JP4425654B2 - Water-soluble transition metal-diamine complex, method for producing the same, and use thereof - Google Patents

Description

  The present invention relates to a water-soluble optically active transition metal-diamine complex useful as a catalyst for various organic synthesis reactions, particularly a hydrogen transfer asymmetric hydrogenation reaction, and a method for producing optically active secondary alcohols using the same.

Conventionally, many transition metal complexes have been used as catalysts for organometallic reactions. In particular, noble metal complexes are expensive, but are highly active, stable and easy to handle. In particular, the progress of asymmetric synthesis reactions using asymmetric complex catalysts has been remarkable, and there have been many reports that have achieved high efficiency in organic synthesis reactions that are inefficient.
Among them, in particular, many asymmetric reactions catalyzed by asymmetric complexes having optically active phosphine ligands have been developed and industrialized. In addition, for example, many complexes in which an optically active nitrogen compound is coordinated to a transition metal such as ruthenium, rhodium, and iridium have excellent performance as a catalyst for an asymmetric synthesis reaction, and the performance of this catalyst is improved. Therefore, many optically active nitrogen compounds having a special structure have been developed so far (Non-patent Document 1, etc.).
For example, a complex in which optically active Np-toluenesulfonyl-1,2-diphenylethylenediamine described in Non-Patent Document 2 and Non-Patent Document 3 is coordinated to ruthenium as a ligand has been reported. However, the reaction using this ligand is carried out in an organic solvent, and there is no example carried out in water. In addition, when trying to produce pharmaceutical intermediates and the like by the methods described in these, since many of the intermediates are solids, it is difficult to separate the obtained intermediate and the catalyst by a distillation operation or the like.

Thus, separation of the catalyst and the product is one of the problems that cannot be avoided, but in particular, in homogeneous catalysis, the catalyst used is easily dissolved in the organic phase, so the separation of the catalyst and the product is difficult. Requires complicated methods such as distillation and recrystallization. One solution to this problem is to use a water-soluble catalyst and perform the reaction in a solvent system containing water, so that the product dissolves in the organic phase and the catalyst dissolves in the aqueous phase. It is conceivable that the catalyst can be easily separated. Under such circumstances, many developments of water-soluble phosphine ligands have been reported.
For example, Patent Document 1 discloses an asymmetric hydrogenation reaction using sulfonated-BINAP. However, there is no description about the reuse of the catalyst dissolved in water after hydrogenation once.
Non-Patent Document 4 reports a hydrogen transfer reduction reaction using a ligand obtained by sulfonating the para-position of the phenyl group of benzenesulfonyl-1,2-diaminocyclohexane. However, since this reaction is performed in isopropanol-water as a solvent, the product must be separated by distillation.
Non-Patent Document 5 describes a diphenylethylenediamine derivative in which a tosyl group is introduced into one amino group and the ortho position of the phenyl group is sulfonated, and the diphenylethylenediamine derivative is used as an asymmetric hydrogenation catalyst. -It has been reported that an asymmetric hydrogenation reaction is carried out in a mixed solvent of dichloromethane. However, in Non-Patent Document 5, there is no description about a method for synthesizing a complex, and it is necessary to use a phase transfer catalyst for the asymmetric hydrogenation reaction. Had problems.

JP-A-5-170780 Chem Rev., 92, 1051-1069 (1992) J. Am. Chem. Soc., Vol.117, 7562-7563 (1995) J. Am. Chem. Soc., Vol.118, 4916-4917 (1996) Tetrahedron Lett., Vol.42, 4041-4043 (2001) Organic Letters, Vol.5, No.12, 2103 (2003) Angewandt Chemie, Int. Ed. Engl., 36, No. 3, 288 (1997) Angewandt Chemie, Int. Ed. Engl., 36, No. 3, 286 (1997)

  The present invention has been made in view of the current situation as described above. For example, the present invention is a novel metal complex catalyst capable of obtaining an optically active alcohol from a ketone with high yield and optical purity by performing a reaction using the catalyst as a catalyst. An object of the present invention is to provide a recyclable water-soluble transition metal complex that can be used in an aqueous solvent and can be easily separated from a reaction product by liquid separation after the reaction. To do.

［式中、Ｒ^１及びＲ^２は夫々独立して、水素原子、置換基を有していてもよい炭化水素基又は−ＳＯ_２Ｒ^１３（但し、Ｒ^１３は置換基を有していてもよい炭化水素基、カンフォリル基又は置換アミノ基を示す。）を示し、Ｒ^３〜Ｒ^１２は夫々独立して、水素原子、置換基を有していてもよい炭化水素基、置換基を有していてもよい複素環基、置換基を有していてもよいアルコキシ基、置換基を有していてもよいアリールオキシ基、置換基を有していてもよいアラルキルオキシ基又は−ＳＯ_３Ｒ^１４（但し、Ｒ^１４は水素原子又は金属原子を示す。）を示し、Ｍは遷移金属を示し、Ｘはハロゲン原子を示し、Ｌは配位子を示す。但し、Ｒ^３〜Ｒ^１２のうちの少なくとも１つは−ＳＯ_３Ｒ^１４である。］で表される水溶性遷移金属−ジアミン錯体に関する。 The present invention relates to the following general formula (1)

[Wherein, R ¹ and R ² are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) or —SO ₂ R ¹³ (provided that R ¹³ may have substituent (s); A hydrocarbon group, a camphoryl group or a substituted amino group.), R ^{3 to} R ¹² each independently have a hydrogen atom, a hydrocarbon group which may have a substituent, or a substituent. An optionally substituted heterocyclic group, an optionally substituted alkoxy group, an optionally substituted aryloxy group, an optionally substituted aralkyloxy group or —SO ₃ R ¹⁴ (wherein R ¹⁴ represents a hydrogen atom or a metal atom), M represents a transition metal, X represents a halogen atom, and L represents a ligand. However, at least one of R ^{3 to} R ¹² is —SO ₃ R ¹⁴ . ] It is related with the water-soluble transition metal-diamine complex represented by this.

  Moreover, this invention relates to the optically active substance of the said water-soluble transition metal-diamine complex.

［式中、Ｒ^１及びＲ^２は夫々独立して、水素原子、置換基を有していてもよい炭化水素基又は−ＳＯ_２Ｒ^１３（但し、Ｒ^１３は置換基を有していてもよい炭化水素基、カンフォリル基又は置換アミノ基を示す。）を示し、Ｒ^３〜Ｒ^１２は夫々独立して、水素原子、置換基を有していてもよい炭化水素基、置換基を有していてもよい複素環基、置換基を有していてもよいアルコキシ基、置換基を有していてもよいアリールオキシ基、置換基を有していてもよいアラルキルオキシ基又は−ＳＯ_３Ｒ^１４（但し、Ｒ^１４は水素原子又は金属原子を示す。）を示す。但し、Ｒ^３〜Ｒ^１２のうちの少なくとも１つは−ＳＯ_３Ｒ^１４である。］で表される水溶性ジアミン化合物と、一般式（３）
［ＭＸ_ｍＬ_ｎ］_ｐ （３）
（式中、Ｍは遷移金属を示し、Ｘはハロゲン原子を示し、Ｌは配位子を示し、ｍは２又は３を示し、ｎは０又は１を示し、ｐは１又は２を示す。）で表される遷移金属化合物とを反応させることを特徴とする、上記水溶性遷移金属−ジアミン錯体の製造方法に関する。 Furthermore, the present invention relates to a general formula (2)

[Wherein, R ¹ and R ² are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) or —SO ₂ R ¹³ (provided that R ¹³ may have substituent (s); A hydrocarbon group, a camphoryl group or a substituted amino group.), R ^{3 to} R ¹² each independently have a hydrogen atom, a hydrocarbon group which may have a substituent, or a substituent. An optionally substituted heterocyclic group, an optionally substituted alkoxy group, an optionally substituted aryloxy group, an optionally substituted aralkyloxy group or —SO ₃ R ¹⁴ (wherein R ¹⁴ represents a hydrogen atom or a metal atom). However, at least one of R ^{3 to} R ¹² is —SO ₃ R ¹⁴ . And a water-soluble diamine compound represented by the general formula (3)
[MX _m L _n ] _p (3)
(In the formula, M represents a transition metal, X represents a halogen atom, L represents a ligand, m represents 2 or 3, n represents 0 or 1, and p represents 1 or 2. It is related with the manufacturing method of the said water-soluble transition metal-diamine complex characterized by reacting with the transition metal compound represented by this.

  Furthermore, in the present invention, the water-soluble diamine compound represented by the general formula (2) is an optically active water-soluble diamine compound, and the resulting water-soluble transition metal-diamine complex is an optically active water-soluble transition metal- It is related with the manufacturing method of the said water-soluble transition metal-diamine complex which is a diamine complex.

［式中、Ｒ^１及びＲ^２は夫々独立して、水素原子、置換基を有していてもよい炭化水素基又は−ＳＯ_２Ｒ^１３（但し、Ｒ^１３は置換基を有していてもよい炭化水素基、カンフォリル基又は置換アミノ基を示す。）を示し、Ｒ^３、Ｒ^５〜Ｒ^８及びＲ^１０〜Ｒ^１２は夫々独立して、水素原子、置換基を有していてもよい炭化水素基、置換基を有していてもよい複素環基、置換基を有していてもよいアルコキシ基、置換基を有していてもよいアリールオキシ基、置換基を有していてもよいアラルキルオキシ基又は−ＳＯ_３Ｒ^１４（但し、Ｒ^１４は水素原子又は金属原子を示す。）を示す。］］で表される水溶性ジアミン化合物に関する。 Further, the present invention provides a compound represented by the general formula (2b)

[Wherein, R ¹ and R ² are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) or —SO ₂ R ¹³ (provided that R ¹³ may have substituent (s); R ³ , R ^{5 to} R ⁸ and R ^{10 to} R ¹² may each independently have a hydrogen atom or a substituent, which represents a good hydrocarbon group, camphoryl group or substituted amino group. A hydrocarbon group, a heterocyclic group which may have a substituent, an alkoxy group which may have a substituent, an aryloxy group which may have a substituent, or a substituent A good aralkyloxy group or —SO ₃ R ¹⁴ (wherein R ¹⁴ represents a hydrogen atom or a metal atom). ] It is related with the water-soluble diamine compound represented by this.

  Furthermore, this invention relates to the optically active substance of the said water-soluble diamine compound.

  Furthermore, the present invention relates to an asymmetric synthesis catalyst comprising the optically active water-soluble transition metal-diamine complex.

The present invention also provides the optically active water-soluble diamine compound and the general formula (3).
[MX _m L _n ] _p (3)
(In the formula, M represents a transition metal, X represents a halogen atom, L represents a ligand, m represents 2 or 3, n represents 0 or 1, and p represents 1 or 2. And an asymmetric synthesis catalyst comprising a transition metal compound represented by:

［式中、Ｒ^２１及びＲ^２２は夫々独立して、置換基を有していてもよい炭化水素基、置換基を有していてもよい複素環基又はフェロセニル基を示す（但し、Ｒ^２１及びＲ^２２は同一とはならない。）。また、Ｒ^２１とＲ^２２とが互いに結合して、カルボニル基の炭素原子と一緒になって環を形成していてもよい。］で表されるケトン類を、上記何れかの不斉合成触媒の存在下、水溶媒中で不斉水素化反応させることを特徴とする、一般式（５）

（式中、＊は不斉炭素を示し、Ｒ^２１及びＲ^２２は前記と同じ。）で表される光学活性２級アルコール類の製造方法に関する。 Furthermore, the present invention relates to a general formula (4)

[Wherein, R ²¹ and R ²² each independently represent a hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a ferrocenyl group (provided that R ²¹ And R ²² are not the same). R ²¹ and R ²² may be bonded to each other to form a ring together with the carbon atom of the carbonyl group. Wherein the ketone represented by the general formula (5) is subjected to an asymmetric hydrogenation reaction in an aqueous solvent in the presence of any of the above-mentioned asymmetric synthesis catalysts.

(Wherein, * represents an asymmetric carbon, and R ²¹ and R ²² are the same as described above).

  Furthermore, this invention relates to the manufacturing method of the said optically active secondary alcohol which recycles the asymmetric synthesis catalyst after use.

  In the asymmetric hydrogenation reaction using the optically active water-soluble transition metal-diamine complex of the present invention as a catalyst, the catalyst can be recycled, leading to cost reduction. Moreover, since the asymmetric hydrogenation reaction using the optically active water-soluble transition metal-diamine complex of the present invention as a catalyst can be carried out in an aqueous solvent, it can also be said to be an asymmetric hydrogenation reaction considering the environment.

In the general formulas (1), (2) and (2b), examples of the hydrocarbon group which may have a substituent represented by R ¹ or R ² include a hydrocarbon group and a substituted hydrocarbon group. .
Examples of the hydrocarbon group include an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an aralkyl group, and the like.

The alkyl group may be linear, branched or cyclic, and examples thereof include an alkyl group having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms. Specific examples include, for example, methyl group, ethyl Group, n-propyl group, 2-propyl group, n-butyl group, 2-butyl group, isobutyl group, tert-butyl group, n-pentyl group, 2-pentyl group, tert-pentyl group, 2-methylbutyl group, 3-methylbutyl group, 2,2-dimethylpropyl group, n-hexyl group, 2-hexyl group, 3-hexyl group, tert-hexyl group, 2-methylpentyl group, 3-methylpentyl group, 4-methylpentyl group 2-methylpentan-3-yl group, heptyl group, octyl group, nonyl group, decyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group Group, and the like.
The alkenyl group may be linear or branched, for example, an alkenyl group having 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms. Specific examples include, for example, Ethenyl group, propenyl group, 1-butenyl group, pentenyl group, hexenyl group and the like.
The alkynyl group may be linear or branched, and examples thereof include alkynyl groups having 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms. Specific examples include, for example, Ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 3-butynyl group, pentynyl group, hexynyl group and the like.

Examples of the aryl group include an aryl group having 6 to 14 carbon atoms, and specific examples include a phenyl group, a tolyl group, a xylyl group, a 1-naphthyl group, a 2-naphthyl group, and an anthryl group.
Examples of the aralkyl group include groups in which at least one hydrogen atom of the alkyl group is substituted with the aryl group. For example, an aralkyl group having 7 to 15 carbon atoms is preferable, and specific examples include, for example, a benzyl group, 2-phenethyl group, 1-phenylpropyl group, 3-naphthylpropyl group and the like can be mentioned.
Preferred hydrocarbon groups for R ¹ and R ² include an alkyl group, an aryl group, and an aralkyl group.

Examples of the substituted hydrocarbon group (hydrocarbon group having a substituent) include hydrocarbon groups in which at least one hydrogen atom of the hydrocarbon group is substituted with a substituent. Examples thereof include a substituted alkyl group, a substituted aryl group, a substituted alkenyl group, a substituted alkynyl group, and a substituted aralkyl group.
Examples of the substituent include a hydrocarbon group, a halogen atom, a halogenated hydrocarbon group, an alkoxy group, an aryloxy group, an aralkyloxy group, and a substituted amino group.

The hydrocarbon group as a substituent is exactly the same as the above hydrocarbon group.
Examples of the halogen atom as a substituent include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Examples of the halogenated hydrocarbon group as a substituent include groups in which at least one hydrogen atom of the above hydrocarbon group is halogen-substituted (for example, fluorine substitution, chlorine substitution, bromine substitution, iodine substitution, etc.). Preferable examples of the halogenated hydrocarbon group include a halogenated alkyl group. As the halogenated alkyl group, for example, a halogenated alkyl group having 1 to 10 carbon atoms is preferable, and specific examples thereof include, for example, chloromethyl group, bromomethyl group, 2-chloroethyl group, 3-bromopropyl group. Group, fluoromethyl group, fluoroethyl group, fluoropropyl group, fluorobutyl group, fluoropentyl group, fluorohexyl group, fluoroheptyl group, fluorooctyl group, fluorononyl group, fluorodecyl group, difluoromethyl group, difluoroethyl group, Fluorocyclohexyl group, trifluoromethyl group, 2,2,2-trifluoroethyl group, 3,3,3-trifluoropropyl group, pentafluoroethyl group, 3,3,4,4,4-pentafluorobutyl group Perfluoro-n-propyl group, perfluoroi Propyl group, perfluoro-n-butyl group, perfluoroisobutyl group, perfluoro-tert-butyl group, perfluoro-sec-butyl group, perfluoropentyl group, perfluoroisopentyl group, perfluoro-tert-pentyl group, perfluoro-n-hexyl group Perfluoroisohexyl group, perfluoroheptyl group, perfluorooctyl group, perfluorononyl group, perfluorodecyl group, 2-perfluorooctylethyl group, perfluorocyclopropyl group, perfluorocyclopentyl group, perfluorocyclohexyl group and the like.

Examples of the alkoxy group as the substituent include linear, branched or cyclic, for example, an alkoxy group having 1 to 6 carbon atoms, and specific examples thereof include, for example, a methoxy group, an ethoxy group, and n- Propoxy group, 2-propoxy group, n-butoxy group, 2-butoxy group, isobutoxy group, tert-butoxy group, n-pentyloxy group, 2-methylbutoxy group, 3-methylbutoxy group, 2,2-dimethylpropyl Examples include an oxy group, an n-hexyloxy group, a 2-methylpentyloxy group, a 3-methylpentyloxy group, a 4-methylpentyloxy group, a 5-methylpentyloxy group, and a cyclohexyloxy group.
Examples of the aryloxy group as a substituent include an aryloxy group having 6 to 14 carbon atoms, and specific examples thereof include a phenoxy group, a naphthyloxy group, and an anthryloxy group.
Examples of the aralkyloxy group as a substituent include an aralkyloxy group having 7 to 12 carbon atoms, and specific examples thereof include, for example, benzyloxy group, 2-phenethyloxy group, 1-phenylpropoxy group, 2- Phenylpropoxy group, 3-phenylpropoxy group, 1-phenylbutoxy group, 2-phenylbutoxy group, 3-phenylbutoxy group, 4-phenylbutoxy group, 1-phenylpentyloxy group, 2-phenylpentyloxy group, 3- Phenylpentyloxy group, 4-phenylpentyloxy group, 5-phenylpentyloxy group, 1-phenylhexyloxy group, 2-phenylhexyloxy group, 3-phenylhexyloxy group, 4-phenylhexyloxy group, 5-phenyl Hexyloxy group, 6-phenylhexyloxy group And the like.

Examples of the substituted amino group as a substituent include an amino group in which one or two hydrogen atoms of the amino group are substituted with a substituent such as an amino protecting group. Any amino protecting group as a substituent of the substituted amino group can be used as long as it is usually used as an amino protecting group.For example, `` PROTECTIVE GROUPS IN ORGANIC SYNTHESIS THIRD EDITION (JOHN WILEY & SONS, INC (1999) "as specific examples of the amino protecting group include, for example, alkyl group, aryl group, aralkyl group, acyl group, alkoxycarbonyl group, aryloxycarbonyl. Group, aralkyloxycarbonyl group, substituted sulfonyl group and the like.
The alkyl group, aryl group and aralkyl group in the amino protecting group are the same as those described for the hydrocarbon group.
The acyl group may be linear, branched or cyclic, and examples thereof include C1-C20 acyl groups derived from carboxylic acids such as aliphatic carboxylic acids and aromatic carboxylic acids. Examples include formyl group, acetyl group, propionyl group, butyryl group, pivaloyl group, pentanoyl group, hexanoyl group, lauroyl group, stearoyl group, benzoyl group and the like.

The alkoxycarbonyl group may be linear, branched or cyclic, and examples thereof include an alkoxycarbonyl group having 2 to 20 carbon atoms. Specific examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, 2-propoxycarbonyl group, n-butoxycarbonyl group, tert-butoxycarbonyl group, pentyloxycarbonyl group, hexyloxycarbonyl group, 2-ethylhexyloxycarbonyl group, lauryloxycarbonyl group, stearyloxycarbonyl group, cyclohexyloxycarbonyl group, etc. Is mentioned.
Examples of the aryloxycarbonyl group include an aryloxycarbonyl group having 7 to 20 carbon atoms, and specific examples thereof include a phenoxycarbonyl group and a naphthyloxycarbonyl group.
Examples of the aralkyloxycarbonyl group include an aralkyloxycarbonyl group having 8 to 20 carbon atoms, and specific examples thereof include a benzyloxycarbonyl group, a phenethyloxycarbonyl group, a 9-fluorenylmethyloxycarbonyl group, and the like.

Examples of the substituted sulfonyl group include a substituted sulfonyl group represented by R ^a —SO ₂ — (R ^a represents a hydrocarbon group, a substituted hydrocarbon group or a substituted amino group). The hydrocarbon group, substituted hydrocarbon group and substituted amino group represented by ^Ra are the same as the above-described groups. Specific examples of the substituted sulfonyl group include a methanesulfonyl group, a trifluoromethanesulfonyl group, a benzenesulfonyl group, a p-toluenesulfonyl group, and a —SO ₂ N (CH ₃ ) ₂ group.

  Specific examples of the amino group substituted with an alkyl group, that is, the alkyl-substituted amino group include, for example, N-methylamino group, N, N-dimethylamino group, N, N-diethylamino group, N, N-diisopropylamino. And mono- or dialkylamino groups such as N-cyclohexylamino group. Specific examples of an amino group substituted with an aryl group, that is, an aryl-substituted amino group include, for example, an N-phenylamino group, an N, N-diphenylamino group, an N-naphthylamino group, and an N-naphthyl-N-phenylamino group. And mono- or diarylamino groups such as groups. Specific examples of the amino group substituted with an aralkyl group, that is, an aralkyl-substituted amino group include mono- or diaralkylamino groups such as an N-benzylamino group and an N, N-dibenzylamino group. Specific examples of the amino group substituted with an acyl group, that is, the acylamino group include, for example, formylamino group, acetylamino group, propionylamino group, pivaloylamino group, pentanoylamino group, hexanoylamino group, benzoylamino group, and the like. Can be mentioned.

Specific examples of the amino group substituted with an alkoxycarbonyl group, that is, the alkoxycarbonylamino group include, for example, a methoxycarbonylamino group, an ethoxycarbonylamino group, an n-propoxycarbonylamino group, an n-butoxycarbonylamino group, and a tert-butoxy. Examples thereof include a carbonylamino group, a pentyloxycarbonylamino group, and a hexyloxycarbonylamino group.
Specific examples of the amino group substituted with an aryloxycarbonyl group, that is, the aryloxycarbonylamino group include, for example, an amino group in which one hydrogen atom of the amino group is substituted with the aryloxycarbonyl group described above, Specific examples thereof include a phenoxycarbonylamino group and a naphthyloxycarbonylamino group.
Specific examples of the amino group substituted with an aralkyloxycarbonyl group, that is, an aralkyloxycarbonylamino group include a benzyloxycarbonylamino group.
Specific examples of the amino group substituted with a substituted sulfonyl group include —NHSO ₂ CH ₃ , —NHSO ₂ C ₆ H ₅ , —NHSO ₂ C ₆ H ₄ CH ₃ , —NHSO ₂ CF ₃ , —NHSO ₂ N ( CH ₃ ) _{2 and the} like.

The general formula (1), (2) and in ^(2b), R 1, ^R in the _-SO 2 ^{R 13} represented by ^{2, R 13} substituent substituted hydrocarbon group and substituted have shown by The amino group may be the same as described above. In the case where the hydrocarbon group which may have a substituent is a substituted hydrocarbon group, preferred substituents are alkyl groups having 1 to 5 carbon atoms, alkenyl groups having 2 to 5 carbon atoms, and 1 to 5 carbon atoms. Examples thereof include an alkoxy group, an alkyl-substituted amino group having 1 to 5 carbon atoms, and an acylamino group having 2 to 3 carbon atoms.

In the general formulas (1), (2) and (2b), the hydrocarbon group which may have a substituent represented by R ^{3 to} R ¹² is the substituent described in the above R ¹ and R ^2. It may be the same as the hydrocarbon group which may have.
Examples of the heterocyclic group which may have a substituent include a heterocyclic group and a substituted heterocyclic group. Examples of the heterocyclic group include an aliphatic heterocyclic group and an aromatic heterocyclic group.
Examples of the aliphatic heterocyclic group include 2 to 14 carbon atoms and at least one hetero atom, preferably 1 to 3 hetero atoms such as a nitrogen atom, an oxygen atom and / or a sulfur atom. , 5 to 8 membered, preferably 5 or 6 membered monocyclic aliphatic heterocyclic group, polycyclic or condensed aliphatic heterocyclic group. Specific examples of the aliphatic heterocyclic group include pyrrolidyl-2-one group, piperidino group, piperazinyl group, morpholino group, morpholinyl group, tetrahydrofuryl group, tetrahydropyranyl group and the like.
As the aromatic heterocyclic group, for example, it has 2 to 15 carbon atoms and contains at least one hetero atom, preferably 1 to 3 hetero atoms such as nitrogen atom, oxygen atom and / or sulfur atom. Examples thereof include a 5- to 8-membered, preferably 5- or 6-membered monocyclic heteroaryl group, polycyclic or condensed ring heteroaryl group, and specific examples thereof include a furyl group, a thienyl group, a pyridyl group, and a pyrimidyl group. Group, pyrazyl group, pyridazyl group, pyrazolyl group, imidazolyl group, oxazolyl group, thiazolyl group, benzofuryl group, benzothienyl group, quinolyl group, isoquinolyl group, quinoxalyl group, phthalazyl group, quinazolyl group, naphthyridyl group, cinnolyl group, benzimidazolyl group Benzoxazolyl group, benzothiazolyl group, acridyl group, acridinyl group and the like.
Examples of the substituted heterocyclic group (heterocyclic group having a substituent) include heterocyclic groups in which at least one hydrogen atom of the heterocyclic group is substituted with a substituent. Examples of the substituted heterocyclic group (a heterocyclic group having a substituent) include a substituted aliphatic heterocyclic group and a substituted aromatic heterocyclic group. The substituent may be the same as the substituent in the hydrocarbon group which may have the substituent described in the above R ¹ and R ² .

The alkoxy group which may have a substituent, the aryloxy group which may have a substituent, and the aralkyloxy group which may have a substituent are the substituents described above for R ¹ and R ^2. A hydrocarbon group that may have a group, an alkoxy group that may have a substituent, an aryloxy group that may have a substituent, and a substituent. It can be the same as a good aralkyloxy group.

The general formula (1), represented by ^{R 14} in _-SO 3 ^{R 14} in (2) and in ^(2b), R 3 ^{to R 12} in ^{R 14} and the formula in _-SO 3 ^{R 14} represented (2b) Examples of the metal atom include alkali metals and alkaline earth metals.
Examples of the alkali metal include lithium, sodium, potassium, rubidium, cesium and the like.
Examples of the alkaline earth metal include magnesium, calcium, strontium, barium and the like.

In the general formula (1), examples of the transition metal represented by M include group 8 to group 9 transition metals in the periodic table. For example, ruthenium, rhodium, iridium, and the like are preferable.
In the general formula (1), examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a chlorine atom, a bromine atom, and an iodine atom are preferable.

In the general formula (1), the ligand represented by L is preferably a neutral ligand. Examples of the neutral ligand include aromatic compounds optionally substituted with an alkyl group, olefin compounds, and other neutral ligands.
Examples of the aromatic compound that may be substituted with an alkyl group include unsubstituted aromatic compounds and alkyl-substituted aromatic compounds. Benzene etc. are mentioned as an unsubstituted aromatic compound. Examples of the alkyl-substituted aromatic compound include an aromatic compound in which at least one hydrogen atom of the aromatic compound is substituted with an alkyl group having 1 to 3 carbon atoms such as a methyl group, an ethyl group, a propyl group, and an isopropyl group. Is mentioned. Specific examples of the alkyl-substituted aromatic compound include toluene, p-cymene, hexamethylbenzene, 1,3,5-trimethylbenzene (mesitylene) and the like.
Examples of the olefin compound include ethylene, cyclopentadiene, 1,5-cyclooctadiene (cod), norbornadiene (nbd), pentamethylcyclopentadiene, and the like.
Other neutral ligands include N, N-dimethylformamide (DMF), acetonitrile, benzonitrile, acetone, chloroform and the like.

（式中、＊は不斉炭素を示し、Ｒ^１〜Ｒ^１２、Ｍ、Ｘ及びＬは前記と同じ。）で表される光学活性水溶性遷移金属−ジアミン錯体がより好ましい。 The water-soluble transition metal-diamine complex represented by the general formula (1) includes both a racemate and an optically active form, and the following general formula (1a)

(Wherein * represents an asymmetric carbon, and R ^{1 to} R ¹² , M, X, and L are the same as described above), and an optically active water-soluble transition metal-diamine complex is more preferable.

（式中、Ｒ^１〜Ｒ^３、Ｒ^５〜Ｒ^８、Ｒ^１０〜Ｒ^１２、Ｒ^１４、Ｍ、Ｘ及びＬは前記と同じ。）で表される水溶性遷移金属−ジアミン錯体が挙げられる。 As a preferable example of the water-soluble transition metal-diamine complex represented by the general formula (1), for example, the following general formula (1b)

(Wherein, R ^{1 to} R ³ , R ^{5 to} R ⁸ , R ^{10 to} R ¹² , R ¹⁴ , M, X, and L are the same as those described above). .

（式中、＊は不斉炭素を示し、Ｒ^１〜Ｒ^３、Ｒ^５〜Ｒ^８、Ｒ^１０〜Ｒ^１２、Ｒ^１４、Ｍ、Ｘ及びＬは前記と同じ。）で表される光学活性水溶性遷移金属−ジアミン錯体が挙げられる。
一般式（１ｃ）表される光学活性水溶性遷移金属−ジアミン錯体は、また、一般式（１ｂ）で表される水溶性遷移金属−ジアミン錯体の好ましい例でもある。 Moreover, as a preferable example of the water-soluble transition metal-diamine complex represented by the general formula (1a), for example, the following general formula (1c)

(In the formula, * represents an asymmetric carbon, and R ^{1 to} R ³ , R ^{5 to} R ⁸ , R ^{10 to} R ¹² , R ¹⁴ , M, X, and L are the same as described above). A water-soluble transition metal-diamine complex is mentioned.
The optically active water-soluble transition metal-diamine complex represented by the general formula (1c) is also a preferred example of the water-soluble transition metal-diamine complex represented by the general formula (1b).

  Examples of the optically active water-soluble transition metal-diamine complex of the present invention include (1R, 2R), (1S, 2S), (1R, 2S), (1S, 2R) isomers, preferably (1R, 2R). ), (1S, 2S) isomers.

Specific examples of the optically active water-soluble transition metal-diamine complex represented by the general formula (1c) include the following compounds.

（式中、Ｒ^１〜Ｒ^１２及び＊は前記と同じ。）で表される光学活性水溶性ジアミン化合物がより好ましい。 The water-soluble diamine compound represented by the general formula (2) includes both a racemate and an optically active isomer, but the following general formula (2a)

(Wherein R ^{1 to} R ¹² and * are the same as described above) are more preferable.

（式中、Ｒ^１〜Ｒ^３、Ｒ^５〜Ｒ^８、Ｒ^１０〜Ｒ^１２及びＲ^１４は前記と同じ。）で表される水溶性ジアミン化合物が挙げられる。 As a preferable example of the water-soluble diamine compound represented by the general formula (2), for example, the following general formula (2b)

(Wherein R ^{1 to} R ³ , R ^{5 to} R ⁸ , R ^{10 to} R ¹² and R ¹⁴ are the same as described above).

（式中、Ｒ^１〜Ｒ^３、Ｒ^５〜Ｒ^８、Ｒ^１０〜Ｒ^１２、Ｒ^１４及び＊は前記と同じ。）で表される光学活性水溶性ジアミン化合物が挙げられ、更に好ましい例としては、下記一般式（２ｅ）

（式中、Ｒ^２、Ｒ^３、Ｒ^５〜Ｒ^８、Ｒ^１０〜Ｒ^１４及び＊は前記と同じ。）で表される光学活性水溶性ジアミン化合物が挙げられる。 Preferable examples of the water-soluble diamine compound represented by the general formula (2b) include, for example, the following general formula (2c)

(Wherein, R ^{1 to} R ³ , R ^{5 to} R ⁸ , R ^{10 to} R ¹² , R ¹⁴ and * are the same as described above). Is the following general formula (2e)

(Wherein R ² , R ³ , R ^{5 to} R ⁸ , R ^{10 to} R ^14, and * are the same as described above), and an optically active water-soluble diamine compound.

  Examples of the optically active water-soluble diamine compound represented by the general formula (2c) of the present invention include (1R, 2R), (1S, 2S), (1R, 2S), and (1S, 2R) isomers. Include (1R, 2R) and (1S, 2S) isomers.

  Specific examples of the optically active water-soluble diamine compound represented by the general formula (2c) include, for example, (1R, 2R) -1,2-di (4-sodiumoxysulfonylphenyl) ethylenediamine, (1S, 2S) -1,2-di (4-sodiumoxysulfonylphenyl) ethylenediamine and the like.

  Specific examples of the optically active water-soluble diamine compound represented by the general formula (2e) include, for example, (1R, 2R)-(N-benzenesulfonyl) -1,2-di (4-sodiumoxysulfonylphenyl). Examples include ethylenediamine and (1S, 2S)-(N-benzenesulfonyl) -1,2-di (4-sodiumoxysulfonylphenyl) ethylenediamine.

Specific examples of the transition metal compound represented by the general formula (3) used in the present invention include, for example, [RuCl ₂ (benzene)] ₂ , [RuBr ₂ (benzene)] ₂ , [RuI ₂ (benzene)]. ₂ , [RuCl ₂ (p-cymene)] ₂ , [RuBr ₂ (p-cymene)] ₂ , [RuI ₂ (p-cymene)] ₂ , RuCl ₂ (hexamethylbenzene)] ₂ , [RuBr ₂ (hexamethylbenzene)] ₂ , [RuI ₂ (hexamethylbenzene)] ₂ , [RuCl ₂ (mesitylene)] ₂ , [RuBr ₂ (mesitylene)] ₂ , [RuI ₂ (mesitylene)] ₂ , [RuCl ₂ (pentamethylcyclopentadiene)] ₂ , [RuBr _{2 (pentamethylcyclopentadiene)] 2, [RuI} 2 (pentamethylcyclopentadiene)] 2, [RuCl 2 (cod)] 2, [RuBr 2 (cod)] 2, [RuI 2 (cod)] 2, [ _{uCl 2 (nbd)] 2,} [RuBr 2 (nbd)] 2, [RuI 2 (nbd)] 2, RuCl 3 hydrate, RuBr ₃ hydrate, RuI ₃ hydrate, [RhCl ₂ (benzene) ] ₂ , [RhBr ₂ (benzene)] ₂ , [RhI ₂ (benzene)] ₂ , [RhCl ₂ (p-cymene)] ₂ , [RhBr ₂ (p-cymene)] ₂ , [RhI ₂ (p-cymene) )] ₂ , RhCl ₂ (hexamethylbenzene)] ₂ , [RhBr ₂ (hexamethylbenzene)] ₂ , [RhI ₂ (hexamethylbenzene)] ₂ , [RhCl ₂ (mesitylene)] ₂ , [RhBr ₂ (mesitylene)] ₂ , [RhI _{2 (mesitylene)] 2, [} RhCl 2 (pentamethylcyclopentadiene)] 2, [RhBr 2 (pentamethylcyclopentadiene)] 2, [RhI 2 (pentamethylcyclopentadiene)] 2, [RhCl 2 (cod)] 2, _{RhBr 2 (cod)] 2,} [RhI 2 (cod)] 2, [RhCl 2 (nbd)] 2, [RhBr 2 (nbd)] 2, [RhI 2 (nbd)] 2, RhCl 3 hydrate, RhBr ₃ hydrate, RhI _{3 hydrate, [IrCl 2 (benzene)]} 2, [IrBr 2 (benzene)] 2, [IrI 2 (benzene)] 2, [IrCl 2 (p-cymene)] 2, [IrBr ₂ (p-cymene)] ₂ , [IrI ₂ (p-cymene)] ₂ , IrCl ₂ (hexamethylbenzene)] ₂ , [IrBr ₂ (hexamethylbenzene)] ₂ , [IrI ₂ (hexamethylbenzene)] ₂ , [IrCl _{2 (mesitylene)] 2, [} IrBr 2 (mesitylene)] 2, [IrI 2 (mesitylene)] 2, [IrCl 2 (pentamethylcyclopentadiene)] 2, [IrBr 2 (pentamethylcyclopentadiene)] 2, [IrI _{(Pentamethylcyclopentadiene)] 2, [IrCl} 2 (cod)] 2, [IrBr 2 (cod)] 2, [IrI 2 (cod)] 2, [IrCl 2 (nbd)] 2, [IrBr 2 (nbd)] 2 _{, [IrI 2 (nbd)]} 2, IrCl 3 hydrate, IrBr ₃ hydrate, IrI ₃ hydrate, and the like.

The water-soluble transition metal-diamine complex represented by the general formula (1) of the present invention can be produced, for example, as follows.
1) Introduction of a substituted sulfonyl group at the N position Introduction of a substituted sulfonyl group at the N position can be carried out by a method known per se.
First, a compound to be introduced with a substituted sulfonyl group at the N-position, for example, diphenylethylenediamine, preferably a diamine such as optically active diphenylethylenediamine, and a sulfonylating agent, if necessary, are reacted in a suitable solvent in the presence of a base. N-mono or di (substituted sulfonyl) -diphenylethylenediamine, preferably optically active N-mono (substituted sulfonyl) -diphenylethylenediamine [in the above general formula (2a), either R ¹ or R ² is − A water-soluble diamine compound which is SO ₂ R ¹³ (R ¹³ is the same as above). ] Or an optically active N-di (substituted sulfonyl) -diphenylethylenediamine [in the general formula (2a), R ¹ and R ² are —SO ₂ R ¹³ (R ¹³ is the same as above)]. ] Can be obtained. The diphenylethylenediamine may have a substituent on the phenyl group.

As the sulfonylating agent, for example, the general formula (6)
_{^{R 13 -SO 2 -X 1 (6}} )
(Wherein, X ¹ represents a halogen atom, and R ¹³ is the same as described above), and the like.
In the general formula (6), examples of the halogen atom represented by X ¹ include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Specific examples of the sulfonyl halides represented by the general formula (6) include, for example, methanesulfonyl chloride, ethanesulfonyl chloride, benzenesulfonyl chloride, p-toluenesulfonyl chloride, trifluoromethanesulfonyl chloride, 2,4,6-mesi. Examples include acetylsulfonyl chloride, 2,4,6-triisopropylbenzenesulfonyl chloride, 4-methoxybenzenesulfonyl chloride, 4-chlorobenzenesulfonyl chloride and the like.
The usage-amount of a sulfonylating agent is suitably selected from the range of 0.8-5 mol normally with respect to 1 mol of diphenylethylenediamine, Preferably it is 1-2 mol, More preferably, it is 1-1.2 mol.

Examples of the base include inorganic bases and organic bases. Examples of the inorganic base include salts of alkaline and alkaline earth metals such as potassium carbonate, potassium hydroxide, lithium hydroxide, sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydroxide, magnesium carbonate, calcium carbonate, and water. Examples thereof include metal hydrides such as oxide, sodium hydride, sodium borohydride and lithium aluminum hydride.
Examples of the organic base include potassium methoxide, sodium methoxide, lithium methoxide, sodium ethoxide, potassium isopropoxide, potassium tert-butoxide, potassium naphthalenide, sodium acetate, potassium acetate, magnesium acetate, calcium acetate and the like. Alkali / alkaline earth metal salts, triethylamine, diisopropylethylamine, N, N-dimethylaniline, piperidine, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.3.0] non-5-ene, Organic amines such as 1,8-diazabicyclo [5.4.0] undec-7-ene, tri-n-butylamine, N-methylmorpholine, methylmagnesium bromide, ethylmagnesium bromide, propylmagnesium bromide, methyl lithium Ethyllithium, propyl lithium, n- butyl lithium, organic metal compounds such as tert- butyl lithium, and the like quaternary ammonium salts.
Of these bases, organic amines are particularly preferred.
The usage-amount of a base is normally selected suitably from 1.0-2.0 equivalent with respect to diamine, Preferably it is 1.1-1.2 equivalent.

Examples of the solvent used in the reaction include aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and xylene, dichloromethane, 1,2-dichloroethane, and chloroform. , Halogenated hydrocarbons such as carbon tetrachloride, o-dichlorobenzene, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,3-dioxolane Ethers such as acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc., esters such as methyl acetate, ethyl acetate, n-butyl acetate, methyl propionate, formamide, N, N-di Amides such as chill formamide, N, N- dimethylacetamide, sulfoxides such as dimethyl sulfoxide, cyano-containing organic compounds such as acetonitrile, N- methylpyrrolidone, water and the like. These solvents may be used alone or in appropriate combination of two or more.
The usage-amount of a solvent is suitably selected from the range of 2-10 times capacity normally with respect to diamine, Preferably it is 5-10 times capacity.

The reaction temperature is appropriately selected from the range of usually 0 to 50 ° C, preferably 0 to 10 ° C.
The reaction time is appropriately selected from the range of usually 3 to 20 hours, preferably 5 to 10 hours.
The obtained N-mono or di (substituted sulfonyl) -diphenylethylenediamine, preferably optically active N-mono or di (substituted sulfonyl) -diphenylethylenediamine, may be subjected to post-treatment, purification, or the like as necessary after the reaction. Good. Specific methods of the post-treatment include per se known separation and purification methods such as solvent extraction, liquid conversion, phase transfer, salting out, crystallization, recrystallization, and various chromatography.

（式中、Ｒ^２、Ｒ^３、Ｒ^５〜Ｒ^８及びＲ^１０〜Ｒ^１４は前記と同じ。）で表される水溶性ジアミン化合物、好ましくは上記一般式（２ｅ）で表される光学活性水溶性ジアミン化合物が得られるか、又は、上記一般式（２）においてＲ^１及びＲ^２が水素原子である一般式（２ｆ）

（式中、Ｒ^３、Ｒ^５〜Ｒ^８、Ｒ^１０〜Ｒ^１２及びＲ^１４は前記と同じ。）で表される水溶性ジアミン化合物、好ましくは上記一般式（２ａ）においてＲ^１及びＲ^２が水素原子である一般式（２ｇ）

（式中、Ｒ^３、Ｒ^５〜Ｒ^８、Ｒ^１０〜Ｒ^１２、Ｒ^１４及び＊は前記と同じ。）で表される光学活性水溶性ジアミン化合物が得られる。また、置換スルホニル基を導入していないジフェニルエチレンジアミンからは、上記一般式（２ｆ）で表される水溶性ジアミン化合物、好ましくは上記一般式（２ｇ）で表される化合物が得られる。
反応終了後、必要に応じてアルカリ水溶液で中和する等は任意である。中和に用いられるアルカリ水溶液としては、水酸化ナトリウム水溶液、水酸化カリウム水溶液等が挙げられる。
得られた水溶性ジアミン化合物、好ましくは光学活性水溶性ジアミン化合物は、反応後、必要に応じて後処理、精製等を行ってもよい。後処理の具体的な方法等は上記した通りである。 2) Sulfonation N-mono or di (substituted sulfonyl) -diphenylethylenediamine obtained in 1) above, preferably optically active N-mono or di (substituted sulfonyl) -diphenylethylenediamine, or diphenylethylenediamine, preferably optically active Sulfonation of diphenylethylenediamine can be easily performed by a method known per se, for example, using concentrated sulfuric acid or fuming sulfuric acid.
In the present invention, it is preferable to perform sulfonation after introducing a substituted sulfonyl group first.
That is, N-mono or di (substituted sulfonyl) -diphenylethylenediamine obtained in 1) above, preferably optically active N-mono or di (substituted sulfonyl) -diphenylethylenediamine, or diphenylethylenediamine, preferably optically active diphenylethylenediamine. From diphenylethylenediamine introduced with a substituted sulfonyl group by sulfonation in a mixed solution of fuming sulfuric acid (30% SO ₃ —H ₂ SO ₄ ) -concentrated sulfuric acid, from the general formula (2d)

(Wherein R ² , R ³ , R ^{5 to} R ⁸ and R ^{10 to} R ¹⁴ are the same as above), preferably an optical activity represented by the above general formula (2e) A water-soluble diamine compound is obtained, or in the general formula (2), R ¹ and R ² are hydrogen atoms.

(Wherein R ³ , R ^{5 to} R ⁸ , R ^{10 to} R ¹² and R ¹⁴ are the same as described above), preferably R ¹ and R ² in the general formula (2a). Is a hydrogen atom (2g)

(Wherein R ³ , R ^{5 to} R ⁸ , R ^{10 to} R ¹² , R ¹⁴ and * are the same as described above). Moreover, from the diphenylethylenediamine which has not introduce | transduced the substituted sulfonyl group, the water-soluble diamine compound represented by the said general formula (2f), Preferably the compound represented by the said general formula (2g) is obtained.
After completion of the reaction, neutralization with an aqueous alkali solution is optional as required. Examples of the alkaline aqueous solution used for neutralization include a sodium hydroxide aqueous solution and a potassium hydroxide aqueous solution.
The obtained water-soluble diamine compound, preferably the optically active water-soluble diamine compound, may be subjected to post-treatment, purification, or the like as necessary after the reaction. The specific method of post-processing is as described above.

3) Sulfamidation (in the case of a water-soluble diamine compound in which a substituted sulfonyl group is not introduced at the N position)
The sulfamidation can be performed by a method known per se, such as the method described in 1) above.
For example, the water-soluble diamine compound represented by the general formula (2f) obtained in 2) above, preferably the optically active water-soluble diamine compound represented by the general formula (2g) and the sulfonylating agent, If necessary, by reacting in an appropriate solvent in the presence of the base as described above, the water-soluble diamine compound represented by the general formula (2d), preferably the optical activity represented by the general formula (2e). A water-soluble diamine compound is obtained.

The usage-amount of a sulfonylating agent is suitably selected from the range of 0.8-5 mol normally with respect to 1 mol of water-soluble diamine compounds, Preferably it is 1-2 mol, More preferably, it is 1-1.2 mol.
The usage-amount of a base is suitably selected from the range of 2-5 equivalent normally with respect to a water-soluble diamine compound, Preferably it is 2-2.5 equivalent.
Examples of the solvent include the solvents exemplified in the above (1), preferably amides such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide and the like. These solvents may be used alone or in appropriate combination of two or more. Among these solvents, N, N-dimethylformamide is a water-soluble diamine compound represented by the above general formula (2d) as a reaction substrate, preferably an optically active water-soluble diamine represented by the above general formula (2e). This is preferred because it dissolves the compound.
The usage-amount of a solvent is suitably selected from the range of 5-30 times capacity normally with respect to a water-soluble diamine compound, Preferably it is 10-20 times capacity.

The reaction temperature is appropriately selected from the range of usually 0 to 40 ° C, preferably 0 to 10 ° C.
The reaction time is appropriately selected from the range of usually 2 to 10 hours, preferably 3 to 5 hours.
The obtained water-soluble diamine compound represented by the above general formula (2d), preferably the optically active water-soluble diamine compound represented by the above general formula (2e) is subjected to post-treatment, purification, etc. as necessary after the reaction. May be performed. The specific method of post-processing is as described above.

The water-soluble diamine compound represented by the general formula (2d) thus obtained is useful as a ligand or the like constituting the transition metal complex, and in particular, the optical compound represented by the general formula (2e). The active water-soluble diamine compound is useful as a ligand constituting the transition metal complex used in the asymmetric synthesis, an optical resolution agent, and the like.
The water-soluble transition metal-diamine complex represented by the general formula (1) of the present invention, preferably the optically active water-soluble transition metal-diamine complex represented by the general formula (1a) is described in Non-Patent Document 7 and the like. For example, it can be produced as follows.
That is, a water-soluble diamine compound represented by the general formula (2), preferably a water-soluble diamine compound represented by the general formula (2a) and a transition metal compound represented by the general formula (3), for example. It can be obtained by reacting according to a conventional method. Moreover, in the said General formula (3), when using the transition metal compound whose n is 0, it obtains by making the said water-soluble diamine compound, the said transition metal compound, and a neutral ligand react according to a conventional method. be able to. Here, the transition metal compound in which n in the general formula (3) is 0 may be a hydrate.

The amount of the transition metal compound represented by the general formula (3) is usually 0.1 to 1.0 equivalent, preferably 0.2 to 0.5 equivalent, based on the water-soluble diamine compound. Selected.
The production of the water-soluble transition metal-diamine complex is preferably performed in the presence of a solvent. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene, xylene, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, o-dichlorobenzene, methanol, ethanol, 2 Examples include alcohols such as -propanol, n-butanol, 2-ethoxyethanol, and benzyl alcohol. These solvents may be used alone or in appropriate combination of two or more.
The usage-amount of a solvent is suitably selected from the range of 10-40 times capacity normally with respect to a water-soluble diamine compound, Preferably it is 10-20 times capacity.

The water-soluble transition metal-diamine complex can be produced in the presence of a base as necessary. As the base, an organic base is preferable, and specifically, triethylamine, diisopropylethylamine, N, N-dimethylaniline, piperidine, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.3.0] non- Organic amines such as 5-ene, 1,8-diazabicyclo [5.4.0] undec-7-ene, tri-n-butylamine, tetramethylethylenediamine, N-methylmorpholine, potassium methoxide, sodium methoxide, Alkali / alkali earth metal alkoxides such as lithium methoxide, sodium ethoxide, potassium isopropoxide, potassium tert-butoxide, lithium methoxide, potassium naphthalenide and the like can be mentioned.
The usage-amount of a base is suitably selected from the range of 0.5-5 equivalent normally with respect to a water-soluble diamine compound, Preferably it is 1-3 equivalent.

The reaction temperature is not particularly limited because it varies depending on the type of water-soluble diamine compound, transition metal compound, and the like, but it is usually appropriately selected from the range of 0 to 100 ° C, preferably 20 to 80 ° C.
The reaction time is not particularly limited because it naturally varies depending on the reaction temperature, the type of the water-soluble diamine compound, the transition metal compound, and the like, but is usually appropriately selected from the range of 1 to 24 hours, preferably 1 to 8 hours.

  The water-soluble transition metal-diamine complex represented by the above general formula (1) of the present invention thus obtained is useful as a catalyst for organic synthesis reaction and the like, and particularly represented by the above general formula (1a). The optically active water-soluble transition metal-diamine complex is useful, for example, as a catalyst for asymmetric synthesis, especially as an asymmetric hydrogenation catalyst.

（上記式中、Ｒ^１〜Ｒ^１２、Ｍ、Ｘ、Ｌ及び＊は前記と同じ。） In the water-soluble transition metal-diamine complex represented by the above general formula (1a) of the present invention, for example, as described in Non-Patent Document 6 or 7, the water solubility represented by the above general formula (1a). When the transition metal-diamine complex is used as an asymmetric hydrogenation catalyst, for example, the water-soluble transition metal-diamine complex is represented by the following general formula (1-1) in the asymmetric hydrogenation reaction. A diamine-hydride complex, preferably an optically active water-soluble transition metal-diamine-hydride complex represented by the following general formula (1a-1). In addition, after completion of the asymmetric hydrogenation reaction, the water-soluble transition metal-diamine complex is a water-soluble transition metal-amide complex represented by the following general formula (1-2), preferably the following general formula (1a-2). It is an optically active water-soluble transition metal-amide complex represented by: These water-soluble transition metal-diamine-hydride complexes and water-soluble transition metal-amide complexes are also included in the category of the water-soluble transition metal-diamine complex of the present invention.

(In the above formula, R ^{1 to} R ¹² , M, X, L and * are the same as above.)

Next, the manufacturing method of the optically active alcohol of this invention is demonstrated.
In the general formulas (4) and (5), the hydrocarbon group which may have a substituent represented by R ²¹ and R ²² represents a hydrocarbon group and a substituted hydrocarbon group, and has a substituent. The preferable heterocyclic group represents a heterocyclic group and a substituted heterocyclic group. A hydrocarbon group and a heterocyclic group are the same as each group demonstrated in the said General formula (1).
Examples of the substituted hydrocarbon group (hydrocarbon group having a substituent) include hydrocarbon groups in which at least one hydrogen atom of the hydrocarbon group is substituted with a substituent. Examples of the substituted hydrocarbon group include a substituted alkyl group, a substituted aryl group, a substituted alkenyl group, a substituted alkynyl group, and a substituted aralkyl group.
Examples of the substituted heterocyclic group (heterocyclic group having a substituent) include heterocyclic groups in which at least one hydrogen atom of the heterocyclic group is substituted with a substituent. Examples of the substituted heterocyclic group include a substituted aliphatic heterocyclic group and a substituted aromatic heterocyclic group.

  Substituents for substituted hydrocarbon groups and substituted heterocyclic groups include hydrocarbon groups, heterocyclic groups, alkoxy groups, aryloxy groups, aralkyloxy groups, alkoxycarbonyl groups, aryloxycarbonyl groups, aralkyloxycarbonyl groups, acyl groups. , Acyloxy group, alkylthio group, aralkylthio group, arylthio group, halogen atom, halogenated hydrocarbon group, alkylenedioxy group, amino group, substituted amino group, cyano group, nitro group, hydroxy group, carboxy group, sulfo group, A sulfonyl group, a substituted silyl group, etc. are mentioned.

  The hydrocarbon group and heterocyclic group as a substituent are the same as each group demonstrated in the said General formula (1). The halogen atom, halogenated hydrocarbon group, alkoxy group, aryloxy group, aralkyloxy group and substituted amino group are the same as the groups described as substituents in the above general formula (1). The acyl group, alkoxycarbonyl group, aryloxycarbonyl group, aralkyloxycarbonyl group and sulfonyl group are the same as the groups described as substituents of the amino group in the substituted amino group as the substituent in the general formula (1). is there.

Examples of the acyloxy group as a substituent include an acyloxy group having 2 to 18 carbon atoms derived from a carboxylic acid such as an aliphatic carboxylic acid and an aromatic carboxylic acid. Specific examples include, for example, an acetoxy group and a propionyloxy group. , Butyryloxy group, pivaloyloxy group, pentanoyloxy group, hexanoyloxy group, lauroyloxy group, stearoyloxy group, benzoyloxy group and the like.
The alkylthio group may be linear, branched or cyclic, and examples thereof include an alkylthio group having 1 to 6 carbon atoms. Specific examples include, for example, a methylthio group, an ethylthio group, an n-propylthio group, a 2- Examples thereof include a propylthio group, an n-butylthio group, a 2-butylthio group, an isobutylthio group, a tert-butylthio group, a pentylthio group, a hexylthio group, and a cyclohexylthio group.
Examples of the arylthio group include an arylthio group having 6 to 14 carbon atoms, and specific examples include a phenylthio group and a naphthylthio group.
As an aralkylthio group, a C7-C15 aralkylthio group is mentioned, for example, As a specific example, a benzylthio group, 2-phenethylthio group, etc. are mentioned, for example.
When the substituent is an alkylenedioxy group, for example, two adjacent hydrogen atoms of the aromatic ring in the aryl group or aralkyl group are substituted with an alkylenedioxy group. Examples of the alkylenedioxy group include an alkylenedioxy group having 1 to 3 carbon atoms. Specific examples thereof include a methylenedioxy group, an ethylenedioxy group, a trimethylenedioxy group, and a propylenedioxy group. Can be mentioned.
Examples of the substituted silyl group include a tri-substituted silyl group in which three hydrogen atoms of the silyl group are substituted with a substituent such as a hydrocarbon group such as an alkyl group, an aryl group, and an aralkyl group described above. Specific examples include a trimethylsilyl group, a tert-butyldimethylsilyl group, a tert-butyldiphenylsilyl group, and a triphenylsilyl group.
These substituents may be further substituted with the above substituents.

In the general formula (4), when R ²¹ and R ²² are bonded to each other to form a ring together with the carbon atom of the carbonyl group, the ring may be monocyclic, polycyclic, condensed Any of a ring may be sufficient, for example, a 4-8 membered ring etc. are mentioned. Moreover, in the carbon chain which comprises a ring, you may have -O-, -NH-, etc. Specific examples of the ring in the case where R ²¹ and R ²² are bonded to each other to form a ring together with a carbonyl group include a cyclopentanone ring, a cyclohexanone ring, such as a 5- to 7-membered lactone ring, such as 5-7 membered lactam ring etc. are mentioned. The ring to be formed may be any ring as long as the carbon atom of the carbonyl group in the general formula (4) can become an asymmetric carbon by an asymmetric hydrogenation reaction.

The ketone represented by the general formula (4) may be a prochiral ketone. Specific examples of the ketones represented by the general formula (4) include, for example, methyl ethyl ketone, acetophenone, benzalacetone, 1-indanone, 3,4-dihydro- (2H) -naphthalenone ferrocenyl methyl ketone, and the like. Examples thereof include the compounds shown below.

  Specific examples of the optically active alcohol represented by the general formula (5) obtained by the production method of the present invention include 2-butanol and phenethyl alcohol.

The method for producing the optically active secondary alcohol of the present invention, that is, the asymmetric hydrogenation reaction of the ketone represented by the general formula (4) can be carried out by a method known per se, and the asymmetric according to the present invention. It is carried out in the presence of a synthesis catalyst.
As the asymmetric synthesis catalyst according to the present invention, the asymmetric synthesis catalyst comprising the optically active water-soluble transition metal-diamine complex represented by the general formula (1a) produced as described above, and / or the above An asymmetric synthesis catalyst comprising the optically active water-soluble diamine compound represented by the general formula (2c) and the transition metal compound represented by the general formula (3) can be mentioned.
The asymmetric hydrogenation reaction using the latter asymmetric synthesis catalyst is a so-called in situ reaction.

When the asymmetric hydrogenation reaction is performed using the optically active water-soluble transition metal-diamine complex represented by the above general formula (1a), it can be performed, for example, by the method described in Non-Patent Document 7.
Further, asymmetric hydrogen is generated in situ using an asymmetric synthesis catalyst comprising the optically active water-soluble diamine compound represented by the general formula (2c) and the transition metal compound represented by the general formula (3). For example, the method described in Non-Patent Document 3 can be used.
When the asymmetric hydrogenation reaction is performed in situ, a reaction mixture heated and stirred for 1 to several hours in advance may be used.
The amount of the asymmetric synthesis catalyst used is appropriately selected from the range of usually 10 ^-1 to 10 ^-4 equivalents, preferably 10 ^-2 to 10 ^-3 equivalents, relative to the ketones.

The method for producing an optically active secondary alcohol of the present invention, that is, the asymmetric hydrogenation reaction of the ketones represented by the general formula (4) is performed by a hydrogen transfer reaction.
In the asymmetric hydrogenation reaction by hydrogen transfer reaction, it is preferable that a hydrogen donating substance is present in the reaction system. The hydrogen-donating substance is an organic compound and / or an inorganic compound, and any compound can be used as long as it can donate hydrogen in the reaction system by, for example, thermal action or catalytic action.
Examples of the hydrogen donating substance include formic acid or a salt thereof, a combination of formic acid and a base, hydroquinone, phosphorous acid, alcohols and the like. Among these, formic acid or a salt thereof, a combination of formic acid and a base, alcohols and the like are particularly preferable.

Examples of formic acid salts in formic acid or salts thereof include formic acid metal salts such as alkali metal salts and alkaline earth metal salts of formic acid, ammonium salts, and substituted amine salts.
Any formic acid salt form or substantially formic acid salt form may be used in the combined reaction system of formic acid and base.
Examples of the alkali metal that forms a salt with formic acid include lithium, sodium, potassium, rubidium, and cesium. Examples of the alkaline earth metal include magnesium, calcium, strontium, barium and the like.
Bases for forming formic acid metal salts such as alkali metal salts and alkaline earth metal salts of these formic acids, ammonium salts, substituted amine salts, etc., and bases in a combination of formic acid and bases include ammonia, inorganic bases, An organic base etc. are mentioned.
Examples of the inorganic base include potassium carbonate, potassium hydroxide, lithium hydroxide, sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydroxide, magnesium carbonate, calcium carbonate and other alkali or alkaline earth metal salts, hydrogenated Examples thereof include metal hydrides such as sodium, sodium borohydride, lithium aluminum hydride and the like.
Examples of the organic base include alkali metal alkoxides such as potassium methoxide, sodium methoxide, lithium methoxide, sodium ethoxide, potassium isopropoxide, potassium tert-butoxide, potassium naphthalenide, sodium acetate, potassium acetate, acetic acid. Alkali / alkaline earth metal salts such as magnesium and calcium acetate, triethylamine, diisopropylethylamine, N, N-dimethylaniline, piperidine, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.3.0] nona Organic amines such as -5-ene, 1,8-diazabicyclo [5.4.0] undec-7-ene, tri-n-butylamine, N-methylmorpholine, methylmagnesium bromide, ethylmagnesium bromide, odor Propyl Magnesium, methyl lithium, ethyl lithium, propyl lithium, n- butyl lithium, organic metal compounds such as tert- butyl lithium, and the like quaternary ammonium salts.

  As the alcohol as a hydrogen-donating substance, lower alcohols having a hydrogen atom at the α-position are preferable. Specific examples include methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol and the like. Among them, isopropanol is preferable.

In the method for producing an optically active secondary alcohol of the present invention, the hydrogen-donating substance to be used is preferably water-soluble because the asymmetric hydrogenation reaction is carried out with an aqueous solvent described later as a solvent. In view of economics, formic acid alkali metal salts, alkaline earth metal salts, ammonium salts, substituted amine salts and the like can be mentioned.
The amount of the hydrogen-donating substance used is appropriately selected from the range of usually 2 to 20 equivalents, preferably 4 to 10 equivalents, with respect to the ketones. After the reaction, when the product is separated and the remaining aqueous phase is reused, the hydrogen source formate consumed in the reaction may be replenished.

The method for producing an optically active secondary alcohol of the present invention is preferably performed using water as a solvent. By reacting with an aqueous solvent, the aqueous phase containing the produced secondary alcohol and the water-soluble transition metal-amide complex can be easily separated, and the aqueous phase containing the separated water-soluble transition metal-amide complex can be separated. It can be used repeatedly, that is, recycled (reused).
The amount of water used is selected in consideration of the type, solubility, economy, etc. of the ketones that are the reaction substrate, but is usually 5 to 50 times by mass, preferably 10 to 40 times by mass with respect to the substrate. It is selected appropriately.

In the method for producing an optically active secondary alcohol of the present invention, water and an organic solvent may be used in combination according to the type of ketones used.
Examples of the organic solvent used include aromatic hydrocarbons such as benzene, toluene and xylene, aliphatic hydrocarbons such as pentane, hexane, heptane and octane, and halogens such as dichloromethane, chloroform, carbon tetrachloride and dichloroethane. Hydrocarbons such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, tetrahydrofuran, dioxane, dioxolane and the like such as methanol, ethanol, 2-propanol, n-butanol, tert-butanol, benzyl alcohol Alcohols such as ethylene glycol, propylene glycol, 1,2-propanediol, glycerin and other polyhydric alcohols such as N, N-dimethylformamide, N, N Amides such as dimethylacetamide, acetonitrile, N- methylpyrrolidone, dimethyl sulfoxide and the like. These solvents may be used alone or in appropriate combination of two or more.
The amount of the organic solvent used is appropriately selected from the range of usually 1 to 10 times, preferably 2 to 5 times the volume of the ketone used.

The reaction temperature is appropriately selected from the range of usually 15 to 100 ° C., preferably 20 to 80 ° C. in consideration of economy and the like, and it is usually desirable to carry out at a relatively low temperature.
While the reaction time naturally varies depending on the type and amount of the asymmetric hydrogenation catalyst used, the type and concentration of the ketone compound used, the reaction conditions such as the reaction temperature, etc., it may be from several minutes to several tens of hours, usually from 4 to 48. It is suitably selected from the time, preferably in the range of 6 to 24 hours.
The method for producing an optically active alcohol of the present invention can be carried out regardless of whether the reaction format is batch or continuous.

In the production method of the present invention, the aqueous solution of the asymmetric synthesis catalyst used in the previous asymmetric hydrogenation reaction can be recovered and used. That is, in the production method of the present invention, the asymmetric synthesis catalyst can be recycled (reused or reused).
Recovery of the asymmetric synthesis catalyst and its aqueous solution can be carried out by employing an operation usually performed from the reaction solution (reaction system).
That is, after completion of the hydrogenation reaction, if necessary, an organic solvent or water is added to the reaction solution to form two phases. If the aqueous phase is separated from the two-phase reaction solution, an aqueous solution of the asymmetric synthesis catalyst is recovered. can do.
The recovered aqueous solution of the asymmetric synthesis catalyst (the aqueous phase separated after the hydrogenation reaction) can be reused (recycled) for the asymmetric hydrogenation reaction of ketones without any post-treatment or purification. .
If necessary, the asymmetric synthesis catalyst can be easily recovered from the separated aqueous phase by an operation such as concentration.

  When the aqueous phase is separated after completion of the hydrogenation reaction, any organic solvent used as necessary can be used as long as it is phase-separated from water. Specific examples thereof include, for example, pentane, Aliphatic hydrocarbons such as hexane, heptane, octane, decane, cyclohexane, aromatic hydrocarbons such as benzene, toluene, xylene, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, Ethers such as tetrahydrofuran, 1,4-dioxane, 1,3-dioxolane, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, o-dichlorobenzene Etc. Gen hydrocarbons, methyl acetate, ethyl acetate, n- butyl, esters of methyl propionate and the like. These organic solvents may be used alone or in appropriate combination of two or more.

On the other hand, the isolated and recovered asymmetric catalyst can be reused for asymmetric hydrogenation of ketones after post-treatment and purification, etc., but is used for other asymmetric hydrogenation reactions. You can also
Recycled ketones in the hydrogenation reaction using the recovered asymmetric catalyst, that is, the aqueous phase containing the asymmetric synthesis catalyst recovered from the reaction solution (reaction system) and the isolated asymmetric synthesis catalyst. When using (recycling), it is optional to adjust the amount of the asymmetric synthesis catalyst as appropriate, such as adding a new asymmetric synthesis catalyst as necessary.
The optically active secondary alcohol thus obtained is useful as a pharmaceutical intermediate or a liquid crystal material.

EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited at all by these Examples.
In the following examples, the apparatus used for measuring physical properties is as follows.
1) Gas chromatography (GLC):
Column TC-WAX, L30m × 0.25mm
Column Chiraldex G-PN, L30m x ID 0.25mm
2) Specific optical rotation: JASCO JSCO DIP-360 type optical rotation meter 3) ¹ H-NMR, ¹² C-NMR: Model number DRX-500, manufactured by BURUKER 5) HPLC: Column Hypersil SAS (Cl) 5 μm, L = 250mm

Synthesis of (1R, 2R) -diphenylethylene-1,2-diamine monobenzenesulfamide (1R, 2R) -diphenylethylene-1,2-diamine 2.5 g (14.2 mmol), triethylamine 1.72 g (17 mmol) ) And 10 ml of methylene chloride were added dropwise over 2 hours while maintaining a 5 ml solution of 3 g (14.1 mmol) of benzenesulfonyl chloride in 10 ml of methylene chloride under a nitrogen atmosphere. The cooling bath was removed and the reaction was further stirred for 3 hours, and then allowed to stand overnight. The solvent was recovered to obtain 5.82 g of crude (1R, 2R) -diphenylethylene-1,2-diamine monobenzenesulfamide as a solid. This was ground in 40 ml of ethyl acetate, and insoluble matters were removed by filtration. Insoluble matter dry weight 1.38 g. In silica gel TLC (ethyl acetate), three spots of the raw material (origin) and (1R, 2R) -diphenylethylene-1,2-diamine monosulfamide and disulfamide were observed.
The ethyl acetate solution of (1R, 2R) -diphenylethylene-1,2-diamine monobenzenesulfamide as the filtrate was purified by silica gel chromatography (ethyl acetate). Thus, 2.76 g (white powder) of purified (1R, 2R) -diphenylethylene-1,2-diamine monobenzenesulfamide was obtained. Yield: 55.5%. (HPLC: 98.3%)
¹ H-NMR (MeOH) δ: 3.99 (1 H, d, 8.8 Hz), 4.41 (1 H, d, 8.8 Hz), 6.7 (2 H, d, 7.5 Hz), 6. 9 (3H, m), 7.08 (5H, m), 7.2 (2H, t, 7.5Hz), 7.33 (1H, t, 7.5Hz), 7.49 (2H, d, 8.1 Hz) ppm.
¹² C-NMR (MeOH) δ: 62.3, 66.7, 127.8, 127.9, 128, 128.4, 128.5, 128.6, 128.7, 128.8, 129.2 129.6, 133, 139.7, 142 ppm.

Synthesis of (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine.
The reaction was performed using a 50 ml reaction vessel purged with nitrogen. To a mixed solution of 11.1 g (113.57 mmol) of concentrated sulfuric acid cooled to 0 ° C. and 22.8 g of 30% fuming sulfuric acid (30% SO ₃ —H ₂ SO ₄ ) (SO ₃ = 85.5 mmol), (1R , 2R) -diphenylethylene-1,2-diamine monobenzenesulfamide 1.59 g (4.54 mmol) was added in about 5 minutes. After stirring at 5 ° C. or lower for 6 hours, the cooling bath was removed and the mixture was allowed to stand for 4 days. The reaction solution was carefully quenched into 500 g of crushed ice, then neutralized with 50% aqueous sodium hydroxide and made alkaline. This aqueous solution was concentrated by distillation to obtain 80.8 g of a block-like white solid. In order to remove sodium sulfate in the concentrate, the block-shaped white solid was crushed, 150 ml of 10% aqueous methanol was added, and the mixture was heated to reflux for 30 minutes. This was filtered while hot to separate sodium sulfate (dry weight 79.5 g). The filtrate was concentrated under reduced pressure and then dried under high vacuum to give 4.24 g of solid. This solid was heated and refluxed again in 14.4 ml of 10% aqueous methanol for 30 minutes, cooled to room temperature, filtered, and the filtrate was concentrated and dried under high vacuum to obtain 2.2 g of an off-white solid.
¹ H-NMR confirmed that the off-white solid was (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine.
The analysis values are as follows.
[Α] _D ²⁰ = −80.2 (c = 1, H ₂ O).
¹ H-NMR (CD ₃ OD) δ: 4.37 (2H, s), 7.18 (2H, dt, 7.7 Hz, 1 to 3 Hz, protons at the 6th and 6 ′ positions of the phenyl group), 7 .32 (2H, t, 7.7 Hz, protons at the 5th and 5 'positions of the phenyl group), 7.65 to 7.68 (4H, m, the 2nd, 2' and 4th positions of the phenyl group 4'-position proton) ppm.
¹³ C-NMR (CD ₃ OD) δ: 59.8, 124.4, 126.1, 130, 131.2, 138.4, 143.5 ppm.
The structure of this solid product was determined as (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine by NMR spectrum (heavy water) and mass spectrum (ESI measurement method). It was done.
NMR: ¹³ C-NMR; signals at δ = 143.5, 138.4 ppm are the 3rd and 3 ′ position carbons of SO ₃ Na bonded, 3 ′ position carbon, 131.2, 130, 126.4 and 124. 4 ppm is attributed to benzene core carbon, and 59.9 ppm to 1,2-diaminoethylene carbon.
ESI mass spectrum (m / z); ESI +: 417 (M + 1), 439 (M + Na), 395 (M-Na) and 812, 834 and 856 derived from a cluster of two molecules. ESI-: 393 (M-23), 371 (M-2Na) and 765, 787 and 809 derived from a cluster of two molecules.
¹ H-NMR (500 MHz, D ₂ O, ppm, Hz): 4.37 (2H, s, protons at positions 1 and 2 of ethylene), 7.18 (2H, dt, 7.7 Hz, 1 to 3 Hz, 6 and 6 'protons of the phenyl group), 7.32 (2H, t, 7.7 Hz, 5 and 5' protons of the phenyl group). 7.63-7.68 (4H, m, protons at positions 2 and 2 ′ and positions 4 and 4 ′ of the phenyl group). The proton at the 2-position of the phenyl group (same as 2'-position) has substituents at the 1-position and 3-position, so the J value different from the protons at other positions, A small 0.9-2 Hz is observed. On the other hand, the J values of adjacent protons at positions 4 and 5, and positions 5 and 6 are 7.7 Hz, respectively.

(1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine and [RhCl ₂ (pentamethyl cycladiene)] ₂ (hereinafter abbreviated as [Cp * RhCl ₂ ] ₂ . Asymmetric hydrogen transfer reduction of acetophenone with ammonium formate
Under nitrogen atmosphere, (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine 4.4 mg (0.0105 mmol), [Cp * RhCl ₂ ] ₂ 2.57 mg (0 .0041 mmol), 0.2 g (1.66 mmol) of acetophenone, 0.42 g (6.7 mmol) of ammonium formate and 4 ml of water were stirred and reacted at 80 ° C. for 20 hours. The organic layer was extracted with diisopropyl ether, dehydrated with anhydrous magnesium sulfate, and concentrated to obtain crude optically active (1R) -phenethyl alcohol. GC: conversion 99.3%, selectivity 99.8%. Asymmetric yield 60.2% ee.

Asymmetric hydrogen transfer reduction metal complex of acetophenone using (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine, [Cp * IrCl ₂ ] ₂ and ammonium formate [ The asymmetric hydrogen transfer reduction of acetophenone was carried out in the same manner as in Example 3 except that IrCl ₂ (pentamethyl cyclopentadiene)] ₂ (hereinafter abbreviated as [Cp * IrCl ₂ ] ₂ ) was used and the reaction time was 18 hours. The crude optically active (1R) -phenethyl alcohol was obtained. GC: Conversion 73.4%, selectivity 99.8%. Asymmetric yield 58% ee.

Asymmetric hydrogen transfer reduction of acetophenone using (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine, [Cp * RhCl ₂ ] ₂ and sodium formate under a nitrogen atmosphere, (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine 6.5 mg (1.66 mmol) [Cp * RhCl ₂ ] ₂ 5.13 mg (0.0082 mmol), acetophenone A solution consisting of 0.2 g (1.66 mmol), sodium formate 0.46 g (6.7 mmol) and water 4 ml was stirred and reacted at 50 ° C. for 3 hours. The organic layer was extracted with diisopropyl ether, dehydrated with anhydrous magnesium sulfate, and concentrated to obtain crude optically active (1R) -phenethyl alcohol. GC: conversion 98.8%, selectivity 99.4%. Asymmetric yield 64.9% ee.

Asymmetric hydrogen transfer reduced metal complex of acetophenone using (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine, [Cp * IrCl ₂ ] ₂ and sodium formate [Cp * using IrCl _{2] 2,} all except that the reaction time was 22 hours in example 5 and the same way acetophenone asymmetric hydrogen transfer reduction was carried out crude optically active (1R) - was obtained phenethyl alcohol. GC: conversion 94.4%, selectivity 99.8%. Asymmetric yield 68.2% ee.

Synthesis of (1R, 2R) -di (3,3′ -sodiumoxysulfonylphenyl) ethylene-1,2-diamine benzenesulfamide (1R, 2R) -di (3,3′-sodium under nitrogen atmosphere A solution consisting of 0.5 g (1.2 mmol) of oxysulfonylphenyl) ethylene-1,2-diamine, 0.242 g (2.4 mmol) of triethylamine and 10 ml of DMF was cooled to 5 ° C. or lower. To this solution, 2.5 ml of a DMF solution of 0.2545 g (1.44 mmol) of benzenesulfonyl chloride was added dropwise over 3 hours while maintaining at 5 ° C. or lower. The mixture was further stirred and reacted at the same temperature for 2.5 hours, and then allowed to stand overnight. DMF in the reaction solution was recovered by distillation to obtain 0.75 g of crude (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine benzenesulfamide.
HPLC composition of product: (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine monobenzenesulfamide 52.8%, dibenzenesulfamide 5.5 %, Unreacted (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine 1.8%.

Asymmetric hydrogen transfer reduction of acetophenone using crude (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine benzenesulfamide and [Cp * RhCl ₂ ] ₂ Crude (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine benzenesulfamide 7.5 mg (0.0166 mmol), [Cp * RhCl ₂ ] ₂ 47 mg (0.0083 mmol), 0.2 g (1.66 mmol) of acetophenone, 4 ml of water, and 0.92 g (13.4 mmol) of sodium formate were mixed and stirred at 80 ° C. for 17 hours for reaction. The product was extracted with diisopropyl alcohol, dehydrated with anhydrous magnesium sulfate and concentrated to obtain crude (1R) -phenethyl alcohol. GC: conversion 99.3%, selectivity 99.9%. Asymmetric yield 52.9% ee.

Asymmetric of acetophenone using crude (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine benzenesulfamide and [RuI ₂ (p-cymene)] ₂ Hydrogen transfer reduction Crude (1R, 2R) -di (3,3′-sodiumoxysulfonylphenyl) ethylene-1,2-diamine in benzenesulfamide 7.5 mg (0.0166 mmol), [RuI ₂ (p- cymene)] ₂ 4.1 mg (0.0083 mmol), acetophenone 0.2 g (1.66 mmol), and 4 ml of water were stirred and reacted at 50 ° C. for 1.5 hours, and then sodium formate 0.92 g (13 .4 mmol) was added and the mixture was stirred and reacted at the same temperature for 6 hours. The product was extracted with n-hexane, dehydrated with anhydrous magnesium sulfate, and then concentrated to obtain crude (1S) -phenethyl alcohol. GC: conversion 95.8%, selectivity 99.8%. Asymmetric yield 91.7% ee.

Reusing (recycling) asymmetric synthesis catalysts used in asymmetric hydrogenation reactions
In Example 8, after the reaction, 0.2 g (1.66 mmol) of acetophenone was added to the aqueous phase after extracting the product with diisopropyl alcohol, and the mixture was stirred and reacted at 80 ° C. for 12 hours. After the reaction, the same treatment as in Example 8 was performed to obtain crude (1R) -phenethyl alcohol. Conversion 95.6%, selectivity 99.8%. Asymmetric yield 91.7% ee.

  The optically active water-soluble transition metal-diamine complex of the present invention is useful as a catalyst for various organic synthesis reactions, particularly hydrogen transfer asymmetric reduction reaction, and is useful as a pharmaceutical intermediate or liquid crystal material. Can be used effectively in the manufacture of In addition, since the complex catalyst of the present invention can be recycled, the cost can be reduced, and since the asymmetric hydrogenation reaction can be performed in an aqueous solvent, an asymmetric hydrogenation reaction in consideration of the environment is possible. It is extremely important to contribute to this business.

Claims (14)

The following general formula (1)

[In the formula, ^{R 1} and ^{R 2} each independently represent a hydrogen source Komata is _-SO 2 ^{R 13 (where, R 13} represents a phenyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms R ³ , R ^{5 to} R ⁸ and R ^{10 to} R ¹² represent a hydrogen atom, R ⁴ and R ⁹ represent —SO ₃ R ¹⁴ (wherein R ¹⁴ represents a hydrogen atom or an alkali metal atom). M) represents a ruthenium, rhodium or iridium atom , X represents a halogen atom, L represents benzene, mesitylene, p-cymene, hexamethylbenzene, pentamethylcyclopentadiene, 1,5-cyclooctadiene or Indicates norbornadiene . ] The water-soluble transition metal-diamine complex represented by this.   The water-soluble transition metal-diamine complex according to claim 1, wherein M is rhodium and L is pentamethylcyclopentadiene in the general formula (1).   The water-soluble transition metal-diamine complex according to claim 1 or 2, which is an optically active substance. General formula (2)

[In the formula, ^{R 1} and ^{R 2} each independently represent a hydrogen source Komata is _-SO 2 ^{R 13 (where, R 13} represents a phenyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms R ³ , R ^{5 to} R ⁸ and R ^{10 to} R ¹² represent a hydrogen atom, R ⁴ and R ⁹ represent —SO ₃ R ¹⁴ (wherein R ¹⁴ represents a hydrogen atom or an alkali metal atom). .) showing the. And a water-soluble diamine compound represented by the general formula (3)
[MX _m L _n ] _p (3)
(In the formula, M represents a ruthenium, rhodium or iridium atom , X represents a halogen atom, L represents benzene, mesitylene, p-cymene, hexamethylbenzene, pentamethylcyclopentadiene, 1,5-cyclooctadiene or norbornadiene. Wherein m represents 2 or 3, n represents 0 or 1, and p represents 1 or 2.), a transition metal compound represented by the following formula: Of water-soluble transition metal-diamine complex.   The production method according to claim 4, wherein, in the general formula (3), M is rhodium and L is pentamethylcyclopentadiene. Water-soluble diamine compound represented by the general formula (2) is an optically active water-soluble diamine compound, resulting soluble transition metal - diamine complex is optically active water-soluble transition metal - a diamine complex according to claim 4 Or the manufacturing method of 5 . General formula (2b)

[In the formula, ^{R 1} and ^{R 2} each independently represent a hydrogen source Komata is _-SO 2 ^{R 13 (where, R 13} represents a phenyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms .) ^indicates, R ^3, R 5 ~R ⁸ and ^R 10 ^{to R 12} represents a water MotoHara ^{child, R 14} represents a hydrogen atom or an alkali metal atom. ] The water-soluble diamine compound represented by this. The water-soluble diamine compound according to claim 7 , which is an optically active substance.   An asymmetric synthesis catalyst comprising the optically active water-soluble transition metal-diamine complex according to claim 3. The optically active water-soluble diamine compound according to claim 8 and the general formula (3)
[MX _m L _n ] _p (3)
(In the formula, M represents a ruthenium, rhodium or iridium atom , X represents a halogen atom, L represents benzene, mesitylene, p-cymene, hexamethylbenzene, pentamethylcyclopentadiene, 1,5-cyclooctadiene or norbornadiene. Wherein m represents 2 or 3, n represents 0 or 1, and p represents 1 or 2.).   The asymmetric synthesis catalyst according to claim 10, wherein, in the general formula (3), M is rhodium and L is pentamethylcyclopentadiene. General formula (4)

[Wherein, R ²¹ and R ²² each independently represents a hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a ferrocenyl group (provided that R ²¹ And R ²² are not the same). R ²¹ and R ²² may be bonded to each other to form a ring together with the carbon atom of the carbonyl group. In the presence of the asymmetric synthesis catalyst according to claim 9 and / or the asymmetric synthesis catalyst according to claim 10 in the absence of a surfactant and a phase transfer catalyst. In which the asymmetric hydrogenation reaction is carried out, the general formula (5)

(Wherein, * represents an asymmetric carbon, and R ²¹ and R ²² are the same as described above). The manufacturing method of Claim 12 which recycles the asymmetric synthesis catalyst after use. In the production method according to claim 12, after the completion of the hydrogenation reaction is carried out the hydrogenation reaction with an aqueous solution containing an asymmetric synthesis catalyst obtained reaction solution was separated, the manufacturing method according to claim 13 .