2016-07-05 Procédé de production d'un composé optiquement actif, et sel de triazolium utilisé en tant que catalyseur dans ledit procédé WO2017006929A1 (fr)

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Citations (1)

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JP2012082155A (ja) * 2010-10-08 2012-04-26 Nagoya Univ トリアゾリウム塩及びその製造方法、アジドアルコール並びに不斉反応によるアルキル化オキシインドールの製造方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012082155A (ja) * 2010-10-08 2012-04-26 Nagoya Univ トリアゾリウム塩及びその製造方法、アジドアルコール並びに不斉反応によるアルキル化オキシインドールの製造方法

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Title
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