JP4855196B2 - Substituted optically active diphosphine compounds - Google Patents

Description

  The present invention is characterized in that an optically active diphosphine compound having two benzene rings of a biphenyl skeleton is introduced with oxygen-containing functional groups bonded by oxygen atoms such as alkoxy groups at the 4-position and 4'-position of the benzene ring. A novel diphosphine compound, a transition metal complex containing the diphosphine compound, an asymmetric synthesis catalyst comprising the transition metal complex, and an asymmetric reduction reaction of the unsaturated compound in the presence of the transition metal complex The present invention relates to a method for producing an optically active compound.

In recent years, asymmetric synthesis reactions using a transition metal complex containing a diphosphine ligand are required to construct various diphosphine ligands in order to further improve the performance of the reaction. , (5,6), (5 ′, 6 ′)-bis (methylenedioxy) biphenyl-2,2′-diyl) groups have been reported, specifically, ((5,6), (5 ′, 6 ′)-bis (methylenedioxy) biphenyl-2,2′-diyl) bis (diphenylphosphine) (hereinafter referred to as SEGPHOS) is described.
In addition, Patent Document 2 describes an asymmetric diphosphine compound in which a methoxy group is introduced into a benzene ring different from methylenedioxybenzene. In addition, there is no description of a synthesis example of a symmetric diphosphine compound having a methoxy group introduced, and a reaction for conducting an asymmetric hydrogenation reaction using the diphosphine compound as a ligand. No examples are given.
Non-Patent Document 1 describes the synthesis of a SEGPHOS derivative in which the methylene proton of methylenedioxybenzene is substituted with fluorine and its use in an asymmetric hydrogenation reaction as a ruthenium complex. It has not been. Non-Patent Document 2 describes the synthesis of a SEGPHOS derivative in which the methylene proton of methylenedioxybenzene is substituted with an alkyl group, and its use in an asymmetric hydrogenation reaction as a ruthenium complex. There is almost no improvement in cognitive ability.
Patent Document 3 describes ligands substituted at the 3,3′-position, and Patent Document 2 describes ligands having different substitution forms on the two benzene rings. It is complicated and the substrate / catalyst ratio in asymmetric hydrogenation is about 100, which is insufficient, and it is difficult to use it industrially.

Japanese Patent Laid-Open No. 10-182678 WO02 / 40492 pamphlet WO02 / 40491 pamphlet Synthesis, 2004, 326 Tetrahedron: Asymmetry, 2004, 15, 2185

  The present invention has been made in view of the above circumstances, and provides a method for producing an optically active compound with good yield and asymmetric yield, and more specifically, a method for producing an optically active compound by an asymmetric hydrogenation reaction. For the purpose. Moreover, this invention provides the catalyst for asymmetric synthesis containing the transition metal complex for the said manufacturing method, especially the catalyst for asymmetric hydrogenation reaction. Furthermore, the present invention provides a novel diphosphine compound useful as a ligand for the transition metal complex, and a novel transition metal complex containing the diphosphine compound.

  As a result of intensive studies to solve the above problems, the present inventors have found that diphosphine in which oxygen-containing functional groups such as alkoxy groups are introduced at the 4-position and 4'-position of two methylenedioxybenzenes of SEGPHOS. A catalyst comprising a transition metal complex having a compound as a ligand is used in the production of optically active compounds, particularly in the asymmetric hydrogenation reaction of unsaturated compounds. The present invention was completed by finding out that it has good economic efficiency and workability and has excellent properties as a catalyst for asymmetric synthesis, particularly a catalyst for asymmetric hydrogenation reaction.

  That is, the present invention provides the following general formula (1)

(Wherein two R ¹ are the same or different and each represents a heterocyclic group which may have a hydrocarbon may have a substituent hydrogen group or a substituent, two R ² and R ³ independently represents a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent, and two Qs are the same or different and represent a spacer.
It is related with the diphosphine compound represented by these. The diphosphine compound represented by the general formula (1) of the present invention is an axially asymmetric compound due to rotation hindrance of two benzene rings, and may be either a racemate or an optically active substance. The ligand in the catalyst is preferably an optically active substance.

  In addition, the present inventors have found that a catalyst comprising a diphosphine oxide compound, which is a derivative of the above-mentioned diphosphine compound, is more effective than the conventional one in the production of optically active compounds, particularly in the asymmetric hydrogenation reaction of unsaturated compounds. The present inventors have found that the compound has excellent properties as a catalyst for asymmetric synthesis, particularly a catalyst for asymmetric hydrogenation reaction, with good yield and optical purity, and also good economic efficiency and workability.

  That is, the present invention further includes the following general formula (6):

（式中、２個のＲ^１は同一又は異なって、置換基を有していてもよい炭化水素基又は置換基を有していてもよい複素環基を示し、２個のＲ^２及びＲ^３は夫々独立して、置換基を有していてもよい炭化水素基又は置換基を有していてもよい複素環基を示し、２個のＱは同一又は異なって、スペーサーを示す。）
で表されるジフェニルホスフィンオキシド化合物に関する。

(Wherein two R ¹ are the same or different and each represents a heterocyclic group which may have a hydrocarbon may have a substituent hydrogen group or a substituent, two R ² and R ³ independently represents a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent, and two Qs are the same or different and represent a spacer.
The diphenylphosphine oxide compound represented by these.

Moreover, this invention relates to the transition metal complex which contains the diphosphine compound represented by the said General formula (1) as a ligand. The present invention relates to the use of a diphosphine compound represented by the general formula (1) as a ligand of a transition metal complex.
Furthermore, the present invention relates to an asymmetric synthesis catalyst comprising the transition metal complex, preferably an asymmetric reduction reaction catalyst or an asymmetric hydrogenation reaction catalyst. The present invention relates to the use of the transition metal complex as a catalyst for asymmetric synthesis, preferably a catalyst for asymmetric reduction reaction or a catalyst for asymmetric hydrogenation reaction.

  The present invention also relates to a method for producing a chiral compound by reacting a compound having a prochiral center in the presence of the above-described catalyst for asymmetric synthesis of the present invention. More specifically, the present invention relates to a method for producing a chiral compound by subjecting a compound having a prochiral center to a reduction reaction in the presence of the asymmetric reduction reaction catalyst of the present invention. More specifically, the present invention relates to a method for producing a chiral compound by hydrogenating a compound having a prochiral center in the presence of the asymmetric hydrogenation reaction catalyst of the present invention.

The present invention will be described in detail as follows.
(1) General formula (1) described above (wherein, two R ^{1 s} are the same or different and may have a hydrocarbon group which may have a substituent or a heterocycle which may have a substituent. Each of ^two R ² and R ³ independently represents a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent; Q is the same or different and represents a spacer.
(2) The diphosphine compound according to (1), wherein the diphosphine compound represented by the general formula (1) is an optically active diphosphine compound.
(3) General formula (6) described above (wherein, two R ^{1 s} are the same or different and may have a hydrocarbon group which may have a substituent or a heterocycle which may have a substituent. Each of ^two R ² and R ³ independently represents a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent; Q is the same or different and represents a spacer.)
(4) The diphenylphosphine oxide compound according to (3), wherein the diphenylphosphine oxide compound represented by the general formula (6) is an optically active diphenylphosphine oxide compound.
(5) An asymmetric ligand containing the optically active diphosphine compound according to (2).
(6) An asymmetric catalyst comprising the optically active diphosphine compound according to (2) or the optically active diphenylphosphine oxide compound according to (4).
(7) A transition metal complex comprising the diphosphine compound according to (1) or (2).
(8) A transition metal complex obtained by reacting the diphosphine compound according to (1) or (2) above with a transition metal complex precursor.
(9) The transition metal complex according to (7) or (8), wherein the transition metal complex is an optically active transition metal complex.
(10) An asymmetric catalyst containing the optically active transition metal complex according to (9).
(11) An asymmetric catalyst comprising the diphosphine compound according to (2) and a transition metal complex precursor.
(12) The asymmetric catalyst according to (10) or (11), wherein the asymmetric catalyst according to (10) or (11) is a catalyst for asymmetric synthesis.
(13) The catalyst for asymmetric synthesis according to (12), wherein the catalyst for asymmetric synthesis is a catalyst for asymmetric reduction reaction.
(14) A method for producing an optically active compound, wherein a compound having a prochiral center is reacted in the presence of the asymmetric catalyst according to (10) or (11).
(15) Use of the optically active diphosphine compound according to (2) as an asymmetric ligand.
(16) The transition metal complex according to (7) is represented by the following general formula (11) or general formula (12):
_{M m L n X p Y q} (11)
_{[M m L n X p Y} q] Z s (12)
(In the above formula, L represents an optically active form of the diphosphine compound represented by the general formula (1), M represents a transition metal, X represents a halogen atom, a carboxylate group, an allyl group, 1,5-cyclohexane. And octadiene or norbornadiene, Y represents a ligand, Z represents an anion or cation, n represents an integer of 1 to 5, and m, p, q, and s represent integers of 0 to 5.)
The transition metal complex according to (7), which is a transition metal complex represented by the formula:

In the ligand of the present invention, an oxygen-containing functional group bonded with an oxygen atom such as an alkoxy group is introduced into the 4-position and 4′-position of the optically active diphosphine compound having two benzene rings of a biphenyl skeleton. It is characterized by this. The two benzene rings of the diphosphine compound represented by the general formula (1) of the present invention have axial asymmetry due to rotation hindrance. And it is known that the change of the dihedral angle by two benzene rings in the biphenyl skeleton of the diphosphine compound contributes to the stereoselectivity of the asymmetric hydrogenation reaction.
The present inventors have introduced an oxygen-containing functional group bonded to an oxygen atom such as an alkoxy group at positions 4 and 4 ′ of the benzene ring of an optically active diphosphine compound having two benzene rings of a biphenyl skeleton. It was confirmed by chemical calculation that the dihedral angle due to two benzene rings in the biphenyl skeleton of the diphosphine compound changed. Due to this structural change, the catalyst for asymmetric synthesis comprising a transition metal complex containing the diphosphine compound represented by the general formula (1) of the present invention as a ligand has a good yield and asymmetric yield. It is thought that the production of the compound was made possible. In addition, by replacing unnecessary reactive sites in the synthesis in advance, halogenation and coupling reactions are easy and selective, and by increasing the fat solubility, handling during purification and post-reaction purification is possible. It becomes easy and the target optically active diphosphine compound can be produced efficiently.

The diphosphine compound represented by the general formula (1) of the present invention will be described.
In the general formula (1), two of R ¹ are have may have a substituent hydrocarbon group or a substituent shown also heterocyclic group, two R ¹ are the same or Although it may be different, it is preferable that the two R ¹ are the same. Further, two R ² and R ³ each independently represent a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent.

Examples of the hydrocarbon group which may have a substituent represented by R ^{1 to} R ³ 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 alkadienyl group, an aryl group, an aralkyl group, and the like.
The alkyl group may be linear, branched or cyclic, for example, linear or branched alkyl having 1 to 20 carbon atoms, preferably 1 to 15 carbon atoms, more preferably 1 to 10 carbon atoms. And a monocyclic, polycyclic, condensed cyclic, or bridged cyclic cycloalkyl group having 3 to 20 carbon atoms, preferably 3 to 15 carbon atoms, more preferably 3 to 10 carbon atoms, Specific examples thereof include, for example, methyl group, ethyl group, n-propyl group, 2-propyl group, n-butyl group, 1-methylpropyl group, isobutyl group, tert-butyl group, n-pentyl group, 1- Methylbutyl group, tert-pentyl group, 2-methylbutyl group, 3-methylbutyl group, 2,2-dimethylpropyl group, n-hexyl group, 1-methylpentyl group, 1-ethylbutyl 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, lauryl group, stearyl group, cyclopropyl group, A cyclobutyl group, a cyclopentyl group, a cyclohexyl group, etc. are mentioned.

The alkenyl group may be linear or branched, and examples thereof include alkenyl groups having 2 to 20 carbon atoms, preferably 2 to 15 carbon atoms, and more preferably 2 to 10 carbon atoms. Specific examples thereof include Examples thereof include a vinyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonenyl group, and a decenyl group.
The alkynyl group may be linear or branched, and examples thereof include alkynyl groups having 2 to 20 carbon atoms, preferably 2 to 15 carbon atoms, and more preferably 2 to 10 carbon atoms. Examples include ethynyl group, propynyl group, butynyl group, pentynyl group, hexynyl group and the like.
The alkadienyl group may have two double bonds in the chain of the alkyl group, and may be linear, branched or cyclic. For example, it has 4 or more carbon atoms, preferably 4 to 20 carbon atoms, more preferably Examples thereof include alkadienyl groups having 4 to 15 carbon atoms, more preferably 4 to 10 carbon atoms. Specific examples thereof include 1,3-butadienyl group, 2,3-dimethyl-1,3-butadienyl group and the like. Can be mentioned.

Examples of the aryl group include monocyclic, polycyclic, and condensed cyclic aryl groups having 6 to 20 carbon atoms, preferably 6 to 15 carbon atoms. Specific examples thereof include, for example, a phenyl group, A naphthyl group, an anthryl group, a biphenyl group, etc. are mentioned.
The aralkyl group includes, for example, an aralkyl group having 7 to 20 carbon atoms, preferably 7 to 15 carbon atoms, in which at least one hydrogen atom of the alkyl group is substituted with the aryl group. Examples include benzyl group, 1-phenylethyl group, 2-phenylethyl group, 1-phenylpropyl group, 3-naphthylpropyl group and the like.

Examples of the substituted hydrocarbon group (hydrocarbon group having a substituent) include a hydrocarbon group in which at least one hydrogen atom of the above-described hydrocarbon group is substituted with a substituent, such as a substituted alkyl group, a substituted alkenyl group. Group, substituted alkynyl group, substituted alkadienyl group, substituted aryl group, substituted aralkyl group and the like. The substituent will be described later.
Specific examples of the substituted alkyl group in the specific examples of the substituted hydrocarbon group include a methoxymethyl group. Specific examples of the substituted aryl group include a tolyl group (for example, 4-methylphenyl group), xylyl group (for example, 3,5-dimethylphenyl group), 4-methoxy-3,5-dimethylphenyl group, 4-methoxy-3. , 5-di-tert-butylphenyl group and the like.

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 3 to 14 carbon atoms and at least 1, preferably 1 to 3 hetero atoms such as a nitrogen atom, an oxygen atom and / or a sulfur atom. Examples thereof include an 8-membered, preferably 5- or 6-membered monocyclic aliphatic heterocyclic group, and a 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 thiolanyl group.
Examples of the aromatic heterocyclic group include 2 to 15 carbon atoms and at least one, preferably 1 to 3 hetero atoms such as nitrogen atom, oxygen atom and / or sulfur atom. Member, preferably 5- or 6-membered monocyclic heteroaryl group, polycyclic or condensed ring heteroaryl group, and specific examples thereof include, for example, furyl group, thienyl group, pyridyl group, pyrimidyl group. , Pyrazyl group, pyridazinyl group, pyrazolyl group, imidazolyl group, oxazolyl group, thiazolyl group, benzofuryl group, benzothienyl group, quinolyl group, isoquinolyl group, quinoxalinyl group, phthalazinyl group, quinazolinyl group, naphthyridinyl group, cinimidazolinyl group, benzoimidazolyl group A benzoxazolyl group, a benzothiazolyl group, an acridinyl group, etc. are mentioned.
As the substituted heterocyclic group (heterocyclic group having a substituent), a heterocyclic group in which at least one hydrogen atom of the heterocyclic group is substituted with a substituent, that is, a substituted aliphatic heterocyclic group and a substituted aromatic group A heterocyclic group is mentioned.

  Examples of the substituent in the above-described hydrocarbon group and heterocyclic group include a hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, a halogen atom, and a halogenated hydrocarbon. Group, an alkoxy group which may have a substituent, an aryloxy group which may have a substituent, an aralkyloxy group which may have a substituent, a hetero which may have a substituent An aryloxy group, an optionally substituted alkylthio group, an optionally substituted arylthio group, an optionally substituted aralkylthio group, and optionally having a substituent Heteroarylthio group, optionally substituted acyl group, optionally substituted acyloxy group, optionally substituted alkoxycarbonyl group, optionally substituted Good aryloki Carbonyl group, aralkyloxycarbonyl group which may have a substituent, alkylenedioxy group which may have a substituent, nitro group, amino group, substituted amino group, cyano group, sulfo group, substituted silyl group Hydroxy group, carboxy group, optionally substituted alkoxythiocarbonyl group, optionally substituted aryloxythiocarbonyl group, optionally substituted aralkyloxythiocarbonyl group , An alkylthiocarbonyl group which may have a substituent, an arylthiocarbonyl group which may have a substituent, an aralkylthiocarbonyl group which may have a substituent, or a substituent Good carbamoyl group, substituted phosphino group, aminosulfonyl group, alkoxysulfonyl group, oxo group and the like can be mentioned. The hydrocarbon group, heterocyclic group, aryl group, alkyl group, alkyl group in the alkoxy group, and aralkyl group used in the description herein are the groups described above. The heteroaryl group is the same as the aromatic heterocyclic group described above. The acyl group is a group in which a carbonyl group is bonded to the hydrocarbon group described above, and the alkylene group is a divalent group in which one hydrogen atom is removed from the alkyl group described above. Indicates.

Two Qs represent spacers, and the two Qs may be the same or different, but two Qs are preferably the same. Examples of the spacer include a divalent organic group which may have a substituent such as an alkylene group, an arylene group, and a heteroarylene group. The alkylene group is the same as the alkylene group described above, the arylene group is a divalent aryl group in which one hydrogen atom is removed from the aryl group, and the heteroarylene group is the aromatic heterocyclic ring described above. A divalent group in which one hydrogen atom is further removed from the group. The divalent organic group has at least one heteroatom or atomic group such as an oxygen atom, a carbonyl group, a sulfur atom, an imino group or a substituted imino group inserted at an arbitrary position in the carbon chain of the organic group. It may be what was done. Furthermore, the divalent organic group may have a substituent. The substituents in the substituent and the substituted imino group are the same as those described above. As the spacer, an alkylene group is preferable.
As the alkylene group in the spacer Q, for example, a linear or branched alkylene group having 1 to 10 carbon atoms is preferable, and specific examples thereof include a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, a hexamethylene group. Examples include a methylene group, a heptamethylene group, an octamethylene group, a nonamethylene group, a decamethylene group, a propylene group, and a dimethylmethylene group.
Specific examples of the alkylene group having a substituent include a difluoromethylene group.

Specific examples of the diphosphine compound represented by the general formula (1) of the present invention include, for example,
[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
[4,4′-bi- (7-ethoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
[4,4′-bi- (7-n-propoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
[4,4′-bi- (7-n-butoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
[4,4′-bi- (7-phenoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methylphenyl) phosphine],
[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (3,5-dimethylphenyl) phosphine],
[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methoxy-3,5-dimethylphenyl) phosphine],
[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methoxy-3,5-di-tert-butylphenyl) Phosphine] and the like. In the present specification, 1,3-benzodioxole represents 1,2-methylenedioxybenzene, and the numbering thereof is one in which the oxygen atom is 1. These compounds are represented by the following chemical structural formulas.

  Further examples include diphosphine compounds represented by the following formulas.

In order to use the diphosphine compound represented by the general formula (1) of the present invention as an asymmetric ligand, an optically active substance thereof is used. As a specific example of the optically active diphosphine compound represented by the general formula (1), that is, the optically active diphosphine compound represented by the general formula (1), for example, as the (+) isomer,
(+)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(+)-[4,4′-bi- (7-ethoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(+)-[4,4′-bi- (7-n-propoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(+)-[4,4′-bi- (7-n-butoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(+)-[4,4′-bi- (7-phenoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(+)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methylphenyl) phosphine],
(+)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (3,5-dimethylphenyl) phosphine],
(+)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methoxy-3,5-dimethylphenyl) Phosphine],
(+)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methoxy-3,5-di-tert) -Butylphenyl) phosphine] and the like, and these can be represented by the following chemical structural formulas.

  Moreover, the diphosphine compound shown below is mentioned as another example of (+) body.

Moreover, as an example of the (-) body diphosphine compound, like the above-mentioned (+) body, for example,
(−)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(−)-[4,4′-bi- (7-ethoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(−)-[4,4′-bi- (7-n-propoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(−)-[4,4′-bi- (7-n-butoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(−)-[4,4′-bi- (7-phenoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine),
(−)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methylphenyl) phosphine],
(−)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (3,5-dimethylphenyl) phosphine],
(−)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methoxy-3,5-dimethylphenyl) Phosphine],
(−)-[4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methoxy-3,5-di-tert -Butylphenyl) phosphine] and the like. These (−)-diphosphine compounds can be represented by the following chemical structural formulas.

  Moreover, the compound etc. which are represented by a following formula are mentioned.

The diphosphine compound represented by the general formula (1) of the present invention can be produced by a conventional method, a method according to steps 1 to 4 shown below, or the like.
(1) Step 1
The following general formula (2)

(In the formula, X ² represents a halogen atom, and R ¹ and Q are the same as above.)
And a compound represented by the following general formula (3)
PR ² R ³ (═O) X ³ (3)
(Wherein X ³ represents a halogen atom, and R ² and R ³ are the same as described above.)
Is reacted with a phosphonic acid halide represented by the following general formula (4) in the presence of magnesium in an appropriate solvent.

(In the formula, R ^{1 to} R ³ and Q are the same as described above.)
The phosphine oxide compound represented by these is manufactured.
(2) Step 2
The phosphine oxide compound represented by the general formula (4) obtained in the step (1) is reacted with a halogenating agent in the presence of a lithium compound and a base as necessary in a solvent as necessary. The following general formula (5)

（式中、Ｘ^４はハロゲン原子を示し、Ｒ^１〜Ｒ^３及びＱは前記と同じ。）
で表される４−ハロゲノホスフィンオキシド化合物を製造する。
（３）工程３
前記の工程（２）で得られた一般式（５）で表される４−ハロゲノホスフィンオキシド化合物を、適当な溶媒中でカップリング反応させることにより、次の一般（６）

(In the formula, X ⁴ represents a halogen atom, and R ^{1 to} R ³ and Q are the same as described above.)
The 4-halogenophosphine oxide compound represented by these is manufactured.
(3) Process 3
The 4-halogenophosphine oxide compound represented by the general formula (5) obtained in the above step (2) is subjected to a coupling reaction in an appropriate solvent, whereby the following general (6)

(In the formula, R ^{1 to} R ³ and Q are the same as above.)
The diphenylphosphine oxide compound represented by these is manufactured.
(4) Step 4
The target diphosphine compound represented by the general formula (1) is produced by reducing the diphenylphosphine oxide compound represented by the general formula (6) obtained in the step (3) in an appropriate solvent. be able to.

In the general formula (2), the halogen atom represented by X ² and the halogen atom represented by X ³ in the general formula (3) are each independently a fluorine atom, a chlorine atom, or a bromine atom. And iodine atom.
Specific examples of the compound represented by the general formula (2) include, for example, 6-bromo-4-methoxy-1,3-benzodioxole, 6-bromo-4-ethoxy-1,3-benzodioxyl. Sole, 6-bromo-4-n-propoxy-1,3-benzodioxole, 6-bromo-4-n-butoxy-1,3-benzodioxole, 6-bromo-4-phenoxy-1, 3-benzodioxole etc. are mentioned, If these compounds and other compounds are illustrated by a chemical structural formula, the compound etc. which are represented by a following formula will be mentioned.

Specific examples of the phosphonic acid halide represented by the general formula (3) are, for example,
Diphenylphosphonic acid chloride, di (4-methylphenyl) phosphonic acid chloride, di (3,5-dimethylphenyl) phosphonic acid chloride, di (4-methoxy-3,5-dimethylphenyl) phosphonic acid chloride, di (4- (Methoxy-3,5-di-tert-butylphenyl) phosphonic acid chloride and the like. If these compounds and other compounds are exemplified by chemical structural formulas, the compounds represented by the following formulas may be mentioned.

Specific examples of the phosphine oxide compound represented by the general formula (4) that can be produced in the above-described step (1) include (4-methoxy-1,3-benzodioxole) -6-yl-diphenyl. Phosphine oxide, (4-Ethoxy-1,3-benzodioxole) -6-yl-diphenylphosphine oxide, (4-n-propoxy-1,3-benzodioxole) -6-yl-diphenylphosphine oxide (4-n-butoxy-1,3-benzodioxole) -6-yl-diphenylphosphine oxide, (4-phenoxy-1,3-benzodioxole) -6-yl-diphenylphosphine oxide, 4-methoxy-1,3-benzodioxole) -6-yl-di (4-methylphenyl) phosphine oxide, (4-methoxy-1, -Benzodioxole) -6-yl-di (3,5-dimethylphenyl) phosphine oxide, (4-methoxy-1,3-benzodioxole) -6-yl-di (4-methoxy-3, 5-dimethylphenyl) phosphine oxide, (4-methoxy-1,3-benzodioxole) -6-yl-di (4-methoxy-3,5-di-tert-butylphenyl) phosphine oxide, and the like. When these compounds and other compounds are exemplified by chemical structural formulas, compounds represented by the following formulas can be mentioned.

In the step (1), the amount of the compound represented by the general formula (2) and the phosphonic acid halide represented by the general formula (3) is phosphonic acid halogen represented by the general formula (3). The compound is appropriately selected from the range of usually 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to the compound represented by the general formula (2).
The usage-amount of magnesium is normally selected from the range of 1-5 equivalent normally with respect to the compound represented by the said General formula (2), Preferably it is 1-3 equivalent.
Examples of the solvent include aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and xylene, dichloromethane, 1,2-dichloroethane, chloroform, and tetrachloride. Carbon, halogenated hydrocarbons such as o-dichlorobenzene, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,3-dioxolane, 2- Examples include ethers such as methyltetrahydrofuran and cyclopentylmethyl ether, sulfoxides such as dimethyl sulfoxide, and N-methylpyrrolidone. These solvents may be used alone or in appropriate combination of two or more.
The amount of the solvent used is appropriately selected from the range of usually 1 to 20 times the volume, preferably 2 to 10 times the volume of the compound represented by the general formula (2).
While the reaction temperature varies depending on the raw materials used, the type of solvent, and the like, it is usually appropriately selected from the range of 0 ° C. to reflux of the solvent, preferably 15 to 40 ° C.
The reaction time is appropriately selected from the range of usually 0.1 to 24 hours, preferably 5 to 12 hours.
The phosphine oxide compound represented by the general formula (4) produced in the step (1) is used for the next reaction as it is, or after being subjected to post-treatment, purification, isolation, etc. as necessary. Also good. Specific means such as post-treatment, purification, and isolation include means known per se, such as solvent extraction, salting out, crystallization, recrystallization, various chromatography, and the like.
In addition, the compound represented by the general formula (2) and the phosphonic acid halide represented by the general formula (3) may be commercially available products or those appropriately produced.

The phosphine oxide compound represented by the general formula (4) produced in the step (1) is reacted with a halogenating agent in the presence of a lithium compound and a base as necessary in a solvent as necessary. Thus, the 4-halogenophosphine oxide compound represented by the general formula (5) can be produced.
In the general formula (5), examples of the halogen atom represented by X ⁴ include a chlorine atom, a bromine atom, and an iodine atom.
Specific examples of the 4-halogenophosphine oxide compound represented by the general formula (5) include, for example, (4-iodo-7-methoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide, (4-Iodo-7-ethoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide, (4-iodo-7-n-propoxy-1,3-benzodioxole) -5 Yl-diphenylphosphine oxide, (4-iodo-7-n-butoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide, (4-iodo-7-phenoxy-1,3-benzodio Xol) -5-yl-diphenylphosphine oxide, (4-iodo-7-methoxy-1,3-benzodioxole) -5-yl-di (4-methyl) Phenyl) phosphine oxide, (4-iodo-7-methoxy-1,3-benzodioxole) -5-yl-di (3,5-dimethylphenyl) phosphine oxide, (4-iodo-7-methoxy-1) , 3-Benzodioxol) -5-yl-di (4-methoxy-3,5-dimethylphenyl) phosphine oxide, (4-iodo-7-methoxy-1,3-benzodioxole) -5 Il-di (4-methoxy-3,5-di-tert-butylphenyl) phosphine oxide, and the like. If these compounds and other compounds are exemplified by chemical structural formulas, compounds represented by the following formulae: Etc.

Examples of the lithium compound used in the step (2) include organic lithium compounds such as alkyllithium, aryllithium and aralkyllithium, and among them, alkyllithium is preferable.
Specific examples of alkyl lithium include methyl lithium, ethyl lithium, n-butyl lithium, tert-butyl lithium and the like.
As the organic lithium compound, a commercially available product may be used, or an appropriately manufactured product such as a reaction of lithium metal and an organic halide may be used.
The usage-amount of a lithium compound is normally selected from the range of 1-5 equivalent normally with respect to the phosphine oxide compound represented by the said General formula (4), Preferably it is 1-3 equivalent.
Examples of the halogenating agent include inorganic halogenating agents and organic halogenating agents. Specific examples of the inorganic halogenating agent include, for example, alkali metal halides such as lithium bromide, sodium bromide, potassium fluoride and potassium iodide, phosphorus halides such as phosphorus trichloride and phosphorus tribromide, fluorine , Halogens such as chlorine, bromine and iodine. Specific examples of the organic halogenating agent include succinimides such as N-chlorosuccinimide and N-bromosuccinimide. Among these halogenating agents, halogens are preferable, and halogens such as chlorine, bromine and iodine are more preferable.

The usage-amount of a halogenating agent is normally selected from the range of 1-5 equivalent normally with respect to the phosphine oxide compound represented by the said General formula (4), Preferably it is 1-3 equivalent.
Examples of the base used as necessary include inorganic bases and organic bases.
Examples of the inorganic base include salts of alkali metals or 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 the like. Examples thereof include metal hydrides such as hydroxide, sodium hydride, 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 such as sodium acetate, potassium acetate, Organic acid salts of alkali metals or alkaline earth metals such as magnesium acetate and calcium acetate, such as diisopropylamine, triethylamine, diisopropylethylamine, N, N-dimethylaniline, piperidine, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.3.0] Non-5-ene, 1,8-diazabicyclo [5.4.0] undec-7-ene, tri-n-butylamine, N-methylmorpholine and other organic amines, quaternary ammonia Salts and the like. Among these bases, organic amines are preferable.
The usage-amount of a base is suitably selected from the range of 1-5 equivalent normally with respect to the phosphine oxide compound represented by the said General formula (4), Preferably it is 1-3 equivalent.

Examples of the solvent used as necessary include aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and xylene, dichloromethane, and 1,2-dichloroethane. , Halogenated hydrocarbons such as chloroform, carbon tetrachloride, o-dichlorobenzene, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,3 -Ethers such as dioxolane, 2-methyltetrahydrofuran, cyclopentylmethyl ether, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, methanol, ethanol, 2-pro Alcohols such as diol, n-butanol, 2-ethoxyethanol, benzyl alcohol, polyhydric alcohols such as ethylene glycol, 1,2-propanediol, 1,3-propanediol, glycerin, methyl acetate, ethyl acetate, acetic acid Esters such as n-butyl and methyl propionate, amides such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, sulfoxides such as dimethyl sulfoxide, cyano-containing organic compounds such as acetonitrile, N- Examples include methyl pyrrolidone and water. These solvents may be used alone or in appropriate combination of two or more.
The amount of the solvent to be used varies depending on the raw material, halogenating agent, type of solvent and the like, but is usually selected appropriately from the range of 0.1 to 25 times volume, preferably 5 to 15 times volume.
The reaction temperature varies depending on the halogenating agent to be used, the type of solvent, and the like, but is usually appropriately selected from the range of −78 ° C. to reflux of the solvent, preferably −78 to 0 ° C.
The reaction time is appropriately selected from the range of usually 0.11 to 24 hours, preferably 2 to 10 hours.
Even if the 4-halogenophosphine oxide compound represented by the general formula (5) produced in the step (2) was used in the next reaction as it was, it was subjected to post-treatment, purification, isolation and the like as necessary. It may be used later. Specific means for post-treatment, purification, isolation and the like are the same as described above.

The 4-halogenophosphine oxide compound represented by the above general formula (5) produced in the step (2) is subjected to a coupling reaction in an appropriate solvent to thereby produce diphenyl represented by the above general formula (6). Phosphine oxide compounds can be produced.
Specific examples of the diphenylphosphine oxide compound represented by the general formula (6) include, for example, [4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-. Diyl-bis (diphenylphosphine oxide), [4,4′-bi- (7-ethoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine oxide), [4 4'-bi- (7-n-propoxy-1,3-benzodioxole)]-5,5'-diyl-bis (diphenylphosphine oxide), [4,4'-bi- (7-n- Butoxy-1,3-benzodioxole)]-5,5′-diyl-bis (diphenylphosphine oxide), [4,4′-bi- (7-phenoxy-1,3-benzodioxole)] -5,5'-diyl-bis (diphenylphosphite Oxide), [4,4′-bi- (7-methoxy-1,3-benzodioxole)]-5,5′-diyl-bis [di (4-methylphenyl) phosphine oxide], [4 4'-bi- (7-methoxy-1,3-benzodioxole)]-5,5'-diyl-bis [di (3,5-dimethylphenyl) phosphine oxide], [4,4'-bi -(7-methoxy-1,3-benzodioxole)]-5,5'-diyl-bis [di (4-methoxy-3,5-dimethylphenyl) phosphine oxide], [4,4'-bi -(7-methoxy-1,3-benzodioxole)]-5,5'-diyl-bis [di (4-methoxy-3,5-di-tert-butylphenyl) phosphine oxide] and the like. If these compounds and other compounds are illustrated by chemical structural formulas, Compounds represented by the serial type and the like.

The coupling reaction in the step (3) is preferably performed in the presence of a coupling reagent such as a metal. Examples of the metal include copper, zinc, magnesium, manganese and the like, and copper is preferable.
The usage-amount of a coupling reagent is suitably selected from the range of 1-10 equivalent normally with respect to 4-halogenophosphine oxide compound, Preferably it is 2-5 equivalent.
The coupling reaction is preferably performed in the presence of a solvent. Examples of the solvent include aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and xylene, dichloromethane, 1,2-dichloroethane, chloroform, and tetrachloride. Carbon, halogenated hydrocarbons such as o-dichlorobenzene, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,3-dioxolane, 2- Ethers such as methyltetrahydrofuran and cyclopentylmethyl ether, alcohols such as methanol, ethanol, 2-propanol, n-butanol, 2-ethoxyethanol and benzyl alcohol, acetone, methyl Ketones such as tilketone, methyl isobutyl ketone, cyclohexanone, esters such as methyl acetate, ethyl acetate, n-butyl acetate, methyl propionate, amides such as formamide, N, N-dimethylformamide, 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 1-15 times capacity | capacitance normally with respect to the 4-halogenophosphine oxide compound represented by the said General formula (5), Preferably it is 2-10 times capacity.
The reaction temperature varies depending on the metal used, the type of solvent, and the like, but is usually appropriately selected from the range of 50 to 200 ° C, preferably 80 to 150 ° C.
The reaction time is appropriately selected from the range of usually 1 to 15 hours, preferably 2 to 10 hours.
The diphenylphosphine oxide compound represented by the general formula (6) produced in the step (3) is subjected to post-treatment, purification, isolation, etc. as necessary even if it is optically resolved as it is. After that, optical division may be performed. Specific means for post-treatment, purification, isolation and the like are the same as described above.

The optically active form of the diphenylphosphine oxide compound represented by the general formula (6) can be easily obtained by using a known optical resolution method. Known optical resolution methods include those by high performance liquid chromatography using an optically active column and the formation of diastereomeric salts with an optically active acidic compound in a solvent. Examples of the solvent include aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and xylene, dichloromethane, 1,2-dichloroethane, chloroform, and tetrachloride. Carbon, halogenated hydrocarbons such as o-dichlorobenzene, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,3-dioxolane, 2- Ethers such as methyltetrahydrofuran and cyclopentylmethyl ether, alcohols such as methanol, ethanol, 2-propanol, n-butanol, 2-ethoxyethanol and benzyl alcohol, acetone, methyl Ketones such as tilketone, methyl isobutyl ketone, cyclohexanone, esters such as methyl acetate, ethyl acetate, n-butyl acetate, methyl propionate, amides such as formamide, N, N-dimethylformamide, 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.
Examples of the optically active acidic compound include (+) or (−)-tartaric acid, (+) or (−)-dibenzoyl tartaric acid, (+) or (−)-toluoyl tartaric acid, (+) or (−)-pivaloyl tartaric acid. , (+) Or (−)-camphorsulfonic acid, (+) or (−)-mandelic acid, and the like.
The diphenylphosphine oxide compound represented by the general formula (6) of the present invention produced by such a method can be used using the optically active diphenylphosphine oxide compound as an asymmetric catalyst.
Examples of the asymmetric reaction when the optically active diphenylphosphine oxide compound is used as the asymmetric catalyst include asymmetric synthesis reactions such as an aldol reaction.

The diphosphine compound represented by the general formula (1) of the present invention is produced by reducing the diphenylphosphine oxide compound represented by the general formula (6) produced in the step (3) in an appropriate solvent. can do.
The reduction reaction in step (4) may be performed in the presence of a reducing agent such as a silane compound. Examples of the silane compound include trichlorosilane.
The amount of the reducing agent used is appropriately selected from the range of usually 5 to 20 equivalents, preferably 5 to 15 equivalents, relative to the diphenylphosphine oxide compound represented by the general formula (6).
The reduction reaction is preferably performed in the presence of a base. The base may be the same as the base described in the above step (2).
The usage-amount of a base is normally selected suitably from the range of 5-20 equivalent with respect to the diphenylphosphine oxide compound represented by the said General formula (6), Preferably it is 5-15 equivalent.
Examples of the solvent include aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and xylene, dichloromethane, 1,2-dichloroethane, chloroform, and tetrachloride. Carbon, halogenated hydrocarbons such as o-dichlorobenzene, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,3-dioxolane, 2- Ethers such as methyltetrahydrofuran and cyclopentylmethyl ether, methanol, ethanol, 2
Alcohols such as propanol, n-butanol, 2-ethoxyethanol, benzyl alcohol, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, esters such as methyl acetate, ethyl acetate, n-butyl acetate, methyl propionate , Amides such as formamide, N, N-dimethylformamide, 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 normally selected suitably from the range of 0.12-25 times capacity with respect to the diphenylphosphine oxide compound represented by the said General formula (6), Preferably it is 5-15 times capacity.
The reaction temperature varies depending on the base used, the type of solvent, and the like, but is usually selected from the range of room temperature to 200 ° C, preferably 100 to 150 ° C.
The reaction time is appropriately selected from the range of usually 0.1 to 15 hours, preferably 2 to 10 hours.
The diphosphine compound represented by the general formula (1) of the present invention produced in the step (4) may be used as it is or after post-treatment, purification, isolation, etc. It may be used as Specific means for post-treatment, purification, isolation and the like are the same as described above.

Any of the above steps may be performed in an inert gas atmosphere. Examples of the inert gas include argon gas and nitrogen gas.
The optically active diphosphine compound represented by the general formula (1) of the present invention produced by such a method is prepared by using the optically active diphosphine compound as an asymmetric catalyst and in the presence of a transition metal complex. When used as an asymmetric ligand in an asymmetric synthesis carried out in situ or in an asymmetric reduction reaction such as an asymmetric hydrogenation reaction, the desired optically active substance can be obtained in good yield and asymmetric yield.
Examples of the asymmetric reaction in the case of using an optically active diphosphine compound as an asymmetric catalyst include asymmetric synthesis reactions such as Baylis-Hillman reaction.

Examples of the transition metal complex of the present invention include transition metal complexes represented by the following general formula (11) or (12).
_{M m L n X p Y q} (11)
_{[M m L n X p Y} q] Z s (12)
(In the above formula, L represents a diphosphine compound represented by the above general formula (1), M represents a transition metal, X represents a halogen atom, a carboxylate group, an allyl group, 1,5-cyclooctadiene or norbornadiene. Y represents a ligand, Z represents an anion or cation, m and n each independently represents an integer of 1 to 5, and p, q and s each independently represent an integer of 0 to 5 Is shown.)
In the general formulas (11) and (12), the diphosphine compound represented by the general formula (1) represented by L is preferably an optically active substance. In this case, when L is an optically active substance of the diphosphine compound represented by the general formula (1) (that is, an optically active diphosphine compound represented by the general formula (1)), the transition metal of the present invention is used. The complex is an optically active transition metal complex.

In the general formulas (11) and (12), the transition metal represented by M is the same or different, and examples thereof include transition metals of Groups 8 to 10 of the periodic table, and specific examples thereof include ruthenium (Ru). ), Rhodium (Rh), iridium (Ir), palladium (Pd), nickel (Ni) and the like.
Examples of the ligand represented by Y are the same or different and include neutral ligands such as aromatic compounds and olefin compounds, and amines.
Examples of the aromatic compound include benzene, p-cymene, 1,3,5-trimethylbenzene (mesitylene), hexamethylbenzene and the like. Examples of the olefin compound include ethylene, 1,5-cyclooctadiene, cyclopentadiene, norbornadiene and the like. Other neutral ligands include N, N-dimethylformamide (DMF), acetonitrile, benzonitrile, acetone, chloroform and the like.
As amines, 1,2-diphenylethylenediamine (DPEN), 1,2-dicyclohexylethylenediamine, 1,2-diaminocyclohexane, ethylenediamine, 1,1-bis (4-methoxyphenyl) -2-isopropylethylenediamine (DAIPEN) And the like, aliphatic amines such as triethylamine, and aromatic amines such as pyridine.
Examples of the halogen atom represented by X include a chlorine atom, a bromine atom, and an iodine atom.

In the general formula (12), as the anion represented by Z, Z is BF ₄ , ClO ₄ , OTf, NO ₃ , PF ₆ , SbF ₆ , AsF ₆ , BPh ₄ , BH ₄ , BF ₄ , Cl, Br, I, I ₃ , sulfonate and the like can be mentioned. Here, Tf represents a triflate group (SO ₂ CF ₃ ).
Examples of the cation include the following general formula (13)
[(R ¹¹ ) ₂ NH ₂ ] ⁺ (13)
(In the formula, two R ^11's are the same or different and each represents a hydrogen atom or a hydrocarbon group optionally having a substituent).
In the general formula (13), the hydrocarbon group which may have a substituent represented by R ¹¹ is the same as the hydrocarbon group which may have a substituent described above for the general formula (1). It is. Examples of the hydrocarbon group optionally having a substituent represented by R ¹¹ include an alkyl group having 1 to 5 carbon atoms, a cycloalkyl group, and a phenyl group and a substituent which may have a substituent. Even if it does, a benzyl group etc. are more preferable.
Specific examples of such cations include [Me ₂ NH ₂ ] ⁺ , [Et ₂ NH ₂ ] ⁺ , [Pr ₂ NH ₂ ] ^{+ and the} like.

Below, the preferable aspect of the said transition metal complex of this invention is demonstrated.
[1] General formula (11)
_{M m L n X p Y q} (11)
1) When M is Ir or Rh, X is Cl, Br or I, and m = n = p = 2 and q = 0.
2) When M is Ru, (i) when X represents Cl, Br or I, and Y represents a trialkylamino group, m = n = 2, p = 4, and q = 1.
(Ii) When X represents Cl, Br or I and Y represents a pyridyl group or a ring-substituted pyridyl group, m = n = 1, p = 2, and q = 2.
(Iii) When X is a carboxylate group, m = n = 1, p = 2, and n2 = q = 0.
(Iv) When X is Cl, Br or I, m = n = p = 2 and q = 0.
3) When M is Pd, (i) when X is Cl, Br or I, m = n = 1, p = 2, q = 0.
(Ii) When X is an allyl group, m = n = p = 2 and q = 0.
4) When M is Ni, when X is Cl, Br or I, m = n = 1, p = 2, q = 0.

[2] General formula (12)
_{[M m L n X p Y} q] Z s (12)
1) When M is Ir or Rh, X is 1,5-cyclooctadiene or norbornadiene, Z is BF ₄ , ClO ₄ , OTf, PF ₆ , SbF ₆ or BPh ₄ and m = n = p = S = 1, q = 0, m = s = 1, n = 2, p = q = 0, or m = s = 1, n = 1, p = q = 0.
2) When M is Ru, (i) X is Cl, Br or I, Y is a neutral ligand such as an aromatic compound or an olefin compound, Z is Cl, Br, I, I ₃ , Sulfonate, m = n = p = s = q = 1.
(Ii) Z is BF ₄ , ClO ₄ , OTf, PF ₆ , SbF ₆ or BPh ₄ , and m = n = 1, p = q = 0, and s = 2.
(Iii) When Z is an ammonium ion, m = n = 2, p = 5, and q = 0.
3) When M is Pd and Ni, Z is BF ₄ , ClO ₄ , OTf, PF ₆ , SbF ₆ or BPh ₄ , m = n = 1, p = q = 0, s = 2.

The transition metal complex of the present invention as described above can be obtained, for example, by reacting the optically active diphosphine compound represented by the general formula (1) with a transition metal complex precursor.
Here, “obtained by reacting” means a transition metal complex obtained by post-treatment as necessary, a transition metal complex isolated and / or purified after post-treatment, post-treatment or It means a transition metal complex or the like that uses the reaction mixture as it is without isolation or purification.
The transition metal complex of the present invention can be obtained by reacting the diphosphine compound of the present invention or the diphosphine compound of the present invention and other asymmetric ligands with a transition metal complex precursor.
As a transition metal complex precursor, for example, the following general formula (15)
[MX _p Y _q ] Z _s (15)
(Wherein, M, X, Y, Z, p, q, and s are the same as described above) and the like.
Specific examples of the transition metal complex precursor represented by the general formula (15) used in the present invention include the case where the transition metal represented by M in the general formula (15) is ruthenium, rhodium and iridium. Then, 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 (penta methylcyclopentadiene)] ₂ , [RuCl ₂ (cod)] _n , [RuBr ₂ (cod)] _n , [RuI ₂ (cod)] _n , [RuCl ₂ (nbd)] _n , [RuBr ₂ (nbd)] _n , _{[RuI 2 (nbd)] n} , RuCl 3 hydrate, RuBr ₃ hydrate, RuI _{3 hydrate, [RhCl 2 (cyclopentadiene)]} 2, [RhBr 2 (cyclopentadiene)] 2, [RhI 2 (cyclopentadiene )] ₂ , [RhCl ₂ (pentamethylcyclopentadiene)] ₂ , [RhBr ₂ (pentamethy
lcyclopentadiene)] ₂ , [RhI ₂ (pentamethylcyclopentadiene)] ₂ , [RhCl ₂ (cod)] _n , [RhBr ₂ (cod)] _n , [RhI ₂ (cod)] _n , [RhCl ₂ (nbd)] _n , _{[RhBr 2 (nbd)] n} , [RhI 2 (nbd)] n, [Rh (cod) 2] SbF 6, RhCl 3 hydrate, RhBr ₃ hydrate, RhI ₃ hydrate, [IrCl ₂ ( cyclopentadiene)] ₂ , [IrBr ₂ (cyclopentadiene)] ₂ , [IrI ₂ (cyclopentadiene)] ₂ , [IrCl ₂ (pentamethylcyclopentadiene)] ₂ , [IrBr ₂ (pentamethylcyclopentadiene)] ₂ , [IrI ₂ (pentamethylcyclopentadiene) _{2 [IrCl 2 (cod)] n} , [IrBr 2 (cod)] n, [IrI 2 (cod)] n, [IrCl 2 (nbd) _{n, [IrBr 2 (nbd)} ] n, [IrI 2 (nbd)] n, IrCl 3 hydrate, IrBr ₃ hydrate, IrI ₃ hydrate, and the like. In the above formula, n represents a positive number, cod represents 1,5-cyclooctadiene, and nbd represents norbornadiene.

Below, the manufacturing method of the transition metal complex of this invention is demonstrated concretely.
In addition, the symbol used in the formula of the transition metal complex shown below is respectively L is 1) the optically active diphosphine compound of the present invention, or 2) the optically active diphosphine compound of the present invention and other asymmetric coordination. Tf represents a triflate group (SO ₂ CF ₃ ), Ph represents a phenyl group, and Ac represents an acetyl group. Specific examples include those using a bidentate ligand as an asymmetric ligand in order to avoid complexity.
[1] Rhodium complex:
The rhodium complex can be produced, for example, according to the method described in “Chemical Course of 4th Edition” edited by The Chemical Society of Japan, Vol. 18, Organometallic Complex, pages 339-344, 1991 (Maruzen). Specifically, bis (cycloocta-1,5-diene) rhodium (I) tetrafluoroborate and the diphosphine compound of the present invention, or the diphosphine compound of the present invention and other asymmetric ligands are reacted. Can be obtained.
Specific examples of the rhodium complex include the following complexes.
_{[Rh (L) Cl] 2} , [Rh (L) Br] 2, [Rh (L) I] 2, [Rh (cod) (L)] BF 4, [Rh (cod) (L)] ClO 4 [Rh (cod) (L)] PF ₆ , [Rh (cod) (L)] BPh ₄ , [Rh (cod) (L)] OTf, [Rh (nbd) (L)] BF ₄ , [Rh (Nbd) (L)] ClO ₄ , [Rh (nbd) (L)] PF ₆ , [Rh (nbd) (L)] BPh ₄ , [Rh (nbd) (L)] OTf, [Rh (L) ₂ ] ClO ₄ , [Rh (L) ₂ ] PF ₆ , [Rh (L) ₂ ] OTf, [Rh (L) ₂ ] BF ₄

[2] Ruthenium complex:
The ruthenium complex can be obtained, for example, according to the method described in T. Ikariya et al., J. Chem. Soc., Chem. Commun., 1985, 922, etc. Specifically, [Ru (cod) Cl ₂ ] _n and the diphosphine compound of the present invention, or the diphosphine compound of the present invention and an asymmetric ligand are heated and refluxed in a toluene solvent in the presence of triethylamine. Can be manufactured.
It can also be obtained by the method described in K. Mashima et al., J. Chem. Soc., Chem. Commun., 1989, 1208. Specifically, [Ru (p-cymene) I ₂ ] ₂ and the diphosphine compound of the present invention, or the diphosphine compound of the present invention and another asymmetric ligand are heated and stirred in dichloromethane and ethanol. Obtainable.
Specific examples of the ruthenium complex include the following complexes.
Ru (OAc) ₂ (L), Ru ₂ Cl ₄ (L) ₂ NEt ₃ , [RuCl (benzone) (L)] Cl, [RuBr (benzone) (L)] Br, [RuI (benzene) (L) ] I, [RuCl (p-cymene) (L)] Cl, [RuBr (p-cymene) (L)] Br, [RuI (p-cymene) (L)] I, [Ru (L)] (BF _{4) 2, [Ru (L} )] (ClO 4) 2, [Ru (L)] (PF 6) 2, [Ru (L)] (BPh 4) 2, [Ru (L)] (OTf) 2 , Ru (OCOCF ₃ ) ₂ (L), [{RuCl (L) ₂ } (μ-Cl) ₃ ] [Me ₂ NH ₂ ], [{RuCl (L)} ₂ (μ-Cl) ₃ ] [Et _{2 NH 2], [{RuBr} (L) 2} (μ-Cl) 3] [Me ₂ NH
₂ ], [{RuBr (L) ₂ } (μ-Cl) ₃ ] [Et ₂ NH ₂ ], RuCl ₂ (L), RuBr ₂ (L), RuI ₂ (L), RuCl ₂ (L) (diamine) ), RuBr ₂ (L) (diamine), RuI ₂ (L) (diamine), [{RuI (L)} ₂ (μ-I) ₃ ] [Me ₂ NH ₂ ], [{RuI (L)} ₂ (Μ-I) ₃ ] [Et ₂ NH ₂ ], RuCl ₂ (L) (pyridine), RuBr ₂ (L) (pyridine), RuI ₂ (L) (pyridine)

[3] Iridium complex:
The iridium complex can be obtained, for example, according to the method described in K. Mashima et al., J. Organomet. Chem., 1992, 428, 213 and the like. Specifically, the diphosphine compound of the present invention, or the diphosphine compound of the present invention and other asymmetric ligands, and [Ir (cod) (CH ₃ CN) ₂ ] BF ₄ are stirred and reacted in tetrahydrofuran. Can be obtained.
Specific examples of the iridium complex include the following complexes.
_{[Ir (L) Cl] 2} , [Ir (L) Br] 2, [Ir (L) I] 2, [Ir (cod) (L)] BF 4, [Ir (cod) (L)] ClO 4 , [Ir (cod) (L)] PF ₆ , [Ir (cod) (L)] BPh ₄ , [Ir (cod) (L)] OTf, [Ir (nbd) (L)] BF ₄ , [Ir (Nbd) (L)] ClO ₄ , [Ir (nbd) (L)] PF ₆ , [Ir (nbd) (L)] BPh ₄ , [Ir (nbd) (L)] OTf

[4] Palladium complex:
The palladium complex can be obtained, for example, according to the method described in Y. Uozumi et al., J. Am. Chem. Soc., 1991, 9887. Specifically, it can be obtained by reacting the diphosphine compound of the present invention or the diphosphine compound of the present invention and other asymmetric ligands with π-allyl palladium chloride.
Specific examples of the palladium complex include the following complexes.
PdCl ₂ (L), (π-allyl) Pd (L), [(Pd (L)] BF ₄ , [(Pd (L)) ClO ₄ , [(Pd (L)) PF ₆ , [(Pd ( L)) BPh ₄ , [(Pd (L)) OTf

[5] Nickel complex:
The nickel complex can be obtained, for example, by a method described in “Chemical Course of 4th Edition” Vol. 18, Organometallic Complex, page 376, 1991 (Maruzen), edited by the Chemical Society of Japan. In addition, according to the method described in Y. Uozumi et al., J. Am. Chem. Can be obtained by dissolving in a mixed solvent of 2-propanol and methanol and stirring with heating.
Specific examples of the nickel complex include the following complexes.
NiCl ₂ (L), NiBr ₂ (L), NiI ₂ (L)

  In addition, the transition metal complex of the present invention comprises an optically active diphosphine compound represented by the above general formula (1) and a transition metal complex precursor, and is used as a catalyst for asymmetric synthesis without isolation or purification. It may be used as a catalyst for asymmetric reduction reaction. This is a so-called asymmetric reduction reaction performed in situ.

The transition metal complex of the present invention is an optically active transition metal complex having an optically active diphosphine compound represented by the above general formula (1) as an asymmetric ligand. Accordingly, the optically active transition metal complex of the present invention can be used as an asymmetric catalyst such as an asymmetric synthesis catalyst, particularly an asymmetric reduction reaction catalyst, when an unsaturated compound is subjected to an asymmetric reduction reaction. An optically active compound can be obtained with good yield and asymmetric yield.
Moreover, the catalyst for asymmetric synthesis containing the optically active diphosphine compound represented by the general formula (1) of the present invention and the transition metal complex precursor is represented by the general formula (1) as an asymmetric ligand. In particular, as a catalyst for an asymmetric reduction reaction, it is used when an unsaturated compound is subjected to an asymmetric reduction reaction, whereby the desired optically active compound is obtained in the same manner as described above. A uniform yield can be obtained.
The method for producing the optically active compound of the present invention is carried out in the presence of the catalyst for asymmetric synthesis of the present invention. Examples of the method for producing an optically active compound of the present invention include a method for producing an optically active compound by subjecting an unsaturated compound to an asymmetric reduction reaction. Hereinafter, the method for producing an optically active compound of the present invention will be described taking as an example a method for producing an optically active compound by asymmetric reduction of an unsaturated compound.

In the method for producing an optically active compound by performing an asymmetric reduction reaction of an unsaturated compound, the asymmetric reduction reaction is carried out by using the asymmetric synthesis catalyst as an asymmetric reduction reaction catalyst. In the presence of In this case, the asymmetric reduction reaction is performed by an asymmetric hydrogenation reaction, and the asymmetric reduction reaction catalyst is used as an asymmetric hydrogenation reaction catalyst.
The asymmetric reduction reaction is performed in the presence of a hydrogen source. Examples of the hydrogen source include hydrogen gas and a hydrogen donating substance.
Here, a preferable asymmetric reduction reaction in the present invention includes an asymmetric hydrogenation reaction. The asymmetric hydrogenation reaction includes a catalytic asymmetric hydrogenation reaction performed in the presence of hydrogen gas, and a hydrogen donating substance. And hydrogen transfer asymmetric hydrogenation reaction carried out in the presence of.
What is necessary is just to perform the manufacturing method of the optically active compound of this invention as follows, for example.
That is, an optically active compound that is a hydride of the unsaturated compound can be obtained by subjecting the unsaturated compound to an asymmetric hydrogenation reaction in the presence of the catalyst for asymmetric hydrogenation reaction and the hydrogen source. In addition, the said reaction contains this invention which contains the mixture with the transition metal complex of this invention, the asymmetric ligand of this invention, and a transition metal complex precursor as needed in the reaction system (in reaction mixture). The asymmetric hydrogenation reaction catalyst, the asymmetric ligand of the present invention, and / or a transition metal complex precursor may be further added.

The unsaturated compound used in the method for producing an optically active compound of the present invention is preferably a prochiral compound, and examples thereof include compounds such as alkenes, ketones, imines, ketocarboxylic acids, and ketoalkenes.
As the alkenes, prochiral alkenes are preferable, and examples thereof include alkenes represented by the following general formula (21).

  As the ketones, prochiral ketones are preferable, and examples thereof include ketones represented by the following general formula (22).

  As imines, prochiral imines are preferable, and examples include imines represented by the following general formula (23).

  As the ketocarboxylic acids, prochiral ketocarboxylic acids are preferable, and examples thereof include ketocarboxylic acids represented by the following general formula (24).

  As the ketoalkene, prochiral ketoalkenes are preferable, and examples thereof include ketoalkenes represented by the following general formula (25).

In the general formulas (21) to (25), the groups represented by R ^{31 to} R ⁴⁵ may be any groups as long as they do not adversely influence the reaction, and include, for example, a hydrogen atom and a substituent. A hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, a halogen atom, a halogenated hydrocarbon group, an alkoxy group which may have a substituent, and a substituent which may have A good aryloxy group, an aralkyloxy group which may have a substituent, a heteroaryloxy group which may have a substituent, an alkylthio group which may have a substituent, and a substituent. An arylthio group which may have a substituent, an aralkylthio group which may have a substituent, a heteroarylthio group which may have a substituent, an acyl group which may have a substituent, and a substituent An acyloxy group which may have An optionally substituted alkoxycarbonyl group, an optionally substituted aryloxycarbonyl group, an optionally substituted aralkyloxycarbonyl group, and an optionally substituted alkylenedioxy group A nitro group, an amino group, a substituted amino group, a cyano group, a sulfo group, a substituted silyl group, a substituted silyloxy group, a hydroxy group, a carboxy group, an optionally substituted alkoxythiocarbonyl group, and a substituent. Aryloxythiocarbonyl group which may have a substituent, aralkyloxythiocarbonyl group which may have a substituent, alkylthiocarbonyl group which may have a substituent, arylthiocarbonyl which may have a substituent Group, an aralkylthiocarbonyl group which may have a substituent, a carbamoyl group which may have a substituent, Conversion phosphino group, aminosulfonyl group, a group such as alkoxy sulfonyl group, group in which the unsaturated compound may be present are selected appropriately.

In the general formulas (24) and (25), Q ¹¹ and Q ¹² represent a spacer or a bond. The spacers represented by Q ¹¹ and Q ¹² may be the same as those described in the general formula (1) and the like. R ³¹ and R ³² , R ³¹ and R ³³ , R ³¹ and R ³⁴ , R ³² and R ³³ , R ³² and R ³⁴ , R ³³ and R ³⁴ , R ³⁵ and R ³⁶ , R ³⁸ and R ³⁹ , R ³⁸ or ^{R 39} and ^{R 37, R 40} and ^{Q 11, R 40} and ^{R 41, R 41} and ^{Q 11, R 42} and ^{Q 12, R 44} and ^{Q 12, R 42} and ^{R 43, R 42} and ^{R 44} Alternatively, R ⁴⁵ , R ⁴³ and R ⁴⁴ , R ⁴³ and R ⁴⁵ , and R ⁴⁴ and R ⁴⁵ may be bonded to form a ring. Examples of the ring to be formed include a case where a ring is formed by bonding with an alkylene group or an alkylenedioxy group. In addition, the ring to be formed may further have a substituent (the substituent will be described later).

In the case where the unsaturated compound is a prochiral compound, the groups represented by R ^{31 to} R ⁴⁵ in the above general formulas (21) to (25) are hydrides of the obtained prochiral compound, which are optically active compounds. Any group can be used.

Each group in the above formula will be described. However, unless otherwise specified, substituents will be described later.
Examples of the hydrocarbon group which may have a substituent 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 alkadienyl 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 20 carbon atoms, preferably 1 to 15 carbon atoms, more preferably 1 to 10 carbon atoms. Examples include, for example, methyl group, ethyl group, n-propyl group, 2-propyl group, n-butyl group, 1-methylpropyl group, isobutyl group, tert-butyl group, n-pentyl group, 1-methylbutyl group. Tert-pentyl group, 2-methylbutyl group, 3-methylbutyl group, 2,2-dimethylpropyl group, n-hexyl group, 1-methylpentyl group, 1-ethylbutyl 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, lauryl Group, stearyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group and the like.

The alkenyl group may be linear or branched, for example, an alkenyl group having 2 to 20 carbon atoms, preferably 2 to 15 carbon atoms, more preferably 2 to 10 carbon atoms, and specific examples thereof include: Examples thereof include a vinyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonenyl group, and a decenyl group.
The alkynyl group may be linear or branched, for example, an alkynyl group having 2 to 20 carbon atoms, preferably 2 to 15 carbon atoms, more preferably 2 to 10 carbon atoms, and specific examples thereof include: Examples include ethynyl group, propynyl group, butynyl group, pentynyl group, hexynyl group and the like.

  The alkadienyl group may have two double bonds in the chain of the alkyl group, and may be linear, branched or cyclic, for example, having 4 or more carbon atoms, preferably 4 to 20 carbon atoms, more preferably Examples thereof include alkadienyl groups having 4 to 15 carbon atoms, more preferably 4 to 10 carbon atoms. Specific examples thereof include 1,3-butadienyl group, 2,3-dimethyl-1,3 butadienyl group and the like. It is done.

Examples of the aryl group include an aryl group having 6 to 20 carbon atoms, preferably 6 to 15 carbon atoms, and specific examples thereof include a phenyl group, a naphthyl group, an anthryl group, and a biphenyl group.
As the aralkyl group, for example, an aralkyl group having 7 to 20 carbon atoms, preferably 7 to 15 carbon atoms, in which at least one hydrogen atom of the alkyl group is substituted with the above-described aryl group, is exemplified. Examples include benzyl group, 1-phenylethyl group, 2-phenylethyl group, 1-phenylpropyl group, 3-naphthylpropyl group and the like.

Examples of the substituted hydrocarbon group (hydrocarbon group having a substituent) include a hydrocarbon group in which at least one hydrogen atom of the hydrocarbon group is substituted with a substituent, such as a substituted alkyl group and a substituted alkenyl group. , Substituted alkynyl group, substituted alkadienyl group, substituted aryl group, substituted aralkyl group and the like.
Specific examples of the substituted alkyl group in the specific examples of the substituted hydrocarbon group include a methoxymethyl group. Specific examples of the substituted aryl group include a tolyl group (for example, 4-methylphenyl group), xylyl group (for example, 3,5-dimethylphenyl group), 4-methoxy-3,5-dimethylphenyl group, 4-methoxy-3. , 5-di-tert-butylphenyl group and the like.

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 3 to 14 carbon atoms and at least 1, preferably 1 to 3 hetero atoms such as a nitrogen atom, an oxygen atom and / or a sulfur atom. Examples thereof include an 8-membered, preferably 5- or 6-membered monocyclic aliphatic heterocyclic group, and a 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 thiolanyl group.
Examples of the aromatic heterocyclic group include 3 to 8 carbon atoms having 2 to 15 carbon atoms and containing at least one, preferably 1 to 3 hetero atoms such as nitrogen, oxygen and / or sulfur atoms. Member, preferably 5- or 6-membered monocyclic heteroaryl group, polycyclic or condensed ring heteroaryl group, and specific examples thereof include, for example, furyl group, thienyl group, pyridyl group, pyrimidyl group. , Pyrazyl group, pyridazinyl group, pyrazolyl group, imidazolyl group, oxazolyl group, thiazolyl group, benzofuryl group, benzothienyl group, quinolyl group, isoquinolyl group, quinoxalinyl group, phthalazinyl group, quinazolinyl group, naphthyridinyl group, cinimidazolinyl group, benzoimidazolyl group Benzoxazolyl group, benzothiazolyl group, acridyl group, acridinyl group, etc. .
As the substituted heterocyclic group (heterocyclic group having a substituent), a heterocyclic group in which at least one hydrogen atom of the heterocyclic group is substituted with a substituent, that is, a substituted aliphatic heterocyclic group and a substituted aromatic group A heterocyclic group is mentioned.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
The halogenated hydrocarbon group is a group in which at least one hydrogen atom of the hydrocarbon group is halogenated (eg, fluorinated, chlorinated, brominated, iodinated, etc.), that is, at least one of the hydrocarbon groups. And a group in which a hydrogen atom is substituted with a halogen atom. Examples of the halogenated hydrocarbon include a halogenated alkyl group, a halogenated aryl group, and a halogenated aralkyl group.
Examples of the halogenated alkyl group include a halogenated alkyl group having 1 to 20 carbon atoms. Specific examples thereof include a chloromethyl group, a bromomethyl group, a chloroethyl group, a bromopropyl group, a fluoromethyl group, and a 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, perfluoro-n-propyl, perfluoroisopropyl, perfluoro-n-butyl, perfluoroisobutyl, perfluoro-tert-butyl, perfluoro-sec-butyl, perfluoropentyl, perfluoroiso Pentyl group, perfluoro-tert-pentyl group, perfluoro-n-hexyl group, perfluoroisohexyl group, perfluoroheptyl group, perfluorooctyl group, perfluorononyl group, perfluorodecyl group, perfluorooctylethyl group, perfluorocyclopropyl group, perfluorocyclopentyl Group, perfluorocyclohexyl group and the like. The halogenated alkyl group is preferably a halogenated alkyl group having 1 to 10 carbon atoms.
Examples of the halogenated aryl group include a halogenated aryl group having 6 to 20 carbon atoms. Specific examples thereof include a 2-fluorophenyl group, a 3-fluorophenyl group, a 4-fluorophenyl group, and a 2-chlorophenyl group. 3-chlorophenyl group, 4-chlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group, 2-iodophenyl group, 3-iodophenyl group, 4-iodophenyl group, 2-tri Fluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 2-trichloromethylphenyl group, 3-trichloromethylphenyl group, 4-trichloromethylphenyl group, perfluorophenyl group, perfluoronaphthyl group, perfluoro Anthryl group, perfluorobiphenyl Etc. The. The aryl group is preferably a halogenated aryl group having 6 to 15 carbon atoms.
Examples of the halogenated aralkyl group include a halogenated aralkyl group having 7 to 20 carbon atoms, and specific examples thereof include a 2-fluorobenzyl group, a 3-fluorobenzyl group, a 4-fluorobenzyl group, and a 2-chlorobenzyl group. 3-chlorobenzyl group, 4-chlorobenzyl group, 4-bromobenzyl group, 4-iodobenzyl group, 2-trifluoromethylbenzyl group, 3-trifluoromethylbenzyl group, 4-trifluoromethylbenzyl group, 4 -A trichloromethylbenzyl group, a perfluorobenzyl group, etc. are mentioned. The halogenated aralkyl group is preferably a halogenated aralkyl group having 6 to 15 carbon atoms.

Examples of the alkoxy group which may have a substituent include an alkoxy group and a substituted alkoxy group.
Examples of the alkoxy group may be linear, branched or cyclic, for example, an alkoxy group having 1 to 20 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, and 2-propoxy group. Group, n-butoxy group, 2-butoxy group, isobutoxy group, tert-butoxy group, n-pentyloxy group, 2-methylbutoxy group, 3-methylbutoxy group, 2,2-dimethylpropyloxy group, n-hexyl Examples thereof include an oxy group, a 2-methylpentyloxy group, a 3-methylpentyloxy group, a 4-methylpentyloxy group, a heptyloxy group, an octyloxy group, a nonyloxy group, a decyloxy group, and a cyclohexyloxy group. The alkoxy group is preferably an alkoxy group having 1 to 10 carbon atoms, more preferably an alkoxy group having 1 to 6 carbon atoms.
Examples of the substituted alkoxy group (an alkoxy group having a substituent) include an alkoxy group in which at least one hydrogen atom of the alkoxy group is substituted with a substituent.

Examples of the aryloxy group which may have a substituent include an aryloxy group and a substituted aryloxy group.
Examples of the aryloxy group include an aryloxy group having 6 to 20 carbon atoms, and specific examples thereof include a phenyloxy group, a naphthyloxy group, and an anthryloxy group. The aryloxy group is preferably an aryloxy group having 6 to 14 carbon atoms.
Examples of the substituted aryloxy group (aryloxy group having a substituent) include aryloxy groups in which at least one hydrogen atom of the aryloxy group is substituted with a substituent.

Examples of the aralkyloxy group which may have a substituent include an aralkyloxy group and a substituted aralkyloxy group.
Examples of the aralkyloxy group include an aralkyloxy group having 7 to 20 carbon atoms, and specific examples thereof include benzyloxy group, 1-phenylethoxy group, 2-phenylethoxy 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 Etc. The. The aralkyloxy group is preferably an aralkyloxy group having 7 to 12 carbon atoms.
Examples of the substituted aralkyloxy group (aralkyloxy group having a substituent) include aralkyloxy groups in which at least one hydrogen atom of the aralkyloxy group is substituted with a substituent.

Examples of the heteroaryloxy group which may have a substituent include a heteroaryloxy group and a substituted heteroaryloxy group.
The heteroaryloxy group includes, for example, at least 1, preferably 1 to 3 hetero atoms such as nitrogen atom, oxygen atom, sulfur atom, etc., and 2 to 20 carbon atoms, preferably carbon atoms. Specific examples thereof include 2-pyridyloxy group, 2-pyrazyloxy group, 2-pyrimidyloxy group, 2-quinolyloxy group, and the like.
Examples of the substituted heteroaryloxy group (heteroaryloxy group having a substituent) include heteroaryloxy groups in which at least one hydrogen atom of the aralkyloxy group is substituted with a substituent.

Examples of the alkylthio group which may have a substituent include an alkylthio group and a substituted alkylthio group.
The alkylthio group may be linear, branched or cyclic, and examples thereof include an alkylthio group having 1 to 20 carbon atoms. Specific examples thereof include a methylthio group, an ethylthio group, an n-propylthio group, and 2-propylthio group. Group, n-butylthio group, 2-butylthio group, isobutylthio group, tert-butylthio group, pentylthio group, hexylthio group, cyclohexylthio group and the like. The alkylthio group is preferably an alkylthio group having 1 to 10 carbon atoms, and more preferably an alkylthio group having 1 to 6 carbon atoms.
Examples of the substituted alkylthio group (an alkylthio group having a substituent) include an alkylthio group in which at least one hydrogen atom of the alkylthio group is substituted with a substituent.
Examples of the arylthio group which may have a substituent include an arylthio group and a substituted arylthio group. Examples of the arylthio group include an arylthio group having 6 to 20 carbon atoms, and specific examples thereof include a phenylthio group and a naphthylthio group. The arylthio group is preferably an arylthio group having 6 to 14 carbon atoms.
Examples of the substituted arylthio group (arylthio group having a substituent) include arylthio groups in which at least one hydrogen atom of the arylthio group is substituted with a substituent.
Examples of the aralkylthio group which may have a substituent include an aralkylthio group and a substituted aralkylthio group. Examples of the aralkylthio group include an aralkylthio group having 7 to 20 carbon atoms, and specific examples include a benzylthio group and a 2-phenethylthio group. The aralkylthio group is preferably an aralkylthio group having 7 to 12 carbon atoms.
Examples of the substituted aralkylthio group (aralkylthio group having a substituent) include an aralkylthio group in which at least one hydrogen atom of the aralkylthio group is substituted with a substituent.

Examples of the heteroarylthio group which may have a substituent include a heteroarylthio group and a substituted heteroarylthio group.
The heteroarylthio group includes, for example, at least 1, preferably 1 to 3 hetero atoms such as nitrogen atom, oxygen atom, sulfur atom, etc., and 2 to 20 carbon atoms, preferably carbon atoms. Specific examples thereof include 2-pyridylthio group, 2-benzimidazolylthio group, 2-benzoxazolylthio group, 2-benzthiazolylthio group, and the like.
Examples of the substituted heteroarylthio group (heteroarylthio group having a substituent) include heteroarylthio groups in which at least one hydrogen atom of the heteroarylthio group is substituted with a substituent.

Examples of the acyl group that may have a substituent include an acyl group and a substituted acyl group.
The acyl group may be linear, branched or cyclic, and examples thereof include C1-C20 acyl groups derived from acids such as carboxylic acid, sulfonic acid, sulfinic acid, phosphinic acid and phosphonic acid.
Examples of the carboxylic acid-derived acyl group include acyl groups derived from carboxylic acids such as aliphatic carboxylic acids and aromatic carboxylic acids. For example, -CORb [wherein Rb may have a hydrogen atom or a substituent. A hydrocarbon group which may have a good hydrocarbon group or a substituent and the like (the hydrocarbon group which may have this substituent and the heterocyclic group which may have a substituent are the above-mentioned It may be the same as each group described in. ]. Specific examples of acyl groups derived from carboxylic acids include formyl, acetyl, propionyl, butyryl, pivaloyl, pentanoyl, hexanoyl, lauroyl, stearoyl, benzoyl, 1-naphthoyl, 2-naphthoyl Groups and the like. The acyl group is preferably an acyl group having 2 to 18 carbon atoms.
A sulfonyl group is mentioned as an acyl group derived from a sulfonic acid. As the sulfonyl group, for example, Rc—SO ₂ — [Rc represents a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent (having the substituent). The hydrocarbon group which may be substituted and the heterocyclic group which may have the substituent may be the same as each group described above. ] The substituted sulfonyl group represented by this is mentioned. Specific examples of the sulfonyl group include a methanesulfonyl group, a trifluoromethanesulfonyl group, a benzenesulfonyl group, and a p-toluenesulfonyl group.
Examples of the acyl group derived from sulfinic acid include a sulfinyl group. As the sulfinyl group, for example, Rd-SO- [Rd represents a hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a substituted amino group (the substituent is The hydrocarbon group which may have and the heterocyclic group which may have a substituent may be the same as each group described above, and the substituted amino group will be described later. The substituted sulfinyl group represented by this is mentioned. Specific examples of the sulfinyl group include a methanesulfinyl group, a tert-butylsulfinyl group, and a benzenesulfinyl group.
A phosphinyl group is mentioned as an acyl group derived from phosphinic acid. As the phosphinyl group, for example, (Re) ₂ -PO- [two Re are the same or different and each represents a hydrocarbon group which may have a substituent (the carbon which may have the substituent) The hydrogen group may be the same as the hydrocarbon group which may have the substituent described above.) ] The substituted phosphinyl group represented by this is mentioned. Specific examples of the phosphinyl group include a dimethylphosphinyl group and a diphenylphosphinyl group.
Examples of the acyl group derived from phosphonic acid include a phosphonyl group. As the phosphonyl group, for example, (RfO) ₂ -PO- [2 Rf are the same or different and each represents a hydrocarbon group which may have a substituent (the carbon which may have the substituent). The hydrogen group may be the same as the hydrocarbon group which may have the substituent described above.) ] The substituted phosphonyl group represented by this is mentioned. Specific examples of the phosphonyl group include a dimethylphosphonyl group and a diphenylphosphonyl group.
Examples of the substituted acyl group (acyl group having a substituent) include an acyl group in which at least one hydrogen atom of the acyl group is substituted with a substituent.

Examples of the acyloxy group which may have a substituent include an acyloxy group and a substituted acyloxy group.
Examples of the acyloxy group include C2-C20 acyloxy groups derived from carboxylic acids such as aliphatic carboxylic acids and aromatic carboxylic acids, and specific examples thereof include acetoxy groups, propionyloxy groups, butyryloxy groups, and pivaloyloxy. Group, pentanoyloxy group, hexanoyloxy group, lauroyloxy group, stearoyloxy group, benzoyloxy group and the like. The acyloxy group is preferably an acyloxy group having 2 to 18 carbon atoms.
Examples of the substituted acyloxy group (acyloxy group having a substituent) include acyloxy groups in which at least one hydrogen atom of the acyloxy group is substituted with a substituent.

Examples of the alkoxycarbonyl group which may have a substituent include an alkoxycarbonyl group and a substituted alkoxycarbonyl group.
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 substituted alkoxycarbonyl group (an alkoxycarbonyl group having a substituent) include an alkoxycarbonyl group in which at least one hydrogen atom of the alkoxycarbonyl group is substituted with a substituent.
Examples of the aryloxycarbonyl group which may have a substituent include an aryloxycarbonyl group and a substituted aryloxycarbonyl group.
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 substituted aryloxycarbonyl group (aryloxycarbonyl group having a substituent) include aryloxycarbonyl groups in which at least one hydrogen atom of the aryloxycarbonyl group is substituted with a substituent.
Examples of the aralkyloxycarbonyl group which may have a substituent include an aralkyloxycarbonyl group and a substituted aralkyloxycarbonyl 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 aralkyloxycarbonyl group (aralkyloxycarbonyl group having a substituent) include an aralkyloxycarbonyl group in which at least one hydrogen atom of the aralkyloxycarbonyl group is substituted with a substituent.

Examples of the aminosulfonyl group include an aminosulfonyl group represented by Rg—SO ₂ — (Rg represents an amino group or a substituted amino group). The substituted amino group represented by Rg may be the same as the substituted amino group described later. Specific examples of the aminosulfonyl group include an aminosulfonyl group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, a diphenylaminosulfonyl group, and the like.

As the alkoxysulfonyl group, for example, Rh—SO ₂ — (Rh is an alkoxy group which may have a substituent, an aryloxy group which may have a substituent, or an aralkyl which may have a substituent. An alkoxysulfonyl group represented by the following formula: The alkoxy group which may have a substituent represented by Rh, the aryloxy group which may have a substituent and the aralkyloxy group which may have a substituent have a substituent described later. It may be the same as the optionally substituted alkoxy group, the optionally substituted aryloxy group and the optionally substituted aralkyloxy group. Specific examples of the alkoxysulfonyl group include a methoxysulfonyl group, an ethoxysulfonyl group, a phenoxysulfonyl group, and a benzyloxysulfonyl group.

Examples of the substituted amino group include a chain or cyclic 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 can be used as long as it is usually used as an amino protecting group. The group etc. which are described as are mentioned. Specific examples of the amino protecting group include a hydrocarbon group that may have a substituent such as an alkyl group, an aryl group, and an aralkyl group, an acyl group that may have a substituent, and a substituent. And an alkoxycarbonyl group which may be substituted, an aryloxycarbonyl group which may have a substituent, an aralkyloxycarbonyl group which may have a substituent, a substituted sulfonyl group and the like.
The hydrocarbon group which may have a substituent such as an alkyl group, an aryl group and an aralkyl group in the amino protecting group may have an acyl group which may have a substituent, or a substituent. The alkoxycarbonyl group, the aryloxycarbonyl group which may have a substituent, the aralkyloxycarbonyl group and the substituted sulfonyl group which may have a substituent are the same as the groups described above.
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 an 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 N-benzylamino group and N, N-dibenzylamino group.
Moreover, di-substituted amino groups such as N-methyl-N-phenylamino group and N-benzyl-N-methylamino group can be mentioned.
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, a phenethyloxycarbonylamino group, and the like.
Specific examples of the amino group substituted with a substituted sulfonyl group, for _{example, -NHSO 2 CH 3, -NHSO 2} C 6 H 5, -NHSO 2 C 6 H 4 CH 3, include -NHSO ₂ CF _3, etc. .
Moreover, as a cyclic amino group, the case where it couple | bonds with an alkylene group and forms a nitrogen-containing ring, etc. are mentioned, for example. The alkylene group may be linear or branched, for example, an alkylene group having 1 to 6 carbon atoms. Specific examples include, for example, a methylene group, an ethylene group, a propylene group, a trimethylene group, 2-methylpropylene. Group, pentylene group, 2,2-dimethylpropylene group, 2-ethylpropylene group and the like. The alkylene group may have an oxygen atom, a nitrogen atom, a carbonyl group or the like or a double bond at an end of the alkylene group or at any position in the chain.

Examples of the alkoxythiocarbonyl group which may have a substituent include an alkoxythiocarbonyl group and a substituted alkoxythiocarbonyl group. Examples of the alkoxythiocarbonyl group may be linear, branched or cyclic, and examples thereof include an alkoxythiocarbonyl group having 2 to 20 carbon atoms. Specific examples thereof include a methoxythiocarbonyl group, an ethoxythiocarbonyl group, n-propoxythiocarbonyl group, 2-propoxythiocarbonyl group, n-butoxythiocarbonyl group, tert-butoxythiocarbonyl group, pentyloxythiocarbonyl group, hexyloxythiocarbonyl group, 2-ethylhexyloxythiocarbonyl group, lauryloxy A thiocarbonyl group, a stearyloxythiocarbonyl group, a cyclohexyloxythiocarbonyl group and the like can be mentioned.
Examples of the substituted alkoxythiocarbonyl group (alkoxythiocarbonyl group having a substituent) include alkoxythiocarbonyl groups in which at least one hydrogen atom of the alkoxythiocarbonyl group is substituted with a substituent.

Examples of the aryloxythiocarbonyl group which may have a substituent include an aryloxythiocarbonyl group and a substituted aryloxythiocarbonyl group. Examples of the aryloxythiocarbonyl group include an aryloxythiocarbonyl group having 7 to 20 carbon atoms, and specific examples thereof include a phenoxythiocarbonyl group and a naphthyloxythiocarbonyl group.
Examples of the substituted aryloxythiocarbonyl group (aryloxythiocarbonyl group having a substituent) include aryloxythiocarbonyl groups in which at least one hydrogen atom of the aryloxythiocarbonyl group is substituted with a substituent.

Examples of the aralkyloxythiocarbonyl group which may have a substituent include an aralkyloxythiocarbonyl group and a substituted aralkyloxythiocarbonyl group. Examples of the aralkyloxythiocarbonyl group include an aralkyloxythiocarbonyl group having 8 to 20 carbon atoms. Specific examples thereof include a benzyloxythiocarbonyl group, a phenethyloxythiocarbonyl group, and 9-fluorenylmethyloxythio. A carbonyl group etc. are mentioned.
Examples of the substituted aralkyloxythiocarbonyl group (aralkyloxythiocarbonyl group having a substituent) include an aralkyloxythiocarbonyl group in which at least one hydrogen atom of the aralkyloxythiocarbonyl group is substituted with a substituent.

The alkylthiocarbonyl group which may have a substituent includes an alkylthiocarbonyl group and a substituted alkylthiocarbonyl group. The alkylthiocarbonyl group may be linear, branched or cyclic, and examples thereof include an alkylthiocarbonyl group having 2 to 20 carbon atoms. Specific examples thereof include a methylthiocarbonyl group, an ethylthiocarbonyl group, and n-propyl. Thiocarbonyl group, 2-propylthiocarbonyl group, n-butylthiocarbonyl group, tert-butylthiocarbonyl group, pentylthiocarbonyl group, hexylthiocarbonyl group, 2-ethylhexylthiocarbonyl group, laurylthiocarbonyl group,
A stearylthiocarbonyl group, a cyclohexylthiocarbonyl group, etc. are mentioned.
Examples of the substituted alkylthiocarbonyl group (alkylthiocarbonyl group having a substituent) include an alkylthiocarbonyl group in which at least one hydrogen atom of the alkylthiocarbonyl group is substituted with a substituent.
Examples of the arylthiocarbonyl group which may have a substituent include an arylthiocarbonyl group and a substituted arylthiocarbonyl group. Examples of the arylthiocarbonyl group include an arylthiocarbonyl group having 7 to 20 carbon atoms, and specific examples thereof include a phenylthiocarbonyl group and a naphthylthiocarbonyl group.
Examples of the substituted arylthiocarbonyl group (arylthiocarbonyl group having a substituent) include arylthiocarbonyl groups in which at least one hydrogen atom of the arylthiocarbonyl group is substituted with a substituent.
Examples of the aralkylthiocarbonyl group which may have a substituent include an aralkylthiocarbonyl group and a substituted aralkylthiocarbonyl group. Examples of the aralkylthiocarbonyl group include an aralkylthiocarbonyl group having 8 to 20 carbon atoms, and specific examples thereof include a benzylthiocarbonyl group, a phenethylthiocarbonyl group, and a 9-fluorenylmethylthiocarbonyl group. .
Examples of the substituted aralkylthiocarbonyl group (aralkylthiocarbonyl group having a substituent) include an aralkylthiocarbonyl group in which at least one hydrogen atom of the aralkylthiocarbonyl group is substituted with a substituent.

  Examples of the carbamoyl group that may have a substituent include a carbamoyl group and a substituted carbamoyl group. Examples of the substituted carbamoyl group include carbamoyl groups in which one or two hydrogen atoms of an amino group in the carbamoyl group are substituted with a substituent such as a hydrocarbon group which may have a substituent. The hydrocarbon group which may have a substituent may be the same as the hydrocarbon group which may have a substituent described above. Specific examples of the substituted carbamoyl group include an N-methylcarbamoyl group, an N, N-diethylcarbamoyl group, and an N-phenylcarbamoyl group.

  Examples of the substituted phosphino group include a phosphino group in which one or two hydrogen atoms of the phosphino group are substituted with a substituent such as a hydrocarbon group which may have a substituent. The hydrocarbon group which may have a substituent may be the same as the hydrocarbon group which may have a substituent described above. Specific examples of the substituted phosphino group include a dimethylphosphino group, a diethylphosphino group, a diphenylphosphino group, and a methylphenylphosphino group.

As the substituted silyl group, for example, three hydrogen atoms of the silyl group may be substituted with a substituent such as a hydrocarbon group which may have the above substituent, an alkoxy group which may have the above substituent. And tri-substituted silyl groups. Specific examples of the substituted silyl group include trimethylsilyl group, triethylsilyl group, tri (2-propyl) silyl group, tert-butyldimethylsilyl group, tert-butyldiphenylsilyl group, triphenylsilyl group, tert-butylmethoxyphenylsilyl. Group, tert-butoxydiphenylsilyl group and the like.
Examples of the substituted silyloxy group include a hydrocarbon group having 1 to 18 carbon atoms, in which 1 to 3 hydrogen atoms of the silyloxy group may have the above substituent, and the above substituent. And tri-substituted silyloxy groups substituted with a substituent such as an alkoxy group. Specific examples of the substituted silyloxy group include trimethylsilyloxy group, triethylsilyloxy group, tri (2-propyl) silyloxy group, tert-butyldimethylsilyloxy group, tert-butyldiphenylsilyloxy group, triphenylsilyloxy group, tert -Butylmethoxyphenylsilyloxy group, tert-butoxydiphenylsilyloxy group and the like.

In the general formula (24), the group represented by R ⁴¹ may be a metal atom such as an alkali metal. Further, the carboxy group and the sulfo group may be a metal salt such as a metal atom such as an alkali metal. Examples of the alkali metal include lithium, sodium, potassium, rubidium, cesium and the like.

In the case of forming a ring, for example, R ³¹ and R ³² , R ³¹ and R ³³ , R ³¹ and R ³⁴ , R ³² and R ³³ , R ³² and R ³⁴ , R ³³ and R ³⁴ , R ³⁵ and R ^36, and ^{R 38} and ^{R 39, R 38} or ^{R 39} and ^{R 37, R 40} and ^{Q 11, R 40} and ^{R 41, R 41} and ^{Q 11, R 42} and ^{Q 12, R 44} and ^{Q 12, R 42} When R ⁴³ , R ⁴² and R ⁴⁴ or R ⁴⁵ , R ⁴³ and R ⁴⁴ , R ⁴³ and R ⁴⁵ , and R ⁴⁴ and R ⁴⁵ form a ring to form a ring, for example, it has a substituent. The case where it combines with the alkylene group which may be substituted, the alkylene dioxy group which may have a substituent, etc. and forms a ring etc. are mentioned. The ring to be formed may be monocyclic, polycyclic or condensed, and examples thereof include aliphatic rings such as 4- to 8-membered rings and aromatic rings.
As for the alkylene group which may have the said substituent, an alkylene group and a substituted alkylene group are mentioned. The alkylene group may be linear or branched, for example, an alkylene group having 1 to 6 carbon atoms, and specific examples thereof include, for example, an ethylene group, a propylene group, a trimethylene group, a 2-methylpropylene group, 2,2-dimethylpropylene group, 2-ethylpropylene group and the like can be mentioned. In addition, the carbon chain constituting the ring may have an oxygen atom, a sulfur atom, an imino group, a substituted imino group, a carbonyl group (C═O), a thiocarbonyl group (C═S), or the like. Specific examples of the ring in the case of forming a ring include a cyclopentane ring, a cyclohexane ring, such as a 5- to 7-membered lactone ring, such as a 5- to 7-membered lactam ring, a cyclopentanone ring, and a cyclohexanone ring. The ring to be formed is preferably a ring in which a carbon atom at a site to be asymmetrically hydrogenated can become an asymmetric carbon by a homogeneous asymmetric hydrogenation reaction. The substituent in the substituted imino group is the same as the substituent described later.
Examples of the substituted alkylene group (an alkylene group having a substituent) include an alkylene group in which at least one hydrogen atom of the alkylene group is substituted with a substituent,
Examples of the alkylenedioxy group which may have a substituent include an alkylenedioxy group and a substituted alkylenedioxy group. The alkylenedioxy group includes, for example, an alkylenedioxy group having 1 to 3 carbon atoms, and specific examples thereof include a methylenedioxy group, an ethylenedioxy group, and a trimethylenedioxy group. And propylenedioxy group.
Examples of the substituted alkylenedioxy group (an alkylenedioxy group having a substituent) include alkylenedioxy groups in which at least one hydrogen atom of the alkylenedioxy group is substituted with a substituent. Specific examples of the substituted alkylenedioxy group include a difluoromethylenedioxy group.

Examples of the spacer include a divalent organic group which may have a substituent such as an alkylene group, an arylene group, and a heteroarylene group. The divalent organic group has at least one heteroatom or atomic group such as an oxygen atom, a carbonyl group, a sulfur atom, an imino group, or a substituted imino group at an end of the organic group or at any position in the chain. You may do it. The substituent in the substituted imino group is the same as the substituent described later.
Examples of the alkylene group include an alkylene group having 1 to 10 carbon atoms, and specific examples thereof include a methylene group, an ethylene group, a trimethylene group, a propylene group, a tetramethylene group, a pentamethylene group, a hexamethylene group, and a heptamethylene group. , Octamethylene group, nonamethylene group, decamethylene group and the like.
Examples of the arylene group include an arylene group having 6 to 20 carbon atoms, and specific examples thereof include a phenylene group, a biphenyldiyl group, a binaphthalenediyl group, and a bisbenzodioxolediyl group.
Examples of the heteroarylene group include 3 to 8 members having 2 to 20 carbon atoms and containing at least one, preferably 1 to 3 hetero atoms such as a nitrogen atom, an oxygen atom and / or a sulfur atom, Preferred examples include 5- or 6-membered monocyclic heteroarylene groups, polycyclic or condensed ring heteroarylene groups, and specific examples thereof include bipyridinediyl group, bisbenzothioldiyl group, and bisthioldiyl group. Is mentioned.
Examples of the divalent organic group having a different atom or atomic group include —CH ₂ —O—CH ₂ —, —C ₆ H ₄ —O—C ₆ H ₄ — and the like.
These divalent organic groups may be substituted with a substituent described later.

Examples of the substituent include a hydrocarbon group that may have a substituent, a heterocyclic group that may have a substituent, a halogen atom, a halogenated hydrocarbon group, and a substituent. A good alkoxy group, an aryloxy group which may have a substituent, an aralkyloxy group which may have a substituent, a heteroaryloxy group which may have a substituent, and a substituent. An alkylthio group which may have a substituent, an arylthio group which may have a substituent, an aralkylthio group which may have a substituent, a heteroarylthio group which may have a substituent, and a substituent An optionally substituted acyl group, an optionally substituted acyloxy group, an optionally substituted alkoxycarbonyl group, an optionally substituted aryloxycarbonyl group, and a substituted group. You may Aralkyloxycarbonyl group, alkylenedioxy group which may have a substituent, nitro group, amino group, substituted amino group, cyano group, sulfo group, substituted silyl group, hydroxy group, carboxy group, substituent An alkoxythiocarbonyl group which may have a substituent, an aryloxythiocarbonyl group which may have a substituent, an aralkyloxythiocarbonyl group which may have a substituent, and an alkylthiocarbonyl which may have a substituent A group, an arylthiocarbonyl group which may have a substituent, an aralkylthiocarbonyl group which may have a substituent, a carbamoyl group which may have a substituent, a substituted phosphino group, an aminosulfonyl group, Examples include an alkoxysulfonyl group and an oxo group. These substituents may be the same as the groups described above.

The alkylenedioxy group which may have a substituent as a substituent is, for example, an alkylene dioxy group in which two hydrogen atoms adjacent to the aromatic ring in the aryl group or aralkyl group may have a substituent. Substituted with an oxy group. Examples of the alkylenedioxy group which may have a substituent include an alkylenedioxy group and a substituted 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 alkylenedioxy group (an alkylenedioxy group having a substituent) include an alkylenedioxy group in which at least one hydrogen atom of the alkylenedioxy group is substituted with the substituent. Specific examples of the substituted alkylenedioxy group include a difluoromethylenedioxy group.

  Specific examples of alkenes include the compounds shown below.

  Specific examples of ketones include, for example, methyl ethyl ketone, acetophenone, benzalacetone, 1-indanone, 3,4-dihydro- (2H) -naphthalenone ferrocenyl methyl ketone, and the following compounds, for example. It is done.

  Specific examples of imines include the compounds shown below.

  Specific examples of ketocarboxylic acids include the compounds shown below.

  Specific examples of ketoalkenes include the compounds shown below.

The unsaturated compound may have a chiral center in the molecule.
The unsaturated compound hydride obtained by the production method of the present invention is preferably an optically active compound. That is, in the present invention, the hydrogenation reaction is preferably an asymmetric hydrogenation reaction. Therefore, the optically active compound preferably obtained in the present invention is an optically active compound corresponding to each unsaturated compound. For example, compounds obtained by hydrogenating alkenes are optically active alkanes, compounds obtained by asymmetric hydrogenating ketones are optically active alcohols, and hydrogenating reaction of imines. The compound obtained by the reaction is an optically active amine, the compound obtained by hydrogenating the ketocarboxylic acid is an optically active hydroxy ester, and the compound obtained by hydrogenating the ketoalkene is a hydroxyalkene. , Hydroxyalkanes and / or ketoalkanes, respectively.

  Examples of optically active alkanes obtained by asymmetric hydrogenation reaction of alkenes include optically active alkanes represented by the following general formula (31).

  Examples of optically active alcohols obtained by asymmetric hydrogenation reaction of ketones include optically active alcohols represented by the following general formula (32).

  Examples of the optically active amines obtained by asymmetric hydrogenation reaction of imines include optically active amines represented by the following general formula (33).

  Examples of the optically active hydroxyesters obtained by asymmetric hydrogenation reaction of ketocarboxylic acids include optically active hydroxyesters represented by the following general formula (34).

  Optically active hydroxyalkenes, optically active hydroxyalkanes and optically active ketoalkanes obtained by asymmetric hydrogenation reaction of ketoalkenes are represented by, for example, the following general formulas (35) to (37), respectively.

In the above formula, * represents an asymmetric carbon, and R ^{31 to} R ⁴⁵ , Q ¹¹ and Q ¹² are the same as above. However, for example, in the general formula (32), when R ³⁵ = R ³⁶ or when any one of R ³⁵ and R ³⁶ is a hydrogen atom, depending on the types of R ^{31 to} R ⁴⁵ , It may not be possible.
Specific examples of the optically active compound include, for example, hydrides obtained from the respective compounds exemplified as the unsaturated compound.
In addition, the obtained optically active compound may be subjected to post-treatment such as purification and isolation as necessary, or after functional group protection and the like, and then post-treatment such as purification and isolation as necessary. Good. The specific method of post-processing is the same as the above.

The pressure of the hydrogen gas used as the hydrogen source may be in a hydrogen atmosphere, and even 0.1 MPa or less is sufficient, but usually 0.1 to 20 MPa, preferably 0.2 to 0.2 in consideration of economy and operability. It is suitably selected from the range of 10 MPa. In consideration of economy, it is possible to maintain high activity even at 1 MPa or less.
Examples of the hydrogen donating substance used as the hydrogen source include formic acid or salts thereof, a combination of formic acid and a base, hydroquinone, cyclohexadiene, 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.
In addition, the combination of formic acid and base may be any one in which formic acid is in the form of a formic acid salt or substantially in the form of a formic acid salt in the reaction system.
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 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.
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.
Examples of the organic base include alkali metal alkoxide such as potassium methoxide, sodium methoxide, lithium methoxide, sodium ethoxide, potassium isopropoxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, acetic acid Sodium / potassium acetate / magnesium acetate / calcium acetate alkali / alkaline earth metal acetates, triethylamine, diisopropylethylamine, N, N-dimethylaniline, piperidine, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [ 4.3.0] nona-5-ene, 1,8-diazabicyclo [5.4.0] undec-7-ene, tri-n-butylamine, organic amines such as N-methylmorpholine, methyl bromide Organometallic compounds such as nesium, ethylmagnesium bromide, propylmagnesium bromide, tert-butylmagnesium chloride, tert-butylmagnesium bromide, methyllithium, ethyllithium, propyllithium, n-butyllithium, tert-butyllithium, A quaternary ammonium salt etc. are mentioned.

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.
The usage-amount of a hydrogen-donating substance is suitably selected from the range of 0.1-100 equivalent normally with respect to an unsaturated compound, Preferably it is 0.5-20 equivalent.

The asymmetric hydrogenation reaction can be performed in a solvent as necessary. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene, and xylene, aliphatic hydrocarbons such as pentane, hexane, heptane, and octane, and halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, and dichloroethane. , Diethyl ether, diisopropyl ether, tert-butyl methyl ether, cyclopentyl methyl ether, dimethoxyethane, tetrahydrofuran, dioxane, dioxolane, 2-methyltetrahydrofuran ethers, methanol, ethanol, 2-propanol, n-butanol, tert-butanol Alcohols such as benzyl alcohol, polyhydric alcohols such as ethylene glycol, 1,2-propanediol, 1,3-propanediol and glycerin, N, N-dimethylphenol Amides such as muamide, N, N-dimethylacetamide, ketones such as acetone and methyl isobutyl ketone, esters such as methyl acetate, ethyl acetate and butyl acetate, acetonitrile, N-methylpyrrolidone, dimethyl sulfoxide, water and the like It is done. These solvents may be used alone or in appropriate combination of two or more.
The amount of the solvent used is not particularly limited because it varies depending on the type, solubility, economy, etc. of the unsaturated compound to be used. For example, when alcohol is used as the solvent, a low concentration of 1% or less depending on the unsaturated compound to be used. To a solvent-free or solvent-free state. What is necessary is just to select suitably the usage-amount of a solvent, for example so that it may become normally 0-200 times amount with respect to a reaction substrate, Preferably it is the range of 0-40 times amount.
The reaction temperature is not particularly limited because it varies depending on the type and amount of the catalyst to be used and the type of unsaturated compound to be used. Is appropriately selected. The reaction can be carried out at a low temperature of −30 to 0 ° C. or at a high temperature of 100 to 250 ° C.
The reaction time varies depending on the type and amount of the catalyst to be used, the type and concentration of the unsaturated compound to be used, the reaction conditions such as the reaction temperature and hydrogen pressure, but is usually 1 minute to 48 hours, preferably 10 minutes to 24. It is appropriately selected from the time range.
The asymmetric hydrogenation reaction can be carried out regardless of whether the reaction mode is batch or continuous. Moreover, it can carry out in reaction containers used in this field, such as a flask, a reaction kettle, and an autoclave.
The asymmetric hydrogenation reaction can be performed in the presence of an additive as necessary. Examples of the additive include an acid, a fluorine-containing alcohol, a base, a quaternary ammonium salt, a quaternary phosphonium salt, a halogen, and a reducing agent.

Examples of the acid include inorganic acids, organic acids, Lewis acids and the like.
Examples of the inorganic acid include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, tetrafluoroboric acid, perchloric acid, periodic acid and the like.
Examples of organic acids include formic acid, acetic acid, valeric acid, hexanoic acid, citric acid, chloroacetic acid, dichloroacetic acid, trichloroacetic acid, trifluoroacetic acid, benzoic acid, salicylic acid, oxalic acid, succinic acid, malonic acid, phthalic acid, Examples thereof include carboxylic acids such as tartaric acid, malic acid and glycolic acid, and sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoromethanesulfonic acid.
Examples of the Lewis acid include aluminum halides such as aluminum chloride and aluminum bromide, dialkylaluminum halides such as diethylaluminum chloride, diethylaluminum bromide and diisopropylaluminum chloride, triethoxyaluminum, triisopropoxyaluminum, and tri-tert. -Trialkoxyaluminum such as butoxyaluminum, titanium halide such as titanium tetrachloride, tetraalkoxytitanium such as tetraisopropoxytitanium, boron trifluoride, boron trichloride, boron tribromide, boron trifluoride diethyl ether complex, etc. And zinc halides such as boron halide, zinc chloride and zinc bromide.
These acids may be used alone or in appropriate combination of two or more.
The usage-amount of an acid is suitably selected from the range of 0.0001-100 equivalent normally with respect to an unsaturated compound, Preferably it is 0.001-10 equivalent.

As the fluorinated alcohol, a fluorinated aliphatic alcohol is preferred. Specific examples of the fluorinated aliphatic alcohol include saturated or unsaturated fluorinated aliphatic alcohols having 2 to 10 carbon atoms. Specific examples of the fluorine-containing aliphatic alcohol include, for example, 2,2,2-trifluoroethanol, 2,2-difluoroethanol, 3,3,3-trifluoropropanol, 2,2,3,3,3- Pentafluoropropanol, 2,2,3,3-tetrafluoropropanol, 3,3,4,4,4-pentafluorobutanol, 4,4,5,5,5-pentafluoropentanol, 5,5,6 , 6,6-pentafluorohexanol, 3,3,4,4,5,5,6,6,6-nonafluorohexanol, 1,1,1,3,3,3-hexafluoro-2-propanol, etc. Is mentioned. These fluorine-containing aliphatic alcohols may be used alone or in appropriate combination of two or more.
The usage-amount of a fluorine-containing alcohol is normally selected suitably from 0.01-100 equivalent with respect to an unsaturated compound, Preferably it is 0.1-10 equivalent.

Examples of the base include inorganic bases and organic bases. Examples of the inorganic base include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide, metal carbonates such as sodium carbonate, potassium carbonate, magnesium carbonate, and calcium carbonate, sodium bicarbonate, potassium bicarbonate, and the like. Metal hydrogen carbonates, metal hydrides such as lithium hydride, sodium hydride and potassium hydride, ammonia and the like. Examples of the organic base include lithium methoxide, lithium ethoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, potassium naphthaleni. Sodium acetate, potassium acetate, magnesium acetate, calcium acetate, lithium diethylamide, lithium diisopropylamide, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, lithium diphenylphosphide, sodium diphenylphosphine Fido, alkaline and alkaline earth metal salts such as potassium diphenylphosphide, triethylamine, diisopropylethylamine, N N-dimethylaniline, piperidine, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,8-diazabicyclo [5.4.0] undec-7-ene , Organic amines such as tri-n-butylamine and N-methylmorpholine, methyllithium, ethyllithium, n-propyllithium, isopropyllithium, n-butyllithium, sec-butyllithium, tert-butyllithium, phenyllithium, methyl Magnesium chloride, ethylmagnesium chloride, n-propylmagnesium chloride, isopropylmagnesium chloride, n-butylmagnesium chloride, sec-butylmagnesium chloride, tert-butylmagnesium chloride, phenylmagnesium chloride, methylmer Organometallic compounds such as gnesium bromide, ethyl magnesium bromide, n-propyl magnesium bromide, isopropyl magnesium bromide, n-butyl magnesium bromide, sec-butyl magnesium bromide, tert-butyl magnesium bromide, phenyl magnesium bromide, the above asymmetric coordination Examples thereof include optically active substances (optically active diamine compounds) and racemic bodies of the diamine compounds exemplified as the children.
The usage-amount of a base is normally suitably selected from the range of 0-100 equivalent with respect to an unsaturated compound, Preferably it is 0-10 equivalent.

Examples of the quaternary ammonium salt include quaternary ammonium salts having 4 to 24 carbon atoms. Specific examples of the quaternary ammonium salt include tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, triethylbenzylammonium chloride, tetrabutylammonium triphenyldifluorosilicate, and the like.
The usage-amount of a quaternary ammonium salt is suitably selected from the range of 0-100 equivalent normally with respect to an unsaturated compound, Preferably it is 0-10 equivalent.
Examples of the quaternary phosphonium salt include quaternary phosphonium salts having 4 to 36 carbon atoms. Specific examples of the quaternary phosphonium salt include tetraphenylphosphonium chloride, tetraphenylphosphonium bromide, tetraphenylphosphonium iodide, methyltriphenylphosphonium chloride, methyltriphenylphosphonium bromide, methyltriphenylphosphonium iodide and the like.
The amount of the quaternary phosphonium salt used is appropriately selected from the range of usually 0 to 100 equivalents, preferably 0 to 10 equivalents, relative to the unsaturated compound.
Examples of halogen include bromine and iodine.
The amount of halogen used is appropriately selected from the range of usually 0 to 100 equivalents, preferably 0 to 10 equivalents, relative to the unsaturated compound.

Examples of the reducing agent include sodium borohydride, lithium aluminum hydride, lithium diisobutylaluminum hydride and the like.
The usage-amount of a reducing agent is suitably selected from the range of 0-100 equivalent normally with respect to an unsaturated compound, Preferably it is 0-10 equivalent.
The above additives may be used alone or in combination of two or more as appropriate.

  The optically active compound obtained by the production method of the present invention is useful as an intermediate, a fragrance, or the like of medical or agricultural chemicals.

The present invention is characterized in that an alkoxy group or the like is introduced into the 4-position and 4′-position of an optically active diphosphine compound having two methylenedioxybenzenes. It is useful as a catalyst component having an asymmetric catalytic activity for an asymmetric hydrogenation reaction with respect to such unsaturated compounds.
In addition, the diphosphine compound of the present invention can be easily and selectively subjected to halogenation and coupling reactions by preliminarily substituting unnecessary reaction points during synthesis, and can also be reacted by increasing fat solubility. Handling at the time of purification becomes easy, and the target optically active diphosphine compound can be produced efficiently. Therefore, a hydride of the unsaturated compound, particularly an optically active compound useful as an intermediate or a fragrance for pharmaceuticals, agricultural chemicals, etc., by a reaction using a transition metal complex containing the optically active diphosphine compound as a ligand as a catalyst. Not only can it be obtained with good efficiency and optical purity, but workability is improved, and furthermore, it can be obtained with good economic efficiency.
This is an effect.
The transition metal complex having the optically active diphosphine compound of the present invention, particularly the optically active transition metal complex into which a methoxy group is introduced, is characterized by being brown. Thereby, the progress of the reaction can be visually confirmed more easily than the conventional one.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.
In the following examples, the apparatus used for measuring physical properties is as follows.
NMR: DRX-500 (BRUKER JAPAN CO. LTD.)
¹ H-NMR; 500.13 MHz
³¹ P-NMR; 202.46 MHz
Gas Chromatography (GC): GLC Agilent 6850 Series
High performance liquid chromatography (HPLC): Hitachi LaCrom 7000

(1) Synthesis of (7-methoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide 0.27 g (11.1 mmol) of magnesium piece was weighed into a three-necked flask and purged with nitrogen. Then, 2 mL of tetrahydrofuran (hereinafter referred to as THF) was added. Stirring was started, and a mixed solution of 2.34 g of 5-bromo-7-methoxy-1,3-benzodioxole and 10 ml of THF was added dropwise at 20 to 32 ° C. over 2 hours. After further stirring at room temperature for 1.5 hours, a mixed solution of 2.63 g of diphenylphosphonic chloride and 6 mL of THF was added dropwise at 23 ° C. to 38 ° C. over 1 hour, and the reaction was stirred at 40 ° C. for 2 hours. Thereafter, the reaction mixture was poured into 11 mL of 1N hydrochloric acid little by little under ice cooling, and stirred for 30 minutes. The reaction product was extracted twice with 20 mL of dichloromethane, washed twice with 15 mL of 2.5% aqueous sodium hydrogen carbonate solution and twice with 15 mL of water, and the organic phase was dried over anhydrous magnesium sulfate. The solid obtained by distilling off the solvent under reduced pressure was dissolved by heating in 32 mL of ethyl acetate, and then recrystallized at 0 ° C. to obtain 2.65 g of the title compound.
¹ H-NMR (CDCl ₃ ): δ 3.87 (3H, s), 6.03 (2H, s), 6.60 (1H, dd, J = 11.7, 1.3 Hz), 7.07 (1H, dd, J = 13.4, 1.2 Hz) ), 7.45-7.55 (6H, m), 7.56-7.71 (4H, m).

(2) Synthesis of (4-iodo-7-methoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide (2-1) 0.83 g (8.17 mmol) of diisopropylamine under a nitrogen stream Was dissolved in 6 mL of THF. Stirring was started, and 5.1 mL of n-butyllithium n-hexane solution (1.6 M) was added dropwise at −10 ° C. over 20 minutes, followed by stirring at the same temperature for 2.5 hours. A solution prepared by dissolving 2.40 g (6.81 mmol) of (7-methoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide in 48 mL of THF was added dropwise to this solution at −10 ° C. over 30 minutes. The stirring was continued for 30 minutes at the same temperature. 1.73 g (6.81 mmol) of iodine was added to the obtained mixed solution, then the temperature was raised to room temperature, and the reaction was further stirred for 3 hours. Under cooling with ice, 10 mL of 1N hydrochloric acid was added, and the reaction product was extracted twice with 25 mL of dichloromethane. This was washed twice with 10 mL of 5% aqueous sodium hydrogen carbonate solution and twice with 20 mL of water, and the organic phase was dried over anhydrous magnesium sulfate. The solid obtained by distilling off the solvent under reduced pressure was dissolved by heating in 15 mL of ethyl acetate, and then recrystallized at 0 ° C. to obtain 0.63 g of the title compound.
¹ H-NMR (CDCl ₃ ): δ
3.60 (3H, s), 6.10 (2H, s), 6.70 (1H, d, J = 14.3Hz), 7.48-7.50 (4H, m),
7.55-7.56 (2H, m), 7.70-7.74 (4H, m).

(2-2) 0.36 g (3.52 mmol) of diisopropylamine was dissolved in 8 mL of THF under a nitrogen stream. Stirring was started, and 2.0 mL of n-butyllithium n-hexane solution (1.6 M) was added dropwise at −78 ° C. over 15 minutes, followed by stirring at −78 ° C. to −40 ° C. for 1.5 hours. . A solution of 1.00 g (2.83 mmol) of (7-methoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide in 24 mL of THF was added to this solution at −78 ° C. to −75 ° C. at 20 ° C. The solution was added dropwise over a period of 30 minutes, and stirring was continued at the same temperature for 30 minutes. To the obtained mixed solution, 0.79 g (3.12 mmol) of iodine was added at −78 ° C. to −75 ° C. over 30 minutes, and then the temperature was raised to room temperature, followed by further stirring reaction for 3 hours. Under ice cooling, 6 mL of 10% aqueous sodium thiosulfate was added, and the solvent was distilled off under reduced pressure at 40 ° C. The reaction product was extracted twice with 20 mL of ethyl acetate. The organic layer was washed once with 5 mL of 1N hydrochloric acid, once with 5 mL of 1N aqueous sodium hydrogen carbonate, twice with 5 mL of water, and dried over anhydrous magnesium sulfate. The solid obtained by distilling off the solvent under reduced pressure was dissolved by heating in 6 mL of ethyl acetate, and then recrystallized at 0 ° C. to obtain 0.57 g of the title compound. ¹ H-NMR result was consistent with (2-1).

(3) Synthesis of (±)-[4,4′-bis (7-methoxy-1,3-benzodioxole)]-5-diyl-diphenylphosphine oxide As obtained in (2-1) above (4-iodo-7-methoxy-1,3-benzodioxole) -5-yl-diphenylphosphine oxide (1.6 g, 3.34 mmol) was weighed into a three-necked flask and replaced with nitrogen. Thereafter, 8 mL of dimethylformamide (hereinafter referred to as DMF) was added. Heating and stirring were started, and 0.64 g (10.1 mmol) of copper powder was added at 95 ° C., followed by stirring and reaction at the same temperature for 4 hours. The reaction mixture was cooled to room temperature, poured into 20 mL of water, and filtered through celite. The reaction product was extracted from the obtained filtrate twice with 20 mL of dichloromethane, and the organic phase was dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography to obtain 0.9 g of the title compound.
¹ H-NMR (CDCl ₃ ): δ 3.68 (6H, s), 5.28 (2H, d, J = 1.6 Hz), 5.71 (2H, d, J = 1.6 Hz), 6.47 (2H, d, J = 5.0 Hz), 7.26-7.37 (6H, m), 7.41-7.46 (6H, m), 7.59-7.63 (4H, m), 7.71-7.75 (4H, m).
³¹ P-NMR (CDCl ₃ ): δ 30.4

(4) Optically active liquid chromatography fractionation of (±)-[4,4′-bis (7-methoxy-1,3-benzodioxole)]-5-diyl-diphenylphosphine oxide (±)-( 4,2-bis (7-methoxy-1,3-benzodioxole))-5-diyl-diphenylphosphine oxide (hereinafter sometimes referred to as (±) -SEGPHOSO ₂ -4-MeO) 0.82 g Was dissolved in 80 mL of 1,2-dichloroethane and purified by preparative purification under the following liquid chromatography conditions to obtain (+)-(4,4-bis (7-methoxy-1) having an optical purity of 99.2% ee. , 3-benzodioxole))-5-diyl-diphenylphosphine oxide (hereinafter referred to as (+)-SEGPHOSO _2-4 -MeO).
Liquid chromatography conditions: HPLC Waters 600E used, column SUMICHIAL OA-3100 used, eluent
Hexane: 1,2-dichloroethane: ethanol = 40: 20: 40

(5) Synthesis of (+)-[4,4-bis (7-methoxy-1,3-benzodioxole)]-5-diyl-diphenylphosphine ((+)-SEGPHOS-4-MeO) 4) (+)-SEGPHOSO _2-4 -MeO 0.36 g (0.52 mmol) was weighed into a three-necked flask and purged with nitrogen, followed by 18 mL of toluene and 1.36 g (11.2 mmol) of dimethylaniline. And stirring was started at room temperature. To the mixed solution, 1.38 g (10.2 mmol) of trichlorosilane was added at room temperature, heated to 105 ° C. over 2.5 hours, and stirred at the same temperature for 4 hours. The reaction mixture was ice-cooled, 15 mL of 15% aqueous sodium hydroxide solution was added, and the mixture was stirred at room temperature for 30 min. After separation, the reaction product in the aqueous layer was extracted twice with 20 mL of toluene and combined with the previous organic layer. The obtained organic layer was washed twice with 15 mL of 1N hydrochloric acid and twice with 20 mL of water, and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain 0.32 g (yield 93%) of the title compound as a white solid.
¹ H-NMR (CDCl ₃ ): δ 3.68 (6H, s), 5.28 (2H, d, J = 1.6 Hz), 5.71 (2H, d, J = 1.6 Hz), 6.47 (2H, d, J = 5.0 Hz), 7.26-7.37 (6H, m), 7.41-7.46 (6H, m), 7.59-7.63 (4H, m), 7.71-7.75 (4H, m).
³¹ P-NMR (CDCl ₃ ): δ -11.0

Preparation of [RuCl (p-cymene) ((+)-SEGPHOS-4-MeO)] Cl Weigh 100 mg (0.15 mmol) of (+)-SEGPHOS-4-MeO produced in Example 1 into a 20 mL Schlenk tube. After nitrogen substitution, 4 mL of ethanol, 4 mL of dichloromethane, and 43.5 mg of [RuCl ₂ (p-cymene)] ₂ were added, and the reaction was stirred at 50 ° C. for 3 hours. After evaporating the solvent under reduced pressure, the residue was vacuum-dried to obtain 140 mg of the title compound as a yellow-orange solid.
³¹ P-NMR (CDCl ₃ ): δ 26.4 (d, J = 62.1 Hz), 41.5 (d, J = 62.1 Hz).

Preparation of [Me ₂ NH ₂ ] [{RuCl ((+)-SEGPHOS-4-MeO)} ₂ (μ-Cl) ₃ ] [RuCl (p-cymene) ((+) −) obtained in Example 2 SEGPHOS-4-MeO)] Cl (140 mg, 142 μmol) and dimethylamine hydrochloride (13.9 mg, 170 μmol) were weighed into a 30 ml Schlenk tube and purged with nitrogen. Then, 4 mL of 1,4-dioxane was added at 115 ° C. The reaction was allowed to stir for 16 hours. Excess dimethylamine hydrochloride was filtered off from the reaction mixture under nitrogen, and the solvent was distilled off from the obtained filtrate under reduced pressure, followed by vacuum drying to obtain 125 mg of the title compound as a brown solid.
³¹ P-NMR (CDCl ₃ ): δ 50.7 (d, J = 37.5 Hz), 51.5 (d, J = 38.9 Hz).

4. Asymmetric hydrogenation reaction of ethyl 4-chloro-3-oxo-butanoate [RuCl (p-cymene) ((+)-SEGPHOS-4-MeO)] Cl obtained in the same manner as in Example 2. After 9 mg (6.1 μmol) was put into a stainless steel autoclave and purged with nitrogen, 5 mL of THF, 5 mL of ethanol, 10.0 g (60.8 mmol) of ethyl 4-chloro-3-oxo-butanoate were added, and the mixture was heated at 100 ° C., hydrogen The reaction was stirred at a pressure of 1.0 MPa for 4.5 hours. As a result of measuring the reaction mixture by GLC, the objective optically active ethyl 4-chloro-3-hydroxybutanoate was obtained with a conversion of 85.1% and an optical purity of 95.2% ee. The conversion rate was measured by a conventional method using HP Innowax, and the optical purity was measured by a conventional method using CHIRALCEL OJ.

Asymmetric hydrogenation reaction of methyl 2-oxo-3-phenylpropionate [Me ₂ NH ₂ ] [{RuCl ((+)-SEGPHOS-4-MeO)} ₂ (μ-Cl) obtained in Example 3 ₃ ] 5.0 mg (5.6 μmol) was placed in a stainless steel autoclave and purged with nitrogen, followed by methanol 1.5 mL and methyl 2-oxo-3-phenylpropionate 500 mg (2.8 mmol), The reaction was stirred at a hydrogen pressure of 5.0 MPa for 17 hours. As a result of measuring the reaction mixture by GLC, the objective optically active methyl 2-hydroxy-3-phenylpropionate was obtained with a conversion of 100% and an optical purity of 91.3% ee. The conversion rate was measured by a conventional method using NEUTRA BOND-1, and the optical purity was measured by a conventional method using CP CHIRASILDEX-CB.

Asymmetric hydrogenation reaction of ethyl 2-oxo-4-phenylbutanoate [Me ₂ NH ₂ ] [{RuCl ((+)-SEGPHOS-4-MeO)} ₂ (μ-Cl) obtained in Example 3 ₃ ] After putting 4.3 mg (4.8 μmol) into a stainless steel autoclave and carrying out nitrogen substitution, ethanol 1.5 mL and ethyl 2-oxo-4-phenylbutanoate 500 mg (2.4 mmol) were added, The reaction was stirred at a hydrogen pressure of 5.0 MPa for 17 hours. As a result of measuring the reaction mixture by GLC, the objective optically active ethyl 2-hydroxy-4-phenylbutanoate was obtained with a conversion of 100% and an optical purity of 79.7% ee. The conversion rate was measured by a conventional method using NEUTRA BOND-1, and the optical purity was measured by a conventional method using CP CHIRASILDEX-CB.

Asymmetric hydrogenation reaction of acetol [Me ₂ NH ₂ ] [{RuCl ((+)-SEGPHOS-4-MeO)} ₂ (μ-Cl) ₃ ] obtained in Example ₃ 6.0 mg (6.7 μmol) ) Was placed in a stainless steel autoclave and purged with nitrogen. Then, 1.0 mL of methanol and 500 mg (6.7 mmol) of acetol were added, followed by stirring and reaction at 65 ° C. and a hydrogen pressure of 3.0 MPa for 7 hours. As a result of measuring the reaction mixture by GLC and HPLC, the objective optically active 1,2-propanediol was obtained with a conversion of 100% and an optical purity of 94.2% ee. The conversion rate was measured by a conventional method using TC-FFAP, and the optical purity was measured using CHIRALCEL OJ-H.

Asymmetric hydrogenation reaction of ethyl 4-chloro-3-oxo-butanoate [Me ₂ NH ₂ ] [{RuCl ((+)-SEGPHOS-4-MeO)} ₂ (μ-Cl ₃ ] 5.4 mg (6.1 μmol) was placed in a stainless steel autoclave and purged with nitrogen, followed by 4 mL of ethanol and 2.0 g (12.2 mmol) of ethyl 4-chloro-3-oxo-butanoate. The mixture was stirred at 4 ° C. and a hydrogen pressure of 3.0 MPa for 4 hours. As a result of measuring the reaction mixture by GLC and HPLC, the objective optically active ethyl 4-chloro-3-hydroxybutanoate was obtained with a conversion of 100% and an optical purity of 94.1% ee. The conversion rate was measured by a conventional method using HP Innowax, and the optical purity was measured by CHIRALCEL OJ-H.

  The present invention provides a novel diphosphine compound useful as a ligand for an asymmetric catalyst in asymmetric synthesis, and the catalyst for asymmetric synthesis using the diphosphine compound of the present invention as a ligand is a pharmaceutical, agricultural chemical. The diphosphine compound of the present invention, a complex using the same, a catalyst using the same, and the catalyst are useful as a catalyst for producing optically active compounds useful as intermediates and the like in high yield and optical purity The method for producing an optically active compound using has industrial applicability.

Claims (14)

The following general formula (1)

(Wherein two R ¹ are the same or different which may be coal hydrocarbon group, two of R ² and R ³ are independently a methyl group as a location substituent, tert- butyl and methoxy A hydrocarbon group which may have a group selected from the group consisting of groups , and two Qs are the same or different and each represents a methylene group, a dimethylmethylene group or a difluoromethylene group .)
The diphosphine compound represented by these. The diphosphine compound according to claim 1, wherein the diphosphine compound represented by the general formula (1) is an optically active diphosphine compound having axial asymmetry . The following general formula (6)

(Wherein two R ¹ are the same or different which may be coal hydrocarbon group, two of R ² and R ³ are independently a methyl group as a location substituent, tert- butyl and methoxy A hydrocarbon group which may have a group selected from the group consisting of groups , and two Qs are the same or different and each represents a methylene group, a dimethylmethylene group or a difluoromethylene group .)
The diphenylphosphine oxide compound represented by these. The diphenylphosphine oxide compound according to claim 3, wherein the diphenylphosphine oxide compound represented by the general formula (6) is an optically active diphenylphosphine oxide compound having axial asymmetry .   An asymmetric catalyst comprising the optically active diphosphine compound according to claim 2 or the optically active diphenylphosphine oxide compound according to claim 4.   A transition metal complex comprising the diphosphine compound according to claim 1.   A transition metal complex obtained by reacting the diphosphine compound according to claim 1 or 2 with a transition metal complex precursor. The transition metal complex according to claim 6 or 7 , wherein the transition metal complex is an optically active transition metal complex comprising the optically active diphosphine compound according to claim 2 . An asymmetric catalyst comprising the optically active transition metal complex according to claim 8 .   An asymmetric catalyst comprising the diphosphine compound according to claim 2 and a transition metal complex precursor. Claim 9 or asymmetric catalyst according to 10, the asymmetric catalyst according to claim 9 or 10 as a catalyst for asymmetric synthesis. The catalyst for asymmetric synthesis according to claim 11 , wherein the catalyst for asymmetric synthesis is a catalyst for asymmetric reduction reaction. In the presence of an asymmetric catalyst according to claim 9 or 10, it is reacted with a compound having a prochiral center, method for producing an optically active compound.   Use of the optically active diphosphine compound according to claim 2 as an asymmetric ligand.