Catalyst – solid sorbent – or support therefor: product or process – Catalyst or precursor therefor – Organic compound containing
Reexamination Certificate
1998-05-19
2001-04-10
Bell, Mark L. (Department: 1755)
Catalyst, solid sorbent, or support therefor: product or process
Catalyst or precursor therefor
Organic compound containing
C502S162000, C585S277000
Reexamination Certificate
active
06214763
ABSTRACT:
FIELD OF THE INVENTION AND PRIOR ART
The present invention relates to the field of asymmetric hydrogenation and, more particularly, to the use of novel Ru chiral catalysts for the asymmetric hydrogenation of substrates which, as a result of their weak donor capability and of their hindered structures, have proved heretofore very difficult or impossible to hydrogenate.
A great number of chiral metal catalysts has been used in the past to asymmetrically hydrogenate a variety of substrates.
In the context of the present invention, we can cite in particular the efforts of two research groups which actively studied the synthesis of Ru chiral catalysts, obtained from the Ru(II) complex of formula [(COD)Ru(2-methylallyl)
2
] (COD═cyclo-1,5-octadiene).
Thus, J.-P. Genet and his collaborators have published work related to catalysts of formula [Ru(P*-P*)(2-methylallyl)
2
], wherein P*−P* represents a diphosphine ligand of the type of those currently known under abbreviated designations such as DIOP, CHIRAPHOS, PROPHOS, BDPP, CBD, NORPHOS, DEGUPHOS, BPPM, BINAP, R-DuPHOS (R═methyl or ethyl), BIPHEMP or yet DIPAMP (see, for example, J.-P. Genet et al., Tetrahedron: Asymmetry 1991, 2, 43). Such catalysts were obtained by heating the above-mentioned Ru(II) complex together with the appropriate chelating diphosphine, in a solvent such as hexane or toluene, such as to replace the cyclooctadiene with the chiral phosphine.
Upon subsequent work (see, for example, WO 91/02588; J.-P. Genet, Acros Organics Acta, 1994, 1, 1-8; J.-P. Genet et al., Tetrahedron: Asymmetry, 1994, 5, 665-690), these authors described the transformation of such catalysts via protonation by means of aqueous acids such as HBr, HCl, HF or HBF
4
, in strongly coordinating solvents, capable of playing a role in stabilizing the coordination structure around the metal, which structure, according to the same authors, is of the hexacoordinate type. This kind of catalysts, which can be prepared in situ, proved to be useful for the asymmetric hydrogenation, in protic or strongly electron-donating solvents (methanol, ethanol or their mixtures with other solvents), of substrates comprising carbonyl groups and acyclic ethylenic bonds.
Other studies (see, for example, F. Heiser et al., Tetrahedron: Asymmetry, 1991, 2, 51-62; EP 643 052; EP 398 132; EP 570 674) have resulted in reports of the use of catalysts prepared in situ for hydrogenating a variety of substrates, starting from the same ruthenium complex, but following a process according to which a mixture of said complex and an appropriate diphosphine ligand is treated with namely CF
3
COOH, once again in an electron-donor solvent able to stabilize the coordinating structure of the metal.
These catalysts, and others obtained according to similar processes described in the cited references, reveal themselves very efficient in the asymmetric hydrogenation of various substrates, often good electron-donor substrates capable of coordinating the Ru, and are typically used with protic solvents, or mixtures of protic and aprotic solvents. However, they proved to be inefficient when used, under the prior art conditions, for the hydrogenation of substrates possessing heavily hindered ethylenic bonds, for example tetrasubstituted double bonds, in particular when the latter are part of ring systems.
In published International patent application N° WO 97/18894, filed on Nov. 20, 1996, we describe new Ru catalysts and teach their successful use for asymmetrically hydrogenating this type of particularly hindered substrates. More particularly, there is described the hydrogenation of cyclopentenone derivatives of formula (II)
wherein R
1
represents a linear or branched C
1
to C
4
alkyl radical and R
2
represents a saturated or unsaturated, linear or branched, C
1
to C
8
hydrocarbon radical, the hydrogenation of which had proved impossible until our discovery of novel catalysts obtained by an original process.
The catalysts described in the above-mentioned patent application were obtained by a method which comprised treating equimolar amounts of an appropriate Ru complex, for example [(COD)Ru(2-methylallyl)
2
] and a chelating diphosphine with an acid of formula HX, wherein X is a non-coordinating anion, said acid being used in a ratio not exceeding 2 molar equivalents per mole of the Ru complex and the treatment being carried out in a non-coordinating or weakly coordinating medium, under an inert atmosphere.
Such catalysts were able to successfully hydrogenate substrates (formula II), amongst others, to provide their corresponding saturated homologues in strictly cis-configuration and with an enantiomeric excess of at least 60% in the (+)-1R-isomer. Such catalysts, and their use in asymmetric hydrogenation reactions, provided a breakthrough of outstanding importance for the single-step conversion of unsaturated substrates which had previously proved impossible to hydrogenate, into their saturated homologues. Moreover, their use in the conversion of substrates (formula II) proved particularly valuable in the case of methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate, the asymmetric hydrogenation of which provided, in a single step, the preferred optically active isomer of methyl dihydrojasmonate or Hedione® (origin: Firmenich S A, Geneva, Switzerland), a well-known and widely used perfume ingredient.
In fact, amongst the four possible Hedione® stereoisomers, methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate is known to develop at their best the odor characters, and namely the jasmine note, for which Hedione® is notorious, while the strength of this isomer's odor is also superior to that of the other isomers by several orders of magnitude. Therefore, the production of methyl (+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate in an optically pure state, or of isomer mixtures which contain essentially this isomer, is of capital importance in the fragrance industry.
DESCRIPTION OF THE INVENTION
One object of the present invention is a ruthenium catalyst obtainable by a process which comprises putting into contact an appropriate Ru complex, a chelating diphosphine and an acid comprising a non-coordinating anion, said Ru complex and chelating diphosphine being present in equimolar amounts, the contact occurring in a non-coordinating or weakly coordinating medium and under an oxygen-free atmosphere, wherein the acid comprising the non-coordinating anion is used in an amount of about 1 molar equivalent per mole of the Ru complex.
Reference to “about 1 molar equivalent of acid per mole of Ru complex” signifies here a molar ratio between these two components which does not significantly differ from 1, and is preferably comprised within a range of between 0.95 and 1.10, more preferably from 1.0 to 1.10.
The above-mentioned catalysts of the invention provide surprisingly good results when used in the hydrogenation of substrates (formula II) in particular, but can also be conveniently used for the hydrogenation of substrates of general formula (III)
as defined in claim
12
. Preferred embodiments of the hydrogenation process of the invention relate to the hydrogenation of substrates (formula III) having a carbon-carbon double bond in one of the positions indicated by the dotted lines which is at least trisubstituted, i.e. not more than one amongst the R
2
, R
3
and R
4
groups represents hydrogen.
It will be apparent to the person skilled in the art from the disclosure which follows that the catalysts of the invention can also be successfully used in the hydrogenation of ethylenic bonds less sterically hindered than those of preferred substrates (formula III) described above. However, they are most advantageously used in the one-step conversion of the preferred substrates (III) defined above into their saturated homologues, as is apparent hereafter, particularly those wherein the double bond is tetrasubstituted.
We have in fact ascertained that the catalysts of the invention can be successfully and generally used in asymmetric hydroge
Dobbs Daniel A.
Trauch Valentin Rautens
Vanhessche Koenraad P. M.
Bell Mark L.
Firmenich SA
Pasterczyk J.
Pennie & Edmonds LLP
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