Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
2002-02-19
2004-01-27
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C562S480000, C562S553000
Reexamination Certificate
active
06683208
ABSTRACT:
The present invention relates to optically active diphosphines. It is also targeted at their preparation according to a process for the resolution of the racemic mixture of the said phosphines to optically active isomers.
More precisely, the subject of the invention is new optically active bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] diphosphines and the process for the resolution of the racemic bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] mixture.
The invention also relates to new optically active metal complexes comprising the said phosphines and to their use in a process for the preparation of optically active carboxylic acids and/or derivatives according to a process for the hydrogenation of &agr;,&bgr;-unsaturated carboxylic acids and/or derivatives.
The preparation of a mixture of bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] diastereoisomers has been described by F. Mathey et al. in Bull. Soc. Chim. Fr., 129, pp. 1-8 (1992).
The starting material in the synthesis of the latter is 1-phenyl-3,4-dimethylphosphole (II) described by F. Mathey et al. in Synthesis, 1983, pp. 983.
The starting point is the preparation of 3,3′,4,4′-tetramethyl-1,1′-diphosphole (IV). To this end, 1-phenyl-3,4-dimethylphosphole (II) is reacted in THF with lithium metal according to the following reaction:
At the end of the reaction, aluminium chloride is introduced in order to trap the phenyllithium produced during the reaction.
In a following stage, (III) is dimerized by the action of diiodine I
2
in THF. For more details on the preparation of (IV), reference may be made to the article by F. Mathey et al., Organometallics, 1983, 2, 1234.
On heating to approximately 140° C., the compound (IV) rearranges to (V), which reacts with diphenylacetylene according to the Diels-Alder reaction, to give bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene].
A practical embodiment is given on page 6 of the publication by F. Mathey et al. in Bull. Soc. Chim. Fr., 129, pp. 1-8 (1992).
However, the writers obtained, as mentioned on page 3, right-hand column, lines 7 and 8, a mixture of two diastereoisomers subsequently identified by the Applicant Company as being a meso (I m)—RS,SR—and a racemate (I r)—RR,SS—called (13b) and (13a) respectively in the article.
The publication mentions the separation of the two diastereoisomers by formation of a palladium(II) chelate. To do this, a description is given of the separation of the mixture of diastereoisomers obtained by reaction with PdCl
2
(PhCN)
2
in dichloroethane, resulting in (VI m) and (VI r), and the separation by chromatography on silica gel, followed by elution and then by a decomplexation carried out by NaCN.
The two diastereoisomers, on the one hand the meso (I m) and, on the other hand, the racemate (I r), are thus recovered separately.
The document of the state of the art does not describe the separation of the enantiomers.
The problem of resolving two enantiomers is difficult to solve when the chirality is carried by the phosphorus.
An object of the present invention is to provide new, bidentate, optically active disphosphines which are chiral on the phosphorus and which cannot be racemized.
Another object of the present invention is to make available a process which makes it possible to obtain them according to a process for resolving the racemic bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] mixture.
Finally, another object of the invention is to have available a process for the preparation of optically active carboxylic acids and/or derivatives according to a process for the hydrogenation of &agr;,&bgr;-unsaturated carboxylic acids and derivatives which makes use of metal complexes using the optically active diphospine as ligand.
According to a first subject of the present invention, new optically active bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] diphosphines have been found which correspond to the following formulae:
According to another subject of the invention, the racemic bis[1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene] mixture is resolved according to a process which comprises reacting it with a palladium and/or platinum complex as chiral auxiliary in an organic solvent, thus forming diastereoisomer complexes, and then resolving the said optically pure complexes.
In accordance with the process of the invention, a palladium complex is used. This type of chiral auxiliary is widely described in the literature, in particular by Sei Otsuka et al. in Journal of the American Chemical Society, 93, pp. 4301 (1971).
A platinum complex can also be used and reference may more particularly be made to the work by A. C. Cope [Journal of the American Chemical Society, 90, pp. 909 (1968)].
The chiral complex used more particularly corresponds to the general formula (VII):
in the said formula:
M represents palladium and/or platinum,
R
1
, R
2
, R
3
and R
4
represent a hydrogen atom or an alkyl radical having from 1 to 10 carbon atoms or a cycloalkyl radical having from 3 to 10 carbon atoms,
R
3
and R
4
are different and at least one of the two represents a hydrogen atom,
R has the meaning given for R
1
, R
2
, R
3
and R
4
,
X represents a halogen atom,
n is a number from 0 to 4,
when n is greater than 1, two R radicals and the 2 successive atoms of the benzene ring can form, between them, a ring having from 5 to 7 carbon atoms.
More preferentially, the complex used corresponds to the abovementioned formula in which R
1
, R
2
, R
3
and R
4
represent a hydrogen atom or a methyl radical, X represents a chlorine atome and n is equal to 0.
When n is equal to 2, two R radicals form a benzene ring.
Mention may be made, as more specific examples of palladium complexes which are suitable for the present invention, obtained without distinction from (R)-(+)- or (S)-(−)-N,N-dimethylphenylethylamine, of:
The amount of complex of the abovementioned metals, expressed as metal, is generally from 0.5 to 1 metal atom per phosphorus atom.
An organic solvent is used which dissolves all the reactants. The solvent must be inert with respect to the diphosphine.
Mention may be made, as non-limiting examples of solvents which are suitable in the process of the invention, of:
aliphatic hydrocarbons and more particularly paraffins such as, in particular, pentane, hexane, heptane, octane, isooctane, nonane, decane, undecane, tetradecane, petroleum ether and cyclohexane; aromatic hydrocarbons such as, in particular, benzene, toluene, xylenes, ethylbenzene, diethylbenzenes, trimethylbenzenes, cumene, pseudocumene or petroleum fractions composed of a mixture of alkylbenzenes, in particular fractions of Solvesso® type,
halogenated aliphatic or aromatic hydrocarbons, and mention may be made of: perchlorinated hydrocarbons such as, in particular, trichloromethane or tetrachloroethylene; partially chlorinated hydrocarbons, such as dichloromethane, dichloroethane, tetrachloroethane, trichloroethylene, 1-chlorobutane or 1,2-dichlorobutane; or monochlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene or mixtures of different chlorobenzenes.
Benzene and toluene are preferred among all these solvents.
The concentration of the diphosphine in the reaction solvent is preferably between 0.05 and 1 mol/liter and more particularly still between 0.05 and 0.2 mol/liter.
Separation is advantageously carried out at ambient temperature, generally between 15° C. and 25° C.
It preferably takes place under a controlled atmosphere of inert gases. A rare gas atmosphere, preferably of argon, can be set up but it is more economical to use nitrogen.
A mixture of complexes of palladium or platinum and of diphosphine corresponding to each enantiomer is obtained.
Another subject of the invention is the intermediate product, namely the metal complex with the diphosphines of formula:
in the said formulae M represents palladium or platinum, X a halogen atom, preferably chlorine, and A symbolizes the residue of a chiral metal complex c
Mathey Francois
Mercier Francois
Robin Frederic
Spagnol Michel
Rhone-Poulenc Chimie
Vollano Jean F.
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