JP2008201760A - Optically active spiro compound and its production method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an optically active spiro compound which can be simply and easily produced with no use of a route through an optical resolution process which has conventionally been almost essential. <P>SOLUTION: This compound is represented by general formula (1) (wherein R<SP>1</SP>and R<SP>2</SP>may be the same or different and are each a hydrogen atom, an alkyl, cycloalkyl, aryl, halogen or haloalkyl group; Z<SP>1</SP>and Z<SP>2</SP>may be the same or different and are each a divalent hydrocarbon group; and Z<SP>3</SP>and Z<SP>4</SP>may be the same or different and are each a divalent group). <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a spiro compound useful as a ligand of a functional metal complex, an optically active substance thereof, and a production method thereof.

Conventionally, many reports have been made on transition metal complexes that can be used as catalysts for asymmetric reactions such as asymmetric hydrogenation, asymmetric isomerization, and asymmetric hydrosilylation. Among them, complexes in which an optically active compound is coordinated to a transition metal such as ruthenium, rhodium, iridium, and palladium are widely known as having excellent performance as a catalyst for asymmetric synthesis reaction. As an optically active ligand in such complexes, therefore C ₂ symmetric optically active spiro compound having heteroatoms in the structure which can form many metal chelate complexes, would be useful as a ligand for asymmetric reactions It is done.

  Examples of spiro compounds as ligands synthesized so far include, for example, spirophosphinite compounds (Non-Patent Document 1), spirophosphine compounds (Non-Patent Document 2), spirobisisoxazoline compounds (Non-Patent Document 3), and the like. Examples have been reported. However, the synthesis of these compounds requires complicated operations. In addition, in order to obtain the optically active substance, it is necessary to resolve the diastereomer or racemate of the compound itself or a compound that is a synthetic intermediate thereof.

  An example of using a cobalt catalyst as an example of catalytic synthesis of a spiro compound is given, but the yield is 33% at the maximum, which is not efficient (Non-patent Document 4). Examples of enantioselective synthesis of spiro compounds include an example of utilizing an intramolecular C—H insertion reaction using a rhodium catalyst, but the product yield and optical purity are not sufficient. (Non-patent document 5).

Teterahedron: Asymmetry, 9, 3185 (1998) Angew. Chem. Int. Ed. , 44, 1118 (2005) Org. Lett. , 1, 1795 (1999) Org. Lett. , 1, 2141 (1999) Chem. Comm. , 1604 (2001)

Since the catalyst for the asymmetric synthesis reaction as described above is required to have diversity depending on the purpose of the reaction, the development of ligands having various structures is still continued. Moreover, it not synthesized only in C ₂ symmetric optically active spiro compound, as described above is limited way. Therefore, if a spiro compound having an axially asymmetric structure with high optical purity can be synthesized using a substrate that is relatively easy to obtain, with a small number of steps, the optical resolution step, which was almost essential in the conventional method, can be performed. Without passing, an axially asymmetric spiro compound is obtained. It is an object of the present invention to provide such a production method and to provide a novel spiro compound that can be produced as such.

As a result of repeated studies on the synthesis of a compound having a C ₂ symmetry axis, the present inventors have made a spirobipyridine by intramolecular [2 + 2 + 2] cyclization reaction of a tetrayne compound with a rhodium catalyst having an optically active ligand. The inventors have found that a spiro compound having a type structure can be obtained, and have completed the present invention.

（式（１）中、Ｒ^１及びＲ^２は同一または異なっていてもよく、水素原子、アルキル基、シクロアルキル基、アリール基、ハロゲン原子又はハロアルキル基を表す。Ｚ^１及びＺ^２は同一又は異なっていてもよく、二価の炭化水素基を表し、Ｚ^３及びＺ^４は同一又は異なっていてもよく二価基を表す。）
［２］ 下記一般式（１＊）で表される光学活性化合物。

（式（１＊）中、Ｒ^１及びＲ^２は同一または異なっていてもよく、水素原子、アルキル基、シクロアルキル基、アリール基、ハロゲン原子又はハロアルキル基を表す。Ｚ^１及びＺ^２は同一又は異なっていてもよく、二価の炭化水素基を表し、Ｚ^３及びＺ^４は同一又は異なっていてもよく二価基を表す。＊は不斉であることを表す。）
［３］ ロジウム金属と光学活性ビスホスフィンとを含む触媒を用いて、下記一般式（２）で表されるテトライン化合物を分子内［２＋２＋２］付加環化反応させる前項［２］に記載の化合物の製造方法。

（式（２）中、Ｒ^１及びＲ^２は同一または異なっていてもよく、水素原子、アルキル基、シクロアルキル基、アリール基、ハロゲン原子又はハロアルキル基を表す。Ｚ^１及びＺ^２は同一又は異なっていてもよく、二価の炭化水素基を表し、Ｚ^３及びＺ^４は同一又は異なっていてもよく二価基を表す。）
［４］ ロジウム金属と光学活性ビスホスフィンとを含む触媒が下記一般式（３）で表される化合物である前項［３］に記載の製造方法。
［Ｒｈ(Ｌ)_ｍ(Ｙ)_ｎ］Ｘ （３）
（式（３）中、Ｌは下記式（４）で表される光学活性ビスホスフィンを表し、Ｙは非共役ジエン化合物を表し、Ｘはカウンターアニオンを表す。また、ｍは１又は２の整数を表し、ｎは０又は１の整数を表す。但し、ｍ＝１のとき、ｎ＝０又はｎ＝１であり、ｍ＝２のときはｎ＝０である。）
Ｒ^３Ｒ^４Ｐ−Ｑ−ＰＲ^５Ｒ^６ （４）
（式（４）中、Ｒ^３、Ｒ^４、Ｒ^５及びＲ^６は、それぞれ独立して置換基を有していてもよいアリール基又は置換基を有していてもよいシクロアルキル基を表し、Ｒ^３とＲ^４とで及び／又はＲ^５とＲ^６とで環を形成してもよい。Ｑは置換基を有していてもよい二価のアリーレン基又はフェロセンジイル基を表す。）
［５］ ロジウム金属と光学活性ビスホスフィンとを含む触媒が、調製後即時使用されることを特徴とする前項［４］に記載の製造方法。
［６］ ロジウム金属と光学活性ビスホスフィンとを含む触媒を調製する際に、水素ガスを用いてオレフィン性配位子を脱離させることを特徴とする前項［４］又は［５］に記載の製造方法。 The present invention includes the following contents.
[1] A compound represented by the following general formula (1).

(In Formula (1), R ¹ and R ² may be the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a halogen atom or a haloalkyl group. Z ¹ and Z ² are the same or They may be different and represent a divalent hydrocarbon group, and Z ³ and Z ⁴ may be the same or different and represent a divalent group.)
[2] An optically active compound represented by the following general formula (1 *).

(In formula (1 *), R ¹ and R ² may be the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a halogen atom or a haloalkyl group. Z ¹ and Z ² are the same. Alternatively, they may be different and each represents a divalent hydrocarbon group, and Z ³ and Z ⁴ may be the same or different and each represents a divalent group.
[3] Using the catalyst containing rhodium metal and optically active bisphosphine, the tetrain compound represented by the following general formula (2) is subjected to intramolecular [2 + 2 + 2] cycloaddition reaction of the compound according to the above item [2] Production method.

(In Formula (2), R ¹ and R ² may be the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a halogen atom or a haloalkyl group. Z ¹ and Z ² are the same or They may be different and represent a divalent hydrocarbon group, and Z ³ and Z ⁴ may be the same or different and represent a divalent group.)
[4] The production method according to [3], wherein the catalyst containing rhodium metal and optically active bisphosphine is a compound represented by the following general formula (3).
[Rh (L) _m (Y) _n ] X (3)
(In formula (3), L represents an optically active bisphosphine represented by the following formula (4), Y represents a non-conjugated diene compound, X represents a counter anion, and m represents an integer of 1 or 2. N represents an integer of 0 or 1. However, when m = 1, n = 0 or n = 1, and when m = 2, n = 0.
^{R 3 R 4 P-Q-} PR 5 R 6 (4)
(In the formula (4), R ³ , R ⁴ , R ⁵ and R ⁶ each independently represent an aryl group which may have a substituent or a cycloalkyl group which may have a substituent. , R ³ and R ⁴ and / or R ⁵ and R ⁶ may form a ring, and Q represents a divalent arylene group or a ferrocenediyl group which may have a substituent.
[5] The production method according to [4], wherein the catalyst containing rhodium metal and optically active bisphosphine is used immediately after preparation.
[6] The method described in [4] or [5] above, wherein when preparing the catalyst containing rhodium metal and optically active bisphosphine, the olefinic ligand is eliminated using hydrogen gas. Production method.

  According to the method of the present invention, a tetrayne compound having two cyano groups is enantioselected in one step by subjecting a [2 + 2 + 2] cyclization reaction in the molecule in the presence of a catalyst containing rhodium metal and optically active bisphosphine. Since optically active spiro compounds can be produced, optically active spiro compounds can be easily produced using a substrate that is relatively easily available. You can get a body. The optically active spiro compound having a spirobipyridine structure obtained by the present invention can be easily produced, and is useful as a ligand of a functional metal complex or a metal catalyst for asymmetric synthesis.

Hereinafter, the present invention will be specifically described.
The spiro compound according to the present invention is a compound represented by the general formulas (1) and (1 *) described above, has a spirobipyridine structure, and is manufactured by the manufacturing method of the present invention described in detail later. Can do.

In the general formulas (1) and (1 *), R ¹ and R ² represent a hydrogen atom, an alkyl group, a cycloalkyl group, or an aryl group.
Here, the alkyl group represented by R ¹ and R ² is a linear or branched alkyl group having, for example, 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms. Groups. Specific examples include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, s-butyl group, isobutyl group, t-butyl group, pentyl group, and hexyl group. These alkyl groups may be substituted with an alkoxy group. Examples of the alkoxy group substituted on the alkyl group include an alkoxy group having 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms. Specific examples of the alkoxy group substituted for the alkyl group include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, s-butoxy group mt-butoxy group, pentyloxy group, hexyl. An oxy group etc. are mentioned.

Examples of the cycloalkyl group represented by R ¹ and R ² include a cycloalkyl group having 3 to 8 carbon atoms, and specific examples thereof include, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclo group. A heptyl group, a cyclooctyl group, etc. are mentioned.
These cycloalkyl groups may have a substituent. Examples of the substituent substituted on the cycloalkyl group include an alkyl group and an alkoxy group. Examples of the alkyl group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, s-butyl group, isobutyl group, t-butyl group, pentyl group and hexyl group. Examples of the alkoxy group include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, s-butoxy group, t-butoxy group, pentyloxy group, and hexyloxy group. Can be mentioned.

Examples of the aryl group represented by R ¹ and R ² include an aryl group having 6 to 18 carbon atoms, and specific examples thereof include a phenyl group, a naphthyl group, an anthryl group, a phenanthryl group, and a biphenyl group. . These aryl groups may have a substituent, and examples of the substituent include linear or branched alkyl having 1 to 6 carbon atoms such as a methyl group, an ethyl group, an isopropyl group, and a t-butyl group. Group; linear or branched alkoxy group having 1 to 6 carbon atoms such as methoxy group, ethoxy group, isopropoxy group and t-butoxy group; halogen atom such as chlorine atom, bromine atom and fluorine atom; In addition, a plurality of these substituents may be substituted on the aryl group. Specific examples of the aryl group having these substituents include, for example, p-tolyl group, m-tolyl group, o-tolyl group, 3,5-xylyl group, 3,5-di-t-butylphenyl group, p -T-butylphenyl group, p-methoxyphenyl group, 3,5-di-t-butyl-4-methoxyphenyl group, p-chlorophenyl group, m-fluorophenyl group and the like can be mentioned.

Examples of the halogen atom represented by R ¹ and R ² include a chlorine atom, a bromine atom, and a fluorine atom.

Examples of the haloalkyl group represented by R ¹ and R ² include haloalkyl groups having 1 to 4 carbon atoms such as a trifluoromethyl group, a pentafluoroethyl group, and a trichloromethyl group.

In the general formulas (1) and (1 *), the divalent hydrocarbon group represented by Z ¹ and Z ² may have a methylene chain which may have a substituent, and a substituent. A good arylene group is mentioned.

  Examples of the methylene chain that may have a substituent include a methylene chain having 1 to 4 carbon atoms, and specific examples include a methylene group, an ethylene group, and a trimethylene group. Examples of the substituent of the methylene chain include an alkyl group and a halogen atom. Specific examples of the substituent include an alkyl group having 1 to 4 carbon atoms such as a methyl group and an ethyl group, and a fluorine atom.

  Examples of the arylene group which may have a substituent include an arylene group having 6 to 18 carbon atoms, and specific examples include a phenylene group and a naphthalenediyl group. Examples of the phenylene group include o or m-phenylene group, and the phenylene group includes, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, s-butyl group, isobutyl group and alkyl groups such as t-butyl group; alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, s-butoxy group, isobutoxy group and t-butoxy group; fluorine atom, chlorine It may be substituted with a halogen atom such as an atom.

Examples of the divalent group represented by Z ³ and Z ⁴ in the general formulas (1) and (1 *) include an oxygen atom, a sulfur atom, a methylene chain, NR ^N , Si (R ^Si ) _{2 and the} like. Here, R ^N is an alkyl group, an aryl groups, alkanesulfonyl groups, Aline sulfonyl group or an acyl group. R ^Si represents an alkyl group or an aryl group, or Si (R ^Si ) ₂ may form a ring.

Examples of the methylene chain represented by Z ³ and Z ⁴ include a linear or branched methylene chain. For example, a methylene group, an ethylene group, a trimethylene group, a propylene group, an isopropylidene group, a 2,3-butanediyl group, a difluoro A methylene group etc. are mentioned.

The alkyl group represented by R Si in R N and Si (R Si) 2 in NR N, for example, for example, linear or branched alkyl group having 1 to 6 carbon atoms, specific examples described above Such an alkyl group is mentioned.

The aryl group represented by R ^N and R ^Si, for example, an aryl group having 6 to 18 carbon atoms, an aryl group such as mentioned above as specific examples.

The alkanesulfonyl group and Aline sulfonyl group represented by R ^N in NR ^N, for example, methanesulfonyl group, trifluoromethanesulfonyl group, a benzenesulfonyl group, p- toluenesulfonyl group and the like.

The acyl group represented by R ^N, such as linear or branched aliphatic acyl group having 2 to 10 carbon atoms, or an aromatic acyl group, and specific examples include acetyl group, propanoyl group, Examples include butyryl group, pivaloyl group, methoxycarbonyl group, ethoxycarbonyl group, t-butoxycarbonyl group, benzyloxycarbonyl group, benzoyl group, and p-nitrobenzoyl group.

Examples of the ring formed of Si (R ^Si ) ₂ include a silolane ring, a silinan ring, and a silepane ring.

  In the present invention, among the compounds represented by the general formula (1), the optically active compound represented by the above general formula (1 *) is preferable.

  Next, a method for producing an optically active spiro compound that can produce the spiro compound of the present invention (simply referred to as “the production method of the present invention”) will be described.

  In the production method of the present invention, as described in the following scheme, a tetrain compound represented by the general formula (2) is reacted in the presence of a catalyst containing a rhodium metal and an optically active bisphosphine compound. An optically active compound represented by the general formula (1 *) described above is produced by selective [2 + 2 + 2] cycloaddition.

Examples of the meanings represented by the symbols R ¹ , R ² , Z ¹ , Z ² , Z ³ and Z ⁴ and the groups represented by the symbols in the general formula (2) described also in the scheme are as described above. The meanings and examples of the general formulas (1) and (1 *) described above are the same.

  The catalyst containing rhodium metal and optically active bisphosphine used in the production method of the present invention will be described.

As a rhodium source of rhodium metal which is one of the catalyst components used in the present invention, a rhodium compound is used, and a preferable rhodium compound includes a rhodium (I) complex coordinated with an olefinic ligand. . Specific rhodium (I) complexes include [Rh (cod) ₂ ] X, [Rh (nbd) ₂ ] X, [RhCl (ethylene) ₂ ] ₂ , [RhCl (cod)] ₂ , [RhCl (nbd )] _{2 and the} like. In the complex chemical formula, X represents a counter anion, cod represents 1,5-cyclooctadiene, and nbd represents norbornadiene.

Examples of the optically active bisphosphine which is another catalyst component used in the present invention include those represented by the following general formula (4).
^{R 3 R 4 P-Q-} PR 5 R 6 (4)
(Wherein R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents an aryl group which may have a substituent or an optionally substituted cycloalkyl group, and R ³ And R ⁴ and / or R ⁵ and R ⁶ may form a ring, and Q represents a divalent arylene group or ferrocenediyl group which may have a substituent.

In the above formula, examples of the aryl group which may have a substituent represented by R ³ , R ⁴ , R ⁵ and R ⁶ include an aryl group having 6 to 14 carbon atoms, specifically Includes a phenyl group, a naphthyl group, an anthryl group, a phenanthryl group, a biphenyl group, and the like. These aryl groups may have a substituent, and examples of the substituent include an alkyl group, an alkoxy group, an aryl group, and a heterocyclic group.

  Examples of the alkyl group as a substituent of the aryl group include linear or branched alkyl groups having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, Specific examples include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, s-butyl group, isobutyl group and t-butyl group.

Examples of the alkoxy group as the substituent of the aryl group include linear or branched alkoxy groups having 1 to 6 carbon atoms, specifically, methoxy group, ethoxy group, n-propoxy group, isopropoxy group. Group, n-butoxy group, s-butoxy group, isobutoxy group, t-butoxy group and the like.
Examples of the aryl group as a substituent for the aryl group include an aryl group having 6 to 14 carbon atoms, and specific examples include a phenyl group, a naphthyl group, an anthryl group, a phenanthryl group, and a biphenyl group.

  Examples of the heterocyclic group as the substituent of the aryl group include an aliphatic heterocyclic group and an aromatic heterocyclic group. The aliphatic heterocyclic group has, for example, 2 to 14 carbon atoms and at least one hetero atom. Preferably 5 to 8 member, preferably 5 or 6 membered monocyclic, polycyclic or condensed ring aliphatic heterocycles containing 1 to 3 hetero atoms such as nitrogen atom, oxygen atom and sulfur atom. A cyclic group is mentioned. Specific examples of the aliphatic heterocyclic group include 2-oxopyrrolidyl group, piperidino group, piperazinyl group, morpholino group, tetrahydrofuryl group, tetrahydropyranyl group, tetrahydrothienyl group and the like. On the other hand, the aromatic heterocyclic group has, for example, 2 to 15 carbon atoms and includes at least one hetero atom, preferably 1 to 3 hetero atoms such as nitrogen, oxygen, and sulfur atoms. ˜8-membered, preferably 5- or 6-membered monocyclic, polycyclic or fused-ring heteroaryl group, specifically, furyl group, thienyl group, pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl Group, pyrazolyl group, imidazolyl group, oxazolyl group, thiazolyl group, benzofuryl group, benzothienyl group, quinolyl group, isoquinolyl group, quinoxalyl group, phthalazinyl group, quinazolinyl group, naphthyridinyl group, cinnolinyl group, benzimidazolyl group, benzooxazolyl group And benzothiazolyl group.

Examples of the optionally substituted cycloalkyl group represented by R ³ , R ⁴ , R ⁵ and R ⁶ include a 5-membered or 6-membered cycloalkyl group. Examples of the alkyl group include a cyclopentyl group and a cyclohexyl group. On the ring of these cycloalkyl groups, 1 to 2 or more may be substituted with a substituent such as an alkyl group or an alkoxy group mentioned as the substituent for the aryl group.

Moreover, as a ring which may be formed by R ³ and R ⁴ and / or R ⁵ and R ⁶ , as a ring including a phosphorus atom to which R ³ , R ⁴ , R ⁵ and R ⁶ are bonded, A four-membered ring, a five-membered ring or a six-membered ring is mentioned. Specific examples of the ring include phosphetane ring, phosphorane ring, phosphane ring, 2,4-dimethylphosphetane ring, 2,4-diethylphosphetane ring, 2,5-dimethylphosphorane ring, 2,5-diethyl. A phosphorane ring, a 2,6-dimethylphosphane ring, a 2,6-diethylphosphane ring, etc. are mentioned, These rings may be optically active substances.

  Examples of the divalent arylene group which may have a substituent represented by Q include a phenylene group, a biphenyldiyl group and a binaphthalenediyl group. Examples of the phenylene group include o or m-phenylene group, and the phenylene group includes methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, s-butyl group, isobutyl group and t-butyl group. Alkyl groups such as groups; alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, s-butoxy group, isobutoxy group and t-butoxy group; hydroxyl group, amino group or substituted amino group It may be substituted with a group or the like. The biphenyldiyl group and the binaphthalenediyl group preferably have a 1,1′-biaryl-2,2′-diyl type structure, and the biphenyldiyl group and the binaphthalenediyl group are alkyl groups as described above. And an alkoxy group, for example, an alkylenedioxy group such as a methylenedioxy group, an ethylenedioxy group, and a trimethylenedioxy group, a hydroxyl group, an amino group, a substituted amino group, and the like. The ferrocenediyl group may also have a substituent, and examples of the substituent include the alkyl group, alkoxy group, alkylenedioxy group, hydroxyl group, amino group, and substituted amino group described above.

  Specific examples of the optically active bisphosphine represented by the general formula (4) include known bisphosphines, and one of them is a compound represented by the following general formula (5).

（式中、Ｒ^７及びＲ^８は、それぞれ独立して、ハロゲン原子、アルキル基およびアルコキシ基から選ばれる置換基で置換されていてもよいフェニル基を示すか、またはシクロペンチル基もしくはシクロヘキシル基を示す。）

(Wherein R ⁷ and R ⁸ each independently represent a phenyl group which may be substituted with a substituent selected from a halogen atom, an alkyl group and an alkoxy group, or a cyclopentyl group or a cyclohexyl group) .)

Examples of the alkyl group as the substituent of the phenyl group in R ⁷ and R ⁸ include linear or branched alkyl groups having 1 to 6 carbon atoms such as a methyl group and a t-butyl group, Examples of the alkoxy group as a substituent of the phenyl group include linear or branched alkoxy groups having 1 to 6 carbon atoms such as a methoxy group and a t-butoxy group, and a halogen as a substituent of the phenyl group. As an atom, a chlorine atom, a bromine atom, a fluorine atom etc. are mentioned, for example.

Specific examples of R ⁷ and R ⁸ include, for example, phenyl group, p-tolyl group, m-tolyl group, 3,5-xylyl group, pt-butylphenyl group, p-methoxyphenyl group, p-chlorophenyl. Group, cyclopentyl group, cyclohexyl group and the like.

  Moreover, the binaphthyl ring which is the basic skeleton of the compound represented by the general formula (5) may be substituted with a substituent, and examples of the substituent include alkyl groups such as a methyl group and a t-butyl group; Examples thereof include alkoxy groups such as methoxy group and t-butoxy group; triarylsilyl groups such as trialkylsilyl group such as trimethylsilyl group, triisopropylsilyl group and t-butyldimethylsilyl group, and triphenylsilyl group.

Another specific example of the optically active bisphosphine represented by R ³ R ⁴ PQQPR ⁵ R ⁶ is a compound represented by the following general formula (6).

（式中、Ｒ^９及びＲ^１０は、それぞれ独立して、ハロゲン原子、アルキル基およびアルコキシ基から選ばれる置換基で置換されていてもよいフェニル基、シクロペンチル基又はシクロヘキシル基を示す。Ｒ^１１、Ｒ^１２、Ｒ^１４及びＲ^１５は、同一又は異なっていてもよく、水素原子、アルキル基、アルコキシ基、アシルオキシ基、ハロゲン原子、ハロアルキル基又はジアルキルアミノ基を示す。Ｒ^１３とＲ^１６は、同一又は異なっていてもよく、アルキル基、アルコキシ基、アシルオキシ基、ハロゲン原子、ハロアルキル基又はジアルキルアミノ基を示す。Ｒ^１１、Ｒ^１２及びＲ^１３のうちの二つで置換基を有していてもよいメチレン鎖又は置換基を有していてもよい（ポリ）メチレンジオキシ基を形成していてもよく、Ｒ^１４、Ｒ^１５及びＲ^１６のうちの二つで置換基を有していてもよいメチレン鎖又は置換基を有していてもよい（ポリ）メチレンジオキシ基を形成していてもよい。また、Ｒ^１３とＲ^１６とで置換基を有していてもよいメチレン鎖又は置換基を有していてもよい（ポリ）メチレンジオキシ基を形成していてもよい。）

(In the formula, R ⁹ and R ¹⁰ each independently represent a phenyl group, a cyclopentyl group, or a cyclohexyl group, which may be substituted with a substituent selected from a halogen atom, an alkyl group, and an alkoxy group. R ¹¹ , R ¹² , R ¹⁴ and R ¹⁵ may be the same or different and each represents a hydrogen atom, an alkyl group, an alkoxy group, an acyloxy group, a halogen atom, a haloalkyl group or a dialkylamino group, and R ¹³ and R ¹⁶ are the same. Or may be different and represents an alkyl group, an alkoxy group, an acyloxy group, a halogen atom, a haloalkyl group or a dialkylamino group, and two of R ¹¹ , R ¹² and R ¹³ may have a substituent. A good methylene chain or a (poly) methylenedioxy group which may have a substituent may be formed, and R ¹⁴ , R ¹⁵ and R ¹⁶ may form a methylene chain which may have a substituent or a (poly) methylenedioxy group which may have a substituent. R ¹³ and R ¹⁶ may form a methylene chain which may have a substituent or a (poly) methylenedioxy group which may have a substituent.

Examples of the alkyl group as a substituent of the phenyl group in R ⁹ and R ¹⁰ include linear or branched alkyl groups having 1 to 6 carbon atoms such as a methyl group and a t-butyl group, Examples of the alkoxy group as a substituent of the phenyl group include linear or branched alkoxy groups having 1 to 6 carbon atoms such as a methoxy group and a t-butoxy group, and a halogen as a substituent of the phenyl group. Examples of the atom include a chlorine atom, a bromine atom, and a fluorine atom, and a plurality of these substituents may be substituted on the phenyl group. Specific examples of R ⁹ and R ¹⁰ include, for example, phenyl group, p-tolyl group, m-tolyl group, o-tolyl group, 3,5-xylyl group, 3,5-di-t-butylphenyl group, Examples include p-t-butylphenyl group, p-methoxyphenyl group, 3,5-di-t-butyl-4-methoxyphenyl group, p-chlorophenyl group, m-fluorophenyl group, cyclopentyl group, cyclohexyl group and the like. .

In addition, examples of the alkyl group represented by R ^{11 to} R ¹⁶ include linear or branched alkyl groups having 1 to 6 carbon atoms such as a methyl group and a t-butyl group. As the alkoxy group, For example, a linear or branched alkoxy group having 1 to 6 carbon atoms such as a methoxy group and a t-butoxy group can be mentioned. Examples of the acyloxy group include an acetoxy group, a propanoyloxy group, a trifluoroacetoxy group, Examples thereof include acyloxy groups having 2 to 10 carbon atoms such as benzoyloxy groups. Examples of halogen atoms include chlorine atoms, bromine atoms and fluorine atoms. Examples of haloalkyl groups include trifluoromethyl groups. Examples thereof include haloalkyl groups having 1 to 4 carbon atoms, and examples of the dialkylamino group include a dimethylamino group and a diethylamino group. .

When forming a methylene chain which may have a substituent at two of R ¹¹ , R ¹² and R ¹³ , and having a substituent at two of R ¹⁴ , R ¹⁵ and R ¹⁶ As the methylene chain in the case of forming an optional methylene chain, for example, a methylene chain having 3 to 5 carbon atoms is preferable, and specific examples include a trimethylene group, a tetramethylene group, and a pentamethylene group. Examples of the substituent in the methylene chain which may have the substituent include an alkyl group and a halogen atom. Specific examples thereof include, for example, an alkyl group having 1 to 6 carbon atoms as described above. And a fluorine atom.

In addition, two of R ¹¹ , R ¹² and R ¹³ may form a (poly) methylenedioxy group which may have a substituent, and two of R ¹⁴ , R ¹⁵ and R ¹⁶ Specific examples of the (poly) methylenedioxy group in forming a (poly) methylenedioxy group which may have a substituent include, for example, a methylenedioxy group, an ethylenedioxy group, and trimethylene A dioxy group etc. are mentioned. In addition, examples of the substituent substituted on the (poly) methylenedioxy group include an alkyl group and a halogen atom. Specific examples thereof include, for example, an alkyl group having 1 to 6 carbon atoms and fluorine as described above. An atom etc. are mentioned.

  Specific examples of the optically active bisphosphine compounds represented by the general formulas (5) and (6) include 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, 2,2′-bis [ Di (p-tolyl) phosphino] -1,1′-binaphthyl, 2,2′-bis [di (m-tolyl) phosphino] -1,1′-binaphthyl, 2,2′-bis [di (3 5-xylyl) phosphino] -1,1′-binaphthyl, 2,2′-bis [di (pt-butylphenyl) phosphino] -1,1′-binaphthyl, 2,2′-bis [di (p -Methoxyphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [di (3,5-di-t-butyl-4-methoxyphenyl) phosphino] -1,1'-binaphthyl, 2, 2'-bis [di (cyclopentyl) phosphino]- , 1′-binaphthyl, 2,2′-bis [di (cyclohexyl) phosphino] -1,1′-binaphthyl, 2,2′-bis (diphenylphosphino) -5,5 ′, 6,6 ′, 7 , 7 ′, 8,8′-octahydro-1,1′-binaphthyl, 2,2′-bis (di-p-tolylphosphino) -5,5 ′, 6,6 ′, 7,7 ′, 8,8 '-Octahydro-1,1'-binaphthyl, 2,2'-bis (di-m-tolylphosphino) -5,5', 6,6 ', 7,7', 8,8'-octahydro-1,1 '-Binaphthyl, 2,2'-bis (di-3,5-xylylphosphino) -5,5', 6,6 ', 7,7', 8,8'-octahydro-1, 1'- Binaphthyl, 2,2′-bis (di-p-tertiarybutylphenylphosphino) -5,5 ′, 6,6 ′, 7,7 , 8,8′-octahydro-1,1′-binaphthyl, 2,2′-bis (di-p-methoxyphenylphosphino) -5,5 ′, 6,6 ′, 7,7 ′, 8,8 '-Octahydro-1,1'-binaphthyl, 2,2'-bis (di-p-chlorophenylphosphino) -5,5', 6,6 ', 7,7', 8,8'-octahydro-1 , 1′-binaphthyl, 2,2′-bis (dicyclopentylphosphino) -5,5 ′, 6,6 ′, 7,7 ′, 8,8′-octahydro-1,1′-binaphthyl, 2, 2′-bis (dicyclohexylphosphino) -5,5 ′, 6,6 ′, 7,7 ′, 8,8′-octahydro-1,1′-binaphthyl, ((4,4′-bi-1, 3-benzodioxole) -5,5′-diyl) bis (diphenylphosphine), (4,4′-bi-1, 3-benzodioxole) -5,5′-diyl) bis (bis (3,5-dimethylphenyl) phosphine), ((4,4′-bi-1,3-benzodioxole) -5, 5'-diyl) bis (bis (3,5-di-t-butyl-4-methoxyphenyl) phosphine), ((4,4'-bi-1,3-benzodioxole) -5, 5 ' -Diyl) bis (bis (4-methoxyphenyl) phosphine), ((4,4'-bi-1,3-benzodioxole) -5,5'-diyl) bis (dicyclohexylphosphine), ((4 , 4'-bi-1,3-benzodioxole) -5,5'-diyl) bis (bis (3,5-di-t-butylphenyl) phosphine), 2,2'-bis (diphenylphos Fino) -4,4 ′, 6,6′-tetramethyl-5,5′-dimethoxy -1,1'-biphenyl, 2,2'-bis (di-p-methoxyphenylphosphino) -4,4 ', 6,6'-tetramethyl-5,5'-dimethoxy-1,1'- Biphenyl, 2,2′-bis (diphenylphosphino) -4,4 ′, 6,6′-tetra (trifluoromethyl) -5,5′-dimethyl-1,1′-biphenyl, 2,2′- Bis (diphenylphosphino) -4,6-di (trifluoromethyl) -4 ′, 6′-dimethyl-5′-methoxy-1,1′-biphenyl, 2-dicyclohexylphosphino-2′-diphenylphosphino -4,4 ', 6,6'-tetramethyl-5,5'-dimethoxy-1,1'-biphenyl, 2,2'-bis (diphenylphosphino) -6,6'-dimethyl-1,1 -Biphenyl, 2,2'-bis (diphenyl) Phosphino) -4,4 ′, 6,6′-tetramethyl-1,1′-biphenyl, 2,2′-bis (diphenylphosphino) -3,3 ′, 6,6′-tetramethyl-1, 1'-biphenyl), 2,2'-bis (diphenylphosphino) -4,4'-difluoro-6,6'-dimethyl-1,1'-biphenyl, 2,2'-bis (diphenylphosphino) -4,4'-bis (dimethylamino) -6,6'-dimethyl-1,1'-biphenyl, 2,2'-bis (di-p-tolylphosphino) -6,6'-dimethyl-1,1 '-Biphenyl, 2,2'-bis (di-o-tolylphosphino) -6,6'-dimethyl-1,1'-biphenyl, 2,2'-bis (di-m-fluorophenylphosphino) -6 , 6′-dimethyl-1,1′-biphenyl, 1,11- Bis (diphenylphosphino) -5,7-dihydrobenzo [c, e] oxepin, 2,2′-bis (diphenylphosphino) -6,6′-dimethoxy-1,1′-biphenyl, 2,2 ′ -Bis (diphenylphosphino) -5,5 ', 6,6'-tetramethoxy-1,1'-biphenyl, 2,2'-bis (di-p-tolylphosphino) -6,6'-dimethoxy-1 , 1′-biphenyl, 2,2′-bis (diphenylphosphino) -4,4 ′, 5,5 ′, 6,6′-hexamethoxy-1,1′-biphenyl, 1,2-bis (2 , 5-dimethylphosphorano) benzene, 1,2-bis (2,5-diethylphosphorano) benzene, 1,2-bis (2,5-diisopropylphosphorano) benzene, 1- (2,5-dimethylphosphone) Rano) -2- (diphenyl) Sufino) benzene, 1,1'-bis (2,4-diethyl-phosphotransferase Tano) ferrocene, and the like.

  Besides these, specific examples of the optically active bisphosphine compound that can be used in the present invention include, for example, N, N-dimethyl-1- [1 ′, 2-bis (diphenylphosphino) ferrocenyl] ethylamine, 2 , 3-bis (diphenylphosphino) butane, 1-cyclohexyl-1,2-bis (diphenylphosphino) ethane, 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphos Fino) butane, 1,2-bis [(o-methoxyphenyl) phenylphosphino] ethane, 1,2-bis (2,5-dimethylphosphorano) ethane, 5,6-bis (diphenylphosphino) -2 -Norbornene, N, N'-bis (diphenylphosphino) -N, N'-bis (1-phenylethyl) ethylenediamine, 1,2-bi (Diphenylphosphino) propane, 2,4-bis (diphenylphosphino) pentane, and the like.

The catalyst used in the present invention is a catalyst containing rhodium metal as described above as a catalyst component and an optically active bisphosphine, for example, a compound represented by the following general formula (3).
[Rh (L) _m (Y) _n ] X (3)
(In Formula (3), L represents an optically active bisphosphine represented by R ³ R ⁴ PQ-PR ⁵ R ⁶ , Y represents a non-conjugated diene compound, and X represents a counter anion. m represents an integer of 1 or 2, and n represents an integer of 0 or 1. However, when m = 1, n = 0 or n = 1, and when m = 2, n = 0. R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents an aryl group which may have a substituent or an optionally substituted cycloalkyl group, and R ³ and R ⁴ And / or R ⁵ and R ⁶ may form a ring, and Q represents a divalent arylene group or ferrocenediyl group which may have a substituent.

In the above formula, the optically active bisphosphine represented by L ³ R ⁴ PQQPR ⁵ R ⁶ is as described above.

  Next, the compound represented by the general formula (3), which is an example of a catalyst containing rhodium metal and optically active bisphosphine used in the present invention, will be described in more detail.

  In the general formula (3), the non-conjugated diene compound represented by Y may be cyclic or non-cyclic, and when the non-conjugated diene compound is a cyclic non-conjugated diene compound, it is monocyclic, polycyclic or condensed. Any of a cyclic ring shape may be used. Further, the non-conjugated diene compound may be a non-conjugated diene compound substituted with a substituent, that is, a substituted non-conjugated diene compound, and the substituent is not particularly limited as long as the substituent does not adversely affect the production method of the present invention. Not. Preferred non-conjugated diene compounds include, for example, 1,5-cyclooctadiene (hereinafter abbreviated as COD), bicyclo [2,2,1] hepta-2,5-diene (also referred to as 2,5-norbornadiene). Hereinafter, abbreviated as NBD), 1,5-hexadiene and the like.

In the general formula (3), examples of the counter anion represented by X include BF ₄ , ClO ₄ , CF ₃ SO ₃ (hereinafter abbreviated as OTf), PF ₆ , SbF ₆ , B (3, 5- ( _{CF 3) 2 C 6 H 3} ) 4 and BPh _4, and the like.

  The compound represented by the general formula (3) used in the present invention is, for example, a rhodium-olefin obtained by a known method in an inert gas atmosphere or commercially available as shown in the following scheme 1. After the coordination complex is reacted with, for example, the optically active bisphosphine represented by L in an organic solvent such as methanol, ethanol, isopropanol, butanol, toluene, and tetrahydrofuran, MX (M is a monovalent metal cation). An ion, and X represents the same meaning as described above), and a counter anion exchange reaction is performed (this yields the compound (A) or (B) in Scheme 1), or hydrogen gas is further added. The olefinic ligand can be eliminated by acting (this yields the compound (C) in Scheme 1).

Scheme 1

  As shown in the following scheme 2, the compound represented by the general formula (3) used in the present invention is an optical activity represented by L in a rhodium-bisolefin complex that has been subjected to a counter anion exchange reaction in advance. It can also be obtained by reacting bisphosphine or by further desorbing the olefinic ligand with hydrogen gas.

Scheme 2

  The addition amount of the optically active bisphosphine represented by L with respect to the number of moles of the central metal of the rhodium-olefin coordination complex as shown in Scheme 1 and Scheme 2 is when a part of bisphosphine undergoes oxidation. Therefore, it is desirable that the amount be 1.0 to 2.4 times mol, more preferably 1.05 to 2.2 times mol.

In the present invention, as the rhodium-olefin coordination complex used when preparing the compound represented by the general formula (3) as a catalyst, various complexes can be handled by selecting an olefin ligand. From the viewpoint of availability, [Rh (COD) Cl] ₂ which is a rhodium complex of COD and [Rh (NBD) Cl] ₂ which is a rhodium complex of NBD are particularly preferable.

  Further, in the counter anion exchange reaction, it is preferable in terms of handling to use, for example, silver salt (AgX) as MX.

In addition, although the catalytically active species in the compound represented by the general formula (3) is [Rh (L) _m ] X, a compound that is a precursor thereof, for example, the compound [Rh ( L) (COD)] X can also be used in the production method of the present invention.

  For example, the compound represented by the general formula (3) such as the compounds (A), (B) and (C) described in the above scheme can be used as a catalyst in the production method of the present invention without any particular purification after preparation. Can be used. Furthermore, in the production method of the present invention, a catalyst containing rhodium metal and optically active bisphosphine can be used immediately after preparation. Specifically, a rhodium compound and optically active bisphosphine are reacted. What is necessary is just to prepare this catalyst and to add the said tetrain compound subsequently.

  The reaction solvent used in the production method of the present invention is not particularly limited as long as it does not adversely influence the reaction. For example, amides such as N, N-dimethylformamide, formamide, N, N-dimethylacetamide, For example, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, o-dichlorobenzene, aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, cyclohexane, such as benzene, Aromatic hydrocarbons such as toluene and xylene, non-nucleophilic alcohols such as tert-butanol, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran 1,4-dioxane, sulfoxides such as ethers and such as dimethyl sulfoxide and 1,3-dioxolane. These reaction solvents may be used alone or in appropriate combination of two or more.

  In the production method of the present invention, the usage amount of the catalyst containing rhodium metal and optically active bisphosphine in terms of rhodium metal is usually about 1 to 10 mol% with respect to the tetrain compound of the formula (2) of the reaction substrate. It is enough.

  In the production method of the present invention, the reaction temperature for the intramolecular [2 + 2 + 2] cycloaddition reaction of the tetrain compound described above varies depending on the substrate used, but is usually −20 ° C. to 100 ° C., preferably 0 ° C. to The range is 50 ° C. The reaction time is naturally 30 minutes to 30 hours, preferably 1 hour to 20 hours, although it naturally varies depending on the substrate used. The reaction is preferably performed in an inert gas such as nitrogen or argon.

  After completion of the reaction, the desired compound can be obtained by performing post-treatment operations usually performed in this field and combining purification methods such as crystallization, distillation, and various chromatographies alone or in appropriate combination.

EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited at all by these Examples.
The optical purity was measured by HPLC (high performance liquid chromatography) using an optically active column.

Examples 1 to 9 Production of optically active spirobipyridine compounds

According to the reaction formula of this scheme, an optically active compound having a spirobipyridine type structure, that is, an optically active spirobipyridine compound was produced as follows.
First, optically active bisphosphine (0.010 mmol), [Rh (COD) ₂ ] BF ₄ (4.1 mg, 0.010 mmol) and 1.0 mL of methylene chloride shown in Table 1 below were placed in a Schlenk tube under an argon atmosphere. In addition, after stirring for 5 minutes, hydrogen gas was introduced into the Schlenk tube and stirred for 30 minutes. Subsequently, the reaction solution was concentrated under reduced pressure to dryness, and 0.5 mL of methylene chloride was added. To this solution, 0.5 mL of a methylene chloride solution of a tetrain compound (0.10 mmol) shown in the above-mentioned scheme (R is shown in Table 1 below) was added and stirred at room temperature for 16 to 24 hours. Subsequently, the solvent was distilled off, and purification was performed by silica gel column chromatography (methylene chloride / ethyl acetate = 100/3) to obtain the desired product.
The tetrain compound and optically active bisphosphine in each of Examples 1 to 9, stirring time, and results are shown in Table 1 below.

Incidentally, the above table 1 in _{(R) -Segphos, (R)} -H 8 -BINAP, (R) -BINAP, (R) -tol-BINAP and (R) -xyl-BINAP respectively the following compounds Represents.

Examples 10 to 11 Production of optically active spirobipyridine compounds

According to the reaction formula of this scheme, an optically active spirobipyridine compound was produced as follows.
First, under argon atmosphere, optically active bisphosphine (0.010 mmol), [Rh (COD) ₂ ] BF ₄ (4.1 mg, 0.010 mmol) and methylene chloride 1.0 mL shown in Table 2 below were added to a Schlenk tube. After stirring for 5 minutes, hydrogen gas was introduced into the Schlenk tube and stirred for 30 minutes. Subsequently, the reaction solution was concentrated under reduced pressure to dryness, and 0.5 mL of methylene chloride was added. To this solution, 0.5 mL of a methylene chloride solution of a tetrain compound (0.10 mmol) shown in the above scheme (R is shown in Table 2 below) was added and stirred at room temperature for 24 hours. Subsequently, the solvent was distilled off, and purification was performed by silica gel column chromatography (methylene chloride / ethyl acetate = 100/3) to obtain the desired product.
The tetrain compound, the optically active bisphosphine and the results in each of Examples 10 to 11 are shown in Table 2 below.

(Example 12) Production of optically active spirobipyridine compound

According to the reaction formula of this scheme, an optically active spirobipyridine compound was produced as follows.
First, under an argon atmosphere, (R) -H ₈ -BINAP (0.010 mmol), [Rh (COD) ₂ ] BF ₄ (4.1 mg, 0.010 mmol) and 1.0 mL of methylene chloride were added to a Schlenk tube, After stirring for 5 minutes, hydrogen gas was introduced into the Schlenk tube and stirred for 30 minutes. Subsequently, the reaction solution was concentrated under reduced pressure to dryness, and 0.5 mL of methylene chloride was added. To this solution was added a 0.5 mL solution of a tetrain compound (0.10 mmol) in methylene chloride, and the mixture was stirred at room temperature for 24 hours. Next, the solvent was distilled off, and the residue was purified by silica gel column chromatography (methylene chloride / ethyl acetate = 100/3) to obtain the desired product with a yield of 99% and an optical purity of 18% ee. The optical rotation of this product was (−).

  The structure and physical property data of the optically active spirobipyridine compounds obtained in Examples 1 to 5 and 10 to 12 are shown below.

Example 1:

Example 2:

Example 3:

Example 4:

Example 5:

Example 10:

Example 11:

Example 12:

Claims (6)

A compound represented by the following general formula (1).

(In Formula (1), R ¹ and R ² may be the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a halogen atom or a haloalkyl group. Z ¹ and Z ² are the same or They may be different and represent a divalent hydrocarbon group, and Z ³ and Z ⁴ may be the same or different and represent a divalent group.) An optically active compound represented by the following general formula (1 *).

(In formula (1 *), R ¹ and R ² may be the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a halogen atom or a haloalkyl group. Z ¹ and Z ² are the same. Alternatively, they may be different and each represents a divalent hydrocarbon group, and Z ³ and Z ⁴ may be the same or different and each represents a divalent group. Using a catalyst containing a rhodium metal and an optically active bisphosphine, the tetrain compound represented by the following general formula (2) is represented by the following general formula (1 *) for intramolecular [2 + 2 + 2] cycloaddition reaction. A method for producing an optically active compound.

(In Formula (2), R ¹ and R ² may be the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a halogen atom or a haloalkyl group. Z ¹ and Z ² are the same or They may be different and represent a divalent hydrocarbon group, and Z ³ and Z ⁴ may be the same or different and represent a divalent group.)

(In formula (1 *), R ¹ and R ² may be the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a halogen atom or a haloalkyl group. Z ¹ and Z ² are the same. Alternatively, they may be different and each represents a divalent hydrocarbon group, and Z ³ and Z ⁴ may be the same or different and each represents a divalent group. The production method according to claim 3, wherein the catalyst containing rhodium metal and optically active bisphosphine is a compound represented by the following general formula (3).
[Rh (L) _m (Y) _n ] X (3)
(In formula (3), L represents an optically active bisphosphine represented by the following formula (4), Y represents a non-conjugated diene compound, X represents a counter anion, and m represents an integer of 1 or 2. N represents an integer of 0 or 1. However, when m = 1, n = 0 or n = 1, and when m = 2, n = 0.
^{R 3 R 4 P-Q-} PR 5 R 6 (4)
(In the formula (4), R ³ , R ⁴ , R ⁵ and R ⁶ each independently represent an aryl group which may have a substituent or a cycloalkyl group which may have a substituent. , R ³ and R ⁴ and / or R ⁵ and R ⁶ may form a ring, and Q represents a divalent arylene group or a ferrocenediyl group which may have a substituent.   The production method according to claim 4, wherein the catalyst containing rhodium metal and optically active bisphosphine is used immediately after preparation.   6. The method according to claim 4, wherein the olefinic ligand is desorbed using hydrogen gas when preparing a catalyst containing rhodium metal and optically active bisphosphine.