Process for synthesis of enantiomerically enriched...

Details Process for synthesis of enantiomerically enriched... Process for synthesis of enantiomerically enriched...

2002-01-11

2002-12-10

Kumar, Shailendra (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

C560S155000, C568S008000, C568S012000, C556S136000

Reexamination Certificate

active

06492544

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for the synthesis of a &bgr;-amino acid by enantioselective catalytic hydrogenation of a prochiral N-acetylated &bgr;-aminoacrylic acid.
2. Discussion of the Background
Because of their structural similarity to a-amino acids, &bgr;-amino acids may exhibit quasi-analogous behavior. Thus, intensive research in the chemical and pharmaceutical industry has been focused on &bgr;-amino acids with the aim to synthesize new bioactive agents with improved characteristics. One of the areas receiving attention is the enantioselective synthesis of &bgr;-amino acids.
In a recently published article (J. Org. Chem. 1999, 64, 6907), Zhang et al. describe the enantioselective catalytic hydrogenation of N-acylated &bgr;-aminoacrylic acids with rhodium catalysts carrying chiral ligands such as BICP and MeDuPHOS. The significance of the teaching by Zhang et al. is that relatively high hydrogen pressures and nonpolar aprotic solvents, among other factors, appear to be most favorable for the enantioselective catalytic hydrogenation. Furthermore, only the Rh-BICP complex yields high enantiomeric excesses for the corresponding Z-isomer at high pressures close to 20 bar, whereas the Rh-MeDuPHOS catalyst achieves only moderate to poor values.
Noyori et al. have also performed corresponding hydrogenation experiments (Tetrahedron: Asymmetry 1991, 2, 543554), albeit with less favorable results.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a process for the synthesis of a &bgr;-amino acid that is readily applicable on an industrial scale and therefore superior to the known processes, particularly from the economic and ecological viewpoints.
It is another object of the present invention to provide a process for the synthesis of a &bgr;-amino acid that proceeds at a low hydrogen pressure and shorter hydrogenation times than known processes.
This and other objects have been achieved by the present invention the first embodiment which includes a process for synthesis of an enantiomerically enriched N-acylated &bgr;-amino acid, comprising:
enantioselectively catalytically hydrogenating a prochiral N-acylated &bgr;-aminoacrylic acid in a polar solvent;
wherein said by hydrogenating is carried out in the presence of a compound of formula (I)
wherein
each of R
1
, R
2
, R
3
, R
4
independently of one another represents C
1
-C
8
)-alkyl, (C
2
-C
8
)-alkoxyalkyl, (C
6
-C
18
)-aryl, (C
7
-C
19
)-aralkyl, (C
3
-C
3
-C
18
)-heteroaryl, (C
4
-C
19
)-heteroaralkyl, (C
1
-C
8
)-alkyl-(C
6
-C
18
)-aryl, (C
1
-C
8
)-alkyl-(C
3
-C
18
)-heteroaryl, (C
3
-C
8
)-cycloalkyl, (C
1-C
8
)-alkyl-(C
3
-C
8
)-cycloalkyl or (C
3
-C
8
)-cycloalkyl-(C
1
-C
8
)-alkyl; and
A represents a (C
2
-C
5
)-alkylene bridge, a 1,2-(C
3
-C
8
)-cycloalkylene bridge or a 1,3-(C
3
-C
8
)-cycloalkylene bridge, which can contain one or more double bonds and/or can be substituted with one or more (C
1
-C
8
)-alkyl, (C
1
-C
8
)-aryl, (C
1
-C
8
)-alkoxy, (C
2
-C
8
)-alkoxyalkyl, (C
6
-C
18
)-aryl or (C
3
-C
3
)-cycloalkyl and/or can contain a hetero atom selected form the group consisting of N, O, P and S in said aryl ring;
with the proviso that A is not permitted to be a 2,2′-(1,1′-binaphthylene) group.


REFERENCES:
patent: 6172249 (2001-01-01), Berens et al.
patent: WO 99/59721 (1999-11-01), None
K. Achiwa, et al., Tetrahedron Letters, No. 13, XP-002198461, pp. 1119-1120, “Catalytic Asymmetric Synthesis of Optically Active &bgr;-Amino Acids”, 1978.
G. Zhu, et al., J. Org. Chem., vol. 64, No. 18, XP-002198462, pp. 6907-6910, “Highly efficient Asymmetric Synthesis of &bgr;-Amino Acid Derivatives via Rhodium-Catalyzed Hydrogenation of &bgr;(Acylamino) Acrylates”, 1999.
W. D. Lubell, et al., Tetrahedron Asymmetry, vol. 2, No. 7, XP-001042293, pp. 543-554, “Enantioselective Synthesis of &bgr;-Amino Acids Based on Binap—Ruthenium (II) Catalyzed Hydrogenation”, 1991.
D. Heller, et al., J. Org. Chem., vol. 66, No. 20, XP-002198463, pp. 6816-6817, “Pressure Dependent Highly Enantioselective Hydrogenation of Unsaturated &bgr;-Amino Acid Precursors”, 2001.
Zhu et al, J. Org. Chem., vol. 64, pp. 6907-6910, 1999.

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