Phosphine ligands with amino acid groups, method for their...

Details Phosphine ligands with amino acid groups, method for their... Phosphine ligands with amino acid groups, method for their...

1999-12-10

2001-10-09

Killos, Paul J. (Department: 1623)

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

Organic compounds

Carboxylic acids and salts thereof

C562S443000, C560S105000

Reexamination Certificate

active

06300517

ABSTRACT:

The present invention relates to new chiral phosphine ligands containing amino acid groups, a process for preparing them and their use as catalyst constituents.
Phosphines have generally found a wide variety of uses in industry. They are suitable, for example, as antioxidants, metal extractants, flame retardant impregnants, stabilizers for olefins and trioxane, as starting compounds for Wittig reagents and as ligands for metal complex catalysts. Owing to their wide variety of forms, they also represent intermediates for the preparation of further organic compounds which may or may not contain phosphorus.
Since the phosphines contain a trivalent phosphorus atom in the molecule, they display complexing properties toward numerous metals and metal ions, particularly those from the transition series, which can be utilized for preparing corresponding metal complex catalysts which are employed in industrial processes.
Of particular importance is the development of ligands for catalyst systems which are used, for example, in the hydroformylation of olefins. Here, catalyst systems containing tertiary phosphines or phosphites as ligands have been found to be particularly useful.
Further phosphines which are of interest are those which are suitable for preparing chiral metal complexes. Examples of known phosphines of this type are the diphosphine S,S-2,4-bis[bis-(p-N,N-dimethylamino-phenyl)phosphino]pentane (Catalysis Letters 5 (1990) 183-188) and also N,N-dimethyl-[2-(diphenylphosphino)phenyl]-1(R)-ethylamine (Can. J. Chem. 64, (1986), 1930-1935). The Pt and Rh complexes of 2S,4S-(N-tert-butoxycarbonyl)-4-diphenylphosphino-2-[(di-tert-butylphosphino)methyl]-pyrrolidines and the corresponding dibenzophospholyl derivatives are active catalysts for the enantioselective hydroformylation of vinylaromatics and the enantioselective hydrogenation of prochiral olefins (Organometallics, 10 (1991), 1183-1189; J. Org. Chem. 45 (1990), 4728-4739). Rh(l) complexes of amphiphilic bidentate phosphines such as 2,2′-bis[phenyl(3-pyridyl)phosphinomethyl]-1,1′-biphenyl have been used for the hydroformylation of 1-octene. Owing to their amphiphilic character, these ligands can be recovered from the reaction mixtures by acid extraction (J. Chem. Soc., Dalton Trans. (1996), 2143-2154). Thiophosphorylprolines, thiophosphorylphenylglycines and thiophosphorylphenylalanines have been used as building blocks for the synthesis of phosphinyl-substituted peptides. Their Rh(l) complexes are of interest as novel bioconjugated and immobilized catalysts (Angew. Chem., 108 (1996), 963-966; J. Org. Chem. 61, (1996), 2922-2923).
In view of the particular importance of chiral phosphines, there is interest in preparing new compounds of this group, not only to supplement the range of possible applications but also to enrich and expand the range by varying material properties and structural features.
This object is achieved by compounds of the formula I
where
R
1
is hydrogen, a C
1
-C
7
-alkyl radical, a C
6
-C
10
-aryl radical or a monovalent metal, preferably sodium or potassium,
R
2
is hydrogen or a C
1
-C
7
-alkyl radical,
R
3
is hydrogen or an —NR
5
R
6
radical, where R
5
and R
6
are identical or different and are hydrogen or C
1
-C
7
-alkyl or C
6
-C
10
-aryl radicals,
R
4
is a C
1
-C
7
-alkyl or C
6
-C
10
-aryl radical and
m is 0 or 1.
Preferred compounds of the formula I are phosphinophenyl-substituted amino acids of the formula II based on phenylglycine
where R
2
is hydrogen or methyl and R
4
is a C
1
-C
7
-alkyl or phenyl radical and the phosphinophenyl radical —PPh(R
4
) is located in the ortho or para position relative to the amino acid substituent —C(NH
2
)(R
2
)(COOH).
As compounds of the formula I, preference is also given to phosphinophenyl-substituted amino acids of the formula III based on phenylalanine
where R
2
is hydrogen or a C
1
-C
7
-alkyl radical, in particular methyl, and R
4
is a C
1
-C
7
-alkyl or phenyl radical and the phosphinophenyl radical —PPh(R
4
) is located in the ortho or para position relative to the amino acid substituent —CH
2
—C(NH
2
)(R
2
)(COOH).
The invention also provides a process for preparing compounds of the formula I by reaction of fluorophenyl-substituted compounds of the formula IV
where
R
2
is hydrogen or a C
1
-C
7
-alkyl radical,
R
3
is hydrogen or an —NR
5
R
6
radical, where R
5
and R
6
are identical or different and are hydrogen or C
1
-C
7
-alkyl or aryl radicals,
m is 0 or 1 and
M is sodium or potassium,
with a phosphide of the formula V
Ph(R
4
)PM  V
where
R
4
is a C
1
-C
7
-alkyl or C
6
-C
10
-aryl radical, in particular a phenyl radical, and
M is sodium or potassium,
and subsequent acid hydrolysis of the reaction mixture.
The reaction is usually carried out in an organic polar aprotic solvent such as 1,2-dimethoxyethane or tetrahydrofuran at a temperature of 80-120° C.
Preference is given to reacting sodium or potassium salts of 4-fluoro-&agr;-phenylglycine (IVa), 4-fluoro-&agr;-phenyl-&agr;-methylglycine (IVb) and &bgr;-(4-fluorophenyl)-&agr;-alanine (IVc) as compounds of the formula IV with the potassium phosphides Ph(R
4
)PK as compounds of the formula V, where R
4
is a C
1
-C
7
-alkyl or phenyl radical.
While the sodium and potassium salts of 4-fluoro-&agr;-phenylglycine (IVa) and &bgr;-(4-fluorophenyl)-&agr;-alanine (IVc) are commercially available substances, the sodium or potassium salts of 4-fluoro-&agr;-phenyl-&agr;-methylglycine (IVb) can be prepared via a Bucherer reaction by reacting 4-fluoroacetophenone with potassium cyanide and ammonium carbonate to form a hydantoin of the formula VI as intermediate,
which is hydrolyzed using aqueous sodium hydroxide.
The novel compounds of the formula I are suitable as ligands for metal complexes which can be used as catalysts for reactions to form C—C, C—H, C—N, C—Si or C═O bonds.


REFERENCES:
Gilbertson et al., “Palladium . . . Amino Acids”, J. Org. Chem. vol. 61, 1996, pp. 2922-2923.
Tepper et al, “A Systematic . . . Moieties”, Tetrahedron Letters, vol. 38, No. 13, Mar. 1997, pp. 2257-2258.

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