JP2000154195A - Optically active diaminophosphine-coordinated transition metal complex - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new transition metal complex containing a chiral diaminophosphine capable of being simply synthesized at a low cost under mild conditions as a ligand and useful as an asymmetric catalyst for unsaturated organic compounds, etc. SOLUTION: An optically active diaminophosphine-coordinated transition metal complex of formula I [R is a (substituted) aryl or a (substituted) 3-8C cycloalkyl; (n) is 0 or 1; M is a transition metal; A is a counter ion; (m) is an integer of 0-4; L1 and L2 are each independently or together form a ligand] or formula II. The transition metal complex is useful as an unsaturated catalyst for unsaturated organic compounds, etc. The transition metal is obtained by reacting an optically active 2,2'-bipiperidine or 2,2'-bipyrrolidine of formula III or IV with a halophosphine of formula V (X is a halogen) and subsequently reacting the obtained optically active diaminophosphine derivative with a compound containing a transition metal such as rhodium, rethenium, palladium or iridium.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an optically active diaminophosphine-coordinated transition metal complex useful as an asymmetric catalyst for unsaturated organic compounds and the optically active diaminophosphine ligand, and further relates to the ligand and its synthesis. The present invention relates to a method for producing an intermediate and a method for asymmetricizing an unsaturated organic compound using the complex.

[0002]

2. Description of the Related Art In recent years, asymmetric synthesis using a diamine ligand has been actively performed. For example, asymmetric reduction using diaminocyclohexane (K. Onuma et al .; Bu
ll. Chem. Soc. Jpn., 1980, p. 201
6), asymmetric aldol condensation using 1,2-diphenylethylenediamine (EJ Corey. Et al .;
Am. Chem. Soc., 1989, 111 , p. 549.
3) Asymmetric deprotonation using (-)-sparteine (ST Kerrick, P. Peak; J. Am. Ch.
em. Soc., 1991, 113 , p. 9708) and the like, and it is expected that diamine ligands can be used for such asymmetric synthesis.

[0003] In recent years, there have been many reports on the use of a transition metal-chiral phosphine catalyst to asymmetricize an unsaturated bond (R. Noyori, "ASYMMETRIC").
CATALYSIS IN ORGANIC SYN
THESIS ", John Wiley & Sons, I
nc., 1994). In this document, for example, rhodium-
An example is disclosed in which N-acetyldehydrophenylalanine is asymmetrically reduced using a chiral phosphine catalyst to produce optically active N-acetylphenylalanine (18).
１９19).

Further, in the literature, such a catalyst is used, for example, for asymmetric isomerization of olefins (pages 95 to 119), asymmetric hydrosilylation of unsaturated organic compounds (pages 124 to 131),
Aldehyde formation reaction by asymmetric hydroformylation of olefins (pages 162 to 167), ester or carboxylic acid formation reaction by asymmetric hydrocarbonylation of olefins
(Pages 167 to 169), an asymmetric olefin (Hec)
k) Many examples of applying the reaction (pages 191 to 192) have been reported.

In such catalysts, in particular, BINAP
The ligand is a robust Face-Edge-System
-Edge-system) and is widely used for asymmetric catalysts.

The following are typical phosphine ligands, B
An example of an INAP synthesis process will be described.

Embedded image

Embedded image

In the above-mentioned BINAP synthesis, a high temperature of 300 ° C. is required in the bromination step of alcohol, and special equipment is required because hydrogen bromide is generated. In addition, the phosphine oxide reduction step requires an expensive silicon reagent, which increases the cost, and is not necessarily a method suitable for production on an industrial scale.

[0008]

DISCLOSURE OF THE INVENTION The present invention relates to a novel catalyst which exhibits an asymmetric catalytic activity equivalent to that of a BINAP catalyst, a ligand which can be synthesized easily and inexpensively under mild conditions, and which can be used for the catalyst. , And a method for producing them.

[0009]

Means for Solving the Problems As a result of repeated studies to solve the above-mentioned problems, the present inventors have found that the use of a specific optically active diaminophosphine ligand having a bipiperidine or bipyrrolidine structure has led to an improvement. The present inventors have found that such an asymmetric catalyst can be obtained, and have found that the ligand can be easily and inexpensively synthesized under mild conditions, thereby completing the present invention.

That is, the present invention includes the following contents. An optically active diaminophosphine coordinated transition metal complex represented by the following general formula (I) or (II).

Embedded image (In the formula, R represents an aryl group which may have a substituent or a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, n represents an integer of 0 or 1, and M represents a transition metal. Indicates that
A ^- represents a counter ion, m represents an integer of 0 to 4,
L ¹ and L ² each represent a ligand independently or L ¹ and L ² are integrated. )

An optically active diaminophosphine derivative represented by the following general formula (III) or (IV):

Embedded image (In the formula, R represents an aryl group which may have a substituent or a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, and n represents an integer of 0 or 1.)

Wherein the optically active compound represented by the following formula (V) or (VI) is reacted with a halophosphine represented by the following formula (VII):
A method for producing an optically active diaminophosphine derivative represented by (IV).

Embedded image (In the formula, n represents an integer of 0 or 1.)

Embedded image (In the formula, R represents an aryl group which may have a substituent or a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, and X represents a halogen atom.)

The racemic 2,2'-bipiperidine consisting of (S, S)-and (R, R) -2,2'-bipiperidine represented by the following formulas (VIII) and (IX) is used as an optically active carboxylic acid. Formula (VIII) or characterized by optical resolution with an acid
A method for producing the optically active 2,2'-bipiperidine represented by (IX).

Embedded image

[0014] A method for asymmetricalization of an unsaturated organic compound, comprising using the optically active diamine-coordinated transition metal complex.

An optically active amino acid derivative represented by the general formula (XI), wherein the dehydroamino acid derivative represented by the general formula (X) is asymmetrically reduced using the optically active diamine-coordinated transition metal complex. Manufacturing method.

Embedded image (Wherein R ¹ represents a hydrogen atom, an optionally substituted alkyl group, which may have an optionally substituted aryl group or a substituted aralkyl group, R ² is substituted A lower alkyl group which may have a group or a phenyl group which may have a substituent, wherein R ³ represents either OR ⁴ or NH ₂ , wherein, in OR ⁴ , R ⁴ is hydrogen Atom, a sodium atom, a lower alkyl group which may have a substituent or an aryl group which may have a substituent.)

Embedded image (In the formula, R ¹ , R ² and R ³ have the same meanings as described above.)

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

In the general formulas (I) and (II), R represents an aryl group which may have a substituent or a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent.

Examples of the aryl group which may have a substituent include tolyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, 3,5-dimethyl-4-methoxyphenyl, phenyl and the like. No.

Examples of the cycloalkyl group having 3 to 8 carbon atoms which may have a substituent include cyclopentyl and cyclohexyl.

The substituent which may have a substituent is not particularly limited as long as the effect of the present invention is not impaired. For example, the substituent may have 1 to 1 carbon atoms such as a methyl group and an ethyl group.
And lower alkoxyl groups having 1 to 4 carbon atoms, such as lower alkyl groups, methoxy groups and ethoxy groups, halogen atoms such as chlorine and bromine, and sulfonic acid groups.

R is preferably a phenyl group, a tolyl group or a cyclohexyl group, more preferably a phenyl group or a tolyl group, and particularly preferably a phenyl group.

In the optically active diaminophosphine-coordinated transition metal complex represented by formula (I) or (II), four Rs may be different from each other, but the formation of isomers is suppressed in the asymmetric reaction. From the viewpoint, it is more preferable that all four Rs are the same.

In the general formulas (I) and (II), n is 0 or 1.
Indicates an integer. That is, when n is 0, the following formula (I)
-A, a compound having a pyrrolidine structure as shown in (II) -a, and when n is 1, the following formulas (I) -b, (II)-
The compound has a piperidine structure as shown in FIG.

Embedded image

In the general formulas (I) and (II), M represents a transition metal. Preferred examples of the transition metal include rhodium, ruthenium, palladium, iridium and the like.

In particular, asymmetric reduction of unsaturated organic compounds,
In an asymmetric hydrosilylation reaction of an unsaturated organic compound and an asymmetric isomerization reaction of an olefin, rhodium and ruthenium are preferred.

In the general formulas (I) and (II), m represents an integer of 0 to 4.

In the general formulas (I) and (II), A ^- represents a counter ion. Preferred examples of the counter ion include Cl ⁻ , B
^{r -, F -, I -} , ClO 4 -, PF 6 -, BF 4 - and the like can be given.

In the general formulas (I) and (II), L ¹ and L ² each represent a ligand independently or L ¹ and L ² are integrated. Any ligand may be used as long as it coordinates with the transition metal.

Preferred examples include halogens such as chlorine and bromine, carboxylate compounds having 2 to 10 carbon atoms such as acetate ion, propionate ion and itaconic acid ion, and alcohols having 1 to 10 carbon atoms such as methanol and ethanol. Compounds, C5-C10 aromatic compounds such as benzene, C5-C20 cycloalkyldienes such as 1,5-cyclooctadiene and norbornadiene or C5-C20 alkyldienes, diamine compounds, amine compounds , BINAP, aminophosphines such as optically active diaminophosphine represented by the general formula (III) or (IV) of the present invention, and the like. In addition, the preferable ligand illustrated above may have a substituent. The substituent is not particularly limited as long as the effect of the present invention is not impaired. For example, the substituent has 1 to 1 carbon atoms such as a methyl group and an ethyl group.
Examples thereof include a lower alkyl group having 4 carbon atoms, an alkoxyl group having 1 to 4 carbon atoms such as a methoxy group and an ethoxy group.

The optically active diamine-coordinated transition metal complex represented by the general formula (I) or (II) is prepared by complexing an optically active aminophosphine (III) or (IV) with a transition metal by a method known to those skilled in the art. It can be manufactured by making

The case where the transition metal is monovalent and the ligand L is a diene compound will be described as an example. In this case, the transition metal complex of the present invention comprises M as the transition metal, ligand as the ligand (optically active aminophosphine), A ^{− as} the counter ion,
Diene diene compound and halogen and ^{X, + A [M (ligand} ) (diene)] - can be represented as can be produced by the following reaction. _{[M (diene) X] 2} + ligand + Na + A - ↓ [M (ligand) (diene)] + A -

The diene complex of the optically active aminophosphine and the transition metal is complexed in a solvent such as dichloromethane, benzene, toluene, methanol, ethanol, isopropanol, tetrahydrofuran, acetone or a mixed solvent thereof. The temperature of the complexing reaction is 0 ° C to 50 ° C, preferably 20 ° C to 30 ° C. Reaction time is 3 minutes to 1
Time, preferably 5 to 10 minutes. After completion of the reaction, crystallization is carried out with acetone, dichloromethane, diethyl ether, ethyl acetate, benzene, toluene alone or in a mixed solvent of two or more kinds, whereby crystals of an optically active aminophosphine metal complex are obtained. The obtained crystals can be identified by X-ray structural analysis.

As an example, [M (diene) X] ₂ (1.
0 eq.) And Na ⁺ A ^- (1.4 eq) is dissolved in a solvent such as acetone, to which ligand (1.4 eq) was added, stirred for 5 to 10 minutes at room temperature. A solvent such as dichloromethane is added thereto, and the salt is removed by filtration. Then, the filtrate is concentrated to about 20%. The crystals of the target complex can be obtained by leaving the crystals in an inert atmosphere such as argon to precipitate crystals and filtering off the crystals.

Optically active aminophosphine (III) or (I
V) can be produced by reacting an optically active diamine (V) or (VI) with a halophosphine (VII) in the presence of a base such as triethylamine in a solvent such as toluene, dichloromethane or diethyl ether. .
The reaction temperature is 0 ° C to 50 ° C, preferably 20 ° C to 30 ° C. The reaction time is 30 minutes to 5 hours, preferably 1 to 2 hours. The solvent is distilled off from the reaction mixture by distillation under reduced pressure, and the obtained solid is dissolved in a solvent such as acetone, crystallized by adding a solvent such as water dropwise, recrystallized as necessary, and filtered to remove the solid. Can be obtained.

As the halophosphine, chlorodiphenylphosphine, chlorodicyclohexylphosphine, chlorocyclohexylphenylphosphine, chloroditolylphosphine, chlorodi (o-methoxyphenyl) phosphine, chlorodi (m-methoxyphenyl) phosphine,
Chlorodi (p-methoxyphenyl) phosphine, chlorodi (3,5-dimethyl-4-methoxyphenyl) phosphine and the like can be exemplified. In the reaction, the halophosphine is preferably used in an amount of 2.2 to 2.4 molar equivalents when the optically active diamine is equivalent to 1 equivalent.

Solvents used for crystallization include water, methanol, ethanol, isopropanol, n-propanol, diethyl ether, petroleum ether, tetrahydrofuran, methyl-tert-butyl ether, methyl isobutyl ketone, acetone, cyclohexane, hexane,
Ethyl acetate, benzene, toluene, pentane, dichloromethane, chloroform, acetonitrile, dioxane and the like can be mentioned, and they are used alone or in a mixed solvent of two or more.

Next, a method for producing the optically active diamine (V) or (VI) will be described. First, in the general formula (V) or (VI), a compound in the case of n = 1, that is, 2,2′-optically active 2,2′-bipiperidine represented by the formula (VIII) or (IX) The racemate of bipiperidine can be obtained by optical resolution with an optically active carboxylic acid.

Specifically, a racemic 2,2′-bipiperidine is reacted with an optically active carboxylic acid in a solvent, and the solubility of the two diastereomeric salts formed is utilized to obtain a poorly soluble diastereomeric salt. An optically active 2,2′-bipiperidine can be obtained by separating and obtaining a stereomeric salt and decomposing the salt with an alkali.

Heretofore, as a method for synthesizing optically active 2,2'-bipiperidine, a method has been known in which a racemic compound is converted to a cobalt complex and optically resolved using a camphorsulfonic acid derivative (M. Sato, Y. Sato, S. et al. Yano, S.Yo
Shikawa; J. CHEM. SOC. DALTON
TRANS, 1985, p. 895-8) requires a cobalt complex formation and a cobalt complex decomposition reaction, requires a long number of steps, and is not suitable for an industrial production method.

2,2'-Bipiperidine can be synthesized by reducing 2,2'-bipyridine with hydrogen gas in the presence of a metal catalyst. For example, platinum oxide, palladium, ruthenium, and rhodium can be used as the metal catalyst, and the reaction is carried out at a hydrogen pressure of 10 KPa to 1300 KPa, preferably 200 to 1000 KPa. Pyridine ring nucleus reduction with potassium hydroxide and a nickel-aluminum alloy is also possible. The 2,2′- thus obtained
By recrystallizing bipiperidine into hydrochloride,
It is separated into a meso form and a racemic form, and the racemic 2,2′-bipiperidine is subjected to optical resolution. The optical resolving agents used for the optical resolution of 2,2′-bipiperidine are (+) − and (−) −
Tartaric acid, (+)-and (-)-malic acid, (+)-and (-)-10-camphorsulfonic acid, (+)-and (-)-pyroglutamic acid, (+)-and (-)- Optical activity such as aspartic acid, (+)-and (-)-phenylethanesulfonic acid, (+)-and (-)-mandelic acid, (+)-and (-)-cis-2-benzamidocyclohexanecarboxylic acid Carboxylic acid is mentioned, and the amount used at that time is preferably 0.5 to 2.0 equivalents.

Solvents include water, methanol, ethanol,
Isopropanol, n-propanol, diethyl ether, petroleum ether, tetrahydrofuran, methyl ter
Examples include t-butyl ether, methyl isobutyl ketone, acetone, cyclohexane, hexane, ethyl acetate, benzene, toluene, pentane, dichloromethane, chloroform, acetonitrile, dioxane, and the like. These solvents are used alone or as a mixture of two or more. For example, when tartaric acid is used as the optically active carboxylic acid,
When L-tartaric acid acts as an optical resolving agent, (R,
The optically active 2,2'-bipiperidine L-tartrate of the (R) -form and the optically active 2,2'-bipiperidine-D-tartrate of the (S, S) -form when the D-tartaric acid is acted on the other hand. Since each crystallizes selectively, it can be separated, metathesized with an alkali such as aqueous sodium hydroxide, and separated into a desired optically active 2,2′-bipiperidine and an optically active tartaric acid as a resolving agent. it can. Thereafter, for example, by extraction with a suitable organic solvent such as dichloromethane, optically active 2,2′-bipiperidine can be obtained. At this time, the temperature at which the aqueous solution of tartaric acid is added to the organic solvent solution of 2,2′-bipiperidine is from room temperature to 80 ° C., preferably 5 ° C.
The temperature is preferably 0 to 60 ° C., and the mixing ratio and the amount of the organic solvent and water that do not cause the system to become cloudy may be used.

In the general formula (V) or (VI),
Compound when n = 0, that is, formula (XII) or (XIII)

Embedded image For the optically active 2,2′-bipyrrolidine represented by
For example, [T.Oishi, M.Hirama, LRSi
ta, S. Masamune; SYNTHESIS, p.
789 (1991)] and a method for performing optical resolution using optically active tartaric acid.

The optically active diaminophosphine metal complexes (I) and (II) thus obtained were prepared according to the method described in Noyor
i, “ASYMMETRIC CATALYSIS I
NORGANIC SYNTHESIS ”, John W
Like the asymmetric catalyst described in Iley & Sons (1994), it is widely expected to be applied as an asymmetric catalyst in organic synthesis.

That is, unsaturated organic compounds, especially olefin structures, ketone structures and imine structures (C = C bond, C =
It is useful as an asymmetric catalyst for an organic compound having an O bond and a C = N bond.

That is, as described in the above literature, for example, an asymmetric reduction reaction of an unsaturated organic compound (95 to
119), asymmetric hydrosilylation of unsaturated organic compounds (pages 124 to 131), aldehyde formation reaction by asymmetric hydroformylation of olefins (pages 162 to 167), ester or carboxylic acid formation by asymmetric hydrocarbonylation of olefins It is useful as an asymmetric catalyst for use in reactions (pages 167 to 169), asymmetric Heck reactions of olefins (pages 191 to 192), and the like. Various reaction conditions for these reactions can be easily and appropriately set by those skilled in the art based on the above-mentioned literature and known techniques.

Here, for example, in the case of hydrosilylation, the action of an optically active diaminophosphine metal complex on an unsaturated organic compound may be carried out in the presence of a silylating agent.
(R. Noyori, "ASYMMETRIC CTAL
YSIS IN ORGANIC SYNTHESI
S ", published by John Wiley & Sons, 19
1994, pp. 124-131). Examples of the silylating agent include those represented by the following general formula.

Embedded image (R ^{5 to} R ¹³ are each independently a hydrogen atom, a halogen atom,
It shows an alkyl group which may have a substituent and an aryl group which may have a substituent. )

The halogen atom is preferably Cl, the alkyl group optionally having a substituent is preferably a lower alkyl group having 1 to 4 carbon atoms, and the aryl group optionally having a substituent is phenyl. And a naphthyl group are preferred.

The substituent having a substituent is not particularly limited as long as the effect of the present invention is not impaired.
Examples thereof include lower alkyl groups such as a methyl group and an ethyl group, alkoxy groups such as a methoxy group and an ethoxy group, and halogen atoms such as chlorine.

The resulting hydrosilylated compound is
By hydrolysis, the compound can be converted to a compound in which a silyl group is replaced by hydrogen. (R. Noyori, "AS
YMMETRIC CATALYSIS IN ORGA
NIC SYNTHESIS ”, John Wiley
& Sons, 1994, pp. 124-131).

For example, in an aldehyde formation reaction by asymmetric hydroformylation of an olefin, an organic compound having an olefinic bond is prepared by reacting an organic compound having an olefinic bond in the presence of hydrogen and carbon monoxide, as described in the above-mentioned references, pages 162 to 167. The reaction may be carried out using a transition metal complex of

For example, in an ester or carboxylic acid forming reaction by asymmetric hydrocarbonylation of an olefin, an organic compound having an olefinic bond is converted to carbon monoxide and an alcohol or water as described in the above-mentioned references, pages 167 to 169. The reaction may be carried out using the transition metal complex of the present invention in the presence.

The present inventors will explain the usefulness of the complex of the present invention, taking as an example the application to the asymmetric reduction of a specific dehydroamino acid as shown in the following scheme.

Embedded image

In the general formulas (X) and (XI), R ¹ represents a hydrogen atom, an alkyl group which may have a substituent, an aryl group which may have a substituent or a substituent. R ² represents an optionally substituted lower alkyl group or an optionally substituted phenyl group; R ³ represents OR ⁴ or NH ₂ . Here, in OR ⁴ , R ⁴ represents a hydrogen atom, a sodium atom, a lower alkyl group which may have a substituent, or an aryl group which may have a substituent.

R ¹ is, for example, a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which may have a substituent, an aryl group having 6 to 15 carbon atoms which may have a substituent or An aralkyl group having 7 to 20 carbon atoms which may have a group is exemplified.

Examples of R ³ include a hydrogen atom, a sodium atom, an alkyl group having 1 to 4 carbon atoms which may have a substituent or a phenyl group which may have a substituent.

R ⁴ is, for example, a hydrogen atom, a sodium atom, an alkyl group having 1 to 4 carbon atoms which may have a substituent or a carbon atom having 6 to 15 carbon atoms which may have a substituent.
Aryl group.

When the compound has a substituent, examples of the substituent include an alkoxy group, a nitro group, an alkyl group and a halogen atom.

Examples of specific dehydroamino acids include:
N-acetyldehydrophenylalanine, N-acetyldehydroalanine, N-acetyldehydro-p-chlorophenylalanine and the like can be mentioned.

The asymmetric reduction of the dehydroamino acid is carried out in an autoclave in the presence of a solvent at a hydrogen pressure of 1 to 100 atm, preferably 8 atm or more. As the solvent, for example, alcohols such as methanol, ethanol, isopropanol, n-propanol and the like, and single solvents such as chloroform, dichloromethane, benzene, toluene, tetrahydrofuran and a mixture of two or more solvents are used. The base mass with respect to the catalyst is 10 to 10,000 times mol, and the reaction temperature is 15 ° C to
100 ° C, preferably 20 to 50 ° C, reaction time is 3 to 1
68 hours.

For example, using an optically active N, N'-bis- (diphosphino) -2,2'-bipiperidine rhodium complex,
When asymmetric reduction of acetyldehydrophenylalanine is performed, acetylphenylalanine can be obtained in a quantitative yield with an asymmetric yield of 96.5% ee. This is based on the 84% ee (A. Miyasita, A. Yasud) of the asymmetric reduction of rhodium-BINAP complex of acetyldehydrophenylalanine.
a, H .; Takaya, K. Toriumi, T. Sou
chi and R. Noyori .; Am. Che
m. Soc., 1980, 102, p. 7932), and confirmed to have excellent asymmetric reduction catalytic activity.

[0061]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Reference Examples and Examples, but the present invention is of course not limited thereto.

Here, a method for synthesizing the (R, R) is shown.
The (S, S) -form is synthesized according to the (R, R) -form, using D-tartaric acid instead of L-tartaric acid.

Reference Example 1: Synthesis of 2,2'-bipiperidine Aldrich Chemical C
Company, Inc.), 2,2'-dipyridyl (3.0
(0 mg, 19.2 mmol) and 50 ml of a suspension of platinum oxide (600 mg, 1.76 mmol) manufactured by Kawaken Fine Chemical Co., Ltd. in tetrahydrofuran were set in an autoclave, and stirred at 100 ° C. under 120 atm of hydrogen for 16 hours.
After completion of the reaction, the mixture was filtered, the solvent was distilled off, and the residue was dried under vacuum to obtain a colorless liquid (3.22 g, 100%).

¹ H-NMR (CDCl ₃ ) d = 1.00-1.
45 (m, 6H), 1.51-1.84 (m, 8H), 2.2
1-2.29 (m, 1H), 2.37-1.40 (m, 1
H), 2.52-2.57 (m, 2H), 3.04-3.1
^{0 (m, 2H) 13 C} -NMR (CDCl 3) d = 24.73,24.82,
26.61, 26.95, 28.19, 29.23, 46.9
^{2,47.62,61.54,61.85 MS (ESI) MH + =} 169.2 HRMS (FAB) calcd _{[C 10 H 21 N 2 (MH} +) as] 169.1705, analysis 169. 1706

Reference Example 2: Synthesis of racemic-2,2'-bipiperidine 2,2'-bipiperidine (11.13 g, 66.15 mmol
Concentrated hydrochloric acid was added to l) to adjust the pH to about 2, the solvent was distilled off, and the residue was dried under vacuum to obtain a white solid. This solid was ground in a mortar, dissolved in an ethanol solution (96 ml) by heating under reflux, and allowed to stand overnight to precipitate plate-like crystals. The crystals are taken out by filtration, dried, NMR, H
Analysis by PLC revealed that the product was a meso form (5.03 g, yield 63%, purity 100%). When the filtrate was allowed to stand at room temperature, crystals precipitated. The crystals were collected by filtration, dried, and analyzed by NMR and HPLC. As a result, the crystals were found to be racemic (3.42).
g, yield 43%, purity 100%).

¹ H-NMR (CDCl ₃ ) d = 1.1-1-1.
43 (m, 6H), 1.52-1.74 (m, 8H), 2.2
2-2.30 (m, 1H), 2.52-2.61 (m, 2
H), 3.04-3.10 (m, 2H ) 13 C-NMR (CDCl 3) d = 24.63,26.82,
29.12, 46.81, 61.43 MS (ESI) MH ⁺ = 169.2 HRMS (FAB) calculated [as C ₁₀ H ₂₁ N ₂ (MH ⁺ )] 169.1705, analytical 169.1698

Example 1 Synthesis of (R, R) -2,2′-piperidine.L-tartrate At 60 ° C., racemic 2,2′-bipiperidine (2.9)
18 g, 17.34 mmol) in methanol (8.
0 ml) to L-tartaric acid (2.60 g, 17.34 mmol).
An aqueous solution (2.6 ml) of 1) was added, and methanol (24 ml) was further added. The mixture was stirred at 60 ° C. for 10 minutes, and left to stand at room temperature to precipitate white crystals. The crystals were removed by filtration and dried in vacuo to give a white solid (1.96 g, 71.2%). The crystals were recrystallized from 40 ml of methanol and 2.1 ml of water to obtain white crystals (1.44 g, 53.9%) having a melting point of 168 to 170 ° C.

¹ H-NMR (D ₂ O) d = 1.80-1.9
0 (m, 2H), 1.99-2.16 (m, 4H), 2.2
9-2.38 (m, 1H), 3.42-3.47 (m, 4
H), 3.85-3.90 (m, 2H), 4.52 (d,
4H) ¹³ C-NMR (D ₂ O) d = 29.74, 35.31, 5
3.48, 67.53, 79.95, 183.59

Elemental analysis value (as C ₁₄ H ₂₆ N ₂ O ₆ ) Calculated value for CHN (%) 52.8 8.2 8.8 Analysis value (%) 52.9 8.2 8.9

Example 2 Synthesis of (R, R) -2,2'-Bipiperidine (R, R) -2,2'-Bipiperidine tartrate (1.395)
g, 4.38 mmol) in 2N aqueous sodium hydroxide solution
(8.0 ml) and dichloromethane (20 ml) were added and extracted with dichloromethane. The dichloromethane layer was dried over potassium carbonate, distilled off under reduced pressure, and then dried under vacuum to obtain white crystals having a melting point of 34 to 35 ° C (683.9 mg, 92.0%).
I got

¹ H-NMR (CDCl ₃ ) d = 1.1-1-1.
43 (m, 6H), 1.52-1.74 (m, 8H), 2.2
2-2.30 (m, 1H), 2.52-2.61 (m, 2
H), 3.04-3.10 (m, 2H ) 13 C-NMR (CDCl 3) d = 24.63,26.82,
29.12, 46.81, 61.43

Example 3 N, N'-bis (diphenylphosphino)-(R, R) -2,
Synthesis of 2′-Bipiperidine Triethylamine (1.19 ml, 1.19 ml) was added to a toluene solution (40 ml) of (R, R) -2,2′-bipiperidine (683.9 mg, 4.06 mmol) in an ice bath under an argon atmosphere.
8.53 mmol), and 10 minutes later, chlorodiphenylphosphine (1.53 ml, 8.53 mmol)
Was added dropwise and stirred at room temperature for 1 hour. After completion of the reaction, the mixture was filtered, the solvent of the filtrate was distilled off, and the residue was dried under vacuum to obtain a white amorphous substance (1.44 g). The amorphous was dissolved in acetone (40 ml), water was added dropwise, and the mixture was stirred at 0 ° C. to precipitate a white solid. Filter and dry under vacuum, mp 2
28-230 ° C (dec.) White solid (248.8m
g, 11.0%).

¹ H-NMR (CDCl ₃ ) d = 0.51-0.
58 (m, 2H), 1.02-1.09 (m, 2H), 1.3
2-1.86 (m, 8H), 2.94-3.01 (m, 2
H), 3.23-3.33 (m, 2H), 4.09-4.13.
(m, 2H), 6.92-7.75 (m, 20H)

Example 4 Rhodium-N, N'-bis (diphenylphosphino)-
Synthesis of (R, R) -2,2'-bipiperidine complex Under an argon atmosphere, [Rh (1,5-cyclooctadiene) Cl] ₂ (105.2 mg, 0.213 mmol) and sodium perchlorate (73. 0mg, 0.596mmo
l) N, N'-bis (diphenylphosphino)-(R, R) -2,2'-bipiperidine (240 mg, 0.447 mmol) was added to an acetone solution (1.0 ml) of
After stirring for 2 minutes, dichloromethane (2 ml) was added, the mixture was filtered, and the solvent was distilled off until the filtrate became about 1 ml. When left under an argon flow of about 10 ml / min for 3 days, wine red crystals were precipitated. Filter and dry under vacuum at room temperature for 24 hours, mp 165-166 ° C (dec.).
An orange solid (157.4 mg, 87.0%) was obtained.

Example 5 N, N'-bis (diphenylphosphino)-(R, R) -2,
Synthesis of 2'-bipyrrolidine In an ice bath under an argon atmosphere, a toluene solution (7 ml) of (R, R) -2,2'-bipyrrolidine (384.5 mg, 2.48 mmol) was added to triethylamine (0.64 ml,
4.58 mmol) and then chlorodiphenylphosphine (0.82 ml, 4.58 mmol) over 10 minutes.
Was added dropwise and stirred at room temperature for 2 hours. After completion of the reaction, the mixture was filtered, the solvent of the filtrate was distilled off, and the residue was dried under vacuum to obtain a white amorphous substance (1.44 g). The amorphous was dissolved in acetone (20 ml) at 60 ° C., water (4.2 ml) was added dropwise, and the mixture was stirred at 0 ° C. for 30 minutes to separate a white viscous liquid. After filtration, the resulting white viscous liquid was dried under vacuum to obtain a white amorphous liquid (4) having a melting point of 142 to 144 ° C. (dec.).
51 mg, 35.8%).

¹ H-NMR (CDCl ₃ ) d = 1.43-1.
92 (m, 8H), 2.63-2.74 (m, 2H), 2.9
5-3.05 (m, 2H), 4.13-4.20 (m, 2
H), 7.27-7.40 (m, 20H)

Example 6 Rhodium-N, N'-bis (diphenylphosphino)-
Synthesis of (R, R) -2,2'-bipyrrolidine complex Under argon atmosphere, manufactured by Strem Chemicals, [Rh (1,5-cyclooctadiene) Cl] ₂ (15
6 mg, 0.316 mmol) and sodium perchlorate (1
07.1 mg, 0.876 mmol) in acetone (2.
0 ml) in N, N'-bis (diphenylphosphino)-(R,
R) -2,2'-Bipyrrolidine) (350 mg, 0.688 m
mol), and the mixture was stirred at room temperature for 5 minutes, dichloromethane (7 ml) was added, the mixture was filtered, and the solvent was distilled off until the filtrate became about 2 ml. When left under an argon flow of about 50 ml / min for 2 hours, wine red crystals were precipitated. Filter and dry under vacuum at room temperature for 24 hours, mp 18
An orange solid at 3 to 184 ° C (dec.) (191.
9 mg, 71.8%).

[0078] Elemental analysis _{C H N (C 40 H 46} N 2 P 2 as ClO ₆ Rh) calculated value (%) 58.7 5.7 3.4 ANALYSIS value (%) 56.8 5.6 3.1 Identified by X-ray structural analysis.

Example 7 Rhodium-N, N'-bis (diphenylphosphino)-
Asymmetric hydrogenation of α-acetaminocinnamic acid with (R, R) -2,2′-bipiperidine complex In a 50 ml glass inner cylinder for autoclave, the bipiperidine type catalyst obtained in Example 4 (2.54 mg, 0.003 mmol)
l), α-acetaminocinnamic acid (62.8 mg, 0.3
mmol), lyophilized degassed ethanol (2.5 ml) was added, a hydrogen pressure of 8 atm was applied, the vessel was sealed and stirred at room temperature.

After 20 hours, the hydrogen pressure had decreased by 0.1 atm. The glass inner cylinder was taken out of the autoclave, washed with dichloromethane, the solution was concentrated by an evaporator, isolated by a short column (SiO ₂ , ethyl acetate), and the melting point was 1.
Yellow solid at 71-173 ° C (60.0 mg, 100%)
I got Optical purity ee by HPLC is 96.5% (L form)
Met.

¹ H-NMR (CDCl ₃ ) d = 1.78 (s,
3H), 2.78-2.88 (m, 1H), 3.01-3.09
(m, 1H), 3.34 (brs, 1H), 4.35-4.4
5 (m, 1H), 7.16-7.31 (m, 5H), 8.1
6-8.21 (d, 1H)

Example 8 Rhodium-N, N'-bis (diphenylphosphino)-
Asymmetric hydrogenation of α-acetaminocinnamic acid with (R, R) -2,2′-bipyrrolidine complex The bipyrrolidine-type catalyst obtained in Example 6 (1.97 mg, 0.0023 mmol) was placed in a 50 ml glass inner cylinder for an autoclave.
l), α-acetaminocinnamic acid (209 mg, 1.0 m
mol) and freeze-dried and degassed ethanol (2.5
ml), hydrogen pressure of 8 atm was applied, sealed, and stirred at room temperature.

After 20 hours, the hydrogen pressure had decreased by 0.5 atm. The glass inner cylinder was taken out of the autoclave, washed with dichloromethane, the solution was concentrated by an evaporator, isolated by a short column (SiO ₂ , ethyl acetate), and the melting point was 1.
71-173 ° C yellow solid (206.9 mg, 99%)
I got Optical purity ee is 87.5% (L form) by HPLC.
Met.

¹ H-NMR (CDCl ₃ ) d = 1.78 (s,
3H), 2.78-2.88 (m, 1H), 3.01-3.09
(m, 1H), 3.34 (brs, 1H), 4.35-4.4
5 (m, 1H), 7.16-7.31 (m, 5H), 8.1
6-8.21 (d, 1H)

[0085]

As described above, a novel optically active diaminophosphine-coordinated transition metal complex useful as an asymmetric catalyst can be obtained by an inexpensive and industrially suitable method.

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Claims (7)

[Claims] An optically active diaminophosphine coordinated transition metal complex represented by the general formula (I) or (II). Embedded image (In the formula, R represents an aryl group which may have a substituent or a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, n represents an integer of 0 or 1, and M represents a transition metal. Indicates that
A ^- represents a counter ion, m represents an integer of 0 to 4,
L ¹ and L ² each represent a ligand independently or L ¹ and L ² are integrated. ) 2. An optically active diaminophosphine derivative represented by the general formula (III) or (IV). Embedded image (In the formula, R represents an aryl group which may have a substituent or a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, and n represents an integer of 0 or 1.) 3. The optically active diaminophosphine according to claim 2, wherein the halophosphine represented by the general formula (VII) is reacted with the optically active compound represented by the general formula (V) or (VI). A method for producing a derivative. Embedded image (In the formula, n represents an integer of 0 or 1.) (In the formula, R represents an aryl group which may have a substituent or a cycloalkyl group having 3 to 8 carbon atoms which may have a substituent, and X represents a halogen atom.) 4. The compound represented by the formulas (VIII) and (IX),
Formula (VIII) or (IX), wherein a racemate of 2,2'-bipiperidine consisting of S)-and (R, R) -2,2'-bipiperidine is optically resolved with an optically active carboxylic acid. A method for producing the expressed optically active 2,2'-bipiperidine. Embedded image 5. The method for producing optically active 2,2′-bipiperidine according to claim 4, wherein the optically active carboxylic acid is optically active tartaric acid. 6. A method for asymmetrizing an unsaturated organic compound, comprising using the optically active diaminophosphine coordinated transition metal complex according to claim 1. 7. An asymmetric reduction of the dehydroamino acid derivative represented by the general formula (X) using the optically active diamine-coordinated transition metal complex according to claim 1, wherein the compound is represented by the general formula (XI). For producing an optically active amino acid derivative to be produced. Embedded image (Wherein R ¹ represents a hydrogen atom, an optionally substituted alkyl group, which may have an optionally substituted aryl group or a substituted aralkyl group, R ² is substituted A lower alkyl group which may have a group or a phenyl group which may have a substituent, wherein R ³ represents either OR ⁴ or NH ₂ , wherein, in OR ⁴ , R ⁴ is hydrogen Atom, a sodium atom, a lower alkyl group which may have a substituent or an aryl group which may have a substituent.) (In the formula, R ¹ , R ² and R ³ have the same meanings as described above.)