Process for production of optically active aminophosphinylbutanoic acids

1. A process for producing optically active aminophosphinylbutanoic acids represented by the formula (2):

wherein R 1 represents an alkyl group having 1 to 4 carbon atom(s), R 2 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atom(s), R 3 represents an alkyl group having 1 to 4 carbon atom(s), an alkoxy group having 1 to 4 carbon atom(s),

an aryl group, an aryloxy group, or a benzyloxy group, and R 4 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atom(s); and * represents an asymmetric carbon atom, comprising asymmetrically hydrogenating a compound represented by the formula (1):

wherein R 1 represents an alkyl group having 1 to 4 carbon atom(s), R 2 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atom(s), R 3 represents an alkyl group having 1 to 4 carbon atom(s), an alkoxy group having 1 to 4 carbon atom(s), an aryl group, an aryloxy group, or a benzyloxy group, and R 4 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atom(s) in the presence of a ruthenium-optically active phosphine complex, wherein the optically active phosphine compound constituting the ruthenium-optically active phosphine complex is an optically active substance of phosphine represented by the formula (3):

wherein each of R 5 , R 6 , R 7 , and R 8 independently represents a phenyl group that may be substituted with a substituent selected from a group consisting of a halogen atom, a lower alkyl group, and a lower alkoxy group, a cyclopentyl group, or a cyclohexyl group, or the formula (4):

wherein each of R 9 , R 10 , R 11 , and R 12 independently represents a phenyl group that may be substituted with a substituent selected from a group consisting of a halogen atom, a lower alkyl group, and a lower alkoxy group, a cyclopentyl group, or a cyclohexyl group; R 13 , R 14 , 16 , and 17 independently represent a hydrogen atom, an alkyl group, an alkoxy group, an acyloxy group, a halogen atom, a haloalkyl group, or a dialkylamino group, and R 15 and R 18 represent an alkyl group, an alkoxy group, an acyloxy group, a halogen atom, a haloalkyl group, or a dialkylamino group; two of R 13 , R 14 , and R 15 may form a methylene chain that may have a substituent or a (poly)methylenedioxy group that may have a substituent and two of R 16 and R 17 and R 18 may form a methylene chain that may have a substituent or a (poly)methylenedioxy group that may have a substituent; and further, R 15 and R 18 may form a methylene chain that may have a substituent or a (poly)methylenedioxy group that may have a substituent.

2. The process according to claim 1 , wherein the ruthenium-optically active phosphine complex is a complex represented by the following formula (5):

(Ru a W b X c L d ) e Y f Z g   (5)

wherein L represents the optically active substance of phosphine represented by the formula (3) or (4) as in claim 1 ; X represents chlorine (Cl), bromine (Br), or iodine (I); and further, combinations of values represented by a, b, c, d, e, f, and g and substances represented by W, Y, and Z are any of the combinations listed in i) to vi):

i) a=2, b=0, c=4, d=2, e=1, f=1, g=0, and Y represents N(CH 2 CH 3 ) 3 ;

ii) a=1, b=1, c=1, d=1, e=1, f=1, g=0, W represents benzene, p-cymene, or mesitylene, and Y represents chlorine (Cl), bromine (Br), or iodine (I);

iii) a=1, b=0, c=1, d=1, e=2, f=3, g=1, Y represents (μ-Cl), (μ-Br), or (μ-I), and Z represents (CH 3 ) 2 NH 2 or (CH 3 CH 2 ) 2 NH 2 ;

iv) a=1, b=2, c=0, d=1, e=1, f=0, g=0, and W represents CH 3 CO 2 or CF 3 CO 2 ;

v) a=1, b=1, c=1, d=2, e=1, f=0, g=0, W represents hydrogen (H);

vi) a=3, b=0, c=5, d=3, e=1, f=1, g=0, Y represents chlorine (Cl), bromine (Br), or iodine (I).

3. The process according to claim 1 , wherein the optically active phosphine compound constituting the ruthenium-optically active phosphine complex has a bidentate coordination property and at the same time an axial asymmetry.

4. The process according to claim 1 , wherein the asymmetric hydrogenation is carried out in the presence of a base compound.

5. The process according to claim 2 , wherein the asymmetric hydrogenation is carried out in the presence of a base compound.

6. The process according to claim 3 , wherein the asymmetric hydrogenation is carried out in the presence of a base compound.

7. The process according to claim 4 , wherein the base compound is selected from the group consisting of a carbonate of an alkaline metal or alkaline earth metal; an alkoxide or phenoxide of an alkaline metal; and a hydroxide of an alkaline metal or an alkaline earth metal.

8. The process according to claim 5 , wherein the base compound is selected from the group consisting of a carbonate of an alkaline metal or alkaline earth metal; an alkoxide or phenoxide of an alkaline metal; and a hydroxide of an alkaline metal or an alkaline earth metal.

9. The process according to claim 6 , wherein the base compound is selected from the group consisting of a carbonate of an alkaline metal or alkaline earth metal; an alkoxide or phenoxide of an alkaline metal; and a hydroxide of an alkaline metal or an alkaline earth metal.

10. The process according to claim 1 , wherein the amount of the ruthenium-optically active phosphine complex is about 1/200 to 1/10000 in a molar ratio to aminophosphinylbutenoic acids represented by the formula (1).

11. The process according to claim 2 , wherein the ruthenium-optically active phosphine complex is a complex selected from the group consisting of [RuCl (p-cymene)((S)-binap)]Cl, [RuCl((R)-segphos)] 2 (μ-Cl) 3 (Et 2 NH 2 ), [RuCl ((R)-t-binap)] 2 (μ-Cl) 3 (Et 2 NH 2 ) and [RuCl (p-cymene)((R)-binap)]Cl.