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Novel bisphosphane catalysts
The present invention relates to novel bisphosphane catalysts. In particular, the invention relates to catalysts of the general formula (I).
Enantiomerically enriched chiral ligands are employed in asymmetric synthesis and asymmetric catalysis. It is essentially a matter here of optimum matching of the electronic and the stereochemical properties of the ligands to the particular catalysis problem. An important aspect of the success of these classes of compounds is attributed to the creation of a particularly asymmetric environment around the metal centre by these ligand systems. In order to use such an environment for an effective transfer of the chirality, it is advantageous to control the flexibility of the ligand system as inherent limitation of the asymmetric induction.
Within the substance class of phosphorus-containing ligands, cyclic phosphines, in particular the phospholanes, have achieved particular importance. Bidentate chiral phospholanes are, for example, the DuPhos and BPE ligands employed in asymmetric catalysis. In the ideal case, however, a diversely modifiable chiral ligand base matrix which can be varied within wide limits in respect of its steric and electronic properties is available.
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WO03/084971 discloses catalyst systems with which, in particular, exceptionally positive results can be achieved in hydrogenation reactions. Above all, the catalyst types derived from maleic anhydride and cyclic maleimide evidently create, in their characteristic as chiral ligands, such a good environment around the central atom of the complex employed that for some hydrogenation reactions these complexes are superior to the best hydrogenation catalysts currently known. Nevertheless, in some uses they lack the necessary stability due to the relatively active groups in the five-ring backbone.
It is therefore the object of this invention to provide a ligand skeleton which has a stability which is analogous to that of the known phosphane ligands but is moreover increased compared to this, and can be varied within wide limits in respect of electronic and steric circumstances and has comparably good catalytic properties. In particular, the invention is based on the object of providing novel bidentate and chiral phosphane ligand systems for catalytic purposes, which are easy to prepare in a high enantiomer purity.
This object is achieved according to the claims. Claim 1 relates to novel enantiomerically enriched organophosphorus ligands. The dependent subclaims 2 and 3 relate to preferred embodiments. Claims 4 and 5 are directed at advantageous complexes which can serve as catalysts. Claim 6 relates to a process according to the invention for the preparation of the novel bisphospholanes. Claims 7 to 15 are directed at preferred uses of these complexes.
As a result of providing enantiomerically enriched bidentate organophosphorus ligands of the general formula
(I)
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wherein
* denotes a stereogenic centre,
R1, R4, R5, R8 independently of one another denote
(C1-C8)-alkyl, (C1-C8)-alkoxy, HO-(C1-C8)-alkyl,
(C2-C8) -alkoxyalkyl, (C6-C18)-aryl, (C7-C19) -aralkyl,
(C3-C18) -heteroaryl, (C4-C19) -heteroaralkyl,
(C1-C8) -alkyl- (C6-C18) -aryl,
(C1-C8) -alkyl- (C3-C18) -heteroaryl, (C3-C8) -cycloalkyl,
(C1-C8) -alkyl- (C3-C8) -cycloalkyl or
(C3-C8) -cycloalkyl- (C1-C8) -alkyl,
R2, R3, R6, R7 independently of one another denote R1 or H, wherein in each case adjacent radicals R1 to R8 can be bonded to one another by a (C3-C5)-alkylene bridge, which can contain one or more double bonds or heteroatoms, such as N, 0, P or S, Q can be 0, NR2 or S
W = S, CR"R3 or C=X, where X is chosen from the group consisting of CR2R3, 0 and NR2, the object is achieved in a surprising and nevertheless relatively simple nature and manner. The ligand systems disclosed here are decidedly stable compared with the corresponding particularly good analogous compounds of the prior art, and for this reason it is also possible to use these ligands under more extreme reaction conditions. Furthermore, in some respects they show either a faster and/or more selective reactivity compared with the systems of the prior art.
In respect of ligand systems which are preferably to be employed, those which are characterized in that they contain as radicals R2, R3, R6, R7 (C1-C8)-alkoxy,
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(C2-C8)-alkoxyalkyl or H are possible. A ligand in which R1, R4, R8, R5 are (C1-C8) -alkyl, in particular methyl or ethyl, (C6-C18)-aryl, in particular phenyl, (C1-C8) -alkoxy or (C2-C8) -alkoxyalkyl is very particularly preferred. In these cases R2, R3, R6, R7 are extremely preferably H. Ligands of the formula (I) according to the invention which have an enantiomer enrichment of > 90 %, preferably > 95 %, are furthermore preferred.
In the ligand systems according to the invention, all the C atoms in the phospholane ring can optionally build up a stereogenic centre.
The invention also provides complexes which contain the
ligands according to the invention and at least one
transition metal.
Suitable complexes, in particular of the general formula
(V), contain ligands of the formula (I) according to the
invention
[MxPyLzSq]Ar (V)
wherein, in the general formula (V), M represents a metal centre, preferably a transition metal centre, L represents identical or different coordinating organic or inorganic ligands and P represents bidentate organophosphorus ligands of the formula (I) according to the invention, S represents coordinating solvent molecules and A represents equivalents of non-coordinating anions, and wherein x and y correspond to integers greater than or equal to 1 and z, q and r correspond to integers greater than or equal to 0.
The upper limit of the sum of y + z + q is determined by the coordination centres available on the metal centres, where not all coordination sites have to be occupied. Complex compounds having an octahedral, pseudo-octahedral, tetrahedral, pseudo-tetrahedral or tetragonal-planar coordination sphere, which can also be distorted, around the particular transition metal centre are preferred. The
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sum of y + z + q in such complex compounds is less than or equal to 6.
The complex compounds according to the invention contain at least one metal atom or ion, preferably a transition metal atom or ion, in particular of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel or copper, in any catalytically relevant oxidation level.
Preferred complex compounds are those having less than four metal centres, particularly preferably those having one or two metal centres. In this context, the metal centres can be occupied by different metal atoms and/or ions.
Preferred ligands L of such complex compounds are halide, in particular Cl, Br and I, diene, in particular cyclooctadiene and norbornadiene, olefin, in particular ethylene and cyclooctene, acetato, trifluoroacetato, acetylacetonato, allyl, methallyl, alkyl, in particular methyl and ethyl, nitrile, in particular acetonitrile and benzonitrile, as well as carbonyl and hydrido ligands.
Preferred coordinating solvents S are amines, in particular triethylamine, alcohols, in particular methanol, ethanol and i-propanol, and aromatics, in particular benzene and cumene.
Preferred non-coordinating anions A are trifluoroacetate, trifluoromethanesulfonate, BF4, C1O4, PF6, SbF6 and BAr4, wherein Ar can be (C6-C18) -aryl.
In this context, the individual complex compounds can contain different molecules, atoms or ions of the individual constituents M, P, L, S and A.
Compounds which are preferred among the complex compounds of ionic structure are those of the type [RhP(diene)] +A-, wherein P represents a ligand of the formula (I) according to the invention.
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The invention also provides a process for the preparation of the compounds of the general formula (I). This preferably starts from a compound of the general formula
(II)
wherein
Q, W can assume the abovementioned meaning
X represents a nucleofugic leaving group, which is reacted
with at least 2 equivalents of a compound of the general
formula (III)
in which R1 to R4 can assume the meaning given above and M can be a metal of the group consisting of Li, Na, K, Mg and Ca or represents a trimethylsilyl group. In respect of the preparation of the starting compounds and the conditions of the reactions, reference is made to the following literature (DE10353831; WO03/084971; EP592552; US5329015) .
A possible variant of the preparation of the ligands and complexes is shown in the following equation:
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a)HNO3 (98 %) , from 0. Scherer, F. Kluge Chem. Ber. (1966), 1973-1983; b) and c) in accordance with standard instructions; d) C11CI2, 2.5 h, reflux, 80 ? strength ethanol, from H. J. Pins Rec. Trav. Chim. 68 (1949) 419-425; e) H2SO4 (cone), 2 h, 100 °C, from McBee J. Am. Chem. Soc. 77 (1955) 4379-4380; f) EtOH, 1.5 h, reflux, from McBee J. Am. Chem. Soc. 78 (1956) 491-493; g) and h) in accordance with standard instructions.
The preparation of the metal-ligand complex compounds according to the invention just shown can be carried out in situ by reaction of a metal salt or a corresponding pre-complex with the ligands of the general formula (I). A metal-ligand complex compound can moreover be obtained by reaction of a metal salt or a corresponding pre-complex with the ligands of the general formula (I) and subsequent isolation.
Examples of the metal salts are metal chlorides, bromides, iodides, cyanides, nitrates, acetates, acetylacetonates, hexafluoroacetylacetonates, tetrafluoroborates, perfluoroacetates or triflates, in particular of palladium,
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platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel or of copper.
Examples of the pre-complexes are:
cyclooctadienepalladium chloride, cyclooctadienepalladium
iodide,
1, 5-hexadienepalladium chloride, 1,5-hexadienepalladium
iodide, bis(dibenzylideneacetone)palladium,
bis(acetonitrile)palladium(II) chloride,
bis(acetonitrile)palladium(II) bromide,
bis(benzonitrile)palladium(II) chloride,
bis(benzonitrile)palladium(II) bromide,
bis(benzonitrile)palladium(II) iodide, bis(allyl)palladium,
bis(methallyl)palladium, allylpalladium chloride dimer,
methallylpalladium chloride dimer,
tetramethylethylenediaminepalladium dichloride,
tetramethylethylenediaminepalladium dibromide,
tetramethylethylenediaminepalladium diiodide,
tetramethylethylenediaminepalladiumdimethyl,
cyclooctadieneplatinum chloride, cyclooctadieneplatinum iodide, 1,5-hexadieneplatinum chloride,
1,5-hexadieneplatinum iodide, bis(cyclooctadiene)platinum, potassium (ethylenetrichloroplatinate),
cyclooctadienerhodium(I) chloride dimer, norbornadienerhodium(I) chloride dimer,
1, 5-hexadienerhodium(I) chloride dimer, tris(triphenylphosphane)rhodium(I) chloride,
hydridocarbonyltris(triphenylphosphane)rhodium(I) chloride,
bis(norbornadiene)rhodium(I) perchlorate,
bis(norbornadiene)rhodium(I) tetrafluoroborate,
bis(norbornadiene)rhodium(I) triflate,
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bis (acetonitrilecyclooctadiene)rhodium(I) perchlorate,
bis(acetonitrilecyclooctadiene)rhodium(I)
tetrafluoroborate,
bis(acetonitrilecyclooctadiene)rhodium(I) triflate,
bis{acetonitrilecyclooctadiene)rhodium(I) perchlorate,
bis(acetonitrilecyclooctadiene)rhodium(I)
tetrafluoroborate,
bis(acetonitrilecyclooctadiene)rhodium(I) triflate,
cyclopentadienerhodium(III) chloride dimer, pentamethylcyclopentadienerhodium(III) chloride dimer,
(cyclooctadiene) Ru (r]3-allyl) 2, ( (cyclooctadiene) Ru) 2 (acetate)4, ((cyclooctadiene)Ru)2 (trifluoroacetate)4, RuCl2
50 % and < 100 %. The ee value is calculated as follows: ([Enantiomerl]-[Enantiomer2])/([Enantiomerl]+[Enantiomer2])=ee value
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In the context of the invention, the naming of the complexes and ligands according to the invention includes all the possible diastereomers, whereby the two optical antipodes of a particular diastereomer are also intended to
be named.
With their configuration, the complexes and catalysts described here determine the optical induction in the product. It goes without saying that the catalysts employed in racemic form also deliver a racemic product. A subsequent cleavage of the racemate then delivers the enantiomerically enriched products again. However, this is registered in the general knowledge of the person skilled in the art.
N-Acyl groups are to be understood as meaning protective groups which are generally conventionally employed for protection of nitrogen atoms in amino acid chemistry. Such groups which are to be mentioned in particular are: formyl, acetyl, Moc, Eoc, phthalyl, Boc, Alloc, Z, Fmoc, etc.
The literature references cited in this specification are regarded as contained in the disclosure.
In the context of the invention, membrane reactor is understood as meaning any reaction vessel in which the catalyst of enlarged molecular weight is enclosed in a reactor, while low molecular weight substances are fed to the reactor or can leave it. The membrane here can be integrated directly into the reaction space or incorporated outside in a separate filtration module, in which the reaction solution flows continuously or intermittently through the filtration module and the retained product is recycled into the reactor. Suitable embodiments are described, inter alia, in WO98/22415 and in Wandrey et al. in Yearbook 1998, Verfahrenstechnik und Chemieingenieurwesen [Process Technology and Chemical Engineering], VDI p. 151 et seq.; Wandrey et al. in Applied
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Homogeneous Catalysis with Organometallic Compounds, vol. 2, VCH 1996, p. 832 et seq.; Kragl et al., Angew. Chem. 1996, 6, 684 et seq.
In the context of the invention, a polymer-enlarged ligand/complex is to be understood as meaning a ligand/complex in which the polymer enlarging the molecular weight is bonded covalently to the ligands.
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Descriptions of the drawings:
Fig. 1 shows a membrane reactor with dead-end filtration. The substrate 1 is transferred via a pump 2 into the reactor space 3, which contains a membrane 5. In the reactor space, which is operated with a stirrer, are the catalyst 4, the product 6 and unreacted substrate 1, in addition to the solvent. Low molecular weight 6 is chiefly filtered off via the membrane 5.
Fig. 2 shows a membrane reactor with cross-flow filtration. The substrate 7 is transferred here via the pump 8 into the stirred reactor space, in which are also solvent, catalyst 9 and product 14. A solvent flow which leads via a heat exchanger 12, which may be present, into the cross-flow filtration cell 15 is established via the pump 16. The low molecular weight product 14 is separated off here via the membrane 13. High molecular weight catalyst 9 is then passed back with the solvent flow, if appropriate again via a heat exchanger 12, if appropriate via the valve 11, into the reactor 10.
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Examples:
Preparation of 3,4-dichloro-thiophene-2,5-dione [S
compound]
according to the literature: 0. Scherer, F. Kluge Chem.
Ber. 99, 1966, 1973-1983
5 g tetrachlorothiophene are stirred with 13 ml HN03 for five minutes and the resulting brown solution is then poured on to ice. The precipitate which has precipitated out is filtered off rapidly over a frit and recrystallized from cyclohexane. Slightly yellowish crystals are obtained in a yield of approx. 35 %.
13C-NMR (CDC13) : 143.5 (=C-C1), 183.6 (C=O)
Preparation of 4,5-dichloro-cyclopent-4-ene-l,2-dione [CH2
compound]
according to the literature: McBee et al. J. Chem. Soc. Am.
78, 1956, 489-491
0.85 g of the tetrachloro compound is stirred in 25 ml ethanol for 1.5 hours under reflux, while passing a stream of argon through the mixture. After cooling to room temperature and addition of 30 ml water, the mixture is concentrated on a rotary evaporate and a white precipitate precipitates out. Yield approx. 60 %.
1H-NMR (acetone-d6) : 3.38 (CH2) ;
13C-NMR (acetone-d6) : 43.1 (CH2) , 151.4 (=C-C1, >C=, =CC12) , 189.7 (C=O);
Elemental analysis: Ccaic. 36.40 %, CfoUnd 36.20 %;
Hcalc. 1.22 %, Hfound 1-20 % ;
Mass spectrometry: M+ = 164
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Preparation of the bisphospholane compounds and Rh complexes thereof
0.75 mM (124 mg [CH2 compound] or 137 mg [S compound]) in 2 ml THF are is initially introduced into the reactor at 0 °C, and a solution of 285 mg (2 eq)
trimethylsilylphospholane in 2 ml THF is slowly added via a cannula. The mixture is stirred overnight and the volatile constituents are removed in vacuo. The red residue is employed directly for formation of the complex. For this, the crude product was taken up in 3 ml CH2Cl2 and the mixture was slowly added dropwise at 0 °C to a solution of 305 mg [Rh (cod) 2] BF4 in 2 ml CH2C12. After stirring for 2 hours at room temperature, the complex was precipitated with ether and, after filtration, washed twice with ether. Yields approx. 50 %.
S compound complex:
31P-NMR (CDCI3) : Crude product of the ligand:
+11.1 ppm;
XH-NMR (CDCI3) : Complex
5.66 (2H, m, Hcod), 5.00 (2H, m, Hcod), 2.97 (2H, m, CH-P), 2.59 - 2.11 (18 H, CH-P, CH2) ; 1.51 (6 H, dd, CH3) , 1.34 (6 H, dd, CH3) ; overlapped by the bischelate complex;
13C-NMR (CDCI3) : Complex
108.5 (m, CHcod), 94.6 (m, CHcod), 40.1 (m, CH-P), 38.5 (m, CH-P), 37.6 (CH2), 35.2 (CH2) , 31.8 (CH2) , 28.6 (CH2) , 17.2 (m, CH3) , 13.9 (CH3) ; C=O and C=C signals not visible;
31P-NMR (CDCI3) : Complex:
+ 65.3 ppm (d, J = 151 Hz) to 90 % and
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CH2 compound complex:
31P-NMR (CDC13) : Crude product of the ligand:
+2.0 ppm;
XH-NMR (CDCI3) : Complex
5.53 (2H, m, Hcod), 4.95 (2H, m, Hcod), 3.65 (2H, s, CH2) , 2.96 (2H, m, CH-P) , 2.61 - 2.14 (16 H, CH-P, CH2) ; 1.45 (6 H, dd, CH3), 1.15 (6 H, dd, CH3) ;
13C-NMR (CDCI3) : Complex
192.9 (d, C=0), 174.8 (m, C=C); 107.4 (m, CHcod), 92.9 (m, CHcod), 50.8 (CH2), 39.3 (m, CH-P), 37.8 (m, CH-P), 37.8 (CH2), 35.5 (CH2), 31.9 (CH2) , 28.7 (CH2) , 17.3 (m, CH3) , 13.8 (CH3) ;
31P-NMR (CDCI3) : Complex: + 63.2 ppm (d, J = 150 Hz)
General hydrogenation instructions
0.005 mmol pre-catalyst (S compound complex or CH2 compound complex) and 0.5 mmol prochiral substrate are initially introduced into an appropriate hydrogenating vessel under an H2 atmosphere and the mixture is temperature-controlled at 25 °C. After addition of the appropriate solvent (7.5 ml methanol, tetrahydrofuran or methylene chloride) and pressure compensation (to atmospheric pressure), the hydrogenation is started by starting the stirring and beginning the automatic recording of the gas consumption under isobaric conditions. After the end of the uptake of
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gas, the experiment is ended and the conversion and selectivity of the hydrogenation are determined by means of gas chromatography.
Hydrogenation results:
Catalyst S compound complex CH2 compound complex
Substrate Solv. % ee % ee
Acetamidocinnamic acid methyl ester MeOH 93.3 R; 88.9 R (30 % 96.5 R
THF 94.5 R 98.7 R
CH2C12 80.9 R (8 % con.) 82.7 R
Itaconic acid dimethyl ester MeOH 6.2 S; racemate 36.4 S
THF 13.0 S (50 % con. ) 64.9 S
CH2C12 95.9 S (40 % con. ) 98.9 S
Me>=\ MeOH 0.8 R (70 % con.) 78.8 R
Ac-NH COOMeZ-l THF 17.6 R (5 % con.) 48.2 R
CH2C12 79.7 R (20 % con.);
Me COOMe MeOH 4.5 R (20 % con.) 88.3 R
Ac-NHE-l THF 47.1 R (32 % con. ) 93.9 R
CH2C12 98.9 R
Me}=\ MeOH 62.5 R
Ac-NH COOBnZ-OBn THF 77.1 R
CH2C12 7 9.9 R (65 % con.)
Me COOBn MeOH 97.1 R
Ac-NHE-OBn THF 97.5 R
CH2C12 98.5 R (92 % con.)
/-Pr MeOH 2.7 S (10 % con.) 2.0 R
Ac-NH COOEt THF 58.2 S
Z CH2C12 69.7 S (75 % con.)
/-Pr COOEt MeOH 83.6 S
) Ac-NH THF 99.4 S
E CH2C12 99.0 S
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Patent claims:
1. Enantiomer-enriched bidentate organophosphorus ligands
of the general formula (I)
wherein
* denotes a stereogenic centre,
R1, R4, R5, R8 independently of one another denote
(C1-C8) -alkyl, (C1-C8) -alkoxy, HO- (C1-C8) -alkyl,
(C2-C8)-alkoxyalkyl, (C6-C18)-aryl, (C7-C19) -aralkyl,
(C3-C18) -heteroaryl, (C4-C19) -heteroaralkyl,
(C1-C8) -alkyl- (C6-Ci8) -aryl,
(C1-C8) -alkyl- (C3-C18) -heteroaryl, (C3-C8) -cycloalkyl,
(C1-C8) -alkyl- (C3-C8) -cycloalkyl or
(C3-C8) -cycloalkyl- (C1-C8) -alkyl,
Rz, R3, R°, R1 independently of one another denote R1
or H,
wherein in each case adjacent radicals R1 to R8 can be
bonded to one another by a (C3-C5)-alkylene bridge,
which can contain one or more double bonds or
heteroatoms, such as N, 0, P or S,
Q can be 0, NR2 or S,
W = S, CR2R3 or C=X, where X is chosen from the group
consisting of CR2R3, 0 and NR2.
2. Ligands according to claim 1,
characterized in that
R2, R3, R6, R7 are (C1-C8)-alkoxy, (C2-C8) -alkoxyalkyl
or H.
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3. Ligands according to one or more of the preceding
claims,
characterized in that
the compounds of the formula (I) have an enantiomer
enrichment of > 90 %, preferably > 95 %.
4. Complex containing the ligands according to claim 1-3
and at least one transition metal.
5. Complex containing the ligands according to claim 1 -
3 with palladium, platinum, rhodium, ruthenium,
osmium, iridium, cobalt, nickel or copper.
6. Process for the preparation of the ligands according
to claim 1-3,
characterized in that
a compound of the general formula (II)
wherein
Q, W can assume the meaning given in claim 1,
X represents a nucleofugic leaving group,
is reacted with at least 2 equivalents of a compound
of the general formula (III)
in which R1 to R4 can assume the meaning given in claim 1 and
M can be a metal of the group consisting of Li, Na, K, Mg and Ca or is a trimethylsilyl group.
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7. Use of a complex compound according to claim 4 or 5 as
a catalyst for asymmetric reactions.
8. Use of a complex compound according to claim 4 or 5 as
a catalyst for asymmetric hydrogenation,
hydroformylation, rearrangement, allylic alkylation, cyclopropanation, hydrosilylation, hydride transfer reactions, hydroboronations, hydrocyanations, hydrocarboxylations, aldol reactions or the Heck reaction.
9. Use of a complex compound according to claim 4 or 5 as
a catalyst for asymmetric hydrogenation and
hydroformylation.
10. Use according to claim 9
characterized in that
an E/Z mixture of prochiral N-acylated p-aminoacrylic acids or derivatives thereof is hydrogenated.
11. Use according to one or more of claims 7 - 10,
characterized in that
it is carried out by means of hydrogenation with hydrogen gas or by means of transfer hydrogenation.
12. Use according to claim 11, where it relates to
hydrogenation with hydrogen gas,
characterized in that
the hydrogenation is carried out under a hydrogen pressure of 0.1 to 100 bar, preferably 0.5 to 10 bar.
13. Use according to claim 11,
characterized in that
it is carried out at temperatures of from -20 °C to 100 °C, preferably 0 °C to 50 °C.
14. Use according to one or more of the preceding claims 7
- 13,
characterized in that
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the ratio of substrate/catalyst chosen is between 50,000:1 and 10:1, preferably 1,000:1 and 50:1.
15. Use according to one or more of the preceding claims 7 - 14,
characterized in that the catalysis is carried out in a membrane reactor.