JP5011262B2 - Phosphine compound - Google Patents

Description

  The present invention relates to a novel phosphine compound.

There have been many reports on transition metal complex catalysts that can be used for catalytic asymmetric synthesis such as asymmetric hydrogenation, asymmetric hydrosilylation, asymmetric hydroformylation, and asymmetric isomerization. Yes. Among these, transition metal complexes such as ruthenium, iridium, rhodium, palladium, and nickel having optically active phosphine as a ligand have been reported to have excellent performance as a catalyst for asymmetric synthesis reaction, and are industrialized. There are some (see, for example, Non-Patent Document 1).
On the other hand, phosphole compounds have long been studied for their synthesis and physical properties, but there are few examples of their application to synthesis and asymmetric reactions of optically active substances.
In recent years, several optically active diphosphine ligands having a phosphole moiety have been reported and applied to asymmetric hydrogenation reactions (see, for example, Non-Patent Documents 2 and 3).
Further, chiral transition metal complexes of chiral bis (phosphorane) having a chiral 1,4-diol cyclic sulfate as a precursor (see, for example, Patent Document 1), diphosphine derivatives (for example, see Patent Document 2), diphosphole derivatives (for example, Patent Literature 3), isophosphinic acid (for example, Patent Literature 4) and the like have been proposed.

JP-T 6-508848 JP-A-7-149777 Special Table 2002-527444 JP-T-2002-527445 Ryoji Noyori, Asymmetric Catalysis in Organic Synthesis, (USA), Ed. , Willy & Sons, 1994. J. et al. Mol. Cat. (Switzerland), 1992, 72, p. 21-25 Organometallics, (USA), 2001, 20, p. 1014-1019

However, in order to synthesize these optically active diphosphine ligands having a phosphole moiety, it is necessary to go through the carbon-phosphorus bond cleavage of the corresponding 1-phenylphosphole compound with metallic lithium. There is a problem in terms of
In addition, these ligands may not have sufficient selectivity (chemical selectivity, enantioselectivity) and catalytic activity depending on the target reaction or reaction substrate, and may need to be improved.

  Accordingly, an object of the present invention is to provide a novel phosphine compound.

  As a result of intensive studies to solve the above problems, the present inventors have found that a transition metal catalyst of a primary phosphine having a specific structure, particularly a phosphine compound derived from an axially asymmetric optically active substance thereof, The present inventors have found that these problems can be solved as an asymmetric hydrogenation reaction catalyst and have completed the present invention.

  That is, the present invention provides the following general formula (2)

Wherein R ⁵ and R ⁶ are each independently a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a di (1 to 5 alkyl) amino group, An 8-membered cyclic amino group or a halogen atom; R ⁷ represents a di (C 1-5 alkyl) amino group, a 5- to 8-membered cyclic amino group or a halogen atom; and R ⁵ and R ⁶ represent R ⁶ and R ⁷ may be combined with each other to form a methylenedioxy group, an ethylenedioxy group, or a trimethylenedioxy group.)
And a primary phosphine compound characterized by being an axially asymmetric optically active substance.

  In addition, although optically active primary phosphine having a biaryl skeleton is mentioned in Patent Document 1, only a chemical structure is presented, and no method for producing the compound is described. In addition, there is no description regarding optically active substances.

  Further, the present invention provides the following general formula (1)

(In formula, R < ¹ > and R < ² > are respectively independently a hydrogen atom, the C1-C10 alkyl group which may have a substituent, and the C1-C10 which may have a substituent. An alkoxy group having 2 to 10 carbon atoms, an optionally substituted alkenyl group having 2 to 10 carbon atoms, an optionally substituted di (1 to 5 alkyl) amino group, and a substituent. It may have a 5- to 8-membered cyclic amino group, a 5- to 8-membered alicyclic group which may have a substituent, an aryl group which may have a substituent, and a substituent. R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents a hydrogen atom, a carbon number, or an aralkyl group, an optionally substituted heterocyclic group, a tri-substituted silyl group or a halogen atom; 1-5 alkyl groups, 1-5 alkoxy groups, di (1-5 alkyl) amino groups, 5- to 8-membered cyclic amino groups Or a halogen atom; R ⁷ is an alkyl group of 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, diamino group (containing 1-5 alkyl carbon atoms), 5- to 8-membered cyclic amino group or a halogen R ³ and R ⁴ , R ⁵ and R ⁶ , R ⁶ and R ⁷ are bonded together to form a condensed benzene ring, a condensed substituted benzene ring, a trimethylene group, a tetramethylene group, and a pentamethylene group. Group, methylenedioxy group, ethylenedioxy group or trimethylenedioxy group may be formed.)
The phosphine compound represented by these is provided.

  Furthermore, this invention provides the catalyst for asymmetric synthesis containing the transition metal phosphine complex which uses the phosphine compound represented by General formula (1) as a ligand, and this transition metal phosphine complex.

  The novel phosphine compounds of the present invention are particularly useful as ligands for transition metal complexes. The transition metal phosphine complex is useful as a catalyst for asymmetric synthesis reaction. A novel phosphine compound useful as this ligand can be prepared by a relatively inexpensive production method. Furthermore, by using this catalyst, an asymmetric hydride having a high optical purity can be obtained in a high yield, which is extremely useful industrially.

  Hereinafter, the present invention will be described in detail.

In the phosphine compound represented by the general formula (1) of the present invention, specific examples of the alkyl group having 1 to 10 carbon atoms represented by R ¹ and R ² include, for example, a methyl group, an ethyl group, and an n-propyl group. Isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group and the like. The alkyl group may have 1 to 4 functional groups inert to the asymmetric synthesis reaction as a substituent. Here, examples of the substituent include a hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, and the like. Alkoxy groups; halogen atoms such as fluorine, chlorine, bromine and iodine.

Specific examples of the alkoxy group having 1 to 10 carbon atoms represented by R ¹ and R ² include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy Group, tert-butoxy group, pentoxy group, hexyloxy group, heptyloxy group, octyloxy group, nonyloxy group, decyloxy group and the like. The alkoxy group may have 1 to 4 functional groups that are inert to the asymmetric synthesis reaction as a substituent. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. A hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, or the like, an alkoxy group having 1 to 4 carbon atoms; fluorine, chlorine, Examples thereof include halogen atoms such as bromine and iodine.

Specific examples of the alkenyl group having 2 to 10 carbon atoms represented by R ¹ and R ² include, for example, vinyl group, allyl group, 1-propenyl group, isopropenyl group, 1-butenyl group, 2-butenyl group, 2 -A methylallyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonenyl group, a decenyl group and the like can be mentioned. The alkenyl group may have 1 to 4 functional groups that are inert to the asymmetric synthesis reaction as a substituent. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. Hydroxyl group; alkoxy group having 1 to 4 carbon atoms such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group; phenyl group; fluorine , Halogen atoms such as chlorine, bromine and iodine.

Specific examples of the di (C 1-5 alkyl) amino group represented by R ¹ and R ² include, for example, a dimethylamino group, a diethylamino group, a di-n-propylamino group, a diisopropylamino group, a di-n- Examples thereof include a butylamino group, a diisobutylamino group, a disec-butylamino group, a ditert-butylamino group, and a dipentylamino group. The di (C1-5 alkyl) amino group may have 1 to 4 functional groups that are inert to the asymmetric synthesis reaction as a substituent. Here, examples of the substituent include a hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, and the like. Alkoxy groups; halogen atoms such as fluorine, chlorine, bromine and iodine.

Specific examples of the 5- to 8-membered cyclic amino group represented by R ¹ and R ² include a pyrrolidino group and a piperidino group. The cyclic amino group may have 1 to 4 functional groups inert to the asymmetric synthesis reaction as substituents. As a substituent, a C1-C4 alkoxy group, a halogen atom, etc. are mentioned, for example.

Specific examples of the 5- to 8-membered alicyclic group which may have a substituent represented by R ¹ and R ² include, for example, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, and the like. Can be mentioned. Examples of the substituent of the 5- to 8-membered alicyclic group include an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom. You may have 1-4 of these substituents. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. A hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, or the like, an alkoxy group having 1 to 4 carbon atoms; fluorine, chlorine, Examples thereof include halogen atoms such as bromine and iodine.

Specific examples of the aryl group which may have a substituent represented by R ¹ and R ² include 6 to 10 carbon atoms such as a phenyl group, a naphthalen-1-yl group, and a naphthalen-2-yl group. Of the aryl group. Examples of the substituent for the aryl group include an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom. You may have 1-5 of these substituents. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. A hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, or the like, an alkoxy group having 1 to 4 carbon atoms; fluorine, chlorine, Examples thereof include halogen atoms such as bromine and iodine.

Specific examples of the aralkyl group which may have a substituent represented by R ¹ and R ² include, for example, benzyl group, α-phenethyl group, β-phenethyl group, α-phenylpropyl group, β-phenylpropyl group. Aralkyl groups having 7 to 15 carbon atoms in total, such as a group, γ-phenylpropyl group, and naphthylmethyl group. Examples of the substituent for the aralkyl group include an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom. You may have 1-4 of these substituents. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. A hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, or the like, an alkoxy group having 1 to 4 carbon atoms; fluorine, chlorine, Examples thereof include halogen atoms such as bromine and iodine.

Specific examples of the heterocyclic group which may have a substituent represented by R ¹ and R ² include, for example, a nitrogen atom such as a 2-pyridyl group, a 2-furyl group, a 2-thienyl group, an oxygen atom, and the like. Examples thereof include a 5- or 6-membered heterocyclic group having 1 to 3 heteroatoms selected from sulfur atoms. Examples of the substituent of the heterocyclic group include an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom. You may have 1-4 of these substituents. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. A hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, or the like, an alkoxy group having 1 to 4 carbon atoms; fluorine, chlorine, Examples thereof include halogen atoms such as bromine and iodine.

Specific examples of the tri-substituted silyl group represented by R ¹ and R ² include, for example, trimethylsilyl group, triethylsilyl group, triisopropylsilyl group, dimethylisopropylsilyl group, diethylisopropylsilyl group, dimethyl (2,3-dimethyl- 2-butyl) silyl group, tert-butyldimethylsilyl group, tri (C1-C6 alkyl) silyl group such as dimethylhexylsilyl group; for example, di (C1-C6 alkyl) such as dimethylcumylsilyl group (C6-C18 aryl) silyl group; for example, di (C6-C18 aryl) (C1-C6 alkyl) silyl group such as tert-butyldiphenylsilyl group and diphenylmethylsilyl group; for example, triphenyl Tri (C6-C18 aryl) silyl group such as silyl group; for example, tribenzylsilyl And tri (carbon atoms having 7 to 19 aralkyl) silyl groups such as a tri-p-xylylsilyl group.

Specific examples of the halogen atom represented by R ¹ and R ² include fluorine, chlorine, bromine, iodine and the like.

Among these, preferable R ¹ and R ² include a hydrogen atom; a carbon which may have a substituent such as a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, or a tert-butyl group. Alkyl groups of 1 to 4; alkenyl groups which may have a substituent such as vinyl group and styryl group; dialkylamino groups such as dimethylamino group and diethylamino group; 5- to 8-members such as pyrrolidino group and piperidino group A cyclic amino group of: phenyl group, 4-tolyl group, 3,5-xylyl group, 3,5-di (tert-butyl) -4-methoxyphenyl group, naphthalen-1-yl group, naphthalen-2-yl group Aryl groups having 6 to 10 carbon atoms which may have substituents such as: aralkyl groups having 7 to 15 carbon atoms in total such as benzyl group and α-phenylethyl group; 2-pyridyl group, 2-furyl group, 2- Heterocyclic groups such as enyl; a trimethylsilyl group, can be exemplified trialkylsilyl group such as tert- butyldimethylsilyl group.

Particularly preferable examples of R ¹ and R ² include a hydrogen atom; a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, a tert-butyl group, a trifluoromethyl group, and a phenyl group.

Specific examples of the alkyl group having 1 to 5 carbon atoms represented by R ^{3 to} R ⁶ include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group. , Tert-butyl group, pentyl group and the like.

Specific examples of the alkoxy group having 1 to 5 carbon atoms represented by R ^{3 to} R ⁶ include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy Group, tert-butoxy group, pentoxy group and the like.

Specific examples of the di (C 1-5 alkyl) amino group represented by R ^{3 to} R ⁶ include a dimethylamino group, a diethylamino group, a di-n-propylamino group, a diisopropylamino group, and a di-n-butylamino group. Group, diisobutylamino group, disec-butylamino group, ditert-butylamino group, dipentylamino group and the like.

Specific examples of the 5- to 8-membered cyclic amino group represented by R ^{3 to} R ⁶ include a pyrrolidino group and a piperidino group.

Specific examples of the halogen atom represented by R ^{3 to} R ⁶ include fluorine, chlorine, bromine, iodine and the like.

Among these, preferable R ^{3 to} R ⁶ include a hydrogen atom; an alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, and a tert-butyl group; Group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, tert-butoxy group and other alkoxy groups; dimethylamino group, diethylamino group and other dialkylamino groups; pyrrolidino group, piperidino group and other 5-8 Examples thereof include a member cyclic amino group.

Particularly preferred examples of R ³ and R ⁴ include a hydrogen atom.
Particularly preferable examples of R ⁵ and R ⁶ include a hydrogen atom and a methoxy group.

Specific examples of the alkyl group having 1 to 5 carbon atoms represented by R ⁷ include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert- A butyl group, a pentyl group, etc. are mentioned.

Specific examples of the alkoxy group having 1 to 5 carbon atoms represented by R ⁷ include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert -A butoxy group, a pentoxy group, etc. are mentioned.

Specific examples of the di (C 1-5 alkyl) amino group represented by R ⁷ include a dimethylamino group, a diethylamino group, a di-n-propylamino group, a diisopropylamine group, a di-n-butylamino group, and diisobutyl. An amino group, a disec-butylamino group, a ditert-butylamino group, a dipentylamino group, etc. are mentioned.

Specific examples of the 5- to 8-membered cyclic amino group represented by R ⁷ include a pyrrolidino group and a piperidino group.

Specific examples of the halogen atom represented by R ⁷ include fluorine, chlorine, bromine, iodine and the like.

Among these, preferred R ⁷ is an alkyl group having 1 to 4 carbon atoms such as methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, tert-butyl group; methoxy group, ethoxy group, n -Alkoxy groups such as propoxy group, isopropoxy group, n-butoxy group, tert-butoxy group; dialkylamino groups such as dimethylamino group and diethylamino group; 5- to 8-membered cyclic amino groups such as pyrrolidino group and piperidino group Can be illustrated.

Particularly preferred examples of R ⁷ include a methyl group and a methoxy group.

In the phosphine compound represented by the general formula (1) of the present invention, R ³ and R ⁴ , R ⁵ and R ⁶ , R ⁶ and R ⁷ are combined together to form a condensed benzene ring or a condensed substituted benzene ring. , Trimethylene group, tetramethylene group, pentamethylene group, methylenedioxy group, ethylenedioxy group or trimethylenedioxy group may be formed.
Among these, R ⁶ and R ⁷ are preferably taken together to form a condensed benzene ring, a condensed substituted benzene ring, a trimethylene group, a tetramethylene group, a pentamethylene group, a methylenedioxy group, an ethylenedioxy group, or The thing which formed the trimethylene dioxy group can be illustrated.
Particularly preferably, R ⁶ and R ⁷ are combined to form a condensed benzene ring, a condensed substituted benzene ring, a tetramethylene group, a methylenedioxy group, a methylenedioxy group or an ethylenedioxy group. be able to.
Moreover, as a substituent of the said condensed substituted benzene ring, the functional group inactive to asymmetric synthesis reaction is mentioned, You may have 1-4. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. A hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, or the like, an alkoxy group having 1 to 4 carbon atoms; fluorine, chlorine, Examples thereof include halogen atoms such as bromine and iodine.

  The phosphine compound (1) of the present invention is an axially asymmetric optically active substance (enantiomer), a racemate, and a mixture thereof, but is preferably a single axially asymmetric optically active substance (enantiomer).

  As the phosphine compound (1) of the present invention, in particular, the following general formula (1 ′);

(Wherein R ^{1 ′} and R ^{2 ′} each independently represents a hydrogen atom, an optionally substituted alkyl group having 1 to 5 carbon atoms, or an optionally substituted aryl group. R ^{6 ′} represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, or a halogen atom; R ^{7 ′} represents an alkyl group having 1 to 5 carbon atoms, 1 carbon atom Represents an alkoxy group of ˜5 or a halogen atom; and R ^{6 ′} and R ^{7 ′} are taken together to form a condensed benzene ring, a condensed substituted benzene ring, a tetramethylene group, a methylenedioxy group or an ethylenedioxy group. Group may be formed.)
The phosphine compound represented by these is preferable.

In the phosphine compound represented by the general formula (1 ′) of the present invention, specific examples of the alkyl group having 1 to 5 carbon atoms represented by R ^{1 ′} and R ^{2 ′} include, for example, methyl group, ethyl group, n -Propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group and the like can be mentioned. The alkyl group may have 1 to 4 substituents such as a halogen atom. Specific examples of the substituted alkyl group include a trifluoromethyl group.

Specific examples of the aryl group which may have a substituent represented by R ^{1 ′} and R ^{2 ′} include a phenyl group, a naphthalen-1-yl group, and a naphthalen-2-yl group. Examples of the substituent for the aryl group include an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom. You may have 1-5 of these substituents. Here, examples of the substituent include alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. A hydroxyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, or the like, an alkoxy group having 1 to 4 carbon atoms; fluorine, chlorine, Examples thereof include halogen atoms such as bromine and iodine.

Specific examples of the alkyl group having 1 to 5 carbon atoms represented by R ^{6 ′} include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, Examples thereof include a tert-butyl group and a pentyl group.

Specific examples of the alkoxy group having 1 to 5 carbon atoms represented by R ^{6 ′} include, for example, a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, and a sec-butoxy group. , Tert-butoxy group, pentyloxy group and the like.

Specific examples of the halogen atom represented by R ^{6 ′} include fluorine, chlorine, bromine, iodine and the like.

Specific examples of the alkyl group having 1 to 5 carbon atoms represented by R ^{7 ′} include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, Examples thereof include a tert-butyl group and a pentyl group.

Specific examples of the alkoxy group having 1 to 5 carbon atoms represented by R ^{7 ′} include, for example, a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, and a sec-butoxy group. , Tert-butoxy group, pentyloxy group and the like.

Specific examples of the halogen atom represented by R ^{7 ′} include fluorine, chlorine, bromine, iodine and the like.

R ^{6 ′} and R ^{7 ′} may each independently form a condensed benzene ring, a condensed substituted benzene ring, a tetramethylene group, a methylenedioxy group or an ethylenedioxy group, preferably , A condensed benzene ring, a tetramethylene group, or a methylenedioxy group.

  The phosphine compound (1 ′) is an axially asymmetric optically active substance (enantiomer), a racemate, and a mixture thereof, and is preferably a single axially asymmetric optically active substance (enantiomer).

The primary phosphine compound represented by the general formula (2) is a production intermediate of the phosphine compound represented by the general formula (1).
In the primary phosphine compound represented by the general formula (2) of the present invention, specific examples of R ⁵ , R ⁶ and R ⁷ are the same groups as described above.

  The primary phosphine compound of the present invention is an axially asymmetric optically active substance (enantiomer), a racemate, and a mixture thereof, and is preferably a single axially asymmetric optically active substance (enantiomer).

  Among the phosphine compounds of the present invention, the following general formula (2 ′);

(Wherein R ^{6 ′} and R ^{7 ′} have the same meanings as described above.)
A primary phosphine compound represented by the formula is particularly preferred.

The primary phosphine compound represented by the general formula (2 ′) is a production intermediate of the phosphine compound represented by the general formula (1 ′).
In the primary phosphine compound represented by the general formula (2 ′) of the present invention, specific examples of R ^{6 ′} and R ^{7 ′} include the same groups as described above.

  The primary phosphine compound represented by the general formula (2 ′) of the present invention is an axially asymmetric optically active substance (enantiomer), a racemate and a mixture thereof, but a single axially asymmetric optically active substance (enantiomer) ) Is preferable.

  The phosphine compound (1) of the present invention can be produced, for example, according to the following reaction formula.

(In the formula, X represents a halogen atom, preferably a bromine atom, and R ^{1 to} R ⁷ are the same as described above.)

That is, a Grignard reagent obtained from Compound (3) and magnesium is reacted with excess diethyl chlorophosphate ((EtO) ₂ POCl) in an organic solvent such as ether or tetrahydrofuran to obtain Compound (4), and lithium diisopropylamide ( Compound (5) is obtained by reacting ferric chloride in the presence of LDA), and then reduced with trimethylsilyl chloride (TMSCl) and lithium aluminum hydride (LiAlH ₄ ). A phosphine compound (1) is obtained by reacting alkadiin in the presence of alkyllithium such as n-butyllithium or n-propyllithium.

  In order to avoid complexity, the following formula (7)

(+)-Isomer ((+)-4,4′-bi-1,3-benzodioxole) -5,5′-diylbis ( The method for producing the compound of the present invention will be specifically described by taking 2,5-dimethylphosphoro) (hereinafter sometimes referred to as (+)-MP ² -SEGPHOS) as an example. However, the present invention is not limited to this example.

(+)-MP ² -SEGPHOS is produced by the method shown by the following reaction formula.

(In the formula, * indicates axial asymmetric optical activity.)

A Grignard reagent prepared from 3,4-methylenedioxyphenyl bromide (3 ′) is reacted with diethyl chlorophosphate to synthesize phosphonate (4 ′). Next, ferric chloride (FeCl ₃ ) is added to phosphonate (4 ′) in the presence of lithium diisopropylamide to obtain racemic diphosphate (5 ′) (see Japanese Patent Application Laid-Open No. 2000-16998). Example 4). The racemic diphosphate (5 ′) thus obtained was optically resolved using (−)-toluoyl tartaric acid ((−)-DTT), and then trimethylsilyl chloride (TMSCl) / lithium aluminum hydride ( by reduction using _{LiAlH 4), ((-)} - 4,4'- bi-1,3-benzodioxole) -5,5'-diyl bis phosphine (8) ((-) - H ^2- SEGPHOS) may be obtained. Finally, (8) is reacted with 2,4-hexadiyne in the presence of n-butyllithium to obtain the desired (+)-MP ² -SEGPHOS ((+)-(7)).

(+)-H ² -SEGPHOS is obtained by optical resolution using (+)-toluoyl tartaric acid, and (−)-MP ² -SEGPHOS is obtained by using (+)-H ² -SEGPHOS. Is obtained.

  The optically active compound (7) can also be obtained by optical resolution of an enantiomer from a racemic compound using an optically active column or the like. The optically active compound (2) can also be obtained by optical resolution of enantiomers from a racemic compound using an optically active column or the like.

For compounds in which R ¹ and R ² are other than a methyl group, the target compound can be obtained by using an alkadiin corresponding to 2,4-hexadiyne. Corresponding alkadiins include 3,5-octadiyne, 4,6-decadiyne, 2,7-dimethyl-3,5-octadiyne, 5,7-dodecadiine, 3,8-dimethyl-4,6-decadiyne, 2, 9-dimethyl-4,6-decadiyne, 2,2,7,7, -tetramethyl-3,5-octadiyne, 6,8-tetradecadiyne, 4,9-dimethyl-5,7-dodecadiine, 2, 11-dimethyl-5,7-dodecadiyne, 1,1,1,6,6,6-hexafluoro-2,4-hexadiyne, 1,3-diphenylbutadiyne, 1,3-bis (4-tolyl)- Butadiyne, 1,3-bis (3,5-xylyl) -butadiyne, 1,3-bis (naphthalen-1-yl) -butadiyne, 1,3-bis (naphthalen-2-yl) -butadiyne, 1,3 -Screw (3 5-di (tert- butyl) -4-methoxyphenyl) - butadiyne and the like.

In the phosphine compound (1) of the present invention and the primary phosphine compound represented by the general formula (2), R ⁵ is a hydrogen atom, and R ⁶ and R ⁷ together form a methylenedioxy group. Other than those described above, other aryl halides can be used in place of 3,4-methylenedioxyphenyl bromide. Specifically, 3-methoxyphenyl bromide, 3-ethoxyphenyl bromide, 3-methylphenyl bromide, 3-methylphenyl bromide, 3,4-ethylenedioxyphenyl bromide, 3,4-trimethylenedioxyphenyl bromide, Examples include 2-naphthyl bromide.

In the above method, R ¹ and R ² are methyl groups, R ³ , R ⁴ and R ⁵ are hydrogen atoms, and R ⁶ and R ⁷ are combined to form a methylenedioxy group (1) ) And the primary phosphine compound represented by the general formula (2) can be used similarly.

  The phosphine compound (1) of the present invention thus obtained forms a transition metal phosphine complex as a ligand. Examples of the transition metal forming this complex include iridium, rhodium, ruthenium, palladium, nickel, copper and platinum. Examples of the complex formed include transition metals represented by the following general formula (9). A phosphine complex is mentioned as a preferable thing.

[M _m L _n W _p U _q ] _r Z _s (9)

Wherein M is a transition metal selected from the group consisting of iridium, rhodium, ruthenium, palladium, nickel, copper and platinum; L is a phosphine compound represented by the general formula (1); U, m, n, p, q, r, s are (i) when M is iridium or rhodium, (i) W is chlorine, bromine or iodine, and m = n = p = 1, r = 2 and q = s = 0, (ii) W is 1,5-cyclooctadiene or norbornadiene, Z is BF ₄ , ClO ₄ , OTf (Tf is a triflate group (SO ₃ CF ₃₎ ), PF ₆ , SbF ₆ or BPh ₄ (Ph represents a phenyl group), m = n = p = r = s = 1, q = 0, and (iii) Z is _{, BF 4, ClO 4, OTf} , PF 6, a SbF ₆ or _{BPh 4, m = r = s} = , N = 2, q = 0, and (b) when M is ruthenium, (i) W is chlorine, bromine or iodine, Z is a trialkylamine, and m = p = s = 1, n = r = 2, q = 0, (ii) W is chlorine, bromine or iodine, Z is a pyridyl group or a ring-substituted pyridyl group, and m = n = r = s = 1 P = 2, q = 0, (iii) W is a carboxylate group, m = n = r = 1, p = 2, q = s = 0, and (iv) W is chlorine , Bromine or iodine, Z is dimethylformamide or dimethylacetamide, m = n = r = 1, p = 2, q = 0, s is an integer of 0-4, (v) W is , Chlorine, bromine or iodine, U is chlorine, bromine or iodine, Z is a dialkylammonium ion, m = n = p = Q = 3, r = s = 1, (vi) W is chlorine, bromine or iodine, U is an aromatic compound or olefin which is a neutral ligand, Z is chlorine, Bromine, iodine or I ₃ , m = n = p = q = r = s = 1, (vii) Z is BF ₄ , ClO ₄ , OTf, PF ₆ , SbF ₆ or BPh ₄ ; m = n = r = 1, p = q = 0, s = 2, and (viii) W and U may be the same or different, and are a hydrogen atom, chlorine, bromine, iodine, carboxyl group Or an anionic group, Z is a diamine compound, and m = n = p = q = r = s = 1, (c) when M is palladium, (i) W is chlorine, Bromine or iodine, m = n = r = 1, p = 2, q = s = 0, (ii) W is an allyl group, m = n = p = r = 1 Q = s = 0, and (iii) Z is BF ₄ , ClO ₄ , OTf, PF ₆ , SbF ₆ or BPh ₄ , m = n = r = 1, p = q = 0, s = (Iv) W is an alkyl nitrile, benzonitrile, phthalonitrile, pyridine, dimethyl sulfoxide, dimethylformamide, dimethylacetamide or acetone having 1 to 5 carbon atoms, and Z is BF ₄ , ClO ₄ , OTf , PF ₆ , SbF ₆ or BPh ₄ , m = n = r = 1, p = s = 2, q = 0, and (d) when M is nickel, (i) W is chlorine, Bromine or iodine, m = n = r = 1, p = 2, q = s = 0, and (ii) Z is BF ₄ , ClO ₄ , OTf, PF ₆ , SbF ₆ or BPh ₄ , M = n = r = 1, p = q = 0, s = 2, and (e) when M is copper, W , Hydrogen atom, fluorine, chlorine, bromine or iodine, m = p = 4, n = 2, r = 1, q = s = 0, and (f) when M is platinum, (i) W Is an alkyl nitrile, benzonitrile, phthalonitrile, pyridine, dimethyl sulfoxide, dimethylformamide, dimethylacetamide or acetone having 1 to 5 carbon atoms, and Z is BF ₄ , ClO ₄ , OTf, PF ₆ , SbF ₆ or BPh. ₄ and m = n = r = 1, p = s = 2, q = 0, (ii) W is chlorine, bromine or iodine, m = n = r = 1, p = 2, q = s = 0, (iii) W is chlorine, bromine or iodine, U is SnCl ₂ , m = n = q = r = 1, p = 2, s = 0 (Iv) W is chlorine, bromine or iodine, U is SnCl ₃ , m = n = p = q = r = 1, s = 0. )

  Although it does not restrict | limit especially as a manufacturing method of a transition metal phosphine complex (9), For example, it can manufacture using the method shown next, or a method according to this. In the following transition metal phosphine complex formula, cod is 1,5-cyclooctadiene, nbd is norbornadiene, Ac is an acetyl group, acac is acetylacetonate, dmf is dimethylformamide, and en is ethylenediamine. , DPEN represents diphenylethylenediamine, and Tf represents a trifluoromethanesulfonyl group.

Rhodium complex: As a specific example for producing a rhodium complex, for example, described in the Chemical Society of Japan, “Fourth Edition, Experimental Chemistry Course”, Volume 18, Organometallic Complex, 1991, pp. 339-344 (Maruzen) According to the method of bis (1,5-cyclooctadiene) rhodium (I) tetrafluoroborate ([Rh (cod) ₂ ] BF ₄ ) and the phosphine compound (1) of the present invention are reacted to synthesize. can do.
Specific examples of the rhodium complex include the following.
[Rh (L) Cl] ₂ , [Rh (L) Br] ₂ , [Rh (L) I] ₂ , [Rh (cod) (L)] OTf, [Rh (cod) (L)] BF ₄ ,
[Rh (cod) (L)] ClO ₄ , [Rh (cod) (L)] SbF ₆ , [Rh (cod) (L)] PF ₆ , [Rh (cod) (L)] BPh ₄ ,
[Rh (nbd) (L)] OTf, [Rh (nbd) (L)] BF ₄ , [Rh (nbd) (L)] ClO ₄ , [Rh (nbd) (L)] SbF ₆ ,
[Rh (nbd) (L)] PF ₆ , [Rh (nbd) (L)] BPh ₄ , [Rh (L) ₂ ] OTf, [Rh (L) ₂ ] BF ₄ ,
[Rh (L) ₂ ] ClO ₄ , [Rh (L) ₂ ] SbF ₆ , [Rh (L) ₂ ] PF ₆ , [Rh (L) ₂ ] BPh ₄

Ruthenium complex: As a method for producing a ruthenium complex, for example, according to the literature (J. Chem. Soc., Chem. Commun., 922, 1985), [(1,5-cyclooctadiene) Dichlororuthenium] ([Ru (cod) Cl ₂ ] _n ) and the phosphine compound (1) of the present invention can be prepared by heating to reflux in an organic solvent in the presence of a trialkylamine. Further, according to the method described in JP-A No. 11-269185, bis [dichloro (benzene) ruthenium] ([Ru (benzone) Cl ₂ ] ₂ ) and the phosphine compound (1) of the present invention are present in the presence of a dialkylamine. It can be prepared by heating to reflux in an organic solvent. Further, in accordance with the method described in the literature (J. Chem. Soc., Chem. Commun., 1208, 1989), bis [diiodo (para-cymene) ruthenium] ([Ru (p-cymene) I _{2 2} ) and the phosphine compound (1) of the present invention can be prepared by heating and stirring in an organic solvent. Furthermore, Ru ₂ Cl ₄ (L) ₂ obtained according to the method described in the literature (J. Chem. Soc., Chem. Commun., Page 992, 1985) according to the method described in JP-A-11-189600. It can be synthesized by reacting NEt ₃ and a diamine compound in an organic solvent.
Specific examples of the ruthenium complex include the following.
Ru (OAc) ₂ (L), Ru (OCOCF ₃ ) ₂ (L), Ru ₂ Cl ₄ (L) ₂ NEt ₃ ,
[[RuCl (L)] ₂ (μ-Cl) ₃ ] [Me ₂ NH ₂ ], [[RuBr (L)] ₂ (μ-Br) ₃ ] [Me ₂ NH ₂ ],
[[RuI (L)] ₂ (μ-I) ₃ ] [Me ₂ NH ₂ ], [[RuCl (L)] ₂ (μ-Cl) ₃ ] [Et ₂ NH ₂ ],
[[RuBr (L)] ₂ (μ-Br) ₃ ] [Et ₂ NH ₂ ], [[RuI (L)] ₂ (μ-I) ₃ ] [Et ₂ NH ₂ ],
RuCl ₂ (L), RuBr ₂ (L), RuI ₂ (L), [RuCl ₂ (L)] (dmf) _n , RuCl ₂ (L) (pyridine) ₂ ,
RuBr ₂ (L) (pyridine) ₂ , RuI ₂ (L) (pyridine) ₂ , RuCl ₂ (L) (2,2′-dipyridine),
RuBr ₂ (L) (2,2′-dipyridine), RuI ₂ (L) (2,2′-dipyridine),
[RuCl (benzone) (L)] Cl, [RuBr (benzone) (L)] Br, [RuI (benzone) (L)] I,
[RuCl (p-cymene) (L)] Cl, [RuBr (p-cymene) (L)] Br, [RuI (p-cymene) (L)] I,
[RuI (p-cymene) (L)] I ₃ , [Ru (L)] (OTf) ₂ , [Ru (L)] (BF ₄ ) ₂ , [Ru (L)] (ClO ₄ ) ₂ ,
[Ru (L)] (SbF ₆ ) ₂ , [Ru (L)] (PF ₆ ) ₂ , [Ru (L)] (BPh ₄ ) ₂ , [RuCl ₂ (L)] (en),
[RuBr ₂ (L)] (en), [RuI ₂ (L)] (en), [RuH ₂ (L)] (en), [RuCl ₂ (L)] (DPEN),
[RuBr ₂ (L)] (DPEN), [RuI ₂ (L)] (DPEN), [RuH ₂ (L)] (DPEN)

Iridium Complex: As a method for producing an iridium complex, for example, according to the method described in the literature (J. Organomet. Chem., 1992, 428, 213), the phosphine compound (1) of the present invention and [( It can be prepared by reacting 1,5-cyclooctadiene) (acetonitrile) iridium] tetrahydroborate ([Ir (cod) (CH ₃ CN) ₂ ] BF ₄ ) with stirring in an organic solvent. .
Specific examples of the iridium complex include the following.
_{[Ir (L) Cl] 2} , [Ir (L) Br] 2, [Ir (L) I] 2, [Ir (cod) (L)] OTf, [Ir (cod) (L)] BF 4,
[Ir (cod) (L)] ClO ₄ , [Ir (cod) (L)] SbF ₆ , [Ir (cod) (L)] PF ₆ , [Ir (cod) (L)] BPh ₄ ,
[Ir (nbd) (L)] OTf, [Ir (nbd) (L)] BF ₄ , [Ir (nbd) (L)] ClO ₄ , [Ir (nbd) (L)] SbF ₆ ,
[Ir (nbd) (L)] PF ₆ , [Ir (nbd) (L)] BPh ₄ , [Ir (L) ₂ ] OTf, [Ir (L) ₂ ] BF ₄ , [Ir (L) ₂ ] ClO ₄ ,
[Ir (L) ₂ ] SbF ₆ , [Ir (L) ₂ ] PF ₆ , [Ir (L) ₂ ] BPh ₄ , IrCl (cod) (CO) (L),
IrBr (cod) (CO) (L), IrI (cod) (CO) (L)

Palladium complex: As a method for producing a palladium complex, for example, literature (J. Am. Chem. Soc., 1991, 113, 9887; J. Chem. Soc., Dalton Trans., 2246-2249, 1980; Tetrahedron Letters, 37, 6351-6354, 1996), the phosphine compound (1) of the present invention and π-allyl palladium chloride ([(π-allyl) PdCl] ₂ ) Can be prepared by reacting.
Specific examples of the palladium complex include the following.
PdCl ₂ (L), PdBr ₂ (L), PdI ₂ (L), Pd (OAc) ₂ (L), Pd (OCOCF ₃ ) ₂ (L),
[(Π-allyl) Pd (L)] Cl, [(π-allyl) Pd (L)] Br, [(π-allyl) Pd (L)] I,
[(Π-allyl) Pd (L)] OTf, [(π-allyl) Pd (L)] BF ₄ , [(π-allyl) Pd (L)] ClO ₄ ,
[(Π-allyl) Pd (L)] SbF ₆ , [(π-allyl) Pd (L)] PF ₆ , [(π-allyl) Pd (L)] BPh ₄ ,
[(Pd (L))] (OTf) ₂ , [(Pd (L))] (BF ₄ ) ₂ , [(Pd (L))] (ClO ₄ ) ₂ , [[(Pd (L))] (SbF ₆ ) ₂ ,
[(Pd (L))] (PF ₆ ) ₂ , [(Pd (L))] (BPh ₄ ) ₂ , PhCH ₂ Pd (L) Cl, PhCH ₂ Pd (L) Br,
PhCH ₂ Pd (L) I, PhPdCl (L), PhPdBr (L), PhPdI (L), Pd (L), [Pd (L) (PhCN) ₂ ] (BF ₄ ) ₂

Nickel complex: As a method for producing a nickel complex, for example, the method of the Chemical Society of Japan, “Fourth Edition, Experimental Chemistry Course”, Vol. 18, Organometallic Complex, 1991, page 376 (Maruzen), literature (J Am. Chem. Soc., 1991, 113, 9887), the phosphine compound (1) of the present invention and nickel chloride (NiCl ₂ ) are dissolved in an organic solvent and heated. It can be prepared by stirring.
Specific examples of the nickel complex include the following.
NiCl ₂ (L), NiBr ₂ (L), NiI ₂ (L)

Copper complex: As a method for producing a copper complex, for example, according to the method of the Chemical Society of Japan “4th edition Experimental Chemistry Course” Vol. 18, Organometallic Complex, 1991, pp. 444-445 (Maruzen), The phosphine compound (1) of the present invention and copper (I) chloride (CuCl ₂ ) can be prepared by dissolving in an organic solvent and stirring with heating.
Specific examples of the copper complex include the following.
Cu ₄ F ₄ (L) ₂ , Cu ₄ Cl ₄ (L) ₂ , Cu ₄ Br ₄ (L) ₂ , Cu ₄ I ₄ (L) ₂ , Cu ₄ H ₄ (L) ₂

Platinum complex: As a method for producing a platinum complex, for example, the phosphine compound (1) of the present invention and dibenzonitrile dichloroplatinum (in accordance with the method described in the literature (Orgomometallics, 1991, Vol. 10, page 2046)) ( PtCl ₂ (PhCN) ₂ ) can be prepared by dissolving in an organic solvent and heating and stirring, and a Lewis acid (SnCl ₂ or the like) may be added as necessary.
Specific examples of the platinum complex include the following.
PtCl ₂ (L), PtBr ₂ (L), PtI ₂ (L), PtCl ₂ (L) (SnCl ₂ ), PtCl (L) (SnCl ₃ )

  The transition metal phosphine complex having the optically active compound (especially enantiomer) of the phosphine compound (1) of the present invention as a ligand is a transition metal complex catalyst for asymmetric synthesis reaction, particularly a transition metal complex catalyst for asymmetric hydrogenation reaction, It is useful as a transition metal complex catalyst for asymmetric isomerization reaction, a transition metal complex catalyst for asymmetric hydroformylation reaction, and the like. In the phosphine compound (1) of the present invention, the racemate is also useful as a production intermediate for the corresponding optically active compound.

  When a transition metal phosphine complex is used as a catalyst, it may be used after the purity of the complex is increased, but the complex may be used without purification.

Among the transition metal phosphine complexes, ruthenium and optically active compound (4,4′-bi-1,3-benzodioxole) -5,5′-diylbis (2,5-dimethylphosphole (MP ^The transition metal phosphine complex containing ^2- SEGPHOS) as a ligand is a complex containing BINAP or SEGPHOS, which are optically active phosphine compounds having similar biaryl moieties, in the asymmetric hydrogenation of N-acetamidocinnamic acid. Higher enantioselectivity can be provided.

  When the asymmetric hydrogenation reaction is performed using the transition metal phosphine complex of the present invention, examples of the substrate to be asymmetrically hydrogenated include carbonyl compounds, imines, olefins, and the like. Specifically, α-ketoesters , Β-ketoesters, γ-ketoesters, α-hydroxyketones, β-hydroxyketones, allyl ketones, α, β-unsaturated ketones, enamides, enol esters, allyl alcohols, α, β- And unsaturated carboxylic acids. Preferably, α, β-unsaturated carboxylic acids are used.

  The reaction conditions for carrying out the asymmetric hydrogenation reaction using the transition metal phosphine complex of the present invention can vary depending on the substrate, complex, etc. used, but cannot generally be said, but usually at a reaction temperature of 0 to 100 ° C. For 2 to 30 hours under a hydrogen pressure of 1.0 to 10.0 MPa. The amount of the transition metal phosphine complex of the present invention to be used with respect to the substrate is about 1/500 to 1/10000 (molar ratio). The reaction solvent is stable and can be used as long as it does not affect the substrate or product. Specifically, lower alcohols such as methanol, ethanol and isopropanol, tetrahydrofuran and the like can be used. Ethers, halogenated hydrocarbons such as methylene chloride, chlorobenzene and the like are used. The amount of use may vary depending on the solubility of the substrate and the like. About 1 to 100 times the volume (ml / g) is used.

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. In addition, the apparatus used for the measurement of the physical property in each Example is as follows.
¹ H NMR: DRX500 (500 MHz) manufactured by Bruker
³¹ P NMR: DRX500 (202 MHz) manufactured by Bruker
Melting point: MP-500D manufactured by Yanaco
Optical rotation: JASCO Corporation DIP-4
Gas chromatography: 5890-II manufactured by Hewlett Packard
High performance liquid chromatography: HP1100 manufactured by Hewlett Packard
Mass spectrometry: M-80B manufactured by Hitachi, Ltd.

Example 1 of (+)-(4,4′-bi-1,3-benzodioxole) -5,5′-diylbis (2,5-dimethylphosphole ((+)-MP ² -SEGPHOS) Composition

(A) Synthesis of (−)-(4,4′-bi-1,3-benzodioxole) -5,5′-diylbis (diethylphosphonate) ((−)-5 ′) Diphosphate (6) 204.5 g (478 mmol), (-)-ditoluoyltartaric acid 153.6 g (478 mmol) obtained by the method disclosed in [Example 4] of Japanese Patent No. 16998 and butyl acetate 510 Add mL and heat to 105 ° C. After cooling to room temperature and stirring overnight, the produced solid was collected by filtration. After adding dichloromethane 1000 mL, 1 mol / L sodium hydroxide aqueous solution 1000 mL and stirring for 0.5 hour, liquid separation was carried out. The organic layer was washed with water and a saturated aqueous sodium chloride solution in that order, and then dried over anhydrous sodium sulfate. When the solvent was distilled off, 55.0 g of the title compound was obtained with an optical purity of 98.2% ee.
To 55.0 g (106 mmol) of the total amount of the title compound thus obtained, 41.3 g (106 mmol) of (−)-ditoloyltartaric acid and 137 mL of butyl acetate were added and heated to reflux. After air cooling, the generated solid was collected by filtration, and then 500 mL of dichloromethane and 500 mL of a 1 mol / L aqueous sodium hydroxide solution were added. After stirring for 0.5 hour, the oil layer was washed with a 1 mol / L sodium hydroxide aqueous solution, water and saturated brine in that order, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 43.7 g of the title compound having an optical purity of 100% ee (yield 21%).
Optical purity was measured by HPLC.

[Α] _D ²⁴ : -50.5 (c 1.0, CHCl ₃ )

Of: (b) (-) - (4,4'- bi-1,3-benzodioxole) -5,5'-diyl bis phosphine (8 (- -) (- -) H 2 -SEGPHOS) Synthesis A solution of 19.3 g (50.9 mmol) of lithium aluminum hydride in tetrahydrofuran was cooled to −30 ° C., and 64.7 mL (50.9 mmol) of chlorotrimethylsilane was added dropwise while keeping the temperature at −20 ° C. or lower. did. After stirring at −30 ° C. for 30 minutes, a solution of 43.7 g (8.49 mmol) of (−)-diphosphate ((−)-6) in 150 mL of tetrahydrofuran was added. After stirring at room temperature for 1 hour, a mixed solution consisting of 20 mL of methanol and 60 mL of tetrahydrofuran was carefully added dropwise. Subsequently, methanol 20 mL, water 40 mL, and 1 mol / L sodium hydroxide aqueous solution were sequentially added and stirred. After removing the solid by Celite filtration, the solvent was distilled off under reduced pressure to obtain 22.7 g of the title compound (yield 87%, 99.8% ee). In addition, optical purity was measured in accordance with a conventional method using optically active HPLC (Chiralcel OD).

EI-MS: m / z 307 (M + 1) ^+
1 H NMR (CDCl ₃ ) δ: 3.59 (4H, d, J = 203.5 Hz), 5.90 (4H, s), 6.75 (2H, d, J = 7.6 Hz), 7.13 (2H, m)
³¹ P NMR (CDCl ₃ ) δ: 130.3 (t, J = 202.4 Hz)
[Α] _D ²⁴ : -58.0 (c 1.0, CHCl ₃ )

(C) (+)-[(4,4′-bi-1,3-benzodioxole) -5,5′-diyl] bis (2,5-dimethylphosphole) ((+)-MP ² -SEGPHOS) (-)-H ² -SEGPHOS 3.4 g (11.1 mmol) and 2,4-hexadiyne 4.5 g (2 eq) were dissolved in toluene 50 mL and tetrahydrofuran 10 mL. Heated to ° C. To this mixed solution, 3.5 mL (0.5 eq) of 1.6 mol / L n-butyllithium hexane solution was added dropwise. After stirring at 40 degrees for 2 hours, methanol was added and the solvent was distilled off. The residue was purified by silica gel chromatography to obtain 604 mg of the title compound. (Yield 13%, optical purity 99.6% ee). In addition, optical purity was measured in accordance with a conventional method using optically active HPLC (Chiralcel OD).

Mp: 228-230 ° C
EI-MS: m / z 462 ([M] ⁺ )
¹ H NMR (CDCl ₃ ) δ: 2.00 (6H, s), 2.03 (6H, s), 5.94 (2H, d, J = 1.1 Hz), 6.03 (2H, d , J = 1.1 Hz), 6.30-6.53 (6H, m), 6.77 (2H, d, J = 8.2 Hz)
³¹ P NMR (CDCl ₃ ) δ: 3.2 (s)
[Α] _D ²⁴ : +134.70 (c 1.0, CHCl ₃ )

Example 2 (+)-[(4,4′-bi-1,3-benzodioxole) -5,5′-diyl] bis (2,5-diphenylphosphole) ((+)-P ³ -SEGPHOS) (-)-H ² -SEGPHOS 3.0 g (9.8 mmol), 2,4-diphenylbutadiyne 3.96 g (19.6 mmol) in toluene 90 mL, tetrahydrofuran 3 mL Dissolved and cooled to 0 ° C. To this mixed solution, 2.45 mL (3.92 mmol) of 1.6 mol / L n-butyllithium hexane solution was added dropwise. The reaction solution was stirred at 0 ° C. for 2 hours, then warmed to room temperature, and further stirred for 2 hours. Subsequently, methanol was added and the solvent was distilled off. The residue was purified by silica gel chromatography to obtain 3.29 g of the title compound. (Yield 47%, optical purity 99.7% ee). The optical purity was measured according to a conventional method using optically active HPLC (Chiralcel OD).

EI-MS: m / z 711 (M + 1) ^+
1 H NMR (CDCl ₃ ) δ: 5.23 (2H, d, J = 1.6 Hz), 5.57 (2H, d, J = 1.6 Hz), 6.62 (2H, d, J = 8.2 Hz), 6.69 (2H, td, J = 2.2, 8.2 Hz), 6.74-8.10 (24H, m)
³¹ P NMR (CDCl ₃ ) δ: −1.8 (s)
[Α] _D ²⁴ : +164.3 (c 1.0, CHCl ₃ )

Example 3 Synthesis of [Rh (cod) ((+)-MP ² -SEGPHOS)] OTf (+)-MP ² -SEGPHOS 50 mg (0.108 mmol) was dissolved in 3 mL of dichloromethane, and [Rh (cod ₂ ) OTf 50.6 mg (0.108 mmol) was added dropwise to 3 mL of dichloromethane. After stirring at room temperature for 4 hours, the solvent was distilled off under reduced pressure. The solid was washed 3 times with 5 mL of hexane and then dried under reduced pressure to give 90 mg of the title compound.

³¹ P NMR (CD ₂ Cl ₂ ) δ: 39.6 (d, J = 130.5 Hz)

Example 4 Synthesis of [RuCl (p-cymene) ((+)-MP ² -SEGPHOS)] Cl (+)-MP ² -SEGPHOS 50.0 mg (0.108 mmol), [RuCl ₂ (p-cymene) )] ₂ 33.1 mg (0.054 mmol) was dissolved in 2.5 mL of dichloromethane and 2.5 mL of ethanol, and the mixture was stirred at 50 ° C. for 4 hours. Next, the solvent was distilled off under reduced pressure to obtain 76 mg of the title compound. (Yield 92%)

³¹ P NMR (CD ₂ Cl ₂ ) δ: 41.4 (d, J = 58.0 Hz), 45.6 (d, J = 58.0 Hz)

Example 5 Synthesis of Ru (OAc) ₂ ((+)-MP ² -SEGPHOS) (+)-MP ² -SEGPHOS 100.0 mg (0.216 mmol), [RuCl ₂ (p-cymene)] ₂ 66 .1 mg (0.108 mmol) was dissolved in dichloromethane (2.5 mL) and ethanol (2.5 mL), and the mixture was stirred at 50 ° C. for 4 hours. Next, 53.2 mg (0.648 mmol) of sodium acetate and 5 mL of 1,4-dioxane were added, and the mixture was stirred at 100 ° C. overnight. The reaction mixture was filtered, and the solvent was evaporated under reduced pressure to give the title compound (154 mg). (Yield 92%)

³¹ P NMR (CD ₂ Cl ₂ ) δ: 83.4 (s)

Example 6 Synthesis of [Rh (cod) ((+)-P ³ -SEGPHOS)] OTf (+)-P ³ -SEGPHOS 50.0 mg (0.070 mmol) was dissolved in 3 mL of dichloromethane, and [Rh (Cod) ₂ ] OTf 50.6 mg (0.070 mmol) was added dropwise to 3 mL of dichloromethane. After stirring at room temperature for 4 hours, the solvent was distilled off under reduced pressure. The solid was washed 3 times with 5 mL of hexane and then dried under reduced pressure to give 79 mg of the title compound.

³¹ P NMR (CD ₂ Cl ₂ ) δ: 24.7 (d, J = 136.1 Hz)

Example 7 Asymmetric hydrogenation reaction of N-acetamidocinnamic acid Under a nitrogen atmosphere, [RuCl (p-cymene) (L)] Cl 0.0024 mmol, N-acetamidocinnamic acid 100 mg (0.487 mmol), sodium 29.1 mg (> 95%, 0.511 mmol) of methoxide and 1 mL of methanol were placed in a stainless steel autoclave and stirred for 15 hours under the conditions of 60 ° C. and hydrogen pressure of 3.0 MPa. The conversion rate and optical purity of the reaction product were measured by ¹ H NMR (CD ₃ OD) and HPLC, respectively. As a comparative example, the same reaction was performed using L replaced with (S) -SEGPHOS.
The results are shown in Table 1.

In Example 7 in which hydrogenation was performed using the transition metal complex catalyst having MP ² -SEGPHOS of the present invention as a ligand, the optical purity was extremely excellent at 60% ee. The conversion rate is also a sufficiently high value of 83%, which is a range that can be covered by making the reaction time a little longer. On the other hand, in the comparative example in which hydrogenation was performed using SEGPHOS having a similar biaryl skeleton, the conversion was excellent at 99% or more, but the optical purity was extremely poor at 28% ee. From the results, it can be seen that MP ² -SEGPHOS of the present invention is a very useful ligand in carrying out asymmetric hydrogenation.

Claims (1)

The following general formula (2)

(Where
R ⁵ is, shows a hydrogen atom,
R ⁶ and R ⁷ are formed together with each other physician, form a methylenedioxy group, ethylenedioxy group or trimethylenedioxy group. )
A primary phosphine compound represented by the formula: wherein the primary phosphine compound is an axially asymmetric optically active substance.