Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
1998-11-06
2001-04-24
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C546S150000, C549S404000, C564S012000, C564S092000
Reexamination Certificate
active
06222072
ABSTRACT:
TECHNICAL FIELD
This invention relates to a process for producing an optically active amine. More specifically, this invention relates to a process for producing an optically active amine which is adapted for use as an intermediate in synthesizing physiologically active compounds such as pharmaceuticals and agricultural chemicals, as a functional material such as a liquid crystal, and as a starting material in synthesizing fine chemicals.
BACKGROUND TECHNOLOGY
A common process for producing an optically active amine is the process wherein a nitrogen functional group is introduced in an optically active alcohol by substitution reaction (See, for example, C. P. Chen et al., Tetrahedron Lett., 32, 7175 (1991); A. S. Thompson et al., J. Org. Chem. 58, 5886 (1993), etc) This process, however, is associated with a safety problem due to the use of an azide compound which suffer from the risk of explosion, and as a consequence, the control of the production process was complicated.
In view of such situation, various production processes have been proposed wherein an optically active amine compound is directly produced from the corresponding imine by an asymmetric reducing reaction. (For a general review, see, for example, Shohei HASHIGUCHI et al., Journal of Synthetic Organic Chemistry Japan, 55, 99 (1997)). A known process is the process wherein an imine is asymmetrically hydrogenated by using a rhodium, iridium or titanium complex having a chiral ligand. This process, however, required use of hydrogen atmosphere at a pressure as high as 40 to 130 atm., and the preparation of the catalyst was quite complicated.
Another process is the hydride reducing process wherein an imine is reduced by using an optically active metal hydride comprising a metal hydride complex compound such as lithium aluminum hydride or sodium borohydride or a metal hydride such as diborane modified with an optically active protonic compound. Exemplary such process is asymmetric hydride reduction process using an optically active hydride modified with an optically active alcohol, amine, or amino alcohol. This process, however, requires the use of an equivalent amount of the optically active compound.
In view of such situation, many investigations have been conducted to develop a hydride reducing process wherein the asymmetricity source of only catalytic amount is required. For example, in a process using oxazaborolidine complex, an asymmetric reducing reaction using a catalytic amount of the oxazaborolidine complex is realized as in the case of the asymmetric reducing reaction of a ketone. However, when the amount of the asymmetricity source, namely, the complex is reduced from the equivalent amount to the catalytic amount in this process, the resulting product suffers from significantly reduced optical purity. In addition, use of the borane-sulfide complex for the reducing agent also resulted in the complexity of the process, requiring countermeasures for safety, odor, and the like.
SUMMARY OF THE INVENTION
In view of such situation, an object of the present invention is to provide a novel process for producing an optically active amine which is adapted for use as an intermediate in synthesizing physiologically active compounds such as pharmaceuticals and agricultural chemicals, as a functional material such as a liquid crystal, and as a starting material in synthesizing fine chemicals, and such an optically active amine is produced by using a hydride reducing agent which is convenient to handle, and at a high catalytic efficiency through use of a catalytic amount of a chiral auxiliary.
To solve such situation, the inventors of the present invention have made an intensive study on the production of the optically active amine from an imine by using hydride reducing agents with good handling convenience. As a result of such study, the inventors found that the object as described above can be accomplished by the reaction using an optically active metal compound for the catalyst.
In order to solve the situation as described above, there is provided according to the present invention a process for producing an optically active amine comprising the step of reacting an imine with a hydride reagent in the presence of an optically active metal compound.
The present invention also provides a process for producing an optically active amine comprising the step of reacting an imine with a hydride reagent in the presence of an optically active metal compound and an alcohol compound.
The present invention also provides a process for producing an optically active amine comprising the step of reacting an imine with a hydride reagent in the presence of an optically active metal compound and a carboxylic acid compound.
The present invention also provides a process for producing an optically active amine comprising the step of reacting an imine with a hydride reagent in the presence of an optically active metal compound, an alcohol compound and a carboxylic acid compound.
In the process of the present invention, the optically active metal compound used for the catalyst is preferably an optically active cobalt (II) complex.
In the process of the present invention, it is particularly preferable that the optically active cobalt (II) complex comprises a compound represented by the following general formula (a):
wherein R
1
and R
2
are different from each other, and are independently hydrogen atom, a straight chain or branched alkyl group or an aryl group which may be optionally substituted with a substituent; and R
1
and R
1
or R
2
and R
2
may together form a ring; and R
3
, R
4
and R
5
are the same or different from each other, and are independently hydrogen atom, a straight chain or branched alkyl group, an aryl group, an acyl group, or an alkoxycarbonyl group which may be optionally substituted with a substituent; and R
4
, R
5
, and the carbon atoms having R
4
and R
5
bonded thereto may together form a ring.
BEST MODE FOR CARRYING OUT THE INVENTION
Next the process for producing an optically active amine according to the present invention (hereinafter referred to as “the process of the present invention”) is described in detail.
It should be noted that the language “a process . . . comprising the step of reacting an imine with a hydride reagent in the presence of an optically active metal compound” means either that the process consists of the step of reacting an imine with a hydride reagent in the presence of an optically active metal compound, or that the process comprises such step and one or more other steps.
In the process of the present invention, the imine used for the starting material is not limited to any particular type as long as the imine used is a prochiral compound which has a carbon-nitrogen double bond, and the imine used may be adequately selected in accordance with the desired optically active amine.
The process of the present invention is particularly suitable for producing the optically active amine by using the imine represented by the following general formula (b):
for the starting material to thereby produce the corresponding optically active amine.
In the formula (b), R
6
, R
7
, R
8
and R
9
may be the same or different from each other, and may be hydrogen atom, a halogen atom, nitro group, nitroso group, cyano group, an alkoxy group, an aryloxy group, silyl group, an alkoxycarbonyl group, thiocarbonyl group, an alkoxythiocarbonyl group, an amino group, an amine oxide group, a hydrazine group, a hydrazone group, an acylhydrazone group, a sulfide group, a sulfinyl group, a sulfonyl group, a phosphino group, a phosphinyl group, a phosphorus group, an acyl group, a straight chain or branched alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, or an aryl group, which may be optionally substituted with a substituent. Typical halogen atoms for the R
6
, R
7
, R
8
and R
9
include fluorine, chlorine and bromine; and typical alkoxy groups include methoxy group, ethoxy group, and benzyloxy group. Typical aryloxy groups include phenoxy group, and typical alkoxycarbonyl groups include m
Mukaiyama Teruaki
Nagata Takushi
Sugi Kiyoaki
Yamada Toru
Barts Samuel
Birch & Stewart Kolasch & Birch, LLP
Mitsui Chemicals Inc.
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