CA1109479A - PROCESS FOR PRODUCING OPTICALLY ACTIVE .alpha.- HYDROXYCARBOXYLIC ACID ESTER - Google Patents
PROCESS FOR PRODUCING OPTICALLY ACTIVE .alpha.- HYDROXYCARBOXYLIC ACID ESTERInfo
- Publication number
- CA1109479A CA1109479A CA297,758A CA297758A CA1109479A CA 1109479 A CA1109479 A CA 1109479A CA 297758 A CA297758 A CA 297758A CA 1109479 A CA1109479 A CA 1109479A
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- Prior art keywords
- acid ester
- optically active
- butane
- bis
- alpha
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
- B01J31/2414—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom comprising aliphatic or saturated rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/822—Rhodium
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- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Furan Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
An optically active .alpha.-hydroxycarboxylic acid ester is produced by asymmetric hydrogenation of an .alpha.-ketocarboxylic acid ester in the presence of a rhodium complex having a phosphine ligand having an optically active substituent group which present is derived from natural sources.
An optically active .alpha.-hydroxycarboxylic acid ester is produced by asymmetric hydrogenation of an .alpha.-ketocarboxylic acid ester in the presence of a rhodium complex having a phosphine ligand having an optically active substituent group which present is derived from natural sources.
Description
The present invention relates to a process for pro-ducing an optically active ~-hydroxycarboxylic acid ester. More particularly, it relates to a process for producing an optically active ~-hydroxycarboxylic acid ester by asymmetric hydrogenation of an ~-ketocarboxylic acid ester in the presence of a rhodium complex having a phosphine ligand having an optically active substituent group which is derived from natural sources.
The optically active ~-hydroxycarboxylic acid esters are physiologically active compounds in natural materials such as lactic acid esters, mandelic acid ester and pantoyl lactones.
It is well-known that optically active D-(-)-pantoyl lactone is an important intermediate for producing pantothenic acid, pantetheine and Coenzyme A. Calcium pantothenate has been produced on an industrial scale as one of the vitamins. Panto-thenic acid is a component of Coenzyme A and has coenzymatic activity. Pantothenyl alcohol and pantothenyl ethyl ether as the derivatives of pantothenic acid have been produced in an industrial scale. Calcium pantothenate can be produced by reacting pantolactone with calcium salt of ~-alanine without a racemization (E.H. Wilson, J. Weijlard and M. Tishler, J. Amer.
Chem. Soc., 76 5177 (1954) ). In the production, it is impor-tant to consider how to produce D-(-)-pantoyl lactone. In the production of pantetheine, pantothenyl alcohol and pantothenyl ethyl ether, it is also important to consider the same problem.
The products of the present invention are important as inter-mediates for the synthesis of amino acids and derivatives thereof.
It is known to produce the optically active ~-hydroxy-carboxylic acid ester from an ~-ketocarboxylic acid ester by the hydrogenation in the presence of a catalyst, as follows.
1) A method of hydrogenation of an optically active ~-ketocarboxylic acid ester in the presence of a catalyst (A. McKenzie, J. Chem. Soc., 87, 1373 (1905); Mitsui and Kanai J.
4~79 Japanese Chem. Soc., _, 179 (1966).
The optically active ~-hydroxycarboxylic acid esters are physiologically active compounds in natural materials such as lactic acid esters, mandelic acid ester and pantoyl lactones.
It is well-known that optically active D-(-)-pantoyl lactone is an important intermediate for producing pantothenic acid, pantetheine and Coenzyme A. Calcium pantothenate has been produced on an industrial scale as one of the vitamins. Panto-thenic acid is a component of Coenzyme A and has coenzymatic activity. Pantothenyl alcohol and pantothenyl ethyl ether as the derivatives of pantothenic acid have been produced in an industrial scale. Calcium pantothenate can be produced by reacting pantolactone with calcium salt of ~-alanine without a racemization (E.H. Wilson, J. Weijlard and M. Tishler, J. Amer.
Chem. Soc., 76 5177 (1954) ). In the production, it is impor-tant to consider how to produce D-(-)-pantoyl lactone. In the production of pantetheine, pantothenyl alcohol and pantothenyl ethyl ether, it is also important to consider the same problem.
The products of the present invention are important as inter-mediates for the synthesis of amino acids and derivatives thereof.
It is known to produce the optically active ~-hydroxy-carboxylic acid ester from an ~-ketocarboxylic acid ester by the hydrogenation in the presence of a catalyst, as follows.
1) A method of hydrogenation of an optically active ~-ketocarboxylic acid ester in the presence of a catalyst (A. McKenzie, J. Chem. Soc., 87, 1373 (1905); Mitsui and Kanai J.
4~79 Japanese Chem. Soc., _, 179 (1966).
2. A method of asymmetric hydrogenation in the pre-sence of a rhodium complex having an optically active phosphine ligands having ferrocenyl group (Mise, Hayashi and Kumada Chem.
Soc. Japan, 35th Annual Meeting Abstract lK-20 (1976)).
However, in the method 1), an equivalent amount or more of the optically active compound is required as the starting material in the asymmetric synthesis whereas in the present invention only a catalytic amount of the optically active com-pound is used to obtain the desired compound. Accordingly, themethod 1) is disadvantageous.
In method 2) the optically active phosphine is a com-pound having complicated structure and metal component, which is not easily produced because the synthesis includes an optical resolution and the optical yield is low.
Heretofore, D-(-)-pantoyl lactone has been produced by optical resolution of pantonyl lactone in racemic form with e.g. quinine and ephedrine. In accordance with the method, only maximum 50% of the yield can be obtained. Since L-(+)-pantonyl lactone has no physiological activity, it must be ~ converted to pantonyl lactone in racemic form by severeracemization otherwise it is wasted.
The present invention provides an indusLrial process for obtaining an optically active ~-hydroxycarboxylic acid este having high optical purity at high yield.
The present invention to produce an optically active ~ -hydroxycarboxylic acid ester by using a complex having optically active ligands which is derived from natural sources and have high optical purity and easily obtained as ligand of the catalyst.
According to the present invention there is provided a process for producing an optically active ~-hydroxycarboxylic 7~
acid ester which comprises asymmetric hydrogenation at a hydrogen pressure of 1 to 50 atmospheres of an ~-keto-- 2a -1~9~7~
-arboxylic acid ester in the presence of a rhodlum complex with a phosphine ligand having an optically active substituent group which is derived from natural sources.
Suitable ~-ketocarboxylic acid ester for use in the process of the present invention include pyruvic acid esters such as methyl pyruvate and n-propyl pyruvate; benzoylformic acid esters such as ethyl phenylglyoxylate and cyclohexyl phenylgly-oxylate; alkyl chain type ~-ketocarboxylic acid esters such as methyl pentylglyoxylate and ethyl octylglyoxylate; and c~-ketolac-tones such as ~-keto-R,~-dimethyl-~-butyrolactone.
The catalyst for use in the process of the present invention is rhodium complex with a phosphine ligand having an optically active substituent group which is derived from a natur- -al source. The phosphines having an optically active substituent group which is derived from a natural source can be dioxolans having the formula ~ ~ 3 4 wherein the asterisk (*) represents an optically active position and Rl to R4 respectively represent an alkyl or aryl group and R5 and R6 represent hydrogen atom, an alkyl, aryl, alkoxy, aminocarbonyl, carboxyl, ester, cyano alkylthio or arylthio group, or pyrrolidines having the formula Rl R2 P - ~ ~ R6 ...................... (II) 7' R
wherein the asterisk (*) represents an optically active position and R to R respectively represent an alkyl or aryl group;
R5 and R6 respectively represent hydrogen atom or an alkyl or l7~
aryl group; R represents hydrogen atom or an alkyl, aryl, ester, amino, carboxyl or cyano group.
Suitable dioxolans having the formula (I) include (2R, 3R)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphos-phino) butane and (2S, 3S)-2,3-O-isopropylidene-2,3-dihydroxy-1, 4-bis(diphenylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-iso-propylidene-2,3-dihydroxy-1,4-bis-(dibenzophosphoryl) butane;
(2R, 3R) or (2S, 3S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (di-o-tolylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-isopro-pylidene-2,3-dihydroxy-1,4-bis(di-m-tolylphosphino) butane;
(2R, 3R) or (2S, 3S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (di-2,5-xylylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-benzylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane;
(2R, 3R) or (2S, 3S)-2,3-O-cyclohexylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-cyclopentylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane;
and (2R, 3R) or (2S, 3S)-2,3-O-cyclohexylidene-2,3-dihydroxy-1,4-bis(cyclohexylphenylphosphino) butane.
Suitable pyrrolidines having the formula (II) include (2S, 4S)-N-t-butoxycarbonyl-4-diphenylphosphino-2-diphenylphos-phino-methyl pyrrolidine; (2S, 4S)-N-methoxycarbonyl-4-diphenyl-phosphino-2-diphenylphosphino-methyl pyrrodine; and (2S, 4S)-4-diphenylphosphino-2-diphenylphosphino-methyl pyrrolidine.
In the process of the presentiinvention, it is prefer-able to use a solvent. Suitable solvents include aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol and ethanol; ethers such as tetrahydrofuran, mono-glyme and mixtures thereof.
In the process of the present invention, the starting material of ~-ketocarboxylic acid ester is dissolved in a solvent and the rhodium complex catalyst is added at a catalytic amount of 0.01 to 1.0 mole % and the reaction is carried out in hydrogen under atmos~)heric r)ressure or hi(lher pressure. The reac~ion is ;moothly performed at room temperature without using the special heating or coolin~ means and the product can ~e obtained at sub- -stantially stoichiometric yield. Tn order to reduce the reaction time, it is preferable to perform the reaction under higher pressure such as several to several -tens atms, and at higher temperatures.
The present invention will be further illustrated by the following Examples.
EX~MPLE 1:
Under argon atmosphere, 38 mg of [Rh(1,5-cyclooctadiene) CQ]2 and 100 mg of (2S, 4S)-N-butoxycarbonyl-4-diphenylphosphino -2-diphenylphosphinomethyl pyrrolidine (hereinafter referring to as BPPM) were dissolved in 8 ml of tetrahydrofuran to prepare a solution of the catalyst.
In an autoclave, the solution of the catalyst and 3.90 g of n-propyl pyruvate were charged and the reaction was carried out under hydrogen at a pressure of 20 atm. at 20C for 24 hours with stirring to complete the reaction. The solvent was distilled off from the reaction mixture and the product was distilled to obtain 3.76 g of n-propyl (+)- lactate having a boiling point of 62C/ll mmllg, [(~]D + 9.17 (neat) and an optical purity of 76%
(yield: 95%).
EXAMPLES 2 to 15:
In accordance with the process of Example 1 except various ~-ketocarboxylic acid esters, optically active ligands and solvents, the optically active ~-hydroxycarboxylic acid esters t were produced. The results are shown in Table 1.
In Table 1, the optically active ligand (-)-DIOP means (2R, 3R)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (diphenyl-phosphino) butane and (+)- DIOP means (2S, 3S)-2,3-O-isopropyli-dene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane.
11~947~
EXAMPL~ 16:
In accordance with the process of Example 1, 19 mg of [Rh(1,5-cyclooctadiene) CQ]2 and 50 mg of an optically active ligand of BPPM were dissolved in 4 ml of tetrahydrofuran to pre-pare a solution of the catalyst.
In an autoclave, the solution of the catalyst and 1.92 g of ~-keto-R,~-dimethyl-~-butyrolactone were charged and the reaction was carried out under hydrogen of 50 atm. at 20C for 24 hours with stirring to complete the reaction.
The solvent was distilled off from the reaction mixture and the product was purified by passing through a short silica gel chroma-tography column using n-hexane-ether as elute to obtain 1.89 g of (-)-pantoyl lactone having a melting point of 89 to 91C and [~]D5 -25.3 (C.2.00; H2O) and an optical activity of 50%
(yield: 97%).
; EXAMPLES 17 and 18:
In accordance with the process of Example 16 except using various optically active ligands and solvents, the optically active (-)-pantoyl lactone was produced. The results are also shown in Table 1.
Note: BPPM, (-)-DIOP,(+)-DIOP are defined above.
PhH: benzene THF: tetrahydrofuran MeOfl: methanol Monoglyme: 1,2-dimethoxyethane EXAMPLE 19:
In accordance with the process of Example 16, 24.2 mg of [Rh(1,5-cyclooctadiene CQ]2 and 60.2 mg of BPPM were dissolved in 8 ml of benzene to prepare the solution of the catalyst. In an autoclave, the solution of the catalyst and 1.28 g of ~-keto-~,~-dimethyl-~-butyrolactone were charged and the reaction was r carried out under initial hydrogen pressure of 50 atm at 30C for -- - - - - w - ~
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11~9~7g 48 hours with st:irring in a thermostat-tcmperature-controlled bath. The reaction was completed at a conversion of 100%. The solvent ancl the catalyst were separated as the process of Example 16 to obtain 1.28 g of (-)-pantoyl lactone having [~]D -42.5 (C.2.046-H20) and an optical purity of 83.9%
(yield: 98.4~).
EXAMPLE 20:
In accordance with the process of Example 19 except varying the reaction temperature to 40C and the initial hydrogen pressure to 20 atm the reaction was carried out and the reaction mixture was distilled under a reduced pressure without separating the catalyst to obtain 1.20 g of (-) pantoyl lactone having a boiling point of 92C/4 mmllg a melting point of 89 to 91C, [~]D
-43.3 (C.2.033:H20) and an optical purity of 85.4% (yield: 92.3%).
EXAMPLE 21:
In accordance with the process of Example 19 except varying the reaction temperature to 50C, the reaction and the separation were carried out to obtain 1.23 g of (-) pantoyl lactone having [~]25 _43.0o (C. 2.042 : ~12) and an optical purity of 84.8% (yield: 94.6%).
EX~MPLE 22:
In accordance with the process of Example 20 except varying the reaction temperature to 70C, the reaction and the separation were carried out to obtain 1.18 g of (-) pantoyl lac-tone having [~]D5 -39.1 (C. 2.128 : H2O) and an optical purity of 77.1% (yield: 90.7%).
EXAMPLE 23:
In accordance with the process of Example 21 except using 8 ml of toluene as the solvent; the reaction and the separ-ation were carried out to obtain 1.25 g of (-) pantoyl lactone having [~]D5 ~39 4 (C. 2.032 : 112O) and an optical purity of 77.7~ (yield: 96.2%).
g
Soc. Japan, 35th Annual Meeting Abstract lK-20 (1976)).
However, in the method 1), an equivalent amount or more of the optically active compound is required as the starting material in the asymmetric synthesis whereas in the present invention only a catalytic amount of the optically active com-pound is used to obtain the desired compound. Accordingly, themethod 1) is disadvantageous.
In method 2) the optically active phosphine is a com-pound having complicated structure and metal component, which is not easily produced because the synthesis includes an optical resolution and the optical yield is low.
Heretofore, D-(-)-pantoyl lactone has been produced by optical resolution of pantonyl lactone in racemic form with e.g. quinine and ephedrine. In accordance with the method, only maximum 50% of the yield can be obtained. Since L-(+)-pantonyl lactone has no physiological activity, it must be ~ converted to pantonyl lactone in racemic form by severeracemization otherwise it is wasted.
The present invention provides an indusLrial process for obtaining an optically active ~-hydroxycarboxylic acid este having high optical purity at high yield.
The present invention to produce an optically active ~ -hydroxycarboxylic acid ester by using a complex having optically active ligands which is derived from natural sources and have high optical purity and easily obtained as ligand of the catalyst.
According to the present invention there is provided a process for producing an optically active ~-hydroxycarboxylic 7~
acid ester which comprises asymmetric hydrogenation at a hydrogen pressure of 1 to 50 atmospheres of an ~-keto-- 2a -1~9~7~
-arboxylic acid ester in the presence of a rhodlum complex with a phosphine ligand having an optically active substituent group which is derived from natural sources.
Suitable ~-ketocarboxylic acid ester for use in the process of the present invention include pyruvic acid esters such as methyl pyruvate and n-propyl pyruvate; benzoylformic acid esters such as ethyl phenylglyoxylate and cyclohexyl phenylgly-oxylate; alkyl chain type ~-ketocarboxylic acid esters such as methyl pentylglyoxylate and ethyl octylglyoxylate; and c~-ketolac-tones such as ~-keto-R,~-dimethyl-~-butyrolactone.
The catalyst for use in the process of the present invention is rhodium complex with a phosphine ligand having an optically active substituent group which is derived from a natur- -al source. The phosphines having an optically active substituent group which is derived from a natural source can be dioxolans having the formula ~ ~ 3 4 wherein the asterisk (*) represents an optically active position and Rl to R4 respectively represent an alkyl or aryl group and R5 and R6 represent hydrogen atom, an alkyl, aryl, alkoxy, aminocarbonyl, carboxyl, ester, cyano alkylthio or arylthio group, or pyrrolidines having the formula Rl R2 P - ~ ~ R6 ...................... (II) 7' R
wherein the asterisk (*) represents an optically active position and R to R respectively represent an alkyl or aryl group;
R5 and R6 respectively represent hydrogen atom or an alkyl or l7~
aryl group; R represents hydrogen atom or an alkyl, aryl, ester, amino, carboxyl or cyano group.
Suitable dioxolans having the formula (I) include (2R, 3R)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphos-phino) butane and (2S, 3S)-2,3-O-isopropylidene-2,3-dihydroxy-1, 4-bis(diphenylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-iso-propylidene-2,3-dihydroxy-1,4-bis-(dibenzophosphoryl) butane;
(2R, 3R) or (2S, 3S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (di-o-tolylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-isopro-pylidene-2,3-dihydroxy-1,4-bis(di-m-tolylphosphino) butane;
(2R, 3R) or (2S, 3S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (di-2,5-xylylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-benzylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane;
(2R, 3R) or (2S, 3S)-2,3-O-cyclohexylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-O-cyclopentylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane;
and (2R, 3R) or (2S, 3S)-2,3-O-cyclohexylidene-2,3-dihydroxy-1,4-bis(cyclohexylphenylphosphino) butane.
Suitable pyrrolidines having the formula (II) include (2S, 4S)-N-t-butoxycarbonyl-4-diphenylphosphino-2-diphenylphos-phino-methyl pyrrolidine; (2S, 4S)-N-methoxycarbonyl-4-diphenyl-phosphino-2-diphenylphosphino-methyl pyrrodine; and (2S, 4S)-4-diphenylphosphino-2-diphenylphosphino-methyl pyrrolidine.
In the process of the presentiinvention, it is prefer-able to use a solvent. Suitable solvents include aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol and ethanol; ethers such as tetrahydrofuran, mono-glyme and mixtures thereof.
In the process of the present invention, the starting material of ~-ketocarboxylic acid ester is dissolved in a solvent and the rhodium complex catalyst is added at a catalytic amount of 0.01 to 1.0 mole % and the reaction is carried out in hydrogen under atmos~)heric r)ressure or hi(lher pressure. The reac~ion is ;moothly performed at room temperature without using the special heating or coolin~ means and the product can ~e obtained at sub- -stantially stoichiometric yield. Tn order to reduce the reaction time, it is preferable to perform the reaction under higher pressure such as several to several -tens atms, and at higher temperatures.
The present invention will be further illustrated by the following Examples.
EX~MPLE 1:
Under argon atmosphere, 38 mg of [Rh(1,5-cyclooctadiene) CQ]2 and 100 mg of (2S, 4S)-N-butoxycarbonyl-4-diphenylphosphino -2-diphenylphosphinomethyl pyrrolidine (hereinafter referring to as BPPM) were dissolved in 8 ml of tetrahydrofuran to prepare a solution of the catalyst.
In an autoclave, the solution of the catalyst and 3.90 g of n-propyl pyruvate were charged and the reaction was carried out under hydrogen at a pressure of 20 atm. at 20C for 24 hours with stirring to complete the reaction. The solvent was distilled off from the reaction mixture and the product was distilled to obtain 3.76 g of n-propyl (+)- lactate having a boiling point of 62C/ll mmllg, [(~]D + 9.17 (neat) and an optical purity of 76%
(yield: 95%).
EXAMPLES 2 to 15:
In accordance with the process of Example 1 except various ~-ketocarboxylic acid esters, optically active ligands and solvents, the optically active ~-hydroxycarboxylic acid esters t were produced. The results are shown in Table 1.
In Table 1, the optically active ligand (-)-DIOP means (2R, 3R)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (diphenyl-phosphino) butane and (+)- DIOP means (2S, 3S)-2,3-O-isopropyli-dene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane.
11~947~
EXAMPL~ 16:
In accordance with the process of Example 1, 19 mg of [Rh(1,5-cyclooctadiene) CQ]2 and 50 mg of an optically active ligand of BPPM were dissolved in 4 ml of tetrahydrofuran to pre-pare a solution of the catalyst.
In an autoclave, the solution of the catalyst and 1.92 g of ~-keto-R,~-dimethyl-~-butyrolactone were charged and the reaction was carried out under hydrogen of 50 atm. at 20C for 24 hours with stirring to complete the reaction.
The solvent was distilled off from the reaction mixture and the product was purified by passing through a short silica gel chroma-tography column using n-hexane-ether as elute to obtain 1.89 g of (-)-pantoyl lactone having a melting point of 89 to 91C and [~]D5 -25.3 (C.2.00; H2O) and an optical activity of 50%
(yield: 97%).
; EXAMPLES 17 and 18:
In accordance with the process of Example 16 except using various optically active ligands and solvents, the optically active (-)-pantoyl lactone was produced. The results are also shown in Table 1.
Note: BPPM, (-)-DIOP,(+)-DIOP are defined above.
PhH: benzene THF: tetrahydrofuran MeOfl: methanol Monoglyme: 1,2-dimethoxyethane EXAMPLE 19:
In accordance with the process of Example 16, 24.2 mg of [Rh(1,5-cyclooctadiene CQ]2 and 60.2 mg of BPPM were dissolved in 8 ml of benzene to prepare the solution of the catalyst. In an autoclave, the solution of the catalyst and 1.28 g of ~-keto-~,~-dimethyl-~-butyrolactone were charged and the reaction was r carried out under initial hydrogen pressure of 50 atm at 30C for -- - - - - w - ~
tD
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I-ml- ~m~ ~--+ ~ + ~_ ~ + ~
. ~ ~1 ~ CO ~ ~ ~ ~ ~ ~n O O ~n _10- 00- . ~. om- . . . . ~ ,_ _I` co ~ o I~ O O ~ n ~I _l ~I O CO
_ _ w~:~3 ~w w a~ o _~ o W Ul W ~1 _~ ~ ,~
- ~- ~ n O W CO I_ ~D I_ ~I ~ ~ .
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. . ., .
11~9~7g 48 hours with st:irring in a thermostat-tcmperature-controlled bath. The reaction was completed at a conversion of 100%. The solvent ancl the catalyst were separated as the process of Example 16 to obtain 1.28 g of (-)-pantoyl lactone having [~]D -42.5 (C.2.046-H20) and an optical purity of 83.9%
(yield: 98.4~).
EXAMPLE 20:
In accordance with the process of Example 19 except varying the reaction temperature to 40C and the initial hydrogen pressure to 20 atm the reaction was carried out and the reaction mixture was distilled under a reduced pressure without separating the catalyst to obtain 1.20 g of (-) pantoyl lactone having a boiling point of 92C/4 mmllg a melting point of 89 to 91C, [~]D
-43.3 (C.2.033:H20) and an optical purity of 85.4% (yield: 92.3%).
EXAMPLE 21:
In accordance with the process of Example 19 except varying the reaction temperature to 50C, the reaction and the separation were carried out to obtain 1.23 g of (-) pantoyl lactone having [~]25 _43.0o (C. 2.042 : ~12) and an optical purity of 84.8% (yield: 94.6%).
EX~MPLE 22:
In accordance with the process of Example 20 except varying the reaction temperature to 70C, the reaction and the separation were carried out to obtain 1.18 g of (-) pantoyl lac-tone having [~]D5 -39.1 (C. 2.128 : H2O) and an optical purity of 77.1% (yield: 90.7%).
EXAMPLE 23:
In accordance with the process of Example 21 except using 8 ml of toluene as the solvent; the reaction and the separ-ation were carried out to obtain 1.25 g of (-) pantoyl lactone having [~]D5 ~39 4 (C. 2.032 : 112O) and an optical purity of 77.7~ (yield: 96.2%).
g
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for producing an optically active .alpha.-hydroxy-carboxylic acid ester which comprises the asymmetric hydrogenation under a hydrogen pressure of 1 to 50 atmospheres of an .alpha.-ketocarboxylic acid ester selected from a pyruvic acid ester, a benzoylformic acid ester, an alkylglyoxylic acid ester and an .alpha.-ketolactone in the presence of a rhodium complex with a phosphine ligand having an optically active substituent group which is derived from natural sources, the phosphine being selected from a dioxolan having optically active positions at least at 2- and 3-positions which has the formula wherein the asterisk (*) represents an optically active position;
R1 to R4 respectively represent an alkyl or aryl group; and R5 and R6 respectively represent hydrogen atom, an alkyl, aryl, alkoxy, amino, carbonyl, carboxyl, ester, cyano, alkylthio or arylthio group, and a pyrrolidine having optically active positions at least at 2- and 3-positions which has the formula wherein the asterisk (*) represents an optically active position;
R1' to R4' respectively represent alkyl or aryl group; R5' and R6' respectively represent hydrogen atom or an alkyl or aryl group;
R7' represents hydrogen atom or an alkyl, aryl, ester, amino, carboxyl or cyano group.
R1 to R4 respectively represent an alkyl or aryl group; and R5 and R6 respectively represent hydrogen atom, an alkyl, aryl, alkoxy, amino, carbonyl, carboxyl, ester, cyano, alkylthio or arylthio group, and a pyrrolidine having optically active positions at least at 2- and 3-positions which has the formula wherein the asterisk (*) represents an optically active position;
R1' to R4' respectively represent alkyl or aryl group; R5' and R6' respectively represent hydrogen atom or an alkyl or aryl group;
R7' represents hydrogen atom or an alkyl, aryl, ester, amino, carboxyl or cyano group.
2. A process as claimed in claim 1, in which the dioxolan is selected from (2R, 3R)-2,3-0-3R)-2,3-0-isoropylidene-2,3-dihydroxy-1-4-bis(diphenylphosphino) butane and (2S, 3S)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane;
(2R, 3R) or (2S, 3S)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis (dibenzophosphoryl butane; (2R, 3R) or (2S, 3S)-2,3-0-isopropyli-dene-2,3-dihydroxy-1,4-bis(di-o-tolylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(di-m-tolyl-phosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(di-2,5-xylylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-benzylidene-2,3-dihydroxy-1,4-bis(diphenylphos-phino) butane; (2R, 3R) or (2S, 3S)-2,3-0-cyclohexylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-cyclopentylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane; and (2R, 3R) or (2S, 3S)-2,3-0-cyclohexylidene-2,3-di-hydroxy-1,4-bis(cyclohexylphenylphosphino) butane.
(2R, 3R) or (2S, 3S)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis (dibenzophosphoryl butane; (2R, 3R) or (2S, 3S)-2,3-0-isopropyli-dene-2,3-dihydroxy-1,4-bis(di-o-tolylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(di-m-tolyl-phosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(di-2,5-xylylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-benzylidene-2,3-dihydroxy-1,4-bis(diphenylphos-phino) butane; (2R, 3R) or (2S, 3S)-2,3-0-cyclohexylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane; (2R, 3R) or (2S, 3S)-2,3-0-cyclopentylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane; and (2R, 3R) or (2S, 3S)-2,3-0-cyclohexylidene-2,3-di-hydroxy-1,4-bis(cyclohexylphenylphosphino) butane.
3. A process as claimed in claim 1, in which the pyrrolidine is selected from (2S, 4S)-N-t-butoxycarbonyl-4-diphenyl-phosphino-2-diphenylphosphinomethyl pyrrolidine; (2S, 4S)-N-methoxycarbonyl-4-diphenylphosphinomethyl pyrrolidine; and (2S, 4S)-4-diphenylphosphino-2-diphenylphosphinomethyl pyrroli-dine.
4. A process as claimed in claim 1, 2 or 3 in which the .alpha.-ketocarboxylic acid ester is selected from methyl pyruvate and propyl pyruvate, ethyl phenyl glyoxylate, cyclohexyl gly-oxylate methyl pentylglyoxylate, ethyl octylglyoxylate; and .alpha.-keto-.beta.,.beta.-dimethyl-?-butyrolcatone.
5. A process according to claim 1 wherein the.
reaction is carried out by dissolving the .alpha.-ketocarboxylic acid ester in a solvent.
reaction is carried out by dissolving the .alpha.-ketocarboxylic acid ester in a solvent.
6. A process according to claim 5, wherein the solvent is an aromatic hydrocarbon, an alcohol, an ether or a mixture thereof.
7. A process according to claim 1, 2 or 3 wherein the .alpha.-ketocarboxylic acid ester is a pyruvic acid ester, to obtain an optically active lactic acid ester.
8. A process according to claim 1, 2 or 3 wherein the .alpha.-ketocarboxylic acid ester is .alpha.-keto-.beta.,.beta.-dimethyl-?-butyrolactone to obtain an optically active pantoyl lactone.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20293/1977 | 1977-02-28 | ||
| JP2029377A JPS53105421A (en) | 1977-02-28 | 1977-02-28 | Preparation of optical active alpha-hydroxycarboxylic acid esters acid esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1109479A true CA1109479A (en) | 1981-09-22 |
Family
ID=12023106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA297,758A Expired CA1109479A (en) | 1977-02-28 | 1978-02-27 | PROCESS FOR PRODUCING OPTICALLY ACTIVE .alpha.- HYDROXYCARBOXYLIC ACID ESTER |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS53105421A (en) |
| CA (1) | CA1109479A (en) |
| CH (1) | CH635815A5 (en) |
| GB (1) | GB1592536A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4343741A (en) * | 1981-04-22 | 1982-08-10 | Hoffmann-La Roche Inc. | Chiral phosphines |
| US4539411A (en) * | 1982-02-05 | 1985-09-03 | Hoffmann-La Roche Inc. | Rhodium complexes of chiral phosphines |
| US5508435A (en) * | 1992-07-29 | 1996-04-16 | Merck & Co., Inc. | Asymmetric hydrogenation of beta- or gamma-ketoesters and beta- or gamma-ketoamides |
| CA2121308C (en) * | 1993-04-19 | 2001-07-24 | Toshihiro Omatsu | Rhodium-containing catalyst |
| EP2141145B1 (en) * | 2008-06-30 | 2013-02-20 | ThyssenKrupp Uhde GmbH | Efficient and highly enantioselective Rh-catalyzed hydrogenations of unsaturated lactate precursors with chiral bisphospholanes as ligands |
-
1977
- 1977-02-28 JP JP2029377A patent/JPS53105421A/en active Granted
-
1978
- 1978-02-27 CA CA297,758A patent/CA1109479A/en not_active Expired
- 1978-02-27 GB GB771178A patent/GB1592536A/en not_active Expired
- 1978-02-27 CH CH209078A patent/CH635815A5/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| GB1592536A (en) | 1981-07-08 |
| JPS5622859B2 (en) | 1981-05-27 |
| CH635815A5 (en) | 1983-04-29 |
| JPS53105421A (en) | 1978-09-13 |
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