Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2002-05-13
2004-04-20
Kumar, Shailendra (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
Reexamination Certificate
active
06723871
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a practically valuable and novel process for producing an optically active alcohol, which comprises a step of subjecting a &bgr;-keto ester to an asymmetric reduction in the presence of an optically active catalyst.
BACKGROUND OF THE INVENTION
Hitherto, the following are known as methods for synthesizing optically active 4,4,4-trifluoro- or 4,4,4-trichloro-3-hydroxybutanoate esters: 1) a method of obtaining an optically active 4,4,4-trifluoro-3-hydroxybutanoate ester by selective enzymatic hydrolysis of the ester group of a 4,4,4-trifluoro-3-hydroxybutanoate ester, which is a racemic mixture, used as a starting material using a lipase and extraction of unhydrolyzed (R)-enantiomer (JP-A-8-289799); 2) a method of obtaining a hydrolyzed (R)-enantiomer by acetylation of the hydroxyl group of a 4,4,4-trifluoro-3-hydroxybutanoate ester, which is a racemic mixture, and successive enzymatic hydrolysis with a lipase (J. Org. Chem., Vol. 63, pp. 8058-8061 (1998)); 3) a method of obtaining an optically active 4,4,4-trifluoro-3-hydroxybutanoate ester by ester exchange through a reaction of an optically active 4,4,4-trifluoro-3-hydroxybutanoate ester with an alcohol in the presence of an ammonium salt of a sulfonic acid derivative (JP-A-3-151348); 4) a method of obtaining an optically active 4,4,4-trifluoro-3-hydroxybutanoate ester or 4,4,4-trichloro-3-hydroxybutanoate ester by reduction of a 4,4,4-trifluoro-3-oxobutanoate ester or 4,4,4-trichloro-3-oxobutanoate ester using baker's yeast (Tetrahedron Asymmetry, Vol. 9, pp. 285-292 (1997)); 5) a method of obtaining an optically active 4,4,4-trifluoro-3-hydroxybutanoate ester by asymmetric ester exchange of a 4,4,4-trifluoro-3-hydroxybutanoate ester, which is a racemic mixture, with a vinyl ester using an enzyme derived from a microorganism or wheat germ (JP-A-5-219986); 6) a method of obtaining an optically active 4,4,4-trifluoro-3-hydroxybutanoate ester by hydrogenation of a 4,4,4-trifluoro-3-oxobutanoate ester in the presence of a nickel catalyst supporting an optically active compound (JP-A-9-268146); 7) a method of obtaining an optically active 4,4,4-trichloro-3-hydroxybutanoate ester by asymmetric hydrogenation of a 4,4,4-trichloro-3-oxobutanoate ester using an optically active BINAP catalyst (JP-A-63-310847); 8) a method of conducting a reaction of a 4,4,4-trifluoro-3-hydroxybutanoate ester, which is a racemic mixture, with acetic anhydride using a lipase to obtain an unreacted 4,4,4-trifluoro-3-hydroxybutanoate ester as an optically active one (JP-A-3-254694); and so forth.
However, in the above synthetic methods of optically active alcohols, the following have been found to be problems: the synthetic methods using enzymes require tedious operations and process controls and have limitations on kinds of reaction substrates, and also alcohols having an absolute configuration are restricted to specific ones; in the case of using a 4,4,4-trifluoro-3-hydroxybutanoate ester, which is a racemic mixture, as a reaction substrate, the yield of optically active 4,4,4-trifluoro-3-hydroxybutanoate ester having a desired configuration is 50% or less; in the case of reducing a 4,4,4-trifluoro-3-oxobutanoate ester or a 4,4,4-trichloro-3-oxobutanoate ester using baker's yeast, the resulting 4,4,4-trifluoro-3-hydroxybutanoate ester or 4,4,4-trichloro-3-hydroxybutanoate ester has a low optical purity; and a 4,4,4-trifluoro-3-hydroxybutanoate ester or 4,4,4-trichloro-3-hydroxybutanoate ester obtainable by asymmetric hydrogenation using a nickel catalyst supporting an optically active compound or an optically active Ru-BINAP catalyst has an insufficient optical purity. In particular, in the fields of medicines and functional materials, it is important to obtain a compound having a specific absolute configuration in a good optical purity, and thus it is necessary to solve the problems in the above methods.
SUMMARY OF THE INVENTION
An object of the invention is to provide a novel production process capable of obtaining an optically active alcohol having a desired absolute configuration in a high optical purity by subjecting a &bgr;-keto ester such as a 3-perfluoroalkyl-3-oxopropionate ester or a 3-trichloroalkyl-3-oxopropionate ester to asymmetric reduction in simple and convenient operations.
Under such circumstances, as a result of extensive studies, the present inventors have found that, by subjecting a &bgr;-keto ester represented by the general formula (I) such as a 4,4,4-trifluoro-3-oxobutanoate ester or a 4,4,4-trichloro-3-oxobutanoate ester to hydrogen-transfer type asymmetric reduction in the presence of an optically active ruthenium-diamine complex represented by the general formula (II), a corresponding optically active alcohol is obtained in a high optical purity. Based on a result of further examinations, they have accomplished the invention.
Heretofore, the methods of obtaining an optically active hydroxy compound by subjecting a carbonyl compound to asymmetric hydrogen-transfer type reduction using an optically active ruthenium-diamine complex represented by the general formula (II) have been known (JP-A-10-236986, J. Am. Chem. Soc., Vol. 118, pp. 2521-2522 (1996)). However, these methods are a method for producing an optically active alcohol having an acetylene bond by subjecting a carbonyl compound having an acetylene bond to asymmetric hydrogen-transfer type reduction and a method of an optically active hydroxy compound by subjecting a carbonyl compound such as an aryl alkyl ketone to asymmetric hydrogen-transfer type reduction. Although a description of a &bgr;-keto acid derivative exists in JP-A-10-236986, there is no concrete example with regard to the compound and also, when an acetoacetate ester as a &bgr;-keto acid derivative has been subjected to asymmetric reduction using an optically active ruthenium-diamine complex, no reduction has proceeded. However, the inventors have found that, in the case that a 4,4,4-trifluoro-3-oxobutanoate ester or a 4,4,4-trichloro-3-oxobutanoate ester is subjected to an asymmetric hydrogen-transfer type reduction, a corresponding optically active alcohol is obtained in a high optical purity, and as a result of further extensive examinations, they have accomplished the invention.
Namely, the invention relates to:
(1) a process for producing an optically active alcohol represented by the general formula (III):
(wherein * represents an asymmetric carbon atom, R
1
represents a C
1
-C
10
linear or branched perfluoroalkyl or perchloroalkyl group and R
2
represents a C
1
-C
6
lower alkyl group or benzyl group which may have a substituent), which comprises a step of subjecting a &bgr;-keto ester represented by the general formula (I):
(wherein R
1
and R
2
each has the same meaning as described above) to a hydrogen-transfer reaction in the presence of an optically active ruthenium-diamine complex represented by the general formula (II):
(wherein * represents an asymmetric carbon atom, R
3
and R
4
are the same or different and each represents an alkyl group or phenyl group or a cycloalkyl group which may have an alkyl group, or R
3
and R
4
may form an alicyclic ring unsubstituted or substituted by an alkyl group together with adjacent carbon atoms, R
5
represents methanesulfonyl group; trifluoromethanesulfonyl group; benzene sulfonyl group or naphthyl group which may be substituted by an alkyl group, an alkoxy group, or a halogen atom; camphorsulfonyl group; an alkoxycarbonyl group; or benzoyl group which may be substituted by an alkyl group, R
6
represents hydrogen atom or an alkyl group, Ar represents an aromatic compound which may be substituted by an alkyl group, and X represents a halogen atom),
(2) the process for producing an optically active alcohol as described in above (1), wherein R
1
is a C
1
-C
7
linear or branched perfluoroalkyl or perchloroalkyl group,
(3) the process for producing an optically active alcohol as described in above (1), wherein R
3
and R
4
of the optically active ruthenium-diamine complex (II) ar
Miura Takashi
Tada Ken-ichi
Kumar Shailendra
Takasago International Corporation
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