WO2007013697A1 - Sel d'ammonium quaternaire optiquement actif axi-asymmetrique et procede de production d'un $g(a)-amino acide ou d'un derive de celui-ci a l'aide du sel d'ammonium quaternaire - Google Patents

Sel d'ammonium quaternaire optiquement actif axi-asymmetrique et procede de production d'un $g(a)-amino acide ou d'un derive de celui-ci a l'aide du sel d'ammonium quaternaire Download PDF

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WO2007013697A1
WO2007013697A1 PCT/JP2006/315456 JP2006315456W WO2007013697A1 WO 2007013697 A1 WO2007013697 A1 WO 2007013697A1 JP 2006315456 W JP2006315456 W JP 2006315456W WO 2007013697 A1 WO2007013697 A1 WO 2007013697A1
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group
alkyl
halogen atom
substituted
branched
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PCT/JP2006/315456
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Japanese (ja)
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Keiji Maruoka
Jun Matsumoto
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Nagase & Co., Ltd.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • 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
    • B01J31/0231—Halogen-containing compounds
    • 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
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0239—Quaternary ammonium compounds
    • 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
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
    • 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
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/46—C-H or C-C activation
    • 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
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/90—Catalytic systems characterized by the solvent or solvent system used
    • B01J2531/98—Phase-transfer catalysis in a mixed solvent system containing at least 2 immiscible solvents or solvent phases
    • B01J2531/985—Phase-transfer catalysis in a mixed solvent system containing at least 2 immiscible solvents or solvent phases in a water / organic solvent system

Definitions

  • the present invention relates to an optically active quaternary ammonium salt having axial asymmetry and a method for producing the same.
  • the present invention further relates to a method for producing an optically active amino acid and an derivative thereof using the optically active quaternary ammonium salt having this axial asymmetry as a phase transfer catalyst.
  • the ⁇ ; -alkyl monoamino acid represented by the formula H 2 NCH (R) COOH is a very important naturally occurring amino acid.
  • Most of a-alkyl- ⁇ _amino acids are present in animals, plants, microorganisms, etc. as L-forms having L-configuration at the ⁇ -position carbon, and this L-form constitutes a polypeptide chain.
  • D form exists as a non-protein compound in plants, fungi, and microorganisms.
  • ⁇ , hedialkyl _ ⁇ -amino acids represented by the formula H 2 NC (R) (R ') COOH are stereochemically stable, and when incorporated into peptides, they are enzymatically hydrolyzed by proteases. It is a compound that has been attracting attention in recent years due to its inherent function, such as being difficult to be affected (Bellier, B. et al., J. Med. Chera., 1997, 40 ⁇ , p. 3947 and ossel, E. Et al., Tetrahedron Asymmetry, 1997, 8, p.1305).
  • peptide having enhanced activity an effective enzyme inhibitor, and a chiral construct block for the synthesis of compounds having various biological activities.
  • an effective enzyme inhibitor for example, it can be used as a peptide having enhanced activity, an effective enzyme inhibitor, and a chiral construct block for the synthesis of compounds having various biological activities.
  • Such ⁇ , ⁇ -dialkyl mono ⁇ -amino acids have been studied for preparation by catalytic asymmetric reaction. No effective preparation method has been found.
  • phase transfer catalysts that enable stereoselective alkylation of glycine derivatives are gaining importance in the field of process chemistry due to their application.
  • many studies have been conducted on the design of phase transfer catalysts, primarily using cinchona alkaloid derivatives, and several useful methods have been reported (e.g. Shioiri, T. et al., Stimulating (See Concepts in Chemistry: Vogtle, F. et al., WILEY- VCH: Weinheim, 2000, p. 123 and 0 'Donnell, MJ, Aldrichimica Acta, 2001, 34, p. 3).
  • phase transfer catalyst when such a phase transfer catalyst is used, there are various problems such as the use of a halogen-based solvent, a long time for the reaction, and low temperature conditions.
  • a chiral phase transfer catalyst derived from a cinchona al forceloid is not very useful.
  • an optically active quaternary ammonium salt having axial asymmetry can be prepared and used as a phase transfer catalyst for stereoselectively synthesizing the above-mentioned amino acids 2 0 0 1-4 8 8 6 6, JP 2 0 3 3 8 1 9 7 6, and 0oi, T. et al., J. Am. Chem. Soc., 2000, 122, (See p. 5 228).
  • An object of the present invention is to provide a chiral phase transfer catalyst having a simplified structure that can be produced with fewer processes. Furthermore, an object of the present invention is to provide a chiral phase transfer catalyst that can be expected to improve stereoselectivity in an asymmetric reaction by including a long-chain alkyl group in the catalyst structure.
  • the present invention provides a compound represented by the following formula (I):
  • R ⁇ R 1 ', R 2 , R 2', R 3, R 3 ', R 4, R 4', R 5, R 5 ', R 6 and R 6' are each independently,
  • NHCOR 9 (wherein, R 9 is branched even if well and halo substituted by Gen atoms C i C alkyl group);
  • (ix) may be branched or ringed and may be substituted with a halogen atom.
  • (X) to form a branched or ring may be substituted in good and halogen 'atom, an alkenyl group of C 2 -C 6;
  • (X i) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C 2 -C 6;
  • Halogen atom which may be branched and may be substituted with a halogen atom ⁇ to ⁇ Alkyl group, cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently , A hydrogen atom or an alkyl group which may be substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (C 1 -C 4 alkyl) carbamoyl group, N, N—di (C 1 -C 4 alkyl) a strong rubermoyl group, or one NHCOR 9 (wherein R 9 is a C 4 -C 4 alkyl group which may be branched and substituted with a halogen atom).
  • R 9 is a C 4 -C 4 alkyl group which may be branched and substituted with a halogen atom.
  • aryl group optionally substituted, aryl group,
  • R 9 is a C 1 -C 4 alkyl group that may be branched and optionally substituted with a halogen atom
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • a C C alkyl group which may be branched and may be substituted by a halogen atom,
  • Branched c 1 may be substituted in good and halogen atom have to c 5 alkoxy group
  • Ha port Gen atoms may be branched and Ha port Gen atoms optionally substituted C 4 alkyl group, 'Shiano group, one NR 2.
  • R 21 (wherein, R 20 and R 21 are each independently a hydrogen atom, or a halogen atom is one or Ji-Ji alkyl group which may be substituted by) a nitro group, Karupamoiru group, N-(Ci C alkyl) force Rubamoiru group, N, N-di (C 1 -C 4 alkyl Le) force Rubamoiru group or a NHCOR 9 (wherein, R 9 is a common and halogen atoms be branched, An optionally substituted Ci CT alkyl group), an aryl group, Ciano group,
  • R 2 ° and R 21 are each independently a hydrogen atom or a C 4 to C 4 alkyl group optionally substituted with a haguchi atom
  • R 9 is Ji may be substituted with well and halogen atoms be branched ⁇ . ⁇ Alkyl group
  • a heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Branched C 1 may be substituted with at best 'and halogen atoms optionally -C 4 alkyl group,
  • C 1 -C 4 alkyl group Cyano group, one NR 20 R 21 ('where R 20 and R 21 is each independently a hydrogen atom or a Ci C alkyl group optionally substituted with a halogen atom), a nitro group, a force rubermoyl group, N- (C 1 -C 4 alkyl) force rubermoyl Group, N, N—di (C 1 -C 4 alkyl) force rubamoyl group, or one NHCOR 9 (wherein R 9 may be branched and substituted with a halogen atom C ⁇ C An alkyl group), an aryl group, Ciano group,
  • R 20 and R 21 are each independently a hydrogen atom, or at any good c ⁇ c alkyl group optionally substituted by a halogen atom),
  • NHCOR 9 (wherein it is a Ci C alkyl group that may be branched or substituted with a halogen atom),
  • Branched C 1 may be substituted in good and halogen atoms optionally -C 4 alkyl group,
  • a 5 alkoxy group which may be branched and optionally substituted with a halogen atom
  • a halogen atom which may be branched and optionally substituted with a halogen atom, a CC alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently A hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with a halogen atom), a nitro group, a rubamoyl group, N- (Ci C alkyl) force rubermoyl group, N, N—di (ji ⁇ .
  • R 2 ° and R 21 are each independently a hydrogen atom or an alkyl group optionally substituted with a halogen atom
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • R 7 may form a branch or a ring and may be substituted with a halogen atom C 13 to C 3 .
  • R 8 may form a branch or a ring, and may be substituted with a halogen atom.
  • RR 1 ′, R 2 of the compound represented by the above formula (I), R 2 ′, R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 and R 6 ′ are each independently
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • Halogen atoms, branched C 1 may be substituted in good and halogen atoms optionally -C 4 alkyl group, Shiano group, _NR 20 R 21 (wherein, R 20 and R 21 are each independently , A hydrogen atom or a halogen atom which may be substituted with a hydrogen atom or a halogen atom), a nitro group, a strong rubamoyl group, an N- (di-alkyl), a rubamoyl group, N, N-di ( CC alkyl) or a carbamoyl group, or one NHCOR 9 (wherein R 9 is a C i to C 4 alkyl group which may be branched and may be substituted with a halogen atom '). You may have an ariel group,
  • R 2 ° and R 21 are each independently a hydrogen atom or a Ci C alkyl group optionally substituted with a haguchi atom
  • R 9 is a Ci to C 4 alkyl group which may be branched and may be substituted with a halogen atom
  • Halogen atoms
  • n 0, 1 or 2 and R is a branched or optionally substituted alkyl group which may be substituted with a halogen atom
  • Ci C alkyl group which may be branched and may be substituted with a halogen atom
  • Ci ′ to C 5 alkoxy group which may be branched and may be substituted with a halogen atom
  • a halogen atom which may be branched and substituted with a halogen atom
  • An alkyl group, a cyano group, one NR 20 R 21 (wherein R 20 and R 21 are each independently a hydrogen atom or a C 1 -C 4 alkyl optionally substituted by a halogen ′ atom) N- (C 1 -C 4 aralkyl) carpamoinole group, N, N-di (C 1 -C 4 alkanol) force rubamoyl group, or one NHCOR 9 (wherein, R 9 is a is branched optionally substituted in well and Ha port Gen atoms optionally C i to C 4 alkyl group) may be substituted with, Ariru group,
  • R 2 ° and R 21 are each independently a hydrogen atom or a Ci C alkyl group optionally substituted with a haguchi atom
  • R 9 is a Ci C alkyl group which may be branched and optionally substituted with a halogen atom
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • the formula RR 1 'R 2, R 2 ' of the compound represented by (I), - R 3, R 3 ', R 4, R 4', R 5, R 5 ', R 6 And R 6 ′ are each independently a hydrogen atom, 3, 4, 5_trifluorophenyl group, 3, 4, 5—trichlorophenyl group, 3, 4-difluorophenyl group, 3-nitrophenyl group, Nyl group, 3-Cyanophenyl group, Benzthiophene 2-yl group, 3, '5 -Difluoro mouth phenyl group, 3-Trifluoro mouth methyl phenyl group, 2, 4-Difluorophenyl group, 3-Methylsulfururphe -Group, 3, 5-bis (trif.
  • the compound represented by the above formula (I) has the following formula:
  • R 7 of the compound represented by the formula (I) is a C 13 to C 22 alkyl group which may form a branch or a ring.
  • R 7 and R 8 of the compound represented by formula (I) are the same.
  • the present invention also provides a method for producing a compound represented by the above formula (I), which comprises the following formula (I I):
  • R ⁇ R 1 ', R 2 , R 2', R 3, R 3 ', R 4, R 4', R 5, R 5 ', R 6 and R 6' are each independently,
  • R 20 and R 21 are each independently a hydrogen atom or a C to C 4 alkyl group optionally substituted with a haguchigen atom
  • (Ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C 1 -C 6;
  • (X i) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C 2 -C 6;
  • Branched C 1 may be substituted in good and halogen atoms optionally -C 4 alkyl group,
  • C 1 to C 5 may be branched and may be substituted with a halogen atom
  • a halogen atom which may be branched and substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are Independently, a hydrogen atom or a halogen atom that may be substituted with an alkyl group), a nitro group, a strong rubamoyl group, N- (CC alkyl) a strong rubamoyl group, N, N-di (C 1 -C 4 alkyl le ') force Rubamoiru group or a NHCOR 9 (where,, R 9 is a branched even if well and Ha port Gen atoms optionally substituted C ⁇ C 4 alkyl group An aryl group, which may be substituted with
  • R 2 ° and R 21 are each independently a hydrogen atom or a C 4 to C 4 aralkyl group optionally substituted with a haguchi atom
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • An alkyl group which may be branched and optionally substituted with a haguchigen atom C Cs alkoxy group which may be branched and may be substituted with a halogen atom, halogen atom, CC alkyl group which may be branched and which may be substituted with a halogen atom, a cyano group, one NR 20 R 21 (wherein, R 20 and R 21 are each independently a hydrogen atom, or at any good C 1 -C 4 alkyl group optionally substituted by a halogen atom), a nitro group, a force Rubamoiru group, N- (. ⁇ .
  • R 2 and R 21 are each independently a hydrogen atom or a 4 alkyl group optionally substituted with a halogen atom
  • R 9 is an alkyl group which may be branched and may be substituted with a halogen atom
  • a heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Branched C 1 may be substituted in good and halogen atoms optionally -C 4 alkyl group, Ci Cs alkoxy group which may be branched and may be substituted with a halogen atom,
  • a halogen atom which may be branched and optionally substituted with a halogen atom, an alkyl group, a cyano group, one NR 20 R 21 (wherein R 20 and R 21 are each independently a hydrogen atom; Or an alkyl group optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (C 1 -C 4 alkyl) a strong rubamoyl group, N, N—di (di-alkyl) R ′) substituted with a strong rubermoyl group, or one NHCOR 9 (wherein R 9 may be branched and substituted with a halogen atom and may be a C to C 4 alkyl group). You may have an ariel group,
  • R 2C and R 21 are each independently either hydrogen atom, or at any good C 1 -C 4 alkyl group optionally substituted by a halogen atom),
  • R 9 is a c 1 -c 4 alkyl group which may be branched and may be substituted with a halogen atom
  • n 0, 1 or 2 and R is a Ci C alkyl group which may be branched and substituted with a halogen atom
  • Ci C alkyl group which may be branched and may be substituted with a halogen atom
  • Ci C alkyl group optionally substituted by a halogen atom, Shiano group, one NR 20 R 21 (wherein, R 20 and R 21 are each independently a hydrogen atom, or is or may ⁇ ⁇ alkyl group which may be substituted by a halogen atom), Nitro group, strong rubermoyl group, N- (di ⁇ ⁇ di ⁇ alkyl) carbamoyl group, N, N-di (di-alkyl) force rubamoyl group, or one NHCOR 9 (where R 9 is branched) A Ci C alkyl group which may be substituted with a halogen atom and may be substituted with an aryl group,
  • R 2 and R 21 are each independently a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with a halogen atom
  • Z is a halogen atom
  • R 7 may form a branch or a ring and may be substituted with a halogen atom C 13 to C 3 .
  • R 8 which may be branched or form a ring and may be substituted by a halogen atom, an alkyl group of C Cso.
  • I 1 , R 1 ′, RR 2 ′, ⁇ R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, of the compound represented by the above formula (II), R 6 and R 6 ′ are independent
  • (X i V) an aryl group, wherein the aryl group is 'optionally branched' and optionally substituted with a halogen atom,
  • Halogen atoms, branched C 1 -C 4 optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR 20 R 21 (wherein, R 20 and R 21 are each independently And may be substituted with a hydrogen atom or a halogen atom.
  • ⁇ ⁇ Alkyl group nitro group, force rubamoyl group, N- (Ci C alkyl) carbamoyl group, N, N-di ( C 1 -C 4 alkyl Le) force Rubamoiru group or a NHCOR 9 (wherein, in R 9 is branched C 1 may be substituted in good and halogen atoms optionally -C 4 alkyl group) Optionally substituted, aryl group, Ciano group,
  • R 2 G and R 21 are each independently a hydrogen atom or a Ci to C 4 alkyl group optionally substituted with a haguchi atom
  • R 9 is a C 4 to C 4 alkyl group which may be branched and may be substituted with a halogen atom
  • n 0, 1 or 2, and R is a branch and may have and Ci ⁇ C may be substituted with a halogen atom 4 alkyl Le group is there) ;
  • alkyl group which may be branched and optionally substituted with a halogen atom
  • R 2 ° and R 21 are each independently a hydrogen atom, or a good or C! ⁇ C 4 alkyl group is optionally substituted by C port Gen atoms) ,
  • R 9 is a C 1 -C 4 alkyl group that may be branched and optionally substituted with a halogen atom
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • the formula RR 1 'R 2, R 2 ' of the compound represented by (II), R 3, R 3 ', R 4, R 4', R 5, R 5 ', R 6 and R 6 ' is their respective independently a hydrogen atom, 3, 4, 5-trifluorophenyl group, 3, 4, 5-trichloro port phenyl group, 3, 4-diphenyl Honoré Oro phenylene Honoré group, 3- Nitrophenyl group, 3-cyanophenyl group, benzothiophenyl-2-yl group, 3,5-difluorophenyl 'group, 3-trifluoromethylphenyl group, 2,4-difluorophenylol group, 3- Methinolesulfonino fenenole group, 3,5-bis (Trifluoromethyl) phenyl group, 4_nitrophenyl group, 4-cyanophenyl group, 4_trifluoromethylphenyl group, and 3,5-bis (3,5'-bis (trifluoromethyl
  • the compound represented by the above formula (I I) has the following formula (11,):
  • R 1 and R 1 ' are each independently a hydrogen atom, 3, 4, 5-trifluorophenyl group, 3, 4, 5-trichloro port Hue - group, 3, 4-di Fluorophenyl group, 3-diphenyl group, 3-cyanophenyl group, benzothiophenyl 2-yl group, 3,5-difluorophenyl group, 3-trifluoromethylphenyl group, 2,4-difluorophenyl group , 3-methylsulfurphenyl group, 3,5-bis (trifluoromethyl) phenyl group, 4_ nitrophenyl group, 4-cyanophenenyl group, 4-trifluoromethylphenyl group, and 3,5-bis ( 3 ', 5, one bis a (triflate Ruo ii methyl) Hue) group is selected from the group consisting of phenyl group, and R 7, R 8 and Z are each independently formula (II ) Is defined in the same way as the compound represented by Is a
  • the secondary amine R 7 represented by the above formula (II) may form a branch or a ring, C! 3 to C 22 alkyl 3 ⁇ 4.
  • R 7 and R 8 of the secondary amine represented by the above formula (II) are the same.
  • the present invention also provides a compound represented by the formula (VI):
  • R 1 R 1 ′, R 2 , R 2 ′, R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 and R 6 ′ are each independently
  • R 20 and R 21 are each independently a hydrogen atom or a Ci C alkyl group which may be substituted with a halogen atom);
  • (Ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C 1 -C 6;
  • (X) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C 2 -C 6;
  • Ci C 5 alkoxy group which may be branched and may be substituted with a halogen atom
  • Halogen atoms, branched C 1 -C 4 optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR 20 R 21 (wherein, R 20 and R 21 are each independently A hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, an N- (C 1 -C 4 alkyl) carbamoyl group, N , N-di (C 1 -C 4 alkyl) force rubamoyl group, or one NHCOR 9 (wherein R 9 may be branched and may be substituted with a halogen atom.
  • R 2 ° and R 21 are each independently a hydrogen atom or a 4 alkyl group optionally substituted with a haguchi atom
  • NHCOR 9 (wherein R 9 is optionally branched and substituted with a halogen atom to an alkyl group), and
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Branched C 1 may be substituted in good and halogen atoms optionally -C 4 alkyl group,
  • Halogen atoms, branched C 1 -C 4 optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR 20 R 21 (wherein, R 20 and R 21 are each independently It may be substituted with a hydrogen atom or a halogen atom, which is an alkyl group), a nitro group, a strong rubamoyl group, N- (Ci C alkyl) a strong rubamoyl group, N, N-di (Ji-jikyl) force rubermoyl group, or one NHCOR 9 (wherein R 9 is a C 1 -C 4 alkyl group which may be branched and may be substituted with a halogen atom) Optionally substituted with an aryl group,
  • R 9 is a C 1 -C 4 alkyl group that may be branched and optionally substituted with a halogen atom
  • a heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
  • alkyl group which may be branched and optionally substituted with a halogen atom
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • a halogen atom which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently hydrogen atom or is either an alkyl group which may be substituted by a halogen atom), a nitro group, a force Rubamoiru group, N-(0 ⁇ 4 alkyl) force Rubamoiru group, N, N-di (C 1 ⁇ C 4 alkyl) a strong rubermoyl group, or one NHCOR 9 (wherein R 9 is a C 4 to C 4 alkyl group which may be branched and may be substituted with a divalent atom) Optionally substituted with an aryl group,
  • R 2 ° and R 21 are each independently a hydrogen atom or a C to C 4 alkyl group optionally substituted with a halo atom
  • R 9 is a C 1 -C 4 aralkyl group which may be branched and may be substituted with a halogen atom
  • alkyl group which may be branched and optionally substituted with a halogen atom
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • Halogen atom which may be branched and optionally substituted with a halogen atom ⁇ to ⁇ Alkyl group, cyano group, _NR 20 R 21 (where R 20 and R 21 are independently Substituted by hydrogen atom or halogen atom Which may be c 1 to c is 4 or alkyl group), a nitro group, a force Rubamoiru group, N- (C 1 ⁇ C 4 alkyl) force Rubamoiru group, N, N-di (Ci C alkyl Le) force Rubamoiru A group, or one NHCOR 9 wherein R 9 is a Ci CT alkyl group which may be branched and optionally substituted with a halogen atom, an aryl group,
  • R 2Q and R 21 are each independently a hydrogen atom or a C! To C 4 alkyl group optionally substituted with a halo atom
  • R 9 is an alkyl group which may be branched and substituted with a halogen atom
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • R 7 may form a branch or a ring, and may be substituted with a halogen atom C 13 to C 3 .
  • R 8 is an alkyl group which may form a branch or a ring and may be substituted with a halogen atom
  • R 14 and R 15 are each independently (i) a hydrogen atom; or
  • a C to C 5 alkoxy group which may be branched and optionally substituted with a halogen atom,
  • Halogen atom which may be branched and optionally substituted with a halogen atom CC alkyl group, cyano group, one NR 30 R 31 (where R 30 and R 31 are each independently hydrogen N- (C 1 -C 4 alkyl) force rubamoyl group, N, N-di (C!), Or a CC alkyl group optionally substituted by an atom or a halogen atom) C alkyl) substituted with a strong rubermoyl group, or one NHCOR 9 (wherein R 9 is a C 4 to C 4 alkyl group which may be branched and optionally substituted with a halogen atom).
  • R 9 is a C 4 to C 4 alkyl group which may be branched and optionally substituted with a halogen atom.
  • R 3 ° and R 31 are each independently a hydrogen atom or a Ci C alkyl group optionally substituted with a haguchi atom
  • R 16 is
  • an alkyl group and may form a branched or cyclic optionally substituted by a halogen atom C 1 -C 1 Q, the alkyl group,
  • Branched c 1 may be substituted in good and halogen atom have to c 5 alkoxy group
  • R 3 ° and R 31 are each independently a hydrogen atom or an alkyl group which may be substituted with a halogen atom
  • R 9 is a Ci to C 4 alkyl group which may be branched and may be substituted with a halogen atom
  • R 9 is a c 1 -c 4 alkyl group which may be branched and optionally substituted with a halogen atom
  • alkyl group optionally substituted with at least one group selected from the group consisting of:
  • (iii) may be branched or ring and substituted with a halogen atom
  • An alkenyl group of c 2 to c 6 which may be
  • (I V) to form a branched or ring may be substituted with at best force halogen atom, an alkynyl group of C 2 -C 6;
  • alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently a hydrogen atom or a Ci C alkyl group optionally substituted with a halogen atom) ), A nitro group, a strong rubamoyl group, N— (C 1 -C 4 alkyl rubamoyl group, N, N—dialkyl ′) a strong rubamoyl group, or one NHCOR 9 (where R 9 is branched) A C 1 -C 4 alkyl group which may be substituted with a divalent atom, and may be substituted with an aryl group,
  • R 20 and R 21 are each independently a hydrogen atom or a C 4 to C 4 alkyl group optionally substituted with a halogen atom), '
  • R 9 is an alkyl group which may be branched and may be substituted with a halogen atom
  • Halogen atom
  • aralkyl group which is a c 1 -c 6 alkyl group;
  • a ci to C 5 alkoxy group which may be branched and optionally substituted with a halogen atom,
  • a halogen atom which may be branched and substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are independently, either a hydrogen atom, or is or a halogen atom substituted expired C 1 optionally -C 4 alkyl group), a nitro group, a force Rubamoiru group, N- ( ⁇ ⁇ alkyl) Karupamoiru group, N, N-di (. ⁇ Alkynole) Carpamoyl group, or one NHCOR 9 (wherein R 9 is an alkyl group which may be branched and may be substituted with a halogen atom) It ’s good.
  • R 20 and R 21 are each independently a hydrogen atom or a 4- alkyl group optionally substituted with a haguchi atom
  • R 9 is an alkyl group which may be branched and may be substituted with a halogen atom
  • a heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
  • Ci C alkyl group which may be branched and may be substituted with a halogen atom
  • a C Cs alkoxy group which may be branched and may be substituted with a halogen atom
  • a halogen atom which may be branched and may be substituted with a halogen atom, an alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently , A hydrogen atom or an alkyl group which may be substituted with a halogen atom), a utro group, a carb'moyl group, an N— (C 1 -C 4 alkyl) force rubamoyl group, an N, N— Di (C 1 -C 4 alkynole) force rubamoyl group, or one NHCOR 9 (wherein R 9 may be branched and may be substituted with a halogen atom. It is an alkyl group) Optionally substituted with an aryl group,
  • R 20 and R 21 are each independently a hydrogen atom or a Cj to C 4 alkyl group optionally substituted with a halogen atom), ⁇ ⁇
  • R 9 is an alkyl group which may be branched and may be substituted with a halogen atom
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • (V i i i) a heteroaryl group, wherein the heteroaryl group may be branched and substituted with a halogen atom,
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • Halogen atoms, branched C 1 -C 4 optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR 20 R 21 (wherein, R 20 and R 21 are each independently A hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (Ci C alkyl) a strong rubamoyl group, N, N —Di (C 1 -C 4 alkyl) force ruberamoire group, or one NHCOR 9 (wherein R 9 is a Ci-C 4 alkyl group which may be branched and may be substituted with a halogen atom) ) May be substituted with an aryl group,
  • R20 and R2i are each independently a hydrogen atom. Or is or may Ji-Ji alkyl group which may be substituted by a halogen atom),
  • R 9 is a 0 to 0 alkyl group which may be branched and may be substituted with a halogen atom
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • R 17 is a C 1 to C 8 alkyl group which may form a branch or a ring and may be substituted with a halogen atom;
  • R 3 ° and R 31 are each independently a hydrogen atom or a C i to C 4 alkyl group optionally substituted with a haguchi atom
  • R 9 is a CC alkyl group which may be branched and may be substituted with a halogen atom
  • Halogen atom -COR 9 (wherein R 9 is a c 1 -c 4 alkyl group which may be branched and optionally substituted with a halogen atom), and
  • R 9 may be branched and substituted with a halogen atom
  • An aralkyl group optionally substituted with at least one group selected from the group consisting of:
  • (Ii) may form a branched or cyclic and may be substituted by halogen atom, Ariru or substituted Ariru group C 3 -C 9;
  • (I V) to form a branched or ring may be substituted in good and halogen atom, an alkynyl group of c 2 to c 6;
  • a C to C 5 alkoxy group which may be branched and optionally substituted with a halogen atom,
  • a halogen atom which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR 20 R 21 (where, R 20 and R 21 are each independently , A hydrogen atom, or a C 1 -C 4 alkyl group optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, N — (.- alkyl) a strong rubamoyl group, N, N—di (Ji-Ji alkinore) substituted with a strong rubermoyl group, or one NHCOR 9 (wherein R 9 is a Ci C 4 alkyl group which may be branched and may be substituted with a divalent atom) May have been, allyl group,
  • R 2 ° and R 21 are each independently a hydrogen atom or a C to C 4 alkyl group optionally substituted with a haguchi atom
  • R 9 is an alkyl group which may be branched and may be substituted with a halogen atom
  • alkyl group which may be branched and may be substituted with a halogen atom
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • a halogen atom which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently A hydrogen atom, or a Ci C alkyl group optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (Ci C ⁇ alkyl) a strong rubamoyl group, N, N—di ⁇ ⁇ .
  • R 20 and; are each independently a hydrogen atom or a halogen atom, which may be a 4- to 4- alkyl group),
  • a heteroalkyl group optionally substituted with at least one group selected from the group consisting of:
  • V ii may be branched and may be substituted with a halogen atom, C 3 to C 9 propargyl group or substituted propargyl group;
  • w is a functional group having a leaving ability
  • R 2 ′, R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 and R 6 ′ are each independently
  • a C C alkyl group which may be branched and optionally substituted with a halogen atom,
  • a haguchigen atom which may be branched and substituted with a haguchigen atom C Alkyl group, cyano group, one NR 20 R 21 (wherein R 20 and R 21 are each independently a hydrogen atom or a Ci to C 4 alkyl group optionally substituted with a halogen atom) ), A nitro group, a rubamoyl group, N- (C ⁇ C alkyl.) A rubamoyl group, N, N-di (di-alkyl) rubamoyl group, or one NHCOR 9 (where .R 9 is a Ci C alkyl group that may be branched and optionally substituted with a halogen atom), an aryl group,
  • R 2 ° and R 21 are each independently a hydrogen atom or a C 4 to C 4 alkyl group optionally substituted with a haguchi atom
  • R 9 is a c 1 -c 4 alkyl group which may be branched and may be substituted with a halogen atom
  • n 0, 1 or 2 and R may be branched and substituted with a halogen atom Ci C alkyl Group);
  • Ci C 5 alkoxy group which may be branched and may be substituted with a halogen atom
  • Halogen atoms, branched C 1 -C 4 optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR 20 R 21 (wherein, R 20 and R 21 are each independently and, either a hydrogen atom, or at or even better C 1 -C 4 alkyl group optionally substituted by a halogen atom), a nitro group, a force Rubamoiru group, N- (C 1 ⁇ C 4 alkyl cormorants Karupamoiru group, N , N-di (C 1 -C 4 alkyl) force rubamoyl group, or one NHCOR 9 (wherein R 9 may be branched and may be substituted with a halo atom C 1 -C An alkyl group), an aryl group,
  • R 2 ° and R 2 i are each independently a hydrogen atom or a C to C 4 alkyl group optionally substituted with a haguchi atom
  • N, N-di (C, ⁇ C ' 4 alkyl) force rubamoyl group -NHCOR 9 (wherein R 9 is a C ⁇ C alkyl group which may be branched and optionally substituted with a halogen atom), and
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of:
  • RR 1 ′ ⁇ R 2 , R 2 ′, R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 of the compound represented by the above formula (I) And R 6 ′ each independently represents a hydrogen atom, 3, 4, 5-trifluorophenyl group, 3, 4, 5 monotrichlorophenyl group, 3, 4-difluorophenyl group, 3-utrophenyl group, 3-cyanophenyl group, benzothiophene 2-yl group, 3,5-difluorophenyl group, 3-trifluoromethylphenyl group, 2,4-difluorophenyl group, 3 —Methylsulfuruylphenyl group, 3,5-bis (trifluoromethyl) phenyl group, 4-nitrophenyl group, 4-cyanophenyl group, 4-trifluoromethylphenyl group, and 3,5-bis (3 ′ , 5, bis (trifluoromethyl)
  • R 1 and R 1 ′ are each independently a hydrogen atom, 3, 4, 5-trifluorophenyl group, 3, 4, 5-trichlorophenyl group, 3, 4-difunoleolo, Phenyl group, 3--Trophenyl 'group, 3-Cyanophenyl group, Ben Zothiophene 2— ⁇ f group, 3,5-difluorophenyl group, 3-triphenylolenomethylphenyl group, 2,4 difluorophenyl group, 3-methyl 'sulfurylphenyl group, 3,5-bis ( Trifluoromethyl) phenyl group, 4 nitrophenyl group, 4 cyanophenyl group, 4 trifluoromethyl phenyl group, and 3, 5 _bis (3,, 5, 1 bis (trifluoromethyl) ) Phenyl) is a group selected from the group consisting of phenyl groups, and R 7 , R 8 and X— are each independently defined in the same manner as the
  • R 7 of the compound represented by the formula (I) is a C 13 -C 22 alkyl group which may form a branch or a ring.
  • R 7 and R 8 of the compound represented by formula (I) are the same.
  • the compound represented by the formula (I) is used at a ratio of 0.001 mol ° / 0 to 5 mol ⁇ % with respect to 1 mol of the compound represented by the formula (IV). Used.
  • the compound represented by the formula (I) is used at a ratio of 0.005 mol% to 0.5 mol% with respect to 1 mol of the compound represented by the formula (IV). .
  • the present invention also provides a method for producing an optically active ⁇ -amino acid, the method comprising a compound represented by the formula (V I) obtained by the above method:
  • the present invention also provides a method for producing an optically active single amino acid, which comprises a compound represented by the formula (VI) obtained by the above method:
  • the present invention also provides a method for producing an optically active single amino acid, the method comprising a compound represented by the formula (V I) obtained by the above method:
  • R 14 , R 15 , R 16 , R 17 and R 18 are the same as defined above
  • a step of hydrolyzing an imino group (R 14 R 15 C ⁇ N—) of the basic hydrolysis product under acidic conditions
  • a chiral phase transfer catalyst having a more simplified structure is provided.
  • This phase transfer catalyst can be produced with fewer steps than conventional compounds.
  • a chiral phase transfer catalyst that provides high stereoselectivity in an asymmetric alkylation reaction or the like is provided.
  • the phase transfer catalyst of the present invention can be used, for example, in the synthesis of monoalkyl monoamino acid derivatives and ⁇ , ⁇ -dialkyl monoamino acids.
  • an alkyl group of 0 to 0 which may form a branch or a ring is any linear alkyl group having 1 to n carbon atoms, 3 to n carbon atoms And any cyclic alkyl group having 3 to n carbon atoms.
  • arbitrary linear alkyl groups having 1 to 6 carbon atoms include methyl, ethynole, n-propyl ', n-butyl', n-pentyl ', and n-hexyl.
  • Arbitrary branched alkyl groups of 6 include isopropyl ', isobutyl', tert-butyl, isopentyl, etc.
  • optional cyclic alkyl groups of 3 to 6 carbon atoms include cycloptyl ', cyclopentyl, cyclohexyl, etc. Is mentioned.
  • the term “the same alkyl group which may form a branch or a ring and may be substituted with Z or a halogen atom” is a straight chain having 1 to 12 carbon atoms.
  • L 2 is substituted with a halogen atom at any position May be.
  • alkyl group examples include n-heptyl ', isoheptyl, n-octyl, isooctyl, n-decyl, n-dodecyl and the like.
  • N- (di-alkyl) carbamoyl group and N, N-di (C j -C 4 alkyl) carbamoyl “di-alkyl” is a straight-chain alkyl group of 0 to C 4 or C 3 means a branched-chain alkyl group -C 4.
  • C 2 -C n alkenyl group which may form a branch or a ring (where n is an integer) means any straight chain alkenyl group having 2 to n carbon atoms, 3 to n carbon atoms Any branched chain alkenyl group, and 3 to 3 carbon atoms! ! Including any cyclic alkenyl group.
  • an arbitrary straight-chain alkenyl group having 2 to 6 carbon atoms includes: etul ', 1-propenyl 2-propenore, 1-buture, 2-butene Ninore, 1-penteninole, 2-penteninole, 3-penteninole, 4-penteninole, 1-hexenyl, etc., and any branched chain alkenyl group having 3 to 6 carbon atoms includes isopropenyl, 1 —Methyl-1 monopropenyl ', 1-methyl-2 monopropenyl', 2-methyl 1-fu.
  • a C 2 to C 12 alkenyl 'group which may form a branch or a ring and / or may be substituted with a halogen atom has 2 to 1 carbon atoms.
  • alkenyl groups include 1-heptenyl, 2-heptul, 1-octul, 1-decenyl, 1-dodecenyl, and the like.
  • C 2 -C n alkynyl group which may form a branch or a ring (where n is an integer) means any straight chain alkynyl group having 2 to n carbon atoms, 3 to 3 carbon atoms Including any branched alkynyl group of n and any cyclic alkynyl group having 3 to n carbon atoms.
  • Examples of the arbitrary straight chain alkynyl group having 2 to 6 carbon atoms there may be mentioned: Examples of the arbitrary branched alkynyl group having 3 to 6 include 1-methyl-2-propynyl, and examples of the optional cyclic alkynyl group having 3 to 6 carbon atoms include cyclopropyl ether and cyclobutyl ether. Can be mentioned. Further, for example, the term “a C 2 to C 12 alkynyl group which may form a branch or a ring and may be substituted with a halogen atom” has 1 to 1 carbon atoms.
  • alkynyl groups any branched alkynyl group having 3 to 12 carbon atoms, And any cyclic alkynyl group having 3 to 12 carbon atoms, and the hydrogen atom at any position thereof may be substituted with a halogen atom.
  • alkynyl groups include 1-heptul, 1-octynyl, 1-decynyl, 1-dodecynyl and the like.
  • an alkoxy group that may be branched ⁇ to the same (where n is an integer) is an alkoxy group having an arbitrary linear alkyl group having 1 to n carbon atoms and an arbitrary one having 3 to n carbon atoms. And an alkoxy group having a branched alkyl group. Examples include methyloxy, ethyloxy, n-propyloxy, isopropyloxy, tert-butyloxy and the like.
  • aralkyl group examples include benzyl, phenethyl, and naphthylmethyl.
  • heteroarylkyl group examples include pyridylmethyl ′, indolylmethyl, furylmethyl, chenylmethyl, and pyrrolylmethyl.
  • aryl group examples include phenyl, naphthyl, anthryl, phenanthryl and the like.
  • heteroaryl group examples include pyridyl, pyrrolinole, imidazolyl, furyl, indolyl, chenyl, oxazolyl, benzothiol-2-yl, thiazolyl, and tetrazolyl.
  • halogen atom examples include chlorine atom, bromine atom, iodine atom and fluorine atom.
  • halide anion means a halogen ion, and includes a chloride ion, a bromide ion, an iodide ion, and a fluoride ion.
  • the term “optionally forming a branched or ring, C. to C n “Aryl group or substituted aryl group” is a aryl group, or any total number of carbon atoms having substituents at the 1 and Z or 2 and Z or 3 positions, 4 to! ! Of the substituted aryl group.
  • n is an integer
  • 2-butyr, 1-cyclopentenylmethyl, 3-methyl-2-butenyl and the like can be mentioned.
  • the term “optionally branched C 3 -C n propargyl group or substituted propargyl group” is a propargyl group or substituted at the 1 and / or 3 position. It means a substituted propargyl group having 4 to n total carbon atoms having a group.
  • 2-butul ', 3-trimethylsilyl-2-propynyl and the like can be mentioned.
  • the term “functional group having a leaving ability” means an atom or an atomic group that separates from a reaction substrate in a substitution reaction or elimination reaction, that is, a leaving group. Examples thereof include a halogen atom and a sulfonyloxy group.
  • CC 4 alkyl group which may be branched and optionally substituted with a halogen atom
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • a halogen atom which may be branched and optionally substituted with a halogen atom, a C 1 -C 4 alkyl group, a cyano group, one NR 20 R 21 (where R 2 and R 21 are each Independently a hydrogen atom or a C 1 -C 4 alkyl group optionally substituted with a halogen atom), a nitro group, a force rubamoyl group, N— (Ci C alkyl) force rubamoyl group, N, N-di (Ci C alkyl) substituted with a rubamoyl group, or one NHCOR 9 (wherein R 9 is a Ci C alkyl group which may be branched and substituted with a halogen atom). You may have an ariel group, Ciano group,
  • R2i are each independently a hydrogen atom, or at any good C i to C 4 alkyl group optionally substituted with C port plasminogen atoms),
  • R 9 is a C alkyl group that may be branched and optionally substituted with a halogen atom
  • Group consisting of may be described as “Group (Q)”.
  • the quaternary ammonium salt of the present invention has the following formula (I) ′:
  • (X) branched or cyclic and may be substituted or a well and Ha port Gen atom to each other to form Al 'Kenyir group c 2 to c 6;
  • (X i) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C 2 -C 6;
  • Branched C 1 may be substituted in good and halogen atoms optionally -C 4 alkyl 'group,
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • Halogen atom which may be branched and may be substituted with a halogen atom ⁇ to ⁇ Alkyl group, cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently , May be substituted with a hydrogen atom or a halogen atom, which is an alkyl group), a nitro group, a strong rubamoyl group, an N— (Ci C alkyl) carbamoyl group, an N, N—di (C 1 ⁇ C 4 alkyl) Forced rubermoyl group, or one NHCOR 9 (wherein R 9 is a CC alkyl group which may be branched and may be substituted with a halogen atom) Optionally substituted with an aryl group,
  • R 20 and R 21 are each independently a hydrogen atom or a C 4 to C 4 alkyl group optionally substituted with a halogen atom
  • An aralkyl group which may be substituted with at least one group selected from the group (Q) consisting of:
  • (X i V) aryl group wherein the aryl group may be substituted with at least one group selected from the above group (Q), or the 3rd and 4th positions are joined together Optionally substituted with O— (CH 2 ) m — ⁇ 1 (where m is 1 or 2), an aryl group; and
  • R 7 and R 8 are each independently a monovalent organic group, and X scratch, halide Anion, S CN @ -, HS_ ⁇ 4 -, or HF 2 - and the compounds represented by der Ru), preferably Ru pure compound der respect axial asymmetry.
  • the compound represented by the above formula (I) may have any configuration of (S) or (R).
  • the compound represented by the formula (I) is, for example, a phase transfer catalyst for producing an optically active ⁇ -amino acid or a derivative thereof described below, in particular, an ⁇ , hedialkyl mono ⁇ -amino acid or a derivative thereof.
  • the compound represented by the formula (IV) is alkylated with the compound represented by the formula (V) to produce the optically active amino acid represented by the formula (VI) or a derivative thereof. Therefore, when the compound represented by the above formula (I) is used as a phase transfer catalyst, the ammonium moiety constituting the cation of the compound:
  • R 7 and R 8 in the compound represented by the formula (I) are independently derived from the ammonium moiety and the binaphthyl moiety of the cation. It is a group that can maintain reactivity and selectivity, or a group that does not inhibit the reactivity and selectivity, and has a predetermined carbon chain. For example, it is a monovalent organic group that is inert and has a predetermined number of carbon atoms as compared with the above-mentioned anmolybum moiety and binaphthyl moiety.
  • R 7 and R 8 Are each independently a group that is not itself (or itself) rich in reactivity, and thus is a group that does not affect the reaction in the production of the amino acid or derivative thereof described below.
  • R 7 is more specifically C 13 to C 3 which may form a branch or a ring.
  • the alkyl group is preferably a C 13 -C 22 alkyl group which may form a branch or a ring.
  • the lower limit of the number of carbon atoms constituting the alkyl group that may form a branch or a ring is preferably 13 or more, more preferably 15 or more, still more preferably 17 or more, and still more preferably
  • the upper limit of the number of carbon atoms constituting the alkyl group is preferably 30 or less, more preferably 22 or less, even more preferably 21 or less, and even more preferably 20 or less. .
  • R 8 is preferably an alkyl group of 1 to 6 which may form a branch or a ring.
  • R 8 may be a branched or ring-forming alkyl group that may form a branch or a ring, or may be a branched or ring-formed c 13 -c 30 alkyl group (further, preferably may be branched or alkyl Le group forms a ring optionally C 13 even though -C 22) by.
  • the lower limit of the number of carbon atoms constituting the alkyl group is preferably 1 or more
  • the upper limit of the number of carbon atoms constituting the alkyl group is preferably 12 or less, more preferably 8 or less, and even more preferably 5 or less.
  • the lower limit of the number of carbon atoms constituting the alkyl group is preferably 1 or more, more preferably 15 or more, even more preferably 17 or more, and still more preferably 18 or more, and constitutes the alkyl group.
  • the upper limit of the number of carbon atoms is preferably 30 or less, more preferably 22 or less, even more preferably 21 or less, and even more preferably 20 or less.
  • the number of carbon atoms constituting these alkyl groups of R 7 and R 8 can be appropriately selected according to the substrate and reactivity of the alkylation reaction.
  • R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 and R 6 ′ are preferably each independently
  • Ci to C 4 alkyl group which may be branched and may be substituted with a halogen atom
  • a halogen atom which may be branched and optionally substituted with a halogen atom; a Ci C alkyl group, a cyano group, an NR 20 R 21 (where R 20 and R 21 are each independently , A hydrogen atom, or a C 1 -C 4 alkyl group optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, N- (Ci C.
  • N N— Di (Ci C alkyl) substituted with a strong rubermoyl group, or one NHCOR 9 (wherein R 9 is a Ci C alkyl group which may be branched and substituted with a halogen atom). It ’s good.
  • R 20 and R 21 are each independently a hydrogen atom or an alkyl group which may be substituted with a halogen atom
  • NHCOR 9 (wherein R 9 is a Ci C alkyl group which may be branched and may be substituted with a halogen atom),
  • n 0, 1 or 2 and R is a Ci to C 4 alkyl group which may be branched and substituted with a halogen atom) is there) ;
  • Or may be substituted with at least one group selected from the group consisting of O— (CH 2 ) m -0- (where m is 1 or 2 Is)
  • alkyl group which may be branched and optionally substituted with a halogen atom
  • Ci Cs alkoxy 'group which may be branched and optionally substituted with a halogen atom
  • a halogen atom which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently A hydrogen atom or an alkyl group which may be substituted with a halogen atom), a -tro group, a strong rubamoyl group, N— (C 1 -C 4 alkyl) a strong rubamoyl group, N, N— Di (C 1 -C 4 alkynole) force rubamoyl group, or one NHCOR 9 (wherein R 9 may be branched and may be substituted with a halogen atom) ) May be substituted with an aryl group, Ciano group,
  • R 2 and R 2 i are each independently a hydrogen atom or a C i to C 4 aralkyl group optionally substituted with a halogen atom) ,
  • R 9 is a Ci to C 4 alkyl group which may be branched and optionally substituted with a halogen atom
  • a heteroaryl group optionally substituted with at least one group selected from the group consisting of: selected from the group consisting of: More preferably, a hydrogen atom,
  • R 1 and R 1 ′ are each independently a hydrogen atom, 3, 4, 5-trifluorophenyl group, 3, 4, 5-trichlorophenyl group, 3, 4-diphenolo; Lophenyl group, 3-nitrophenyl group, 3-cyanophenyl group, benzothiophenoleyl 2-yl group, 3,5-difluorophenyl 'group, 3-trifluoromethylphenyl group, 2, 4 —Difluor'orophenyl 'group, 3-Methyl'snorhoylphenyl' group, 3,5-Bis (trifluoromethyl) phenyl group, 4-Nitrophenyl group, 4-Sianophenyl group, 4-Trifluoromethylphenol And a group selected from the group consisting of 3,5-bis (3,5'-bis (trifluoromethyl) phenyl) phenyl 'groups, and R 7 , R 8 and X— is each independently a group defined above) Are preferred.
  • R 7 and R 8 can be produced by reacting with a secondary amine represented by the above formula (I).
  • the compound of the above formula (II) can be obtained, for example, from the readily available 1,1′-binaphthyl-2,2′-dicarboxylic acid (see Seki, M. et al., Synthesis, 2000, .1677) and the following scheme 1 (See Ooi, T. et al., J. Org. Chem., 2003, 68, p. 4577).
  • 1, 1 '_ Binaphthyl 2, 2' —dicarboxylic acid is either (S) or (R)
  • dicarboxylic acid (1) is converted to the corresponding diisopropyl ester (2) using isopropyl bromide, catalysts Bu 4 N ⁇ HS0 4 and KF ⁇ '2H 2 0.
  • the resulting compound is converted to the corresponding diisopropyl ester (2) using isopropyl bromide, catalysts Bu 4 N ⁇ HS0 4 and KF ⁇ '2H 2 0.
  • the resulting compound (1) is converted to the corresponding diisopropyl ester (2) using isopropyl bromide, catalysts Bu 4 N ⁇ HS0 4 and KF ⁇ '2H 2 0.
  • the secondary amine of the above formula (I I I) either a commercially available product or a synthesized product can be used.
  • the class II fan of the above formula (III) is, for example, according to the method described in Rajkumar Sunil Singh et al., Chemistry-A European Journal 2002, No. 8, pp.900-909. It can be readily prepared by those skilled in the art by reductive amination with min.
  • the organic solvent used in the step of producing the compound of the above formula (I) by reacting the compound of the above formula (II) with the compound of the above formula (II) includes nitrile solvents (for example, acetonitrile, propionitrile, etc.). Etc.), ether solvents (eg, dioxane ', tetrahydrofuran, isopropyl ether, diethyl ether, dimethoxetane, 2-methoxetyl ether), alcohol solvents (eg, methanol, ethanol, n-propanol, Sopropanol, n -butanol, tert-butanol, etc.). In the present invention, acetonitrile is particularly preferable.
  • the acid scavenger include inorganic bases such as potassium carbonate, sodium carbonate, potassium bicarbonate, and sodium bicarbonate.
  • the secondary amine of formula (III) is preferably used in a proportion of 0.5 to 4 equivalents, more preferably 0.8 to 2 equivalents, relative to the compound of formula (.1 I).
  • the acid scavenger is preferably used in an amount of 1 to 4 equivalents, more preferably about 1 to 2 equivalents, relative to the compound of formula (II).
  • the compound of formula (II) and the secondary amine of formula '(III) are reacted with stirring in a suitable organic solvent in the presence of an acid scavenger.
  • the reaction temperature is preferably from room temperature to the boiling point of the organic solvent, and more preferably the reaction is carried out under heating and reflux. Reaction time is preferred 30 minutes to 24 hours, more preferably 6 to 12 hours.
  • the organic solvent is preferably used in an amount of 5 to 50 times, more preferably 5 to 30 times the volume (mL) / weight (g) ratio with respect to the compound of formula (II).
  • the reaction mixture can be isolated and purified by extraction with dichloromethane, dichloroethane, carbon tetrachloride, etc., silica gel force ram chromatography, etc. to obtain the compound of formula (I).
  • the reaction mixture may be used as it is as a phase transfer catalyst in the method for producing an ⁇ -amino acid derivative described in detail below.
  • pure with respect to axial asymmetry means that among the stereoisomers that can be considered based on axial asymmetry, the presence of one specific isomer is greater than that of the other isomers.
  • the abundance of the one particular isomer is 90% or more, more preferably 95% or more, even more preferably 98% or more.
  • the compounds of formula (I) above X is a halide Anion, if example embodiment, through the following steps, CN @ - halide Anion is S, HS0 4 -, or was converted into HF 2 one It can be a compound.
  • X is S CN or HS0 4 - a method for manufacturing a a a compound of formula (I).
  • the compound of the formula (I) wherein X is a halide anion obtained as described above can be obtained, for example, in a suitable second organic solvent in accordance with the method described in JP-A-2002-173492.
  • X- is converted from halide cation to SCN- by mixing with a saturated aqueous solution of alkali metal thiocyanate.
  • Examples of second organic solvents that can be used in this transformation are: dichloromethan. Chlorohonolem, dichloroethane, tetrahydrofuran, methinole t-petite. Examples include ruether ', diisopropyl ether', and ethyl acetate. Examples of alkali metal thiocyanate include thiocyanate strength and sodium thiocyanate.
  • reaction of the compound of formula (I) where X- is a halide anion and the alkali metal thiocyanate is mixed and contacted in solution under relatively mild conditions such as room temperature.
  • the reaction product that is, the compound of the formula (I) in which X is SCN
  • the reaction product can be easily obtained in a quantitative yield.
  • the compound of formula (I) in which X thus obtained is HS0 4 is further reacted with an alkali metal fluoride salt (for example, potassium fluoride, sodium fluoride or lithium fluoride).
  • an alkali metal fluoride salt for example, potassium fluoride, sodium fluoride or lithium fluoride.
  • alkali metal fluoride salt for example, potassium fluoride, sodium fluoride or lithium fluoride
  • R 1 R 1 ′, R 2 , R 2 ′, R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 and R 6 ′ are represented by the above formula (I It is also possible to obtain the compound represented by '') as defined in).
  • the silyl enol ether used in the above aldol reaction is, for example, a tolylalkylsilyl enol ether.
  • Tolylalkylsilyl Enol ethers can be chlorosilanes such as trimethyl silyl chloride and triethyl silyl chloride in the presence of a carbonyl compound (eg, 2-butanone, 4-pentene-2-one ', jetyl ketone, acetophenone).
  • ketone derivative such as', propiophenone, butyronaphthone ', cycloxyhexanone', 1-oxoindane, 1-tetralone, or 2-tetralone.
  • Examples of the carbonyl compound that reacts with the silylenol ether used in the above-mentioned aldol reaction include a carbonyl compound (the above ketone derivative) that is a precursor of silyl enol ether, acetyl aldehyde, propion aldehyde, butyl aldehyde, Isobutyl aldehyde, Isobarrel aldehyde,-Force Pron aldehyde, Dodecyl aldehyde, + Palmitic aldehyde, Stear aldehyde, Acrolein, Croton aldehyde, Sick mouth Xanthan aldehyde, Benz aldehyde, Annis aldehyde, Nicotine aldehyde Examples include aldehyde compounds such as namaldehyde, ct-naphthoaldehyde, and ⁇ -naphthoaldeh
  • the compound represented by the formula (I a) is used as a catalyst for the aldol 'reaction, and the stereoselectivity of the reaction can be controlled.
  • the compound of formula (I) wherein X— obtained as described above is a halide anion is first contacted with an ion exchange resin to produce a first intermediate.
  • ion exchange resin Any ion exchange resin can be selected by those skilled in the art. Specific examples of ion exchange resins that can be used include Amberlyst A 2 6 (OH) (manufactured by Organo Corporation).
  • a compound of formula (I) where X— is a halide anion with an ion exchange resin can be achieved, for example, by a compound of formula (I) wherein X— is a halide anion. This is done by dissolving the product in a suitable third solvent and passing this solution through a column packed with the ion exchange resin.
  • the third solvent that can be used in performing such contact is preferably an alcohol solvent. Specific examples of the alcohol solvent include, but are not limited to, methyl alcohol, ethyl alcohol, isopropyl alcohol, and normal propyl alcohol.
  • the amount of the compound of the formula (I) in which the above X is a halide anion used in this contact and the amount of the third solvent are not particularly limited and can be appropriately set by those skilled in the art.
  • the resulting first intermediate is then neutralized with an aqueous hydrogen fluoride solution, preferably without removing the solvent.
  • an aqueous hydrogen fluoride solution preferably without removing the solvent.
  • the amount of the hydrogen fluoride aqueous solution used in the present invention is not particularly limited, but is preferably a compound of the formula (I) wherein X is a halide anion from the viewpoint of increasing productivity. On the other hand, it is selected so that an equal amount or more of hydrogen fluoride reacts. This neutralizes the first intermediate, and in the solution X is converted from the halide ayuon to HF 2 _ (lb):
  • the compound represented by the formula (lb) can be easily isolated by removing the solvent using a means commonly used by those skilled in the art.
  • the compound represented by the formula (lb) thus obtained can be used, for example, as a catalyst for producing a diastereoselective and enantioselectively controlled nitro alcohol.
  • alkyl group which may be branched and optionally substituted with a halogen atom
  • Ci C 5 alkoxy group which may be branched and may be substituted with a halogen atom
  • Halogen atom which may be branched and may be substituted with a halogen atom Yes to Yes 4 Alkyl group, cyano group, one NR 30 R 31 (where R 30 and R 31 are each independently A hydrogen atom or an alkyl group optionally substituted with a halogen atom), a nitro group, a carbamoyl group,
  • NR 30 R 31 (wherein R 30 and R 31 are each independently a hydrogen atom or a Ci Ca alkyl group optionally substituted with a halogen atom),
  • R 9 is a Ci C alkyl group which may be branched and optionally substituted with a halogen atom
  • An aryl group optionally substituted with at least one group selected from the group consisting of:
  • Branched C 1 may be substituted in good and halogen atoms have -C 5 alkoxy group
  • R 30 and R 31 are each independently a hydrogen atom or a C 4 to C 4 alkyl group optionally substituted with a haguchi atom
  • N- (C 1 -C 4 alkyl) force rubermoyl group N, N—di (Ci C alkyl ') force rubermoyl group
  • R 9 is an alkyl group which may be branched and may be substituted with a halogen atom
  • R 9 is a Ci C alkyl group which may be branched and optionally substituted with a halogen atom
  • R 9 is a C 1 to C 4 alkyl group which may be branched and may be substituted with a halogen atom
  • alkyl group optionally substituted with at least one group selected from the group consisting of:
  • (Ii .i) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C 2 -C 6;
  • (Iv) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C 2 -C 6;
  • Ci C 5 alkoxy group which may be branched and may be substituted with a halogen atom
  • a halogen atom which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR 20 R 21 (where R 20 and R 21 are each independently A hydrogen atom or an optionally substituted alkyl group), a nitro group, a rubamoyl group,
  • N- (CC alkyl) force rubamoyl group N, N-dialkylol force rubamoyl group, or one NHCOR 9 (where R 9 may be branched and substituted with a halogen atom CC An alkyl group) Optionally substituted with an aryl group,
  • R 20 and R 21 are each independently a hydrogen atom or an alkyl group which may be substituted with a halogen atom
  • aralkyl group which may be a C 1 -C 6 alkyl group;
  • (V i i i) a heteroaryl group, which may be substituted with at least one group selected from the above group (Q);
  • R 17 may form a branch or a ring and is substituted with a halogen atom.
  • a ring or a ring may be formed and may be substituted with a halogen atom.
  • the alkyl group is.
  • a C Cs alkoxy group which may be branched and may be substituted with a halogen atom
  • R 3 ° and R 31 are each independently a hydrogen atom or a Ci to C 4 alkyl group optionally substituted with a haguchi atom
  • R 9 is a c 1 -c 4 alkyl group which may be branched and may be substituted with a halogen atom
  • R 9 is an alkyl group which may be branched and may be substituted with a halogen atom
  • R 9 is a C 1 -C 4 alkyl group which may be branched and optionally substituted with a halogen atom
  • alkyl group optionally substituted with at least one group selected from the group consisting of:
  • (Ii) may form a branched or cyclic and may be substituted with a halogen atom, Ariru or substituted Ariru group c 3 to c 9;
  • (iii) may be branched or ring and substituted with a halogen atom
  • An alkenyl group of c 2 to c 6 which may be
  • (I V) to form a branched or ring may be substituted in good and halogen atom, an alkynyl group of C 2 -C 6;
  • (V i i) may be branched and substituted with a halogen atom
  • a group selected from the group of forces and
  • the media used in the above alkylation process include benzene, toluene, xylene, ethyl ether, isopropyl ether, tetrahydrofuran ', dioxane', mesitylene, ethyl acetate, isopropyl acetate, cyclopentyl methyl ether ', methyl tertiary butyl ether.
  • the medium may be a two-phase medium of water and a medium that does not mix with water.
  • the medium may be preferably used in a volume (mL) / weight (g) ratio of 0.5 to 30 times, more preferably 1 to 25 times with respect to the compound of formula (IV).
  • Examples of the inorganic base used in the alkylation step include lithium hydroxide, sodium hydroxide, lithium hydroxide, calcium hydroxide, rubidium hydroxide, and cesium hydroxide.
  • the inorganic base can be used in an amount of preferably 0.5 equivalents to 100 equivalents, more preferably 0.8 equivalents to 40 equivalents, relative to the compound of formula (IV).
  • the inorganic base may be used in the form of an aqueous inorganic base solution.
  • the inorganic base in the inorganic base permanent solution can be used in an amount of preferably 0.5 equivalents or more, more preferably 0.8 equivalents or more, relative to the compound of the formula (IV).
  • the aqueous inorganic base solution is preferably 20 wZw% to 70 w / w%, more preferably 30 w / w% to 60 wZwG / o.
  • the volume ratio of the medium and the aqueous inorganic base solution is preferably the ratio of the volume of the medium (mL) to the volume of the aqueous inorganic base solution (mL), preferably 7-1: LZ5, more preferably 4-1 1-11.
  • the compound of formula (V) is preferably used in a proportion of 0.5 to 10 equivalents, more preferably 0.8 to 5 equivalents, relative to the compound of formula (IV).
  • Compounds of formula (I) is 1 mole of the compound of Formula (IV), preferably 0.001 mol 0/0 or more, more preferably 0.005 mol% or more It is used as a phase transfer catalyst at the upper limit and preferably at the upper limit of 10 mol% or less, more preferably 5 mol% or less, and even more preferably 0.5 mol% or less.
  • the phase transfer catalyst used in the present invention has a very high catalytic activity, the desired optical activity can be obtained by using only a very small amount of the catalyst per 1 mol of the compound of the formula (IV). Nahiichi amino acid and its derivatives can be obtained.
  • an asymmetric phase-transfer catalyst represented by the formula (I) and an achiral quaternary ammonium salt such as tetraptylammonium promide (TBAB) may be used in combination.
  • TBAB functions as a co-catalyst in the reaction system of the present invention, improves the yield of the resulting ⁇ -amino acid and derivatives thereof, and is asymmetric represented by the formula (I) used in the present invention.
  • the amount of the phase transfer catalyst can be further reduced.
  • the amount of TBAB that can be used in the present invention is preferably 0.005 mole 0 / mole per mole of the compound of the above formula (IV). ⁇ It is 1 mole 0/0, more preferably 0.01% - 0.8 mol 0/0.
  • the alkylation step is also performed at a suitable temperature between _70 ° C. and room temperature, preferably from 20 ° C. to 20 ° C., in air, preferably under an argon atmosphere. This step can be carried out with stirring for an appropriate time until the alkylation reaction has proceeded sufficiently.
  • the reaction time is preferably 30 minutes to 48 hours, more preferably 1 hour to 24 hours.
  • the optically active compound of the formula (VI) can be obtained in high yield and high optical purity.
  • the high optical purity is preferably an optical purity of 80% ee or higher, more preferably 85% ee or higher, even more preferably 90% ee or higher, and even more preferably 95% ee or higher.
  • the present invention provides a method for producing an optically active ⁇ -amino acid. provide.
  • optically active ⁇ -amino acid derivative represented by the optically active formula (VI) obtained by the above method.
  • an optically active ⁇ -amino acid can be produced.
  • acids used in the acid hydrolysis step of imine include inorganic acids (for example, hydrochloric acid, phosphoric acid, sulfuric acid) and organic acids (for example, acetic acid, citrate, p-toluenesulfonic acid).
  • the acid hydrolysis step of the imine is carried out by using a compound of the formula (VI) in an appropriate medium (eg, tetrahydrofuran, toluene, ethanol ', or a combination thereof) and an aqueous solution of the above acid. Proceed by using and treating at an appropriate temperature (eg, room temperature). As a result, an ester derivative of an amino acid having a terminal amino group released as an acidic hydrolysis product can be obtained.
  • an appropriate medium eg, tetrahydrofuran, toluene, ethanol ', or a combination thereof
  • the ester derivative (acid hydrolysis product) of the amino acid obtained in the above step is subjected to a hydrolysis reaction under acidic conditions or basic conditions stronger than the hydrolysis of imine, if necessary.
  • the target amino acid in which the terminal of the acidic hydrolyzate that is, the ester group (one C 0 2 R 1 7 ) constituting the acidic hydrolyzate) becomes a carboxylic acid can be obtained.
  • the ester group (one C 0 2 R 17 ) constituting the optically active compound of formula '(VI) (optically active ⁇ -amino acid derivative) obtained by the above alkylation reaction is converted to basic First hydrolyze under conditions (basic ester hydrolysis step).
  • basic hydrolysis step of this ester a sodium hydroxide aqueous solution or the like An aqueous solution of Lucari can be used.
  • a basic hydrolysis product in which the terminal of the compound (VI) (that is, the ester group (—C0 2 R 17 ) constituting the compound of the formula (VI)) is a carboxylic acid can be obtained.
  • N-) Hydrolyze the part under acidic conditions (acid hydrolysis step of imine).
  • acids used in the acid hydrolysis step of this imine include inorganic acids (eg, hydrochloric acid, phosphoric acid, sulfuric acid) or organic acids (eg, acetic acid, citrate, p-toluenesulfonic acid).
  • the acid hydrolysis step of the imine is carried out by using the basic hydrolyzate in an appropriate medium (for example, tetrahydrofuran, toluene, ethanol, or a combination thereof) using an aqueous solution of the acid. Proceed by processing at an appropriate temperature (eg, room temperature).
  • the target amino acid from which the terminal amino group has been released can be obtained.
  • the amino acid when the amino acid is produced from the compound of the formula (VI), either the first method or the second method described above may be used, and the specific structure of the amino acid actually produced Further, it can be arbitrarily selected by those skilled in the art according to other manufacturing conditions.
  • the NMR spectrum is defined as JEOL JNM-FX.
  • Compound 3 was prepared in the presence of 5m o 1% palladium acetate, 15m o 1% PP h 3 in dimethylformamide, and 3 equivalents of potassium carbonate.
  • a Suzuki-Miyaura cross-force coupling reaction with 3,4,5-trifluorophenylpo-noic acid was carried out at 90 ° C. for 8 hours to obtain Compound 4 in 94% yield.
  • Compound 4 was then reduced with 3 equivalents of Li A 1 H 4 in tetrahydrofuran at 0 ° C. to room temperature, and the resulting compound 5 was then converted to 0.5 equivalents of PB in tetrahydrofuran at 0 ° C.
  • compound 6 (S form) was obtained with a yield of 90%.
  • the R form was also prepared by the same procedure.
  • Table 1 shows the NMR spectrum of the obtained compound 7 (S form).
  • Table 2 shows the NMR spectrum 'of the obtained compound 8 (S form).
  • Table 3 shows the NMR spectrum of the obtained compound 9 (S form).
  • Example 3-1 Preparation of the novel compounds 10> M rn ⁇ run u KIU MgS0 4 NaBH 4, nC 4 9 CH 3 (CH 2) 20 c nO + nC 4 H 9 NH 2 ⁇ 4> HN '4 s
  • novel compound 10 was prepared according to the method described in Rajkumar Sunil Singh et al., Chemistry-A European Journal, 2002, No. 8, pp.900-909. It was prepared as follows.
  • N-docosanal A (324. 6 mg, 1. Ommo l), n-butyramine (73. lmg, 1. Ommo 1), and black mouth form under nitrogen atmosphere 0 mixture of (3 OmL).
  • magnesium sulfate (145 mg, 1.2 mmo 1) was added at 0 ° C.
  • the mixture was stirred for 6 hours at room temperature, filtered, and washed with methanol (3 mL ⁇ 2).
  • the filtrate was cooled to 0 ° C and sodium borohydride (76 mg, 2. Ommol) was added at 0 ° C.
  • black mouth form (2 OmL) was added and washed with water (25 mLX3). Further, the extract was dried over sodium sulfate and concentrated under reduced pressure to obtain Compound 10 (320 mg) in a yield of 84%. '
  • Table 4 shows the NMR spectrum and MS spectrum of the obtained compound 10.
  • Table 5 shows the NMR spectrum of the obtained Compound 11 (R-form).
  • the alkylated Schiff base 16 was further extracted with toluene (5 mL ⁇ 2). This was combined with the recovered toluene layer, 1N hydrochloric acid was further added, and the mixture was stirred at room temperature for 3.5 hours. After recovering the aqueous layer by liquid separation, wash the aqueous layer with toluene (10 mL), pay attention to foaming, and add sodium carbonate until the solution is pH 11 or higher (confirmed with universal pH test paper). The Schiff base 16 was extracted with ethyl acetate (20 mLX 2). The ethyl acetate layer is dried over sodium sulfate and concentrated under reduced pressure.
  • the catalyst containing a long-chain alkyl group (compounds 9 and 11 obtained in Examples 2 and 3-2) was a conventional catalyst (ie, Compared with the compound 7) ′ used in Comparative Example 2, it is possible to carry out a disubstituted alkylation reaction with the same or higher stereoselectivity.
  • a chiral phase transfer catalyst having a simpler structure is provided.
  • This phase transfer catalyst can be produced with fewer steps than conventional compounds, which also reduces costs.
  • a chiral phase transfer catalyst that provides high stereoselectivity in an asymmetric alkylation reaction by including a long-chain alkyl group in the catalyst structure is provided.
  • Such phase transfer catalysts include ⁇ -alkyl mono ⁇ -amino acids and derivatives thereof, and It is very useful for the synthesis of one amino acid and its derivatives. Thus synthesized.
  • Amino acids and their derivatives are useful in the design of peptides with enhanced properties and as effective enzyme inhibitors. It also plays a special role as a chiral construct block for the synthesis of compounds with various biological activities. Therefore, it is useful for the development of new foods and pharmaceuticals.

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Abstract

La présente invention concerne un catalyseur à transfert de phase chiral à structure simplifiée qui peut être produit selon un procédé consistant à faire réagir un dérivé 2,2-diméthylènebromide-1,1'-binaphthyle (qui peut être produit en un relativement petit nombre d'étapes) avec une amine secondaire (qui est immédiatement disponible). Le catalyseur est un composé représenté par la formule (I) comportant un groupe alkyle à chaîne longue R7 dans sa structure chimique. On s'attend à ce que le catalyseur présente une forte stéréosélectivité, même dans une réaction où un catalyseur classique ne présente pas de stéréosélectivité satisfaisante, telle qu'une réaction d'alkylation asymétrique.
PCT/JP2006/315456 2005-07-29 2006-07-28 Sel d'ammonium quaternaire optiquement actif axi-asymmetrique et procede de production d'un $g(a)-amino acide ou d'un derive de celui-ci a l'aide du sel d'ammonium quaternaire WO2007013697A1 (fr)

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