JP2001058999A - Ruthenium compound and production of optically active alcohol compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new ruthenium compound having excellent catalytic asymmetric reduction activity, useful for producing an optically active alcohol, by making the compound include an optically active phosphine and an optically active or racemic diamine as ligands. SOLUTION: This compound is represented by the formula: RuXY(PR1R2 R3)n[R4R5C(NR6R7)-R8R9C(NR10R11)]m [X and Y are each H or an anion; R1 to R3 are each a (substituted)alkyl, a (substituted) cycloalkyl, a (substituted) aralkyl or the like; any of R1 to R3 are each an optically active group; R4 to R11 are each H, a (substituted)alkyl, a (substituted)alkenyl, a (substituted) crcloalkyl, a (substituted)aralkyl or a (substituted)aryl; n and m are each 0-4] such as RuH2(tris-[3- (1R)-1-methoxyethyl}phenyl]phosphine)2-(s,s)- diphenylethylenediamine. The compound of the formula is obtained by properly reacting a phosphine ligand with a diamine ligand and a ruthenium compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a novel ruthenium compound useful for producing optically active alcohols, and a method for producing optically active alcohols using the ruthenium compound as an asymmetric reduction catalyst.

[0002]

2. Description of the Related Art Optically active alcohols are useful as synthetic intermediates for pharmaceuticals and agricultural chemicals, or as liquid crystal materials. Known methods for producing such optically active alcohols include 1) a method using an enzyme such as baker's yeast, and 2) a method for asymmetric hydrogenation of a carbonyl compound using a metal complex catalyst.

[0003] As the method 2), for example, (1) As
ymmetric Catalysis in Org
anic Synthesis. , Pp56-82 (1
994). Ed. R. Noyori, a method for asymmetric hydrogenation of a carbonyl compound having a functional group using an optically active transition metal complex catalyst, (2) Chem. Re
v. , 9 , 1051 (1992).
Method by an asymmetric hydrogen transfer type reduction reaction using an asymmetric complex catalyst of u, Rh and Ir, (3) Oil Chemistry, pp 882-831
(1980) and Advances in Catalyst
sis. , 32 , 215 (1983). Ed. Y. Iz
Umi, a method for asymmetric hydrogenation using a Ni catalyst having a tartaric acid-modified ligand, (4) As
ymmetric Synthesis. , 5 , 4th
Chapter (1985). Ed. J. D. A method by asymmetric hydrosilylation described in Morrison, (5)
J. Chem. Soc. Perkin Trans. I
I, 2039 (1985); Am. Chem. S
oc. , 109 , 5551 (1987), a method for reducing borane in the presence of an asymmetric ligand, (6) A
ngew. Chem. Int. Ed. , 37 , 1703
Asymmetric hydrogenation method described in (1998), and (7) A
nbev. Chem. Int. Ed. 38 , 495 (1
999), and the like.

[0004] However, the method 1) using an enzyme can obtain alcohols having a relatively high optical purity, but the type of the reaction substrate is restricted, and the absolute configuration of the obtained alcohol is limited to a specific one. There is a problem that is.

[0005] Of the above methods 2), the method (1) using an asymmetric hydrogenation catalyst for a transition metal has a high selectivity for a substrate containing a functional group in the molecule, for example, a keto acid. Although optically active alcohols can be produced due to their properties, they have drawbacks in terms of reaction rate and are not effective for relatively simple carbonyl compounds having no functional group in the molecule.

In the method (2), a compound serving as a hydrogen source is essential for the hydrogen transfer reaction. In the method (3), applicable substrates are limited. In the method (4) based on hydrosilylation, the starting material is used. High cost, both disadvantageous compared to asymmetric hydrogenation. Furthermore, the method of (5) based on borane reduction has a problem in borane handling property.

The method (6) reduces the carbonyl group by the action of hydrogen in the presence of a transition metal asymmetric hydrogenation catalyst, an optically active nitrogen-containing compound and a base. However, since both require expensive optically active phosphorus ligands and optically active diamines, they have the disadvantage that the metal complex catalyst becomes expensive and its preparation becomes complicated.

As described in the above method (7), attempts have been made to improve these disadvantages by using a bidentate phosphorus ligand having axial asymmetry. The disadvantage remains that the synthesis of the phosphorous ligand itself is difficult and the preparation of the hydrogenation catalyst is complicated, and furthermore, a hydrogenation catalyst having an unfavorable steric structure is simultaneously formed during the asymmetric reduction reaction, so that the optical yield and There is a problem with substrate selectivity.

[0009]

As described above, various methods for producing optically active alcohols have been heretofore known. However, all of these methods have problems, have high generality, and can be easily carried out. It couldn't be said.

[0010] Accordingly, it has been desired to realize a highly versatile and easily practicable method for producing an optically active alcohol.

The present invention has been made in view of such circumstances, and it is an object of the present invention to provide an easily available optically active phosphine and an easily available optically active or racemic diamine as a ligand. And a practical method for producing optically active alcohols characterized by using this catalyst.

[0012]

The present invention firstly provides a compound of the general formula (1): RuXY (PR ¹ R ² R ³ ) _n [R ⁴ R ⁵ C
^{(NR 6 R 7) -R 8} R 9 C (NR 10 R 11)] m
(1) In the formula, X and Y each independently represent an anion such as a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, or an alkoxyl group, and R ¹ , R ² , and R ³ each independently represent An alkyl group which may have a substituent,
Represents a cycloalkyl group which may have a substituent, an aralkyl group which may have a substituent or an aryl group which may have a substituent, and among R ¹ , R ² and R ³ , At least one is an optically active group.

R ^{4 to} R ¹¹ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or a group which may have a substituent. A good cycloalkyl group, an aralkyl group which may have a substituent or an aryl group which may have a substituent, wherein any one of R ⁴ and R ⁵ and any one of R ⁸ and R ⁹ are bonded Thus, a carbon ring or a nitrogen-containing hetero ring may be formed.
n and m each independently represent 0 or an integer of 1 to 4. A ruthenium compound represented by｝ (also referred to as a “ruthenium complex”) is provided.

Ruthenium compound represented by the general formula (1)
In the compound, the R¹ , R^Two , R ^Three Are independent
And optionally having an optically active alkyl
Active cycloalkyl optionally having a group or a substituent
Optically active aralkyl which may have
Active aryl group which may have a group or a substituent
It is preferred that

R ¹ , R ² and R ³ are all the same group, and may be an optically active alkyl group which may have a substituent;
An optically active cycloalkyl group optionally having a substituent, an optically active aralkyl group optionally having a substituent or an optically active aryl group optionally having a substituent is more preferable. preferable.

The present invention also relates to a second compound of the formula (4): Ra in the presence of a ruthenium compound represented by the general formula (1), preferably in the presence of a catalytic amount of a ruthenium compound.
—CO—Rb (4) (wherein, Ra and Rb are different and have an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or a substituent. A cycloalkyl group which may be substituted, an aralkyl group which may have a substituent or an aryl group which may have a substituent.) General formula (5): Ra-C ^* H (OH) -R
b (5) (wherein Ra and Rb have the same meanings as described above, and C ^* represents an asymmetric carbon atom).

According to the first aspect of the present invention, there is provided a novel ruthenium compound which can be easily synthesized at a low production cost, can be mass-produced, and has excellent catalytic activity for asymmetric reduction. Further, according to the second aspect of the present invention, various optically active alcohols can be easily produced with high optical yield and chemical yield using the ruthenium compound.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
The present invention provides, as described above, a ruthenium compound represented by the general formula (1) and the presence of the ruthenium compound.
A method for producing an optically active alcohol represented by the general formula (5), comprising hydrogenating a carbonyl compound represented by the general formula (4) preferably in the presence of a catalytic amount. is there.

In the ruthenium compound represented by the general formula (1) in the present invention, X and Y each independently represent a hydrogen atom, a carboxyl group, a hydroxyl group, a halogen atom such as fluorine, chlorine, bromine or iodine; , Ethoxy, propoxy, isopropoxy, butoxy, and t-butoxy.

R ¹ , R ² , and R ³ each independently represent a monodentate phosphorus ligand, and specifically include an alkyl group which may have a substituent and a substituent. A cycloalkyl group, an aralkyl group which may have a substituent or an aryl group which may have a substituent.

In the present invention, the above R ¹ , R ² , R ³
Of at least one is an optically active group, R ^1, R
Preferably, all of R ² and R ³ are optically active groups.
More preferably, ¹ , R ² and R ³ are the same optically active group. Here, the “optically active group” refers to the substituents R ¹ , R
² , a group having an asymmetric center in the carbon chain constituting R ³ . That is, it is a group in which at least one of the carbon atoms constituting the carbon chain is an asymmetric carbon atom.

Examples of the alkyl group which may have a substituent include methyl, ethyl, propyl, isopropyl,
Butyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, decyl,
Examples of the optionally substituted cycloalkyl group having an alkyl group having 1 to 20 carbon atoms such as dodecyl, menthyl, and phytyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups having 3 carbon atoms.
Examples of the aralkyl group which may have a substituent are the aralkyl groups having 7 to 8 carbon atoms such as benzyl, α-methylbenzyl, α, α-dimethylbenzyl, α-ethylbenzyl and the like. 20 aralkyl groups, and the aryl group which may have a substituent include aromatic hydrocarbon groups such as phenyl, naphthyl and anthranyl groups, and oxygen-containing aromatic heterocyclic groups such as furanyl and benzofuranyl groups. And a metallocenyl group such as a ferrocenyl group.

Examples of the aryl group include groups represented by the following general formulas (6) to (6 ").

(6) Ar—C ^* H (Or ¹ ) r ² (6 ′) Ar—C ^* H (OSir′r ″ r ′ ″) r ² (6 ″) Ar—C ^* H (OH) r ^Two

In the above equations (6) to (6 ″), r ¹ ,
r ′, r ″, r ′ ″ and r ² are each independently a hydrogen atom, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl,
Isopentyl, neopentyl, tert-pentyl, cyclopentyl, hexyl, cyclohexyl, heptyl,
Cycloheptyl, octyl, cyclooctyl, nonyl,
Decyl, a linear, branched or cyclic alkyl group having 1 to 20 carbon atoms such as a dodecyl group,

Aralkyl having 7 to 20 carbon atoms such as phenylmethyl and diphenylmethyl, phenyl, naphthyl,
Aromatic hydrocarbon groups such as anthranyl groups, furanyl, oxygen-containing aromatic heterocyclic groups such as benzofuranyl groups, metallocenyl groups such as ferrocenyl groups, or trimethylsilyl, te
represents a substituted silyl group such as rt-butyldimethylsilyl and triphenylsilyl. Ar represents an aryl group such as phenyl, α-naphthyl and β-naphthyl which may have a substituent r ³ .

Here, r ³ is, for example, fluorine,
Halogen atom such as chlorine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert
-1 to 20 carbon atoms such as pentyl, cyclopentyl, hexyl, cyclohexyl, heptyl, cycloheptyl, octyl, cyclooctyl, nonyl, decyl, dodecyl groups, etc.
Straight-chain, branched or cyclic alkyl group, methoxy, ethoxy, propoxy, isopropoxy, butoxy, hexyloxy, a linear, branched or cyclic alkoxyl group having 1 to 20 carbon atoms such as cyclohexyloxy group, phenylmethyl,
An aralkyl group having 7 to 20 carbon atoms such as a diphenylmethyl group, an aromatic hydrocarbon group such as a phenyl, naphthyl or anthranyl group, an oxygen-containing aromatic heterocyclic group such as a furanyl or benzofuranyl group, or a metallocenyl group such as a ferrocenyl group. Etc. are fried. Ar may have two or more identical or different substituents r ³ .

The above optically active aryl groups (6) to
Specific examples of (6 ") include 4-{(1 *)-1-hydroxyethyl} phenyl, 3-{(1 *)-1-hydroxyethyl} phenyl, 3-{(1 *)-1- Hydroxyethyl {-5-methylphenyl, 5-methoxy-3-
{(1 *)-1-hydroxyethyl} phenyl, 5-chloro-3-{(1 *)-1-hydroxyethyl} phenyl, 5-fluoro-3-{(1 *)-1-hydroxyethyl} phenyl ,

4-{(1 *)-1-methoxyethyl} phenyl, 3-methoxy-4-{(1 *)-1-methoxyethyl} phenyl, 3-{(1 *)-1-methoxyethyl} Phenyl, 3-{(1 *)-1-methoxyethyl}
-5-methylphenyl, 5-methoxy-3-｛(1 *)
-1-methoxyethyldiphenyl, 5-chloro-3-
{(1 *)-1-methoxyethyl} phenyl, 5-fluoro-3-{(1 *)-1-methoxyethyl} phenyl,
4-{(1 *)-1-benzyloxyethyl} phenyl, 3-{(1 *)-1-benzyloxyethyl} phenyl, 3-{(1 *)-1-benzyloxyethyl}-
5-methylphenyl, 4-{(1 *)-1-phenoxyethyl} phenyl, 3-methoxy-4-{(1 *)-1
-Phenoxyethyl} phenyl, 3-{(1 *)-1-
Phenoxyethyl {phenyl, 3-{(1 *)-1-phenoxyethyl} -5-methylphenyl, 5-methoxy-3-{(1 *)-1-phenoxyethyl} phenyl,
5-chloro-3-{(1 *)-1-phenoxyethyl}
Phenyl, 5-fluoro-3-{(1 *)-1-phenoxyethyl} phenyl,

4-{(1 *)-1- (3,5-dimethylphenoxy) ethyl} phenyl, 3-{(1 *)-1-
(3,5-dimethylphenoxy) ethyl @ phenyl, 3
-{(1 *)-1- (3,5-dimethylphenoxy) ethyl} -5-methylphenyl, 4-{(1 *)-1-trimethylsilyloxyethyl} phenyl, 3-{(1
*)-1-Trimethylsilyloxyethyl @ phenyl,
3-{(1 *)-1-trimethylsilyloxyethyl}
-5-methylphenyl, 4-{(1 *)-1-tert
-Butyldimethylsilyloxyethyldiphenyl, 3-
Methyl-4-{(1 *)-1-tert-butyldimethylsilyloxyethyl} phenyl, 3-{(1 *)-1
-Tert-butyldimethylsilyloxyethyl} phenyl, 3-{(1 *)-1-tert-butyldimethylsilyloxyethyl} -5-methylphenyl, 5-methoxy-3-{(1 *)-1-tert -Butyldimethylsilyloxyethyldiphenyl, 5-chloro-3-
{(1 *)-1-triphenylsilyloxyethyl} phenyl, 5-fluoro-3-{(1 *)-1-triphenylsilyloxyethyl} phenyl,

3-methyl-4-{(1 *)-1-triphenylsilyloxyethyl} phenyl, 3-{(1 *)
-1-triphenylsilyloxyethyl @ phenyl, 3
-{(1 *)-1-triphenylsilyloxyethyl}
-5-methylphenyl, 5-methoxy-3-｛(1 *)
-1-triphenylsilyloxyethyl @ phenyl, 5
-Chloro-3-{(1 *)-1-triphenylsilyloxyethyl} phenyl, 5-fluoro-3-{(1 *)-
1-triphenylsilyloxyethyl @ phenyl, 6-
{(1 *)-1-methoxyethyl} -1-naphthyl, 3
-{(1 *)-1-methoxyethyl} -1-naphthyl,
6-{(1 *)-1-phenoxyethyl} -2-naphthyl, 4-{(1 *)-1-hydroxypropyl} phenyl, 3-{(1 *)-1-hydroxypropyl} phenyl, 3- {(1 *)-1-hydroxypropyl} -5
Methylphenyl,

4-{(1 *)-1-methoxypropyl}
Phenyl, 3-{(1 *)-1-methoxypropyl} phenyl, 3-{(1 *)-1-methoxypropyl} -5
-Methylphenyl, 4-{(1 *)-1-phenoxypropyl} phenyl, 3-{(1 *)-1-phenoxypropyl} phenyl, 3-{(1 *)-1-phenoxypropyl} -5 Methylphenyl, 4-{(1 *)-1-
Hydroxy-2-methylpropyldiphenyl, 3-
{(1 *)-1-hydroxy-2-methylpropyl} phenyl, 3-{(1 *)-1-hydroxy-2-methylpropyl} -5-methylphenyl, 4-{(1 *)-1
-Methoxy-2-methylpropyldiphenyl, 3-
{(1 *)-1-methoxy-2-methylpropyl} phenyl, 3-{(1 *)-1-methoxy-2-methylpropyl} -5-methylphenyl, 4-{(1 *)-1- Phenoxy-2-methylpropyl {phenyl, 3-} (1
*)-1-phenoxy-2-methylpropyl} phenyl, 3-{(1 *)-1-phenoxy-2-methylpropyl} -5-methylphenyl group and the like. Here, (1 *) represents the position of the asymmetric carbon.

[0033] The R ^1, R ^2, R ³ which may have a substituent alkyl group which may have a substituent cycloalkyl group, an optionally substituted aralkyl group,
The substituent of the aryl group which may have a substituent is not particularly limited as long as it does not inhibit the present reaction, as long as it does not inhibit the reaction. . As such a substituent, for example, an appropriate substituent can be selected from a hydrocarbon group, an aryl group, an alkoxy group, a silyloxy group, and a halogen atom.

The monodentate phosphorus ligands (8) to (8 ") corresponding to the above (6) to (6") are described, for example, in Angew. Ch
em. Int. Ed. 37 , 1703 (1998), the ketone body (9) can be asymmetrically reduced (Step A) and derived from the obtained optically active alcohol body (10) (see the following reaction formula).

[0035]

Embedded image

Further, the hydroxyl group of the alcohol compound (10) is protected with a substituent (Rx) (step B), and the obtained ether compound (11) is prepared by, for example, Chem. Commun. , 21
26 (1998), by reacting a Grignard reagent or organolithium (Step C), and then reacting with phosphorus trichloride (Step D) to obtain a monodentate phosphorus ligand having a desired configuration. (8) and (8 ′) can be obtained. By deprotecting Rx, a monodentate phosphorus ligand (8 ″) can be obtained.

In the diamine ligand represented by the general formula (7): [R ⁴ R ⁵ C (NR ⁶ R ⁷ ) —R ⁸ R ⁹ C (NR ¹⁰ R ¹¹ )] R ^{4 to} R ¹¹
Each independently has a hydrogen atom, a linear or branched alkyl group which may have a substituent, a linear or branched alkenyl group which may have a substituent, and a substituent Represents an optionally substituted cycloalkyl group, an optionally substituted aralkyl group, or an optionally substituted aryl group. Further, any one of the above R ⁴ and R ⁵ and R
Any of ¹⁰ and R ¹¹ may form a bond together to form a carbon chain or a nitrogen-containing heterocycle.

In the above formula (7), a linear or branched alkyl group which may have a substituent of R ^{4 to} R ^11, a linear or branched alkenyl group which may have a substituent As a substituent of a cycloalkyl group which may have a substituent, an aralkyl group which may have a substituent or an aryl group which may have a substituent, If there are no substituents, there are no particular restrictions on the substitution position, the type of substituent, the number of substituents, and the like. As such a substituent, for example, an appropriate group selected from a hydrocarbon group, a hydroxy group, an alkoxy group, a carboxyl group, an alkoxycarbonyl group, an amino group, a heterocyclic group, and a halogen atom can be selected.

Examples of the linear or branched alkyl group which may have a substituent include methyl, ethyl, propyl, isopropyl, butyl, sec-butyl and tert.
-Butyl, pentyl, isopentyl, neopentyl, t
Examples thereof include alkyl groups having 1 to 20 carbon atoms such as ert-pentyl, hexyl, heptyl, octyl, nonyl, decyl, and dodecyl groups. Examples of the alkenyl group which may have a substituent include vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3
-Butenyl, 1,3-butanedienyl and the like having 1 to 1 carbon atoms
20 alkenyl groups can be exemplified.

Examples of the cycloalkyl group which may have a substituent include those having 3 to 3 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
8 cycloalkyl groups can be exemplified. Examples of the aralkyl group which may have a substituent include aralkyl groups having 7 to 20 carbon atoms, such as benzyl, α-methylbenzyl, α, α-dimethylbenzyl and α-ethylbenzyl. Can be. Examples of the aryl group which may have a substituent include phenyl, naphthyl, an aromatic hydrocarbon group such as anthranyl group, furanyl,
Oxygen-containing aromatic heterocyclic groups such as benzofuranyl groups, sulfur-containing aromatic heterocyclic groups such as thienyl groups, thienyl, furyl, pyranyl, xanthenyl, pyrrolyl, pyridyl, imidazolyl, indolyl, carbazoyl, phenanthrolyl and other heteromonocyclic or polycyclic Examples include a metallocenyl group such as a formula group and a ferrocenyl group.

Examples of the diamine represented by the general formula (7) include ethylene diamine, propylene diamine,
1,2-diphenylethylenediamine, 2,3-diaminobutane, 1-methyl-2,2-diphenylethylenediamine, 4-methyl-1,2-diamino-1,1-diphenylpentane, 3-methyl-1,2- Diamino-1,
1-diphenylbutane, 1,2-diamino-1,1-di (p-methoxyphenyl) propane, 4-methyl-1,
2-diamino-1,1-di (p-methoxyphenyl) pentane, 3-methyl-1,2-diamino-1,1-di (p-methoxyphenyl) butane, 1,2-diamino-
1,1-di (p-methoxyphenyl) -3-phenylpropane, 1,2-diamino-1,1-dinaphthylpropane, 4-methyl-1,2-diamino-1,1-dinaphthylpentane and the like Examples can be given. When these diamines have an asymmetric carbon, they may be racemic or optically active.

When any of R ⁴ and R ⁵ and any of R ¹⁰ and R ¹¹ are bonded to form a carbocyclic ring, racemic or optically active 1,2-diaminocyclopentane,
Examples thereof include 1,2-diaminocyclohexane and 1,2-diaminocycloheptane. In addition, R ⁴
And any of R ⁵ and any of R ¹⁰ and R ¹¹ form a nitrogen-containing heterocyclic ring which may have a substituent, for example, 2- (aminomethyl) pyrrolidine, 2- (aminomethyl) pyrrolidine,
(1-aminoethyl) pyridine and the like can be exemplified.

The ruthenium compound (1) of the present invention can be synthesized by appropriately reacting a phosphine ligand (PR ¹ R ² R ³ ), a diamine ligand and a ruthenium compound. When a zero-valent ruthenium compound is used as a starting material, for example, a Ru (COD) (COT) complex can be used (where COD represents cyclooctadiene and COT represents cyclooctatriene, respectively).

For example, Organometallic
s. ,4, 1722 (1985).
Ru (COD) (COT) complex and phosphine coordination
Child (PR ¹ R^Two R^Three ) Obtained from Ru (PR¹ R^Two R
^Three )_Two (H_Two )_Two H_Two Reaction of diamine with complex
Phosphine-diamine-ruthenium hydride
A complex (X = Y = H) can be obtained.

That is, hydrocarbon solvents such as pentane, hexane, toluene and xylene, ether solvents such as ether, THF and dioxane, methanol, ethanol,
-1 to 150a in an alcoholic solvent such as propanol
tom, preferably in a hydrogen atmosphere of 5 to 20 atoms,
Ru (COD) (COT) complex, phosphine ligand and diamine are used in a ratio of 1: 1 to 3: 1 to 3, preferably 1: 1 to 1
By reacting at a molar ratio of 1.5: 1 to 1.5 at −50 ° C. to the boiling point of the solvent, preferably at 0 to 50 ° C., a phosphine-diamine-ruthenium hydride complex (X = Y
= H) can be obtained.

A divalent ruthenium compound is used as a starting material.
In this case, for example, ｛RuCl_Two(C₆ H₆ )｝_Two Confusion
The body can be used. For example, Org. Synth
esis. ,71, 1-13 (1993)
According to ｛RuCl_Two (C ₆ H₆ )｝_Two Complexes and phosphes
RuCl obtained from quinone and ligand_Two (PR¹ R^Two R
^Three )_Two (Solvent) To react diamine with x complex
Phosphine-diamine-ruthenium chloride complex
(X = Y = Cl) can be obtained.

In order to synthesize these compounds cheaply and easily, a trivalent ruthenium compound, for example, a hydrate of ruthenium (III) halide (RuX ′ ₃ .xH ₂ O:
Here, X ′ is chlorine, bromine or iodine, and x is 0 to 3
Represents the number of each. ) Is preferred as a starting material. More specifically, for example, “New Experimental Science Course” No. 7
RuCl according to the method described in Vol.
₃ · xH ₂ O and phosphine (PR ¹ R ² R ³⁾ and reacting the obtained phosphine _-. Ruthenium chloride complex ^{_{(RuCl 2 (PR 1 R 2}} R 3) 3), for example, fine Chemicals, 28, 60 (1999), a phosphine-diamine-ruthenium chloride complex (X = Y = Cl) by reacting a diamine.
Can be obtained.

By treating a phosphine-diamine-ruthenium chloride complex (X = Y = Cl) under hydrogenation or hydrogen transfer type reduction reaction conditions, the general formula RuH ₂ (PR ¹ R ² R ³ ) _{2 is obtained.} ｛R ⁴ R ⁵ C (NR ⁶ R
⁷ ) A phosphine-diamine-ruthenium hydride complex represented by —R ⁸ R ⁹ C (NR ¹⁰ R ¹¹ )｝ ₂ (X = Y =
H) can be obtained (hydrogenation of carbonyl compounds).

That is, first, one equivalent of a ruthenium compound represented by RuX ′ ₃ .xH ₂ O and phosphine (PR ¹ R
^By reacting ³ to 10 equivalents, preferably 4 to 6 equivalents of ² R ³ ) in a suitable organic solvent in a temperature range from -50 ° C to the boiling point of the solvent, preferably from room temperature to the boiling point of the solvent, A phosphine-ruthenium chloride complex is obtained. Examples of the organic solvent that can be used here include hydrocarbon solvents such as pentane, hexane, toluene, and xylene; halogenated hydrocarbon solvents such as methylene chloride and chloroform; ethers; THF (tetrahydrofuran);
Ether solvents such as dioxane, alcohol solvents such as methanol, ethanol and 2-propanol, nitrile solvents such as acetonitrile, DMF (N, N-dimethylformamide), N-methylpyrrolidone, 1,3-dimethylimidazolidinone And non-aqueous polar solvents such as DMSO (dimethyl sulfoxide).

Next, 1 equivalent of the obtained phosphine-ruthenium chloride complex is mixed with 1 to 3 equivalents, preferably 1 to 1.5 equivalents of a diamine in a suitable organic solvent at -50 ° C.
The phosphine-diamine-ruthenium chloride complex is obtained by reacting in a temperature range up to the boiling point of the solvent, preferably 0 to 50 ° C. Examples of the organic solvent that can be used here include hydrocarbon solvents such as pentane, hexane, toluene, and xylene; halogenated hydrocarbon solvents such as methylene chloride and chloroform; ethers;
F, ether solvents such as dioxane, alcohol solvents such as methanol, ethanol and 2-propanol, nitrile solvents such as acetonitrile, DMF, N-methylpyrrolidone, 1,3-dimethylimidazolidinone, DMS
And non-aqueous polar solvents such as O.

Further, the obtained phosphine-diamine-
One equivalent of a ruthenium chloride complex is added to an organic solvent at −50.
C to the boiling point of the solvent, preferably 0 to 50C
By reacting 2 to 100 equivalents, preferably 2 to 10 equivalents of a base with hydrogen, a phosphine-diamine-ruthenium hydride complex can be obtained. Examples of the organic solvent that can be used in this reaction include hydrocarbon solvents such as pentane, hexane, toluene, and xylene; halogenated hydrocarbon solvents such as methylene chloride and chloroform; ether solvents such as ether, THF, and dioxane; Alcohol solvents such as ethanol, 2-propanol, etc .; nitrile solvents such as acetonitrile; non-aqueous polar solvents such as DMF, N-methylpyrrolidone, 1,3-dimethylimidazolidinone and DMSO. The base used is NaBH4,
Metal hydrides such as LiAlH ₄ , MeMgBr, EtM
organometallic compounds such as gBr, MeLi, n-BuLi,
KOH, EtOK, t-BuOK, NaOH, EtON
a, t-BuONa, LiOH, EtOLi, t-Bu
Salts of alkali or alkaline earth metals such as OLi, n-B
and quaternary ammonium salts such as u ₄ NBr.

The phosphine-ruthenium chloride complex (X = Y = Cl) comprises 1 equivalent of the phosphine-ruthenium chloride complex and 1 to 3 equivalents of the diamine, preferably 1 to 1 equivalent.
1.5 equivalents and, if desired, an alkali or alkaline earth metal salt or a quaternary ammonium salt, a hydrocarbon solvent such as pentane, hexane, toluene, xylene, or a halogenated hydrocarbon solvent such as methylene chloride or chloroform. ,
Ether solvents such as ether, THF and dioxane; alcohol solvents such as methanol, ethanol and 2-propanol; nitrile solvents such as acetonitrile; DM
In a non-aqueous polar solvent such as F, N-methylpyrrolidone, 1,3-dimethylimidazolidinone, DMSO, and the like, at -50C to
The phosphine-diamine-ruthenium hydride complex (X = Y = H) can also be obtained by reacting in a temperature range up to the boiling point of the solvent, preferably 0 to 50 ° C.

The general formula (1) synthesized as described above
Representative examples of the ruthenium compound represented by are shown in Table 1 below. In Table 1 below, (s, s) -DPEN represents (s, s) -diphenyletherenediamine and (1s,
2s) -CHDN represents 1,2-cyclohexanediamine, and (s) -DAIPEN represents 1-isopropyl-2,2-di (p-methoxyphenyl) ethylenediamine.

[0054]

[Table 1]

[0055]

[Table 2]

[0056]

[Table 3]

[0057]

[Table 4]

[0058]

[Table 5]

[0059]

[Table 6]

[0060]

[Table 7]

[0061]

[Table 8]

[0062]

[Table 9]

[0063]

[Table 10]

[0064]

[Table 11]

[0065]

[Table 12]

[0066]

[Table 13]

[0067]

[Table 14]

[0068]

[Table 15]

[0069]

[Table 16]

[0070]

[Table 17]

[0071]

[Table 18]

[0072]

[Table 19]

[0073]

[Table 20]

[0074]

[Table 21]

[0075]

[Table 22]

[0076]

[Table 23]

The ruthenium compound (1) obtained as described above is useful as a catalyst for asymmetric hydrogenation of carbonyl compounds. This asymmetric hydrogenation reaction is represented by the general formula (4): R
a-CO-Rb With respect to the carbonyl compound represented by (4), the ruthenium compound (1) is 1/100 to 1/100.
1,000,000 (mol / mol), preferably 1
It is used in the range of / 500 to 1 / 100,000. In the hydrogenation reaction using a ruthenium compound in which X and Y are hydrogen atoms in the general formula (1), the ruthenium compound (1) and the carbonyl compound represented by the general formula (4) are mixed in an inert solvent. Then, the reaction can be carried out by applying a hydrogen pressure, stirring in the presence of a hydrogen donor, or applying a hydrogen pressure in the presence of a hydrogen donor.

In the case of the reaction using a ruthenium compound in which X and Y are groups other than hydrogen atoms in the general formula (1), the ruthenium compound (1) and the carbonyl represented by the general formula (4) are used. Compounds are mixed in an inert solvent and subjected to hydrogen pressure in the presence of a base, or in the presence of a hydrogen donor, or by stirring under a hydrogen pressure in the presence of a hydrogen donor. it can.

The amount of the base used can be changed as appropriate, but generally it is preferably from 0.5 to 100 based on 1 equivalent of the ruthenium compound corresponding to the general formulas (1) to (3).
The equivalent is more preferably 2 to 40 equivalents.

The base that can be used is KO
H, EtOK, t-BuOK, NaOH, EtONa,
t-BuONa, LiOH, EtOLi, t-BuOL
a salt of an alkali or alkaline earth metal such as i, n-Bu ₄
Examples thereof include quaternary ammonium salts such as NBr. Others include metal hydrides such as NaBH ₄ and LiAlH ₄ , MeMgBr, EtMgBr, MeL
Organometallic compounds such as i, n-BuLi and the like can also be used.

The inert solvent used in the hydrogenation reaction is not particularly limited as long as it can solubilize the reaction raw materials, the products and the additives. For example, aromatic solvents such as toluene and xylene, aliphatic solvents such as pentane and hexane, halogen-containing hydrocarbon solvents such as methylene chloride, ether solvents such as ether and tetrahydrofuran, methanol, ethanol, 2-propanol, butanol, and benzyl Alcohol solvents such as alcohols, nitrile solvents such as acetonitrile, and non-aqueous polar solvents such as DMF, N-methylpyrrolidone, 1,3-dimethylimidazolidinone, and DMSO can be used.

However, in this reaction, alcohol-based solvents are particularly preferred because the product is alcohol. These liquid solvents can be used alone or as a mixed solvent thereof.

The amount of the solvent used varies depending on the solubility and economical efficiency of the reaction substrate. For example, in the case of using 2-propanol, the concentration of the substrate can be as low as 1% or less and in a state close to no solvent. It is preferably used at 10 to 50% by weight. The hydrogen pressure in this reaction is usually 1 to 20.
It is in the range of 0 atm, preferably in the range of 3 to 100 atm. The reaction temperature is preferably from −30 ° C. to 100 ° C. in view of economy, and it is particularly preferable to carry out the reaction at around room temperature of 25 to 40 ° C. The reaction time is
The reaction is usually completed within a few minutes to 30 hours, depending on the reaction conditions such as the concentration of the reaction substrate, the temperature and the pressure. This reaction can be carried out either in a batch mode or a continuous mode.

[0084]

Next, the present invention will be described in more detail by way of examples. In addition, this invention is not limited at all by the following Examples.

Example 1 RuH ₂ (tris- [3-{(1R) -1-methoxyethyl} phenyl] phosphine) ₂ (S, S) DPEN
Production of (Compound No. I-13) Tris- {3-[(1R) -1-methoxyethyl] phenyl} phosphine 39.6 mg (9.06 × 10 ⁻⁵ mo)
l) in 2-propanol solution (5 ml) was added to Ru (CO 2
D) (COT) 13.0 mg (4.12 × 10 ⁻⁵ mol)
And 8.7 mg of (S, S) -1,2-diphenylphenylenediamine [(S, S) DPEN] (4.15 × 10
^-5 mol) was dissolved in an argon atmosphere, and then stirred under a hydrogen atmosphere at 3 atm for 30 minutes. Then, the reaction solution was filtered, and the filtrate was concentrated to give the title compound (48 m).
g was obtained.

¹ H-NMR (CDCl ₃ , δ ppm):
8-7 (m, 24H), 6.8-6.6 (m, 10
H), 4.6 (m, 2H), 4.1 (m, 2H), 3.
9 (m, 6H), 3.6 (m, 2H), 3.0 (s, 1
8H), 1.4-1.2 (m, 18H) ³¹ P-NMR (CDCl ₃ , δ ppm): 45.5.

Example 2 Synthesis of (1R) -1-phenylethanol In an autoclave, tris- {3-[(1R) -1-
(T-butyldimethylsilyloxy) ethyl] phenyl} phosphine 17.0 mg (2.3 × 10 ⁻⁵ mol)
Ru (COD) in 2-propanol solution (5 ml)
3.7 mg (1.15 × 10 ⁻⁵ mol) of (COT) complex
2.5 mg of (S, S) DPEN (1.15 × 10 ⁻⁵⁾
mol) was dissolved in an argon atmosphere, and then stirred under a hydrogen atmosphere at 3 atm for 30 minutes.

Next, 600 ml (10 mmol) of acetophenone prepared in advance and 0.5 Nt-Bu were added.
2- in which 0.1 ml of an OK / 2-propanol solution was dissolved
1.5 ml of a propanol solution was added to the above reaction solution, and the mixture was stirred under a hydrogen atmosphere at 8 atm for 2 hours. Analysis of the reaction mixture showed that the title compound had a chemical yield of 99% or more, and
It was found that the (R) -isomer was obtained with an optical yield of 81% ee.

Example 3 Synthesis of Tris- {3-[(1R) -1-hydroxyethyl] phenyl} phosphine Tris- {3-[(1R) -1- (t-butyldimethylsilyloxy) ethyl] phenyl} Phosphine 800m
g (1.09 mmol) in THF (10 ml)
3.5 ml of 1Nn-Bu ₄ NF / THF solution was added,
Stirred at room temperature for 6 hours. The reaction solution was concentrated, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1) to give 310 mg (0.78 mmol; yield 7) of the title compound.
1%).

¹ H-NMR (CDCl ₃ , δ ppm):
1.4 (d, 9H), 2.0 (brs, 1H), 4.8
(Q, 3H), 7.2-7.1 (m, 3H), 7.4-
7.3 (m, 9H)

Example 4 Synthesis of (1S) -1-phenylethanol In an autoclave, tris- {3-[(1R) -1-H
[Droxyethyl] phenylphosphine｝ 8.5 mg
(2.16 × 10^-Fivemol) in 2-propanol
(5 ml ml) with Ru (COD) (COT) complex 3.4
mg (1.08 × 10 ^-Fivemol) and (S, S) DPE
2.3 mg (1.08 × 10^-Fivemol) in an argon atmosphere
After dissolving in an atmosphere, 30 minutes under a hydrogen atmosphere of 3 atm
While stirring.

Next, 650 ml (0.55 mmol) of acetophenone prepared in advance and 0.5 NtB
1.5 ml of a 2-propanol solution in which 0.1 ml of a uOK / 2-propanol solution was dissolved was added to the reaction solution,
The mixture was stirred under a hydrogen atmosphere at 8 atm for 2 hours. Analysis of the reaction solution showed that the title compound had a chemical yield of 99% or more,
It was found that the optical yield was 8% ee.

[0093]

As described above, according to the present invention,
A novel ruthenium compound that can be easily synthesized at low cost and can be synthesized in large quantities, and that has excellent asymmetric reduction catalytic activity is provided. Further, according to the present invention, various optically active alcohols can be produced easily and with high optical yield and chemical yield using the ruthenium compound.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) // C07B 61/00 300 C07B 61/00 300 C07M 7:00

Claims (4)

[Claims] 1. General formula (1): RuXY (PR ¹ R ² R ³ ) _n [R ⁴ R ⁵ C (NR ⁶ R ⁷ ) -R ⁸ R ⁹ C (NR ¹⁰ R ¹¹ )] _m (1) In the formula, X and Y each independently represent a hydrogen atom or an anion; R ¹ , R ² and R ³ each independently represent an alkyl group which may have a substituent, Represents an optionally substituted cycloalkyl group, an optionally substituted aralkyl group or an optionally substituted aryl group,
^At least one of ¹ , R ² and R ³ is an optically active group. R ^{4 to} R ¹¹ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or a cycloalkyl which may have a substituent. A aralkyl group which may have a substituent or an aryl group which may have a substituent; and any one of R ⁴ and R ⁵ and any one of R ⁸ and R ⁹ To form a ring. n and m each independently represent 0 or an integer of 1 to 4. A ruthenium compound represented by｝. 2. Formula (1): RuXY (PR ¹ R ² R ³ ) _n [R ⁴ R ⁵ C (NR ⁶ R ⁷ ) -R ⁸ R ⁹ C (NR ¹⁰ R ¹¹ )] _m (1) Wherein X and Y each independently represent a hydrogen atom or an anion; R ¹ , R ² and R ³ each independently represent an optically active alkyl group which may have a substituent; And an optically active cycloalkyl group which may have a substituent, an optically active aralkyl group which may have a substituent or an optically active aryl group which may have a substituent. R ^{4 to} R
¹¹ is each independently a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, a cycloalkyl group which may have a substituent,
Represents an aralkyl group which may have a substituent or an aryl group which may have a substituent, and any one of R ⁴ and R ⁵ and one of R ⁸ and R ⁹ are bonded to form a ring May be formed. n and m each independently represent 0 or an integer of 1 to 4. A ruthenium compound represented by｝. 3. General formula (1): RuXY (PR ¹ R ² R ³ ) _n [R ⁴ R ⁵ C (NR ⁶ R ⁷ ) −R ⁸ R ⁹ C (NR ¹⁰ R ¹¹ )] _m (1) In the formula, X and Y each independently represent a hydrogen atom or an anion; R ¹ , R ² , and R ³ are all the same group, and may have a substituent; A group, an optically active cycloalkyl group which may have a substituent, an optically active aralkyl group which may have a substituent, or an optically active aryl group which may have a substituent. R ^{4 to} R
¹¹ is each independently a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, a cycloalkyl group which may have a substituent,
Represents an aralkyl group which may have a substituent or an aryl group which may have a substituent; and any one of R ⁴ and R ⁵ and any one of R ⁸ and R ⁹ are bonded to form a ring May be formed. n and m each independently represent 0 or an integer of 1 to 4. A ruthenium compound represented by｝. 4. General formula (1): RuXY (PR ¹ R ² R ³ ) _n [R ⁴ R ⁵ C (NR ⁶ R ⁷ ) -R ⁸ R ⁹ C (NR ¹⁰ R ¹¹ )] _m (1) In the formula, X and Y each independently represent a hydrogen atom or an anion; R ¹ , R ² and R ³ each independently represent an alkyl group which may have a substituent, Represents an optionally substituted cycloalkyl group, an optionally substituted aralkyl group or an optionally substituted aryl group,
^At least one of ¹ , R ² and R ³ is an optically active group. R ^{4 to} R ¹¹ each independently represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or a cycloalkyl which may have a substituent. A aralkyl group which may have a substituent or an aryl group which may have a substituent; and any one of R ⁴ and R ⁵ and any one of R ⁸ and R ⁹ To form a ring. n and m each independently represent 0 or an integer of 1 to 4. In the presence of a ruthenium compound represented by｝, a compound represented by the general formula (2): Ra-CO-R
b (2) (wherein, Ra and Rb are different from each other, and may have an alkyl group which may have a substituent, an alkenyl group which may have a substituent, and a cyclo which may have a substituent. A hydrogen atom of a carbonyl compound represented by an alkyl group, an aralkyl group which may have a substituent or an aryl group which may have a substituent. ): Production of optically active alcohols represented by Ra—C ^* H (OH) —Rb (5) (wherein Ra and Rb represent the same meaning as described above, and C ^* represents asymmetric carbon). Method.