JPH0597880A - Novel asymmetric axially chiral aminophosphine derivative - Google Patents

Abstract

(57) [Summary] (Modified) [Objective] To provide a practical and useful ligand for a catalyst for asymmetric synthesis. [Structure] General formula [I] [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, the same benzyl group, 2 R ¹ are cyclic groups each having 4 to 5 carbon atoms, and R ² is a phenyl group ( This may be substituted with 1 to 5 selected from a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom) or a cyclohexyl group, and R ³ , R
⁴ , R ⁷ and R ⁸ are the same or different and each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different and a lower alkyl group or a lower alkoxy group. Represents a trifluoromethyl group, or R ⁴ and R ⁵ , and R ⁶ and R ⁷ together represent an aromatic ring.] An optically active axially chiral aminophosphine derivative.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel axially asymmetric aminophosphine derivative useful as a ligand for a catalyst for various organic synthetic reactions, particularly asymmetric hydrogenation reactions.

[0002]

2. Description of the Related Art Many optically active bisphosphine and aminophosphine ligands have been developed as ligands for asymmetric synthesis catalysts. The present inventors previously changed the electronic and steric environment of each phosphino group of bisphosphine,
It has been discovered that high efficiency of catalytic activity can be achieved by providing different functions (JP-A-63-5094,
JP-A-64-19085). However, aminophosphine derivatives having axial asymmetry are novel.

[0003]

Problems to be Solved by the Invention and Means for Solving the Problems Conventional aminophosphine derivatives are asymmetric hydrosilylation or asymmetric cross-coupling reactions (Chem.
Lett. , 999 (1990), TL Assymm
However, the asymmetric yield is inadequate although it is characterized by "Etry 1 , 151 (1990)" and the like.

Therefore, the present inventors have conceived an axially asymmetric aminophosphine derivative [I] having different electronic and steric environments on nitrogen and phosphorus, and as a result of research, the compounds of the present invention are practical and useful catalysts for asymmetric synthesis. The present invention has been completed by discovering that it is a ligand of

[0005]

[Chemical 18]

[Wherein R ¹ is a lower alkyl group which may be substituted with fluorine, an optionally substituted benzyl group, and two R ¹ are cyclic groups each having 4 or 5 carbon atoms. R ² is a phenyl group (the phenyl group may be substituted with 1 to 5 selected from a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom) or a cyclohexyl group, and R ³ , R ⁴ , R
⁷ , R ⁸ are the same or different and each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R
⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ , R ⁶ and R ⁷ together represent an aromatic ring. According to the above, the axially asymmetric aminophosphine derivative represented by the general formula [I] can be produced by the route described below.

(1) The compound represented by the general formula [I] is
It can be produced by optically resolving the compound represented by the general formula [VI] and then reducing the phosphinyl group.

[0008]

[Chemical 19]

[In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹ are cyclic groups each having 4 or 5 carbon atoms. R ² is a phenyl group (the phenyl group may be substituted with 1 to 5 selected from a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom) or a cyclohexyl group, and R ³ , R ⁴ , R
⁷ , R ⁸ are the same or different and each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R
⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ , R ⁶ and R ⁷ together represent an aromatic ring] The optical resolution can be performed by forming a diastereomeric salt with an acid such as (1S)-(+)-10-camphorsulfonic acid or (-)-O, O'-dibenzoyltartaric acid, but Active column, eg Chiralpak OT
Preparative collection using (+) (manufactured by Daicel) is effective.

The reduction of the phosphinyl group can be carried out as a reducing agent.
For example, reducing agents such as lithium aluminum hydride and trichlorosilane can be used, but silane reduction is effective with trichlorosilane in a solvent such as toluene, chlorobenzene or benzene.

(2) The optical resolution in producing the compound represented by the general formula [I] is a diastereomeric salt or diastereomer utilizing the amino group of the compound represented by the general formula [X]. It can also be done by the formation of certain amide groups.

[0012]

[Chemical 20]

[In the formula, R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different. Differently, a lower alkyl group, a lower alkoxy group,
Represents a trifluoromethyl group, or represents R ⁴ and R ⁵ , R ⁶
And R ⁷ together represent an aromatic ring and X represents a halogen atom.] The optical resolution is preferably performed by forming an amide group which is a diastereomer. Reacting the compound of the general formula [X] with (L) -N-tosylprolyl chloride in the presence of an amine base such as triethylamine or pyridine in an organic solvent such as benzene or methylene chloride. Thus, the diastereomeric amide represented by the general formula [XI] can be produced. At this time, an amine base can also be used as a solvent.

[0014]

[Chemical 21]

[In the formula, R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different. Differently, a lower alkyl group, a lower alkoxy group,
Represents a trifluoromethyl group, or represents R ⁴ and R ⁵ , R ⁶
And R ⁷ together represent an aromatic ring, and X represents a halogen atom.] The obtained diastereomeric amide was separated by silica gel column chromatography, high performance liquid chromatography or the like, and then an aqueous alkali solution such as sodium hydroxide or hydroxide was used. By hydrolyzing in an aqueous potassium solution, an optically active compound represented by the general formula [X] can be produced. At this time, addition of a small amount of ethanol is also preferable.

Further derivation of the optically active compound represented by the general formula [X] can lead to the compound represented by the general formula [I].

(3) The compound represented by the general formula [IX] is
It can be produced by reacting the compound represented by the general formula [VII] with the compound represented by the general formula [VIII].

[0018]

[Chemical formula 22]

[In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹ are cyclic groups each having 4 or 5 carbon atoms. R ² is a phenyl group (the phenyl group may be substituted with 1 to 5 selected from a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom) or a cyclohexyl group, and n is 0 or indicating the number ^{1), R 3, R 4,} R 7, R 8 are the same or different, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R ⁵ and R ⁶ Are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ , R ⁶ and R ⁷
Together represent an aromatic ring, and n represents a number of 0 or 1.]

[0020]

[Chemical formula 23]

[Wherein R ¹ is a lower alkyl group which may be substituted with fluorine, an optionally substituted benzyl group, and two R ¹ are cyclic groups each having 4 or 5 carbon atoms. R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different and a lower Represents an alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ , R ⁶ and R
⁷ together represents an aromatic ring, and X represents a halogen atom]

[0022]

[Chemical formula 24]

[Wherein R ² is a phenyl group (the phenyl group may be substituted with 1 to 5 selected from a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom) or cyclohexyl. Group, n represents a number of 0 or 1), and X ¹ represents a halogen atom.] The reaction is carried out by reacting the compound represented by the general formula [VII] with an organic lithium in an organic solvent such as ether or tetrahydrofuran. The compound represented by the general formula [VIII] can be reacted after lithiation with a reagent or after preparing a Grignard reagent with metallic magnesium, but an organolithium reagent such as n-butyllithium or t-butyllithium is used. The reaction temperature is preferably -50 to -70 ° C.

(4) The compound of the general formula [VII] in which R ¹ is a lower alkyl group which may be substituted with fluorine or a benzyl group which may be substituted is a compound represented by the general formula [X]. Can be produced by reacting with a compound represented by the general formula [XII] in the presence of a base.

[0025]

[Chemical 25]

[In the formula, R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different. Differently, a lower alkyl group, a lower alkoxy group,
Represents a trifluoromethyl group, or represents R ⁴ and R ⁵ , R ⁶
And R ⁷ together represent an aromatic ring, and X represents a halogen atom.]

[0027]

[Chemical formula 26]

[In the formula, Ra ¹ represents a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and X ² represents a halogen atom] Here, it may be substituted with fluorine. The lower alkyl group includes methyl, ethyl, propyl, 2,2,3,3,3-pentafluoropropyl, 2,2,3,3,4,4,4-heptafluorobutyl and the like.

The reaction may be carried out in a solvent such as dimethylformamide, acetone or water-ethanol in the presence of a base such as potassium carbonate, sodium carbonate or sodium hydride in the range of room temperature to the reflux temperature of the solvent. preferable.

When Ra ¹ is a methyl group, the general formula [X]
It can also be produced by adding formic acid and formalin to the compound represented by and refluxing.

(5) The compound represented by the general formula [VII] is
The compound represented by the general formula [XIV] is reacted with the compound represented by the general formula [XIII] in the presence of a base and, if necessary, a copper catalyst such as cuprous bromide or cuprous chloride. It can also be manufactured.

[0032]

[Chemical 27]

[In the formula, R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different. Differently, a lower alkyl group, a lower alkoxy group,
Represents a trifluoromethyl group, or represents R ⁴ and R ⁵ , R ⁶
And R ⁷ together represent an aromatic ring, and X and X ³ are the same or different and represent a halogen atom.]

[0034]

[Chemical 28]

[Wherein R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group is a cyclic group consisting of 4 or 5 carbon atoms in combination with two R ¹ 's. Representing a group] The reaction is preferably carried out in the presence or absence of a solvent such as dimethylformamide or dimethylsulfoxide with the addition of a base such as potassium carbonate or sodium carbonate under heating. At this time, addition of a copper catalyst such as cuprous bromide or cuprous chloride is also preferable. It is also possible to add the compound represented by the general formula [XIV] in excess and substitute the base.

The compounds represented by the general formula [X] and the general formula [XIII] can be synthesized according to the following Chemical Formula 29.

[0037]

[Chemical 29]

The reaction in Chemical formula 29 is easily carried out by the method described below.

A) Halogenation: The halogenation reaction is preferably carried out in an organic solvent such as acetic acid or methylene chloride at a reaction temperature of 10 to 50 ° C. As the halogenating agent, an ordinary halogenating agent can be used, but bromine is particularly preferable.

B) Zandmeier reaction: The Zandmeier reaction is carried out by using sodium nitrite to form a diazonium salt in an organic solvent such as acetic acid, nitric acid or water with hydrobromide, and then
It is preferable to act potassium iodide or cuprous bromide as the halogenating agent. The reaction temperature is preferably 0 to 30 ° C.

C) Reduction of nitro group: In the case of reduction of a nitro group, an ordinary reducing agent can be used, but when other substituents include a halogen atom, an iron-hydrochloric acid system is preferable, and other substitutions are performed. In the case of a group, catalytic reduction using palladium-carbon as a catalyst is preferable. In the case of catalytic reduction, alcohol is suitable as the solvent.

D) Curtius rearrangement: As a method for converting a lower alkoxycarbonyl group into an amino group, a method utilizing Curtius rearrangement is preferable. After the lower alkoxycarbonyl group is hydrolyzed, the obtained carboxylic acid body is treated with thionyl chloride or the like. As an acid chloride, or with an alkyl chlorocarbonate to give an acid anhydride, and then with sodium azide,
It can be converted into an acyl azide form, an isocyanate form by refluxing in an organic solvent such as benzene and toluene, and an amino form by further hydrolyzing with an alkali.

Among the compounds represented by Chemical formula 29, the compounds represented by the general formula [XV] are obtained by reacting the compound represented by the general formula [XVI] and the compound represented by the general formula [XVII] with a metal catalyst. It can be produced by acting in the presence of.

[0044]

[Chemical 30]

[Wherein R ³ and R ⁴ are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁵ is a lower alkyl group, a lower alkoxy group or a trifluoromethyl group. Represents a group or R ⁴
And R ⁵ together represent an aromatic ring, Y ¹ represents a hydrogen atom, a nitro group, a lower alkoxycarbonyl group, and X ⁴ represents a halogen atom or a boric acid group.]

[0046]

[Chemical 31]

[Wherein R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁶ is a lower alkyl group, a lower alkoxy group or a trifluoromethyl group. Represents a group or R ⁶
And R ⁷ together represent an aromatic ring, Y ² represents a hydrogen atom, a nitro group, a lower alkoxycarbonyl group, X ⁵ represents a halogen atom or a boric acid group, and X ⁴ and X ⁵ are boric acid groups at the same time. No.] In the reaction of the compound represented by the general formula [XVI] with the compound represented by the general formula [XVII], X ⁴ and X ⁵
When both are halogen atoms, copper powder, for example, is used as a metal catalyst in an organic solvent such as sulfolane and quinoline,
It is preferable to carry out at a reaction temperature of 170 to 250 ° C. Here, when Y ¹ and Y ² are a nitro group or a lower alkoxycarbonyl group, X ⁴ and X ⁵ are preferably bromine atoms, and when Y ¹ and / or Y ² are hydrogen atoms, an iodine atom Is preferred.

In the reaction between the compound represented by the general formula [XVI] and the compound represented by the general formula [XVII], X ⁴ or X ⁵
Is a boric acid group, a palladium catalyst, particularly tetrakistriphenylphosphine palladium zero-valent complex is used,
It is preferably carried out in an organic solvent such as benzene, toluene or methylene chloride at the reflux temperature of the solvent.

The compounds represented by the general formula [XVI] and the general formula [XVII], which are the starting materials, can be synthesized according to known literature (eg, tetrahedron, 37 , 747 (1981), etc.) or further nitrated. Alternatively, a necessary raw material can be produced by acting an organolithium reagent or the like and then acting with a trialkyl borate.

[0050]

The present invention will now be described with reference to specific examples, but the present invention is not limited to these examples.

[0051] Example 1 3,3'-dimethoxy-2, 2 ', 4,4'-tetra main
Synthesis of tyl -6-nitro- 1,1'-biphenyl 3-iodo-2,6-dimethylanisole (3.0
g), 3-bromo-2,6-dimethyl-4-nitroanisole (3.0 g), copper powder (2.2 g) and sulfolane (40 ml) were stirred at 170 ° C. for 3 hours and then cooled. , Benzene were added, and the insoluble material was filtered off. The filtrate was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel chromatography (n-hexane: methylene chloride = 9: 1) to obtain the desired product (0.78 g) as pale yellow prism crystals (yield 21.6%). Melting point 7
2 to 73 ° C. H-NMR (δ, CDCl ₃ ): 1.83 (3H,
s), 1.87 (3H, s), 2.27 (3H, s),
2.33 (3H, s), 3.67 (3H, s), 3.7
0 (3H, s), 6.47 (1H, d, J = 8.0H
z), 6.90 (1H, d, J = 8.0 Hz), 7.4
8 (2H, s).

Example 2 6'-Bromo-3,3'- dimethoxy-2,2 ', 4 ,
4'-tetramethyl-6-nitro-1,1'-biphenyl
Was dissolved Compound of Example 1 Le a (1.3 g) in acetic acid (20 ml), bromine (0.32 ml) was added under cooling and stirred overnight at room temperature. Ice water was added to the reaction solution and extracted with benzene,
The organic layer was washed with a 10% aqueous sodium hydroxide solution, then with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel chromatography (n-hexane: methylene chloride = 5: 1) to obtain the desired product (1.36 g) as pale yellow plate crystals (yield 83.6%). Melting point 1
08-110 ° C. H-NMR (δ, CDCl ₃ ): 1.87 (6H,
s), 2.27 (3H, s), 2.37 (3H, s),
3.67 (3H, s), 3.77 (3H, s), 7.2
7 (1H, s), 7.73 (1H, s).

Example 36-amino-6'-bromo -3,3'-dimethoxy-
2,2 ', 4,4'-Tet Lamethyl-1,1'-biff Eh
Synthesis of nil The compound of Example 2 (1.36 g), iron powder (0.6 g),
Mixing methanol (20 ml) and concentrated hydrochloric acid (5.4 ml)
The liquid was heated to reflux for 15 hours. Add ice water to the reaction mixture and
Made alkaline with aqueous sodium hydroxide solution to precipitate
Was collected by filtration. The precipitate is extracted with methylene chloride and the extract is
After washing with water, dry over anhydrous magnesium sulfate and concentrate under reduced pressure.
It was The obtained residue is separated and purified by silica gel chromatography.
(N-hexane: methylene chloride = 1: 1), then
The target product (0.91 g) of a rhythm crystal was obtained (yield 72.4).
%). MS (m / s): 363, 365 (M⁺ ).

Example 4 6'-bromo-3,3'- dimethoxy-2,2 ', 4 ,
4'-tetramethyl-6 - dimethylamino-1,1 '-
Synthesis of biphenyl Compound of Example 3 (1.4 g), methyl iodide (0.5 g)
A mixture of g), sodium carbonate (0.6 g), water (13 ml) and ethanol (22 ml) was heated under reflux for 5 hours. The reaction solution was concentrated under reduced pressure, and the residue was extracted with methylene chloride. After washing the organic layer with water, dried over anhydrous magnesium sulfate,
It was concentrated under reduced pressure. The obtained residue is separated and purified by silica gel chromatography (n-hexane: methylene chloride = 1: 1).
To obtain the target product (1.1 g) as white plate crystals (yield 7
3.0%). Melting point 100 to 102 ° C. Elemental analysis (%): as C ₂₀ H ₂₆ BrNO ₂ H-NMR (δ, CDCl ₃ ): 1.83 (3H,
s), 1.90 (3H, s), 2.28 (6H, s),
2.43 (6H, s), 3.67 (6H, s), 6.6
7 (1H, s), 7.23 (1H, s).

[0055] Example 5 3,3'-dimethoxy-2, 2 ', 4,4'-tetra main
Chill-6-dimethylaminopyridine Roh-6'-diphenylphosphine
Synthesis dry tetrahydrofuran (20ml) to the compound of Example 4 nil 1,1' Biff Eniru a (0.51 g) was completely dissolved, and cooled to -70 ° C.. After adding t-butyllithium (1.48 mol / L hexane solution: 1.93 ml) and stirring at the same temperature for 1 hour, chlorodiphenylphosphine oxide (0.34) dissolved in dry tetrahydrofuran (5 ml) was added to the reaction solution.
g) was added dropwise at −60 ° C. or below, and after stirring at the same temperature for 1 hour,
The temperature was gradually returned to room temperature and left overnight. Tetrahydrofuran was distilled off under reduced pressure, and methylene chloride and water were added to the residue for extraction. The organic layer was washed successively with 10% aqueous sodium hydroxide solution and water and then dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was separated and purified by silica gel chromatography (n
-Hexane: methylene chloride = 1:10), and then recrystallized from hexane-benzene to give a white plate-like target compound (0.4
4g) was obtained (yield 65.9%). Melting point 132-134 ° C Elemental analysis (%): as C ₃₂ H ₃₆ NO ₃ P H-NMR (δ, CDCl ₃ ): 1.53 (3H,
s), 1.87 (3H, s), 2.13 (9H, s),
2.27 (3H, s), 3.50 to 3.73 (3H,
s), 7.23-7.76 (12H, m).

[0056] Example 6 3,3'-dimethoxy-2, 2 ', 4,4'-tetra main
Chill-6-dimethylaminopyridine Roh-6'-diphenylphosphine
Using the compound obtained in optical resolution Example 5 nil 1,1' Biff Eniru (500 mg) an optically active column (Chiralpak OT (+) (manufactured by Daicel)), developing solvent n- hexane - isopropyl alcohol Optical resolution was performed at (20: 1). The above-mentioned fractions were collected and concentrated to give white crystals (50 mg). [Α] _D ²³ : + 25.3 ° (c, 0.29, CHCl ₃ ).

[0057] Example 7 (+) - 3,3'-dimethoxyethane carboxymethyl-2,2 ', 4,4' -
Tetramethyl-6-dimethyl Chiruamino 6'diphenyl sulfonyl
Synthesis of phosphino-1,1'- biphenyl In a pressure resistant tube, the compound of Example 6 (50 mg) was dissolved in dry and degassed chlorobenzene (5 ml), triethylamine (0.38 ml), argon stream, under ice cooling. In (3), trichlorosilane (0.24 ml) was added in that order, the atmosphere was replaced with argon, and the tube was sealed and stirred at 140 ° C. for 5 hours.
Under ice cooling, a degassed 20% aqueous sodium hydroxide solution was added to the reaction solution until the white suspension was dissolved, and the atmosphere was replaced with argon, followed by stirring at 70 ° C. for 30 minutes. Subsequently, the mixture was cooled to room temperature, chlorobenzene (5 ml) was added, the organic layer was separated, washed successively with water and saturated brine, and then dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the residue was separated and purified by silica gel chromatography (toluene) to obtain the target product (34 mg) as white prism crystals (yield 70.2).
%). [Α] _D ²³ : + 44.4 ° (c, 0.174, CHCl ₃ ) H-NMR (δ, CDCl ₃ ): 1.55 (3H,
s), 1.99 (3H, s), 2.22 (3H, s),
2.27 (6H, s), 2.32 (3H, s), 3.5
9 (3H, s), 3.73 (3H, m), 6.75 (1
H, s), 6.93 (1H, s), 6.94 to 7.40.
(10H, m).

[0058] Example 8 3'-methoxy-2 ', 4' - dimethyl-2-nitro -
4,6-bis (a trifluoromethyl) -1,1' Biff
Synthesis of phenyl In the same manner as in Example 1 from 3-iodo-2,6-dimethylanisole and 1-bromo-2-nitro-4,6-bis (trifluoromethyl) benzene, the desired product as slightly yellow prism crystals was obtained. (Yield 80%). Melting point 80-81 ° C Elemental analysis (%): as C ₁₇ H ₁₃ F ₆ NO _3. H-NMR (δ, CDCl ₃ ): 1.97 (3H,
s), 2.34 (3H, s), 3.73 (3H, s),
6.75 (1H, d, J = 7.9 Hz), 7.06 (1
H, d, J = 7.9 Hz), 8.21 (1H, s),
8.22 (1H, s).

[0059] Example 9 6'-Bromo-3'-meth carboxymethyl-2 ', 4'-dimethyl-
-2-Nitro-4,6- bis (trifluoromethyl )-
Synthesis of 1,1′-biphenyl The target compound was obtained by treating the compound of Example 8 in the same manner as in Example 2. H-NMR (δ, CDCl ₃ ): 1.83 (3H,
s), 2.25 (3H, s), 3.63 (3H, s),
7.17 (1H, s), 8.01 (1H, s), 8.0
2 (1H, s).

Example 102-amino-6'-bromo -3'-methoxy-2 ',
4'-dimethyl-4,6- Bis (trifluoromethyl )
-1,1'-biphenyl Synthesis of By treating the compound of Example 9 as in Example 3.
The target product of white prism crystals was obtained. Melting point 85-86 ° C. H-NMR (δ, CDCl₃ ): 1.90 (3H,
s), 2.27 (3H, s), 3.33 (5H, s),
7.01 (1H, s), 7.27 (2H, s).

[0061] Example 11 6'-bromo-3'-meth carboxymethyl-2 ', 4'-dimethyl-
-2-dimethylamino - 4,6-bis (trifluoromethanesulfonyl
Chill) -1,1'-bi compound of Example 10 of phenyl and (0.8 g) was added to a solution of 37% formalin (1 ml) and formic acid (20 ml), it was heated under reflux for 5 hours. The mixture was concentrated under reduced pressure, 10% aqueous sodium hydroxide solution was added to the obtained residue, and the mixture was extracted with chloroform.
The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was separated and purified by silica gel chromatography (n
Hexane: methylene chloride = 4: 1) to obtain the target product (0.82 g) as white prism crystals (yield 96.4%). Melting point 65-67 ° C. Elemental analysis (%): as C ₁₉ H ₁₈ BrF ₆ NO H-NMR (δ, CDCl ₃ ): 1.53 (3H,
s), 2.23 (3H, s), 2.50 (6H, s),
3.63 (3H, s), 7.17 (1H, s), 7.3
0 (1H, s), 7.47 (1H, s).

[0062] Example 12 3'-methoxy-2 ', 4' - dimethyl-2-dimethyl-
Amino-6'-diphenyl Ruhosufiniru 4,6-bis
Synthesis of (trifluoromethyl ) -1,1′-biphenyl By treating the compound of Example 11 in the same manner as in Example 5, the target product as white plate crystals was obtained (yield 70.1%). Melting point 122-124 ° C. Elemental analysis (%): as C ₃₁ H ₂₈ F ₆ NO ₂ P H-NMR (δ, CDCl ₃ ): 1.97 (3H,
s), 2.04 (6H, s), 2.28 (3H, s),
3.76 (3H, s), 7.26 to 7.60 (13H,
m).

[0063] Example 13 3'-methoxy-2 ', 4' - dimethyl-2-dimethyl-
Amino-6'-diphenyl Ruhosufiniru 4,6-bis
Optics of (trifluoromethyl ) -1,1'-biphenyl
The compound obtained in Resolution Example 12 was treated in the same manner as in Example 6,
Optical separation was carried out with a developing solvent, n-hexane-isopropyl alcohol (20: 1), using a column for separating optically active substances (Chiral Pack OT (+) (manufactured by Daicel)). The above fractions were collected and concentrated to give white crystals. [Α] _D ²³ : + 30.9 ° (c, 0.29, CHCl ₃ ) 100% ee by HPLC analysis.

[0064] Example 14 (+) - 3'-methoxy - 2 ', 4'-dimethyl-2 -
Dimethylamino-6'-diphenyl phosphinyl - 4,
3,6-Bis (a trifluoromethyl) -1,1'-bi-phenylene
The desired product was obtained as a white prisms treated in the same manner as in Example 7 the compound of Example 13 of the Le (yield 89.9
%). Melting point 164-166 ° C. [α] _D ²³ : + 58.3 ° (c, 0.12, CHCl ₃ ) H-NMR (δ, CDCl ₃ ): 1.50 (3H,
s), 2.00 (6H, s), 2.20 (3H, s),
3.70 (3H, s), 6.70 to 7.40 (13H,
m).

[0065] Example 15 2-Amino-3'-methoxyethanol 2 ', 4'-dimethyl -
4,6-bis (a trifluoromethyl) -1,1' Biff
Synthesis of phenyl The compound of Example 8 (4.3 g) was added to a solution of 5% palladium carbon (1.0 g) and ethanol (50 ml), and the mixture was stirred under a hydrogen atmosphere at room temperature and atmospheric pressure for 15 hours.
The insoluble material was filtered off, and the obtained filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel chromatography (n-hexane: methylene chloride = 1: 2) to obtain the desired product (2.5 g). H-NMR (δ, CDCl ₃ ): 1.90 (3H,
s), 2.27 (3H, s), 3.63 (3H, s),
6.57 (1H, d, J = 8.0 Hz), 6.90 (1
H, d, J = 8.0 Hz), 6.93 (1H, s),
7.20 (1H, s).

[0066] Example 16 2-Bromo-3'-methoxyethanol 2 ', 4'-dimethyl -
4,6-bis (a trifluoromethyl) -1,1' Biff
Dissolved compound of Example 15 of Eniru a (1.5 g) in acetic acid (5 ml), was added to this solution to a solution of sodium nitrite (0.34 g) in concentrated sulfuric acid (2.6 ml). After stirring at room temperature for 1 hour, the reaction solution was mixed with cuprous bromide (0.8 g),
It was added to a mixture of 7% hydrobromic acid aqueous solution (3 ml). After stirring at room temperature for 24 hours, water was added and benzene was extracted. The extract was washed with 10% aqueous sodium hydroxide solution, then with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The obtained residue is separated and purified by silica gel chromatography (n
-Hexane: methylene chloride = 4: 1) to give the desired product (1.
6 g) was obtained. H-NMR (δ, CDCl ₃ ): 1.90 (3H,
s), 2.37 (3H, s), 3.70 (3H, s),
6.57 (1H, d, J = 8.0 Hz), 7.01 (1
H, d, J = 8.0 Hz), 7.87 (1H, s),
8.01 (1H, s).

[0067] Example 17 2-Bromo-3'-methoxyethanol 2 ', 4'-dimethyl -
6'-nitro-4,6- bis (trifluoromethyl )-
Synthesis of 1,1′-biphenyl The compound of Example 16 (5.9 g) was added to 80% concentrated nitric acid (40
ml) and methylene chloride (40 ml) at room temperature for 13
Stir for hours. Extraction with methylene chloride, the organic layer sequentially,
The extract was washed with water, 10% aqueous sodium hydroxide solution and water, and dried over anhydrous sodium sulfate. The residue was separated and purified by silica gel chromatography (n-hexane: methylene chloride = 9:
1) Purification at ℃, the target product (5.4
g) was obtained. GCMS (m / z): 471, 473 (M ⁺ ) H-NMR (δ, CDCl ₃ ): 1.83 (3H,
s), 2.60 (3H, s), 3.70 (3H, s),
7.83 (1H, s), 7.87 (1H, s), 8.0
3 (1H, s).

Example 186'-amino-2-bromo -3'-methoxy-2 ',
4'-dimethyl-4,6- Bis (trifluoromethyl )
-1,1'-biphenyl Synthesis of The compound of Example 17 (1.4 g) was mixed with ethanol (15 m
l), concentrated hydrochloric acid (6 ml) and iron (0.5 g) were added, and 20
After refluxing for an hour, the mixture was concentrated under reduced pressure. 10% sodium hydroxide on the residue
Add an aqueous solution of um to make it alkaline and add methylene chloride.
The insoluble matter was filtered off. Extract the filtrate with methylene chloride,
The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue
Separation and purification by silica gel chromatography (n-hexane: salt
Methylene chloride = 9: 1) and purified to obtain the desired product (0.73
g) was obtained. GCMS (m / z): 441, 443 (M
⁺ ).

[0069] Example 19 2-Bromo-3'-methoxyethanol 2 ', 4'-dimethyl -
6 '- (L) -N- tosylate Rupuroriruamino 4,6 - bi
Scan (trifluoromethyl Le) -1,1' biphenyl merging
Forming (L)-N-tosyl-proline and (0.9 g) was prepared from thionyl chloride (5ml) (L) -N- tosyl prolyl chloride dissolved ride benzene (10 ml), which compound of Example 18 (1 g ) Was added dropwise to a pyridine (10 ml) solution. After stirring at room temperature for 2 hours, the mixture was extracted with benzene, and the organic layer was washed successively with water, diluted hydrochloric acid and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to high performance liquid chromatography (YMCPacked Column D-SIL-7).
Separation with S-7 120A SIL, n-hexane: isopropyl alcohol (20: 1)). The above-mentioned fractions were collected, and the target substance (0.1
5 g) was obtained. Mp ^{_{193~195 ℃ [α] D 23:}} + 99.8 ° (c, 0.35, CHCl 3) H-NMR (δ, CDCl 3): 1.33~3.30
(7H, m), 1.83 (3H, s), 2.30 (6
H, s), 2.33 (3H, s), 3.67 (3H,
s), 7.17 (2H, d, J = 8.0 Hz), 7.5
0 (2H, d, J = 8.0Hz), 7.90 (1H,
s), 7.97 (1H, s), 8.13 (1H, s).

Example 20 (+)-2-Bromo-3' -methoxy-2 ', 4'- di
Methyl-6'-dimethylamino-4,6-bis (g Riff
Synthesis of Luoromethyl) -1,1′- biphenyl The compound of Example 19 (0.15 g) was added to a mixed solution of 10% aqueous sodium hydroxide solution and a small amount of ethanol,
The mixture was heated under reflux at 80 ° C. for 8 hours. The reaction solution was cooled, extracted with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel chromatography (n-hexane: methylene chloride = 4:
1) Purified at ℃, (+)-6'-amino-2-bromo-
3'-methoxy-2 ', 4'-dimethyl-4,6-bis (trifluoromethyl) -1,1'-biphenyl (70
mg) was obtained. This was mixed with water (3 ml) and ethanol (5.
8 ml), sodium carbonate (0.12 g) and methyl iodide (0.10 g) were added, and the mixture was refluxed for 7 hours.
The reaction solution was concentrated under reduced pressure and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel chromatography (n-hexane: methylene chloride = 4: 1) to obtain the desired product (37 m
g) was obtained. [Α] _D ²³ : + 51.49 ° (c, 0.17, CHCl ₃ ) H-NMR (δ, CDCl ₃ ): 1.80 (3H,
s), 2.27 (3H, s), 2.37 (6H, s),
3.60 (3H, s), 6.80 (1H, s), 7.8
0 (1H, s), 7.97 (1H, s).

Example 21 (+)-3'-methoxy- 2 ', 4'-dimethyl-6 '
- dimethylamino-2-diphenylphosphino -4 6
- bis (trifluoromethyl) -1,1' Biff Eniru
In the same manner as in Example 5 except that chlorodiphenylphosphine was used from the compound of Example 20 (37 mg), the desired compound (2
1 mg) was obtained. Melting point 165 to 166 ° C. [α] _D ²³ : + 23.5 ° (c, 0.12, CHCl ₃ ) H-NMR (δ, CDCl ₃ ): 1.23 (3H,
s), 2.27 (3H, s), 2.37 (6H, s),
3.47 (3H, s), 6.73 (1H, s), 6.7
0-7.33 (10H, m), 7.60 (1H, s),
7.83 (1H, s).

[0072] Example 22 1- (6-bromo-3 main butoxy-2,4-dimethyl-off
Eniru) naphthalene - 2 - dissolution Synthesis of yl carboxylic acid methyl 1- (3-methoxy-2,4-dimethylphenyl) naphthalene-2-yl carboxylic acid methyl a (1.5 g) in acetic acid (30 ml), bromine under stirring ( 0.24 ml) was added, and the mixture was stirred overnight at room temperature. Methylene chloride and ice water were added to the reaction solution for extraction. The organic layer was washed successively with 10% aqueous sodium hydroxide solution and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was recrystallized from n-hexane to obtain the desired product (1.3 g). Melting point 97-98 ° C. Elemental analysis (%): as C ₂₁ H ₁₉ BrO ₃ H-NMR (δ, CDCl ₃ ): 1.73 (3H,
s), 2.31 (6H, s), 3.60 (3H, s),
3.63 (3H, s), 6.70 to 7.33 (7H,
m).

[0073] Example 23 2-Amino-1- (6-Bed Romo 3-methoxy-2, 4
- dimethylphenyl) Compound of Example 22 of Na Futaren (0.9 g) of 10% sodium hydroxide solution (30 ml), was added to a solution of ethanol (3 ml), was heated under reflux for 2 hours. After cooling, it was acidified with concentrated hydrochloric acid and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Thionyl chloride (20 ml) was added to the residue, and the mixture was refluxed for 1 hour and concentrated. After adding dry benzene to the residue and concentrating again under reduced pressure,
The residue was dissolved in acetone (40 ml) and cooled to 0 ° C. Sodium azide (4 g) and water (20 m
The solution of l) was added dropwise at 0 ° C or lower, and the mixture was further stirred at 0 ° C for 30 minutes. Water (40 ml) was added to the reaction solution, extracted with benzene, the organic layer was dried over anhydrous sodium sulfate, and then heated under reflux for 1 hour. A 50% aqueous sodium hydroxide solution (10 ml) was added to the reaction solution, and the mixture was heated under reflux for 1 hour. After cooling, the mixture was extracted with benzene, the organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (methylene chloride: n-hexane = 3: 2) to obtain the desired product (0.55 g) as a pale yellow oil.
Got H-NMR (δ, CDCl ₃ ): 1.87 (3H,
s), 2.33 (3H, s), 3.50 (2H, br)
s), 3.73 (3H, s), 6.70 to 7.80 (7
H, m).

[0074] Example 24 1- (6-bromo-3 main butoxy-2,4-dimethyl-off
Synthesis of ( enyl) -2-dimethylaminonaphthalene The compound of Example 23 (0.55 g) was added to water (15 ml),
Ethanol (27 ml), sodium carbonate (0.6
g) and methyl iodide (0.5 g) were added, and the mixture was heated under reflux for 12 hours. The reaction solution was concentrated under reduced pressure, water was added to the residue, extracted with methylene chloride, the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is separated and purified by silica gel column chromatography (methylene chloride: n-hexane = 2: 3).
Then, the target product (0.51 g) was obtained. Melting point 84-85 ° C. H-NMR (δ, CDCl ₃ ): 1.83 (3H,
s), 2.30 (3H, s), 2.57 (6H, s),
3.68 (3H, s), 6.83 to 8.00 (7H,
m).

[0075] Example 25 2-Dimethylamino-1- (6-diphenylphosphine two
-3-methoxy-2, 4-dimethylphenyl) na lid
Synthesis of Ren The target compound (0.4 g) was obtained by treating the compound of Example 24 (0.51 g) in the same manner as in Example 5. Melting point 90-92 ° C. H-NMR (δ, CDCl ₃ ): 1.80 (3H,
s), 2.27 (3H, s), 2.45 (6H, s),
3.73 (3H, s), 6.33 to 7.83 (7H,
m).

Claims (12)

[Claims] 1. A compound represented by the general formula [I]: [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group, and R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and are hydrogen. An atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R ⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ ,
R ⁶ and R ⁷ together represent an aromatic ring], which is an optically active axially asymmetric aminophosphine derivative. 2. In the general formula [I], R ³ , R ⁵ ,
A compound of the general formula [II] in which R ⁶ and R ⁸ are methyl groups and R ⁴ and R ⁷ are methoxy groups [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group]. 3. R ³ and R ⁵ in the general formula [I].
Is a trifluoromethyl group, R ⁴ is a hydrogen atom, R ⁶ and R
^A compound of the general formula [III] in which ⁸ is a methyl group and R ⁷ is a methoxy group [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group]. 4. R ³ and R ⁵ in the general formula [I].
Is a methyl group, R ⁴ is a methoxy group, R ⁶ and R ⁸ are trifluoromethyl groups, and R ⁷ is a hydrogen atom. [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group]. 5. R ³ and R ⁵ in the general formula [I].
Is a methyl group, R ⁴ is a methoxy group, R ⁶ and R ⁷ are together an aromatic ring, and R ⁸ is a hydrogen atom. [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group]. 6. A compound represented by the general formula [VI]: [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group, and R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and are hydrogen. An atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R ⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ ,
R ⁶ and R ⁷ together represent an aromatic ring]. 7. A compound represented by the general formula [VI]: [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group, and R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and are hydrogen. An atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R ⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ ,
R ⁶ and R ⁷ together represent an aromatic ring], and an optically active axially asymmetric aminophosphinyl derivative is obtained. 8. A compound represented by the general formula [VI]: [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group, and R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and are hydrogen. An atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R ⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ ,
R ⁶ and R ⁷ together represent an aromatic ring] to reduce a phosphinyl derivative represented by the general formula [I] [Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ ,
R ⁸ is as described above] and a method for producing an optically active axially asymmetric aminophosphine derivative. 9. A compound represented by the general formula [I]: [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group, and R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and are hydrogen. An atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R ⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ ,
R ⁶ and R ⁷ together represent an aromatic ring] to oxidize a phosphinyl derivative represented by the general formula [VI] [Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ ,
R ⁸ is as described above] and a method for producing an optically active axially asymmetric aminophosphine derivative. 10. A compound represented by the general formula [VII]: [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, and two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different and a lower alkyl group. , A lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ , R ⁶ and R ⁷ together represent an aromatic ring, and X represents a halogen atom]. VIII] [In the formula, R ² represents a phenyl group (the phenyl group may be substituted with 1 to 5 selected from a lower alkyl group, a lower alkoxy group, a trifluoromethyl group or a halogen atom) or a cyclohexyl group, n represents a number of 0 or 1), and X ¹ represents a halogen atom], and a compound represented by the general formula [IX] [Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ ,
R ⁸ and n are as described above]. 11. A compound represented by the general formula [X]: [Wherein R ³ , R ⁴ , R ⁷ , and R ⁸ are the same or different, a hydrogen atom, a lower alkyl group, a lower alkoxy group, and a trifluoromethyl group, and R ⁵ and R ⁶ are the same or different. , A lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ , R ⁶ and R ⁷ together represent an aromatic ring, and X represents a halogen atom] By reacting (L) -N-tosylprolyl chloride with the compound of the general formula [XI] [Wherein R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are as described above], and these are optically resolved and then hydrolyzed. Method for optical resolution of compounds. 12. A compound represented by the general formula [I]: [In the formula, R ¹ is a lower alkyl group optionally substituted with fluorine, an optionally substituted benzyl group, or two R ¹
Together with a cyclic group consisting of 4 or 5 carbon atoms,
R ² is a phenyl group (the phenyl group is a lower alkyl group,
A lower alkoxy group, a trifluoromethyl group or a halogen atom, which may be substituted with 1 to 5) or a cyclohexyl group, and R ³ , R ⁴ , R ⁷ and R ⁸ are the same or different and are hydrogen. An atom, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, R ⁵ and R ⁶ are the same or different and represent a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, or R ⁴ and R ⁵ ,
R ⁶ and R ⁷ together represent an aromatic ring], and an optically active axially chiral aminophosphine derivative is used as a catalyst ligand.